June 27th, 2011
Asprin Dosage in U.S. May Explain Disparity in Ticagrelor Results in PLATO
Although the PLATO trial demonstrated the overall superiority of ticagrelor (Brilinta, AstraZeneca) to clopidogrel in more than 18,000 acute coronary syndrome patients worldwide, approval of the drug in the U.S. has been delayed because of ticagrelor’s lack of effect in the prespecified subgroup of patients from North America. Now, two analyses of the trial, presented at the American Heart Association’s Emerging Science series (a new peer-reviewed venue from the AHA), suggest that the North American findings may be the result of more use of high-dose aspirin in U.S. patients.
Ken Mahaffey presented the results from the analyses, which were performed by the Duke Clinical Research Institute and AstraZeneca. The analyses were not able to rule out chance as an explanation for the results in the North American subgroup, but did show that high-dose aspirin (≥300 mg/day) was used far more often in the U.S. than in the rest of the world (53.6% vs. 1.7% of patients).
Mahaffey reported that in patients taking low-dose aspirin, outcomes were better in the ticagrelor group than in the clopidogrel group. The difference was statistically significant in the rest of the world but not in the U.S.:
- For high-dose aspirin in the U.S., the hazard ratio for CV death, MI, or stroke with ticagrelor was 1.62 (CI 0.99-2.64).
- For patients taking low-dose (≤100 mg/day) aspirin in the U.S., the HR with ticagrelor was 0.73 (CI 0.40-1.33).
- For patients taking high-dose aspirin outside the U.S., the hazard ratio with ticagrelor was 1.23 (CI 0.71-2.14).
- For patients taking low-dose (≤100 mg/day) aspirin outside the U.S., the HR with ticagrelor was 0.78 (CI 0.69-0.87).
In an AHA press release, Mahaffey said that “physicians choosing to use ticagrelor in countries where it is approved and available should consider using a low-dose of maintenance aspirin with the drug.”