title: Time-dependent effects of aspirin on blood pressure and morning platelet reactivity: a randomized cross-over trial.
abstract: Aspirin is used for cardiovascular disease (CVD) prevention by millions of patients on a daily basis. Previous studies suggested that aspirin intake at bedtime reduces blood pressure compared with intake on awakening. This has never been studied in patients with CVD. Moreover, platelet reactivity and CVD incidence is highest during morning hours. Bedtime aspirin intake may attenuate morning platelet reactivity. This clinical trial examined the effect of bedtime aspirin intake compared with intake on awakening on 24-hour ambulatory blood pressure measurement and morning platelet reactivity in patients using aspirin for CVD prevention. In this randomized open-label crossover trial, 290 patients were randomized to take 100 mg aspirin on awakening or at bedtime during 2 periods of 3 months. At the end of each period, 24-hour blood pressure and morning platelet reactivity were measured. The primary analysis population comprised 263 (blood pressure) and 133 (platelet reactivity) patients. Aspirin intake at bedtime did not reduce blood pressure compared with intake on awakening (difference systolic/diastolic: -0.1 [95% confidence interval, -1.0, 0.9]/-0.6 [95% confidence interval, -1.2, 0.0] mm Hg). Platelet reactivity during morning hours was reduced with bedtime aspirin intake (difference: -22 aspirin reaction units [95% confidence interval, -35, -9]). The intake of low-dose aspirin at bedtime compared with intake on awakening did not reduce blood pressure of patients with CVD. However, bedtime aspirin reduced morning platelet reactivity. Future studies are needed to assess the effect of this promising simple intervention on the excess of cardiovascular events during the high risk morning hours.
authors.affiliation: From the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (T.N.B., J.D.S., F.R.R., J.G.v.d.B.); Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands (W.J.J.A.); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (W.J.J.A.); JJ van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands (J.J.Z., J.G.v.d.B.); and Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (J.E., M.V.H.). t.n.bonten@lumc.nl.
authors.forename: Tobias N
authors.initials: TN
authors.lastname: Bonten
authors.affiliation: From the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (T.N.B., J.D.S., F.R.R., J.G.v.d.B.); Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands (W.J.J.A.); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (W.J.J.A.); JJ van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands (J.J.Z., J.G.v.d.B.); and Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (J.E., M.V.H.).
authors.forename: Jaapjan D
authors.initials: JD
authors.lastname: Snoep
authors.affiliation: From the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (T.N.B., J.D.S., F.R.R., J.G.v.d.B.); Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands (W.J.J.A.); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (W.J.J.A.); JJ van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands (J.J.Z., J.G.v.d.B.); and Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (J.E., M.V.H.).
authors.forename: Willem J J
authors.initials: WJ
authors.lastname: Assendelft
authors.affiliation: From the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (T.N.B., J.D.S., F.R.R., J.G.v.d.B.); Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands (W.J.J.A.); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (W.J.J.A.); JJ van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands (J.J.Z., J.G.v.d.B.); and Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (J.E., M.V.H.).
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Zwaginga
authors.affiliation: From the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (T.N.B., J.D.S., F.R.R., J.G.v.d.B.); Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands (W.J.J.A.); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (W.J.J.A.); JJ van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands (J.J.Z., J.G.v.d.B.); and Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (J.E., M.V.H.).
authors.forename: Jeroen
authors.initials: J
authors.lastname: Eikenboom
authors.affiliation: From the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (T.N.B., J.D.S., F.R.R., J.G.v.d.B.); Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands (W.J.J.A.); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (W.J.J.A.); JJ van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands (J.J.Z., J.G.v.d.B.); and Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (J.E., M.V.H.).
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
authors.affiliation: From the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (T.N.B., J.D.S., F.R.R., J.G.v.d.B.); Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands (W.J.J.A.); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (W.J.J.A.); JJ van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands (J.J.Z., J.G.v.d.B.); and Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (J.E., M.V.H.).
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.affiliation: From the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (T.N.B., J.D.S., F.R.R., J.G.v.d.B.); Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands (W.J.J.A.); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (W.J.J.A.); JJ van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands (J.J.Z., J.G.v.d.B.); and Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands (J.E., M.V.H.).
authors.forename: Johanna G
authors.initials: JG
authors.lastname: van der Bom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D055502:Secondary Prevention / Q000379:methods*; D016037:Single-Blind Method; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin
keywords: aspirin; blood pressure; chronotherapy; platelet activation