Trial findings do not support prasugrel monotherapy at the time of primary PCI for STEMI patients

Principal Investigator, Doctor Gaku Nakazawa from Kindai University, Osaka, Japan, explained why the PREMIUM trial was carried out: "Previous randomized trials have demonstrated the safety of 1−3 months of DAPT followed by P2Y12 inhibitor monotherapy compared with 12 months of DAPT.2 However, the safety of initiating prasugrel as monotherapy at the time of contemporary imaging-guided PCI compared with standard 12-month DAPT remains unknown."

The PREMIUM trial was an investigator-initiated, open-label, noninferiority trial conducted at 69 centres in Japan. Participants had a STEMI indicated for primary PCI with current generation platinum‑chromium everolimus-eluting stents. Patients with atrial fibrillation or other indications for oral anticoagulant therapy were excluded. Eligible patients were randomized (1:1) to either prasugrel monotherapy (20 mg loading, 3.75 mg daily) initiated before PCI or standard DAPT with aspirin plus prasugrel for 12 months. Patients at high bleeding risk in the DAPT group could receive DAPT for 3 months then prasugrel monotherapy at the clinician's discretion. A total of 2,280 patients were randomized, with a mean age of around 69 years and 23% were women.

Noninferiority was not demonstrated for prasugrel monotherapy compared with DAPT for the primary endpoint of all-cause death, myocardial infarction or stroke at 12 months. The primary endpoint occurred in 11.0% of patients receiving prasugrel monotherapy and in 8.5% of patients in the DAPT group (hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.02 to 1.75; p=0.40 for noninferiority).

As noninferiority was not met, the major secondary endpoint related to bleeding was not analysed statistically. Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in 5.6% of patients in the prasugrel monotherapy group and 8.4% of patients in the DAPT group at 12 months (HR 0.66; 95% CI 0.47 to 0.91).

Stent-related complications (definite or probable stent thrombosis and clinically driven target lesion revascularization) were similar between groups. In contrast, non-stent related events including non-target lesion revascularisation were more frequent with prasugrel monotherapy.

Doctor Gaku Nakazawa, Kindai University, Osaka, JapanThese findings do not support prasugrel monotherapy at the time of primary PCI for STEMI. It appears that DAPT is needed for at least the first month but the optimum duration of DAPT remains to be determined."

Source:

European Society of Cardiology