1. Department of Medical Innovation, Nagoya City University Graduate School of Medical Sciences.
2. Clinical Research Management Center, Nagoya City University Hospital.
3. Core Laboratory, Nagoya City University Graduate School of Medical Sciences.
4. Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences.
5. Department of Pharmacy, Tokushima University Hospital.
6. Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences.
7. Department of Hospital Pharmacy, Nagoya City University Graduate School of Pharmaceutical Sciences.
8. Department of Pharmacy, Nagoya City University Hospital.
9. Department of Cardiology, Nagoya City University Graduate School of Medical Sciences.
Background: Prasugrel inhibits platelet aggregation more potently and exerts therapeutic action faster than clopidogrel. In the global phase III trial conducted in Western and South American countries that excluded Asian countries, prasugrel reduced ischemic events but increased hemorrhagic risk compared with clopidogrel in patients with acute coronary syndrome scheduled for percutaneous coronary intervention. In the Japanese phase III trial for similar patients, the efficacy of prasugrel compared with clopidogrel was comparable to the global trial, but the safety could not be confirmed because of an insufficient number of patients. Furthermore, given the strict enrollment criteria, the results of these trials may not be applicable to routine clinical practice. Accordingly, we compared the hemorrhagic risk of prasugrel and clopidogrel in real-world settings by analyzing adverse drug event reports in post-marketing stages provided by the Japanese regulatory authorities and the U.S. Food and Drug Administration (FDA).
Methods: We analyzed a total of 3,970 reports for prasugrel (n = 518) or clopidogrel (n = 3,452) between 2014 and 2017 in the Japanese Adverse Drug Event Report (JADER) and a total of 91,914 reports for either prasugrel (n = 5,992) or clopidogrel (n = 85,922) between 2009 and 2019 in the FDA Adverse Event Reporting System (FAERS).
Results: In JADER and FAERS, prasugrel was more frequently and significantly associated with hemorrhagic event reports than clopidogrel. After adjustment for known confounders including age, sex, and concomitant medications (aspirin, anticoagulants, and proton pump inhibitors), the hemorrhagic risk of prasugrel compared with clopidogrel remained significant (adjusted reporting odds ratios [95% CI] for total, intracranial, and gastrointestinal hemorrhagic events = 2.42 [1.97-2.96], 2.45 [1.85-3.24], and 2.27 [1.73-2.97] in JADER, and 2.21 [2.09-2.34], 1.21 [1.09-1.33], and 1.41 [1.29-1.54] in FAERS).
Conclusions: The hemorrhagic risk was found to be greater with prasugrel than clopidogrel in real-world patients, including Japanese patients.
Keywords: Clopidogrel, FDA Adverse Event Reporting System, Hemorrhagic risk, Japanese Adverse Drug Event Report, Prasugrel