AMSTERDAM — Dropping aspirin and utilizing low-dose prasugrel (Effient) alone within the preliminary month of therapy after percutaneous coronary intervention (PCI) did not decrease bleeding danger in contrast with twin antiplatelet remedy (DAPT), and there was a sign of potential hurt by way of elevated subacute stent thrombosis, within the STOPDAPT-3 trial.
“Subsequently, twin antiplatelet remedy with aspirin and a P2Y12 inhibitor ought to nonetheless stay the usual technique not less than for 1 month after PCI,” mentioned the trial’s lead investigator Masahiro Natsuaki, MD, Saga College, Japan.
The STOPDAPT-3 trial was offered on the latest European Society of Cardiology (ESC) Congress 2023 in Amsterdam, the Netherlands.
Designated discussant Marco Valgimigli, MD, Cardiocentro Ticino Basis, Lugano, Switzerland, defined that the present knowledge earlier than this examine was that aspirin withdrawal within the post-acute section after PCI (after 1 month of DAPT onwards) is related to decrease bleeding danger with out affecting ischemic danger, however this STOPDAPT-3 trial is the primary to take a look at the concept of not giving aspirin in any respect.
“This examine is a well-designed, well-conducted trial, and the outcomes are very clear: there isn’t any good thing about dropping aspirin on this early interval with respect to main bleeding, and on the similar time there was some sign for potential hurt,” Valgimigli mentioned.
He identified that the potential hurt was not associated to the co-primary cardiovascular composite endpoint, which did fulfil non-inferiority, though he acknowledged the “beneficiant” non-inferiority margin.
Reasonably, the potential hurt was associated to a rise in subacute stent thrombosis, which was thrice greater within the non-aspirin group (0.58% vs 0.17%).
“Whereas these absolute occasion charges are extraordinarily low, they’re unquestionably greater within the non-aspirin group,” he added.
In his presentation, Natsuaki defined that very brief durations (1-3 months) of DAPT adopted by P2Y12 inhibitor monotherapy has been proven to cut back bleeding occasions with out rising cardiovascular occasions, in contrast with longer durations of DAPT after PCI utilizing drug-eluting stents.
Nonetheless, the incidence of main bleeding occasions inside the 1-month necessary DAPT interval after PCI stays excessive in scientific follow, significantly in sufferers with ACS or excessive bleeding danger.
In single-arm research, use of prasugrel or ticagrelor (Brilinta) alone following new-generation drug-eluting stent implantation was not related to any stent thrombosis in chosen low-risk sufferers with or with out ACS, and it’s thought that eradicating aspirin from the DAPT routine may scale back bleeding occasions early after PCI with out compromising the danger of cardiovascular occasions. Nonetheless, the efficacy and security of this technique has not been confirmed in randomized trials.
STOPDAPT-3 investigated the efficacy and security of prasugrel monotherapy in contrast with 1-month DAPT with aspirin and prasugrel in Japanese sufferers with ACS or excessive bleeding danger present process PCI with cobalt-chromium everolimus-eluting stents.
The examine enrolled 6002 sufferers with ACS or excessive bleeding danger who have been 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 each teams.
There have been two main endpoints: 1) main bleeding occasions (outlined as BARC sort 3 or 5) at 1 month for superiority; and a pair of) cardiovascular occasions (a composite of cardiovascular dying, myocardial infarction, particular stent thrombosis, or stroke) at 1 month for non-inferiority.
The most important secondary endpoint was a composite of the co-primary bleeding and cardiovascular endpoints (cardiovascular dying, myocardial infarction, particular stent thrombosis, stroke, or main bleeding) at 1 month representing internet scientific profit.
Outcomes confirmed that at 1 month, the no-aspirin technique was not superior to DAPT for the co-primary bleeding endpoint, with main bleeding occasions occurring in 4.47% of the prasugrel monotherapy group vs 4.71% of these on DAPT (hazard ratio, 0.95; 95% CI 0.75 – 1.20).
The prasugrel monotherapy technique was non-inferior to DAPT, though there was a relative 50% margin for the co-primary cardiovascular endpoint. Cardiovascular endpoints occurred in 4.12% of prasugrel monotherapy group vs 3.69% of the DAPT sufferers (hazard ratio, 1.12; 95% CI, 0.87 – 1.45; P for non-inferiority = .01).
The most important secondary internet scientific profit endpoint occurred in 7.14% sufferers within the prasugrel monotherapy group and seven.38% sufferers within the DAPT group, with no between-group distinction, indicating the same impact on internet scientific profit for each teams.
Nonetheless, there was an extra of any coronary revascularization (1.15% vs. 0.57%) and particular or possible stent thrombosis (0.71% vs. 0.44%) within the prasugrel monotherapy group in contrast with the DAPT group, whereas particular stent thrombosis was not totally different between the 2 teams (0.47% vs. 0.37%).
In a subgroup evaluation stratified by ACS and non-ACS, the surplus danger for cardiovascular occasions within the no-aspirin group in contrast with the DAPT group was seen in sufferers with ACS, however not in these with out ACS.
Future: Concentrate on Dose and Timing
In his dialogue, Valgimigli mentioned the implications of this trial for scientific follow have been very clear: “Aspirin stays a cornerstone therapy within the periprocedural and acute section of PCI in sufferers with out indications for oral anticoagulation.”
Nonetheless, he added that the examine opens a number of necessary factors for subsequent dialogue.
These embody the function of sort and dose of P2Y12 inhibitor remedy used; particularly, he questioned whether or not the three.75 mg dose of prasugrel was sufficient.
Valgimigli additionally identified that this examine didn’t embody a purely excessive bleeding danger inhabitants, and he mentioned there was nonetheless potential to analyze peri-procedure vs post-procedure aspirin administration.
The STOPDAPT-3 trial was funded by Abbott Medical Japan. Natsuaki stories honoraria from Abbott Medical Japan, Daiichi Sankyo, and Bayer.
European Society Cardiology Congress 2023. Sizzling Line 3 session: Introduced August 26, 2023.