© 2011 NHS Centre for Smoking Cessation and Training (NCSCT)
Authors: Leonie S. Brose, Eleni Vangeli, Robert West and Andy McEwen, 2nd August 2011
In July 2011, the results of a review study on varenicline and cardiovascular disease1 were widely and not always accurately reported in the media.
The authors reviewed 14 double-blind randomised controlled trials; these studies compared the effectiveness of varenicline and a placebo in helping tobacco users to stop. Most of the trials excluded tobacco users with cardiovascular disease within the last six months; one trial included those with stable cardiovascular disease.
A total of 8,216 tobacco users were included in these studies: 4,908 used varenicline and 3,308 used a placebo. The duration of treatment ranged from 7 to 52 weeks and participants were followed up for between 24 and 52 weeks. In this time, 52 (1.06%) participants in the varenicline group experienced a cardiovascular event and 27 (0.82%) in the placebo group. These included any ischemic or arrhythmic adverse cardiovascular events. The difference between the groups was statistically significant which means that, if the authors only looked at this outcome and no others were considered and not reported, there is less than a 1 in 20 chance that it could have occurred without some real underlying difference.
The authors conclude that 1 in 28 smokers treated with varenicline would experience an additional cardiovascular event. However, the difference in the occurrence of cardiovascular events between the varenicline and placebo groups was 0.24% (1.06 – 0.82) which translates into 1 in 417 smokers, not 1 in 28.
An acknowledged source of bias is that the loss to follow-up rate was lower in the varenicline group than the placebo group; so there was more opportunity for adverse events to be detected in the varenicline group and a possibility that events were missed in the placebo group. It is also important to note that with events that are very rare, such as the cardiovascular events in this study, risk estimates are less precise.
One way that the authors could help to establish whether this was a chance finding would be to determine how many of the excess events occurred while on the medication or during a follow-up period when varenicline was no longer being used. It would be less plausible that varenicline had an effect if the cardiovascular events occurred substantially after the medication was no longer being used.
Smoking is a major risk factor for cardiovascular disease; the average smoker has about double the risk of developing heart disease prematurely than a non-smoker.2 Varenicline approximately doubles the chances of stopping smoking.3, 4 When smokers stop smoking, the excess risk of cardiovascular disease goes down by about 50% after the first year.5
The findings of the review indicate that it may be worth investigating cardiovascular events and varenicline further but currently there is little reason to avoid this medication on these grounds. This view is in line with the European Medicines Agency that confirmed a positive benefit-risk balance for varenicline and concluded that its benefits as a smoking-cessation medicine outweigh any slight increase in cardiovascular events.6
Pfizer, the manufacturer of varenicline is conducting a further analysis of the available data on the cardiovascular safety of varenicline, with results expected to be available in 2012.
Leonie Brose and Eleni Vangeli have no conflicts of interest to declare. Robert West undertakes research and consultancy for companies that develop and manufacture smoking cessation medications (Pfizer, J&J, McNeil, GSK, Nabi, Novartis and Sanofi-Aventis). He also is a trustee of QUIT, a charity that provides stop smoking support. Andy McEwen has received travel funding, honoraria and consultancy payments from manufacturers of smoking cessation products (Pfizer, GSK and Novartis). He also receives payment for providing training to smoking cessation specialists and receives royalties from books on smoking cessation. Robert West and Andy McEwen have shares in a patent for a novel nicotine delivery device.