Prasugrel treatment can overcome clopidogrel nonresponsiveness, and with platelet aggregation inhibition, can lead to a low rate of long-term cardiac mortality and stent thrombosis, according to research published in the Journal of the American College of Cardiology: Cardiovascular Interventions.

Patients on clopidogrel treatment with high residual platelet reactivity who undergo percutaneous coronary intervention (PCI) are at significant risk for ischemic events. Plasugrel has been known to provide platelet aggregation inhibition for most clopidogrel nonresponders.

The RECLOSE-3 (Responsiveness to Clopidogrel and Stent Thrombosis) study tested prasugrel treatment in clopidogrel nonresponders undergoing PCI.  Researchers of Careggi Hospital in Florence, Italy screened 1550 patients for nonresponsiveness with a 600 mg dose of dopidogrel and found 302 clopidogrel nonresponders with >70% residual platelet activity on the adenosine diphosphate (ADP) test. 


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The nonresponders switched to 10 mg per day of prasugrel the day of their PCI. After 6 days, researchers performed another ADP test.

“The main finding of the RECLOSE-3 study is that nonresponsiveness to clopidogrel is a modifiable risk factor for cardiac death after PCI,” the authors wrote.  “The RECLOSE-3 shows that clopidogrel nonresponders switching to prasgrel treatment is associated with a 2-year cardiac mortality rate nearly identical to the population of clopidogrel responders in the RECLOSE-2-ACS: 4% and 4.3%, respectively.”

The initial ADP test was approximately 77.6% among the 302 patients. The ADP results decreased to approximately 47.1% when the patients switched to prasugrel. The RECLOSE-3 group had more 3-vessel PCIs and unprotected left main PCIs than the RECLOSE-2-ACS study. Fewer RECLOSE-3 patients were prescribed aspirin and proton pump inhibitors than in RECLOSE-2-ACS.

The data showed a 2-year cardiac mortality rate of 4%compared with the 9.7% mortality rate of the RECLOSE-2-ACS trial (P=.007). The survival rate of freedom from cardiac death and myocardial infarction was approximately 93%. 

After 1 year, 88% of the RECLOSE-3 patients were on thienopyridine treatment and 21% after 2 years. The definite stent thrombosis rate was 0.7%, and the probable stent thrombosis rate was 4.4% (P=.004).

The authors note that, “this patient cohort may be considered representative of the broad spectrum of patients with coronary artery disease who are treated by PCI.” They also suggest that additional studies be conducted to tailor treatment therapies using new antithrombotic agents.

Reference

  1. Valenti R, Marcucci R, Comito V, et al. Prasugrel in Clopidogrel Nonresponders Undergoing Percutaneous Coronary Intervention. J Am Coll Cardiol. 2015;8(12):1563-70. doi: 10.1016/j.jcin.2015.07.010.