Administration-time dependent influence of aspirin on blood pressure in previously untreated hypertensive patients

Several studies have shown statistically significant circadian rhythms in thromboxane and prostacyclin production, circulating platelets, platelet aggregation, clotting and fibrinolytic inhibitors, circulating angiotensin II, angiotensin sensitivity, and the inhibition of platelet aggregation produced by aspirin (ASA). Moreover, ASA exhibits a faster drug-disappearance rate when administered during the morning as compared to the evening. Despite this evidence, previous studies on the potential influence of ASA on blood pressure (BP) have not taken into consideration the chronopharmacological effects of nonsteroidal antiinflammatory drugs. This pilot study investigates the effects of ASA on BP in untreated hypertensive patients who received ASA at different times of the day according to their rest-activity cycle. We studied 78 patients with mild hypertension (36 men), 43.5±11.4 (mean±SD) years of age, divided in 3 groups: non-pharmacological hygienic-dietary recommendations (HDR); HDR and ASA (100 mg/day) on awakening; or HDR and ASA before bedtime. BP and heart rate (HR) were measured every 20 minutes during the day (07:00 to 23:00 hours) and every 30 minutes at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of BP in each group was established by population multiple-component analysis [Fernandez & Hermida. Chronobiol Int. 1998;15:191-204]. After 3 months of non-pharmacological intervention, there was a small and non-significant reduction of BP (1.2 mm Hg for systolic BP, 1.4 mm Hg for diastolic BP; P=0.264). There was no effect of ASA on BP when given on awakening (P=0.211). A BP reduction was, however, highly significant when ASA was given before bedtime (decrease of 7.6 and 6.1 mm Hg in systolic and diastolic BP, respectively; P<0.001). There was no significant change in HR in any group. Results indicate a statistically significant administration-time dependent effect of low-dose ASA on BP in untreated patients with mild hypertension. In any trial of ASA effects, inquiries about the time when subjects took the drug are indicated and may account for discrepancies in the literature. Moreover, the influence of ASA on BP demonstrated here indicates the need to identify and control for ASA effects in patients using this drug before or during their participation in antihypertension medication trials. DGES, PM98-0106; PGICT00-PXI-32205PN; University of Vigo.