Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial

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To evaluate clinical profiles and outcomes in patients with systolic heart failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (heart rate-lowering agent) with respect to diabetic status.

Methods and results

This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with systolic HF, left ventricular ejection fraction ≤35%, and resting heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07–1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13–1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23–1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced 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. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo.


Comorbid diabetes in chronic HF worsens the prognosis of systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients.

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