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A Meta-analysis of Randomized Double-blind Studies

Roland E. Schmieder, MD; Peter Martus, PhD; Arnfried Klingbeil, MD

JAMA. 1996;275(19):1507-1513.

Abstract
Objective.
—To determine the ability of various antihypertensive agents to reduce left ventricular hypertrophy, a strong, blood pressure—independent cardiovascular risk factor, in persons with essential hypertension.

Data Sources.
—MEDLINE, DIMDI, RINGDOC, ADES, EMBASE, and review articles through July 1995 (English-language and full articles only).

Study Selection.
—Meta-analysis of all published articles including only double-blind, randomized, controlled clinical studies with parallel-group design.

Data Extraction.
—Intensive literature search and data extraction according to a prefixed scheme performed independently by 2 investigators. Reduction of left ventricular mass index after antihypertensive therapy with placebos, diuretics, β-blockers, calcium channel blockers, or angiotensin-converting enzyme (ACE) inhibitors was the principal parameter.

Data Synthesis.
—Of 471 identified references describing the effects of antihypertensive drugs on left ventricular hypertrophy, only 39 clinical trials fulfilled the inclusion criteria of our study. We found that the decrease in left ventricular mass index was more marked the greater was the decline in blood pressure (systolic r=0.46, P<.001; diastolic r=0.21, P=.08) and the longer was the duration of therapy (r=0.38, P<.01). After adjustment for different durations of treatment (mean duration of treatment, 25 weeks), left ventricular mass decreased 13% with ACE inhibitors, 9% with calcium channel blockers, 6% with β-blockers, and 7% with diuretics. There was a significant difference between drug classes (P<.01): ACE inhibitors reduced left ventricular mass more than β-blockers (significant, P<.05) and diuretics (tendency, P=.08). Similar differences between drug classes were found with regard to effect on left ventricular wall thickness (P<.05).

Conclusions.
—The database of articles published through July 1995 is small and incomplete, and most of the articles are of poor scientific quality. In this first meta-analysis including only double-blind, randomized, controlled clinical studies, decline in blood pressure, duration of drug treatment, and drug class determined the reductions in left ventricular mass index. The ACE inhibitors seemed to be more potent than β-blockers and diuretics in the reduction of left ventricular mass index; calcium channel blockers were somewhat in the intermediate range. The ACE inhibitors and, to a lesser extent, calcium channel blockers emerged as first-line candidates to reduce the risk associated with left ventricular hypertrophy.

(JAMA. 1996;275:1507-1513)

Author Affiliations
From the Department of Internal Medicine IV, University Erlangen-Nürnberg, Nuremberg, Germany.

Footnotes
Reprints: Roland E. Schmieder, MD, Medizinische Klinik IV, Universität Erlangen-Nürnberg, Breslauer Str 201, 90471 Nuremberg, Germany.

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