Abstract
In several observational studies, patients prescribed calcium channel blockers had higher risks of cardiovascular diseases and mortality than those prescribed other antihypertensive medications. We explored these associations in the Nurses' Health Study. A total of 14 617 women who reported hypertension and regular use of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, or a combination in 1988 were included in the analyses. Cardiovascular events and deaths were ascertained through May 1, 1994. We documented 234 cases of myocardial infarction. Calcium channel blocker monodrug users had an age-adjusted relative risk (RR) of myocardial infarction of 2.36 (95% CI, 1.43 to 3.91) compared with those prescribed thiazide diuretics. Women prescribed calcium channel blockers had a higher prevalence of ischemic heart disease. After adjustment for these and other coronary risk factors, the RR was 1.64 (95% CI, 0.97 to 2.77). Comparing the use of any calcium channel blocker (monodrug and multidrug users) with that of any other antihypertensive agent, the adjusted RR was 1.42 (95% CI, 1.01 to 2.01). An association between calcium channel blocker use and myocardial infarction was apparent among women who had ever smoked cigarettes (covariate-adjusted RR, 1.81; 95% CI, 1.20 to 2.72) but not among never-smokers (RR, 0.94; 95% CI, 0.48 to 1.84). In analyses adjusted only for age, we found a significant elevation in RR of total myocardial infarction among women who used calcium channel blockers compared with those who did not. After adjustment for comorbidity and other covariates, the RR was reduced. Whether the remaining observed elevated risk is real, or a result of residual confounding by indication, or chance, or a combination of the above cannot be evaluated with certainty on the basis of these observational data.
Highlights
In several observational studies, patients prescribed calcium channel blockers had higher risks of cardiovascular diseases and mortality than those prescribed other antihypertensive medications
In a large case-control study of hypertensives initially free of cardiovascular disease, those who suffered an MI were significantly more likely to have been treated with calcium channel blockers than hypertensives who did not suffer an MI.' In two other case-control studies,2'3 no increased risk was seen for hypertensive patients on calcium channel blockers
In a recent case-control study, 27 hypertensive patients who received short-acting calcium channel blockers had a higher risk of cardiovascular events than patients on the long-acting formulation.[4]
Summary
He Nurses' Health Study cohort was established in 1976, when 121701 female registered US nurses 30 to 55 years old returned completed questionnaires sent by mail. On baseline and follow-up questionnaires, nurses have been asked to provide demographic and lifestyle information as well as their disease status.[9] In 1988, information was requested on the regular use of cardiovascular medication, including thiazide diuretics, j8-blockers, calcium channel blockers, and ACE inhibitors. Information on use of calcium channel blockers was not updated until 1994; medication use was not updated in this analysis. The total use of calcium channel blockers in our study population almost doubled. Because the use of long-acting calcium channel blockers was rare in 1988, mostly short-acting formulations were likely to have been prescribed in this population
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