The rate of major adverse cardiovascular events was higher among patients treated with varenicline than those on placebo in a meta-analysis, but the difference was not statistically significant, according to the latest Food and Drug Administration statement on the cardiovascular safety of the smoking cessation drug.
In the study, conducted by the manufacturer at the request of the FDA, major adverse cardiovascular events (MACEs), a composite endpoint of cardiovascular-related death, nonfatal MI, and nonfatal stroke, "were uncommon in both the Chantix and placebo groups, and the increased risk was not statistically significant, which means it is uncertain whether the excess risk for the Chantix group was due to the drug or due to chance," the FDA statement said. Varenicline, a nicotinic receptor partial agonist marketed as Chantix by Pfizer, was approved in 2006.
Courtesy CDC/Debora Cartagena
Patients treated with varenicline had a higher rate of major adverse cardiovascular events compared with patents on placebo, but the difference was not statistically significant.
The first notice issued by the FDA about the drug’s possible cardiac risks was in June 2011. That notice reported the increased risk in a smoking cessation trial of patients with stable cardiovascular disease, prompting the FDA to require the company to conduct the meta-analysis. The FDA statement, dated Dec. 12, says the findings of the meta-analysis are similar to the findings of the smoking cessation study.
The meta-analysis compared the MACE incidence of patients treated for at least 12 weeks, in 15 randomized, double-blind, placebo-controlled studies conducted by Pfizer. Within 30 days of stopping the drug, the incidence of MACE was 0.31% (13 cases among 4,190 patients) in those on the drug, compared with 0.21% (6 cases among 2,812 on placebo). This is comparable to an increase of 6.3 MACE cases per 1,000 patient years of exposure, the FDA said.
In the study, the rates of composite outcomes were higher among those on varenicline "across different time frames and prespecified sensitivity analyses, including various study groupings and cardiovascular endpoints," and while not significantly different, they were consistent, the statement said.
The FDA also points out that cardiovascular mortality and all-cause mortality, components of the MACE endpoint, were lower among the patients on varenicline, although the differences were not significant. The rate of cardiovascular mortality was 0.05% (two cases) among those on varenicline, compared with 0.07% (two cases) among those on placebo. The rate of all-cause mortality was 0.14% among those on varenicline (6 cases), compared with 0.25% (7 cases) among those on placebo.
In the statement, the FDA advises that when weighing the risks and benefits of varenicline, health care professionals should consider the "immediate and substantial" health benefits of quitting smoking, and that "Chantix is effective in helping patients to quit smoking and abstain from it for as long as one year," the FDA advised in the statement. Patients should also be counseled to seek medical help if they develop new or worsening cardiovascular disease symptoms during treatment with varenicline, the statement added.
The results of the meta-analysis have been added to the warnings and precautions section of the drug’s label.
About 2.3 million varenicline prescriptions were dispensed and about 1.26 million patients received prescriptions for the drug from outpatient retail pharmacies in the United States, during the 12-month period ending in September 2012, according to the FDA.
The safety communication is available here. Serious adverse events associated with varenicline should be reported to the FDA at 800-332-1088 or here.