Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial
Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(08)61170-8
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发表时间：
2008-09-06
期刊：
影响因子：
168.9
通讯作者：
Ferrari, Roberto
中科院分区：
文献类型：
--
作者：
Fox, Kim;Ford, Ian;Ferrari, Roberto
背景：伊夫拉定特异性地抑制窦房结的i-f电流以降低心率，而不影响心功能的其他方面。我们的目的是测试使用伊夫拉定降低心率是否可以降低冠心病和左心室收缩功能不全患者的心血管死亡和发病率。在一项随机、双盲、安慰剂对照、平行组试验中，我们招募了10 917名符合条件的冠心病患者，他们的左心室射血分数低于40%。5479名患者接受了5毫克的伊夫拉定治疗，意图增加到每天两次7.5毫克的目标剂量，5438名患者在适当的心血管药物的基础上接受了匹配的安慰剂。主要终点是因急性心肌梗死入院的心血管死亡，以及因新发或恶化的心力衰竭入院的患者。我们根据治疗意向对患者进行了分析。这项研究在ClinicalTrials.gov上注册，编号为NCT00143507。研究发现，基线时的平均心率为每分钟71.6次(SD 9.9)。中位随访期为19个月(IQR 16~24)。伊夫拉定在12个月时使心率降低6次/分(S E0.2)，校正后为安慰剂。大多数(87%)患者在研究药物的同时还接受了β受体阻滞剂的治疗，没有发现安全问题。伊夫拉定不影响主要的复合终点(危险比1.00，95%可信区间0.91比1。1，p=0。94)。1233(22.伊夫拉定组患者发生严重不良事件的比例为5%，对照组为1239例(22.8%)(p=0.70)。在心率为70次/分或更高的预先指定的亚组患者中，伊夫拉定治疗不影响主要的综合结果(风险比0。91，95%可信区间0。81-1.04，p=0.17)，心血管疾病死亡，或因新发或恶化的心力衰竭入院治疗。然而，它确实减少了次要终点：因致命性和非致命性心肌梗死入院(0。，95%可信区间0。49比0。84，p=0。001)和冠状动脉血运重建(0。70，95%可信区间为0。伊夫拉定对心率的解释减慢并不能改善所有稳定性冠状动脉疾病和左心室收缩功能不全患者的心脏结局，但可以用于降低心率在70 bprn或更高的一组患者的冠状动脉疾病结局的发生率。
Background Ivabradine specifically inhibits the I-f 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 12473 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-tip was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (S E 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. 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 prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect 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 bprn or greater.Funding Servier, France.