Candesartan is beneficial in heart failure with mildly reduced ejection fraction

Objective of the post-hoc analysis

The CHARM study included 7598 patients with symptomatic heart failure across the entire spectrum of ejection fraction (EF). Treatment with candesartan resulted in a significant reduction in the risk of the primary endpoint, which included death from CV causes or hospitalization for heart failure, compared to placebo in patients with EF < 0.40. This post-hoc analysis tested the hypothesis that candesartan could also be beneficial in patients with mildly reduced EF. Patients were divided into groups with HFrEF, HFmrEF, and preserved ejection fraction (HFpEF > 0.50).

Findings

The number of patients with HFmrEF (n = 1322) accounted for 17% of the total CHARM study population. During an average follow-up of 2.9 years, the incidence of the primary endpoint was 15.9 in the HFrEF group, 8.5 in the HFmrEF group, and 8.9 in the HFpEF group per 100 patient-years.

The therapeutic effect of candesartan in terms of the incidence of the primary endpoint represented a significant 18% risk reduction in patients with HFrEF (14.4 vs. 17.5 per 100 patient-years; hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.75–0.91; p < 0.001) and a 24% reduction in patients with HFmrEF (7.4 vs. 9.7 per 100 patient-years; HR 0.76; 95% CI 0.61–0.96; p = 0.02). In patients with HFpEF, the risk reduction with candesartan compared to placebo was not statistically significant (8.6 vs. 9.1 per 100 patient-years; HR 0.95; 95% CI 0.79–1.14; p = 0.57).

The authors also compared the incidence of recurrent hospitalizations for heart failure. Candesartan significantly reduced this risk compared to placebo in patients with HFrEF by 32% (HR 0.68; 95% CI 0.58–0.80; p < 0.001) and by 52% in patients with HFmrEF (HR 0.48; 95% CI 0.33–0.70; p < 0.001). In patients with HFpEF, the risk reduction was not significant (HR 0.78; 95% CI 0.59–1.03; p = 0.08).

Conclusion

According to this post-hoc analysis of the CHARM study, treatment with candesartan reduces the risk of death from CV causes or hospitalization for heart failure in patients with ejection fraction up to 0.49.

(zza)

Source: Lund L. H., Claggett B., Liu J. et al. Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. Eur J Heart Fail 2018; 20 (8): 1230–1239, doi: 10.1002/ejhf.1149.