发布日期：2016-05-22
英文标题：
Chronic exposure to ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post-hoc analysis of SHIFT.
作者：Michel Komajda et al.
出处：Eur J Heart Fail. 2016 Sep;18(9):1182-9.
内容介绍：SHIFT 研究共入选了 6558 例窦性心律 HR ≥ 70bpm，LVEF ≤ 35% 的慢性心衰患者，分析了心衰入院患者长期使用伊伐布雷定后的再住院风险。结果显示，在心衰标准治疗基础上联合伊伐布雷定，心血管死亡或再入院的发生风险较安慰剂组显著下降 18%，这一下降趋势在加用伊伐布雷定治疗的 3 个月后即开始显现，并持续至研究结束。对于住院后的心衰患者，在出院早期阶段尽管接受标准治疗，仍存在较高的再住院风险。
摘要展示：
Background: Ivabradine specifi cally inhibits the If current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction.
Methods: Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries.We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 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 appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death,admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507.
Findings: Mean heart rate at baseline was 71·6 (SD 9·9) beats per minute (bpm). Median follow-up was 19 months (IQR 16–24). Ivabradine reduced heart rate by 6 bpm (SE 0·2) at 12 months, corrected for placebo. Most (87%) patients were receiving β blockers in addition to study drugs, and no safety concerns were identifi ed. Ivabradine did not affect the primary composite endpoint (hazard ratio 1·00, 95% CI 0·91–1·1, p = 0·94). 1233 (22·5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22·8%) controls (p = 0·70). In a prespecifi ed subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not aff ect the primary composite outcome (hazard ratio 0·91, 95% CI 0·81–1·04, p = 0·17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0·64, 95% CI 0·49–0·84, p = 0·001) and coronary revascularisation (0·70, 95% CI 0·52–0·93, p = 0·016).
Interpretation: Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.
