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  1. Alistair Lindsay, Editor

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BEAUTIFUL: no go for go slow with ivabradine?

Ivabradine is a pure heart-rate-lowering agent that is a specific inhibitor of the If current in the sinoatrial node; currently it is licensed for the treatment of angina. The BEAUTIFUL (morBidity–mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left-ventricULar dysfunction) trial aimed to determine if heart rate lowering with ivabradine could reduce cardiovascular death and mortality in patients with stable coronary artery disease and impaired systolic function (<40%), as several studies have demonstrated that a high heart rate is an independent predictor of both cardiovascular and all-cause mortality.

A total of 10 917 eligible patients were enrolled in a randomised, double-blind, placebo-controlled, parallel-group manner. Of these, 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to their other cardiac drugs. The primary end point was a composite of cardiovascular death, and admission to hospital for new-onset or worsening heart failure.

Mean (SD) heart rate at baseline was 71.6 (9.9) bpm; over a median follow-up of 19 months ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Of note, 87% patients were concomitantly taking β blockers, but no safety concerns were noted. Ivabradine did not affect the primary composite end point (hazard ratio (HR) = 1.00, p = 0.94), and 1233 patients (22.5%) in the treatment group had serious events, compared with 1239 (22.8%) in the control group (p = 0.17). Treatment did reduce the secondary end points of non-fatal myocardial infarction (HR = 0.64, p = 0.001) and coronary revascularisation (HR = 0.70, p = 0.016).

Thus although the study failed to reach its primary outcome, the data acquired seem to demonstrate the safety of giving ivabradine, even in combination with a β blocker. Although a direct comparison between these two drugs would …

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