Correspondence
Diuretic Therapy and the Risk of Cardiac Arrest
N Engl J Med 1994; 331:1235-1236November 3, 1994
- Article
To the Editor:
Siscovick et al. (June 30 issue)1 report that higher doses of thiazide diuretics were associated with an increased risk of cardiac arrest. They state that they corrected for the differences between the case and control patients, but this may have been difficult because so many factors differed between the two groups. The case patients were older, and in this group the pretreatment systolic blood pressure was higher, the pretreatment heart rate was faster, the duration of hypertension was longer, and there were more men, more smokers, and more patients with diabetes mellitus. Such a group would be expected to have an increased risk of sudden death. Although there does appear to be a direct relation between the dose of thiazide and cardiac arrest, and there was also a reduction in risk among patients taking a thiazide and a potassium-sparing drug, it is difficult to believe that the differences in pretreatment characteristics did not contribute to the primary finding.
1 ReferencesMarvin Moser, M.D.
Yale University School of Medicine, New Haven, CT 06520Ray Gifford, M.D.
Cleveland Clinic, Cleveland, OH 441951
Siscovick DS ,Raghunathan TE ,Psaty BM , et al. Diuretic therapy for hypertension and the risk of primary cardiac arrest. N Engl J Med 1994;330:1852-1857
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Author/Editor Response
The authors reply:
To the Editor: Drs. Moser and Gifford suggest that differences in pretreatment characteristics may have contributed to the primary findings, because factors other than antihypertensive-drug therapy differed between the case and control patients. Such differences are to be expected, since multiple risk factors are related to the occurrence of primary cardiac arrest.1 We too were concerned about a potential confounding effect related to the indication for therapy and other factors. We therefore used three approaches -- restriction, stratification, and multivariate adjustment -- as indicated in our report. The result was a demonstrated effect of the type of diuretic therapy and the dose of thiazide on the risk of primary cardiac arrest after the effects of these other factors had been taken into account.
For all the hypertensive patients who received drug therapy at the health maintenance organization during the 14-year study period, diuretic therapy (both the type and dose) was only weakly related to characteristics such as age, sex, severity or duration of hypertension, cigarette smoking, and diabetes mellitus. For this reason, a multivariate adjustment for these characteristics yielded only slight changes in the estimated odds ratios. Although it is not possible to rule out uncontrolled confounding effects of factors that were not measured, there was little evidence that differences in pretreatment characteristics between case patients and controls accounted for the findings.
1 ReferencesDavid S. Siscovick, M.D., M.P.H.
Thomas D. Koepsell, M.D., M.P.H.
University of Washington, Seattle, WA 98195T.E. Raghunathan, Ph.D.
University of Michigan, Ann Arbor, MI 481061
Schatzkin A ,Cupples LA ,Heeren T ,Morelock S ,Kannel WB . Sudden death in the Framingham Heart Study: differences in incidence and risk factors by sex and coronary disease status. Am J Epidemiol 1984;120:888-899
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