Use of varenicline for smoking cessation and risk of serious cardiovascular events: nationwide cohort study

Abstract

Objective: To investigate whether varenicline is associated with an increased risk of serious cardiovascular events compared with another drug used for smoking cessation, bupropion.

Design: Nationwide historical cohort study.

Setting: Denmark, 2007-10.

Participants: New users of varenicline (n = 17,926) and bupropion (n = 17,926).

Main outcome measures: Individual level data on dispensed drug prescriptions, cardiovascular events, and potential confounders were linked between registries. Cox regression was used to estimate hazard ratios of cardiovascular events in analyses matched for propensity score. The primary outcomes at six months after start of treatment were acute coronary syndrome, ischaemic stroke, and cardiovascular death analysed individually and as a composite of any major event.

Results: There were 57 major cardiovascular events among varenicline users (6.9 cases per 1000 person years) compared with 60 events among bupropion users (7.1 cases per 1000 person years); the hazard ratio for any major event was 0.96 (95% confidence interval 0.67 to 1.39). Varenicline use was not associated with an increased risk of acute coronary syndrome (1.20, 0.75 to 1.91), ischaemic stroke (0.77, 0.40 to 1.48), and cardiovascular death (0.51, 0.13 to 2.02). In subgroup analyses, the risk of any major cardiovascular event was not significantly different between patients with and without a history of cardiovascular disease (1.24 (0.72 to 2.12) and 0.83 (0.51 to 1.36), respectively; P=0.29).

Conclusions: This cohort study found no increased risk of major cardiovascular events associated with use of varenicline compared with bupropion for smoking cessation. On the basis of the upper confidence limit, the data allowed the exclusion of a 40% increased risk of the composite outcome of any major cardiovascular event. While the estimates were less precise for specific outcomes, any differences would be small in absolute terms.

Fig 1 Kaplan-Meier curves of major cardiovascular events among users of varenicline and bupropion. Major cardiovascular event was defined as any of acute coronary syndrome, ischaemic stroke, or cardiovascular death. Primary analysis was major cardiovascular events at six months

Fig 2 Additional analyses of association between varenicline and risk of major cardiovascular events compared with bupropion. Major cardiovascular event was defined as any of acute coronary syndrome, ischaemic stroke, or cardiovascular death. *Six months’ follow-up. †Includes acute coronary syndrome, other ischaemic heart disease, cardiac surgery/invasive cardiac procedure, heart failure/cardiomyopathy, peripheral arterial disease or procedure to treat this condition, and cerebrovascular disease