Open AccessCardiovascular adverse events in the drug‐development program of bupropion for smoking cessation: A systematic retrospective adjudication effort
Author(s) -
Kittle Jessie,
Lopes Renato D.,
Huang Mingyan,
Marquess Marsha L.,
Wilson Matthew D.,
Ascher John,
Krishen Alok,
Hasselblad Vic,
Kolls Brad J.,
Roe Matthew T.,
McGuire Darren K.,
Russell Stuart D.,
Mahaffey Kenneth W.
Publication year - 2017
Publication title -
clinical cardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.263
H-Index - 72
eISSN - 1932-8737
pISSN - 0160-9289
DOI - 10.1002/clc.22744
Subject(s) - bupropion , medicine , placebo , smoking cessation , adverse effect , retrospective cohort study , clinical endpoint , clinical trial , alternative medicine , pathology
Background In 2011, the US Food and Drug Administration requested that GlaxoSmithKline perform retrospective adjudication of cardiovascular ( CV ) events reported in the bupropion drug‐development trials for smoking cessation. Hypothesis Retrospective adjudication of clinical trial data will not increase the identification of adverse events. Methods We performed a comprehensive retrospective analysis of adverse events in 19 previously completed controlled US clinical trials of bupropion marketed for the treatment of smoking cessation, yielding 9479 subjects (5290 bupropion, 2927 placebo, 1018 active control [ ACT ], and 244 treated concurrently with bupropion and ACT ). All adverse events were sent to the Duke Clinical Research Institute for adjudication by Clinical Events Classification (CEC) physician reviewers. The primary endpoint was a composite of major adverse CV events: CV death, nonfatal myocardial infarction ( MI ), and nonfatal stroke. Results Overall, 416 nonfatal CV events in 366 subjects, and 22 deaths, were identified and processed for adjudication. Of these, 7 nonfatal MIs (4 bupropion, 3 placebo, 0 ACT ), 5 nonfatal strokes (1 bupropion, 3 placebo, 1 ACT ), and 9 CV deaths (4 bupropion, 4 placebo, 1 ACT ) were confirmed by the CEC Committee. The primary endpoint occurred in 3/4297 (0.07%) subjects in the bupropion group and in 4/2927 (0.14%) subjects in the placebo group (log‐rank P value: 0.613). Conclusions CV events in bupropion clinical trials for smoking cessation were uncommon, with no observed increase among subjects assigned to bupropion vs placebo. However, this effort was limited by a paucity of quality data.