Meta-analysis Suggests Small Cardiovascular Risk With Chantix
A new meta-analysis of 14 Chantix (varencicline) trials raises safety concerns, perhaps rashly, about the short-term (≤1 year) cardiovascular risks of the drug. And while the absolute effect size with Pfizer's smoking-cessation drug, versus placebo, was tiny (1.06% - 0.82% = 0.24%), the potential cardiovascular effects of Chantix at least make more physiologic sense than some other studies proposing a short-term risk of cancer with certain antidiabetic drugs (like Actos and Avandia).
In a company press release, issued July 4th,* Pfizer said it "stands behind the benefit/risk profile of Chantix" and "expressed concerns about the reliability of the meta-analysis." Specific concerns related to the "appropriateness of the authors' measure of cardiovascular risk...which combines events that do not share a common biological cause." The probable main objection here is the inclusion of arrhythmias in the composite endpoint, which may not have anything to do with the process of vascular disease. Pfizer also stressed the small absolute difference between Chantix- and placebo-treated patients. The company reported that it plans to conduct its own meta-analysis to assess the potential cardiovascular risks of Chantix.
In June, the FDA posted a warning about the potential, albeit small, cardiovascular risks of Chantix. The warning was based on data from a 1-year, randomized, placebo-controlled trial of 700 smokers. Both the efficacy and safety results are tabulated here. Clearly Chantix improves the chances of quitting (which should lower tobacco-related cardiovascular and cancer risks—!), but short-term cardiovascular risks may also exist with use of the drug.
N.B.--For the safety analysis, the n value in the Chantix arm was 353.
Notably this trial was not powered to detect statistically significant differences in the safety analysis portion of the study. The FDA affirmed that, on the basis of these data, it was "requiring the manufacturer to conduct a large, combined analysis (meta-analysis) of randomized, placebo-controlled trials" to further define the potential, short-term cardiovascular risks of Chantix.
* No holiday for public relations.
In a company press release, issued July 4th,* Pfizer said it "stands behind the benefit/risk profile of Chantix" and "expressed concerns about the reliability of the meta-analysis." Specific concerns related to the "appropriateness of the authors' measure of cardiovascular risk...which combines events that do not share a common biological cause." The probable main objection here is the inclusion of arrhythmias in the composite endpoint, which may not have anything to do with the process of vascular disease. Pfizer also stressed the small absolute difference between Chantix- and placebo-treated patients. The company reported that it plans to conduct its own meta-analysis to assess the potential cardiovascular risks of Chantix.
In June, the FDA posted a warning about the potential, albeit small, cardiovascular risks of Chantix. The warning was based on data from a 1-year, randomized, placebo-controlled trial of 700 smokers. Both the efficacy and safety results are tabulated here. Clearly Chantix improves the chances of quitting (which should lower tobacco-related cardiovascular and cancer risks—!), but short-term cardiovascular risks may also exist with use of the drug.
|
Outcome |
Chantix |
Placebo |
P Value |
|
Continuous
quit rate, % |
47 |
14 |
<.0001 |
|
Continuous abstinence rate, % (weeks 9-52) |
19 |
7 |
<.0001 |
|
Nonfatal MI, % |
2.0 |
0.9 |
Not calculated |
|
Need for coronary revascularization, % |
2.3 |
0.9 |
Not calculated |
|
Angina requiring hospitalization, % |
2.3 |
2.3 |
Not calculated |
|
New diagnosis of PVD or PVD procedure, % |
1.4 |
0.9 |
Not calculated |
Notably this trial was not powered to detect statistically significant differences in the safety analysis portion of the study. The FDA affirmed that, on the basis of these data, it was "requiring the manufacturer to conduct a large, combined analysis (meta-analysis) of randomized, placebo-controlled trials" to further define the potential, short-term cardiovascular risks of Chantix.
* No holiday for public relations.
