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Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
Background: Smoking is the leading cause of preventable death worldwide. Although smoking cessation (SC) pharmacotherapies have been shown to have a moderate short-term benefit as a quitting aid, substantial cardiovascular and neuropsychiatric safety concerns have been identified in adverse reporting databases, leading to prescription label warnings by Health Canada and the U.S. FDA. However, recent studies indicate these warnings may be without merit.Objectives: This thesis examined the comparative safety and effectiveness of medications commonly used to aid smoking cessation. The thesis focused on real-world safety of varenicline, bupropion, and nicotine replacement therapy (NRT). It also demonstrated a novel method of measuring comparative effectiveness using drug therapy re-initiation as a proxy for treatment failure. Design and Setting: Retrospective cohort studies using linked de-identified claims data from the British Columbia Ministry of Health and U.S. MarketScan® databases. Outcomes: The primary safety outcome was a composite of cardiovascular hospitalizations. Secondary safety outcomes included: all-cause mortality, a composite of neuropsychiatric hospitalizations, and individual components of the primary outcome. Effectiveness was measured using drug therapy re-initiation. Statistical Analysis: Propensity score adjusted log-binomial and Cox proportional hazards regression models.Results: 116,442 B.C. participants and 618,497 U.S. participants were analyzed. In the U.S., compared to NRT, varenicline was associated with a 20% lower 1-year CV risk [adjusted risk ratio (RR) = 0.80, 95% Confidence Interval (CI): (0.75 – 0.85)] and bupropion was associated with a 25% lower 1-year CV risk [RR=0.75, 95% CI: (0.69 – 0.81)]. Varenicline was associated with a 26% lower 1-year risk of neuropsychiatric hospitalization versus NRT [RR=0.74, 95% CI: (0.71 – 0.76)]. In B.C., compared to NRT, varenicline was associated with a 20% one-year relative risk decrease of neuropsychiatric hospitalization [RR: 0.80, CI: (0.71 – 0.89)], and a 19% one-year relative risk decrease of mortality [RR: 0.81, CI: (0.71 – 0.93)]. We found no significant difference in risk between NRT and bupropion for cardiovascular hospitalizations, neuropsychiatric hospitalizations, or mortality.Conclusions: Compared to NRT, varenicline was associated with fewer serious adverse events, and bupropion the same number of serious adverse events. Varenicline and bupropion were associated with fewer subsequent SC drug episodes.
No abstract available.