血管疾病 29463 例患者中依那普利为基础的 ACEI 方案治疗效果与β受体阻滞剂使用的关系： ADVANCE、EUROPA 和 PROGRESS 试验个体数据的联合分析。
The Treatment Effect of an ACE-Inhibitor Based Regimen with Perindopril in Relation to Beta-Blocker use in 29,463 Patients with Vascular Disease: a Combined Analysis of Individual Data of ADVANCE, EUROPA and PROGRESS Trials.
机构信息
Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
Institut CŒUR Poumon, Lille, France.
出版信息
Cardiovasc Drugs Ther. 2017 Aug;31(4):391-400. doi: 10.1007/s10557-017-6747-9.
INTRODUCTION
In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking.
METHODS
In this retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke.
RESULTS
The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71-0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65-0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68-0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75-1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use.
CONCLUSIONS
These data suggest that the beneficial cardioprotective effects of perindopril treatment are additive to the background beta-blockers use.
简介
在日常实践中，血管紧张素转换酶抑制剂和β受体阻滞剂是心血管疾病患者的基石治疗方法。缺乏明确的数据来评估这些药物联合使用对发病率和死亡率的影响。
方法
在这三个大型培哚普利预后试验（ADVANCE、EUROPA、PROGRESS）的回顾性汇总分析中，对 29463 例血管疾病患者的临床结局进行了评估。对随机接受培哚普利治疗方案或安慰剂的患者进行多变量 Cox 回归分析（治疗效果），并根据背景β受体阻滞剂治疗情况对数据进行分层。主要终点是心血管死亡率、非致死性心肌梗死和卒中的复合终点。
结果
在平均 4.0 年（标准差 1.0）的随访中，β受体阻滞剂/培哚普利组（9.6%；545/5700 例）的主要终点累积发生率明显低于β受体阻滞剂/安慰剂组（11.8%；676/5718 例）（p<0.01）。与安慰剂相比，在现有的β受体阻滞剂治疗基础上加用培哚普利可使主要终点的相对风险降低 20%（风险比（HR）0.80；95%置信区间（CI）0.71-0.90），非致死性心肌梗死降低 23%（HR 0.77；95%CI 0.65-0.91），全因死亡率降低 22%（HR 0.78；95%CI 0.68-0.88）。与安慰剂相比，卒中的治疗获益无显著差异（HR 0.93；95%CI 0.75-1.15）。当根据基线高血压进一步分层数据时，主要终点和心血管终点仍有显著治疗获益。然而，仅在使用背景β受体阻滞剂的高血压患者中观察到死亡率获益。
结论
这些数据表明，培哚普利治疗的有益心脏保护作用与背景β受体阻滞剂的使用具有相加作用。
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