Combination Therapy Versus Monotherapy in Reducing Blood Pressure: Meta-analysis on 11,000 Participants from 42 Trials
Combination Therapy Versus Monotherapy in Reducing Blood Pressure: Meta-analysis on 11,000 Participants from 42 Trials
复制标题
DOI：
10.1016/j.amjmed.2008.09.038
复制
发表时间：
2009-03-01
影响因子：
5.9
通讯作者：
Wald, Nicholas J.
中科院分区：
文献类型：
--
作者：
Wald, David S.;Law, Malcolm;Wald, Nicholas J.
目的：量化任何2类噻嗪类降压药、β受体阻滞剂、血管紧张素转换酶抑制剂和钙通道阻滞剂联合用药对单用1种药物的增量效应，并比较联合用药加倍剂量的效应。方法：析因试验的荟萃分析，其中受试者被随机分配至单用1种药物，单用另一种药物，两种药物一起使用，结果：我们确定了42项试验（10，968名参与者）。单独使用噻嗪类药物时，收缩压平均降低7.3 mm Hg（减去安慰剂），与另一类药物联合使用时降低14.6 mm Hg（减去安慰剂）。β受体阻滞剂的相应降低分别为9.3 mm Hg和18.9 mm Hg，血管紧张素转换酶的相应降低分别为6.8 mm Hg和13.9 mm Hg，钙通道阻滞剂的相应降低分别为8.4 mm Hg和14.3 mm Hg。假设叠加效应，2种药物的预期血压降低与观察到的血压降低密切相关。对于噻嗪类药物、β受体阻滞剂、血管紧张素转换酶抑制剂和钙通道阻滞剂，每类药物与任何其他药物联合治疗相对于1种药物的观察到的血压降低增量与预期血压降低增量的比值分别为：1.04（95%置信区间[CI]，0.88-1.20），1.00（95% CI，0.76-1.24）、1.16（95% CI，0.93-1.39）和0.89（95% CI，0.69-1.09）;总体平均值为1.01（95% CI，0.90-1.12）。比较我们的结果与发表的荟萃分析的同一种药物的不同剂量的结果表明，1种药物的剂量加倍约有五分之一的等效增量效应（0.22 [95%CI，0.19-0.25]）。结论：从这4类药物组合的血压降低可以预测的基础上的累加效应。联合使用2种不同类别的药物所带来的额外血压降低大约是1种药物剂量加倍的5倍。(C)2009爱思唯尔公司All rights reserved.美国医学杂志（2009）122，290-300
OBJECTIVE: To quantify the incremental effect of combining blood pressure-lowering drugs from any 2 classes of thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers over 1 drug alone and to compare the effects of combining drugs with doubling dose.METHODS: Meta-analysis of factorial trials in which participants were randomly allocated to 1 drug alone, another drug alone, both drugs together, or a placebo.RESULTS: We identified 42 trials (10,968 participants). With a thiazide used alone, the mean placebo-subtracted reduction in systolic blood pressure was 7.3 mm Hg and 14.6 mm Hg combined with a drug from another class. The corresponding reductions were 9.3 mm Hg and 18.9 mm Hg with a beta-blocker, 6.8 mm Hg and 13.9 mm Hg with an angiotensin-converting enzyme, and 8.4 mm Hg and 14.3 mm Hg with a calcium channel blocker. The expected blood pressure reduction from 2 drugs together, assuming an additive effect, closely predicted the observed blood pressure reductions. The ratios of the observed to expected incremental blood pressure reductions from combining each class of drug with any other over that from 1 drug were, respectively, for thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers: 1.04 (95% confidence interval [CI], 0.88-1.20), 1.00 (95% CI, 0.76-1.24), 1.16 (95% CI, 0.93-1.39), and 0.89 (95% CI, 0.69-1.09); the overall average was 1.01 (95% CI, 0.90-1.12). Comparison of our results with those of a published meta-analysis of different doses of the same drug showed that doubling the dose of 1 drug had approximately one fifth of the equivalent incremental effect (0.22 [95% CI, 0.19-0.25]).CONCLUSION: Blood pressure reduction from combining drugs from these 4 classes can be predicted on the basis of additive effects. The extra blood pressure reduction from combining drugs from 2 different classes is approximately 5 times greater than doubling the dose of 1 drug. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 290-300