‘Aspirin-Free’ Antiplatelet Strategy Feasible After PCI, Pilot Study Suggests

A small, pilot study testing prasugrel without aspirin after PCI in low-risk patients with stable coronary artery disease suggests monotherapy with the P2Y12 inhibitor is feasible and safe, with investigators reporting a single fatal bleeding event and no cases of definite or probable stent thrombosis.

It is the “first prospective experience of withholding aspirin the day after index PCI,” the researchers say, but should be considered just proof-of-concept at this point. Their findings, which showed prasugrel started immediately after PCI resulted in adequate stent thrombotic protection, can also be partly attributed to the exclusive use of a newer-generation, thin-strut everolimus-eluting stent with a biodegradable polymer (Synergy; Boston Scientific), they note.

“Additionally, we included only patients with noncomplex, nonacute CAD in whom optimal PCI results were achieved,” Norihiro Kogame, MD (Amsterdam University Medical Center, the Netherlands), and colleagues write in their paper published September 16, 2020, in JACC: Cardiovascular Interventions. “In the present trial, maximal consideration for early stent thrombosis resulted in the enrollment of patients with very low bleeding risk, but the efficacy of the aspirin-free strategy in reducing bleeding among patients at high bleeding risk is of interest and should be investigated in a large-scale RCT.”

Michelle O’Donoghue, MD (Brigham and Women’s Hospital, Boston, MA), who recently published a meta-analysis of trials testing shortened dual antiplatelet therapy (DAPT) duration following PCI, called the new study hypothesis-generating, saying that is far too small to have any meaningful clinical impact at this stage. Like the investigators, however, she believes it would be justified to study the strategy in a larger setting.

“The pilot study has taken shape because we’re not sure yet if it may be safe to discontinue aspirin altogether following an initial loading dose,” said O’Donoghue. “It feels almost heretical to not use aspirin for patients after PCI, because we have held onto the belief for so long that aspirin is the cornerstone of antiplatelet therapy. But when you look at the data it doesn’t fully support the additive value of aspirin once a P2Y12 inhibitor is in place.”

The ASET Pilot Study

For the Acetyl Salicylic Elimination Trial (ASET), the study investigators enrolled 201 low-risk patients with stable CAD. Patients with high-risk features for PCI, such as left main disease or chronic total occlusions, were excluded from the trial, as were those with a history of ACS within the past 12 months. Prior to PCI, subjects were loaded with aspirin 300 mg and clopidogrel 600 mg, and all lesions were treated with the Synergy stent. After the procedure, patients were loaded with prasugrel 60 mg while still in the cath lab and then treated with the 10-mg maintenance dose for 3 months. Patients remained free from aspirin for the duration of the study period. 

As documented, there was a single patient who died on day 3 following an intracranial hemorrhage revealed on CT. The event was adjudicated as cardiac death, BARC type 5b bleeding, and hemorrhagic stroke. There were no spontaneous MIs or stent thromboses during 3-month follow-up. There was one unplanned revascularization of a nontarget vessel. The investigators also analyzed adherence to prasugrel, which they reported was 98.3% at 3 months.

It feels almost heretical to not use aspirin for patients after PCI, because we have held onto the belief for so long that aspirin is the cornerstone of antiplatelet therapy. But when you look at the data it doesn’t fully support the additive value of aspirin once a P2Y12 inhibitor is in place. Michelle O’Donoghue

In an editorial, Usman Baber, MD (University of Oklahoma Health Sciences Center, Oklahoma City), and Dominick Angiolillo, MD, PhD (University of Florida College of Medicine, Jacksonville), call the trial a “provocative” extension of the concept of shortening the time aspirin is used in DAPT. They point out that investigators enrolled low-risk patients, which is reasonable given that it was a pilot study, but say that the rationale for withdrawing aspirin is to lower the risk of bleeding in those at much higher risk.

While the editorialists aren’t entirely convinced the strategy is safe, noting the single massive intracranial hemorrhage followed by cardiac death, they agree the study demonstrated “equipoise for withdrawing aspirin immediately after PCI, directly challenging the existing construct of DAPT as mandatory pharmacotherapy after coronary stenting.”  

Paradigm Turned Around

To TCTMD, O’Donoghue said the initial DAPT trials in PCI tested a strategy of P2Y12 inhibition on top of aspirin, which led to questions about how soon the P2Y12 inhibitor could be stopped. That question has since been flipped around. She highlighted the CAPRIE trial, published nearly 25 years ago, that first showed clopidogrel monotherapy had a slight edge over aspirin alone for reducing the risk of MACE and did not increase the risk of bleeding (in fact, clopidogrel was associated with less gastrointestinal bleeding). The thinking now is that adding aspirin to a P2Y12 inhibitor might not lead to further inhibition of platelet aggregation, although this has been debated, she said.

“Taking a step back and looking at the weight of the data, we now have five randomized trials that have looked at a strategy of P2Y12 inhibitor monotherapy after PCI, both in the elective setting or after ACS, but those trials all study a strategy of discontinuing aspirin either at 1 or 3 months,” O’Donoghue commented. “The data to date suggests that by dropping aspirin [at 1 to 3 months] we can reduce the risk of bleeding by 40%. So far there is no indication that comes at the price of increased cardiovascular events. [ASET] takes things to the next step and asks the question if we can in fact immediately discontinue aspirin after PCI.”

Data to date are reassuring there is no signal of harm with respect to ischemic/thrombotic events with discontinuing aspirin in the first few months, said O’Donoghue. The optimal timing for when to stop aspirin, or whether it needs to be given at all, is still unknown.

In their editorial, Baber and Angiolillo attempt to provide some insight into the expanding evidence base for antiplatelet therapy after PCI. For patients at high bleeding risk, which was recently defined by the Academic Research Consortium-High Bleeding Risk (ARC-HBR) group, they recommend 1 month of DAPT followed by a single antiplatelet agent. For those not at high risk for bleeding, the focus should turn to ischemic risk. If there is a low risk of ischemic events, 3 to 6 months of DAPT followed by aspirin monotherapy is recommended. If the patient is at intermediate or high risk for ischemic events, there are a couple of options, including 12 months of DAPT with a potent P2Y12 inhibitor as well as 1 to 3 months of ticagrelor-based DAPT followed by ticagrelor alone.