Evening anti-hypertensive dosing improves blood pressure control and reduce cardiovascular events in hypertensive: a meta-analysis of 40 trials in 44,167 patients
Authors: Sunjaya A.P , Sunjaya A.F 
Published: November 2020

Abstract

Introduction
Nocturnal blood pressure (BP) and early morning BP surge have consistently been found to be a better prognostic marker of cardiovascular outcome than daytime BP. Most anti-hypertensive show greater blood pressure-lowering effect in the first 12 hours compared to the next 12 hours. Several prospective studies have shown better BP regulation and improved cardiovascular risk when anti-hypertensive are ingested at bedtime versus at awakening.

Purpose
In patients with hypertension does evening dosing of anti-hypertensive compared to morning dosing led to better reduction in pressure, blood pressure control and reduced cardiovascular morbidity.

Methods
A meta-analysis was performed based on randomized controlled trials obtained from Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline and Medline ahead of print published between 2000 and 2020. Main outcome measures include mean 24 hour systolic and diastolic blood pressure, cardiovascular events as well as prevalence of blood pressure in control. Data synthesis and analysis was done using RevMan 5.3 using a random effects model.

Results
A total of 40 randomized controlled trials, representing 44,167 patients were included in this meta-analysis. Most studies evaluate the administration of mixed anti-hypertensive with ≥1 medication ingested at bedtime, calcium channel blockers (CCBs) or angiotensin receptor blockers (ARBs) with sample sizes ranging from 30 to 19,084 patients. Evening administration of anti-hypertensive was found to significantly lower 24-hour systolic blood pressure (Mean difference = −1.05, 95% CI: −2.01 to −0.10, p=0.03) and 24-hour diastolic blood pressure (Mean difference = −1.09, 95% CI: −1.68 to −0.50, p=0.0003). Prevalence of controlled blood pressure was found to significantly increase with evening dosing (RR=1.15, 95% CI: 1.03 to 1.28, p=0.01). Significant reduction in cardiovascular events were found in the evening dosing group (RR=0.48, 95% CI: 0.03 to 0.68, p=&lt;0.00001).

Discussion
Reduction in night-time blood pressure especially among non-dippers as reported in previous studies and higher prevalence of controlled blood pressure may explain the greater than 50% reduction in cardiovascular events in the evening dosing group. This marked benefit from a simple and inexpensive strategy certainly has great potential to benefit patients in practice. Even so, few studies have reported the prevalence of blood pressure in control (9 studies) and cardiovascular events (6 studies). Few has also studied this in geriatric populations where night-time hypotension and hypoperfusion may bring the most impact.

Conclusion
For patients with hypertension, evening dosing significantly improves blood pressure control and reduces the risk for cardiovascular events. Careful selection of anti-hypertensive administration time in patients is recommended given the possible benefits.
Anti Hypertensive Dosing Forest Plot

Funding Acknowledgement
Type of funding source: None