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Effect of Antihypertensive Drug Treatment on Cardiovascular Outcomes in Women and Men: A Meta-Analysis of Individual Patient Data from Randomized, Controlled Trials

Francois Gueyffier, MD; Florent Boutitie, MSc; Jean-Pierre Boissel, MD; Stuart Pocock, PhD; John Coope, MD; Jeffrey Cutler, MD; Tord Ekbom, MD; Robert Fagard, MD; Lawrence Friedman, MD; Mitchell Perry, MD; Ronald Prineas, MD; and Eleanor Schron, MS
[+] Article, Author, and Disclosure Information

(The INDANA Investigators) From Claude Bernard University, Lyon, France; London School of Hygiene and Tropical Medicine, London, United Kingdom; Bollington Medical Centre, Cheshire, United Kingdom; National Heart, Lung, and Blood Institute, Bethesda, Maryland; Lund University, Dalby/Lund, Sweden; UZ Pellenberg, Pellenberg, Belgium; Washington University, St. Louis, Missouri; and University of Miami, Miami, Florida. Acknowledgments: The authors thank Margaret Haugh and Marie Elise Jean for linguistic help in preparing the manuscript. Grant Support: The INDANA database was supported by grants from the Association pour la Promotion de la Recherche et de l'Evaluation en Therapeutique, the Societe Francaise d'Hypertension Arterielle, the Fondation pour la Recherche Medicale, and the Hospices Civils de Lyon. Requests for Reprints: Francois Gueyffier, MD, Service de Pharmacologie Clinique, 162 Avenue Lacassagne, BP 3041, 69394 Lyon Cedex 03, France. Current Author Addresses: Drs. Gueyffier and Boissel and Mr. Boutitie: Service de Pharmacologie Clinique, 162 Avenue Lacassagne, BP 3041, 69394 Lyon Cedex 03, France.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;126(10):761-767. doi:10.7326/0003-4819-126-10-199705150-00002
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Background: Trials of drug therapy for hypertension have shown that such therapy has a clear overall benefit in preventing cardiovascular disease. Although these trials have included slightly more women than men, it is still not clear whether treatment benefit is similar for both sexes.

Objective: To quantify the average treatment effect in both sexes and to determine whether available data show significant differences in treatment effect between women and men.

Design: Subgroup meta-analysis of individual patient data according to sex. Analysis was based on seven trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) database and was adjusted for possible confounders.

Patients: 20 802 women and 19 975 men recruited between 1972 and 1990.

Interventions: Primarily β-blockers and thiazide diuretics.

Results: In women, treatment effect was statistically significant for stroke (fatal strokes and all strokes) and for major cardiovascular events. In men, it was statistically significant for all categories of events (total and specific mortality, all coronary events, all strokes, and major cardiovascular events). The odds ratios for any category of event did not differ significantly between men and women. In absolute terms, the benefit in women was seen primarily for strokes; in men, treatment prevented as many coronary events as strokes. Graphical analyses suggest that these results could be completely explained by the difference in untreated risk.

Conclusions: In terms of relative risk, treatment benefit did not differ between women and men. The absolute risk reduction attributable to treatment seemed to depend on untreated risk. These findings underline the need to predict accurately the untreated cardiovascular risk of an individual person in order to rationalize and individualize antihypertensive treatment.


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Figure 1.
Effect of antihypertensive treatment on absolute risk for fatal and nonfatal stroke (left) and fatal and nonfatal coronary events (right).[16][5][6][10][11][12]

The points show subgroups in each trial by sex; the x-axis represents risk in the control group, and the y-axis represents risk in the treatment group. The risk is given as the rate for 1000 patient-years. The two dashed lines represent the odds ratios in women and men. Coope = Coope and Warrender ; HDFP = Hypertension Detection and Follow-up Program ; MRC1 = Medical Research Council trial of treatment of mild hypertension ; MRC2 = Medical Research Council trial of treatment of hypertension in older adults ; SHEP = Systolic Hypertension in the Elderly Program ; STOP = Swedish Trial in Old Patients with Hypertension .

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Figure 2.
Absolute risk reduction of fatal and nonfatal stroke (left) and fatal and nonfatal coronary events (right) by untreated risk level and sex.

The points show the absolute risk reduction on the y-axis with 95% Cls. The x-axis represents the predicted untreated risk. The number next to each point is the number of events observed by tertile. The predicted risk was obtained from a multivariate score established on the control group with the main cardiovascular risk factors: age, baseline smoking habits, blood pressure, serum cholesterol level, diabetes, and history of stroke or myocardial infarction.

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