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Combination antihypertensive therapy beats doubling monotherapy dose

20 March 2009

MedWire News: Blood pressure (BP) reduction from combining drugs from different classes can be predicted on the basis of additive effects, and is approximately five times greater than doubling the dose of a single drug, a study indicates.

Effectiveness of low-dose drug combinations as initial treatment for BP reduction relies on the effects of the combined drugs being additive.

To examine the evidence for this, a team from the London Queen Mary’s School of Medicine and Dentistry, UK, led by David Wald, conducted a meta-analysis of 42 factorial trials involving 10,968 participants in which combinations of any two of thiazides, beta-blockers, ACE inhibitors (ACEIs), and calcium channel blockers (CCBs) were tested against each drug given alone and placebo.

With thiazide used alone, the mean placebo-subtracted reduction in systolic blood pressure was 7.3 mmHg, and 14.6 mmHg combined with a drug from another class. The corresponding reductions were 9.3 mmHg and 18.9 mmHg with beta-blocker, 6.8 mmHg and 13.9 mmHg with ACEI, and 8.4 mmHg and 14.3 mmHg with CCB.

The expected blood pressure reduction from two 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 one drug were, respectively, for thiazides, beta-blockers, ACEIs, and CCBs: 1.04, 1.00, 1.16, and 0.89. The overall average was 1.01.

Comparison of results with those of a published meta-analysis of different doses of the same drug showed that doubling the dose of one drug had approximately one fifth of the equivalent incremental effect (0.22).

Writing in the American Medical Journal, the researchers conclude: “The results leave little doubt over the advantages of adopting low-dose combination blood pressure-lowering treatment as routine initial therapy for all, instead of a monotherapy and stepped-care approach.”

They also note: “Low-dose therapy has the advantage of reducing adverse effects that… are strongly dose related… Using more than two drugs in combination also would increase efficacy”.

MedWire is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

Am J Med 2009; 122: 290–300

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