**6. Evidence of shortened DAPT duration in patients after PCI requiring lifelong oral anticoagulation**

The landscape of evidence for the treatment of patients requiring lifelong oral anticoagulation after PCI has expanded notably in the last years, the main landmarks being (1) the ISAR-TRIPLE trial, where no significant difference was found in the primary endpoint of "net clinical benefit" (which included ischemic and bleeding outcomes) between 6 weeks and six months of triple therapy; [42] (2) the WOEST trial, where a dual pathway strategy (warfarin and clopidogrel) versus standard triple therapy (warfarin, clopidogrel and ASA) reduced bleeding while not increasing thrombotic events; [43] and (3) the advent of the new four direct oral anticoagulants (DOAC) and their specific trials for patients undergoing PCI,


*a Evaluation based on HAS-BLED score: Hypertension, Abnormal renal or liver function, Stroke or ICH history, Bleeding history or bleeding diathesis, Labile INR, Elderly (>65 years), Drugs (concomitant OAC and antiplatelet therapy, NSAIDs).*

*b Evaluation based on (1) clinical factors: diabetes, prior ACS, multivessel CAD, concomitant peripheral artery disease, premature or accelerated CAD, chronic kidney disease, ACS as clinical presentation; (2) anatomical factors: multivessel stenting, complex stenting (left main or last patent vessel stenting, chronic total occlusion intervention), prior stent thrombosis on antiplatelet treatment.*

*TT: Triple therapy; CCS: chronic coronary syndrome.*

#### **Table 3.**

*Recommendations for antithrombotic patients of AF patients undergoing PCI. Adapted from the 2020 ESC ESC/EACTS guidelines for the management of atrial fibrillation [8].*

[dabigatran/RE-DUAL PCI [44]; rivaroxaban/PIONEER AF-PCI [45]; apixaban/ AUGUSTUS [46]; edoxaban/ENTRUST-AF PCI [47]. The new 2020 ESC ESC/ EACTS guidelines for the management of atrial fibrillation is the latest consensus document on the subject, and the only one after the publication of the four DOAC trials for AF patients undergoing PCI [8].

As a whole, these trials evaluated dual (DOAC + P2Y12) vs. triple (VKA + P2Y12 + aspirin) therapy. They included a notable proportion of ACS (37–52%), although the highest risk patients were underrepresented (i.e., culprit lesions in a previously stented segment). Moreover, they all used triple therapy during PCI until randomization (1–14 days post PCI) and the most commonly P2Y12 inhibitor used was clopidogrel, as neither prasugrel or ticagrelor have evidence supporting their safety in combination with an OAC. As per outcomes, they reported a significant reduction of major/clinically significant bleeding, comparable rates of ischemic stroke, similar or non-significantly higher rates of myocardial infarction and stent thrombosis and a neutral effect on major adverse cardiac events and all-cause mortality [48]. Also, it is worth emphasizing that the AUGUSTUS trial is the only one that studied whether the advantages of dual pathway (vs. triple therapy) is independent of the type of OAC.

The ESC guidelines include four recommendations, according to the clinical presentation and the ischemic/bleeding risk balance (**Table 3**). Due to the under-representation of high ischemic risk patients on the trials, the recommendations for this population have a weak level of evidence. The evaluation of the ischemic risk is based on the presence of variables known to pose higher risk in the general population (also previously described in **Table 2**). Regarding the bleeding risk, evaluation with the AF-specific HAS-BLED risk score is recommended. This bleeding risk score has proven to be more useful at predicting bleeding risk in AF patients [49].
