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Implications and Generalizability of Randomized Trials

Cynthia D. Mulrow, MD, MSc; John A. Cornell, PhD; Carlos R. Herrera, MD, MPH; Abdulmajead Kadri, PharmD; Lisa Farnett, PharmD; Christine Aguilar, MD, MPH

JAMA. 1994;272(24):1932-1938.

Abstract
Objective.
—To estimate morbidity and mortality benefits of drug therapy for hypertensive elderly subjects, compare these benefits with effects in younger subjects, and provide a framework for generalizing results derived from trials to actual patients.

Data Sources.
—A literature search using MEDLINE from 1966 to 1993, references from reviews and trial articles, and experts.

Study Selection.
—Randomized trials lasting at least 1 year that evaluated effects of drug treatment on morbidity and mortality outcomes in hypertensive persons.

Data Extraction.
—Four independent reviewers appraised protocol characteristics and quality of selected trials.

Data Synthesis.
—There were 13 trials involving 16 564 elderly persons (age 60 years and older). The prevalence of cardiovascular risk factors, cardiovascular disease, and competing comorbid diseases was lower among trial participants than the general population of hypertensive elderly persons. When the six large high-quality trials were combined, trial results showed 43 subjects (95% confidence interval [CI], 31 to 69) and 61 subjects (95% CI, 39 to 141) needed to be treated for 5 years to prevent one cerebrovascular event and one coronary heart disease event, respectively. Including the other seven trials did not change the results significantly. Only 18 subjects (95% CI, 14 to 25) needed to be treated to prevent one cardiovascular event (cerebrovascular or cardiac). Twelve trials in primarily younger and middle-aged adults involved approximately 33 000 persons. For all outcomes except cardiac mortality, two to fourtimes as many of the younger subjects as the older subjects needed to be treated for 5 years to prevent morbid and mortal events. No significant effect on cardiac mortality was seen among younger subjects, while 78 older subjects (95% CI, 50 to 180) needed to be treated to prevent a fatal cardiac event.

Conclusions.
—Randomized trials demonstrate that treating healthy older persons with hypertension is highly efficacious. Five-year morbidity and mortality benefits derived from trials are greater for older than younger subjects. Extrapolating benefits from trials to individual patients is difficult, but should take into account multiple issues including the patient's risk factors, preexisting cardiovascular disease, and competing comorbid illnesses.

(JAMA. 1994;272:1932-1938)

Author Affiliations
From the Geriatric Research, Education and Clinical Center, the Audie L. Murphy Memorial Veterans Hospital, San Antonio, Tex (Drs Mulrow, Cornell, Kadri, and Farnett), and the University of Texas Health Science Centers at Houston (Dr Herrera) and San Antonio (Drs Mulrow, Cornell, and Aguilar). Dr Mulrow is a Veterans Affairs senior research associate. No financial support was received for this work.

Footnotes
Reprint requests to Audie L. Murphy Memorial Veterans Hospital, Ambulatory Care (11C6), 7400 Merton Minter Blvd, San Antonio, TX 78284 (Dr Mulrow),

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