Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing.
BACKGROUND
Previous studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium-channel blockers (CCBs), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the administration-time dependent antihypertensive efficacy of the slow-release, once-a-day nifedipine gastrointestinal-therapeutic-system (GITS) formulation.


METHODS
We studied 180 untreated hypertensives (86 men and 94 women), 52.5 +/- 10.7 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment.


RESULTS
The BP reduction after treatment was significantly larger with bedtime dosing mainly during night time sleep (P < 0.012). The number of patients with controlled ambulatory BP after treatment was greater with bedtime than morning treatment (P = 0.016). The baseline prevalence of nondipping was unaltered after ingestion of nifedipine on awakening, but reduced from 51 to 35% after bedtime dosing (P = 0.025). The morning surge of BP, a risk factor for stroke, was significantly reduced (P < 0.001) only after bedtime administration of nifedipine. Bedtime in comparison to awakening-time ingestion of nifedipine was also associated with a reduction in the incidence of edema from 13 to 1% (P < 0.001).


CONCLUSIONS
The increased efficacy on ambulatory BP as well as the significantly reduced prevalence of edema after bedtime as compared to morning ingestion of nifedipine should be taken into account when prescribing this medication to patients with essential hypertension.
Hermida
Ramón C
RC
Bioengineering and Chronobiology Laboratories, University of Vigo, Vigo, Spain. rhermida@uvigo.es
Ayala
Diana E
DE
Mojón
Artemio
A
Fernández
José R
JR
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D040242:Risk Reduction Behavior; D020521:Stroke / Q000453:epidemiology
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D009543:Nifedipine