Algorithm-based Tailoring of Dual Antiplatelet Therapy to Improve Outcomes Following Percutaneous Coronary Interventions (TAILOR-DAPT)

Algorithm-based Tailoring of Dual Antiplatelet Therapy to Improve Outcomes Following Percutaneous Coronary Interventions

Algorithm-based Tailoring of Dual Antiplatelet Therapy to Improve Outcomes Following Percutaneous Coronary Interventions

The use of aspirin combined with a P2Y12 inhibitor (dual antiplatelet therapy, DAPT) represents the standard of care for patients undergoing percutaneous coronary intervention (PCI) with stent implantation. The TAILOR-DAPT trial aims to investigate the benefits of a score-based decision-making algorithm to guide DAPT duration compared to a standard-of-care DAPT duration without the use of risk scores in patients undergoing PCI.

Background: The use of aspirin combined with a P2Y12 inhibitor (dual antiplatelet therapy, DAPT) represents the standard of care for patients undergoing percutaneous coronary intervention (PCI) with stent implantation. European guidelines recommend to implement risk scores to guide the duration of DAPT after stent implantation (class IIb, level of evidence A). However, its adoption rate remains exceedingly low in daily clinical practice in part due to the lack of direct evidence obtained from a randomized controlled trial supporting this strategy. Aim: Using a pragmatic study-design, the investigators aim to determine the efficacy and safety of an algorithm-guided strategy for DAPT duration compared to a standard-of-care DAPT without the use of risk scores in patients undergoing PCI with stent implantation. Methodology: This investigator-initiated, single-blind, randomized trial will include a total of 2788 patients aged ≥18 years undergoing PCI with stent implantation. Main exclusion criteria are peri-procedural complications potentially affecting DAPT duration. The study will be nested into a well-running registry to minimize study-related costs (pragmatic trial approach). Patients will be randomized to an algorithm-guided DAPT group or a standard-of-care DAPT group in a 1:1 fashion. In the algorithm-guided group, DAPT duration will be determined according to the PRECISE-DAPT score (≥25 or <25), PCI complexity, and clinical presentation (acute or chronic coronary syndromes). In the standard-of-care DAPT group, treatment duration is at the operator's discretion. The primary endpoint is net adverse clinical events (NACE), a composite of all-cause death, myocardial infarction, stroke, stent thrombosis or Bleeding Academic Research Consortium 2, 3, or 5 bleeding at 1 year. Potential significance: This will be the first study evaluating the impact of a score-based decision-making algorithm integrating bleeding and ischemic risks for DAPT duration among patients undergoing PCI. The hypothesis is that the proposed simple decision-making algorithm minimizes bleeding risk and maximizes ischemic benefit compared to a standard-of-care DAPT regimen. Prospective data obtained from a pragmatic randomized controlled trial embedded into an on-going, well-managed PCI registry database may further enhance the adoption rate of such a strategy in clinical practice.

PRECISE-DAPT score ≥25 Chronic Coronary Syndromes (CCS): DAPT with clopidogrel is discontinued at 1 month. Aspirin is continued until 1 year post randomization. Acute Coronary Syndromes (ACS): DAPT with clopidogrel is discontinued at 3 months. Aspirin is continued until 1 year post randomization. PRECISE-DAPT score <25: Non-complex PCI: DAPT with clopidogrel is discontinued at 6 months post randomization. Aspirin is continued until 1 year post randomization. Complex PCI: DAPT with clopidogrel, prasugrel or ticagrelor is continued until 1 year post randomization. ACS: DAPT with prasugrel or ticagrelor is continued until 1 year post randomization.

All-cause death, myocardial infarction, definite stent thrombosis, stroke or Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding

According to the TAILOR-DAPT modified Non-adherence Academic Research Consortium (NARC) classification

According to the traditional classification (Adherent≥80% of the time from randomization to intended DAPT cessation date)

Inclusion Criteria: PCI with drug eluting stent (DES) implantation Age ≥18 years Ability to sign informed consent before any study-specific procedure Exclusion Criteria: Planned staged PCI (Patients can be enrolled after complete coronary revascularization with no remaining lesions intended for treatment. Patients who have or develop an indication for percutaneous valve intervention can undergo treatment 30 days after full coronary revascularization) Indication for oral anticoagulation Peri-procedural complication which affects DAPT regimen based on the operator's opinion (e.g. untreated flow-limiting angiographic complication, intraprocedural stent thrombosis, persistent vessel occlusion/no-reflow at the end of the procedure, major side-branch occlusion, puncture-site related or other relevant bleeding) Treatment for stent thrombosis at index PCI or within 1 year prior to index PCI Active bleeding requiring medical attention at index PCI The presence of hemodynamic instability (persistent systolic blood pressure below 90mmHg, continuous infusions of catecholamines, clinical signs of hypoperfusion and/or use of percutaneous left ventricular assist devices) Life expectancy less than 1 year Women of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile) Planned surgery within the next 3 months Contraindication or known allergy against aspirin or P2Y12 inhibitors (clopidogrel, ticagrelor, and prasugrel) Participation in another trial