Impact of age on clinical outcomes and response to serelaxin in patients with acute heart failure: An analysis from the RELAX-AHF-2 trial

Abstract

Aims: Acute heart failure (AHF) is a major cause of hospitalizations and death in the elderly. However, elderly patients are often underrepresented in randomized clinical trials. We analysed the impact of age on clinical outcomes and response to treatment in patients enrolled in Relaxin in Acute Heart Failure (RELAX-AHF-2), a study that included older patients than in previous AHF trials.

Methods and results: The RELAX-AHF-2 randomized patients admitted for AHF to infusion of serelaxin or placebo. We examined the association of pre-specified clinical outcomes and treatment effect according to age categories [(years): <65 (n = 1411), 65-74 (n = 1832), 75-79 (n = 1222), 80-84 (n = 1156) and ≥85 (n = 924)]. The mean age of the 6545 patients enrolled in RELAX-AHF-2 was 73.0 ± 11 years. The risk of all-cause and cardiovascular (CV) death (all p < 0.001) as well as the composite endpoint of CV death or heart failure/renal failure rehospitalization through 180 days (p = 0.002) and hospital discharge through day 60 (p = 0.013) were all directly associated with age categories. Age remained independently associated with outcomes after adjustment for clinical confounders and the results were consistent when age was analysed continuously. No clinically significant change in treatment effects of serelaxin was observed across age categories for the pre-specified endpoints (interaction p > 0.05).

Conclusion: Elderly patients are at higher risk of short- and long-term CV outcomes after a hospitalization for AHF. Further efforts are needed to improve CV outcomes in this population.

Keywords: Acute heart failure; Age; Comorbidities; Serelaxin.

Figure 1

Cumulative incidence curves of each endpoint and stacked bar chart for length of in‐hospital stay across age categories. CI, confidence interval; CV, cardiovascular; HF, heart failure; HR, hazard ratio; RF, renal failure.

Figure 2

Continuous association of age (hazard ratio [line] and 95% confidence intervals [shaded area]) for each endpoint. CV, cardiovascular; HF, heart failure; RF, renal failure.

Figure 3

Forest plots of treatment effect of serelaxin versus placebo for each endpoint, according to age categories. CI, confidence interval; CV, cardiovascular; HF, heart failure; HR, hazard ratio; RF, renal failure.