Cardiovascular Events Associated With Smoking Cessation Pharmacotherapies

Abstract

Background Stopping smoking is associated with many important improvements in health and quality of life. The use of cessation medications is recommended to increase the likelihood of quitting. However, there is historical and renewed concern that smoking cessation therapies may increase the risk of cardiovascular disease events associated within the quitting period. We aimed to examine whether the 3 licensed smoking cessation therapies—nicotine replacement therapy, bupropion, and varenicline—were associated with an increased risk of cardiovascular disease events using a network meta-analysis. Methods and Results We searched 10 electronic databases, were in communication with authors of published randomized, clinical trials (RCTs), and accessed internal US Food and Drug Administration reports. We included any RCT of the 3 treatments that reported cardiovascular disease outcomes. Among 63 eligible RCTs involving 21 nicotine replacement therapy RCTs, 28 bupropion RCTs, and 18 varenicline RCTs, we found no increase in the risk of all cardiovascular disease events with bupropion (relative risk [RR], 0.98; 95% confidence interval [CI], 0.54–1.73) or varenicline (RR, 1.30; 95% CI, 0.79–2.23). There was an elevated risk associated with nicotine replacement therapy that was driven predominantly by less serious events (RR, 2.29; 95% CI, 1.39–3.82). When we examined major adverse cardiovascular events, we found a protective effect with bupropion (RR, 0.45; 95% CI, 0.21–0.85) and no clear evidence of harm with varenicline (RR, 1.34; 95% CI, 0.66–2.66) or nicotine replacement therapy (RR, 1.95; 95% CI, 0.26–4.30). Conclusion Smoking cessation therapies do not appear to raise the risk of serious cardiovascular disease events.

Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

“…This patient‐level meta‐analysis found no significant difference in rates of cardiovascular SAEs and low absolute risk of cardiovascular SAEs with the use of varenicline. Finally, a network meta‐analysis conducted by Mills et al also found no evidence of cardiovascular harm with varenicline 6. Our meta‐analysis incorporated safety data from 16 new trials (including 1 conducted in the highest‐risk patient population studied to date), nearly doubling the number of events available to pool.…”

“…However, concerns exist regarding the cardiovascular safety of varenicline. Previous meta‐analyses provided conflicting results regarding the association between varenicline and adverse cardiovascular events 3, 4, 5, 6. In addition, the US Food and Drug Administration (FDA) has issued a warning regarding serious cardiovascular events that may occur in patients taking the drug 7.…”

Short‐Term Safety of Nicotine Replacement in Smokers Hospitalized With Coronary Heart Disease

“…Although NRT has never clearly been associated with harm in the setting of acute CHD, prior concerns were extrapolated from physiologic data in nonsmokers, in short‐term pharmacologic and physiologic experimental settings, or in case reports or small case series, despite the potential pitfalls in using this kind of data to make clinical decisions. Instead, our well‐powered study joins the majority of observational and randomized trials that have demonstrated a lack of any association between NRT use and morbidity, including patients at hospital discharge for CAD, in the medical intensive care unit, and among the general population 6, 7, 8, 27. Furthermore, recent physiologic studies have called into question the universally held belief that NRT is consistently associated with an increase in blood pressure and heart rate, particularly when it is used to replace cigarette smoking during a short‐term hospitalization 28, 29.…”

Comment on E-Cigarettes and Cardiovascular Risk: Beyond Science and Mysticism

“…2 A recent meta-analysis of controlled smoking cessation trials found that, although nicotine replacement therapies (NRTs) had a higher rate of any cardiovascular events, this was driven only by minor events such as heart palpitations; no elevation in the incidence of major adverse cardiovascular events (MACE) was found. 3 Use of NRTs in high-risk individuals was similarly not associated with an elevated risk for MACE. 3 A populationbased case-controlled study among 68 hospitals in the US found that the use of nicotine patches did not elevate the risk of first myocardial infarction.…”

“…3 Use of NRTs in high-risk individuals was similarly not associated with an elevated risk for MACE. 3 A populationbased case-controlled study among 68 hospitals in the US found that the use of nicotine patches did not elevate the risk of first myocardial infarction. 4 A meta-analysis of 34 randomized controlled trials showed that NRTs did not pose any elevated risk for myocardial infarction, stroke, palpitations, angina, arrhythmia, or hypertension compared with placebotreated patients.…”