Aspirin-free prasugrel monotherapy following coronary artery stenting in patients with stable CAD

Selected in JACC: Cardiovascular Interventions by A. N. Calik

The ASET pilot study: a multicenter, single-arm, first-in-human and proof-of-concept trial which included a total of 212 low-risk patients with stable coronary artery disease

Reviewer

Ali Nazmi Calik

@ANazmiCalik

Interventional cardiologist / Cardiologist

Istanbul, Türkiye

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My Comment

Why this study? – the rationale/objective

Recent studies and meta-analyses have focused on the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) and demonstrated promising results of the strategy including a shortened period of DAPT (1 to 3 months) followed by a P2Y12 inhibitor only. 

Nonetheless, the ASET Pilot Study took a step further by investigating whether dropping aspirin at the day after index PCI and proceeding solely with prasugrel is safe and feasible.

How was it executed? – the methodology

The ASET is a multicenter, single-arm, first-in-human and proof-of-concept trial which included a total of 212 low-risk patients with stable coronary artery disease (CAD).

After careful screening, 201 eligible patients (mean age 59.5 years; 35% female) who had an anatomic SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score < 23 before PCI and underwent successful PCI with optimal implantation of newer-generation, thin-strut everolimus-eluting stents (EES) due to stable CAD with evidence of myocardial ischemia by symptoms or non-invasive tests were enrolled to the study. The main exclusion criteria were having a history of acute coronary syndrome (ACS) or PCI within 12 months, high-risk features for PCI (bifurcation lesion, left main disease, chronic total occlusion, saphenous or arterial graft disease) and indication for oral anticoagulant therapy.
Apart from the patients already on long-term antiplatelet therapy, patients were loaded 300 mg aspirin and 600 mg clopidogrel at least two hours before the index PCI. After successful ESS deployment, patients were loaded 60 mg prasugrel in the catheter laboratory and followed for three months with 10 mg prasugrel once-daily therapy.

The primary ischemic endpoint was a composite of cardiac death, spontaneous target vessel myocardial infarction (MI) (48 h after the index procedure), or definite stent thrombosis up to 3 months after the index procedure. The primary safety endpoint was any Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding up to 3 months after the index procedure.

What is the main result?

As regards to the lesion and procedural characteristics, the mean SYNTAX score of the study population was 7.2, and the mean total stent length per patient was 24 mm. Post-procedural TIMI 3 flow grade was achieved in 99.6 % of patients, and adherence to prasugrel monotherapy was 98.5%.

During 3-month follow-up, the primary ischemic (0.5%) and bleeding (0.5%) endpoints occurred in 1 patient who died because of hemorrhagic stroke due to intracranial bleeding (BARC type 5b) after the index procedure. No definite or probable stent thrombosis and spontaneous MI occurred over the study period.

Critical reading and the relevance for clinical practice:

The results of the recent trials (GLOBAL-LEADERS, STOPDAPT-2, SMART-CHOICE, TICO and TWILIGHT) evaluating short-term DAPT in post-PCI patients provided substantial evidence with regards to the safety and efficacy of aspirin-free treatment strategies. Generally, aspirin withdrawal at 1 or 3 months of DAPT followed by a P2Y12 inhibitor-only therapy scheme did not only reduce bleeding events but also provided similar efficacy on ischemic endpoints.

Besides the advanced PCI techniques and drug-eluting stent (DES) technology, the utility of short-term DAPT allowed the ASET pilot study investigators to question whether extending the use of monotherapy with a P2Y12 inhibitor to the immediate post-PCI period is feasible and safe.

Even though no episode of definite stent thrombosis or spontaneous MI were seen under prasugrel monotherapy over the study period, one should consider following limitations of the trial while implementing the results to daily practice.

Firstly, the rationale of aspirin-free antiplatelet strategy with a potent P2Y12 inhibitor aims to reduce bleeding events in high bleeding risk (HBR) patients, while precluding thrombotic complications. Since the ASET population consist of patients with noncomplex coronary artery disease and nonacute presentation, it is not plausible to apply the results of the study to high-risk patients. The authors, however, acknowledge that limitation and justify their strict patient selection criteria with safety concerns for prasugrel monotherapy.

Secondly, although only one case suffered from a fatal bleeding event, this corresponds to a rate of 0.5% over three months in a low-risk patient population and exceeds the bleeding rates (0% - 0.13%) of previous trials with short DAPT strategies that included higher-risk patients.

In a nutshell, aspirin-free prasugrel therapy may be a feasible option in low-risk stable CAD patients after successful PCI with DES, but not ready for clinical implementation before being compared to DAPT in large, properly designed and adequately powered randomized trials.