Evening Dosing of Antihypertensive Therapy to Reduce Cardiovascular Events: A Third Type of Evidence Based on a Systematic Review and Meta-Analysis of Randomized Trials

Nighttime blood pressure strongly predicts cardiovascular events (CVEs). Further, a preliminary trial has shown decreased CVEs from evening vs morning dosing of antihypertensive therapy. Is there additional evidence for evening dosing? The authors systematically classified all hypertension trials as evening dosing trials (EDTs) or usual dosing trials (UDTs). Meta-analyses provided standardized hazard ratios for CVEs for EDTs (HR_EDTs) and UDTs (HR_UDTs). HR_EDTs/HR_UDTs gave the relative risk (RR) from evening vs usual dosing. Among 175 trials, 5 EDTs were discovered. The RR for CVEs (95% confidence limits) from evening vs usual dosing was 0.63 (0.43-0.92; P=016). After adjustment for drug class, the RR was 0.54 (0.34-0.85; P=008). Unlike other EDTs, the Heart Outcomes Prevention Evaluation (HOPE) study administered its entire antihypertensive dose prior to sleep and gave the greatest risk reduction. This study provides a third type of evidence suggesting a beneficial effect from evening dosing of antihypertensive therapy. Head-to-head, multicenter trials are needed to test this strategy.