ATTUD Journal Club Postings

Is Varenicline More Effective than NRT?

In several studies of varenicline vs. placebo, the magnitude of benefit from varenicline appeared to be more than that usually obtained with NRT. Only two randomized trials have directly compared varenicline with NRT. One trial was a large (n=746), well done study (Thorax 63:717) that found varenicline was more effective than standard dose NRT (26% vs. 20% at 1 yr). The other study was a small (n=32) study (Circulation Journal 74:771) that compared varenicline to high dose nicotine patch (52.5 mg initially). It found very high success rates in both conditions and no difference between varenicline and patch (64% vs. 71% at 6 mo). Both the Cochrane meta­analysis (www.cochrane.org ) and a newer type of meta-analysis (Annals Internal Med 44:588) of these two studies concluded that varenicline “appeared” to be more effective than NRT.

In addition, three non-randomized trials compared outcomes of those using varenicline vs. NRT. The first was a large (n=412) study of smokers seen in a English smoking cessation clinic (Addiction 103:146). It found that those using varenicline had higher short-term quit rates than single NRT (72% vs. 58% at 4 wks) and a slightly higher success than combined patch + oral NRT (72% vs. 66%). The second was an analysis of a very large (n=300,000) database of smokers seen in 42 cessation clinics in England (Mayo Clinic Proc 88:226). Again varenicline produced a slightly higher 4 week quit rates than NRT (44% vs. 37%). The third was an analysis of a Czech smoking cessation clinic (n= 855) that found higher 1 yr rates with varenicline than NRT (43% vs. 31%) and that this also occurred when varenicline was compared to combined NRT (Kralikova et al, Addiction, in press). Of course, the problem with these trials is that smokers self-selected into conditions and the results may be due to selection bias, not due to use of varenicline per se.

In summary, except for the one small study comparing varenicline with high-dose nicotine patch, both randomized trials and real-world effectiveness studies found a slightly higher quit rate with varenicline that with NRT. One caveat is that the number of tests of varenicline vs. NRT is small. Another is that the two studies that compared varenicline to combined patch + oral NRT or to high dose patch found less benefit of varenicline; thus, whether varenicline is truly better than combination treatment or high dose patch is not certain and especially needs further testing.

Although the absolute difference in quit rates in the above studies was small (­7%, +6%, +7%, +12% and +17%), given the large benefit of smoking cessation on health, these differences are likely clinically significant. However, given the concerns about varenicline causing psychiatric or cardiovascular adverse events, one could ask whether this small increase is sufficient to recommend varenicline prior to using combined NRT in most smokers? I think we should briefly inform smokers that “varenicline appears to be more effective than nicotine medications but this is still unclear. Also, some believe varenicline may infrequently cause psychiatric and heart side-effects; however, whether varenicline actually causes these side-effects is unclear” and let the smoker decide between combined NRT (I think all smokers should receive combined patch + oral NRT) and varenicline. Among smokers who have a clinically significant current mental disorder (who likely are more prone to psychiatric disease adverse events), I think we give such smokers the information above but recommend first trying combined NRT before varenicline.

Please note that I have received consulting fees and grants from Pfizer, GSK, and others who market varenicline or NRT products.