Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial

Edimar Alcides Bocchi, Salvador Rassi, Guilherme Veiga Guimarães, Argentina, Chile, and Brazil SHIFT Investigators, Edimar Alcides Bocchi, Salvador Rassi, Guilherme Veiga Guimarães, Argentina, Chile, and Brazil SHIFT Investigators

Abstract

Aims: The SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients.

Methods and results: SHIFT was a randomized, double-blind, placebo-controlled trial in symptomatic systolic stable HF, HR ≥ 70 b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta-blocker. ChD HF presented a poor prognosis (all-cause mortality at 2 years was ~60%). The mean twice-daily dose of ivabradine was 6.26 ± 1.15 mg and placebo 6.43 ± 1.55 mg. Ivabradine reduced HR from 77.9 ± 3.8 to 62.3 ± 10.1 b.p.m. (P = 0.005) and improved functional class (P = 0.02). A trend towards reduction in all-cause death was observed in ivabradine arm vs. placebo (P = 0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope.

Conclusions: ChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit-risk profile in ChD HF patients.

Keywords: Chagas disease; Chagasic cardiomyopathy; Heart failure; Heart rate; Ivabradine; SHIFT trial.

© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Heart rate at baseline and during the follow‐up in patients with Chagas disease heart failure treated with ivabradine and placebo (with intra‐group paired t‐test P value).
Figure 2
Figure 2
New York Heart Association functional class at baseline and during the follow‐up in patients with Chagas disease heart failure treated with ivabradine and placebo (χ2 test).
Figure 3
Figure 3
Death and hospitalization events in overall patients with Chagas disease heart failure. (A) Kaplan–Meier survival curves free of any cause of death. (B) Kaplan–Meier survival curves free of death or hospitalization due to heart failure.
Figure 4
Figure 4
Kaplan–Meier cumulative event curves for patients with Chagas disease heart failure. (A) Kaplan–Meier cumulative event curves for death of any cause (with P values). (B) Kaplan–Meier cumulative event curves for SHIFT primary endpoint (cardiovascular death or hospitalization due to worsening heart failure).

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Source: PubMed

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