Aspirin in Reduction of Tension II Study

Aspirin is a cornerstone in the secondary prevention of cardiovascular disease (CVD) and is usually taken on awakening, although evidence regarding optimal time of intake is lacking. Recent studies in healthy subjects with mild hypertension showed that aspirin at bedtime decreases blood pressure (-7/5mmHg), whereas intake of aspirin on awakening does not. Additionally, the investigators found that aspirin at bedtime decreases plasma renin activity, catecholamines and cortisol over 24hrs. Time-dependent effects of aspirin have never been studied in patients with CVD, who may use concomitant antihypertensive drugs. Moreover, platelet reactivity has a circadian rhythm, and intake of aspirin at bedtime may attenuate the morning peak in platelet reactivity. The investigators hypothesize that aspirin intake at bedtime compared with on awakening decreases both blood pressure and platelet reactivity over 24h. A randomized open-label blinded endpoint crossover trial in which 250 patients, recruited from primary care, will be included who use aspirin for secondary prevention of CVD and have a stable blood pressure of 149/94mmHg or lower. Study subjects will randomly use both aspirin on awakening and at bedtime during two intervention periods of three months. Blood pressure will be recorded for 24hrs at the end of each treatment period in the patients' normal daily situation. To assess effects on platelet inhibition, thromboxane-B2 levels will be measured in a 24h urine sample at the end of both treatment periods. The investigators will asses differential effects according to time of intake on gastrointestinal complaints and potential minor bleeding events, as well as compliance. The aim of this study is to evaluate the effect of aspirin taken at bedtime compared with on awakening on blood pressure of subjects with stable CVD. In addition, it will generate insights into the effect of aspirin on platelet reactivity over 24hrs, potential side effects and compliance.