Atherosclerosis Cardiovascular Disease, Cardiovascular Diseases (CVD), Drug Effect
Conditions
Keywords
Statin, Circadian Rhythm, Randomized Controlled Trial, Pragmatic, Outcomes, Cardiovascular disease, Prevention
Brief summary
Statins inhibit hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase which catalyzes the rate-limiting step in cholesterol synthesis. This in turn leads to reductions in concentrations of low-density lipoprotein (LDL) cholesterol and C-reactive protein which reduces the risk of incident atherosclerotic events among individuals both with and without a history of atherosclerotic cardiovascular Several pilot studies have suggested potential benefits of taking statin in the evening rather than in the morning. The primary objective of this study is to examine whether statin administration at bedtime versus in the morning provides a superior reduction in the incidence of major adverse cardiovascular events among patients with or without established atherosclerotic cardiovascular disease, who are already taking statin.
Detailed description
The study is a pragmatic, registry-based, open-label, randomized controlled trial combining the utilization of the Danish nationwide health registries and the official Danish electronic letter system (Digital Post/eBoks) into an innovative, decentralized trial requiring no study visits from participants. The nationwide health registries will be used for identification of potential participants and data collection, including baseline information and follow-up data, while the electronic letter system will be used for sending recruitment letters and communicating with participants. Study participants will provide electronic informed consent from home before inclusion and randomization. The trial will include patients currently in statin treatment regardless of the presence or absence of established cardiovascular disease. Participants will be randomized 1:1 to either statin administration at bedtime or in the morning. The trial is event-driven.
Interventions
DRUGStatin in the evening (such as Simvastatin, Atorvastatin, Rosuvastatin, Pravastatin)
Participants will be instructed to take their Statin daily at approx. 8PM-12AM.
DRUGStatin in the morning (such as Simvastatin, Atorvastatin, Rosuvastatin, Pravastatin)
Participants will be instructed to take their statin upon awakening/or with their breakfast (approx. 6AM-10AM).
Sponsors
Herlev and Gentofte Hospital
Tor Biering-Sørensen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>=18 years * Current treatment with atorvastatin 10-80 mg, rosuvastatin 5-40 mg, simvastatin 10-80 mg or pravastatin 20-40 mg (as recorded in the Danish National Prescription Registry and confirmed by the participant via questionnaire) * Signed informed consent
Exclusion criteria
* none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of hospitalization for myocardial infarction, hospitalization for stroke or cardiovascular death | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | For Hospitalizations: Inpatient, at least 1 night |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization for myocardial infarction | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | Inpatient, at least 1 night |
| Hospitalization for stroke | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | Inpatient, at least 1 night |
| Cardiovascular death | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | — |
| All-cause death | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Any arterial revascularization | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | — |
| Any venous thromboembolism | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | The incidence of Any venous thromboembolism |
| Hospitalization for heart failure | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | The incidence of Hospitalization for heartfailure. For hospitalizations: Inpatient, at least 1 night |
| Hospitalization for rhabdomyolysis | From date of randomization until end of study (up til 5 years) | The incidence of Hospitalization for rhabdomyolysis, Inpatient, at least 1 night. |
| Any incident cancer | From date of randomization until end of study (up til 5 years) | The incidence of any cancer |
| Plasma Lipid levels | From date of randomization until end of study (up til 5 years) | — |
| Any incident hepatic disorder | From date of randomization until end of study (up til 5 years) | The incidence of any hepatic disorder |
| Bleeding episodes requiring hospitalization | From date of randomization until end of study (up til 5 years) | The incidence of any bleeding episodes requiring hospitalization. For hospitalizations: Inpatient, at least 1 night. |
| Any Incident Diabetes mellitus | From date of randomization until end of study (up til 5 years) | The incidence of diabetes mellitus |
| Time of day of hospitalization for stroke | From date of randomization until end of study (up til 5 years) | The time of hospitalization will expressed as the hour of the beginning of the hospitalization. |
| Any incident renal disorder | From date of randomization until end of study (up til 5 years) | The incidence of any renal disorder |
| Plasma C-reactive protein level | From date of randomization until end of study (up til 5 years) | — |
| Time of day of hospitalization for myocardial infarction | From date of randomization until end of study (up til 5 years) | The time of hospitalization will be expressed as the hour of the beginning of the hospitalization |
| Hospitalization for unstable angina | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | Inpatient, at least 1 night |
| Coronary revascularization | Will be assessed in a time-to-first-event approach from date of randomization until end of study (up til 5 years). | — |
Countries
Denmark
Contacts
Primary ContactManan Pareek, MD and PhD
Outcome results
None listed