Table 4. Nicotine Patches continued...
There have been at least 12 published randomized, controlled trials evaluating varenicline versus placebo (or other approved agents for smoking cessation) for its ability to affect abstinence rates related to smoking or the use of smokeless tobacco.[2,4,5,6,7,8,9,10,11,12,13,14] All studies were relatively large (129–607 patients per arm) and involved multiple sites and countries. In all studies, varenicline was statistically better in achieving abstinence rates by self-report and carbon monoxide measures than was placebo, and was often better than the other approved smoking cessation comparator arm. Abstinence rates at 12 weeks can be expected to range from 44% to 49% for varenicline, compared to 11% to 17% for placebo; longer-term rates (52 weeks) range from 14% to 22% for varenicline versus 4% to 8% for placebo.
Most studies evaluated varenicline 1 mg twice a day, using a 1-week titration of 0.5 mg daily for 3 days, 0.5 mg twice a day for 4 days, and then 1 mg twice a day for 11 weeks. However, a few studies evaluated different doses, such as 0.3 mg or 0.5 mg daily or 0.5 mg twice a day, and one study evaluated a flexible dosing schedule during weeks 2 to 12 after all participants were titrated up to 1 mg twice a day in an open-label fashion. From these data, varenicline 0.5 mg twice a day appears to be the minimum dose required to achieve statistically significantly better abstinence rates over placebo.[9,10]
Most studies included healthy smokers, i.e., those without significant comorbidities such as cardiovascular disease or psychiatric disease. One study evaluated varenicline in patients with chronic obstructive pulmonary disease, and another study focused on patients with stable cardiovascular disease. However, no studies have evaluated varenicline use in cancer populations.
More than 3,000 patients in clinical trials received varenicline 1 mg twice a day for 12 to 24 weeks. The side effect profile across these 12 studies [2,4,5,6,7,8,9,10,11,12,13,14] was very consistent (although incidence varied) and comprised the following:
Cardiovascular events often occurred as frequently in the placebo and nicotine replacement arms as in the varenicline arm and overall were rare.
Only one study evaluated varenicline in patients with stable cardiovascular disease. At week 24, this study demonstrated 7-day abstinence rates of 34.9% for varenicline versus 15.9% for placebo (P < .0001); at week 52, these rates were 27.9% for varenicline and 15.9% for placebo (P = .0001). The prevalence of any adjudicated cardiovascular event was 7.1% in the varenicline arm and 5.7% in the placebo arm, for a difference of 1.4%.