Rapid Assessment of Cardiovascular Risk Among Users of Smoking Cessation Drugs Within the US Food and Drug Administration’s Mini-Sentinel Program

Study Questions:

Is varenicline tartrate, used for smoking cessation, associated with an increased risk for cardiovascular disease (CVD) events among patients with CVD?


In July 2011, the Food and Drug Administration (FDA) requested that the Mini-Sentinel program perform a rapid safety assessment of the drug. The Mini-Sentinel program has created a distributed network of electronic health care databases with more than 125 million lives and 350 million person-years of longitudinal observation time. In this rapid assessment, individuals who filled a first prescription for varenicline or the comparator drug, bupropion hydrochloride, between January 1, 2006, and July 5, 2011, were identified. The cohort was further restricted to individuals who were 20 years or older on the date of first varenicline or bupropion dispensing (the index date), and who met the following criteria during the preceding 180 days: were continuously enrolled in the health plan with medical and drug coverage, had no dispensing of either drug, had no diagnoses of acute myocardial infarction or acute coronary event, and had a diagnosis code for tobacco use disorder. The outcome of interest was a composite of cardiovascular endpoints including myocardial infarction or unstable angina recorded as the primary diagnosis in an inpatient or emergency room setting.


The primary analysis identified 89,519 eligible individuals initiating varenicline therapy and 113,378 eligible individuals initiating bupropion therapy who had a tobacco use disorder code. For patients initiated therapy (varenicline vs. bupropion) who had a diagnosis of tobacco use disorder, the adjusted incidence rate ratio (IRR) was 1.02 (95% confidence interval [CI], 0.71-1.47). The results did not vary substantially by age group or sex. In the second analysis, patients who initiated therapy specifically for smoking cessation were compared (varenicline vs. bupropion); the adjusted IRR was 0.98 (95% CI, 0.43-2.23). Last, all patients initiating therapy (varenicline vs. bupropion) were compared. In this third analysis, the adjusted IRR was 1.52 (95% CI, 1.21-1.91).


The authors concluded that this rapid assessment found no consistent evidence of increased CV risk during the first treatment episode of varenicline among individuals with no recent diagnosis of CV events when compared with bupropion use.


Although as the authors point out, this analysis is not a comprehensive evaluation, it does suggest that in a real-world population, there is not strong evidence to suggest that varenicline is associated with an increased risk of cardiovascular disease events among patients using this therapy for smoking cessation.

Keywords: United States Food and Drug Administration, Cardiovascular Diseases, Tobacco Use Disorder, Smoking Cessation, Benzazepines, Bupropion

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