Cardiovascular and neuropsychiatric risks of varenicline: a retrospective cohort study

Daniel Kotz,Wolfgang Viechtbauer,Colin Simpson,Onno C P Van Schayck,Robert West,Aziz Sheikh

doi:10.1016/s2213-2600(15)00320-3

Abstract

SummaryBackgroundVarenicline is an effective pharmacotherapy to aid smoking cessation. However, its use is limited by continuing concerns about possible associated risks of serious adverse cardiovascular and neuropsychiatric events. The aim of this study was to investigate whether use of varenicline is associated with such events.MethodsIn this retrospective cohort study, we used data from patients included in the validated QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients aged 18–100 years (registered for longer than 12 months before data extraction) who received a prescription of nicotine replacement treatment (NRT; reference group), bupropion, or varenicline. We excluded patients if they had used one of the drugs during the 12 months before the start date of the study, had received a prescription of a combination of these drugs during the follow-up period, or were temporary residents. We followed patients up for 6 months to compare incident cardiovascular (ischaemic heart disease, cerebral infarction, heart failure, peripheral vascular disease, and cardiac arrhythmia) and neuropsychiatric (depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders (primary outcomes).FindingsWe identified 164 766 patients who received a prescription (106 759 for nicotine replacement treatment; 6557 for bupropion; 51 450 for varenicline) between Jan 1, 2007, and June 30, 2012. Neither bupropion nor varenicline showed an increased risk of any cardiovascular or neuropsychiatric event compared with NRT (all hazard ratios [HRs] less than 1. Varenicline was associated with a significantly reduced risk of ischaemic heart disease (HR 0·80 [95%CI 0·72–0·87]), cerebral infarction (0·62 [0·52–0·73]), heart failure (0·61 [0·45–0·83]), arrhythmia (0·73 [0·60–0·88]), depression (0·66 [0·63–0·69]), and self-harm (0·56 [0·46–0·68]).InterpretationVarenicline does not seem to be associated with an increased risk of documented cardiovascular events, depression, or self-harm when compared with NRT. Adverse events that do not come to attention of general practitioners cannot be excluded. These findings suggest an opportunity for physicians to prescribe varenicline more broadly, even for patients with comorbidities, thereby helping more smokers to quit successfully than do at present.FundingEgton Medical Information Systems, University of Nottingham, Ministry of Innovation, Science and Research of the German Federal State of North Rhine-Westphalia, Cancer Research UK, Medical Research Council, Commonwealth Fund.

Highlights

Cigarette smoking continues to be one of the leading causes of preventable death, killing nearly 6 million people worldwide each year.[1]
Neither bupropion nor varenicline showed an increased risk of any cardiovascular or neuropsychiatric event compared with nicotine replacement treatment (NRT)
Varenicline, a selective α4β2 nicotine acetylcholine receptor partial agonist, was approved by the US Food and Drug Administration (FDA) and European Medicines Agency as a drug for smoking cessation in 2006, and it has subsequently been recommended by US6 and international[7,8] clinical guidelines.[6,7,8]

Summary

Introduction

Cigarette smoking continues to be one of the leading causes of preventable death, killing nearly 6 million people worldwide each year.[1] Smokers who do not stop lose, on average, a decade of life expectancy.[2] Effective pharmacotherapies to help smokers quit include bupropion, nicotine replacement treatment (NRT), and varenicline.[3,4,5] Varenicline, a selective α4β2 nicotine acetylcholine receptor partial agonist, was approved by the US Food and Drug Administration (FDA) and European Medicines Agency as a drug for smoking cessation in 2006, and it has subsequently been recommended by US6 and international[7,8] clinical guidelines.[6,7,8] Varenicline is more effective than are bupropion[5,9,10,11] and single forms of NRT,[9,12,13] and it has become the most frequently prescribed smoking cessation drug other than NRT.[14] It is effective and safe in increasing long-term smoking cessation rates via smoking reduction in cigarette smokers not willing or able to quit at treatment initiation.[15]

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