心率作为慢性心力衰竭的危险因素（SHIFT）：一项随机安慰剂对照试验中心率与结局的关系。

Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial.

机构信息

Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.

出版信息

Lancet. 2010 Sep 11;376(9744):886-94. doi: 10.1016/S0140-6736(10)61259-7.

DOI:10.1016/S0140-6736(10)61259-7

PMID:20801495

Abstract

BACKGROUND

Raised resting heart rate is a marker of cardiovascular risk. We postulated that heart rate is also a risk factor for cardiovascular events in heart failure. In the SHIFT trial, patients with chronic heart failure were treated with the selective heart-rate-lowering agent ivabradine. We aimed to test our hypothesis by investigating the association between heart rate and events in this patient population.

METHODS

We analysed cardiovascular outcomes in the placebo (n=3264) and ivabradine groups (n=3241) of this randomised trial, divided by quintiles of baseline heart rate in the placebo group. The primary composite endpoint was cardiovascular death or hospital admission for worsening heart failure. In the ivabradine group, heart rate achieved at 28 days was also analysed in relation to subsequent outcomes. Analysis adjusted to change in heart rate was used to study heart-rate reduction as mechanism for risk reduction by ivabradine directly.

FINDINGS

In the placebo group, patients with the highest heart rates (>or=87 beats per min [bpm], n=682, 286 events) were at more than two-fold higher risk for the primary composite endpoint than were patients with the lowest heart rates (70 to <72 bpm, n=461, 92 events; hazard ratio [HR] 2.34, 95% CI 1.84-2.98, p<0.0001). Risk of primary composite endpoint events increased by 3% with every beat increase from baseline heart rate and 16% for every 5-bpm increase. In the ivabradine group, there was a direct association between heart rate achieved at 28 days and subsequent cardiac outcomes. Patients with heart rates lower than 60 bpm at 28 days on treatment had fewer primary composite endpoint events during the study (n=1192; event rate 17.4%, 95% CI 15.3-19.6) than did patients with higher heart rates. The effect of ivabradine is accounted for by heart-rate reduction, as shown by the neutralisation of the treatment effect after adjustment for change of heart rate at 28 days (HR 0.95, 0.85-1.06, p=0.352).

INTERPRETATION

Our analysis confirms that high heart rate is a risk factor in heart failure. Selective lowering of heart rates with ivabradine improves cardiovascular outcomes. Heart rate is an important target for treatment of heart failure.

FUNDING

Servier, France.

摘要

背景

静息心率升高是心血管风险的一个标志物。我们推测，心率也是心力衰竭患者发生心血管事件的一个风险因素。在 SHIFT 试验中，慢性心力衰竭患者接受了选择性降低心率药物伊伐布雷定的治疗。我们旨在通过研究该患者人群中心率与事件之间的关联来检验我们的假设。

方法

我们分析了这项随机试验安慰剂组（n=3264）和伊伐布雷定组（n=3241）的心血管结局，根据安慰剂组中基线心率的五分位数进行分组。主要复合终点是心血管死亡或因心力衰竭恶化而住院。在伊伐布雷定组中，还分析了 28 天时达到的心率与随后的结局之间的关系。使用调整心率变化的分析来研究伊伐布雷定通过降低心率直接降低风险的机制。

结果

在安慰剂组中，心率最高的患者（>或=87 次/分钟[bpm]，n=682，286 例事件）发生主要复合终点的风险是心率最低的患者（70 至<72 bpm，n=461，92 例事件）的两倍多（危险比[HR] 2.34，95%置信区间 1.84-2.98，p<0.0001）。与基线心率相比，心率每增加 1 次，主要复合终点事件的风险就增加 3%，每增加 5 bpm，风险就增加 16%。在伊伐布雷定组中，28 天时达到的心率与随后的心脏结局之间存在直接关联。治疗 28 天时心率低于 60 bpm 的患者在研究期间发生主要复合终点事件的人数较少（n=1192；事件发生率 17.4%，95%置信区间 15.3-19.6），而心率较高的患者则较多。通过调整 28 天时的心率变化，伊伐布雷定的治疗效果得到中和，表明心率降低是伊伐布雷定疗效的主要决定因素（HR 0.95，0.85-1.06，p=0.352）。