Bangalore Sripal, Fakheri Robert, Wandel Simon, Toklu Bora, Wandel Jasmin, Messerli Franz H
New York University School of Medicine, New York, NY, USA
New York University School of Medicine, New York, NY, USA.
BMJ. 2017 Jan 19;356:j4. doi: 10.1136/bmj.j4.
To critically evaluate the efficacy of renin angiotensin system inhibitors (RASi) in patients with coronary artery disease without heart failure, compared with active controls or placebo.
Meta-analysis of randomized trials.
PubMed, EMBASE, and CENTRAL databases until 1 May 2016.
Randomized trials of RASi versus placebo or active controls in patients with stable coronary artery disease without heart failure (defined as left ventricular ejection fraction ≥40% or without clinical heart failure). Each trial had to enroll at least 100 patients with coronary artery disease without heart failure, with at least one year's follow-up. Studies were excluded if they were redacted or compared use of angiotensin converting enzyme inhibitors with angiotensin receptor blockers. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, incident diabetes, and drug withdrawal due to adverse effects.
24 trials with 198 275 patient years of follow-up were included. RASi reduced the risk of all cause mortality (rate ratio 0.84, 95% confidence interval 0.72 to 0.98), cardiovascular mortality (0.74, 0.59 to 0.94), myocardial infarction (0.82, 0.76 to 0.88), stroke (0.79, 0.70 to 0.89), angina, heart failure, and revascularization when compared with placebo but not when compared with active controls (all cause mortality, 1.05, 0.94 to 1.17; P=0.006; cardiovascular mortality, 1.08, 0.93 to 1.25, P<0.001; myocardial infarction, 0.99, 0.87 to 1.12, P=0.01; stroke, 1.10, 0.93 to 1.31; P=0.002). Bayesian meta-regression analysis showed that the effect of RASi when compared with placebo on all cause mortality and cardiovascular mortality was dependent on the control event rate, such that RASi was only beneficial in trials with high control event rates (>14.10 deaths and >7.65 cardiovascular deaths per 1000 patient years) but not in those with low control event rates.
In patients with stable coronary artery disease without heart failure, RASi reduced cardiovascular events and death only when compared with placebo but not when compared with active controls. Even among placebo controlled trials in this study, the benefit of RASi was mainly seen in trials with higher control event rates but not in those with lower control event rates. Evidence does not support a preferred status of RASi over other active controls.
与活性对照或安慰剂相比，严格评估肾素血管紧张素系统抑制剂（RASi）在无心力衰竭的冠心病患者中的疗效。
随机试验的荟萃分析。
截至2016年5月1日的PubMed、EMBASE和CENTRAL数据库。
在无心力衰竭（定义为左心室射血分数≥40%或无临床心力衰竭）的稳定冠心病患者中，RASi与安慰剂或活性对照的随机试验。每项试验必须纳入至少100例无心力衰竭的冠心病患者，且随访至少一年。如果研究被编辑或比较了血管紧张素转换酶抑制剂与血管紧张素受体阻滞剂的使用，则排除该研究。结局指标为死亡、心血管死亡、心肌梗死、心绞痛、中风、心力衰竭、血运重建、新发糖尿病以及因不良反应停药。
纳入了24项试验，随访时间共198275患者年。与安慰剂相比，RASi降低了全因死亡率（率比0.84，95%置信区间0.72至0.98）、心血管死亡率（0.74，0.59至0.94）、心肌梗死（0.82，0.76至0.88）、中风（0.79，0.70至0.89）、心绞痛、心力衰竭和血运重建的风险，但与活性对照相比则未降低（全因死亡率，1.05，0.94至1.17；P = 0.006；心血管死亡率，1.08，0.93至1.25，P < 0.001；心肌梗死，0.99，0.87至1.12，P = 0.01；中风，1.10，0.93至1.31；P = 0.002）。贝叶斯荟萃回归分析表明，与安慰剂相比，RASi对全因死亡率和心血管死亡率的影响取决于对照事件发生率，即RASi仅在对照事件发生率高的试验中（每1000患者年>14.10例死亡和>7.65例心血管死亡）有益，而在对照事件发生率低的试验中则不然。
在无心力衰竭的稳定冠心病患者中，RASi仅与安慰剂相比时可降低心血管事件和死亡风险，与活性对照相比则不然。即使在本研究的安慰剂对照试验中，RASi的益处主要见于对照事件发生率较高的试验，而在对照事件发生率较低的试验中则未观察到。证据不支持RASi相对于其他活性对照具有优先地位。
