Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk

Researchers have found that for high bleeding risk individuals, one month of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with biodegradable-polymer sirolimus-eluting stents reduces bleeding risk and is non-inferior for adverse clinical and cardiac/cerebral events as compared to three months or more of DAPT.¹

The optimal duration of DAPT following PCI has long been a question of interest.^2,3 Professor Marco Valgimigli and colleagues assessed this question in patients prone to bleeding – defining high bleeding risk to include treatment with an oral anticoagulant, recent major bleeding, age >75 years, anemia, or systemic conditions associated with increased bleeding. Importantly, those with high bleeding risk also tend to have a high thrombotic risk.

MASTER DAPT trial. Important because this is the first trial in a high bleeding risk population adequately sized to convincingly demonstrate non-inferiority for ischemia. The new standard of care. pic.twitter.com/jzvxoAbzDg

— Gregg W. Stone MD (@GreggWStone) August 28, 2021

Valgimigli and colleagues enrolled 4,579 patients in a randomized, controlled design to stop dual antiplatelet therapy after 30 days (abbreviated therapy) or to continue for minimally 2 additional months (standard therapy). Of participants enrolled, the mean age was 76 years, 69.3% were men, and 36.2% received concomitant oral anticoagulation. Clinical presentations included ~25% with non-ST elevation myocardial infarction and ~11% with ST-elevation myocardial infarction. Following one-month of DAPT, investigators elected ongoing monotherapy with clopidogrel (56%), ticagrelor (14%), or aspirin (31%).

Among the three ranked primary outcomes, net adverse clinical events occurred in 7.5% versus 7.7% (P<0.001 for noninferiority) and major adverse cardiac or cerebral ischemic events in 6.1% versus 5.9% (P=0.0014 for noninferiority), for abbreviated versus standard groups. There was significantly less major or clinically relevant nonmajor bleeding (6.5% vs. 9.4%, abbreviated versus standard groups, P<0.001 for superiority).

Professor Valgimigli highlighted that “unlike other studies, we did not exclude patients with acute coronary syndrome or limit the number, location, or complexity of the treated lesions. Our results can therefore inform treatment decisions on DAPT at one month after PCI in patients at high risk for bleeding…including those with clinical or angiographic high ischemic risk features.⁴”

#MASTERDAPT is out in @NEJM, short vs standard DAPT in high bleeding risk patients. Will be the most important DAPT Study we see this year. Much respect for the authors. Here’s are some quick thoughts (thread):

– high risk patients (1/3 NSTEMI, 11% STEMI, complex long lesions)

— Robert W. Yeh (@rwyeh) August 28, 2021

Yet, physicians must cautiously assess the generalizability of this study. Participants received the Ultimaster biodegradable sirolimus-eluting stent, raising the question of extrapolation to other later-generation stents. Likewise, the tightness of non-inferiority bounds used in this trial have been questioned.⁵  Further, the single antiplatelet continuation strategy following DAPT was heterogenous in this trial and the optimal strategy may vary from case to case. Lastly, recent trials including STOP-DAPT2 ACS found that one-month of DAPT failed to achieve non-inferiority versus standard 12-month DAPT after ACS in non-high bleeding risk patients.⁶

Barring some limitations to generalizability, Valgimigli and colleagues add practice changing data to the armamentarium of interventional cardiologists weighing the dueling risks and benefits of DAPT. For high-risk patients, shorter may indeed be better.

References

1. Valgimigli M, Frigoli E, et al. Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk. N Engl J Med. 2021 Aug 28. doi: 10.1056/NEJMoa2108749.

2. Watanabe H, Domei T, Morimoto T, et al. Effect of 1-month Dual Antiplatelet Therapy followed by Clopidogrel vs 12-month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients receiving PCI: The STOPDAPT-2 Randomized Clinical Trial. JAMA. 2019;321:2414-2427.

3. Franzone A, McFadden E, Leonardi S, et al. Ticagrelor Alone Versus Dual Antiplatelet Therapy from 1 Month after Drug-eluting Coronary Stenting. J Am Coll Cardiol. 2019;74:2223-2234.

4. Antipolis, S. 1-month Dual Antiplatelet Therapy Post-stent Implant Benefits High Bleeding Risk Patients. European Society of Cardiology Press Release. August 28, 2021. https://www.escardio.org/The-ESC/Press-Office/Press-releases/1-month-dual-antiplatelet-therapy-post-stent-implant-benefits-high-bleeding-risk-patients

5. Ohman EM. The Evolving Post-PCI Antithrombotic Therapies. N Engl J Med. 2021 Aug 28. doi: 10.1056/NEJMe2112747

6. STOP-DAPT2 ACS. Presented by Dr. Hirotoshi Watanabe at the European Society of Cardiology Virtual Congress, August 30, 2021.