Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction (Dan-DAPT)

Rikke Sorensen

Status and phase: Enrolling; Phase 4

Conditions: Myocardial Infarction

Treatments: Genetic: CYP2C19*2/*3; Other: Shorter DAPT duration

Study type: Interventional

Funder types: Other

Identifiers

NCT05262803

2022-500125-32-00

Details and patient eligibility

About

Rationale: Heart attacks are a major cause of death and result from coronary blood clots that require acute coronary intervention and antithrombotic drugs to restore blood flow and prevent new heart attacks. Over time, more potent antithrombotic drugs have been introduced like prasugrel and ticagrelor. These drugs have replaced the older drug, clopidogrel, as approximately 30% of patients are low-responders to clopidogrel for genetic reasons. However, the newer drugs introduce a significant risk of serious bleeding.

Aim: The aim of this trial is to assess a reduced antithrombotic strategy for high bleeding risk patients with heart attacks to reduce bleeding safely.

Hypothesis: Significantly reduced bleeding with a similar preventive effect are expected.

Design: The Dan-DAPT trial include high bleeding risk patients with heart attacks from Danish hospitals (Rigshospitalet, Aarhus, Odense, Aalborg, Roskilde, and Gentofte hospital) and randomize them to standard-of-care or shorter and individualized antithrombotic therapy based on responsiveness to clopidogrel after genetic testing.

Enrollment: 2,808 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. MI caused by atherothrombotic CAD (Type 1 MI) according to "The Fourth Universal Definition of MI", which has been treated with PCI with contemporary drug-eluting stents. This definition of type 1 MI requires the detection of a rise and/or fall of cardiac troponin values with at least one value >99th percentile and at least one of the following criteria assessed by the treating physician:

   • symptoms indicating acute myocardial ischemia
   • new ischemic changes on the electrocardiogram
   • development of pathological Q-waves
   • imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology
   • visible coronary thrombus by angiography

2. PRECISE-DAPT score ≥25

3. Age ≥18 years

Exclusion criteria

1. Contraindications including allergies to ASA or P2Y12 inhibitors
2. Indication for oral anticoagulation
3. Previous stent thrombosis
4. Life expectancy <1 year
5. Resuscitated cardiac arrest with Glasgow Coma Scale <8 and/or need of intubation
6. Prior intracranial hemorrhage
7. Active bleeding (BARC ≥2) at randomization
8. Women who are pregnant, have given birth recently (within the past 90 days), are lactating, or are fertile without contraception
9. Hypertensive crisis (systolic blood pressure >180 mmHg and/or diastolic blood pressure >120 mmHg)
10. Unable to understand and follow study-related instructions or to comply with study protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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2,808 participants in 3 patient groups

Standard-of-care DAPT

No Intervention group

Description:

Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and prasugrel or ticagrelor for 6 months followed by ASA monotherapy.

Genotype-guided DAPT

Experimental group

Description:

DAPT according to CYP2C19\*2/\*3-genotyping for 6 months followed by ASA monotherapy.

Treatment:

Genetic: CYP2C19*2/*3

Shorter genotype-guided DAPT

Experimental group

Description:

DAPT according to CYP2C19\*2/\*3-genotyping for 3 months followed by ASA monotherapy.

Treatment:

Genetic: CYP2C19*2/*3

Other: Shorter DAPT duration