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Challenges with clopidogrel pave potential road for new agents
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Coverage from the Transcatheter Cardiovascular Therapeutics (TCT) 2010 meeting
Some researchers said they think that challenges that come with the use of clopidogrel, including the lack of an optimal duration at 1 year and potential interactions with proton pump inhibitors, may provide space for the development of newer antiplatelet agents.
Robert A. Harrington, MD, director of the Duke Clinical Research Institute, Durham, N.C., provided data from more than a dozen studies analyzing the effects of dual antiplatelet therapy. The agents included in the cluster of analyses included clopidogrel (Plavix, Sanofi-Aventis/Bristol-Myers Squibb), prasugrel (Effient, Eli Lilly) and ticagrelor (Brilinta, AstraZeneca).
Although associations between extended use of clopidogrel and a reduced risk for death have been previously reported, appropriate clopidogrel duration can only be determined within the context of a large-scale randomized clinical trial, Harrington said. One such trial (DAPT) has yet to be completed.
Until then, Harrington said, treatment should be individualized based on the risk-benefit ratio for each patient.
“The bottom line is that, while the recommendations up to a year are clear, beyond that they are much less clear,” he said.
Harrington also noted that clopidogrel’s interactions with proton pump inhibitors (PPIs), and in particular omeprazole (Prilosec, Proctor and Gamble), present care givers using clopidogrel with another challenge. Due to the effect of omeprazole on clopidogrel’s active metabolite, the FDA recently released a statement warning against concomitant use; the warning further stated that separating the doses in time will not reduce the interaction.
TRITON-TIMI 38 data showed that in patients on a PPI at randomization, the incidence of CV death, MI or stroke was roughly 3% lower in those treated with prasugrel than in those treated with clopidogrel.
More recently, the PLATO trial compared clopidogrel and ticagrelor in patients with planned invasive strategy for acute coronary syndromes. Results showed a lower rate of CV death, MI and stroke in patients on ticagrelor than in those on clopidogrel (9% vs. 10.7%; P=.0025).
“New agents, including ticagrelor and prasugrel, clearly beat clopidogrel,” Harrington said, with neither appearing to “have an issue with CYP pathways or PPIs.”
Disclosures:
- Dr. Harrington reports receiving research grants and contracts from AstraZeneca, BMS, Lilly, Merck, Novartis, Portola, Sanofi-Aventis and The Medicines Company. He also reports serving as a consultant for AstraZeneca, BMS, Merck and Novartis.