(read only) smoke-hays.qcd

Varenicline for smoking cessation: Is it a heartbreaker?
See related research article by Singh and colleagues at http://www.cmaj.ca/lookup/doi/10.1503/cmaj.110218.
In this week’s CMAJ, Singh and colleagues1 cardiovascular disease. A considerable evidence Competing interests:
present a meta-analysis assessing the risk of base supported by multiple randomized con- J. Taylor Hays has receivedgrant funding from Pfizer to serious adverse cardiovascular events asso- trolled clinical trials and meta-analyses shows ciated with the use of varenicline for smoking that varenicline consistently more than doubles cessation. The paper raises additional questions the chances of long-term abstinence from to - bacco.5,8,9 Thus, varenicline should be an important scrutiny by the US Food and Drug Administra- tool for reducing cardiovascular events among tion for neuropsychiatric safety concerns,2 and patients who smoke. How then are we to interpret Correspondence to:
within the past month, the drug has been the focus and apply the results of the meta -analysis pro- of another warning regarding an association vided by Singh and colleagues1 to our clinical between it and serious adverse cardiovascular practices? In this regard, there are several impor- CMAJ 2011. DOI:10.1503
events.3 This new warning is based on observa- /cmaj.110804
tions published in a randomized trial of vareni- First, the main result of the meta-analysis, a cline for the treatment of tobacco dependence 72% increased risk of serious cardiovascular among participants with known cardiovascular adverse events, must be tempered by the rarity of disease.4 Certain serious adverse cardio vascular these events among partipants in both treatment events were seen more frequently among partici- groups (1.06% among patients given varenicline pants receiving varenicline than among those and 0.82% among patients given a placebo) — receiving a placebo, but the differences failed to an absolute percent difference of only 0.24%. reach statistical significance and events were Second, as noted by Singh and colleagues, the rate of participants lost to follow-up was greater The concerns about the cardiovascular safety of in the placebo arm than in the treatment arm in varenicline raised by this new warning makes the most of the studies included in the analysis. This meta-analysis by Singh and colleagues1 timely and introduces bias in determining serious, adverse, important. Varenicline is efficacious for smoking cardiovascular events that favours fewer events cessation,5 but could this be one more case in counted among participants given a placebo. which the treatment is worse than the condition Third, cardiac events were adjudicated in only being treated? A measured view of the evidence of a single study.4 As mentioned earlier, in that the harms of smoking compared with the potential study, no significant differences were seen in the harms of varenicline treatment suggests otherwise. incidence of cardiovascular events or in mortality between people receiving varenicline and those British male doctors, Doll and colleagues showed that smoking kills more than half of persistent Finally, although the point estimates for the smokers.6 In the similarly influential Nurses’ number needed to treat (10) and the number needed Health Study (a prospective cohort study), 104 000US women were followed for 20 years, and the relative risk of mortality from coronary heart dis-ease among women who smoked was four to five • When used as a treatment for tobacco dependence, varenicline may be times the risk seen among women who had never associated with an increase in adverse cardiovascular events.
smoked.7 This study also showed that quitting The absolute increase in the rate of serious cardiovascular events associated smoking is associated with a rapid decline in risk with varenicline versus placebo is less than 1% based on analysis of morethan 8200 participants involved in 13 randomized clinical trials.
of death due to coronary heart disease, with over60% of the full potential benefit occurring within Smoking kills more than half of persistent smokers and reduces lifeexpectancy by up to 10 years, whereas smoking cessation rapidly reduces the risk of future cardiovascular events.
Given such evidence, there is no doubt that Varenicline should continue to be used with appropriate caution to limit effective treatment for tobacco dependence will adverse effects, while capitalizing on its benefits for smoking cessation. reduce the risk of death and morbidity related to to treat for harm (28) are similar, the degree of that it is.5,8,9 Is varenicline risk free? Clearly it is uncertainty for the number needed to treat for harm not, as the meta-analysis presented by Singh and (upper bound of 95% confidence interval [CI] 213) colleagues shows.1 However, the risk for serious is considerably greater than it is for the number cardiovascular adverse events is low and is greatly needed to treat (upper bound of 95% CI 13). These outweighed by the benefits of diminishing the results represent a significant degree of uncertainty truly “heartbreaking” effects of smoking.
about the relative good or harm from varenicline,leaving the issue unsettled. As such, how should References
the results of this meta-analysis guide future studies Singh S, Loke YK, Spangler JG, et al. Risk of serious adverse car- diovascular events associated with varenicline: a systematic reviewand meta-analysis. CMAJ 2011; July 4 [Epub ahead of print].
The best outcome from this analysis would be US Food and Drug Administration. The smoking cessation aids more rigorous and adequately powered studies varenicline (marketed as Chantix) and bupropion (marketed asZyban and generics): suicidal ideation and behavior. FDA Drug evaluating the safety of using varenicline among Safety Newsletter 2009;2:1-4.
smokers who have known cardiovascular disease.
Rigotti NA, Pipe AL, Benowitz NL, et al. Efficacy and safety ofvarenicline for smoking cessation in patients with cardiovascular The worst outcome would be for health care disease: a randomized trial. Circulation 2010;121:221-9.
providers to abandon the use of varenicline, US Food and Drug Administration. FDA Drug Safety Commu-nication: Chantix (varenicline) may increase the risk of certain which has proven to be among the most effica- cardiovascular adverse events in patients with cardiovascular cious pharmacotherapies used for the treatment disease. Available: www .fda .gov /drugs /drugsafety /ucm259161 Cahill K, Stead LF, Lancaster T. Nicotine receptor partial ago- nists for smoking cessation. Cochrane Database Syst Rev 2011; “carefully balance” the risks and benefits of Doll R, Peto R, Boreham J, et al. Mortality in relation to smok- varenicline.1 Although their results suggest that ing: 50 years’ observations on male British doctors. BMJ 2004; a measure of caution should be taken in pre- Kenfield SA, Stampfer MJ, Rosner BA, et al. Smoking and scribing varenicline for the treatment of tobacco smoking cessation in relation to mortality in women. JAMA dependence, the small absolute risk of cardio- Eisenberg MJ, Filion KB, Yavin D, et al. Pharmacotherapies for vascular events associated with taking vareni- smoking cessation: a meta-analysis of randomized controlled tri- cline is outweighed by the enormous benefit of reducing cardiovascular morbidity and mortality Treating tobacco use and dependence: 2008 update. Clinicalpractice guideline. Rockville (MD): US Department of Health that can be achieved with successful abstinence and Human Services. Public Health Service; 2008.
Is varenicline a safe drug? Multiple random- Affiliation: J. Taylor Hays is with the Department of Medi-
ized clinical trials and meta-analyses indicate

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