Abstract
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.
Keywords
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Article info
Footnotes
Funding: None.
Conflict of Interest: Nicholas J. Wald and Malcolm Law hold patents (EU1272220 and GB2361186) for a combination pill for the prevention of cardiovascular disease (Polypill) and together with David Wald have interests in its development.
Authorship: All authors had access to the data and played a role in writing this manuscript.
Identification
Copyright
© 2009 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
