Administration Time–Dependent Effects of Aspirin on Blood Pressure in Untreated Hypertensive Patients

Abstract

Abstract-Previous studies on the potential influence of aspirin on blood pressure have not taken into consideration the chronopharmacological effects of nonsteroidal anti-inflammatory drugs. This pilot study investigates the effects of aspirin on blood pressure in untreated hypertensive patients who received aspirin at different times of the day according to their rest-activity cycle. We studied 100 untreated patients with mild hypertension (34 men and 66 women), 42.5Ϯ11.6 (meanϮSD) years of age, randomly divided into 3 groups: nonpharmacological hygienic-dietary recommendations; the same recommendations and aspirin (100 mg/d) on awakening; or the same recommendations and aspirin before bedtime. Blood pressure was measured every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of blood pressure in each group was established by population multiple-component analysis. After 3 months of nonpharmacological intervention, there was a small, nonsignificant reduction of blood pressure (Ͻ1.1 mm Hg; PϾ0.341). There was no change in blood pressure when aspirin was given on awakening (Pϭ0.229). A highly significant blood pressure reduction was, however, observed in the patients who received aspirin before bedtime (decrease of 6 and 4 mm Hg in systolic and diastolic blood pressure, respectively; PϽ0.001). Results indicate a statistically significant administration time-dependent effect of low-dose aspirin on blood pressure in untreated patients with mild hypertension. The influence of aspirin on blood pressure demonstrated in this study indicates the need to quantify and control for aspirin effects in patients using this drug in combination with antihypertensive medication. Key Words: antihypertensive agents Ⅲ blood pressure monitoring, ambulatory Ⅲ heart rate Ⅲ hypertension, mild Ⅲ drug therapy Ⅲ circadian rhythm T here is an extensive literature on the effects of acetylsalicylic acid (ASA, or aspirin), one of the most commonly consumed nonsteroidal anti-inflammatory drugs (NSAID), mainly in the prevention of cardiovascular events. 1-3 Although some of these studies reported average values of office blood pressure (BP) measurements for the patients before and after long-term administration of ASA or placebo, the study of a possible effect from ASA on BP was not a primary objective. In fact, the effect of ASA on BP was evaluated only in a few small studies. 4 -6 It has been reported that NSAID may increase BP both in normotensive and hypertensive subjects. 4,[7][8][9] The effects appear more marked in hypertensive subjects under treatment. 4,7 The mechanisms whereby NSAID may increase BP are not fully understood, nor it is known whether the increase in BP is a long-term effect. In any event, the dose of ASA regularly used to show anti-inflammatory effects is markedly larger than the dose used as anticoagulant 10 and recommended for prevention of cardiovascular events. [1][2][3] ASA use in hypertensive patients is expected to inc...

Differing Administration Time-Dependent Effects of Aspirin on Blood Pressure in Dipper and Non-Dipper Hypertensives

“…10 Most important, the administration time-dependent influence of ASA on BP was demonstrated previously in a randomized trial on healthy women 9 and other independent double-blind, randomized, placebo-controlled clinical trials conducted: first on clinically healthy subjects, 11 a second on normotensive and hypertensive subjects, 12 a third on pregnant women at high risk for preeclampsia, 13 and a fourth in untreated patients with mild hypertension. 14 The findings of these BP studies, all of which used ambulatory BP monitoring (ABPM) to derive primary outcome variables, are consistent; BP-lowering effect of low-dose ASA is achieved when administered at bedtime but not on awakening.…”

“…10 Most important, the administration time-dependent influence of ASA on BP was demonstrated previously in a randomized trial on healthy women 9 and other independent double-blind, randomized, placebo-controlled clinical trials conducted: first on clinically healthy subjects, 11 a second on normotensive and hypertensive subjects, 12 a third on pregnant women at high risk for preeclampsia, 13 and a fourth in untreated patients with mild hypertension. 14 15 Many studies show the extent of the nocturnal BP decline is deterministic of cardiovascular injury and risk. Absence of the normal 10% to 20% sleep-time BP decline (dipper pattern) is associated with elevated risk of end-organ injury, particularly to the heart (left ventricular hypertrophy and myocardial infarct), brain (stoke), and kidney (albuminuria and progression to end-stage renal failure).…”

Aspirin, Non-Aspirin Analgesics and the Risk of Hypertension in the SUN Cohort

“…So far, no interaction has been found, though the number of patients involved in these studies was very small (less than 19 patients). 22,23 On the other hand, Hermida et al reported an inverse association between aspirin intake (100 mg/day) given before bed-time and mean 24 hour BP levels (-6/-4 mm Hg reduction of systolic BP/ diastolic BP) 10 especially in non-dippers. 11 24 Two meta-analyses assessing the association of aspirin and other NSAIDs with BP levels have been published.…”

“…4 Results from different prospective studies conducted in the United States assessing the association between use of aspirin, NSAIDs and other analgesics and the risk of hypertension suggest that chronic users of aspirin, NSAIDS, and acetaminophen have a higher risk of hypertension. [5][6][7][8][9] However, some clinical trials conducted in Spain have shown the opposite effect 10,11 and no previous prospective study has assessed this potential relationship in a European cohort, where a different health system probably means different access to medication and a different pattern of drug use. 12 Our objective was to assess the association between regular use of aspirin and non-aspirin analgesic drugs and the incidence of HTN in a prospective dynamic cohort study consisting of Spanish university graduates, the SUN (Seguimiento Universidad de Navarra, University of Navarra Follow-up) project.…”

Molecular Time

“…161 Clinical applications of chronotherapy promise to improve treatment of a wide range of health concerns in addition to hypertension, as has been well reviewed. [163][164][165][166][167][168][169][170][171] Disregard for diurnal rhythms may contribute to differences in therapeutic efficacy, which may be observed, between nocturnal animal models and human patients. Clinical trials should routinely take into account the differing safety and efficacy profiles over 24-hour daily cycles.…”