Myocardial infarction and stroke associated with diuretic based two drug antihypertensive regimens: population based case-control studyBMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c103 (Published 25 January 2010) Cite this as: BMJ 2010;340:c103
- Inbal Boger-Megiddo, fellow trainee1,
- Susan R Heckbert, professor of epidemiology1,
- Noel S Weiss, professor of epidemiology2,
- Barbara McKnight, professor of biostatistics3,
- Curt D Furberg, professor of public health sciences4,
- Kerri L Wiggins, data manager and analyst1,
- Joseph A C Delaney, postdoctoral fellow3,
- David S Siscovick, professor of medicine and epidemiology1,
- Eric B Larson, executive director and senior investigator5,
- Rozenn N Lemaitre, research scientist1,
- Nicholas L Smith, associate professor of epidemiology1,
- Kenneth M Rice, assistant professor of biostatistics3,
- Nicole L Glazer, research scientist1,
- Bruce M Psaty, professor of medicine and epidemiology1
- 1Cardiovascular Health Research Unit, University of Washington, Seattle, WA 98101, USA
- 2Department of Epidemiology, University of Washington, Seattle, WA 98195-7236
- 3Department of Biostatistics, University of Washington, Seattle, WA 98195
- 4Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1063
- 5Center for Health Studies, Group Health Cooperative, Seattle, WA 98101-1448
- Correspondence to: B M Psaty
- Accepted 14 October 2009
Objective To examine the association of myocardial infarction and stroke incidence with several commonly used two drug antihypertensive treatment regimens.
Design Population based case-control study.
Setting Group Health Cooperative, Seattle, WA, USA.
Participants Cases (n=353) were aged 30-79 years, had pharmacologically treated hypertension, and were diagnosed with a first fatal or non-fatal myocardial infarction or stroke between 1989 and 2005. Controls (n=952) were a random sample of Group Health members who had pharmacologically treated hypertension. We excluded individuals with heart failure, evidence of coronary heart disease, diabetes, or chronic kidney disease.
Exposures One of three common two drug combinations: diuretics plus β blockers; diuretics plus calcium channel blockers; and diuretics plus angiotensin converting enzyme inhibitors or angiotensin receptor blockers.
Main outcome measures Myocardial infarction or stroke.
Results Compared with users of diuretics plus β blockers, users of diuretics plus calcium channel blockers had an increased risk of myocardial infarction (adjusted odds ratio (OR) 1.98, 95% confidence interval 1.37 to 2.87) but not of stroke (OR 1.02, 95% CI 0.63 to 1.64). The risks of myocardial infarction and stroke in users of diuretics plus angiotensin converting enzyme inhibitors or angiotensin receptor blockers were slightly but not significantly lower than in users of diuretics plus β blockers (myocardial infarction: OR 0.76, 95% CI 0.52 to 1.11; stroke: OR 0.71, 95% CI 0.46 to 1.10).
Conclusions In patients with hypertension, diuretics plus calcium channel blockers were associated with a higher risk of myocardial infarction than other common two drug treatment regimens. A large trial of second line antihypertensive treatments in patients already on low dose diuretics is required to provide a solid basis for treatment recommendations.
Contributors: IBM, SRH, and BMP are responsible for the conception and design of this study. IBM, SRH, NSW, BM, JACD, and BMP undertook the analysis and interpretation of the data. Drafting the article or revising it critically for important intellectual content was performed by IBM, SRH, NSW, BM, CDF, KLW, JACD, DSS, EBL, RNL, NLS, KMR, NLG, and BMP. IBM, SRH, NSW, BM, CDF, KLW, JACD, DSS, EBL, RNL, NLS, NLG, and BMP all gave final approval of the version to be published. IBM and BMP act as guarantors of the paper.
Funding: This research was supported in part by grants HL43201 (BMP), HL40628 (BMP), HL60739 (BMP), HL68639 (BMP), HL68986 (SRH), HL73410 (NLS), HL74745 (BMP), HL085251 (BMP), and HL007902 (DSS) from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare (1) No financial support for the submitted work from anyone other than their employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities that might have an interest in the submitted work; (4) No non-financial interests that may be relevant to the submitted work.
Ethical approval: All participants provided written informed consent approved by the Cooperative Human Subjects Review Committee at Group Health.
Data sharing: No additional data available.
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