AMSTERDAM – Dropping aspirin and using low-dose prasugrel (Effient) alone in the initial month of treatment after percutaneous coronary intervention (PCI) failed to lower bleeding risk, compared with dual antiplatelet therapy (DAPT), and there was a signal of possible harm in terms of increased subacute stent thrombosis, in the STOPDAPT-3 trial.
“Therefore, dual antiplatelet therapy with aspirin and a P2Y12 inhibitor should still remain the standard strategy at least for 1 month after PCI,” said the trial’s lead investigator Masahiro Natsuaki, MD, Saga (Japan) University.
The STOPDAPT-3 trial was presented at the recent annual congress of the European Society of Cardiology.
Designated discussant Marco Valgimigli, MD, Cardiocentro Ticino Foundation, Lugano, Switzerland, explained that the current wisdom before this study was that aspirin withdrawal in the postacute phase after PCI (after 1 month of DAPT onwards) is associated with lower bleeding risk without affecting ischemic risk, but this STOPDAPT-3 trial is the first to look at the idea of not giving aspirin at all.
“This study is a well-designed, well-conducted trial, and the results are very clear: Dr. Valgimigli said.
He pointed out that the possible harm was not related to the coprimary cardiovascular composite endpoint, which did fulfill noninferiority, although he acknowledged the “generous” noninferiority margin.
Rather, the possible harm was related to an increase in subacute stent thrombosis, which was three times higher in the nonaspirin group (0.58% vs. 0.17%).
“While these absolute event rates are extremely low, they are unquestionably higher in the nonaspirin group,” he added.
In his presentation, Dr. Natsuaki explained that very short durations (1-3 months) of DAPT followed by P2Y12 inhibitor monotherapy has been shown to reduce bleeding events without increasing cardiovascular events, compared with longer durations of DAPT after PCI using drug-eluting stents.
However, the incidence of major bleeding events within the 1-month mandatory DAPT period after PCI remains high in clinical practice, particularly in patients with ACS or high bleeding risk.
In single-arm studies, use of prasugrel or ticagrelor (Brilinta) alone following new-generation drug-eluting stent implantation was not associated with any stent thrombosis in selected low-risk patients with or without ACS, and it is thought that removing aspirin from the DAPT regimen might reduce bleeding events early after PCI without compromising the risk of cardiovascular events. However, the efficacy and safety of this strategy has not been proven in randomized trials.
STOPDAPT-3 trial
STOPDAPT-3 investigated the efficacy and safety of prasugrel monotherapy compared with 1-month DAPT with aspirin and prasugrel in Japanese patients with ACS or high bleeding risk undergoing PCI with cobalt-chromium everolimus-eluting stents.
The study enrolled 6,002 patients with ACS or high bleeding risk who were randomly assigned to prasugrel monotherapy (3.75 mg/day; the licensed dose in Japan) or to DAPT with aspirin (81-100 mg/day) and prasugrel after a loading dose of prasugrel 20 mg in both groups.
There were two primary endpoints: major bleeding events (defined as BARC type 3 or 5) at 1 month for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month for noninferiority.
The major secondary endpoint was a composite of the coprimary bleeding and cardiovascular endpoints (cardiovascular death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding) at 1 month representing net clinical benefit.
Results showed that, at 1 month, the no-aspirin strategy was not superior to DAPT for the coprimary bleeding endpoint, with major bleeding events occurring in 4.47% of the prasugrel monotherapy group versus 4.71% of those on DAPT (hazard ratio, 0.95; 95% confidence interval, 0.75-1.20).
The prasugrel monotherapy strategy was noninferior to DAPT, although there was a relative 50% margin for the coprimary cardiovascular endpoint. Cardiovascular endpoints occurred in 4.12% of prasugrel monotherapy group versus 3.69% of the DAPT patients (HR, 1.12; 95% CI, 0.87-1.45; P for noninferiority = .01).
The major secondary net clinical benefit endpoint occurred in 7.14% patients in the prasugrel monotherapy group and 7.38% patients in the DAPT group, with no between-group difference, indicating a similar effect on net clinical benefit for both groups.
However, there was an excess of any coronary revascularization (1.15% vs. 0.57%) and definite or probable stent thrombosis (0.71% vs. 0.44%) in the prasugrel monotherapy group compared with the DAPT group, while definite stent thrombosis was not different between the two groups (0.47% vs. 0.37%).
In a subgroup analysis stratified by ACS and non-ACS, the excess risk for cardiovascular events in the no-aspirin group, compared with the DAPT group, was seen in patients with ACS, but not in those without ACS.