Discontinuation of β-blockers and the risk of myocardial infarction in the elderly

Background: It has been shown that the abrupt cessation of treatment with β-adrenoceptor antagonists (β-blockers) increases the risk of myocardial infarction in patients with hypertension. As β-blockers differ in their pharmacokinetic and pharmacodynamic properties, this risk of discontinuation might also differ between subgroups of β-blockers. Objective: To determine whether discontinuation of β-blockers is associated with an increased risk of myocardial infarction in elderly patients and whether the effects of recent cessation differs between subgroups of β-blockers, categorised according to their selectivity, lipophilic profile and intrinsic sympathomimetic activity (ISA). Design: A cohort study in users of β-blockers within the Rotterdam Study, which was a prospective population-based follow-up study of 7983 individuals aged ≥55 years. Patients: We identified 2588 individuals who had been treated with a β-blocker for at least 30 days at any time during the study period of 1 January 1991 to 1 January 2002. In this group, 148 subjects developed incident myocardial infarction. Methods: Detailed information on the medication use and clinical characteristics of all patients were collected from the files of pharmacies, general practices and hospitals. Myocardial infarction was diagnosed on the basis of internationally accepted criteria and verified by a cardiologist. The duration of β-blocker use was calculated from computerised pharmacy records on the basis of the number of dispensed tablets or capsules and the prescribed daily number. For every individual, on the index date (date of myocardial infarction in cases, the same date in controls [defined as any patient who had not experienced a myocardial infarction up to that timepoint]) the usage of β-blockers was determined and classified as either current or as past use. Past use was classified into three different periods: cessation of β-blockers less than 30 days; between 30 and 180 days; and more than 180 days before the index date. The risk of myocardial infarction in the three periods of cessation of exposure were analysed using a Cox proportional hazards model that included potential confounders and cardiac co-medication. These analyses were performed for the whole group and for subgroups of β-blockers. Results: Discontinuation of any β-blocker was not associated with an increased risk of myocardial infarction compared with current use of a β-blocker. Analyses within subgroups showed that discontinuation of selective β-blockers was associated with an increased risk of myocardial infarction compared with current use of any β-blocker within the first 30 days (relative risk [RR] 2.70; 95% CI 1.06, 6.89) and also between 30 and 180 days after discontinuation (RR 2.44; 95% CI 1.07, 5.59). No increased risk was demonstrated in the other β-blocker subgroups. Conclusion: Overall, discontinuation of β-blockers was not associated with an increased risk of myocardial infarction. However, when analysed by β-blocker subgroup, cessation of selective β-blockers was associated with an increased risk of myocardial infarction during the first 180 days after discontinuation.

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