Prasugrel in Clopidogrel Nonresponders Undergoing PCI

Study Questions:

What is the efficacy of prasugrel compared with clopidogrel in clopidogrel nonresponders undergoing percutaneous coronary intervention (PCI)?


The RECLOSE-3 (REsponsiveness to CLOpidogrel and StEnt thrombosis) study screened clopidogrel nonresponders after a 600 mg loading dose of clopidogrel. Clopidogrel nonresponders switched to prasugrel (10 mg/day) the day of the PCI, and an adenosine diphosphate (ADP) test (10 μmol/L of ADP) was performed 6 days after the PCI. The primary endpoint was 2-year cardiac mortality. Patient outcome was compared with the RECLOSE-2–ACS study.


The investigators screened 1,550 patients, of whom 302 were clopidogrel nonresponders. The result of the ADP test was 77.6 ± 6.2%. After switching to prasugrel, the ADP test result decreased to 47.1 ± 16.8%. The 2-year cardiac mortality rate was 4% in the RECLOSE-3 study and 9.7% in nonresponders of the RECLOSE 2-ACS study (p = 0.007). The definite and probable stent thrombosis rates were 0.7% and 4.4%, respectively (p = 0.004). On multivariable analysis, prasugrel treatment was related to the risk of 2-year cardiac death (hazard ratio, 0.32; p = 0.036).


The authors concluded that clopidogrel nonresponsiveness can be overcome by prasugrel.


This nonrandomized study suggests that nonresponsiveness to clopidogrel is a modifiable risk factor for cardiac death after PCI and that clopidogrel nonresponders switching to prasugrel treatment are associated with a 2-year cardiac mortality rate nearly identical to the population of clopidogrel responders. Newer P2Y12 inhibitors such as prasugrel or ticagrelor would appear to be the preferred therapy in true clopidogrel nonresponders. A randomized study comparing ticagrelor and prasugrel among clopidogrel nonresponders would provide additional insight.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Adenosine Diphosphate, Mortality, Percutaneous Coronary Intervention, Piperazines, Risk Factors, Stents, Thiophenes, Thrombosis, Ticlopidine

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