Thomopoulos Costas, Parati Gianfranco, Zanchetti Alberto
aDepartment of Cardiology, Helena Venizelou Hospital, Athens, Greece bDepartment of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano IRCCS cDepartment of Health Sciences, University of Milan Bicocca dScientific Direction, Istituto Auxologico Italiano IRCCS eCentro Interuniversitario di Fisiologia Clinica e Ipertensione, University of Milan, Milan, Italy.
J Hypertens. 2015 Feb;33(2):195-211. doi: 10.1097/HJH.0000000000000447.
In 68 randomized controlled trials (RCTs), blood pressure (BP) lowering was obtained by using drugs of different classes. We have investigated whether BP lowering by any of the major drug classes is effective in reducing the cardiovascular outcomes.
A total of 55 RCTs (19,5 267 individuals) were suitable for drug-class meta-analyses. Risk ratios and their 95% confidence intervals of seven fatal and nonfatal outcomes were estimated by a random-effects model.
Twelve RCTs (48, 898 patients) compared a diuretic with no treatment. SBP/DBP differences of about -12/-5 mmHg were accompanied by significant reductions of all outcomes, including mortality. The same results were obtained by limiting analyses to eight RCTs using low-dose diuretics. Separate analyses for thiazides, chlorthalidone and indapamide (all low dose) showed each subclass was associated with significant reduction of some major outcome. Five RCTs (18 ,724 patients; SBP/DBP difference -10.5/-7 mmHg) showed beta-blockers significantly reduced stroke, heart failure and major cardiovascular events. In RCTs comparing calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) with placebo smaller SBP/DBP differences were achieved, mostly because in the majority of these later RCTs the antihypertensive drug and placebo were added on a background treatment with other antihypertensive agents. Nonetheless, significant reductions of stroke, major cardiovascular events, cardiovascular and all-cause death were obtained with calcium antagonists (10 RCTs, 30, 359 patients); stroke, coronary heart disease, heart failure and major cardiovascular events by ACE inhibitors (12 RCTs, 35, 707 patients); and stroke, heart failure and major cardiovascular events by ARBs (13 RCTs, 65, 256 patients).
BP lowering by all classes of antihypertensive drugs is accompanied by significant reductions of stroke and major cardiovascular events. This supports the concept that reduction of these events is because of BP lowering per se rather than specific drug properties. However, evidence of risk reduction of other events and particularly mortality was obtained so far with some drug classes only. As a result of marked differences in the trial design, total cardiovascular risk, SBP/DBP differences and statistical power, comparisons of meta-analyses of different drug-specific placebo-controlled RCTs appear unwarranted.
在68项随机对照试验（RCT）中，使用不同类别的药物降低了血压（BP）。我们研究了任何一类主要药物降低血压是否能有效降低心血管疾病结局。
共有55项RCT（195267名个体）适合进行药物类别荟萃分析。采用随机效应模型估计7种致命和非致命结局的风险比及其95%置信区间。
12项RCT（48898例患者）将利尿剂与未治疗进行了比较。收缩压/舒张压差异约为-12/-5 mmHg，同时所有结局包括死亡率均显著降低。将分析局限于8项使用低剂量利尿剂的RCT也得到了相同结果。对噻嗪类、氯噻酮和吲达帕胺（均为低剂量）进行的单独分析表明，每个亚类都与某些主要结局的显著降低相关。5项RCT（18724例患者；收缩压/舒张压差异-10.5/-7 mmHg）表明，β受体阻滞剂显著降低了中风、心力衰竭和主要心血管事件的发生率。在将钙拮抗剂、血管紧张素转换酶（ACE）抑制剂和血管紧张素受体阻滞剂（ARB）与安慰剂进行比较的RCT中，收缩压/舒张压差异较小，这主要是因为在大多数这些后期RCT中，降压药和安慰剂是在其他降压药物的背景治疗基础上添加的。尽管如此，钙拮抗剂（10项RCT，30359例患者）使中风、主要心血管事件、心血管疾病和全因死亡显著降低；ACE抑制剂（12项RCT，35707例患者）使中风、冠心病、心力衰竭和主要心血管事件显著降低；ARB（13项RCT，65256例患者）使中风、心力衰竭和主要心血管事件显著降低。
各类降压药物降低血压的同时，中风和主要心血管事件也显著减少。这支持了这样一种观点，即这些事件的减少是由于血压本身的降低，而不是特定药物的特性。然而，目前仅在某些药物类别中获得了降低其他事件尤其是死亡率风险的证据。由于试验设计、总心血管风险、收缩压/舒张压差异和统计效力存在显著差异，对不同药物特异性安慰剂对照RCT的荟萃分析进行比较似乎没有必要。
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