Trials on Timing of Cardiovascular Medication Administration: The Cardiovascular Circadian Chronotherapy Trial Concept

The incidence of certain disease events such as myocardial infarction, stroke, aortic rupture, and sudden cardiac death is affected by the time of day. It is thus theorized that synchronization of medication timing with circadian rhythmicity (or at the minimum, clock time) may improve treatment efficacy and/or reduce the risk of serious adverse events. We launched the C3 (Cardiovascular Circadian Chronotherapy) trial concept to efficiently conduct randomized, controlled, clinical outcome trials of the timing of medication administration. This concept takes advantage of the Danish nationwide administrative health registries for participant identification and collection of baseline and follow-up data as well as the mandatory governmental electronic letter system. Although many of these interventions may only provide small effect sizes, any positive effects from simple changes in the timing of drug administration could potentially lead to large, worldwide prognostic improvements.