RELEASE Trial: Discontinuation vs Continuation of Low‑Dose Acetylsalicylic Acid in Patients ≥65 Years with Stable Chronic Coronary Syndrome – A Non‑Inferiority Study

The primary objective is to determine whether cessation of long‑term aspirin therapy in patients older than 65 years with stable chronic coronary syndrome is non‑inferior to continued aspirin use with respect to the composite net clinical outcome of cardiovascular death, myocardial infarction, stroke, and major bleeding, thereby informing optimal secondary‑prevention strategies in this high‑risk population.

The trial enrolled adult patients of both sexes who were ≥65 years old and had a history of ischemic heart disease/chronic coronary syndrome, defined by a myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting occurring more than two years prior, and who were free from subsequent ischemic cardiovascular events or revascularization procedures. All participants were required to be receiving low‑dose aspirin (≤150 mg daily) at the time of randomization. Selection was based on these clinical criteria; no specific dietary, physical activity, or other lifestyle requirements were stipulated in the protocol. The sponsor did not provide the total number of participants enrolled.

The RELEASE trial is a randomized, double‑blind, controlled study evaluating whether discontinuation of low‑dose aspirin in patients ≥65 years with stable chronic ischemic heart disease is non‑inferior to continued therapy with respect to a hierarchical primary endpoint comprising cardiovascular death, fatal and major bleeding, intracranial bleeding, ischemic stroke, and myocardial infarction, while also assessing predefined secondary endpoints such as all‑cause mortality, hospitalizations, peptic ulcer, and patient‑reported outcomes. Recruitment is planned from September 2026 to September 2029, with each participant undergoing a screening visit to confirm eligibility (age, prior myocardial infarction, PCI, or CABG >2 years, absence of recent ischemic events, and current aspirin use ≤150 mg daily), followed by randomization and initiation of study medication. Subsequent study visits are scheduled at regular intervals (e.g., 1, 3, 6, and 12 months, then annually) to monitor adherence, collect safety and efficacy data, and perform required assessments; the final visit occurs at study completion or upon early discontinuation. Participant involvement therefore extends from the screening visit through the end‑of‑study visit, encompassing up to three years of follow‑up. Early termination of individual participation may occur if a participant experiences any component of the primary composite outcome, develops a protocol‑defined severe adverse event, or withdraws consent, in accordance with study procedures.

Acetylsalicylic acid is supplied as Magnyl DAK, enterotabletter, a gastro‑resistant tablet containing 150 mg per dose, administered orally once daily.

Hjertemagnyl, filmovertrukne tabletter 75 mg, is a film‑coated tablet also containing 150 mg of acetylsalicylic acid per dose, taken orally once daily.

Participants assigned to continued therapy receive one of the above aspirin tablets daily, while those allocated to discontinuation receive no active aspirin; a matching placebo may be used to maintain blinding, and all participants continue background secondary‑prevention measures according to local standard of care.

Dosing is scheduled each morning with water, and adherence is monitored by pill count at each visit, electronic medication‑event monitoring, and participant diaries. Missed doses are recorded and addressed according to protocol‑specified procedures.

Efficacy will be evaluated primarily through a hierarchical composite primary endpoint that includes, in order of priority, cardiovascular death, fatal bleeding (BARC type 5), intracranial bleeding (BARC type 3c), ischemic stroke, myocardial infarction, and other major bleeding events (BARC type 3a requiring transfusion and type 3b requiring surgery). Occurrence of each component will be recorded during the trial period and adjudicated according to the BARC classification system.

Secondary efficacy assessments comprise the individual components of the primary composite, all‑cause mortality, hospitalization for cardiovascular causes, peptic ulcer incidence, and a range of patient‑reported outcomes covering minor bleeding, abdominal pain/discomfort, quality of life, health‑related quality of life, anxiety and depressive symptoms, functional status, angina symptoms, and lifestyle behaviour. These outcomes will be captured through routine clinical follow‑up and structured patient‑reported outcome measures administered at predefined visits throughout the study.