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

Overview

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.

Detailed description

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 a composite of net adverse clinical events (NACE) defined as all-cause death, spontaneous myocardial infarction, stroke, definite stent thrombosis or Bleeding Academic Research Consortium (BARC) 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.

Interventions

• Other Algorithm-guided DAPT duration
  PRECISE-DAPT score ≥25 * Chronic Coronary Syndromes (CCS): Aspirin + clopidogrel for 1 month, followed by clopidogrel monotherapy * Acute Coronary Syndromes (ACS): Aspirin + ticagrelor for 1 month, followed by ticagrelor monotherapy PRECISE-DAPT score \<25: * Non-complex CCS: Aspirin + clopidogrel for 6 months, followed by clopidogrel monotherapy * Non-complex ACS: Aspirin + potent P2Y12 inhibitor for 6 months, followed by potent P2Y12 inhibitor monotherapy * Complex CCS or ACS: Aspirin + P2Y
• Other Standard-of-care DAPT duration
  DAPT strategy at the operators´ discretion in accordance with applicable guidelines

Primary outcome measures

• Net adverse clinical events (NACE) [Time frame: 1 year]

Secondary outcome measures (12)

• Major adverse cardiovascular events (MACE) [Time frame: 1 year]
• Major or clinically relevant non-major bleeding [Time frame: 1 year]
• Major bleeding [Time frame: 1 year]
• Any Bleeding Academic Research Consortium (BARC) bleeding [Time frame: 1 year]
• All-cause death [Time frame: 1 year]
• Cardiovascular death [Time frame: 1 year]
• Myocardial infarction [Time frame: 1 year]
• Spontaneous myocardial infarction [Time frame: 1 year]
• Target lesion failure [Time frame: 1 year]
• Target vessel revascularization [Time frame: 1 year]
• Target vessel myocardial infarction [Time frame: 1 year]
• Target lesion revascularization [Time frame: 1 year]

Eligibility criteria

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 qualifying PCI or within 1 year prior to qualifying PCI
• Active bleeding requiring medical attention at qualifying 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 a drug trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Bosnia and Herzegovina · 1 center

• University Clinical Center of the Republic of Srpska — Banja Luka

Italy · 1 center

• UOC Cardiologia San Giovanni Addolorata Hospital — Roma

Switzerland · 1 center

• Department of Cardiology, Bern University Hospital — Bern

Identifiers

NCT: NCT05732701 · TAILOR-DAPT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗