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Aspirin for Stroke Prevention Taken in the Evening?

2004; Lippincott Williams & Wilkins; Volume: 35; Issue: 12 Linguagem: Inglês

10.1161/01.str.0000147155.08852.12

1524-4628

I Kriszbacher, Miklós Koppán, József Bódis,

Venous Thromboembolism Diagnosis and Management

HomeStrokeVol. 35, No. 12Aspirin for Stroke Prevention Taken in the Evening? Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBAspirin for Stroke Prevention Taken in the Evening? Ildikó Kriszbacher, MSc, Miklós Koppán, MD, PhD and József Bódis, MD, DSc Ildikó KriszbacherIldikó Kriszbacher Institute of Nursing and Clinical Sciences, Faculty of Health Sciences, University of Pécs, Pécs, Hungary , Miklós KoppánMiklós Koppán Institute of Nursing and Clinical Sciences, Faculty of Health Sciences, University of Pécs, Pécs, Hungary and József BódisJózsef Bódis Institute of Nursing and Clinical Sciences, Faculty of Health Sciences, University of Pécs, Pécs, Hungary Originally published28 Oct 2004https://doi.org/10.1161/01.STR.0000147155.08852.12Stroke. 2004;35:2760–2762Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: October 28, 2004: Previous Version 1 To the Editor:We read the article by Yip et al1 with great interest, in which they demonstrated that platelet activation significantly increases in acute ischemic stroke and subtantially decreases thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.1 Their results are very impressive and raise some ideas, particularly associated with the prevention's procedures.According to World Health Organization data, in 1996 4.6 million people in the world died because of cerebrovascular manifestation of atherothrombosis.2 In Hungary, nearly 18 000 people suffer stroke every year, half of whom die within a year. In cases of both cardiovascular and cerebrovascular diseases the significant decrease of morbidity/mortality can only be achieved by increasing the effect of prevention. A major form of secondary prevention is the administration of drugs inhibiting the aggregation of platelets.Aspirin is one of the most common, useful, and inexpensive tools for prevention. The effect of aspirin on platelets is irreversible lasting for the duration of the platelet's life span (≈10 days). Aspirin-mediated inhibition of platelet function occurs within 60 minutes of ingestion.3The incidence of stroke assessed by onset of clinical symptoms exhibits a marked circadian variation with a peak period during the morning. Stroke usually occurs unexpectedly and more frequently in early morning hours (between 5 to 12 pm; see Figure) when the aggregability of thrombocytes is higher.4 Increased platelet aggregation in the morning and perhaps an upright posture may account at least in part for the observed circadian variation of the manifestation of stroke. Download figureDownload PowerPointRelation of plasma serum levels of salicylacid and the daily distribution of the occurrence of acute ischemic stroke. Vertical bar graphs represent daily distribution of incidence of ischemic stroke.4 Line diagrams show serum level of salicylacid in μg/mL taken at 10:00 pm (dotted line) and at 8:00 am (solid line). The maximum plasma concentration of salicylacid occurs 3.5 to 4.0 hours after intake.5 N=total number of patients involved in analysis, SA=salicylacid.For prevention patients usually take aspirin in the morning. The treatment regimen is 1 tablet (100 mg) per day to be swallowed without chewing at least 30 minutes before breakfast. The relation of occurrence of stroke and the change of aspirin's plasma level taking in the morning is demonstrated in the Figure. It is obvious that highest plasma level of the drug occurs after the morning peak-incidence of the thromboembolic event, suggesting lower prophylactic effect of aspirin. Furthermore, this treatment regimen has its highest protective effect during the day, when, synergistically, normal physical activity exerts a protective action on thromboembolic processes. However, this method of daily aspirin administration has its lowest protective value against cardiovascular events during the night and early morning, when the lack of physical activity further augment the cascade of hemorheological events favoring platelet aggregation and subsequent ischemia. In contrast, highest plasma level of aspirin taken late evening (10:00 pm) would be reached prior to the peak-incidence of thromboembolic disorders. We are confident that this time shift in the administration of aspirin would fit better in the circadian scheme of the occurrence of stroke, thus resulting in a significantly more effective prevention. To prove the viability of this concept we propose to set up international, randomized, multicenter studies.1 Yip HK, Chen SS, Liu JS, Chang HW, Kao YF, Lan MY, Chang YY, Lai SL, Chen WH, Chen MC. Serial changes in platelet activation in patients after ischemic stroke: role of pharmacodynamic modulation. Stroke. 2004; 35: 1683–1687.LinkGoogle Scholar2 World Health Organization. World Health Statistics Annual 1995 Geneva: World Health Organization 1996;(B): 800–818.Google Scholar3 Awtry EH, Loscalzo J. Cardiovascular Drugs. Circulation. 2000; 101: 1206–1218.CrossrefMedlineGoogle Scholar4 Lago A, Geffner D, Tembl J, Landete L, Valero C, Baquero M. Circadian variation in acute ischemic stroke: a hospital-based study. Stroke. 1998; 29: 1873–1875.CrossrefMedlineGoogle Scholar5 Aspirin Enteric Coated. Antiplatelet Therapy With Acetylsalicylic Acid. Leverkusen, Germany: Bayer AG. 1999; 39.Google ScholarstrokeahaStrokeStrokeStroke0039-24991524-4628Lippincott Williams & WilkinsResponse:Yip Hon-Kan, , MD, Chen Shun-Sheng, , MD, PhD, and Chen Mien-Cheng, , MD01122004Platelets play a key role in the pathogenesis of atherosclerosis and arterial thrombosis, which are the major contributors to the development of ischemic stroke and acute coronary syndrome.1–3 Antiplatelet therapy is now a mainstay of primary and secondary prevention of death, myocardial infarction, and stroke in various categories of patients.4–6 Previous studies have demonstrated the ischemic stroke to display a diurnal variation with a higher frequency in the early hours of the morning.7,8 Although exactly why this circadian variation occurs remains uncertain, circadian variation of fibrinolysis, platelet aggregability, and arterial blood pressure, with their peak value in the morning, have been suggested to play a key role in this phenomenon.7–9Given the safety, widespread availability, and minimal cost of aspirin therapy, aspirin is one of the most common antiplatelet agents for secondary prevention following an ischemic stroke.10 Aspirin is rapidly absorbed in the upper gastrointestinal tract and results in a measurable inhibition of the platelet function within 60 minutes.11 Additionally, a pharmacokinetic study has demonstrated that the peak serum level of aspirin is generally detected within 3.5 to 4.0 hours following ingestion.12 While considering both the circadian variation of a stroke and the particular pharmacodynamic effect of aspirin, Bodis and colleagues conjectured that taking aspirin in the morning after breakfast, as traditionally recommended, would offer a lower protective effect on recurrent stroke. They proposed that aspirin taken in the late evening, ie, around 10:00 pm, would benefit patients more than aspirin taken during the traditional administration time. To prove the viability of this hypothesis, they propose to set up international, randomized, multicenter studies.We read with great interest regarding their hypothesis and opinion. However, 3 issues should be considered before conducting trials to test their hypothesis. First, if taking aspirin in the late evening could provide additional benefit than taking aspirin in the morning, a concern may arise over whether taking aspirin (100 mg) twice daily might be more protective to patients than daily administration. Second, owing to the benefits of aspirin in treating acute ischemic stroke,10 acute coronary syndrome,3 and in the secondary prevention for cardiovascular and cerebrovascular diseases,4 numerous studies have attempted to evaluate aspirin as a primary prevention strategy.5,6,13 While the results regarding the role of aspirin on the primary prevention of cardiovascular mortality remains inconsistent,4,13,14 aspirin does not appear to significantly affect the primary prevention of a stroke.6,14 These observations motivate the search for a more effective antiplatelet agent other than aspirin for primary stroke prevention in the future. Third, several randomized trials4,5,15 have been conducted to determine the extent of reduction in terms of cardiovascular outcomes by different antiplatelet therapies in patients at risk of ischemic stroke. Clopidogrel, a new thienopyridine derivative that is chemically related to ticlopidine, blocks activation of platelets by selectively and irreversibly inhibiting the binding of adenosine diphosphate (ADP) to its receptor on platelets, subsequently inhibiting the ADP-dependent activation of the Gp IIb-IIIa complex, the major receptor for fibrinogen binding on platelet surface.5 A related study has demonstrated that clopidogrel is more effective than aspirin in reducing the combined risk of ischemic stroke, myocardial infarction, or vascular death.5 Our study16 has provided basic evidence that clopidogrel is more potent than aspirin in suppressing platelet activation after ischemic stroke, and, therefore, further strengthens the conclusions of previous studies.4,5,15 Although testing the hypothesis whether aspirin administered in late evening (at 10:00 pm) would offer greater benefit to patients would be more interesting, identifying a more effective antiplatelet agent for primary or secondary prevention of ischemic stroke would be more meaningful. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Martin-Latry K, Cazaux J, Lafitte M and Couffinhal T (2014) Negative impact of physician prescribed drug dosing schedule requirements on patient adherence to cardiovascular drugs, Pharmacoepidemiology and Drug Safety, 10.1002/pds.3608, 23:10, (1088-1092), Online publication date: 1-Oct-2014. Bonten T, Saris A, van Oostrom M, Snoep J, Rosendaal F, Zwaginga J, Eikenboom J, van der Meer P and van der Bom J (2017) Effect of aspirin intake at bedtime versus on awakening on circadian rhythm of platelet reactivity, Thrombosis and Haemostasis, 10.1160/th14-05-0453, 112:12, (1209-1218), . De Giorgi A, Mallozzi Menegatti A, Fabbian F, Portaluppi F and Manfredini R (2013) Circadian rhythms and medical diseases: Does it matter when drugs are taken?, European Journal of Internal Medicine, 10.1016/j.ejim.2013.03.019, 24:8, (698-706), Online publication date: 1-Dec-2013. Zhu L, Zhou Q, Yan X and Zeng S (2008) Optimal time to take once-daily oral medications in clinical practice, International Journal of Clinical Practice, 10.1111/j.1742-1241.2008.01871.x, 62:10, (1560-1571) Haus E (2007) Chronobiology of hemostasis and inferences for the chronotherapy of coagulation disorders and thrombosis prevention, Advanced Drug Delivery Reviews, 10.1016/j.addr.2006.11.002, 59:9-10, (966-984), Online publication date: 1-Aug-2007. Amory J and Amory D (2007) Dosing Frequency of Aspirin and Prevention of Heart Attacks and Strokes, The American Journal of Medicine, 10.1016/j.amjmed.2006.04.023, 120:4, (e5), Online publication date: 1-Apr-2007. Kriszbacher I, Ajtay Z, Koppán M and Bódis J (2005) Can the Time of Taking Aspirin Influence the Frequency of Cardiovascular Events?, The American Journal of Cardiology, 10.1016/j.amjcard.2005.03.068, 96:4, (608-610), Online publication date: 1-Aug-2005. Manfredini R, Boari B, Smolensky M, Salmi R, la Cecilia O, Maria Malagoni A, Haus E and Manfredini F (2009) Circadian Variation in Stroke Onset: Identical Temporal Pattern in Ischemic and Hemorrhagic Events, Chronobiology International, 10.1081/CBI-200062927, 22:3, (417-453), Online publication date: 1-Jan-2005. Bonten T, Saris A, van Oostrom M, Snoep J, Rosendaal F, Zwaginga J, Eikenboom J, van der Meer P and van der Bom J (2014) Effect of aspirin intake at bedtime versus on awakening on circadian rhythm of platelet reactivity, Thrombosis and Haemostasis, 10.1160/TH-14-05-0453, 112:6 December 2004Vol 35, Issue 12 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000147155.08852.12PMID: 15514187 Originally publishedOctober 28, 2004 PDF download Advertisement