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. 2010 Jan 25:340:c103.
doi: 10.1136/bmj.c103.

Myocardial infarction and stroke associated with diuretic based two drug antihypertensive regimens: population based case-control study

Inbal Boger-Megiddo  1 , Susan R Heckbert, Noel S Weiss, Barbara McKnight, Curt D Furberg, Kerri L Wiggins, Joseph A C Delaney, David S Siscovick, Eric B Larson, Rozenn N Lemaitre, Nicholas L Smith, Kenneth M Rice, Nicole L Glazer, Bruce M Psaty
Affiliations

Myocardial infarction and stroke associated with diuretic based two drug antihypertensive regimens: population based case-control study

Inbal Boger-Megiddo et al. BMJ. .

Abstract

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 beta 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 beta 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 beta 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.

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Conflict of interest statement

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.

Figures

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Fig 1 Relative risk of myocardial infarction in specified subgroups of patients on diuretics and calcium channel blockers, with diuretics plus β blockers as a reference. Odds ratios adjusted for age, sex, index year, smoking, and total cholesterol
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Fig 2 Relative risk of myocardial infarction in specified subgroups of patients on diuretics angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), with diuretics plus β blockers as a reference. Odds ratios adjusted for age, sex, index year, smoking, and total cholesterol
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Fig 3 Relative risk of stroke in specified subgroups of patients on diuretics and calcium channel blockers, with diuretics plus β blockers as a reference. Odds ratios adjusted for age, sex, index year, smoking, and total cholesterol
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Fig 4 Relative risk of stroke in specified subgroups of patients on diuretics and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), with diuretics plus β blockers as a reference. Odds ratios adjusted for age, sex, index year, smoking, and total cholesterol
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