Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure

Abstract

Enlighten -Research publications by members of the University of Glasgow http://eprints.gla.ac.ukT h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 374;16 nejm. BACKGROUNDAmong patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODSAfter a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTSAfter a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P = 0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P = 0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONSIn patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. 1522T h e ne w e ngl a nd jou r na l o f m e dicine A ngiotensin-converting-enzyme (ACE) inhibitors are effective in lowering the risks of death and hospitalization among patients with chronic heart failure and reduced ejection fraction.1,2 As a consequence, there has been interest in other approaches to interruption of the renin-angiotensin system in patients with heart failure. Angiotensin-receptor blockers (ARBs) were the first alternative tested, and in one placebo-controlled trial, candesartan was associated with lower risks of death from cardiovascular causes and hospitalization for heart failure among patients who could not take ACE inhibitors.3 However, in a head-to-head comparison, losartan was not as effective as captopril. 4 The combination of an ARB and an ACE inhibitor has also been examined in two trials involving patients with heart failure. 5,6 In both trials, the addition of an ARB to standard therapy with an ACE inhibitor was associated with a lower risk of hospitalization for heart failure than was standard therapy alone and, in one trial, with a lower risk of death from cardiovascular causes. Neither trial, ...

Eligibility of sacubitril–valsartan in a real‐world heart failure population: a community‐based single‐centre study

“…Looking at other recent major heart failure studies, we can easily observe that the population is younger than our population. The SHIFT study had a mean age of 60.4 years,22 and the ATMOSPHERE study had a mean age of 63.3 years 23. Overall, few clinical trials include persons > 80 years,18, 24, 25 and there is a general problem with clinical studies where patients need to be selected for appropriateness by the individual investigator.…”

Rationale and design of TRANSITION: a randomized trial of pre‐discharge vs. post‐discharge initiation of sacubitril/valsartan

“…Nevertheless, there is a remarkable lack of evidence regarding the optimal management of patients after haemodynamic stabilization following hospitalization for AHF. The landmark studies in HF have predominantly recruited ambulatory patients with chronic ‘stable’ HF 45, 46, 47, 48, 49, 50. The PARADIGM‐HF trial established sacubitril/valsartan as a new evidence‐based therapy in patients with chronic HF, but in common with other major studies, it enrolled patients who were ambulatory at the time of inclusion 38.…”

A 2016-ban publikált új ESC szívelégtelenség irányelv krónikus szívelégtelenség diagnózisára és kezelésére vonatkozó ajánlásai

“…A direkt renin-inhibitor aliskirennel végzett vizsgálatok először akut szívelégtelenségben (ASTRO-NAUT) (23), majd krónikus szisztolés szívelégtelen-ségben is sikertelennek bizonyultak (ATMOSPHERE) (24). A 2016. áprilisban publikált ATMOSPHERE-vizsgálatban (24) sem az aliskiren sem az enalapril+alis-kiren kombináció nem bizonyult non-inferiornak az enalaprilhoz képest.…”