Although all of the chronotherapy trials so far compared the effects of full medication doses on blood pressure (BP) regulation, that were ingested either in the morning or at bedtime, still the trend for the prescription of the same medication(s) as twice-daily divided (BID) doses is frequent.
To throw more light on this issue, Dr. Hermida Ramon Cand coworkers performed the present study that investigated the effects of ingesting split doses of the same hypertension medication, half upon awakening and half at bedtime, on the BP pattern and degree of BP control of patients with resistant hypertension who were enrolled in the Hygia Project, that was designed to prospectively evaluate the cardiovascular risk by 48 hrs ambulatory BP monitoring (ABPM) in primary care centers of Northwest Spain.
Study population consisted of 1463 patients with true resistant hypertension (awake systolic [SBP]/diastolic BP [DBP] means >135/85 mmHg, or asleep SBP/DBP means >120/70 mmHg, while on 3 different hypertension medications, or any patient treated with >4 medications). Among the total enrolled, 809 were men/654 were women. Mean age was 63.9 ± 12.2 years.
1084 among the enrollees ingested the full dose of all BP-lowering medications upon awakening, and 379 ingested split doses of >1 medications BID upon awakening and at bedtime.
Findings from this study showed most of demographic characteristics that included the prevalence of obstructive sleep apnea, metabolic syndrome, and albuminuria were similar among the patients of the two treatment-time regimens.
Complete comparable results were shown by the awake and asleep SBP/DBP mean’s (awake SBP/DBP mean 137.4/78.8 vs. 138.9/77.5 mmHg for patients ingesting all medications upon awakening vs. BID split dosing of >1 medications, P > 0.074; asleep SBP/DBP mean 132.3/71.9 vs. 132.9/70.7 mmHg, P > 0.079). Similarly, fully comparable results between both treatment-time regimens were shown in terms of the prevalence of non-dipping (80.5 vs. 77.3%; P = 0.179) and the proportion of patients with controlled ambulatory BP (P = 0.114).
Notably, no improvements in ambulatory BP control, or reductions in the prevalence of non-dipping were reported with the ingestion of same medications BID as a split dose regimen in patients with resistant hypertension, hence this dose regimen could not be considered as chronotherapy.
In conclusion this study demonstrated that ingestion of full doses of hypertension medications at bedtime is a proper chronotherapeutic approach that shown to result in improved ambulatory BP control and fewer hard and soft cardiovascular events. | 
