Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for Smoking Cessation&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;

Gonzales, David; Rennard, Stephen I.; Nides, Mitchell; Oncken, Cheryl; Azoulay, Salomon; Billing, Clare B.; Watsky, Eric; Gong, Jian; Williams, Kathryn E; Reeves, Karen R.

doi:10.1001/jama.296.1.47

Cited by 1,284 publications

(1,270 citation statements)

References 26 publications

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“…After the removal of duplicates and screening of titles and abstracts, 68 trials underwent full‐text review. In total, 38 RCTs met all eligibility criteria and were included in our meta‐analysis 10, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49…”

Section: Resultsmentioning

confidence: 99%

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

Sterling

Windle

Filion

et al. 2016

JAHA

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BackgroundVarenicline is an efficacious smoking‐cessation drug. However, previous meta‐analyses provide conflicting results regarding its cardiovascular safety. The publication of several new randomized controlled trials (RCTs) provides an opportunity to reassess this potential adverse drug reaction.Methods and ResultsWe searched MEDLINE, EMBASE, and the Cochrane Library for RCTs that compare varenicline with placebo for smoking cessation. RCTs reporting cardiovascular serious adverse events and/or all‐cause mortality during the treatment period or within 30 days of treatment discontinuation were eligible for inclusion. Relative risks (RRs) with 95% CIs were generated by using DerSimonian–Laird random‐effects models. Thirty‐eight RCTs met our inclusion criteria (N=12 706). Events were rare in both varenicline (57/7213) and placebo (43/5493) arms. No difference was observed for cardiovascular serious adverse events when comparing varenicline with placebo (RR 1.03, 95% CI 0.72–1.49). Similar findings were obtained when examining cardiovascular (RR 1.04, 95% CI 0.57–1.89) and noncardiovascular patients (RR 1.03, 95% CI 0.64–1.64). Deaths were rare in both varenicline (11/7213) and placebo (9/5493) arms. Although 95% CIs were wide, pooling of all‐cause mortality found no difference between groups (RR 0.88, 95% CI 0.50–1.52), including when stratified by participants with (RR 1.24, 95% CI 0.40–3.83) and without (RR 0.77, 95% CI 0.40–1.48) cardiovascular disease.ConclusionsWe found no evidence that varenicline increases the rate of cardiovascular serious adverse events. Results were similar among those with and without cardiovascular disease. Given varenicline's efficacy as a smoking cessation drug and the long‐term cardiovascular benefits of cessation, it should continue to be prescribed for smoking cessation.

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Section: Resultsmentioning

confidence: 99%

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

Sterling

Windle

Filion

et al. 2016

JAHA

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“…Thus, β2-containing nAChRs are involved in many of the effects of nicotine that may contribute to nicotine addiction. This may explain why the partial α4β2 agonist varenicline is one of the most effective therapeutics for treating nicotine addiction (Gonzales et al, 2006;Jorenby et al, 2006;Rollema et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

β2 subunit containing acetylcholine receptors mediate nicotine withdrawal deficits in the acquisition of contextual fear conditioning

Portugal

Kenney

Gould

2008

Neurobiology of Learning and Memory

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Acute nicotine enhances contextual fear conditioning, whereas withdrawal from chronic nicotine produces impairments. However, the nicotinic acetylcholine receptors (nAChR) that are involved in nicotine withdrawal deficits in contextual fear conditioning are unknown. The present study used genetic and pharmacological techniques to investigate the nAChR subtype(s) involved in the effects of nicotine withdrawal on contextual fear conditioning. β2 or α7 nAChR subunit knockout (KO) and corresponding wild-type (WT) mice were withdrawn from 12 days of chronic nicotine treatment (6.3 mg/kg/day), and trained with 2 conditioned stimulus (CS; 85 dB white noise) -unconditioned stimulus (US; 0.57mA footshock) pairings on day 13. On day 14, mice were tested for contextual and cued freezing. β2 KO mice did not show nicotine withdrawal-related deficits in contextual fear conditioning, in contrast to WT mice and α7 KO mice. A follow-up study investigated if nicotine withdrawal disrupts acquisition or recall of contextual fear conditioning. The high affinity nAChR antagonist dihydro-beta-erythroidine (DHβE; 3 mg/kg) was administered prior to training or testing to precipitate withdrawal in chronic nicotine-treated C57BL/6 mice. Deficits in contextual fear conditioning were observed in chronic nicotine-treated mice when DHβE was administered prior to training, but not when administered at testing. These results indicate that β2-containing nAChRs, such as the α4β2 receptor, mediate nicotine withdrawal deficits in contextual fear conditioning. In addition, nicotine withdrawal selectively affects acquisition but not recall or expression of the learned response.

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“…In randomized controlled trials, varenicline is more effective than bupropion [28,29]. All patients being treated with varenicline should be observed for neuropsychiatric symptoms including changes in behavior, hostility, agitation, depressed mood, and suicide-related events, including ideation, behavior, and attempted suicide.…”

Section: What To Do In Case Of Relapse? a Practical Algorithmmentioning

confidence: 99%

Handling relapse in smoking cessation: strategies and recommendations

Caponnetto

Keller²,

Bruno

et al. 2012

Intern Emerg Med

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Once established, smoking is a very difficult addiction to break. Many smokers persist in tobacco use for several years and typically cycle through multiple periods of remission and relapse. Smoking cessation is not a single event but a process, and relapse is an ordinary component of this process. While international guidelines place great emphasis on relapse prevention, very little can be found about managing smokers who have relapsed. This article is intended to address the challenge of managing smokers who relapse in the course of a smoking cessation program. This knowledge may lead to an improved smoking cessation outcomes.

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Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for Smoking Cessation<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

Abstract: clinicaltrials.gov Identifier: NCT00141206.

Cited by 1,284 publications

References 26 publications

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

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

β2 subunit containing acetylcholine receptors mediate nicotine withdrawal deficits in the acquisition of contextual fear conditioning

Handling relapse in smoking cessation: strategies and recommendations

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