RAPID: Effectiveness of antiplatelets not so fast in some STEMI patients

A randomized clinical trial that compared prasugrel with ticagrelor in STEMI patients undergoing PCI offered differing results from previous studies that had been based on healthy volunteers or patients with stable coronary artery disease.

The study appeared in the April 16 issue of the Journal of the American College of Cardiology.

Guido Parodi, MD, PhD, of Careggi Hospital in Florence, Italy, and colleagues designed the RAPID (Rapid Activity of Platelet Inhibitor Drugs) study as a noninferiority trial. The randomized two-arm prospective trial enrolled 50 patients with STEMI on bivalirudin monotherapy, half of whom received a loading dose of 60 mg prasugrel (Effient, Eli Lilly/Daiichi Sankyo) and half 180 mg ticagrelor (Brilinta, AstraZeneca) before primary PCI. In both groups, they measured residual platelet reactivity at two, four, eight and 12 hours after the loading dose.

The primary endpoint was residual platelet reactivity at two hours after the loading dose. Secondary endpoints included the percentage of patients with high residual platelet reactivity at two hours after the loading dose and acute stent thrombosis. They defined high residual platelet reactivity using platelet reactivity unit (PRU) values.   

The characteristics of the two groups were similar at baseline. Parodi et al found no differences in PRU values at two hours between the two groups, making prasugrel noninferior to ticagrelor for platelet inhibition at two hours. There also was no difference in clinical event rates.

High residual platelet reactivity, with PRUs of 240 or greater, was found in 44 percent of the prasugrel group and 60 percent of the ticagrelor group two hours after the loading dose. The mean time to achieve PRU below 240 was three hours in the prasugrel group and five hours in the ticagrelor group. Morphine use was associated with a delay in antiplatelet activity.

Parodi et al emphasized that their study, based on STEMI patients in a clinical setting, found wide variability in the response to both new oral antiplatelet agents, with the drugs being effective in only half of the patients at two hours after the loading dose; it took about four hours for the drugs to be fully effective.

They proposed that differences between their results and findings from pharmacodynamic substudies of the TRITON–TIMI-38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel—Thrombolysis in Myocardial Infarction-38) and PLATO (Platelet Inhibition and Patient Outcomes) may come down to the patient populations, since the latter two included few STEMI patients. Drug absorption may differ in STEMI patients and in healthy volunteers or patients with stable coronary artery disease, for instance.

The RAPID researchers underscored the finding that showed high residual platelet reactivity in more than half of the patients. “This means that the majority of the procedures of stenting of the infarct-related artery were performed without functional evidence of a significant antiplatelet effect,” they wrote.

“Given the fact that HRPR [high residual platelet reactivity] is an important determinant of the risk of stent thrombosis, and that the majority of STEMI patients require at least four hours to achieve a sufficient drug effect after a prasugrel or ticagrelor LD [loading dose], we can imagine a significant time window after PPCI, in which many patients are at high risk of stent thrombosis,” they continued. “Thus, all these findings raise the question for the need of different pharmacological strategies in the first hour after STEMI onset.”

They acknowledged that their study was small and relied on only one test (VerifyNow) to assess residual platelet reactivity. Also, all RAPID patients had received bivalirudin monotherapy, and results may differ in patients who get other treatments.