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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.

Meta-analysis of factorial trials in which participants were randomly allocated to 1 drug alone, another drug alone, both drugs together, or a placebo.

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 …