Comparison of Awakening Versus Bedtime Dosing of Aspirin in Pre-Hypertension or Mild Essential Hypertension
Status:
Terminated
Trial end date:
2008-12-01
Target enrollment:
Participant gender:
Summary
Aspirin (ASA) has been shown to provide marked benefits in the prevention of cardiovascular
events, although the potential direct effects of ASA on cardiovascular function remain
uncertain. Previous studies have demonstrated that ASA is a potent antioxidative agent that
markedly reduces vascular production of superoxide in normotensive and hypertensive rats. In
addition, ASA was found to prevent angiotensin II-induced hypertension and cardiovascular
hypertrophy, mainly through its antioxidative properties in preventing the generation of
superoxide, although ASA apparently did not appear to reduce hypertensive levels of blood
pressure (BP). Moreover, recent results have demonstrated that ASA induces nitric oxide (NO)
release from vascular endothelium. No attention has been paid, so far, to potential
administration time-dependent effects in these studies.
Previous laboratory animal and clinical trial research convincingly demonstrates
administration time-dependent (with reference to circadian rhythms) effects of ASA. Thus, the
effects of ASA upon lipoperoxides, β-adrenergic receptors, and BP in clinically healthy
subjects depend on the circadian timing of ASA administration. Most important, the
administration time-dependent influence of ASA on BP was previously demonstrated in a
randomized trial on healthy women and in other independent, double-blind, randomized,
placebo-controlled clinical trials. The first was conducted on clinically healthy subjects, a
second one on normotensive and hypertensive subjects, a third one on pregnant women at high
risk for preeclampsia and a fourth one in previously untreated patients with mild
hypertension. The findings of these BP studies are consistent; the BP-lowering effect of
low-dose ASA is achieved when administered at bedtime but not upon awakening.
In keeping with the chronopharmacological effects of ASA and the previous findings suggesting
that ASA at low dose may have a potential beneficial effect on BP, this prospective,
randomized, double-blind, crossover study will investigate the potential influence of ASA on
BP in subjects with either high-normal BP or diagnosis of mild (grade 1) hypertension. The
subjects will receive low-dose ASA or placebo at different times of the day according to
their rest-activity cycle, and will be evaluated by 48-hour ambulatory BP monitoring before
and after 6 weeks of pharmacologic intervention.