Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.
Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.
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DOI：
10.1136/bmj.b1665
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发表时间：
2009-05-19
期刊：
影响因子：
--
通讯作者：
Wald NJ
中科院分区：
文献类型：
--
作者：
Law MR;Morris JK;Wald NJ
目的了解不同类型降压药预防冠心病和脑卒中的定量疗效，并确定哪些患者应接受降压药治疗。设计分析。数据来源Medline（1966-2007）。研究选择降压药物记录冠心病事件和中风的随机试验。108项试验研究了研究药物与安慰剂（或未服用研究药物的对照组）之间的血压差异（“血压差异试验”），46项试验比较了药物（“药物比较试验”）。7个随机分组的试验同时属于这两类。这些结果是在最大的已发表的队列研究荟萃分析的背景下解释的，总共有95.8万人。参与者46.4万人被分为三个相互排斥的类别：无血管疾病史、冠心病史或中风史的参与者。结果在血压差试验中，β受体阻滞剂在预防有冠心病史的患者再次发生冠心病事件方面具有特殊作用，其风险降低29%(95%置信区间为22%至34%)，而在其他药物试验中，风险降低15%（11%至19%）。额外的效果仅限于心肌梗死后的几年内，与近期无梗死的冠心病患者相比，风险降低了31% （P=0.04）。在其他血压差异试验中（不包括冠心病患者β受体阻滞剂试验中的冠心病事件），收缩压降低10毫米汞柱或舒张压降低5毫米汞柱，冠心病事件减少22%(17%至27%)，卒中减少41%(33%至48%)，类似于队列研究荟萃分析中相同血压差异的25%（冠心病）和36%（卒中）的预期降低。表明这种益处可以用血压降低本身来解释。五种主要降压药（噻嗪类、β受体阻滞剂、血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂和钙通道阻滞剂）在预防冠心病事件和中风方面同样有效（在几个百分点以内），钙通道阻滞剂对中风的预防作用更大（相对风险0.92,95%置信区间0.85 ~ 0.98）。无论治疗前血压如何（收缩压降至110毫米汞柱，舒张压降至70毫米汞柱），有心血管疾病和无心血管疾病的人群中冠心病事件和中风的减少百分比相似。将我们的结果与其他两项研究（血压队列研究和根据剂量确定药物降血压作用的试验的荟萃分析）的结果相结合表明，在治疗前舒张压为90毫米汞柱的60-69岁人群中，三种药物以一半标准剂量联合使用可将冠心病的风险降低46%，卒中的风险降低62%；一种标准剂量的药物只有一半的效果。目前的荟萃分析还显示，钙通道阻滞剂以外的药物（非心脏选择性β阻滞剂除外）可使心力衰竭发生率降低24%(19%至28%)，钙通道阻滞剂可使心力衰竭发生率降低19%（6%至31%）。结论：除了心肌梗死后不久给予β受体阻滞剂的额外保护作用和钙通道阻滞剂在预防卒中方面的次要额外作用外，所有类别的降血压药物在降低血压的情况下，在减少冠心病事件和卒中方面具有相似的作用，因此排除了物质的多效性作用。无论预处理血压和是否存在心血管疾病，心血管疾病事件的比例减少是相同或相似的。可以简化使用降血压药物的指南，以便向各种血压水平的人提供药物。我们的研究结果表明，降低每个人在一定年龄的血压很重要，而不是测量每个人的血压，然后对一些人进行治疗。
Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.
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影响因子：
8.3
作者：
Asmar, RG;London, GM;Safar, ME
通讯作者：
Safar, ME
影响因子：
2.8
作者：
Aronow, WS;Ahn, C;Kronzon, I
通讯作者：
Kronzon, I
影响因子：
24
作者：
Bestehorn, HP;Neumann, FJ;Roskamm, H
通讯作者：
Roskamm, H
DOI：
10.1001/jama.1967.03130240070013
发表时间：
1967-01-01
影响因子：
--
作者：
通讯作者：
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影响因子：
5.1
作者：
Baba, S
通讯作者：
Baba, S