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Prolonged clopidogrel does not affect cancer, mortality
Results from a recent meta-analysis indicate that prolonged clopidogrel therapy in addition to aspirin has no effect on cancer or mortality rates.
In several studies, prolonged clopidogrel therapy has been linked to increased rates of cancer and mortality, according to the researchers.
“If confirmed, even relatively small effects of extended clopidogrel and aspirin therapy on mortality or cancer outcomes would have relevance to millions of cardiovascular patients treated with these agents each year,” they wrote in Circulation: Cardiovascular Interventions.
Because even large single randomized trials are not adequately powered to assess mortality or cancer events, the FDA requested a patient-level meta-analysis be conducted using randomized clinical trial data.
The researchers evaluated patient-level data from six randomized trials comparing prolonged clopidogrel therapy with no or short-duration clopidogrel therapy in addition to aspirin in patients with CVD or cerebrovascular disease. The analysis included 48,817 patients and 94,289 patient-years of follow-up.
The randomized trials included in the meta-analysis were CURE, CHARISMA, ACTIVE-A, CREDO, SPS3 and the DAPT study.
During a median follow-up of 546 days, data demonstrated no differences between prolonged clopidogrel plus aspirin and no or short-duration clopidogrel plus aspirin in the following:
- all-cause mortality (7.23% vs. 7.26%; P = .97);
- CV mortality (5.25% vs. 5.22%; P = .86);
- non-CV mortality (1.98% vs. 2.03%; P = .73);
- cancer-related mortality (0.93% vs. 0.99%; P = .59); and
- new cancer diagnoses (2.97% vs. 2.96%; P > .99).
Prolonged clopidogrel plus aspirin was associated with decreased rates of MI (3.21% vs. 4.05%; P < .0001) and stroke (3.04% vs. 3.75%; P < .0001). However, it was also associated with more fatal bleeding (0.39% vs. 0.27%; P = .03), nonfatal bleeding (4.06% vs. 2.68%; P < .0001) and intracranial hemorrhage (0.43% vs. 0.3%; P = .02).
CV causes accounted for more than 70% of deaths and bleeding only accounted for 5%, yet there was no significant reduction in CV mortality, the researchers noted.
“Although the primary aim of the study was to identify whether a mortality increase was observed, and the lack of such finding was reassuring, the observation of no mortality reduction deserves consideration,” they wrote.
The mortality findings are consistent with an independent meta-analysis conducted by the FDA as well as a previous trial-level meta-analysis of 14 randomized clinical trials. The data on cancer events, however, were limited in these studies, according to the researchers.
Overall, because prolonged clopidogrel was associated with increased bleeding as well as reduced ischemic events, the researchers cautioned against broad use of prolonged dual antiplatelet therapy.
“Together, these findings emphasized the need to select extended antiplatelet therapy only in those patients where the risks of ischemia are not expected to be fully counterbalanced by the risks of bleeding,” they wrote. – by Melissa Foster
Disclosures: The study’s statistical analyses were funded by Sanofi S.A. Please see the study for all of the authors’ relevant financial disclosures.