High On-Treatment Platelet Reactivity After Prasugrel Loading Dose and Cardiovascular Events After Percutaneous Coronary Intervention in Acute Coronary Syndromes

Study Questions:

What is the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events?

Methods:

This was a prospective multicenter study including patients who underwent successful percutaneous coronary intervention (PCI) for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. Major adverse cardiac events included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month.

Results:

A total of 301 patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range, 51-64% and 5-47.6%, respectively; p < 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70).

Conclusions:

The authors concluded that despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition.

Perspective:

The present study reports that a significant number of patients receiving prasugrel for ACS and treated by PCI have insufficient PR inhibition, as assessed by the VASP index. Furthermore, these patients with high on-treatment PR after prasugrel LD had a significantly higher rate of recurrent thrombotic events during the 1-month follow-up period after PCI. These results suggest that PR monitoring to tailor P2Y12-ADP receptor antagonist therapy may be of interest, but given the negative results of the GRAVITAS trial, the concept of an optimal level of PR inhibition to further improve clinical outcomes remains to be confirmed.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery, Interventions and ACS

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Follow-Up Studies, Receptors, Purinergic P2, Thiophenes, Blood Platelets, Piperazines, Coronary Artery Bypass, Stents, Percutaneous Coronary Intervention


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