|Year : 2016 | Volume
| Issue : 3 | Page : 118-120
Alok Kumar Singh
Department of Cardiology, Heritage Hospital, Varanasi, Uttar Pradesh, India
|Date of Web Publication||16-Sep-2016|
Alok Kumar Singh
Department of Cardiology, Heritage Hospital, Varanasi, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Singh AK. Journal watch. Heart India 2016;4:118-20
DANISH Trial  - Defibrillator implantation in patients with nonischemic systolic heart failure
The benefit of an implantable cardioverter defibrillator (ICD) in patients with symptomatic systolic heart failure caused by ischemic cardiomyopathy has been well established. However, the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is due to nonischemic cardiomyopathy has been based primarily on subgroup analyses. The management of heart failure has improved over the last two decades because of introduction of life-saving medical therapy and cardiac resynchronization therapy (CRT).
In this trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.
After a follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68-1.12; P = 0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31-0.82; P = 0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P = 0.29). The final conclusion of this trial was prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care.
The ANNEXA Trial:  The efficacy and safety of andexanet for the reversal of factor Xa inhibitors
Till date, there is no specific antidote which can rapidly reverse the anticoagulation of factor Xa (FXA) inhibitors in patients who have bleeding or need emergency surgery. Andexanet is a recombinant modified human FXA decoy protein. It is catalytically inactive but can bind FXA inhibitors and neutralize the anticoagulant effects of both direct and indirect FXA inhibitors. In patients with atrial fibrillation who were receiving FXA inhibitors, major bleeding occurs at an annualized rate of 2-3%. Patients receiving FXA inhibitors may also need emergency surgery. The ANNEXA-A and ANNEXA-R (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA inhibitors Apixaban (ANNEXA-A) and Rivaroxaban (ANNEXA-R) trials investigated the efficacy and safety of andexanet for the reversal of anticoagulant effects of apixaban or rivaroxaban in healthy volunteers.
The study enrolled 145 healthy individuals 50-75 years of age and randomly assigned them in a 3:1 ratio (ANNEXA-A) or a 2:1 ratio (ANNEXA-R) to receive andexanet or placebo. Each study had two consecutive parts. The researchers examined the intravenous (IV) andexanet bolus alone in part 1 and the IV bolus plus a continuous 120-min infusion in part 2.
Among participants treated with apixaban, anti-FXA activity was reduced by 94% in the andexanet group as compared with 21% in the placebo group (P < 0.001); unbound apixaban concentration was reduced by 9.3 ng/ml versus 1.9 ng/ml (P < 0.001); and thrombin generation was fully restored in 100% versus 11% of the participants (P < 0.001) within 2-5 min when andexanet was administered as a bolus alone.
Among participants treated with rivaroxaban, anti-FXA activity was reduced by 92% in the andexanet group as compared with 18% in the placebo group (P < 0.001); unbound apixaban concentration was reduced by 23.4 ng/ml versus 4.2 ng/ml (P < 0.001); and thrombin generation was fully restored in 96% versus 11% of the participants (P < 0.001) within 2-5 min when andexanet was administered as a bolus alone. The results were similar when andexanet was administered as a bolus plus an infusion. No serious adverse events were observed.
In summary, andexanet rapidly reverse the effects of FXA inhibitors.
Norwegian Coronary Stent Trial (NORSTENT)  - drug-eluting or bare-metal stents for coronary artery disease
The development of percutaneous coronary intervention (PCI) revolutionized the treatment of obstructive coronary artery disease by creating a less invasive revascularization option to coronary artery bypass grafting. In this study from eight centers in Norway, during a 29-month period, 12,425 met the study eligibility criteria, and 9013 (72.5%) were randomly assigned to receive either contemporary drug-eluting stents or bare-metal stents. After a median of 5 years of follow-up, there were neither significant between-group differences in the primary composite outcome of death from any cause or nonfatal spontaneous myocardial infarction nor differences in the individual end-points of death, myocardial infarction, stroke, or hospitalization for unstable angina. The use of bare-metal stents remains an important option for PCI in some patients, including those with a large vessel diameter in whom restenosis rates are low, 7 those who cannot complete the longer duration of dual-antiplatelet therapy recommended for drug-eluting stents because of noncompliance or need for noncardiac surgery, those who cannot afford for drug-eluting stents or history of recent bleeding.
The Sleep Apnea Cardiovascular End-points Trial  - continuous positive airway pressure for prevention of cardiovascular events in obstructive sleep apnea
Obstructive sleep apnea has been associated with an increased risk of cardiovascular disease.  Continuous positive airway pressure (CPAP) is frequently prescribed in patients with obstructive sleep apnea and is effective in reversing hypoxemia and upper airway obstruction. Authors of this trial randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end-point was death from cardiovascular causes, myocardial infarction, stroke or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end-points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. After a mean follow-up of 3.7 years, the primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% CI, 0.91-1.32; P = 0.34). No significant effect on any individual or other composite cardiovascular end-point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood.
Leader Trial  - Liraglutide and cardiovascular outcomes in Type 2 diabetes
The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analog, when added to standard care in patients with Type 2 diabetes, remains unknown. In this double-blind trial, authors randomly assigned patients with Type 2 diabetes and high-cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% CI of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. A total of 9340 patients underwent randomization. The median follow-up was 3.8 years.
The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% CI, 0.78-0.97; P < 0.001 for noninferiority; P = 0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66-0.93; P = 0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74-0.97; P = 0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The overall conclusion of the study was, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with Type 2 diabetes mellitus was lower with liraglutide than with placebo.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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