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Diuretics, β-Blockers, and the Risk for Sudden Cardiac Death in Hypertensive Patients

Arno W. Hoes, MD, PhD; Diederick E. Grobbee, MD, PhD; Jacobus Lubsen, MD, PhD; Arie J. Man in 't Veld, MD, PhD; Emiel van der Does, MD, PhD; and Albert Hofman, MD, PhD
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From Erasmus University Medical School, Rotterdam, the Netherlands. Acknowledgments: The authors thank the municipal authorities in Rotterdam, especially Ronald Lockhorst and his coworkers; Dr. Cremers and his colleagues from the Rotterdam police for their essential contribution to the study; the general practitioners and pharmacists in the Rotterdam area for their enthusiastic support; Margriet Pannevis, PharmD, for obtaining information from the Rotterdam pharmacies; Andrea de Oude-Lubbers, Diane Huizer, Yolanda Bekker, Andrina Cleveringa, Sharmila Bhikha, and Dr. Sjaak Tellekamp for their valuable assistance; Marcel Eijgermans and Dick Tensen for developing the software applications; and Dr. J.P. Vandenbroucke for his helpful comments on the manuscript. Grant Support: By grant 88.145 from the Netherlands Heart Foundation. Requests for Reprints: Arno W. Hoes, MD, PhD, Departments of Epidemiology and Biostatistics and General Practice, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, the Netherlands. Current Author Addresses: Drs. Hoes, Grobbee, and Hofman: Department of Epidemiology and Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, the Netherlands.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;123(7):481-487. doi:10.7326/0003-4819-123-7-199510010-00001
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Objective: To determine whether the use of non-potassium-sparing diuretics and β-blockers is associated with an excess risk for sudden cardiac death in hypertensive patients.

Design: Case-control study.

Setting: Rotterdam, the Netherlands.

Patients: 257 case-patients who had died suddenly while receiving drug therapy for hypertension and 257 living controls also receiving drug therapy for hypertension.

Measurements: Detailed information on medication use and clinical characteristics of all case-patients and controls was collected from the files of general practitioners. Additional information on medication use was obtained from computerized pharmacy records.

Results: Patients receiving non-potassium-sparing diuretics had an increased risk for sudden cardiac death (relative risk, 1.8 [95% CI, 1.0 to 3.1]) compared with a reference group treated primarily with potassium-sparing diuretics. The corresponding relative risk for β-blocker use was 1.7 (CI, 1.1 to 2.6). The use of non-potassium-sparing diuretics without β-blockers was associated with a higher risk for sudden death (relative risk, 2.2 [CI, 1.1 to 4.6]) than was concomitant use of non-potassium-sparing diuretics and β-blockers (relative risk, 1.4 [CI, 0.6 to 3.0]). The risk for sudden cardiac death among recipients of non-potassium-sparing diuretics was more pronounced in those who had been receiving the diuretic for less than 1 year and in those aged 75 years or younger.

Conclusions: The use of non-potassium-sparing diuretics and β-blockers is associated with an increased risk for sudden cardiac death. This association may offset part of the mortality benefit of these drugs in the treatment of hypertension.


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Figure 1.
Antihypertensive medication and the risk for sudden cardiac death in patients aged 75 years or younger (n= 242) and those older than age 75 years (n= 272).Table 2

Relative risks and 95% CIs were adjusted for differences in potential confounders by the use of a multivariate statistical model (see ). Bars represent relative risks and 95% CIs. Ref = reference group consisting of patients receiving antihypertensive drugs other than non-potassium-sparing diuretics and β-blockers; N = patients receiving non-potassium-sparing diuretics without β-blockers; B = patients receiving β-blockers without non-potassium-sparing diuretics; N + B = patients receiving non-potassium-sparing diuretics and β-blockers. * = The value of the higher limit of the CI was 16.0.

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