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

Abstract

AimsThe 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 resultsSHIFT 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.ConclusionsChD 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.

Chagas Disease and Heart Failure: An Expanding Issue Worldwide

“…A subanalysis of the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) reported that ivabradine was effective in reducing heart rate in ChCM and improving functional class, suggesting that ivabradine may have a favourable benefit-risk profile in this population. [85] Specific drugs to eliminate the parasite or its reactions and non-pharmacological or invasive therapies are explained in the following section.…”

Efficacy of ivabradine for heart failure

“…Previous clinical studies have reported that ivabradine can effectively treat patients with HF. [15–27] However, no systematic review has been conducted to assess its efficacy and safety for HF according to the current available published trials. Thus, in the present study, we will systematically investigate the efficacy and safety of ivabradine for patients with HF.…”

Post hoc analyses of SHIFT and PARADIGM‐HF highlight the importance of chronic Chagas' cardiomyopathy Comment on: “Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial” by Bocchi et al.

“…We read with interest the report by Bocchi and colleagues of their post hoc analysis of the Systolic Heart failure treatment with the I f inhibitor ivabradine Trial (SHIFT), examining the effect of study drug in the 38 patients with chronic chagasic cardiomyopathy (CCC). 1 The authors reported that study drug lowered heart rate and improved New York Heart Association class. The sample size was too small to allow estimation of the effect of treatment on mortality or hospitalization.…”