May 25, 2015
EMA Committee Recommends Approval of Evolocumab Evolocumab, an investigational human monoclonal antibody for proprotein convertase subtilisin-kexin type 9 (PCSK9), is one step closer to being available in Europe. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approving evolocumab as an adjunct to diet in patients with elevated cholesterol levels who are unable to reach their recommended LDL-cholesterol goal despite taking an optimal dose of statin. Patients deemed statin intolerant or those in whom a statin is contraindicated would also be eligible for treatment with evolocumab. The committee also recommended that the PCSK9 inhibitor, the first in its class to receive a positive opinion from CHMP, be available to treat patients with homozygous familial hypercholesterolemia (FH). The drug, which requires a subcutaneous injection every 2 or 4 weeks depending on the dose, works by blocking the PCSK9 protein. PSCK9 limits the number of LDL receptors available in the liver and reduces the body's ability to remove LDL cholesterol from the bloodstream. EMA stated that the positive review from CHMP is based on the efficacy of evolocumab for lowering LDL-cholesterol levels in nine studies of patients with hypercholesterolemia/mixed dyslipidemia and in two studies of patients with homozygous FH. The PCSK9 inhibitor was considered safe based on data from more than 6000 patients followed for at least 6 months and more than 1100 patients followed for at least 2 years.
Sitagliptin may prevent heart disease in HIV patients The antidiabetic drug sitagliptin demonstrated beneficial systemic and adipose anti-inflammatory effects in HIV-infected adults with impaired glucose tolerance, according to research published in the Journal of Clinical Endocrinology and Metabolism. It is a randomized, placebo-controlled, double blind study of 36 men and women with HIV, aged 18 to 65 years, who had received combination ART (cART) for the past 6 months and whose immune and virologic statuses were stable. None of the patients had type 2 diabetes or were taking antidiabetes medications, nor did they have an AIDS-defining diagnosis, history of heart failure, chronic kidney or liver dysfunction, pancreatitis, or active malignancy, according to the researchers. Participants were given either 100 mg sitagliptin daily or placebo for 8 weeks. Both glucose area under the curve (P = .002) and oral glucose insulin sensitivity index (P = .04) improved more in patients assigned sitagliptin compared with controls. At 8 weeks, those who received sitagliptin experienced a decrease in plasma high-sensitivity C-reactive protein (hsCRP) and CXCL10 (P ≤ .008) — both discriminative markers for inflammation, particularly in cART-treated HIV patients. This was in sharp contrast to the placebo group, which saw an increase in hsCRP. In addition, in terms of immune regulation, adipose tissue monocyte chemoattractant protein-1 mRNA abundance declined more in patients receiving sitagliptin (P = .01), and epidermal growth factor-like module containing mucin-like hormone receptor 1 mRNA abundance tended to decline more in the treatment arm as well, although this was not statistically significant.
Perioperative Dabigatran Protocol Seems Safe, Doable, Effective In a multicenter Canadian study of more than 500 patients who had to have dabigatran therapy interrupted when they underwent major or minor surgery, adherence to a new specific protocol for stopping and resuming dabigatran was high and the incidence of major bleeding was low. The protocol was largely based on the recommendations that were implemented partway through the phase 3 RE-LY study of the novel oral anticoagulant (NOAC) in patients with atrial fibrillation. However, the current protocol specified exactly when to stop dabigatran, "4 hours, 48 hours, or 96 hours [prior to surgery], depending on the patient's kidney function and [the procedure-related] risk of bleeding. A total of 217 patients (40%) underwent surgery that entailed a high bleeding risk, notably implantable cardioverter defibrillator (ICD) or pacemaker insertion, endoscopy/bronchoscopy with combined polyp removal, abdominal surgery, orthopedic surgery, and brain surgery. The other 324 patients (60%) underwent surgeries classed as having a standard bleeding risk, notably endoscopy (without polyp removal), ablation therapy, and cardiac catheterization. For surgeries with a standard risk of bleeding, the study protocol specified that dabigatran should be stopped 24 hours earlier, 2 days earlier, or 4 days earlier, if a patient's calculated creatinine clearance was >50 mL/min, >30 to 50 mL/min, or <30 mL/min, respectively. For procedures with a high risk of bleeding, the protocol specified that dabigatran should be stopped 2 days earlier, 4 days earlier, or 6 days earlier, respectively, for these levels of creatinine clearance. Dabigatran was stopped according to protocol in 89% of cases and resumed according to protocol in 77% of the cases. Preoperative bridging with heparin was not used, but nine patients received postoperative heparin mainly after bowel surgery when they could not take any oral medication. During the 30-day follow-up, 10 patients (1.8%) each had a major bleeding event, which was managed with a transfusion in six of 10 cases. Another 28 patients (5.2%) had 35 minor bleeding events. One patient had a TIA, which was the only thromboembolic complication in this cohort. There were four deaths unrelated to bleeding or thrombosis.
May 18, 2015
Use of Digoxin Raises Mortality in a new Meta-analysis Digoxin use was linked with a 29% increased risk of mortality in more than 235,000 patients with atrial fibrillation (AF) and with a 14% increased risk of death in more than 91,000 patients with congestive heart failure (CHF) during an average follow-up of 2.5 years, according a new metanalysis published online in the European Heart Journal. The metanalysis includes studies of digoxin published since 1993, comprising 326,426 patients: nine studies in patients with AF, seven in patients with CHF, and three in patients with both conditions. In follow-up ranging from 0.83 to 4.7 years, digoxin use was associated with an increased risk of all-cause mortality. Among all patients, digoxin was associated with an increased relative risk for all-cause mortality (HR = 1.21; 95% CI, 1.07-1.38). In the subgroup of 235,047 patients with AF, those assigned digoxin had a 29% increased mortality risk compared with those not receiving glycosides (HR = 1.29; 95% CI, 1.21-1.39), and in the subgroup of 91,379 patients with congestive HF, digoxin was associated with a 14% increased mortality risk (HR = 1.14; 95% CI, 1.06-1.22). The results are consistent with a post hoc analysis of the DIG trial of digoxin in patients with HF, which found that higher serum digoxin levels (≥ 1.2 ng/mL) were significantly associated with mortality.
Long-term depression may increase stroke risk Long-term depressive symptoms are associated with increased risk for stroke, and this association persists even if the depressive symptoms remit, according to new findings of a study published online in J. Am. Heart Assoc. Researchers evaluated 16,178 participants in the Health and Retirement Study (mean age, 65.7 years; 41.5% men; 78.2% white) who were aged at least 50 years, stroke-free and not institutionalized at baseline. Participants were interviewed biennially from 1998 to 2010.It was observed 1,192 strokes during the study period (mean follow-up, 8.88 years). The authors found that, compared with those who had stable low/no depressive systems, participants with stable high depressive symptoms had elevated risk for stroke (adjusted HR = 2.14; 95% CI, 1.69-2.71), as did those with remitted depressive symptoms (adjusted HR = 1.66; 95% CI, 1.22-2.26). The risk for stroke was not significantly different between those with stable high or remitted symptoms. Stable high depressive symptoms were associated with higher stroke risk across all age, sex and race/ethnicity subgroups. Remitted depressive symptoms were associated with higher stroke risk in women (adjusted HR = 1.86; 95% CI, 1.3-2.66) and non-Hispanic whites (adjusted HR = 1.66; 95% CI, 1.18-2.33), and marginally so in Hispanics (adjusted HR = 2.36; 95% CI, 0.98-5.67).
Physical Activity Linked to Survival in ICD Patients ( ALTITUDE Study) Physical activity may improve survival rates in patients with implantable cardioverter-defibrillators (ICDs), suggests a new analysis from the ALTITUDE registry. The findings, which were published in the Journal of the American Heart Association and included almost 100,000 ICD patients, showed 4-year postprocedure survival rates of 91% in the subgroup that was most active at baseline (mean 33 min/day) vs 50% in the least active group (mean 208 min/day; P&ly;0.001). There was also an adjusted hazard ratio of 1.44 for death (95% CI 1.4–1.5) in participants who had lower mean baseline activity, defined as incremental difference of 30 min/day. The current analysis examined data on 98,437 participants at baseline (defined as 30 to 60 days postimplantation) and at a mean follow-up of 2.2 years. Baseline physical activity was 107.5 min/day. Not surprisingly, the least active group was older than the other five subgroups, in which activity levels ranged from 68 to 208 min/day. A larger percentage of the least active group also had a CRT vs the most active group (53.2% vs 30.4%, P<0.0001). One-year follow-up for the most and least active groups showed survival rates of 98.7% and 86.5%, respectively (P<0.001). The between-group difference in survival became more pronounced over time, with rates of 96.5% vs 71.3%, respectively, at 2 years; 93.9% vs 59.3% at 3 years; and 90.5% vs 50.0% at 4 years.
May 11, 2015
Neprilysin inhibition may accelerate the progression of Alzheimer’s disease. According a new study published online in Eur. Heart Journal , the authors draw attention the potential deleterious effect of neprilysin inhibition on Alzheimer disease. Neprilysin which is also known as the neutral endopeptidase is a protease with a broad range of substrates including natriuretic peptides, vasoactive peptides (endothelin-1, bradykinins), neuropeptides (substance P, enkephalins), and the b-amyloid peptide. Due to its central role in the metabolism of cardiovascular peptides and the b-amyloid peptide, neprilysin has become a research subject for both cardiovascular diseases and Alzheimer’s disease. Neprilysin is responsible for the degradation of natriuretic peptides and other cardiovascular peptides. Neprilysin inhibitors prolong and potentiate the beneficial effects of vasoactive/natriuretic peptides. However, neprilysin degrades both vasoconstrictor and vasodilator peptides. In order to eliminate this limitation, neprilysin inhibitors are combined with an ACEI (omapatrilat) or an ARB (LCZ696). The PARADIGM-HF trial showed that LCZ696 is superior to enalapril for the treatment of chronic heart failure with reduced EF. In Alzheimer’s disease and cerebral amyloid angiopathy, b-amyloid peptide accumulates in the brain. Several proteases degrade b-amyloid peptide, of which the most effective is neprilysin. There are multiple lines of evidence showing the crucial role of neprilysin in Alzheimer’s disease. Therefore, numerous researches are being conducted to modulate neprilysin activity in the brain. When neprilysin inhibitors are used for the treatment of cardiovascular diseases, there is a risk of b-amyloid accumulation in the brain and thus accelerating the progression of Alzheimer’s disease and cerebral amyloid angiopathy. Indeed, since intracerebral infusion of the NEPi provokes Alzheimer disease lesions in animal models. The ongoing PARAGON-HF trial assessing the effect of LCZ696 in heart failure with preserved EF will evaluate cognitive function. However, the duration of follow-up of this trial may not be sufficient to show any deleterious effect of LCZ696 on cognitive function. Therefore, it is important to continue follow-up of the patients after the end of the trials in order to confirm the safety of LCZ696. In summary, the authors draw attention to a potential serious side effect of neprilysin inhibition. Indeed, inhibition of an enzyme responsible from the degradation of a broad range of peptides has a potential for serious side effects. As known from other drugs, some side effects are noticeable after a long time.
Spontaneous bleeding after PCI is as dangerous as MI Percutaneous coronary intervention related bleeding is associated with increased mortality according a new study published in JACC. The effect of spontaneous bleeding occurring after hospital discharge on prognosis is unclear. The study enrolled 32,906 patients (14% with acute coronary syndrome) who had PCI between January, 1996 and December, 2008 in Kaiser Permanente Northern California healthcare delivery system. During 7 and 365 days post-discharge, 530 patients (2.14 per 100 person-years) had spontaneous bleeding. Patients who had a bleeding were older, more likely to be women, had a greater comorbidity burden and more likely to receive warfarin compared to patients without bleeding. The use of antiplatelet therapy was similar between the groups. In the same period, 991 patients (4.26 per 100 person-years) had myocardial infarction. Patients who experienced an MI were older, more likely to be women, had a greater comorbidity burden and lower levels of GFR and Hb compared to patients who did not experience an MI. During mean follow-up of 4.4 years, 4048 deaths occurred. At follow-up, 31% of the patients with spontaneous bleeding died, 32% of the patients with spontaneous MI died, 53.8 of the patients with both spontaneous bleeding and MI died, and 11.4% of the patients without spontaneous bleeding and MI died. The crude annual death rate after spontaneous bleeding (9.4%) and after spontaneous MI (7.6%) was higher compared with patients who experienced neither event (2.6%). The multivariate analysis revealed that bleeding was associated with an increased mortality and risk of death increased by 61% in patients who had bleeding compared to the reference group who had neither bleeding nor MI (adjusted HR: 1.61, 95% CI: 1.30-2.00). Risk of death increased by 91% in patients who had MI compared to the reference group who had neither bleeding nor MI (adjusted HR after MI: 1.91, 95% CI: 1.62 to 2.25). The results were similar in subgroups of elective or urgent PCI.
Outpatient treatment safe for select patients with acute PE Favorable short-term outcomes of patients with pulmonary embolisms after hospital discharge suggest these patients can safely receive outpatient treatment, according to a study published in JAMA Int. Med. The analysis included data from the Cardiovascular Research Network Venous Thromboembolism study, a collaboration of four geographically diverse health care delivery systems. Researchers identified 494 patients (median age, 61 years; range, 48-73) who were diagnosed with PE between 2004 and 2010 and who were discharged from hospital EDs with an anticoagulant prescription within 7 days. The cohort was 73.9% white and 49.2% (n = 243) female. Hospital readmission within 30 days and death within 90 days served as the primary endpoints. Researchers observed that 18.6% (n = 92) of patients with PE returned to the hospital within 30 days, and 7.9% (n = 39) of those patients were readmitted. Eleven patients (2.2%) had a primary diagnosis of hemorrhage during a subsequent hospital visit within 30 days. Researchers noted mortality rates were low. No deaths were reported within the first 7 days after discharge, and only two deaths occurred after 90 days. Patient discharge rates significantly increased during the study period. Approximately 11% of patients with PE were discharged in 2010 vs. 5.6% of patients with PE discharged in 2004 (P ˂ .001 for trend). The investigators acknowledged limitations to their study, including the reliance on ICD-9 codes and pharmacy data to identify patients, as well as the lack of appropriate data to calculate a complete PE severity risk classification. The investigators also were unable to identify the specific reasons for patient disposition plans. Still, mortality rates from this analysis are similar to those from previous clinical trials and suggest outpatient care can be implemented safety for select patients with acute PE, according to the researchers.
May 04, 2015
The 61% of TAVR Patients Alive at 3 Years: UK Registry Analysis Three years after transcatheter aortic-valve replacement (TAVR), 61% of individuals with severe symptomatic aortic stenosis who receive the new valve remain alive, according to data from the UK Transcatheter Aortic Valve Implantation (TAVI) Registry which published in the last issue of JACC: Cardiovascular Interventions . At 5 years, 45.5% of the UK patients who underwent TAVR were still alive. Survival to 3 years was largely predicated on patient characteristics, with baseline renal dysfunction, atrial fibrillation, respiratory disease, impaired left ventricular function, and a higher EuroSCORE (>18.5) associated with an increased risk of mortality, report investigators. The data is based on 870 patients who underwent TAVR in the UK between 2007 and 2009. The mean age of patients at the time of implantation was 82 years, and the minimum time from TAVR to data census was 4.1 years (maximum 7.0 years). Patients in the registry received either the Sapien balloon-expandable valve or the self-expanding CoreValve.
AF is associated with increased risk for non-STEMI After a median follow-up of more than 20 years, researchers found an increased risk of non-ST elevation myocardial infarction (non-STEMI) in patients with atrial fibrillation even when adjusting for cardiovascular and other risk factors. However, there was no association between atrial fibrillation and STEMI. These are the results of Atherosclerosis Risk in Communities study which published online in Circulation. Approximately two-thirds of MI’s in the U.S. each year are non-STEMI, according to the researchers. In addition, an estimated 2.7 million to 6.1 million people in the U.S. have atrial fibrillation, which is a risk factor for stroke. However, researchers said it was unclear if the disease was a risk factor for MI. In this community-based population study, researchers examined 15,792 adults who were interviewed and visited a clinic between 1987 and 1989. They followed up with them on several occasions from 1990 to 2013 and excluded patients who did not have quality echocardiograms at baseline and those with coronary heart disease. The final analysis included 14,462 patients. The mean age was 54 years, 56% of patients were women. Of the patients, 31 had atrial fibrillation at baseline and 1,514 had atrial fibrillation during the follow-up period before having MI. During a median follow-up period of 21.6 years, researchers identified 1,374 incident MI events by contacting patients and examining hospital medical records. There were 829 non-STEMI events and 249 STEMI events. The mean time from atrial fibrillation diagnosis to MI was 4.82 years. Researchers found atrial fibrillation was associated with a 63% increased risk of MI. There was a significantly higher rate of MI in women with atrial fibrillation compared with men.
ISAR-TRIPLE: Net clinical outcomes similar for 6-week vs. 6-month triple therapy Six weeks of triple therapy with oral anticoagulation, aspirin and clopidogrel was not superior to a 6-month regimen for the primary outcome of death, MI, definite stent thrombosis, stroke or TIMI major bleeding at 9 months, according to data from the ISAR-TRIPLE trial. published in the Journal of the American College of Cardiology. The randomized, open-label trial included 614 patients who were receiving concomitant oral anticoagulation and aspirin therapy and underwent drug-eluting stent implantation for stable angina or ACS at centers in Denmark and Germany from September 2008 to December 2013. Patients were randomly assigned to a 6-week (n = 307) or 6-month (n = 307) regimen of clopidogrel therapy 75 mg on top of oral anticoagulation and aspirin. Patients were followed up by phone or at the physician’s office after 6 weeks, 6 months and 9 months. The primary endpoint occurred in 9.8% of the 6-week therapy group vs. 8.8% of the 6-month therapy group (HR = 1.14; 95% CI, 0.68-1.91). Researchers reported no significant difference in the secondary combined ischemic endpoint of cardiac death, MI, definite stent thrombosis and ischemic stroke between the two groups (6 weeks, 4%; 6 months, 4.3%; HR = 0.93; 95% CI, 0.43-2.05). Both durations also were associated with similar rates of TIMI major bleeding (6 weeks, 5.3%; 6 months, 4%; HR = 1.35; 95% CI, 0.64-2.84). In a post-hoc landmark analysis, the 6-month therapy group experienced significantly more bleeding events, as defined by Bleeding Academic Research Consortium (BARC) classifications.
April 27, 2015
Bococizumab reduces LDL in patients with hypercholesterolemia Use of the PCSK9 monoclonal antibody bococizumab in patients with hypercholesterolemia was associated with significant reductions in LDL across all doses according the results of a phase 2b, multicenter, double blind, placebo-controlled, dose-ranging trial which published in Am. J. Cardiol. The study population were 351 adults with hypercholesterolemia (baseline fasting LDL, ≥ 80 mg/dL; triglycerides, ≤ 400 mg/dL; no incidence of CV events within past 6 months). Patients were randomly assigned subcutaneous placebo or bococizumab 50 mg, 100 mg or 10 mg every 2 weeks or bococizumab 200 mg or 300 mg every 4 weeks. The dose was reduced if LDL persistently deceased to 25 mg/dL or lower. The primary endpoint was mean difference in LDL from baseline to week 12. Randomized treatment continued for another 12 weeks to assess the safety of bococizumab. 16% of patients assigned bococizumab 100 mg or 150 mg every 2 weeks had their dose reduced during the study. At 12 weeks, mean change in LDL was –35.4 mg/dL in the 50-mg group, –52.3 mg/dL in the 100-mg group and –54.2 mg/dL in the 150-mg group compared with –2.8 mg/dL in the placebo group. A pharmacokinetic/pharmacodynamics (PK/PD) model-predicted and placebo-adjusted mean change in LDL from baseline to 12 weeks ranged from –36.4 mg/dL for the 50-mg every 2 weeks dose to –72.2 mg/dL for the 150-mg every 2 weeks dose. 44% of patients assigned bococizumab 200 mg and 39% assigned 300 mg every 4 weeks had their dose reduced during the study. At 12 weeks, mean change in LDL was –21.3 mg/dL in the 200-mg group and –38.3 mg/dL in the 300-mg group compared with –1.3 mg/dL in the placebo group. Approximately 70% of patients in the 300 mg-group showed LDL reductions after 2 weeks.
EU Approval Recommended for Edoxaban for Stroke, Systemic Embolism in AF Patients The new oral anticoagulant edoxaban (factor Xa inhibitor) has received approval recommendation from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) for use in the prevention of stroke and systemic embolism in patients with nonvalvular AF, as well as for prevention and treatment of recurrent venous thromboembolism. CHMP is recommending marketing authorization for the medication, which will be available as film-coated tablets in doses of 15, 30, and 60 mg. CHMP reports that soft tissue hemorrhage is the most common treatment-related adverse event, followed by epistaxis and vaginal hemorrhage. The agency also adding that anemia, rash, and abnormal liver-function tests are other common side effects. The full indication notes that it should be used for stroke and systemic embolism in nonvalvular AF patients with congestive heart failure, diabetes, or hypertension who are older than 74 years or who had a transient ischemic attack or stroke previously; and for treatment and prevention in patients with pulmonary embolism (PE) and deep vein thrombosis (DVT). In January of this year, FDA also approved edoxaban to reduce risk of stroke and systemic embolism in patients with nonvalvular AF and to treat DVT and PE. Its approval was based on results from the ENGAGE AF-TIMI 48 trial, which showed that the medication was noninferior to warfarin.
Heart Risk From Amiodarone Plus Hepatitis C Antivirals (EMA) The European Medicines Agancy (EMA) has confirmed a risk of severe bradycardia or heart block when the hepatitis C medicines (sofosbuvir with ledipasvir) or a combination of sofosbuvir and daclatasvir which are used in patients who are also taking the medicine amiodarone. To manage this risk the Agency recommends that amiodarone should only be used in patients taking these hepatitis C medicines if other antiarrhythmics cannot be given. If concomitant use with amiodarone cannot be avoided, patients should be closely monitored. Because amiodarone persists for a long time in the body, monitoring is also needed if patients start such hepatitis C treatments within a few months of stopping amiodarone. The recommendations follow a review of cases of severe bradycardia or heart block in patients taking amiodarone who started treatment with the hepatitis C combinations. It was considered that there was a likely relationship of these events to the medicines. The possible mechanism behind these effects is unknown and further investigation of other cases with sofosbuvir and other hepatitis C medicines is ongoing.
April 20, 2015
FDA approves ivabradine for treatment of HF A drug already available in Europe has been approved by the US Food and Drug Administration for reducing the risk for hospitalization from worsening heart failure. The agent, ivabradine, is indicated for stable patients with heart failure and a heart rate of >70 per minute on maximally tolerated beta-blockers. The approval is based on the international, placebo-controlled SHIFT trial, published in 2010, which randomized >6500 patients in New York Heart Association class II-IV heart failure and left ventricular ejection fraction ≤35%. The trial saw a highly significant 18% drop in risk for cardiovascular death or hospitalization for worsening heart failure over an average of 23 months in patients treated with ivabradine.
FDA Advisory Panel Gives the green light for Cangrelor in PCI The Cardiovascular and Renal Drugs Advisory Committee of the US Food and Drug Administration (FDA) voted 9 to 2, with one member abstaining, that the injectable antiplatelet agent cangrelor should be approved for reducing thrombotic events in PCI. Last year, the committee voted 7 to 2 against recommending cangrelor for PCI because of data problems and they felt that the risk/benefit profile was not sufficiently strong enough. The Medicines Company then underwent further sensitivity analyses and supplied a more simplified application. Earlier this week, FDA reviewers gave a favorable review that the agent now be approved "in patients in whom treatment with an oral P2Y12 platelet inhibitor prior to PCI is not feasible and when glycoprotein IIb/IIIa receptor antagonists are not anticipated to be used." They also noted that PHOENIX was sufficient enough as a stand-alone trial to warrant approval of cangrelor.
Micra Miniature Leadless Pacemaker Gains CE Mark Approval European physicians will now have access to a second leadless pacemaker, as Medtronic announced today the Micra transcatheter pacing system (TPS) has gained CE Mark approval in Europe. The Micra, which is not much larger than a one Euro coin (or nickel) at one-tenth the size of a traditional pacemaker, was approved in Europe as part of the Micra TPS Global Clinical Trial, a larger ongoing study. For the CE Mark approval, European regulators approved the device on safety and efficacy outcomes of 60 patients who had the tiny pacemaker implanted and were followed for 3 months. The device, which is delivered via catheter and eliminates the traditional surgical "pocket," is not approved in the US, but researchers plan to enroll as many as 780 patients from 50 clinical centers as part of the ongoing global trial.
LDL variability predicts CV events in patients with CAD Visit-to-visit LDL variability was independently predictive of CV events in patients with CAD, according to new data from the TNT trial which published in JACC. Researchers evaluated 9,572 patients with CAD and LDL level less than 130 mg/dL who were randomly assigned atorvastatin at doses of 80 mg/day or 10 mg/day. They evaluated visit-to-visit LDL variability from 3 months after randomization to determine its potential impact on CV outcomes. LDL variability measurements included standard deviation, average successive variability, coefficient of variation and variation independent of mean. The primary outcome was incidence of any coronary event. Secondary outcomes were any CV event, death, MI and stroke. in the population studied, standard deviation and average successive variability were lower among those assigned atorvastatin 80 mg/day than in those assigned atorvastatin 10 mg/day (standard deviation, 12.03 ± 9.7 vs. 12.52 ± 7.43; P = .005; average successive variability, 12.84 ± 10.48 vs. 13.76 ± 8.69; P < .0001). The authors also found that each 1-unit standard deviation increase in LDL variability by average successive variability increased the risk of any coronary event by 16% on adjusted analysis (HR = 1.16; 95% CI, 1.1-1.23). They also observed increases in the risk for any CV event (HR = 1.11; 95% CI, 1.07-1.15), death (HR = 1.23; 95% CI, 1.14-1.34), MI (HR = 1.1; 95% CI, 1.02-1.19) and stroke (HR = 1.17; 95% CI, 1.04-1.31). These results were independent of treatment effect and achieved LDL levels, and were consistent after adjustment for medication adherence, according to the researchers.
April 14, 2015
Lead-free cardiac pacemaker shows good safety, performance at 1 year (LEADLESS published)
Confirming a previous report, a leadless cardiac pacemaker system demonstrated stable performance and good safety results at 1 year, according to data from the LEADLESS trial which published online in JACC. The researchers assessed 6-month and 1-year follow-up data for 31 of the 33 patients implanted with the leadless pacemaker between December 2012 and April 2013 (mean age, 76 years; 65% men). At implantation, one patient had cardiac tamponade and died due to massive cerebral artery ischemic infarct, and another required an implantable cardioverter defibrillator and underwent successful retrieval of the leadless pacemaker 7 days after implantation.
There were no pacemaker-related adverse events reported between 3 months and 1 year, the researchers wrote.
Mean pacing threshold at a 0.4-ms pulse width was 0.4 V at 6 months and 0.43 V at 1 year, R-wave amplitude was 10.6 mV at 6 months and 10.3 mV at 1 year, and impedance was 625 ohms at 6 months and 627 ohms at 1 year, according to the researchers.
At 1 year, the rate response sector was activated in 61% of patients, all of whom had an adequate rate response, the researchers found.
EMA Committee Warns of Cardiovascular Risk With High-Dose Ibuprofen
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) is warning of an increased risk of cardiovascular events in patients who take high doses of the anti-inflammatory ibuprofen. The committee, states there is a small increase in the risk of MI and stroke with ibuprofen when taken at doses of 2400 mg/day or higher. The risk, according to the committee, is similar to the risk observed with other nonsteroidal anti-inflammatory drugs (NSAIDs), such as COX-2 inhibitors and diclofenac.
The committee is recommending physicians assess patients' risk factors for cardiovascular conditions before starting them on long-term high-dose ibuprofen. Overall, PRAC says the benefits of high-dose ibuprofen outweigh the small increased risk of cardiovascular events, but physicians should use caution when prescribing and avoid high-dose ibuprofen in select patients. High doses of ibuprofen (2400 mg per day or higher) should be avoided in patients with serious underlying heart or circulatory conditions, such as heart failure, heart disease, and circulatory problems or in those who have previously had a heart attack or stroke," according to PRAC. With 1200 mg of ibuprofen, the most commonly used over-the-counter dose of ibuprofen in the European Union, there is no signal of harm, according to PRAC. The recommendations of the committee also extend to dexibuprofen, which is similar to ibuprofen. A high-dose of dexibuprofen is 1200 mg/day or more.
The recommendations of PRAC will now be sent to the Coordination Group for Mutual Recognition for Decentralized Procedures—Human (CMDh). The CMDh reviews the recommendations of PRAC and will adopt a final position.
Bivalirudin Bests Heparin for Fewer Bleeding Events During PCI (BRIGHT study)
Publication of the multicenter Chinese BRIGHT study has reopened the bivalirudin-heparin debate on treatment for patients undergoing PCI. The randomized trial showed that patients who received bivalirudin after an acute MI had significantly fewer net adverse clinical events (NACE) and bleeding events at 30 days and 1 year than those receiving heparin plus the GP IIb/IIIa inhibitor tirofiban and those receiving heparin alone.
There were no between-group differences in major cardiac events or stroke, in rates of stent thrombosis or acute stent thrombosis, or acquired thrombocytopenia.
The results, are published in the Journal of the American Medical Association.
A total of 2194 adult patients with acute MI were enrolled between August 2012 and June 2013 at 82 centers in China. All were randomly assigned to one of three treatment arms upon arrival in the cath lab for emergency PCI: bivalirudin (n=735; 82.7% men; mean age 57.3 years), heparin (n=729; 81.6% men; mean age 58.1 years), or heparin/tirofiban (n=730; 82.1% men; mean age 58.2 years).
Bivalirudin was given as a bolus of 0.75 mg/kg followed by infusion of 1.75 mg/kg/h during the PCI procedure and for at least 30 minutes but no more than 4 hours afterward. The heparin-only group received a dose of 100 U/kg; the combination group received heparin 60 U/kg and tirofiban 10 µg/kg followed by postprocedure infusions of tirofiban at 0.15 µg/kg/min for 18 to 36 hours.
NACE at 30 days' postprocedure, the primary end point, were reported for 8.8% of the bivalirudin group vs 17% of the heparin/tirofiban group (relative risk [RR] 0.52; 95% CI 0.39–0.69; P<\0.001).NACE also occurred in 13.2% of the heparin-only group (RR 0.67; 95% CI 0.50–0.90; P=0.008).
The 30-day bleeding rate occurred in 4.1% of the patients receiving bivalirudin vs 12.3% of those receiving heparin/tirofiban vs 7.5% of those receiving heparin alone.
One-year follow-up results were similar. At that time, NACE occurred in 12.8% of the bivalirudin group vs 20.5% of the heparin/tirofiban group (P <\0.001) vs 16.5% of the heparin-only group (P=0.05). Bleeding rates at 1 year were 6.3% vs 14.2% and 9.9%, respectively.
April 6, 2015
Dronedarone in Middle Age Linked to More Admissions
Treatment with dronedarone was associated with a higher risk for hospitalization than treatment with amiodarone or other antiarrhythmic drugs, in an observational study involving nongeriatric atrial fibrillation (AF) patients without cardiovascular disease, which published in the last issue of Circulation: Cardiovascular Quality and Outcomes.. In patients age 61 and younger (median age 56) , the risk of AF-related hospitalization was greater with dronedarone than Class Ic (propafenone and flecainide) drugs (hazard ratio 1.59, 95% CI 1.13-2.24), amiodarone (HR 2.63, 95% CI 1.77-3.89) and sotalol (HR 1.72, 95% CI 1.17-2.54). Cardiovascular hospitalization risk also was lower with amiodarone (HR 0.80, 95% CI 0.70-0.92) and sotalol (HR 0.63, 95% CI 0.53-0.75) compared with class Ic drugs.
The study included 8,562 AFpatients between the ages of 49 and 61 without known heart disease identified using health plan claims data. All were prescribed antiarrhythmic drugs (AADs) from the beginning of 2006 to the end of 2010.
The primary outcome was time from first prescription to AF hospitalization, and secondary outcomes were time to cardiovascular and all-cause hospitalization. Just 608 of the 8,562 study participants were treated with dronedarone, compared with 2,984 patients treated with class Ic drugs, 2,065 patients treated with Sotalol, and 2,905 patients treated with amiodarone.
Smoking linked to poor outcomes after revascularization in patients with complex CAD
Cigarette smoking was associated with adverse clinical outcomes, including recurrent MI, stroke and death, in patients with complex CAD undergoing revascularization with CABG or PCI, according to 5-year follow-up data from the SYNTAX trial in a study published online in the Journal of the American College of Cardiology. Researchers analyzed data on smoking status and history collected at baseline, 6 months, 1 year, 3 years and 5 years among participants of the SYNTAX trial (n = 1,793) who underwent CABG or PCI.
At baseline, 1 in 5 patients with complex CAD reported smoking. Of those, 60% stopped smoking after revascularization. Overall, 17.9% of patients had changes in smoking status during the 5-year follow-up.
According to the results, smoking at baseline did not influence death/MI/stroke or major adverse CV and cerebrovascular events at 5-year follow-up. However, when smoking was considered a time-dependent variable, smoking increased the risk for death/MI/stroke (HR = 1.38; 95% CI, 1.02-1.86) and major adverse cardiovascular/cerebrovascular events (HR = 1.28; 95% CI, 1.01-1.61) at follow-up. Baseline smoking status was associated with increased risk for MI, specifically. During follow-up, the effect of smoking as a time-dependent covariate was predominantly on subsequent MI (adjusted HR = 2.08; 95% CI, 1.3-3.32).
During follow-up, 98 patients reported always smoking and 1,374 reported never smoking. Risk for MI and stent thrombosis/graft occlusion was significantly higher among always smokers, but this group did not have increased risk for all-cause revascularization, compared with never smokers.
Additionally, smoking was identified as an independent predictor of death/MI/stroke (HR = 1.8; 95% CI, 1.3-2.5) and major adverse cardiovascular/cerebrovascular events (HR = 1.4; 95% CI, 1.1-1.7). In subgroup analyses, smoking independent predicted poor outcomes in patients who underwent CABG (HR = 1.52; 95% CI, 1.02-2.25) and PCI (HR = 1.26; 95% CI, 0.9-1.75).
SPYRAL HTN program to evaluate renal denervation for uncontrolled hypertension
Medtronic announced with a press release the launch of a clinical trial program that will assess the use of renal denervation in patients with uncontrolled hypertension. The SPYRAL HTN global clinical trial program comprises two prospective, randomized, sham-controlled trials: SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED. The trials will be conducted simultaneously. In both, participants will undergo renal denervation by experienced operators with the Symplicity Spyral catheter and Symplicity G3 radiofrequency generator. SPYRAL HTN-OFF MED will evaluate the impact of renal denervation on BP reduction without the use of antihypertensive medications. SPYRAL HTN-ON MED will assess renal denervation in patients with uncontrolled hypertension despite treatment with three antihypertensive medications; these drugs are not required to be prescribed at maximum tolerated medication dosages, a factor which may have contributed to variability in patient adherence and the large number of medication changes during the SYMPLICITY HTN-3 trial, according to the release.
The trials will include approximately 100 patients with moderate- to high-risk hypertension, enrolled at 20 centers worldwide.
March 23, 2015
CoreValve Bests Surgery at Two-Year Mark Data from a U.S. pivotal trial showed patients who underwent transcatheter aortic valve replacement using CoreValve had a higher two-year survival rate than those who had their valves surgically replaced. The difference in all-cause mortality between the two groups jumped from 4.8 percent at one year to 6.5 percent at the end of the second year. Patients in the TAVR arm also had a lower stroke rate than those in the control group — 10.9 percent versus 16.6 percent. The multicenter clinical trial randomized 747 patients with advanced forms of aortic stenosis to with TAVR or open-heart surgery. The patients had an estimated mortality risk of 15 percent or greater at 30 days and preexisting surgical risk factors such as frailty and disability. The FDA approved the CoreValve system last year for patients in need of aortic valve replacement who are at high or severe risk for surgery. The device is also available in countries that recognize the CE mark
Next-generation subcutaneous ICD system receives FDA approval, CE Mark Boston Scientific Corporation has received FDA and CE Mark approval of the EMBLEM™ Subcutaneous Implantable Defibrillator (S-ICD) System. The EMBLEM S-ICD System is a treatment option that provides protection for patients at risk of sudden cardiac arrest (SCA), yet leaves the heart and vasculature untouched, minimizing the risk of complications associated with conventional transvenous implantable cardioverter-defibrillators (TV-ICDs). A controlled and limited market release has begun in a small number of European centers with a broad European launch scheduled for May 2015 and subsequent U.S. launch planned for the third quarter of 2015. Unlike traditional ICDs that require placement of at least one lead in or on the heart, the S-ICD System is implanted just under the skin and provides the patient the same protection from cardiac arrest without invading the heart and blood vessels. Leads in the heart may be associated with infrequent but serious complications, including lead displacement, fracture and systemic blood infections, or the need for lead extraction, which may lead to hospital readmission, increased mortality and associated costs. The new generation EMBLEM S-ICD System is 19% thinner and is projected to last 40% longer than the previous S-ICD System. These improvements will further improve patient comfort and cosmetic outcomes while reducing the number of times the device will require replacement. The EMBLEM S-ICD System is also enabled for remote patient management through the LATITUDE™ NXT Patient Management System for increased patient convenience.
Anacetrapib lowers LDL in patients with familial hypercholesterolemia (REALIZE trial) One-year treatment with anacetrapib in patients with heterozygous familial hypercholesterolemia was well tolerated and yielded significant decreases in LDL cholesterol. For the phase 3, multicenter, double-blind, randomized, placebo-controlled REALIZE study, researchers evaluated 306 patients with a genotype-confirmed heterozygous familial hypercholesterolemia. Patients were included if they were on a therapeutic dose of statin, such as simvastatin (Zocor, Merck) 40 mg, atorvastatin 20 mg, rosuvastatin (Crestor, AstraZeneca) 5 mg, pitavastatin (Livalo, Kowa Pharmaceuticals) 4 mg, lovastatin 80 mg, or pravastatin 80 mg or higher, or one or more additional lipid-modifying drugs for 6 or more weeks prior to screening. Patients also were required to have LDL levels ≥ 2.59 mmol/L with no history of CVD, or LDL levels ≥ 1.81 mmol/L with a history of CVD. After a 2-week placebo run-in period, patients were randomly assigned 2:1 to daily anacetrapib (Merck) 100 mg (n=204) or matching placebo (n=102) for 1 year. The patients were seen for a 12-week follow-up after the conclusion of anacetrapib treatment to evaluate patient safety when off treatment. The primary efficacy endpoint was s percentage change from baseline in LDL to 1 year. At 1 year, anacetrapib decreased mean LDL levels from 3.3 mmol/L to 2.1 mmol/L (percentage change, 36%; 95% CI, – 39.5 to – 32.5) compared with an increase in LDL with placebo from 3.4 mmol/L to 3.5 mmol/L (percentage change, 3.7%; 95% CI, – 1.2 to 8.6). The difference in percentage change between anacetrapib and placebo was – 39.7% (95% CI, – 45.7 to – 33.7; P < .0001). Patients in the anacetrapib group experienced a higher number of CV events vs. those in the placebo group (4 [2%] of 203 patients vs. 0 of 102 patients; P = .1544), but the percentage of those with adverse events that prompted discontinuation was comparable (12 (6%) of 203 patients vs. 5 [5%] of 102 patients).
Smoking Worsens Outcomes for Patients Following PCI/CABG Smoking is associated with worse clinical outcomes, especially MI, following coronary revascularization, indicating that there is no "smoker's paradox" when smoking status is accounted for across time, the SYNTAX trial shows. The study was published in the last issue of the Journal of the American College of Cardiology. The SYNTAX trial was a prospective, multicenter, randomized trial that compared PCI with CABG surgery in patients with complex CAD. Complex CAD included left main stem disease, triple-vessel disease, or both. A total of 1793 patients were included in the analysis. Smoking status was ascertained for all patients at baseline and at 6 months and 1, 3, and 5 years. The study end point was the impact of smoking on a composite end point of death, MI or stroke after 5 years of follow-up. Some 20% of the cohort was smoking at baseline, but this dropped to 8.6% at 6 months and was still 8.7% at 1 year. At 5 years, smoking was associated with a 38% increased risk of the composite end point of death, MI, or stroke (hazard ratio [HR] 1.38, 95% CI 1.02–1.86; P=0.035). Smoking was also associated with a 28% increased risk of major adverse cardiac and cerebrovascular (MACCE) events (HR 1.28, 95% CI 1.01–1.61; P =0.041). Patients who always smoked had significantly higher rates of MI and stent thrombosis or graft occlusion as well, although not all-cause revascularization, compared with those who had never smoked.Subgroup analysis also showed that smoking independently increased the risk of poor outcomes by 52% in CABG patients (HR 1.52; 95% CI 1.02–2.25; P =0.038) and by 26% for PCI patients (HR 1.26, 95% CI 0.90–1.75; P=0.177). Baseline smoking status was also associated with poor outcomes.
March 16, 2015
FDA approves left atrial appendage closure device The U.S. Food and Drug Administration (FDA) approved the WATCHMAN Left Atrial Appendage (LAA) Closure Device, a first-of-its kind treatment that gives patients with non-valvular atrial fibrillation (AF) an alternative option to long-term warfarin therapy. Watchman is indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores, are deemed by their physicians to be suitable for warfarin; and have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin. The PROTECT AF trial concluded that use of the watchman device for LAA ligation is feasible among patients with nonvalvular AF. The trial demonstrated a noninferior rate of cardiovascular death, stroke or systemic embolism, compared with warfarin alone, which was sustained to five years of follow-up. The PREVAIL trial found that percutaneous closure of the LAA is feasible in patients with AF. Compared with the PROTECT AF trial, there was improved procedural implant success with reduced device-related complications.
Apixaban does not increase bleeding in patients with renal insufficiencies Compared with conventional anticoagulants, use of apixaban resulted in a lower bleeding risk in patients with mild or moderate-to-severe renal impairment, according to results of a meta-analysis published online in Am. J. Cardiol. The researchers performed a meta-analysis and systematic review to assess this risk. They included six randomized controlled trials involving 40.145 patients in their meta-analysis. The results showed that apixaban had a statistically significant lower bleeding risk in patients with mild renal impairment compared with conventional anticoagulants (vitamin K antagonist, warfarin, aspirin, placebo) (RR = 0.80; 95% CI, 0.66-0.96, I2 = 13%). The bleeding risk was similar in patients with moderate-to-severe renal insufficiency (RR = 1.01; 95% CI, 0.49-2.10, I2 = 72%). The study did not examine severe renal impairment, which may have led to underestimation of bleeding risk in the moderate-to-severe renal impairment subgroup.
One-Year, Real-World TAVR Data Help Identify Risks, Benefits In a study published in the Journal of the American Medical Association, with 12.182 patients who underwent transcatheter aortic-valve replacement (TAVR) in clinical practice in the US from November 2011 through June 30, 2013, 1 year after the procedure, 23.7% had died, 4.1% had a stroke, and 26% had either died or had a stroke. Furthermore, following TAVR, 59.8% of the patients, who had a median age of 84, went home rather than to a nursing home or extended-care facility. At 1 year, 46.8% of patients who were alive had not been hospitalized again. Being very elderly, on dialysis, with severe lung disease, or a high STS Predicted Risk of Operative Mortality (STS PROM) score was linked with a higher risk of 1-year mortality, and women who underwent TAVR had a higher risk of stroke than men. Most patients (57.4%) had STS PROM scores below 8%; 30.8% had scores between 8% and 15%; and 11.9% had scores above 15%—which indicates low risk of death from surgery, high risk of death from surgery, and inoperable, respectively. The median STS PROM score was 7.1%, which was lower than in PARTNER A and PARTNER B (11.8% and 11.2%, respectively), but similar to that in the CoreValve study (7.3%), the researchers note. Most patients were either 75 to 84 years old (38.2%) or 85 to 94 years old (47%). Only 12.7% were younger than 75 and 2.1% were 95 or older. About half were women. At 30 days after TAVR, 7% of patients had died and 2.5% had had a stroke.
Low Prevalence of Diabetes Found Among Patients With Familial Hypercholesterolemia The prevalence of type 2 diabetes among patients with familial hypercholesterolemia is significantly lower than unaffected relatives, with the prevalence varying by the type of gene mutation, according to a study published in the last issue of JAMA. Statins have been associated with increased risk for diabetes, but the cause for this is not clear. One theory is that statins increase expression of low-density lipoprotein (LDL) receptors and increase cholesterol uptake into cells including the pancreas, which could cause pancreatic dysfunction. Familial hypercholesterolemia causes decreased LDL transport into cells. Researchers have hypothesised, in patients with familial hypercholesterolemia, decreased pancreatic LDL transport would lessen cell death and ultimately lead to lower rates of diabetes. In the study was assessed the prevalence of type 2 diabetes between patients with familial hypercholesterolemia and their unaffected relatives. The study included all individuals (n = 63,320) who underwent DNA testing for familial hypercholesterolemia in the national Dutch screening program between 1994 and 2014. The prevalence of type 2 diabetes was 1.75% in patients with familial hypercholesterolemia (n = 440/25,137) versus 2.93% in unaffected relatives (n = 1,119/38,183), with adjusted figures indicating that patients with familial hypercholesterolemia had a 51% lower odds of having type 2 diabetes. Prevalence varied by the type of gene mutation. The researchers observed an inverse dose-response relationship between the severity of the familial hypercholesterolemia causing mutation and prevalence of type 2 diabetes.
March 09, 2015
Idarucizumab filed with EMA and Health Canada as Antidote for Dabigatran Boehringer has submitted BI 655075 (idarucizumab) for approval of marketing authorization to the European Medicines Agency (EMA) and Health Canada, for use in patients who require rapid reversal of the anticoagulant effect of dabigatran, the active ingredient in Pradaxa. This follows filing with the FDA. The submissions are based on the results from clinical trials of idarucizumab in volunteers, including elderly and renally impaired individuals. Phase I data showed an immediate, complete and sustained reversal of the anticoagulant effect of dabigatran following the administration of idarucizumab and no pro-thrombotic effect. The submissions also include first interim data from the ongoing RE-VERSE ADTM study. RE-VERSE ADTM is an ongoing global Phase III patient study in which Boehringer Ingelheim continues to evaluate idarucizumab in patients treated with Pradaxa who are in need of emergency intervention, or experience an uncontrolled or life-threatening bleeding event.
TAVR improves quality of life in patients at extreme surgical risk Transcatheter aortic valve replacement yielded substantial improvements in disease-specific and health-related quality of life among patients with severe aortic stenosis at extreme surgical risk, according to new data from the CoreValve U.S. Extreme Risk Pivotal Trial which published online in JACC Intrev. Journal. The new analysis characterized health status outcomes after TAVR with a self-expanding prosthesis. Researchers assessed the health status of patients at baseline and at 1, 6 and 12 months after the procedure using the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Short Form-12 and the EuroQol-5D surveys. Death, KCCQ overall summary score less than 45 or decline in KCCQ overall summary score of 10 points at 6 months indicated poor outcome after TAVR. The transfemoral approach was used in 471 patients. Of those, 93% completed the baseline health status survey, the results of which indicated considerable impairment in all health status measures at baseline. The KCCQ overall summary scores increased by 23.9 points at 1 month, 27.4 points at 6 months and 27.4 points at 12 months (P < .001 for all comparisons). Individual KCCQ subscales that measured total symptoms, physical limitations, social limitations and quality of life showed similar results. Short Form-12 physical and mental scores improved by approximately 5 points from baseline to follow-up at 6 and 12 months (P < .001 for all comparisons). Substantial increases in EuroQOL-5D utilities from baseline to follow-up at 6 and 12 months were also reported (P < .003). The proportion of patients with large KCCQ overall summary score improvement was 58% at 1 month and 59% at 12 months. The proportion of patients with an excellent outcome, defined as survival with a large improvement in KCCQ overall summary score, was 52% at 1 month and 41% at 12 months. In contrast, the proportion of patients with a poor outcome was 39% at 6 months; 22% had died and 16% had very poor quality of life. Preprocedural factors independently associated with poor outcome included wheelchair dependency, lower aortic valve gradient, previous CABG, need for home oxygen and Society of Thoracic Surgeons mortality risk greater than 15%.
Anacetrapib on Top of Optimal Therapy Provides Large LDL-Lowering Benefit in FH (REALIZE study) For patients with heterozygous familial hypercholesterolemia (FH) well treated with existing medical therapy, including high-intensity statins and ezetimibe , the addition of anacetrapib for 1 year further reduced LDL-cholesterol levels and other atherogenic lipoproteins, according to the results of REALIZE study which published in Lancet. Among 204 patients who received anacetrapib, LDL-cholesterol levels were reduced from 127 mg/dL at baseline to 81 mg/dL at 1 year. For the 102 patients who received a placebo, LDL-cholesterol levels increased slightly over the 52 weeks. Treatment with anacetrapib also resulted in a significant increase in HDL-cholesterol levels, with baseline levels doubling after 1 year of treatment (up from 54 mg/dL to 108 mg/dL). The investigators say anacetrapib was well tolerated, with no reported differences in serious adverse events, drug-related adverse events, or adverse events leading to drug discontinuation between the anacetrapib- and placebo-treated patients. The researchers did not observe any changes in blood pressure among the anacetrapib-treated patients, an off-target effect that was observed with torcetrapib. This study was not powered for changes in clinical outcomes, but they did observe a numerically higher, although statistically nonsignificant, number of cardiovascular events among the anacetrapib-treated patients. In total, four patients who received anacetrapib had an adjudicated cardiovascular event (stroke, MI, or unstable angina) vs none in the placebo arm, a finding that warrants watching, say the researchers.
Recent AF Guidelines Would Significantly Expand OAC Use An update of the guidelines for the management of patients with atrial fibrillation (AF)—one that saw a shift from the CHADS2 score to the CHA2DS2-VASc score for stroke risk assessment—significantly increases the number of patients eligible for oral anticoagulant therapy, according to the results of a new analysis published in JAMA: Internal Medicine. Using data from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), the researchers found that the overall proportion of patients recommended for oral anticoagulation increased from 71.8% under the 2011 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) guidelines to 90.8% with the 2014 AHA/ACC/HRS clinical recommendations. Using the new CHA2DS2-VASc score, researchers say that nearly every AF patient older than 65 years of age and nearly every woman with AF would be eligible for oral anticoagulation. In fact, with the 2014 recommendations guiding the management of AF, 98.5% of patients 65 years of age and older and 97.7% of women would receive a definitive recommendation for oral anticoagulant therapy.
March 02, 2015
Heart failure patients who struggle with daily tasks are hospitalised more often and die earlier Heart failure patients who struggle doing daily tasks are more likely to be hospitalised and die early, according to new research published online in the American Heart Association journal Circulation: Heart Failure. The risk is higher for older women, unmarried people and those with chronic conditions that affect mobility and ability, including obesity, dementia, anemia and diabetes, researchers said. Researchers reviewed questionnaires from 1,128 heart failure patients. Half were female, the average age was about 75, and half were married. Eighteen per cent were obese and most had other medical conditions including high blood pressure (87.4%), anemia (57%), diabetes (36.5%), peripheral vascular disease (26.5%) and cerebrovascular disease (almost 30%). Patients were grouped as having minimal, moderate or severe difficulty with daily activities that included getting dressed, using the bathroom, cleaning the house, climbing stairs and taking medications. Most patients had a hard time with at least one daily activity, but there was a corresponding relationship between how easily one could go about their day and overall mortality.
Subcutaneous-ICD patients may be able to undergo MRI scans at 1.5T safely Subcutaneous implantable cardioverter-defibrillator patients may be safe to be exposed to magnetic resonance imaging (MRI) procedures at 1.5T with a pre-specified scanning and monitoring protocol. The results of a first-of-its-kind study exploring the potential for safely imaging patients with the subcutaneous implantable cardioverter system was reported—ahead-of-print in Europace. According the authors, it is estimated that as many as 75% of active cardiac device recipients will become indicated for MRI. However, the majority of such devices are contraindicated for MRI due to potential hazards such as heating of the electrode that resides in the heart, damage to myocardium, elevation of pacing thresholds, unintended induction of ventricular tachycardia or ventricular fibrillation, pacing inhibition, permanent device malfunction, and distortion of the MRI scan. The authors note that none of the components of the S-ICD system are on or in the heart, hence heating near or around the electrode cannot harm the myocardium. However, they say, heating near the S-ICD’s electrode and can may still cause serious patient discomfort. In this single-centre prospective non-controlled study, 15 patients (12 males, mean age 53 years) were enrolled for MRI testing over a period of 18 months. They underwent a total of 22 randomised examinations, which included cardiac, brain, cervical, lumbar and knee scans. Keller et al comment that there was not a specific requirement for an MRI. The S-ICD is currently not certified for use with an MRI. For the scanning protocol, the S-ICD was programmed off to minimise the risk of inappropriate therapy and patients were monitored throughout the procedure with pulse oximetry and standard ECG to detect any arrhythmia. An external defibrillator was available. The S-ICD was evaluated prior and immediately after the scan to verify proper functioning. Patients were also asked to report immediately any pain, torqueing movement, or heating sensation in the area of pocket or electrode. They were also questioned immediately following the MRI to assess any discomfort around the can or electrode.
Tandem Troponin-BNP Readings Predict CRT Outcomes in Heart Failure Tandem measurements of cardiac troponin T (TnT) and brain-type natriuretic peptide (BNP) provide insight into how well patients scheduled for cardiac resynchronization therapy (CRT) will do at 12 months, suggests a multicenter, prospective study published online in Pacing and Clinical Electrophysiology Journal. Classification of patients into high-, intermediate-, and low-risk categories based on the initial biomarkers significantly predicted mortality and risk of heart-failure hospitalization. The study stratified 267 patients at 32 centers, prior to implantation of biventricular pacemakers with defibrillators (CRT-D), into three risk groups based on whether TnT was detectable and BNP elevated. A detectable TnT meant >0.01 ng/mL, whereas an elevated BNP was defined as >440 pg/mL. Patients were defined as high risk when they had both a detectable TnT and a high BNP; intermediate risk if they had either a detectable TnT or a high BNP and low-risk if they had an undetectable TnT and a low BNP. Most of the cohort consisted of men, their mean LVEF was 25%, and just over half had ischemic cardiomyopathy; their mean QRS interval was 155 ms. Within the first year of follow-up, there were 13 deaths and 25 first hospitalizations for heart-failure events among 19 patients. Patients in both the high and the intermediate categories of biomarker risk had significantly worse survival at 1 year than those categorized in the low-risk group (P <0.001). In the multivariate model containing risk group, age, NYHA class, ejection fraction, and QRS duration, the risk group into which patients had been initially categorized retained its independent predictive power for death or HF hospitalization, with a hazard ratio (HR) of 7.34 (95% CI 2.48–021.69) for the high-risk group compared with the low-risk group and 2.50 (95% CI 1.04–6.04) for the intermediate-risk group compared with the low-risk group (P =0.001 for both comparisons). Risk group at baseline was not associated with response to CRT or with likelihood of defibrillator shocks, the authors point out.
February 24, 2015
Dabigatran, rivaroxaban contraindicated in AF patients who are on dialysis More atrial fibrillation patients on dialysis are using dabigatran or rivaroxaban, even though these agents are contraindicated in this patient population, according to a new study published online in Circulation. Using data culled from the Fresenius Medical Care North America End-Stage Renal Disease Database (ESRD), the researchers tracked the use of dabigatran and between October 2010 and October 2014, in 29.277 patients with AF who were undergoing dialysis. In their secondary analysis, the authors followed a group of patients for 2 years to assess their bleeding and stroke outcomes. At baseline, they compared AF patients on warfarin (n = 8,064), aspirin (6,018), dabigatran (n = 281) and rivaroxaban (n = 244). Within this study group, dabigatran was first prescribed 45 days after it received FDA approval in October 2010; the first rivaroxaban prescription came 161 days after FDA approval. Over the 4-year study, 3.1% of patients received dabigatran and 2.8% received rivaroxaban. The use of both drugs increased over time. Overall, 5.9% of patients on dialysis who require anticoagulants are prescribed dabigatran or rivaroxaban. The unadjusted event rates showed that dabigatran had a major bleeding rate of 83.1 events per 100 patient years, rivaroxaban had a rate of 68.4 events, while warfarin had 35.9 events. Mortality rates from bleeding were as follows: dabigatran (19.2 deaths per 100 patient years), rivaroxaban (16.2) warfarin (10.2) and aspirin (7.7). The lowest rates for major and minor bleeding were seen in patients taking aspirin, according to the authors. Compared with warfarin, dabigatran (RR = 1.48, 95% CI, 1.21-1.81) and rivaroxaban (RR = 1.38, 95% CI 1.03-1.83) had a higher risk of major bleeding, the authors wrote. The risk of hemorrhagic death was even greater for dabigatran (RR = 1.78, 95% CI 1.18-2.68) and rivaroxaban (RR = 1.71, 95% CI 0.93-3.12) when compared with warfarin. Patients treated with aspirin had the lowest rates of major and minor bleeding and hemorrhagic death.
Concomitant percutaneous aortic balloon balvotomy plus PCI did not improve outcomes, increased costs Compared with percutaneous aortic balloon balvotomy alone, PCI plus percutaneous aortic balloon balvotomy performed during the same hospitalization was associated with similar in-hospital mortality and complication rates, but increased hospitalization costs among patients aged older than 60 years with aortic stenosis. The development of less-invasive endovascular therapies has yielded a resurgence in the utilization of percutaneous aortic balloon balvotomy (PABV) for high-risk patients as a bridge to transcatheter aortic valve replacement. Using the National Inpatient Sample database (1998-2010), researchers compared outcomes of PABV alone (n = 1,880) with concomitant PCI plus PAVB (n = 247) in a total of 2,127 procedures. The use of PCI plus PABV during the same hospitalization increased 225%, from 5.1% of PABVs in 1998 to 1999 to 16.6% of PABVs in 2009 to 2010 (P < .001). The in-hospital mortality rate was 10.3% in the PCI plus PABV group vs. 10.5% in the PABV alone group. The researchers found that increasing comorbidities (OR = 1.17; 95% CI, 1.01-1.35), unstable patient condition (OR = 6.19; 95% CI, 3.45-11.09), complications (OR = 2.81; 95% CI, 1.85-4.28) and weekend admission (OR = 2.12; 95% CI, 1.23-3.67) were significant predictors of in-hospital mortality after concomitant PCI plus PABV. The rate of in-hospital complications was also similar: 23.4% in the PCI plus PABV group vs. 24.7% in the PABV alone group. The most common complications were postprocedure respiratory failure (8.3%), vascular (7.5%) and cardiac (6.7%). Unstable patient condition was a significant predictor of increased complications (OR = 5.09; 95% CI, 2.97-8.7). While both groups had a similar length of stay, patients who underwent PCI plus PABV had higher costs of hospitalization ($30,089 vs. $18,421; P < 0.001).
No difference in treatment with antiplatelets, anticoagulants after cervical artery dissection (CADISS study) For prevention of stroke, major bleeding or death, it did not matter whether patients with cervical artery dissection were treated with antiplatelet drugs or anticoagulants, according to findings from the CADISS study which published online in Lancet Neurology. The investigators enrolled 250 patients diagnosed with cervical artery dissection (118, carotid dissection; 132, vertebral dissection) at local hospitals in the United Kingdom and Australia. Patients were randomly assigned antiplatelet agents — aspirin, dipyridamole or clopidogrel alone or in dual combination, as determined by the treating physician — or anticoagulation in the form of low–molecular-weight heparin followed by warfarin. The primary endpoint was ipsilateral stroke and death at 3 months. Four cases of ipsilateral stroke occurred: three in the antiplatelet group, one in the anticoagulant group. There was one case of major bleeding, a subarachnoid hemorrhage in the anticoagulant group. No deaths were reported during the study period. The groups did not differ in the incidence of the primary endpoint in the intention-to-treat population (OR = 0.335; 95% CI, 0.006-4.233). A central review of imaging failed to confirm dissection in 52 patients, Markus said. Therefore, the researchers conducted a per-protocol analysis of patients whose dissection was confirmed and also found no difference between the groups in the primary endpoint (OR = 0.346; 95% CI, 0.006-4.39).
February 16, 2015
Better long-term outcomes with CABG vs. PCI, regardless of diabetes status (subanalysis of CREDO-Kyoto study) At 5 years, patients with and without diabetes who had three-vessel and/or left main disease had better rates of cardiac death, MI and coronary revascularization after CABG compared with PCI according a subanalysis of CREDO-Kyoto PCI/CABG study which published online in Am. J. Cardiol. The multicenter Japanese CREDO-Kyoto PCI/CABG Registry Cohort-2 included 15,939 patients with first coronary revascularization. The current analysis focused on 3,982 patients with three-vessel and/or left main disease; 1,998 had diabetes (PCI, n = 1,065; CABG, n = 933) and 1,984 did not have diabetes (PCI, n = 1,123; CABG, n = 861). At 5 years, the cumulative incidence of all-cause mortality was higher for patients who underwent PCI compared with CABG. Among patients without diabetes, the 5-year cumulative incidence rate was 19.8% after PCI vs. 16.2% after CABG (P = 0.01). Among patients with diabetes, the 5-year cumulative incidence rate was 22.9% after PCI vs. 19% after CABG (P =0 .046). When the researchers adjusted for confounding factors, the increased mortality risk after PCI remained significant among patients with diabetes (P = 0.04), but was no longer significant among patients without diabetes (P = 0.29). Compared with CABG, PCI was associated with higher adjusted risks for cardiac death (HR = 1.45; 95% CI, 1-2.51), MI (HR = 2.31; 95% CI, 1.31-4.08) and any coronary revascularization (HR = 3.7; 95% CI, 2.91-4.69) among patients with diabetes. A similar trend was observed in favor of CABG in the patients without diabetes (cardiac death: HR = 1.59; 95% CI, 1.01-2.51; MI: HR = 2.16; 95% CI, 1.2-3.87; any coronary revascularization: HR = 3.3; 95% CI, 2.55-4.25).
Elevated circulating troponin linked to AF risk in older adults (CHS study) In ambulatory older adults, circulating troponin T levels appear to be significantly associated with incident atrial fibrillation, according to recent findings published online in Heart Rhythm Journal. In a prospective cohort study, researchers evaluated 4.262 participants in the Cardiovascular Health Study (CHS), a longitudinal analysis of adults aged 65 years or older without AF at baseline. At enrollment, participants completed a standardized questionnaire pertaining to various health and behavioral risk factors, and also underwent a physical examination. The researchers confirmed patient self-reports through baseline examination, review of medical records or surveys of treating physicians, with follow-up measurements obtained 2 to 3 years later for 2.870 patients. Patients were contacted for follow-up every 6 months after initial assessment. Incident AF was determined through ECG results, hospital discharge diagnoses and Medicare files during a median follow-up of 11.2 years. Cardiac troponin T was undetectable (< 3 ng/L) in 1,419 patients. During follow-up, incident AF occurred in 1,363 participants. Researchers observed a primarily linear association between baseline troponin levels and incident AF after adjusting for age, race, sex, AF risk factors and HF status over time, with a cutoff of 3.25 Log-ng/L, corresponding to a baseline of 24.53 ng/L (HR = 1.39; 95% CI, 1.26-1.53 per log unit increase). After adjustment for demographics, traditional risk factors and incident HF, higher baseline levels of cardiac troponin T were linked to increased risk for incident AF (HR = 1.75; 95% CI, 1.48-2.08 for third troponin T level tertile vs. undetectable levels). Further adjustment for inflammatory biomarkers and hemodynamic strain did not eliminate the significance of this association (HR = 1.38; 95% CI, 1.16-1.65).
Sleep Apnea Signals Poor Survival in Hospitalized HF Patients In a large study of patients who were hospitalized for HF, those who were newly diagnosed with sleep-disordered breathing (sleep apnea) were more likely to die within a few years compared with their peers. Specifically, the hazard ratio for all-cause mortality within 3 years of hospital discharge was 1.57 (95% CI 1.1–2.2; P=0.01) for HF patients with sleep apnea, after adjustment for multiple variables, in this study , published online in the European Heart Journal. Sleep-apnea treatment may improve HF outcomes, and patients who received adequate sleep-apnea treatment appeared to have better short-term survival, but this observational study was not designed to address this, they caution. The researchers performed cardiorespiratory polygraphy on 1117 patients who were hospitalized for heart failure with LVEF <45% in a single center. The screening test detected sleep apnea in 78% of the HF patients: 344 patients (31%) had central sleep apnea and 525 patients (47%) had obstructive sleep apnea. It is important to distinguish between the two types of apnea, since treatment is usually different, according to the authors. In obstructive sleep apnea, the airway collapses on inspiration, whereas in central apnea, patients lose the drive to breathe Compared with the patients without sleep apnea, those with sleep apnea were older (mean age of 60 vs 55) and more likely to be male (77% vs 56%). Of the 1096 patients in the current study who survived until hospital discharge, 110 patients with central sleep apnea (34%), 153 patients with obstructive sleep apnea (32%), and 40 patients without sleep apnea (17%) died within 3 years, mostly from congestive HF. Sleep apnea independently predicted the risk of death during follow-up.
February 9, 2015
Long-term nitrates do not improve prognosis in patients with vasospastic angina Chronic use of nitrate therapy in combination with calcium channel blockers was not associated with improved long-term prognosis in patients with vasospastic angina according a multicenter study published online in Eur. Heart Journal. In the study were included 1.429 patients diagnosed with vasospastic angina between April 2003 and December 2008. Treatment decisions for vasospastic angina were made at the discretion of the attending physicians. Nitrates used included nitroglycerin, isosorbide mononitrate and isosorbide dinitrate and nicorandil. In total, 49% of the cohort received chronic nitrate therapy. Concomitant calcium channel blockers were used in more than 90% of patients who received or did not receive nitrate therapy. Propensity score matching for the entire population identified 413 matched pairs of patients. There were no significant differences in baseline variables for the propensity-matched population. The primary endpoint was major adverse cardiac events, including death, nonfatal MI, hospitalization due to unstable angina and HF/appropriate ICD shocks. All-cause mortality was the secondary endpoint. During a median follow-up of 32 months, primary endpoint occurred in 5.9% of patients. Based on the propensity score-matched analysis, the cumulative incidence of major adverse cardiac events was similar between patients who received chronic nitrate therapy and those who did not (11% vs. 8%, respectively, at 5 years; HR = 1.28; 95% CI, 0.72-2.28). Nicorandil monotherapy was associated with a neutral prognostic effect on vasospastic angina outcomes (HR = 0.8; 95% CI, 0.28-2.27). However, a multivariable Cox model showed a possible hazard with the simultaneous use of conventional nitrates plus nicorandil (HR = 2.14; 95% CI, 1.02-4.47), particularly simultaneous use of nitroglycerin and nicorandil.
High-dose atorvastatin reduced peripheral artery disease (PAD) incidence in post-MI patients (IDEAL sudy) In patients with previous MI, therapy with high-dose atorvastatin significantly decreased the incidence of peripheral arterial disease compared with moderate-dose simvastatin, according to data from the IDEAL study. Further, patients with a history of PAD at baseline had greater risk for future CV events, but this risk was lowered with high-dose atorvastatin. The prospective, randomized, open-label, blinded–outcome-assessment trial compared atorvastatin 80 mg/day (n=4,439) with simvastatin 20 mg/day to 40 mg/day (n=4,449; Zocor, Merck) in patients aged 80 years and older with previous MI. Follow-up occurred at 12 and 24 weeks and then every 6 months. At 24 weeks, simvastatin dose could be increased to 40 mg/day if plasma total cholesterol was greater than 190 mg/dL. Atorvastatin dose could be decreased to 40 mg/day if adverse events were observed. The prespecified outcome was incident PAD. Among patients without PAD at baseline, this outcome was defined as a new clinical diagnosis necessitating diagnostic procedures or interventions. In patients with a history at baseline, this outcome was defined as recurrence of PAD requiring hospitalization. An exploratory post-hoc analysis examined the effect of baseline PAD on clinical outcomes and the benefits of high-dose vs. usual-dose statin treatment. The primary outcome for this analysis was the rate of major coronary events (coronary death, hospitalization for nonfatal MI or cardiac arrest with resuscitation). During a median follow-up of 4.8 years, incident PAD was reported in 2.2% of the high-dose atorvastatin group vs. 3.2% of the moderate-dose simvastatin group (HR = 0.7; 95% CI, 0.53-0.91). Patients with PAD at baseline had an almost twofold greater risk for major coronary events; however, this trend did not persist after researchers adjusted for adverse CV risk profile. Among patients with PAD, major coronary events were less common in the high-dose atorvastatin group (14.4% vs. 20.1%; HR = 0.68; 95% CI, 0.41-1.11). Treatment with high-dose atorvastatin yielded significant decreases in overall CV (P = .046) and coronary events (P = .007) as well as need for coronary revascularization (P = .007).
Left atrial appendage closure reduces burden in nonparoxysmal AF Left atrial appendage closure appears to reduce the burden of nonparoxysmal atrial fibrillation, according to recent findings of a study published in Heart Rhythm Journal. In this prospective, multicenter observational study, researchers evaluated 50 consecutive patients with nonvalvular AF and cardiac implantable electronic devices who underwent left atrial appendage (LAA) closure with the LARIAT device . The patients were enrolled from July 2010 to April 2013. Eligible patients were aged at least 18 years, had at least one risk factor for embolic stroke and were considered poor or ineligible candidates for warfarin therapy. The mean age of the patient population was 70 ± 8.4 years, and the mean duration of AF was 54 ± 40 months. All patients were followed up at three and 12 months after the LARIAT procedure. At baseline and at each follow-up visit, interrogation of cardiac implantable electronic devices was conducted to ascertain AF burden, with the devices reset at each visit to determine burden during the intervening period. Medication lists were also updated at each visit to safeguard the stability of antiarrhythmic drug regimens. Compared with the baseline AF burden of 76% ± 33%, the burden at 3 months was significantly decreased (42% ± 34%; P < .0001). This reduction persisted at the 12-month follow-up (59% ± 26%; P < .001). Results from subgroup analysis indicated a similar decrease in AF burden between patients with paroxysmal AF (n = 19) and nonparoxysmal AF (n = 31) at 3 months. At the 12 month follow-up, the decreased AF burden persisted among those with non-paroxysmal AF, but not those with paroxysmal AF. In the nine patients for whom LAA was due to triggered activity/atrial tachycardia, the AF burden was significantly decreased at 3 (52% ± 35%) and 12 months (42% ± 19%) compared with baseline (84 ± 31%, P < .0001 for both comparisons). The researchers also noted that the reduction to AF burden was significantly lower among three patients who had incomplete LAA closure at both follow-up visits.
February 2, 2015
New permanent pacemaker implantation after TAVR linked to worse clinical outcomes In the PARTNER trial and registry, 8.8% of patients who underwent transcatheter aortic valve replacement with a balloon-expandable valve required new permanent pacemaker implantation. In those patients, new permanent pacemaker implantation was associated with higher rates of repeat hospitalization and mortality at 1 year and a longer duration of hospitalization. Researchers evaluated 1,973 patients without a prior pacemaker who underwent TAVR with a balloon-expandable valve in the PARTNER trial and registry. The goal was to identify predictors and clinical implications of new permanent pacemaker implantation after TAVR. Predictors of permanent pacemaker implantation included right bundle branch block (OR=7.03; 95% CI, 4.92-10.06), prosthesis diameter/left ventricular outflow diameter (OR for each 0.1 increment=1.29; 95% CI, 1.1-1.51), LV end-systolic diameter (OR for each 1 cm=0.68; 95% CI, 0.53-0.87) and treatment in the continued access registry (OR=1.77; 95% CI, 1.08-2.92), according to results of a multivariable analysis. Patients who required permanent pacemaker implantation had a longer mean duration of postprocedure hospitalization compared with those who did not require a pacemaker (7.3 days vs. 6.2 days; P=.001), according to the researchers. At 1 year, compared with no pacemaker, patients who required a permanent pacemaker had higher rates of repeat hospitalization (23.9% vs. 18.2%; P=.05) and higher mortality/repeat hospitalization (42% vs. 32.6%; P=.007), the researchers wrote. However, there was no significant difference between the groups in all-cause mortality at 1 year (26.3% vs. 20.8%; P=.08). The researchers also reported no between-group differences in LV ejection fraction at 1 year.
CABG linked to better outcomes than PCI, but at higher price Patients who underwent CABG had improved outcomes at 4 years but at a higher overall cost compared with PCI, according to results of a cost-effectiveness analysis of the ASCERT study which published online in JACC. The cost-effectiveness analysis used data from the Society of Thoracic Surgeons and American College of Cardiology Foundation databases, which were linked to CMS claims data, and included 86,244 patients who underwent CABG and 103,549 who underwent PCI for stable ischemic heart disease. All patients were older than 65 years and had two- or three-vessel CAD. Researchers assessed costs for the index and observation periods (2004-2008) using diagnosis-related group Medicare reimbursement rates. Costs after the observation period were estimated from average Medicare participant per capita expenditure, according to the abstract. Patients who underwent CABG gained an adjusted average of 0.2525 life-years during the observation period and 0.3801 life-years during a lifetime relative to PCI, according to the results. Compared with PCI, CABG yielded higher adjusted costs for the index hospitalization ($10,670), study period ($8,145) and lifetime ($11,575). The researchers calculated that the lifetime incremental cost-effectiveness ratio of CABG vs. PCI was $30,454 quality-adjusted life-years (QALY) gained.
Morphine associated with delayed antiplatelet activity in patients with STEMI Use of morphine delayed the onset of action of antiplatelet agents in patients with STEMI who were undergoing PCI, according the results from a study published online in Circ. Cardiov. Interv. The study included 300 patients undergoing PCI who were receiving loading doses of prasugrel (n=95; Effient, Eli Lilly/Daiichi Sankyo) or ticagrelor (n=205; Brilinta, AstraZeneca). After the loading dose, all patients had their platelet reactivity assessed by VerifyNow. The researchers hypothesized that there was a potential drug-drug interaction between the currently recommended antiplatelet therapies and morphine in this patient population. Ninety-five patients (32%) also received morphine. Those patients had a higher incidence of vomit compared with patients who did not receive morphine (15% vs. 2%; P=.001). Two hours after the loading dose, P2Y12 reactivity unit was 187 in patients who received morphine compared with 133 in patients who did not receive morphine (P<.001). This difference in P2Y12 reactivity units persisted after the researchers excluded patients with vomit (P<.0001), according to the results. Also at 2 hours, the researchers observed high residual platelet reactivity (P2Y12 reactivity units ≥208) in 53% of patients who received morphine compared with 29% in patients who did not receive morphine (P<.001). No difference was reported based on prasugrel or ticagrelor use, according to the results. Morphine use (OR=2.91; 95% CI, 1.71-4.97) and age (OR=1.03; 95% CI, 1.01-1.05) were identified as independent predictors of high residual platelet reactivity at 2 hours. After the researchers performed propensity score adjustment, the association between morphine and high residual platelet reactivity persisted.
January 26, 2015
Benefit of paclitaxel-coated balloon maintained at 5 years (THUNDER study) Use of a paclitaxel-coated balloon was associated with reduced late lumen loss, binary stenosis and target lesion revascularization at 5-year follow-up according the results of THUNDER study which published in JACC Interventions. Researchers for the THUNDER trial reported 5-year follow-up data on patients with femoropopliteal arteries that were treated with paclitaxel-coated balloons (PCB), angioplasty with paclitaxel in contrast medium or no paclitaxel. The primary outcome of the trial was late lumen loss at 6 months. Freedom from TLR, binary restenosis rate and amputation served as secondary endpoints. The present study evaluated outcomes in patients treated with PCB vs. control, and analyzed late lumen loss at 6 months and TLR up to 5 years based on sex and lesion length. According to the results, the cumulative incidence of TLR was significantly lower in the PCB group compared with the control group during the 5-year follow-up (21% vs. 56%; P=.0005). The researchers also examined patients with angiographic and duplex sonographic follow-up at 5 years (n=31). In those patients, the binary restenosis rate was lower for the PCB group compared with the control group (17% vs. 54%; P=.04). Eight of 54 evaluable patients (15%) died between 24 months and 5 years (12.5% of control group, 16.7% of PCB group). Late lumen loss at 6 months was significantly lower in the PCB group (0.4 ± 1.2 mm vs. 1.7 ± 1.8 mm; P<.001). At 12 months, mean late lumen loss was determined in 69% of the PCB group and 67% of the control group. TLR was performed before 12-month re-angiography in two patients in the PCB group and 14 in the control group. The researchers reported a significant difference in favor of the PCB group (0.7 ± 1.5 mm vs. 1.9 ± 1.9 mm; P=.01). Analysis by sex revealed a similar rate of late lumen loss at 6-month follow-up between men and women in the control group (1.76 mm vs. 1.61 mm) and PCB group (0.42 mm vs. 0.37 mm). However, at 5 years, the cumulative rate of TLR was lower after treatment with a PCB in men compared with women (17% vs. 38%). The cumulative 5-year TLR rate in the control group was higher for men (71% vs. 52%).
Statin therapy benefited real-world patients with heart failure with reduced EF Statin use was associated with improved survival in a registry population of patients with HF with reduced ejection fraction in a study published in Circulation Heart Failure. Previously, statin use was not associated with improved outcomes in patients with HF with reduced ejection fraction (HFrEF) in randomized controlled trials, but the issue had not been studied in an unselected population, or studied in relation to ischemic heart disease, according to the study background. Researchers for the new study analyzed 21,684 patients from the Swedish Heart Failure Registry with HFrEF (mean age, 72 years; 29% women). The cohort included 47% who were treated with statins. The researchers estimated propensity scores for treatment with statins for each patient; 42 baseline characteristics served as independent variables and statin treatment served as the dependent variable. Association between statin use and outcomes were assessed in a 1:1 population match based on propensity score and age. The primary outcome was all-cause mortality. Secondary outcomes included CV mortality, hospitalization for HF and combined all-cause mortality or CV hospitalization. In the matched population, 1-year survival was better for patients treated with statins (83% vs. 79%; HR=0.81; 95% CI, 0.76-0.86). The same was true in the unmatched population after adjustment for propensity score and age (statin group, 85%; no-statin group, 79%; HR=0.84; 95% CI, 0.8-0.89). Survival rates also were higher at 3 years for patients treated with statins (unmatched population, 68% vs. 60%; matched population, 65% vs. 58%) and 5 years (unmatched population, 53% vs. 48%; matched population, 51% vs. 45%). Ischemic heart disease was the only baseline variable that interacted with statin use (P=.001). According to the researchers, patients with ischemic heart disease had better survival rates if on statin treatment (HR=0.76; 95% CI, 0.7-0.82), but statin use did not affect survival rates in those without ischemic heart disease (HR=0.95; 95% CI, 0.85-1.07). Statin use was also associated with lower CV mortality (HR=0.8; 95% CI, 0.75-0.87), HF hospitalization (HR=0.92; 95% CI, 0.86-0.97) and all-cause mortality plus CV hospitalization (HR=0.9; 95% CI, 0.86-0.95), according to the results.
ACC announces late-breaking clinical trials slated for presentation at annual meeting The American College of Cardiology has announced the line-up of late-breaking clinical trials and featured clinical research at the Annual Scientific Session and Expo, held March 14 to 16 in San Diego. According to the ACC, the meeting will highlight five late-breaking clinical trial sessions; two featured clinical research sessions; a “Deep Dive” session to address key elements of the late-breaking clinical trials and implications for patients and practice; and much more. Some of the late-breaking clinical trials slated for presentation include: PROMISE: A randomized comparison of anatomic vs. functional strategies for diagnostic testing in symptomatic patients with suspected CAD. PEGASUS-TIMI 54: A randomized comparison of ticagrelor vs. placebo on a background of aspirin for the prevention of CV events in patients with prior MI. OLSER-1 and 2: Two trials designed to assess the impact of evolocumab on CV outcomes. REGULATE-PCI: A randomized comparison of the REG1 anticoagulation system vs. bivalirudin in patients undergoing PCI. 5-year outcomes of the PARTNER 1 trial, which assessed transcatheter vs. surgical aortic valve replacement. 2-year outcomes of the CoreValve US Pivotal High Risk Trial, which compared self-expanding transcatheter and surgical aortic valve replacement in patients with severe aortic stenosis at high surgical risk. BEST: A comparison of everolimus-eluting stents and bypass surgery in patients with multivessel CAD. Other research scheduled for presentation during featured clinical research sessions include an assessment of dual antiplatelet therapy for longer than 1 year among patients with ACS treated with coronary stents; additional data from IMPROVE-IT on the effect of ezetimibe and simvastatin vs. simvastatin alone on CV events after ACS; the AUGMENT-HF trial of the Algisyl-LVR device with standard medical therapy among patients with advanced HF.
January 19, 2015
Macitentan linked to decreased hospitalization risk in npatients with pulmonary hypertension (SERAPHIN stydy) Treatment with a 10 mg dose of macitentan significantly decreased the risk for and prevalence of all-cause hospitalization among patients with symptomatic pulmonary arterial hypertension, according to findings from the SERAPHIN study which published in JACC Heart Failure Journal. This decrease was driven by a reduction in the risk and rate of hospitalizations due to pulmonary arterial hypertension (PAH) specifically according to the authors. In a multicenter, double-blind, event-driven phase 3 trial, researchers randomly assigned 742 patients aged 12 years or older with symptomatic PAH to receive placebo (n=250), macitentan 3 mg (n=250) or macitentan 10 mg (n=242) once daily until a patient experienced a primary endpoint event or a total of 285 events had occurred across the population (median 115 weeks). The researchers assessed the effects of both macitentan (Opsumit, Actelion Pharmaceuticals) doses on the risk for, rate and duration of all-cause and PAH-specific hospitalization compared with placebo. The effect on the risk for and causes of non-PAH-related hospitalizations were also evaluated. Patients were collected from a total of 151 centers across 39 countries. The cohort was 76.5% female and had a mean age of 45.6 ± 16.1 years. In the 3 mg macitentan group, researchers observed a nonsignificant decrease in the risk for all-cause hospitalization (HR=0.911; 95% CI, 0.623-1.057), while the all-cause hospitalization rate was significantly reduced by 20.5% compared with placebo (P=.0378). The mean number of hospital days for all-cause hospitalization was also 30.6% lower in this group (P=.0278) vs. placebo recipients. Risk for PAH-specific hospitalization was 42.7% lower in the 3 mg group (HR=0.573; 95% CI, 0.405-0.811), while the hospitalization rate was 44.5% lower (P=.0004) and the mean number of PAH-related hospital days decreased by 53.3% (P=.0001) compared with placebo. In the 10 mg macitentan group, risk for all-cause hospitalization was significantly lower (HR=0.677; 95% CI, 0.514-0.891), and researchers also noted a significant 33.1% reduction in the rate of all-cause hospitalization (P=.0005) compared with placebo. The mean number of hospital days decreased by 31% (P=.0336). Risk for PAH-specific hospitalization decreased by 51.6% among these patients (HR=0.484; 95% CI, 0.337-0.697), while the hospitalization rate decreased by 49.8% (P<.0001) and the number of PAH-related days in hospital were reduced by 52.3% (P=.0003) compared with placebo.
Antidote to novel oral anticoagulant ( Factor Xa inhibitors) met primary endpoint (ANNEXA-R study) It was announced the topline results of the phase 3 ANNEXA-R study demonstrating that andexanet alfa, an antidote to the anticoagulant effects of Factor Xa inhibitors, met the primary endpoint with high statistical significance. IV bolus of andexanet alfa was associated with significant and immediate reversal of the anticoagulant activity of rivaroxaban in the first part of the ANNEXA-R study. Andexanet alfa also was well tolerated. The first part of this study included 41 healthy volunteers aged 50 to 75 years who received 20 mg once-daily rivaroxaban for 4 days followed by random assignment to placebo (n=14) or an 800 mg IV bolus of andexanet alfa (n=27). The primary endpoint was anti-Factor Xa levels. It is expected that the full data set will presented at the American College of Cardiology Scientific Sessions in March. The second, ongoing part of the ANNEXA-R study will include 40 healthy volunteers who will receive 20 mg once-daily rivaroxaban for 4 days and will then be randomly assigned to placebo or an 800 mg IV bolus of andexanet alfa followed by a continuous infusion of 8 mg/min for 120 minutes. Data from the second part of this study are anticipated in mid-2015.
Biomarker May Predict Best Smoking Cessation Treatment A genetic biomarker may help predict response to specific smoking cessation treatments, new research published online in Lancet Respiratory Medicine suggests. A multicenter, randomized controlled trial (RCT) of more than 1200 smokers showed that those who had a normal nicotine metabolite ratio had significantly higher quit rates after receiving varenicline for 11 weeks than those receiving a nicotine patch. Although for those who metabolized nicotine slowly, the efficacy of both treatments was equivalent, there were significantly more overall side effects with varenicline. The investigators note that because effectiveness and adverse effects vary widely among pharmacotherapies for treating tobacco dependence, they wanted to examine whether biomarkers in individual smokers could improve outcomes. "The NMR reflects the activity of the liver enzyme CYP2A6, the major nicotine-metabolizing and cotinine-metabolizing enzyme," the researchers report, adding that NMR also reflects both environmental and genetic effects ― unlike CYP2A6 genotyping. The RCT included 1246 adult smokers seeking treatment at one of four North American sites between November 2010 and September 2014. NMR status was determined at baseline through blood samples; 662 of the participants were found to be slow metabolizers of nicotine, and 584 found to be normal metabolizers. The slow metabolizers were less likely than normal metabolizers to be white (P < .0001) and more likely to be male (P = .001), younger (P = .02), and to smoke fewer cigarettes per day (P < .001). Results showed that normal metabolizers had more success with varenicline than with the patch at end of treatment (odds ratio [OR], 2.17; 95% confidence interval, 1.38 - 3.42; P = .001) and 6 months later (OR, 1.81; 95% CI, 1.05 - 3.11; P = .03). Quit rates at end of treatment in this group were 38.5% and 22.5%, respectively; at 6 months, the rates were 22.0% and 13.6%. There was no difference between varenicline and patch for the slow metabolizers at any time point. Although the quit rates were 30.4% and 27.7%, respectively, at end of treatment and 19.1% and 21.6, respectively, at 6 months, these were not significant. However, according to NMR-by-treatment interactions, for the slow metabolizers, side effects were more severe overall with varenicline than with placebo (P = .04). These differences included increases in nausea (P = .0003) and abnormal dreams (P = .005). The NMR-by-treatment interaction was not significant for side effects from the patch vs placebo. Finally, the number needed to treat was 4.9 for varenicline and 26.0 for nicotine patch in the normal metabolizers and 8.1 vs 10.3 in the slow metabolizers
January 12, 2015
Hospital-acquired infections after cardiac surgery linked to cost, length of stay, readmission Hospital cost, length of stay and readmissions were strongly associated with hospital-acquired infections following cardiac surgery, according to data from a new study published in JACC. In this study was investigated the cost associated with major types of hospital-acquired infections within 2 months after cardiac surgery. The researchers prospectively collected data from an observational study in which patients (n=4,320; mean age, 64 years; 66% men) were monitored for infection for 65 days after cardiac surgery, and merged that data with routinely collected financial data. The 2.8% of patients experienced a major hospital-acquired infection during index hospitalization. The most common major infections were pneumonia (48%), sepsis (20%) and Clostridium difficile colitis (18%). The estimated annual cost associated with an infection was $38,000, with 47% of that amount related to ICU services, according to the researchers. They found that on average, the length of stay of patients who had a major hospital-acquired infection was 14 days longer than those who did not. They also found that of the 849 readmissions in the study population, 8.7% were related to major hospital-acquired infections. The cost of readmissions due to infection was approximately threefold higher than the cost of readmissions due to other reasons, according to the researchers.
Niacin lowered PCSK9 levels Niacin is associated with a reduction in PCSK9 levels, according to a new study published in Am. J. Cardiol and this association could help explain how niacin reduces LDL, and could offset increases in PCSK9 levels associated with other lipid-lowering therapies. The researchers conducted three studies to determine the dose-dependence effects of statins on PCSK9 levels, to assess the effect of a fibrate on PCSK9 levels when added to a statin, and to investigate the impact of niacin on PCSK9 levels on the background of statin and/or fibrate therapy. In the first study, 74 people with hyperlipidemia were randomly assigned atorvastatin 10 mg/day, atorvastatin 80 mg/day or placebo for 16 weeks. They found that PCSK9 levels were increased in a dose-dependent fashion with statin therapy compared with placebo (placebo, mean increase 7%; 95% CI, –7 to 21; atorvastatin 10 mg/day, mean increase 19%; 95% CI, –5 to 42; atorvastatin 80 mg/day, mean increase 27%; 95% CI, 12-42; P=.02 vs. placebo). In the second study, 70 patients with carotid atherosclerosis were randomly assigned simvastatin 20 mg/day, simvastatin 80 mg/day or simvastatin 20 mg/day plus extended-release niacin 2 g/day for 12 months. The researchers found that PCSK9 levels increased with statin therapy (simvastatin 20 mg/day, mean change 13%; 95% CI, –14 to 40; simvastatin 80 mg/day, mean change 41%; 95% CI, 27-76; P<.0001), but that PCSK9 decreased with combination simvastatin/niacin therapy (mean change –13%; 95% CI, –3 to –23). In a third, open-label lipid kinetics study, 19 people with dyslipidemia were treated with atorvastatin 10 mg/day for 4 weeks, followed by the addition of fenofibric acid 135 mg/day for 8 weeks, and then the further addition of extended-release niacin 2 g/day for 10 weeks. Adding fenofibric acid led to a 23% (95% CI, 10-36) increase in PCSK9 (P=.001), but the addition of niacin resulted in a subsequent 17% (95% CI, –19 to –5) decrease in PCSK9 (P=.004), according to the researchers. They also found a positive association between changes in PCSK9 levels and changes in LDL levels (P=.006) induced by the addition of niacin.
Elevated blood glucose linked to early death, other events in patients with acute HF Slight elevation in blood glucose was associated with early mortality, future diabetes and future hospitalization among patients with acute HF, even those without diabetes, in a recent study published in Eur. Heart J. In a competing-risk analysis, the researchers evaluated 30-day mortality, new diabetes diagnoses and hospitalization outcomes in a population-based cohort of 16,524 patients (median age, 79 years; 49% men) who presented with acute HF in Ontario, Canada, between 2004 and 2007. Patients were stratified by concentration of blood glucose at presentation: 3.9 mmol/L to 6.1 mmol/L, >6.1 mmol/L to 7.8 mmol/L, >7.8 mmol/L to 9.4 mmol/L, >9.4 mmol/L to 11.1 mmol/L and >11.1 mmol/L. Evaluated outcomes included death at 30 days and 1 year after presentation, CV readmissions, HF readmissions, diabetes-related hospitalizations among patients with pre-existing diabetes and new diabetes diagnoses in those without pre-existing diabetes. Among 9.275 patients without diabetes, blood glucose >6.1 mmol/L at presentation was associated with increased risk for all-cause mortality (HR range=1.26 [95% CI, 1.05-1.5] to 1.5 [95% CI, 1.11-2.02]) and CV-related death (HR range=1.28 [95% CI, 1.03-1.59] to 1.64 [95% CI, 1.16-2.33]). Among 7,249 patients with diabetes, blood glucose >11.1 mmol/L at presentation was associated with increased risk for all-cause mortality (HR=1.48; 95% CI, 1.1-2) and diabetes-related hospitalization (HR=1.39; 95% CI, 1.2-1.61). In all patients, blood glucose >9.4 mmol/L at presentation was associated with increased risk for HF- or CV-related hospitalization (HR range=1.09 [95% CI, 1.02-1.17] to 1.15 [95% CI, 1.07-1.24)]. Among those without diabetes at baseline, the risk for diagnosis of incident diabetes increased with the level of blood glucose at presentation (HR range=1.61 [95% CI, 1.39-1.87] for >6.1-7.8 mmol/L to 3.61 [95% CI, 2.78-4.68] for >11.1 mmol/L).
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