Komajda M. Eur J Heart Fail. 2015 Dec;17(12):1294-301.
SHIFT (Systolic Heart failure treatment with the If inhibitor Ivabradine Trial), exhibited that in patients with chronic systolic HF in sinus rhythm with heart rate ≥70 bpm, Ivabradine, a heart rate-reducing agent, substantially decreased cardiovascular (CV) death or hospitalization for worsening HF vs. placebo. The main results of SHIFT indicated that Ivabradine substantially declines the risk of HF-related consequences in HF patients with left ventricular systolic dysfunction. Komajda M et al., conducted a study to analyse the clinical profiles and consequences of SHIFT patients with or without diabetes, and the efficacy and safety of Ivabradine was explored with respect to diabetic status.
In SHIFT, a randomized controlled trial, patients with sinus rhythm with systolic HF, left ventricular ejection fraction ≤35%, and resting heart rate ≥70 b.p.m were enrolled. Patients were randomly assigned to Ivabradine (titrated to 7.5 mg bid) or placebo. Medical history at baseline indicated diabetic status. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. From the 6505 patients, 30% had diabetes, 32% of whom utilized insulin. The PCE was more common in patients with diabetes i.e. in hospitalization for worsening HF, and was increased in patients treated with insulin.
Ivabradine substantially decreased the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68–0.94 and HR 0.84, 95% CI, 0.75–0.95, respectively; interaction p was non-significant) vs. placebo. Relative reductions in hospitalisation for worsening HF in Ivabradine-treated patients with diabetes was 29% and Ivabradine-treated patients without diabetes was 23% (p ≤0.001). (Figure 1)
Figure 1: Kaplan–Meier curves of the primary composite endpoint, cardiovascular mortality or hospitalization for worsening heart failure, in patients with a history of diabetes mellitus (A) and those without a history of diabetes mellitus (B)
In patients without diabetes, Ivabradine consequentially decreased the relative risks of CV hospitalisation and all-cause hospitalization by 14% (p=0.007) and 12% (p=0.010), respectively, vs. placebo. In patients with diabetes, Ivabradine substantially reduced CV hospitalization and total HF hospitalization by 17% (p=0.011) and 27% (p=0.010).
It was concluded that comorbid diabetes in chronic HF intensifies the prognosis of systolic HF patients, especially if insulin-treated. Independent of the diabetic status of these patients, ivabradine is safe and effective in their administration.
CI: Confidence Interval; HR: Hazard Ratio
