Assessment of quitting versus using aspirin therapy in patients with stabilized coronary artery disease after stenting who require long-term oral anticoagulation: Rationale for and design of the AQUATIC double-blind randomized trial.

Abstract

Background: Antithrombotic management in patients with chronic coronary syndrome and previous stent implantation who require long-term oral anticoagulation is highly challenging in daily practice, especially in those at high residual risk of coronary and vascular events. Dual therapy with oral anticoagulation and aspirin may lead to a higher risk of bleeding, whereas stopping aspirin in high-risk patients with coronary artery disease after percutaneous coronary intervention may lead to recurrent ischaemic events.

Aim: To assess the optimal antithrombotic regimen that should be pursued long term (often lifelong) in these patients.

Methods: The AQUATIC study is a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicentre study conducted in patients with chronic coronary syndrome at high risk of ischaemic events (i.e., stent implantation [> 6 months before inclusion] in a context of previous acute coronary syndrome and/or with high-risk features of ischaemic event recurrences) and requiring long-term oral anticoagulation. For superiority, we ensure 80% power at level α=0.05 to detect a 25% reduction in hazard in the experimental group relative to the control group. Overall, 2000 patients will be randomized in a 1:1 ratio to receive either oral anticoagulation and aspirin or oral anticoagulation and placebo. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization and acute limb ischaemia. Major bleeding according to the International Society on Thrombosis and Haemostasis definition is a secondary safety endpoint that will be assessed as a priority.

Conclusion: The AQUATIC trial will test the efficacy and safety of adding aspirin to long-term oral anticoagulation in patients with chronic coronary syndrome and previous coronary stenting who are at high residual risk of recurrent ischaemic events and require oral anticoagulation.