Combination Therapy Versus Monotherapy in Reducing Blood Pressure: Meta-analysis on 11,000 Participants from 42 Trials

Mean placebo-subtracted systolic blood pressure reduction from a meta-analysis of 42 randomized factorial trials of thiazides, beta-blockers, ACE inhibitors, or calcium channel blockers using each class of drug separately, any 1 of the other 3 classes alone, and in combination with the specified drug class (95% confidence interval). The dashed line represents the expected blood pressure reduction from the combination assuming an additive effect, allowing for the smaller reduction from 1 drug given the lower pretreatment blood pressure because of the other. BP=blood pressure; ACE=angiotensin-converting enzyme.

Ratio of observed to expected incremental blood pressure-lowering effects of adding a drug or doubling the dose according to the class of drug. The expected incremental effect is the incremental blood pressure reduction of the added (or doubled drug), assuming an additive effect and allowing for the smaller reduction from 1 drug (or dose of 1 drug) given the lower pretreatment blood pressure because of the other. ACE=angiotensin-converting enzyme.

Comparison of observed placebo-subtracted reduction in systolic blood pressure of 2 drugs together against the expected effect of 2 drugs together according to the class of drug in factorial trials of 2 blood pressure-lowering drugs (the expected effect assumes a full additive effect and allows for the smaller reduction from 1 drug given the lower pretreatment blood pressure because of the other). Each circle represents a different drug and dose combination within a trial. There are more circles than trials because several trials examine different doses of different drugs. The area of the circle reflects the statistical precision of the points plotted. The diagonal lines are the lines of identity where observed equals expected. ACE=angiotensin-converting enzyme.