Dataset Information

Comparison of Cardiovascular Safety for Smoking Cessation Pharmacotherapies in a Population-Based Cohort in Australia.

ABSTRACT:

Importance

Although concerns exist regarding a potential increased risk of cardiovascular events for smoking cessation pharmacotherapies, there is general consensus that any increased risk associated with their use would be outweighed by the benefits of smoking cessation; thus, clinical guidelines recommend that such pharmacotherapies be offered to everyone who wants to quit smoking. In the interest of minimizing risk to patients, prescribers need evidence indicating how these pharmacotherapies compare with one another in terms of cardiovascular safety.

Objective

To compare the risk of major adverse cardiovascular events (MACE) among individuals initiating varenicline, nicotine replacement therapy (NRT) patches, or bupropion.

Design, setting, and participants

This retrospective, population-based cohort study using linked pharmaceutical dispensing, hospital admissions, and death data was conducted in New South Wales, Australia. Participants included adults who were dispensed a prescription smoking cessation pharmacotherapy between 2008 and 2015 or between 2011 and 2015, depending on the availability of the pharmacotherapies being compared. Pairwise comparisons were conducted for risk of MACE among 122 932 varenicline vs 92 148 NRT initiators; 342 064 varenicline vs 10 457 bupropion initiators; and 102 817 NRT vs 6056 bupropion initiators.

Exposure

First course of the smoking cessation pharmacotherapy of interest.

Main outcomes and measures

The primary outcome was MACE, defined as a composite of acute coronary syndrome, stroke, and cardiovascular death. Secondary outcomes were the individual components of MACE. Inverse probability of treatment weighting with high-dimensional propensity scores was used to account for potential confounding. Cox proportional hazards regression models with robust variance were used to estimate hazard ratios (HRs) and 95% CIs. Data were analyzed January 24, 2019, to September 1, 2021.

Results

The mean (SD) age of included individuals ranged from 41.9 (14.2) to 49.8 (14.9) years, and the proportion of women ranged from 42.8% (52 702 of 123 128) to 52.2% (53 693 of 102 913). The comparison of 122 932 varenicline initiators and 92 148 NRT patch initiators showed no difference in the risk of MACE (HR, 0.87; 95% CI, 0.72-1.07) nor in the risk of the secondary outcomes of acute coronary syndrome (HR, 0.96; 95% CI, 0.76-1.21) and stroke (HR, 0.72; 95% CI, 0.45-1.14). However, decreased risk of cardiovascular death was found among varenicline initiators (HR, 0.49; 95% CI, 0.30-0.79). The results of comparisons involving bupropion were inconclusive owing to wide confidence intervals (eg, risk of MACE: 342 064 varenicline vs 10 457 bupropion initiators, HR, 0.87 [95% CI, 0.53-1.41]; 102 817 NRT patch vs 6056 bupropion initiators, HR, 0.79 [95% CI, 0.39-1.62]).

Conclusions and relevance

The finding of this cohort study that varenicline and NRT patch use have similar risk of MACE suggests that varenicline, the most efficacious smoking cessation pharmacotherapy, may be prescribed instead of NRT patches without increasing risk of major cardiovascular events. Further large-scale studies of the cardiovascular safety of varenicline and NRT relative to bupropion are needed.

SUBMITTER: Havard A

PROVIDER: S-EPMC8630569 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMany placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation.MethodsWe searched the US Centers for Disease Control and Prevention's Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention.ResultsWe identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91-3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12-5.13), bupropion (OR 2.07, 95% CrI 1.73-2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69-2.62), nicotine tablet (OR 2.06, 95% CrI 1.12-5.13) and nicotine gum (OR 1.71, 95% CrI 1.35-2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95-5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09-4.08).InterpretationVarenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.

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