Diuretic Therapy for Hypertension and the Risk of Primary Cardiac Arrest
David S. Siscovick, T.E. Raghunathan, Bruce M. Psaty, Thomas D. Koepsell, Kristine G. Wicklund, Xihong Lin, Leonard Cobb, Pentti M. Rautaharju, Michael K. Copass, and Edward H. Wagner
Background The results of trials of the primary prevention ofcoronary heart disease have suggested that treating hypertensionwith high doses of thiazide diuretic drugs might increase therisk of sudden death from cardiac causes. In contrast, treatmentwith low doses of thiazide reduces the risk of coronary heartdisease.
Methods To examine the association between thiazide treatmentfor hypertension and the occurrence of primary cardiac arrest,we conducted a population-based case-control study among enrolleesof a health maintenance organization. The case patients were114 persons with hypertension who had a primary cardiac arrestfrom 1977 through 1990. The control patients were a stratifiedrandom sample of 535 persons with hypertension. The patients'treatment was assessed with the use of a computerized pharmacydata base. Records of their ambulatory care were reviewed todetermine other clinical characteristics.
Results The risk of primary cardiac arrest among patients receivingcombined thiazide and potassium-sparing diuretic therapy waslower than that among patients treated with a thiazide withoutpotassium-sparing therapy (odds ratio, 0.3; 95 percent confidenceinterval, 0.1 to 0.7). As compared with low-dose thiazide therapy(25 mg daily), moderate-dose therapy (50 mg daily) was associatedwith a moderate increase in risk (odds ratio, 1.7; 95 percentconfidence interval, 0.7 to 4.5), and high-dose therapy (100mg daily) was associated with a larger increase in risk (oddsratio, 3.6; 95 percent confidence interval, 1.2 to 10.8) (Pvalue for trend, 0.02). The addition of a potassium-sparingdrug to low-dose thiazide therapy was associated with a reducedrisk of cardiac arrest (odds ratio, 0.4; 95 percent confidenceinterval, 0.1 to 1.5).
Conclusions Both the dose of thiazide drugs and the additionof potassium-sparing drugs influence the risk of primary cardiacarrest. These results may explain the differences in the effectof antihypertensive therapy on mortality from coronary heartdisease in previous clinical trials.
Source Information
From the Cardiovascular Health Research Unit, the Departments of Medicine (D.S.S., B.M.P., T.D.K., K.G.W., L.C., M.K.C.), Epidemiology (D.S.S., B.M.P., T.D.K.), Biostatistics (T.E.R., X.L.), and Health Services (B.M.P., T.D.K., E.H.W.), University of Washington, Seattle; the Epicore Centre, Division of Cardiology, University of Alberta, Edmonton, Alta., Canada (P.M.R.); and the Center for Health Studies, Group Health Cooperative of Puget Sound, Seattle (E.H.W.). Presented in part at the 33rd annual scientific meeting of the Council on Epidemiology and Prevention of the American Heart Association, Sante Fe, N.M., March 18, 1993.
Address reprint requests to Dr. Siscovick at the Cardiovascular Health Research Unit, Metropolitan Park 2 Bldg., Suite 1360, 1730 Minor Ave., Seattle, WA 98101.
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