Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction

Official title

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

Overview

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.

Interventions

• Genetic CYP2C19*2/*3
  * 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
• Other Shorter DAPT duration
  Duration of DAPT is shortened to 3 months

Primary outcome measures

• BARC type 2-5 bleedings [Time frame: 1 year]
• NACE (Net adverse clinical events) [Time frame: 1 year]

Secondary outcome measures (8)

• MACE (Major adverse cardiovascular events) [Time frame: 3, 6, and 12 months]
• Bleedings according to BARC and TIMI (Thrombolysis in Myocardial Infarction) defintions [Time frame: 3, 6, and 12 months]
• All-cause mortality [Time frame: 3, 6, and 12 months]
• Non-hemorrhagic cardiovascular death [Time frame: 3, 6, and 12 months]
• Ischemic events [Time frame: 3, 6, and 12 months]
• Discontinuation or switch to another antiplatelet drug [Time frame: 3, 6, and 12 months]
• Pharmacoeconomic endpoint including direct and in-direct medical costs [Time frame: 3, 6, and 12 months]
• Self-reported quality of life scores [Time frame: 3, 6, and 12 months]

Eligibility criteria

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

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

Single blind

Primary purpose

Treatment

Study locations

Denmark · 6 centers

• Aalborg University Hospital — Aalborg
• The Heart Centre, Copenhagen University Hospital, Rigshospitalet — Copenhagen
• Herlev and Gentofte University Hospital - Gentofte — Hellerup
• Odense University Hospital — Odense
• Zealand University Hospital — Roskilde
• Aarhus University Hospital — Skejby

Publications

• Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2018 Jan 1;53(1):34-78. doi PMID 29045581
• Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Juni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM; ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persis PMID 32860058
• Costa F, van Klaveren D, James S, Heg D, Raber L, Feres F, Pilgrim T, Hong MK, Kim HS, Colombo A, Steg PG, Zanchin T, Palmerini T, Wallentin L, Bhatt DL, Stone GW, Windecker S, Steyerberg EW, Valgimigli M; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-D PMID 28290994
• Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Postma MJ, de Boer A, Boersma C, Deneer VHM, Ten Berg JM. A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. N Engl J Med. 2019 Oct 24;381(17):1621-1631. doi: 10.1056/NEJMoa1907096. PMID 31479209
• Jacobsen MR, Engstrom T, Torp-Pedersen C, Gislason G, Glinge C, Butt JH, Fosbol EL, Holmvang L, Pedersen F, Kober L, Jabbari R, Sorensen R. Clopidogrel, prasugrel, and ticagrelor for all-comers with ST-segment elevation myocardial infarction. Int J Cardiol. 2021 Nov 1;342:15-22. doi: 10.1016/j.ijcard.2021.07.047. Epub 2021 Jul 24. PMID 34311012
• Jacobsen MR, Jabbari R, Grove EL, Maeng M, Veien K, Hougaard M, Freeman P, Kelbaek H, Charlot MG, Engstrom T, Sorensen R. Genotype-guided de-escalation and abbreviation of dual antiplatelet therapy in patients with myocardial infarction and high bleeding risk: Design and rationale of the investigator-initiated, multicenter, randomized, controlled trial, DAN-DAPT. Am Heart J. 2025 Jul;285:74-81. do PMID 40015616

Identifiers

NCT: NCT05262803 · 2022-500125-32-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗