Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Maggioni, Aldo P.; Greene, Stephen J.; Fonarow, Gregg C.; Böhm, Michael; Zannad, Faı̈ez; Solomon, Scott D.; Lewis, Eldrin F.; Baschiera, Fabio; Hua, Tsushung A.; Gimpelewicz, Claudio; Lesogor, Anastasia; Gheorghiade, Mihai; Coordinators,

doi:10.1093/eurheartj/eht342

Cited by 53 publications

(43 citation statements)

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“…In our trial, patients with diabetes had the treatment stopped prematurely because of regulatory concern about the safety of aliskiren added to an ACE inhibitor in such persons. [15][16][17][18][19] Because of this, we revised our statistical analysis plan to prespecify examination of the effect of combination therapy, as compared with enalapril alone, in patients without diabetes. 13 This analysis showed the same effect of combination therapy as in the trial overall.…”

Section: Discussionmentioning

confidence: 99%

“…13 This intervention was based on the findings of possible harm from aliskiren in patients with diabetes in two other trials (ASTRONAUT and ALTITUDE). 15,16,19 Our trial included a large proportion of patients with diabetes, who had exposure to aliskiren for a median of 24 months despite truncated followup. We did not identify worse outcomes in the patients with diabetes who were treated with combination therapy than in those who were treated with enalapril alone.…”

Section: Discussionmentioning

confidence: 99%

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Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure

et al. 2016

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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, ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure

et al. 2016

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“…More complete renin-angiotensin-aldosterone system blockade in certain HF subgroups has been met with excess complications. 28 It was not possible to compare intermediate and high dose or drugs, and similarly, the studies did not randomized patients to low dose versus placebo. We also did not have access to individual participant data for each study, and thus, we could not estimate study-specific hazard ratio unless reported for the study.…”

Section: Discussionmentioning

confidence: 99%

Dose of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Outcomes in Heart Failure

Khan

Fonarow

Ahmed

et al. 2017

Circ: Heart Failure

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BACKGROUND:The association between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) doses on outcomes in patients with heart failure (HF) with reduced ejection fraction is uncertain. The objective of this study was to investigate the effect of dose of ACEI and ARBs on outcomes and drug discontinuation in patients with HF with reduced ejection fraction. METHODS AND RESULTS:MEDLINE, Ovid SP, and Embase were searched from the inception of these databases till August 2016. Randomized controlled trials that compared high doses of ACEI or ARB against low doses among patients with HF with reduced ejection fraction were included. Pooled analysis was done using a random-effects model, and quality of the studies was assessed by JADAD scale. The main outcomes were all-cause mortality and drug discontinuation. A total of 6 studies (4841 patients in low-dose and 4330 patients in highdose groups) were included. Compared with low dose, high-dose ACEI or ARBs decreased all-cause mortality modestly (relative risk, 0.94; 95% confidence interval (CI), 0. CONCLUSIONS:In patients with HF with reduced ejection fraction, compared with lower doses, higher doses of ACEI and ARB significantly though modestly improved the composite end point of all-cause mortality or HF hospitalization without significantly increasing the chances of discontinuation.

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“…The risk of all-cause mortality with aliskiren significantly decreased at 12 months in nondiabetic patients; these same patients experienced less adverse events from aliskiren. 28 A similar adverse event profile of aliskiren in diabetic patients was seen in another trial in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. 29 These latter investigators concluded that there was no role for aliskiren in patients with type 2 diabetes mellitus; this caveat is likely applicable to the majority of patients with HF and diabetes mellitus as well.…”

Section: Aliskirenmentioning

confidence: 53%