The smoking cessation drug varenicline is associated with a 72% relative increase in the risk in cardiovascular events, new research shows.
A systematic review and meta-analysis by a team of international researchers found varenicline was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo.
The authors called for increased regulatory scrutiny of varenicline, which was prescribed by GPs to nearly one million smokers in England in 2010, NHS figures show.
The researchers studied data from 14 double-blind randomised controlled trials involving 8,216 tobacco users – smokers and users of smokeless tobacco – ranging in duration from seven to 52 weeks.
They found 1.06% of the 4,908 patients taking varenicline 1mg twice daily had adverse events compared with 0.82% of 3,308 patients on a placebo. The small overall difference was still equivalent to a pooled odds ratio of 1.72.
The researchers acknowledged their estimates were ‘imprecise owing to the low event rates [and because] none of the trials was adequately powered to detect individual differences in cardiovascular events.'
But, they argued: ‘Despite the limitations of our analysis, our findings have potential regulatory and clinical implications.'
Study leader Dr Sonal Singh, assistant professor of medicine at John Hopkins University in Baltimore, concluded in the Canadian Medical Association Journal, in which the study is published online: ‘Despite achieving more than two-fold higher rates of abstinence in the trials, which should potentially induce a cardiovascular benefit, the participants taking varenicline experienced an increase risk of serious adverse cardiovascular events.'
Dr Yoon Loke, senior lecturer in clinical pharmacology at the University of East Anglia and a study author, told Pulse: ‘Varenicline has taken off in a big way and in my area GPs are very keen on it, but there are non-medical alternatives. I'm not sure we need drugs for smoking cessation when there are valid non-medical alternatives.'
But Dr Alex Bobak, a GPSI in smoking cessation in Wandsworth, London, said: ‘This is a group of patients who really need good treatments. The researchers have looked at relative risk but not overall benefit, which is the most important thing, and it's also not clear what they mean by significant cardiovascular events. It's certainly food for thought but my advice to GPs would not be to change their prescribing practice.'
Last month the US Food and Drug Administration (FDA) issued a safety warning that varenicline ‘may be associated with a small, increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease.'
But the European Medicines Agency renewed the licence for Champix, the brand name of varenicline, in March, after its Committee for Medicinal Products for Human Use concluded ‘the overall benefit-risk balance of varenicline remains positive'.
A spokesperson for Pfizer, the manufacturer of Champix, said the company is currently working with the FDA to conduct a meta-analysis of the cardiovascular safety of Champix, and added: ‘Pfizer disagrees with the interpretation of the data. The analysis contains several limitations; most notably that it is based on a small number of events, which raises concerns about the reliability of the authors' conclusions.'
CMAJ 2011, online 4 July http://www.cmaj.ca/cgi/doi/10.1503/cmaj.110218