Reference: Eur Heart J. 2019 Oct 22.
Evidence supporting nocturnal dosing of antihypertensives for individual drugs from small trials has existed for many years. Now there are more convincing data from multiple primary care practices and backed up by scheduled ambulatory blood pressure monitoring (ABPM) from over 19,000 hypertensive patients followed for a median of 6.3 years. The Hygia Group was established in Spain to utilize ambulatory blood pressure monitoring routinely, but as this study shows, the ABPM data don’t add much to the primary outcomes of death and vascular events.
The researchers randomized 9,532 patients with ABPM-confirmed hypertension to take their daily medications in the morning and 9,552 to take their meds at bedtime. Although the study controlled the timing of medications, primary care physicians controlled the medication type and dosing. Matching, adherence, and follow-up were good in this study, and a modified intention-to-treat analysis was conducted. The protocol required baseline and annual 48-hour ABPM measurement, with the belief that 48 hours would give more accurate information than 24-hour measurements.
In follow-up, the researchers recorded primary outcomes of stroke, cardiac death, new-onset heart failure, myocardial infarction, or revascularization in 1,752 patients. Nighttime dosing was associated with decreased all-cause mortality (adjusted hazard ratio [HR] 0.55, 95% CI 0.48-0.63) and cardiovascular death (adjusted HR 0.44, 95% CI 0.34-0.56). The Kaplan-Meier cumulative hazard also demonstrated a significant reduction in total cardiovascular events. Data on individual components of the cardiovascular events were not reported. Interestingly, the ABPM data did not demonstrate that lower nocturnal systolic blood pressure or a 10% reduction in nocturnal blood pressure from daytime levels were predictive of different outcomes.
These striking results are not without limitations. This study was conducted in a Caucasian Spanish population and only examined primary prevention. The authors reported only composite risks for coronary outcomes, which could be misleading if most events were revascularization rather than MI or death. Additionally, the primary care clinicians selected significantly more diuretics and beta blockers for the daytime group, and more calcium channel blockers but fewer prescriptions overall for the nocturnally-dosed group. Nevertheless, these data are a wake-up call for clinicians to consider evening dosing for hypertension medications.
For more information, see the topic Hypertension Medication Selection and Management in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.