Overview
DAN-RELEASE is a national, randomized, registry-based trial including 7,000 participants in Denmark. The trial aims to determine whether discontinuation of long-term aspirin therapy is non-inferior to continued aspirin therapy in older adults with stable ischemic heart disease.
Long-term aspirin therapy is recommended for patients with established ischemic heart disease. However, among clinically stable patients years after percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or myocardial infarction (MI), the evidence supporting lifelong aspirin therapy is limited. At the same time, the risk of serious bleeding increases with age.
DAN-RELEASE will therefore compare aspirin discontinuation with continued aspirin therapy in adults aged 65 years or older with stable ischemic heart disease who have remained free from ischemic events for at least two years. The trial will assess whether discontinuing aspirin is non-inferior to continued treatment with respect to cardiovascular and bleeding outcomes.
Description
- Rationale
Current guidelines recommend life-long aspirin therapy in patients with chronic coronary syndrome. The evidence supporting long-term aspirin therapy after myocardial infarction (MI) and for chronic coronary syndrome stems primarily from trials conducted in the 1970s and 1980s. Since then, the clinical landscape of MI has evolved markedly: The use of highly sensitive cardiac troponins has led to the diagnosis of smaller MIs, coinciding with a shift from predominantly large ST-segment elevation MI (STEMI) to smaller non-STEMI. Acute revascularization is now a part of the routine care for MI and many patients with stable coronary artery disease undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Population risk factors have improved, and universal use of statins have contributed to plaque stabilization and reduces progression of disease. As a result, long-term prognosis in patients with MI and chronic coronary syndromes has markedly improved.
Therefore, the absolute ischemic benefit of long-term aspirin therapy may be attenuated, while the risk of bleeding, particularly in older patients, remains clinically relevant. These developments warrant a contemporary re-evaluation of the life-long role of aspirin in long-term secondary prevention of cardiovascular disease, especially in elderly patients with stable disease.
- Objective
To evaluate whether discontinuation of long-term aspirin in elderly patients with stable chronic coronary syndrome is non-inferior to continued aspirin therapy with respect to net clinical outcome.
All clinical outcomes will be registry based except patient-reported outcomes. They will be assessed using questionnaires measuring bleeding symptoms, gastrointestinal discomfort, quality of life and lifestyle behaviour during follow-up.
Trial design:
Investigator-initiated, registry-based, prospective, randomized, open-label, blinded endpoint (PROBE) non-inferiority trial with 1:1 allocation. The trial is conducted as a low-intervention clinical trial using nationwide Danish health registries as the primary data source.
Risk-benefit considerations:
Aspirin is widely used in secondary prevention and is available over the counter, reflecting its well established safety profile and the generally low risk associated with its use. Nevertheless, aspirin is associated with potential adverse effects, including bleeding, gastrointestinal discomfort, and clinically relevant drug interactions, particularly in elderly patients with comorbidities. Based on data from national health registries, the target population - older adults with stable chronic coronary syndrome - represents a clinically stable group with a low event rate of ischemic events. Given that lifelong aspirin therapy is often continued without systematic reassessment, there is a clear ethical justification for evaluating whether continuation remains beneficial - and safe - in an aging population with changing comorbidity profiles.
Eligibility
Inclusion Criteria:
- Age ≥65 years at randomization
- Ischemic heart disease (IHD) with index event (myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)) \>2 years previously
- Since index event free from ischemic cardiovascular events (MI, ischemic stroke, or transitory ischemic attack) or any coronary revascularization procedure (PCI/CABG)
- Currently treated with low dose aspirin (≤150 mg daily)
Exclusion Criteria:
- History of ischemic stroke
- Active treatment with or indication for anti-coagulant or P2Y12-inhibitor therapy
- Indication for antiplatelet treatment other than secondary prevention of IHD according to treating physician (i.e. haematological diseases, peripheral artery disease)
- Any revascularization procedure for peripheral artery disease
- Any history of stent thrombosis or stenting of the left main coronary artery
- Other contraindications to aspirin discontinuation according to treating physician
- Not being able to understand Danish
