Speaker
Scott Garrison MD, PhD, CCFP
Professor, University of Alberta, Department of Family Medicine
Director, Pragmatic Trials Collaborative
Keywords
Hypertension; Blood Pressure; Blood Pressure Medication; Medication Timing
Key Points
- In 2010, the Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares (MAPEC) trial found that hypertensive patients who took once-daily blood pressure (BP) medication at night, as opposed to in the morning, had a 61% reduction in major adverse cardiovascular events (MACE).
- These results came with a credible rationale: BP is higher during the day than overnight, and overnight BP is a better predictor of cardiovascular events than daytime BP. Theoretically, patients taking BP medication at bedtime could preferentially lower overnight BP. But there were also good reasons to be skeptical of the results, and clinical guidelines remained unchanged.
- To further investigate whether the timing of BP medication had an effect on MACE, Dr. Garrison and his team conducted 2 randomized controlled trials: BedMed and BedMed Frail. The former was conducted in a hypertensive primary care population; the latter in a hypertensive continuing care population. They conducted them separately, given the differing risks and benefits for the populations and the likely underrepresentation of frail or complex older patients in BedMed.
- In the early stages, Dr. Garrison came across several unexpected challenges. There were restrictions around data access; regulations around billing for trial-related procedures in British Columbia; and the time it took to identify a data partner.
- In both trials, the intervention group took a once-daily BP medication when getting ready for bed. In BedMed, the control took a once-daily BP medication upon waking up in the morning; in BedMed Frail, the control had no change in their existing routine (which typically meant taking their BP medication in the morning). Given the unique needs of the trial population, BedMed Frail utilized opt-out consenting.
- The primary outcome for both trials was all-cause death or hospitalization/emergency department visit for stroke, acute coronary syndrome, or heart failure. In BedMed, they used an intent-to-treat analysis, with patients participating (via active or passive follow-up) in the study for a median of 4.6 years. In BedMed Frail, they used a modified intent-to-treat analysis, with patients participating for a median of 1.1 years due to high mortality in the study population.
- The research team found that no additional cardiovascular benefit is conveyed from taking BP medication at bedtime. Conversely, their results concluded that these medications can be safely taken at bedtime, so patients should incorporate them into their routine whenever they are least likely to forget it.
Discussion Themes
Dr. Garrison noted that he was more confident in the negative result for the BedMed trial than for BedMed Frail, given that the adjusted hazard ratio of 0.88 and the unadjusted ratio of 0.93 in the latter. A 12% reduction in the outcome (which was largely driven by death) may still be meaningful to patients.
Designing a trial that was workflow-friendly for physicians was a top priority for the research team and was critical to obtaining buy-in for and executing this trial.
A major accomplishment of BedMed and BedMed Frail was developing a network of volunteer physicians and a data partner who would collaborate with the Pragmatic Trials Collaborative on future trials.