Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction

Study Overview
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Brief Summary
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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.

Official Title
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Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction Treated With Percutaneous Coronary Intervention - The Dan-DAPT Trial

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Genetic: CYP2C19*2/*3
* Other: Shorter DAPT duration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 PRECISE-DAPT score ≥25 Age ≥18 years Exclusion Criteria: Contraindications including allergies to ASA or P2Y12 inhibitors Indication for oral anticoagulation Previous stent thrombosis Life expectancy <1 year Resuscitated cardiac arrest with Glasgow Coma Scale <8 and/or need of intubation Prior intracranial hemorrhage Active bleeding (BARC ≥2) at randomization Women who are pregnant, have given birth recently (within the past 90 days), are lactating, or are fertile without contraception Hypertensive crisis (systolic blood pressure >180 mmHg and/or diastolic blood pressure >120 mmHg) Unable to understand and follow study-related instructions or to comply with study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard-of-care DAPT<br>Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and prasugrel or ticagrelor for 6 months followed by ASA monotherapy. | |
| Experimental: Genotype-guided DAPT<br>DAPT according to CYP2C19*2/*3-genotyping for 6 months followed by ASA monotherapy. | Genetic: CYP2C19*2/*3<br>* Non-carriers of CYP2C19*2/*3 loss-of-function alleles: DAPT with clopidogrel and ASA Carriers of CYP2C19*2/*3 loss-of-function alleles: DAPT with prasugrel (or ticagrelor) and ASA<br>|
| Experimental: Shorter genotype-guided DAPT<br>DAPT according to CYP2C19*2/*3-genotyping for 3 months followed by ASA monotherapy. | Genetic: CYP2C19*2/*3<br>* Non-carriers of CYP2C19*2/*3 loss-of-function alleles: DAPT with clopidogrel and ASA Carriers of CYP2C19*2/*3 loss-of-function alleles: DAPT with prasugrel (or ticagrelor) and ASA<br>Other: Shorter DAPT duration<br>* Duration of DAPT is shortened to 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BARC type 2-5 bleedings | A composite of type 2-5 non-access site bleeding according to the Bleeding Academic Research Consortium (BARC) scale, ranging from bleedings that require diagnosis, hospitalization, or treatment by a health care professional (BARC type 2) to fatal bleedings (BARC type 5) | 1 year | 
| NACE (Net adverse clinical events) | A composite of all-cause mortality, recurrent myocardial infarction, definite stent thrombosis, ischemic stroke, and BARC type 3-5 non-access site bleeding | 1 year | 
| MACE (Major cardiovascular events) | A composite of all-cause mortality, recurrent myocardial infarction (MI), definite stent thrombosis, and ischemic stroke | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleedings according to BARC and TIMI (Thrombolysis in Myocardial Infarction) defintions |  | 3, 6, and 12 months | 
| All-cause mortality |  | 3, 6, and 12 months | 
| Non-hemorrhagic cardiovascular death |  | 3, 6, and 12 months | 
| Ischemic events | Recurrent MI, definite/probable stent thrombosis, any (non-)target vessel revascularization, coronary artery bypass grafting, ischemic stroke | 3, 6, and 12 months | 
| Discontinuation or switch to another antiplatelet drug |  | 3, 6, and 12 months | 
| Pharmacoeconomic endpoint including direct and in-direct medical costs | Direct medical costs (e.g. costs for genotyping, medicinal products, re-hospitalization) and indirect costs (e.g. absence from the workforce). | 3, 6, and 12 months | 
| Self-reported quality of life scores | Self-reported quality of life scores according to the EQ-5D-5L questionaries in electronic form | 3, 6, and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High bleeding risk, CYP2C19 genotyping, Dual antiplatelet therapy, Percutaneous coronary intervention