Project Title

Randomized comparisons of morning versus bedtime drug administration: The cardiovascular circadian chronotherapy (C3) trial program

Background

Cardiovascular disease is the second most common cause of death in Denmark. High blood pressure is the most prevalent risk factor for cardiovascular disease and constitutes a major burden on healthcare systems. However, only a third of affected individuals achieve target blood pressures. Most manifest cardiovascular conditions are atherosclerotic in nature and thus predispose to vascular stenosis and thrombosis. An additional common cardiovascular disorder with a strong relation to hypertension is atrial fibrillation, a condition that further perpetuates the risk of stroke and systemic embolism. Several medications used for treatment of these conditions may have additional benefits when administered with dinner or at bedtime rather than early in the morning.

Aim

To examine whether administration of antihypertensive drugs, aspirin, and rivaroxaban at bedtime versus in the morning provides a superior reduction in incident major adverse cardiovascular events.

Methods

A series of open label, randomized, controlled trials. Patients who fulfill relevant inclusion and exclusion criteria will be identified through the National Patient and Prescription Registries, contacted, and asked to participate. Once they sign an informed consent form, study participants will be randomized to receive their once-daily antihypertensive medications, aspirin, and rivaroxaban (as relevant) in the morning versus at bedtime. Outcome data will be collected through the National Patient Registry.