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. 2014 Dec;32(12):2285-95. doi: 10.1097/HJH.0000000000000378.
Antihypertensive treatment is based on randomized controlled trials (RCTs) started since 1966. Meta-analyses comprehensive of all RCTs but limited to RCTs investigating blood pressure (BP) lowering in hypertensive patients are lacking.
Two clinical questions were investigated: the extent of different outcome reductions by BP lowering in hypertensive patients, and the proportionality of outcome reductions to SBP, DBP, and pulse pressure (PP) reductions.
PubMed between 1966 and December 2013 (any language), Cochrane Collaboration Library and previous overviews were used as data sources for identifying and selecting all RCTs comparing the antihypertensive drugs with placebo or less intense BP lowering (intentional BP-lowering RCTs); comparing BP-lowering drugs with placebo without BP-lowering intention, but with BP difference (nonintentional BP-lowering RCTs); and enrolling at least 40% hypertensive patients. RCTs on acute myocardial infarction, heart failure, acute stroke, and dialysis were excluded. RCT quality was assessed by scoring. Risk ratios and 95% confidence interval (CI), standardized to 10/5 mmHg SBP/DBP reduction, of seven fatal and nonfatal outcomes were calculated (random-effects model). The relationships of different outcome reductions to SBP, DBP, and PP reductions were investigated by meta-regressions.
A total of 68 RCTs (245,885 individuals) were eligible, of which 47 (153,825 individuals) were 'intentional' RCTs. All outcomes were reduced (P < 0.001) by BP lowering, stroke [-36% (-29, -42)], and heart failure [-43% (-28, -54)] to a greater extent, with smaller reductions for coronary events [coronary heart disease (CHD): -16% (-10, -21)], cardiovascular [-18% (-11, -24)], and all-cause mortality [-11% (-5, -16)]. Absolute risk reductions were 17 (14, 20) strokes, 28 (19, 35) cardiovascular events, and 8 (4, 12) deaths prevented every 1000 patients treated for 5 years. Logarithmic risk ratios were related to SBP, DBP, and PP reductions (P = 0.001-0.003) for stroke and composite cardiovascular events, but not for CHD.
Meta-analyses of all BP-lowering RCTs involving hypertensive patients provide precise estimates of benefits (larger for stroke and heart failure, but also significant for CHD and mortality). Absolute risk reductions are substantial. Relationships of logarithmic risk ratios with BP reductions imply risk reduction increases progressively to a smaller extent the larger the BP reduction.
自1966年起，抗高血压治疗基于随机对照试验（RCT）。目前缺乏综合所有RCT，但仅限于研究高血压患者血压降低情况的RCT的荟萃分析。
研究两个临床问题：高血压患者血压降低导致不同结局减少的程度，以及结局减少与收缩压（SBP）、舒张压（DBP）和脉压（PP）降低的比例关系。
以1966年至2013年12月期间的PubMed（任何语言）、Cochrane协作图书馆及既往综述作为数据源，用以识别和选择所有将抗高血压药物与安慰剂或降压强度较低药物进行比较的RCT（意向性降压RCT）；将无降压意向但存在血压差异的降压药物与安慰剂进行比较的RCT（非意向性降压RCT）；以及纳入至少40%高血压患者的RCT。排除关于急性心肌梗死、心力衰竭、急性卒中及透析的RCT。通过评分评估RCT质量。计算七种致命和非致命结局的风险比及95%置信区间（CI），并标准化至SBP/DBP降低10/5 mmHg（随机效应模型）。通过荟萃回归研究不同结局减少与SBP、DBP和PP降低的关系。
共有68项RCT（245,885例个体）符合条件，其中47项（153,825例个体）为“意向性”RCT。血压降低使所有结局均减少（P<0.001），卒中[-36%（-29，-42）]和心力衰竭[-43%（-28，-54）]减少幅度更大，冠心病（CHD）[-16%（-10，-21）]、心血管疾病[-18%（-11，-24）]和全因死亡率[-11%（-5，-16）]减少幅度较小。每1000例接受5年治疗的患者中，绝对风险降低分别为17（14，20）例卒中、28（19，35）例心血管事件和8（4，12）例死亡。卒中及复合心血管事件的对数风险比与SBP、DBP和PP降低相关（P = 0.001 - 0.003），但CHD不相关。
对所有涉及高血压患者的降压RCT进行荟萃分析，可精确估计获益情况（卒中及心力衰竭获益更大，但CHD和死亡率也有显著获益）。绝对风险降低幅度很大。对数风险比与血压降低的关系表明，血压降低幅度越大，风险降低幅度逐渐增加，但增加幅度较小。
