Protocol for assessing the hypotensive effect of evening administration of acetylsalicylic acid: study protocol for a randomized, cross-over controlled trial

Ma Victoria Ruíz-Arzalluz, Ma Cruz Gómez Fernández, Natalia Burgos-Alonso, Ernest Vinyoles, Ricardo San Vicente Blanco, Gonzalo Grandes, TAHPS group, Rosa Morros Pedros, Helena Pera, Veronica Arce Arana, Ma Jose Oyarbide Mondaluce, Luz Rodríguez Ibáñez, Mikel Luque Jiménez, Santiago Ayechu Redín, Oihana Ezkurra Galdos, Iñigo Aguirre Arratibel, Jose Francisco Egido Arroyo, Iosune Alberdi Buruaga, Ma Jesus Bernaras Iturrioz, Arnaia Arruti Querejeta, Elisabete Garnetxogoikoetxea Ribera, Juan Carlos Marlasca García, Ana Teresa Martínez Rementería, Loreto Palacio Elua, Violeta Gonzalez Urcelay, Itziar Hernando Mendibil, Ma Carmen Gonzalez Temprano, Julián Bajo García, Jose Antonio Quindimil Vázquez, Gabriel Hernández Iñarra, Jose Félix Zuazagoita Nubla, Lucas Mengual Martínez, Mencía Benitez Camps, Pere Torán Montserrat, Yoseba Cánovas Zaldua, Jordi Ingla Más, Xavier Cos Claramunt, Ma Teresa Amondarain Arratibel, Ma Dolores Marin Vicuña, Idoia Larrañaga-Cortabarria, Miren Uxue Busca Aguirre, Magdalena Cuesta Oritz, Kizkitza Alustiza Arteaga, Ma Antonia Machain Echarri, MaC Milagros Gómez Santamaría, Arnaia Telleria Astarloa, Maria Luisa Garcia Aramaio, Elena Lizaso Guerrico, Amparo Barrueco Iglesias, Josune Madariaga Jurrebaso, Mercedes Armendáriz Múgica, Ana Roncero Gascón, Ma Soledad Romera Alegría, Ana Ormaetxe Merodio, Azucena Ruiz Meléndez, Ma Teresa González Sanchoyerto, María Mercedes Dolores Ferreras Castrillo, MaCecilia Salgueiro, Mónica Vera Marta Garcia Alfaro, Jose Manuel Escudero, Montserrat Montoliu, Ursula Flix, Antonio Negrete, Albert Boada Balmaceda, Nuria Esclans, Carlos Martin, Ma Victoria Ruíz-Arzalluz, Ma Cruz Gómez Fernández, Natalia Burgos-Alonso, Ernest Vinyoles, Ricardo San Vicente Blanco, Gonzalo Grandes, TAHPS group, Rosa Morros Pedros, Helena Pera, Veronica Arce Arana, Ma Jose Oyarbide Mondaluce, Luz Rodríguez Ibáñez, Mikel Luque Jiménez, Santiago Ayechu Redín, Oihana Ezkurra Galdos, Iñigo Aguirre Arratibel, Jose Francisco Egido Arroyo, Iosune Alberdi Buruaga, Ma Jesus Bernaras Iturrioz, Arnaia Arruti Querejeta, Elisabete Garnetxogoikoetxea Ribera, Juan Carlos Marlasca García, Ana Teresa Martínez Rementería, Loreto Palacio Elua, Violeta Gonzalez Urcelay, Itziar Hernando Mendibil, Ma Carmen Gonzalez Temprano, Julián Bajo García, Jose Antonio Quindimil Vázquez, Gabriel Hernández Iñarra, Jose Félix Zuazagoita Nubla, Lucas Mengual Martínez, Mencía Benitez Camps, Pere Torán Montserrat, Yoseba Cánovas Zaldua, Jordi Ingla Más, Xavier Cos Claramunt, Ma Teresa Amondarain Arratibel, Ma Dolores Marin Vicuña, Idoia Larrañaga-Cortabarria, Miren Uxue Busca Aguirre, Magdalena Cuesta Oritz, Kizkitza Alustiza Arteaga, Ma Antonia Machain Echarri, MaC Milagros Gómez Santamaría, Arnaia Telleria Astarloa, Maria Luisa Garcia Aramaio, Elena Lizaso Guerrico, Amparo Barrueco Iglesias, Josune Madariaga Jurrebaso, Mercedes Armendáriz Múgica, Ana Roncero Gascón, Ma Soledad Romera Alegría, Ana Ormaetxe Merodio, Azucena Ruiz Meléndez, Ma Teresa González Sanchoyerto, María Mercedes Dolores Ferreras Castrillo, MaCecilia Salgueiro, Mónica Vera Marta Garcia Alfaro, Jose Manuel Escudero, Montserrat Montoliu, Ursula Flix, Antonio Negrete, Albert Boada Balmaceda, Nuria Esclans, Carlos Martin

Abstract

Background: The objective of this study is to evaluate the antihypertensive effect of bedtime administration of low doses of aspirin in patients with treated hypertension and high cardiovascular risk on low-dose aspirin for secondary prevention, in order to optimize their usual treatment and reduce their cardiovascular risk.

Methods/design: This is a prospective phase IV multicentre, randomised, triple-blind, placebo-controlled, cross-over clinical trial. We will include 258 individuals with hypertension treated with low-dose aspirin for secondary prevention. These patients will be randomly recruited, by approximately 40 primary care physicians collaborating in the study, mainly in the Guipúzcoa West, Bilbao and Barcelona areas. The 258 patients will be randomly allocated to treatments to create two comparable groups. In the first period, the intervention group will take aspirin at night and placebo in the morning, while the control group will take their aspirin in the morning and placebo in the evening for 2 months. After a washout period of 15 to 30 days, there will be a second 2-month period for which groups will swap treatments. Participants will undergo ambulatory blood pressure monitoring at baseline, at the end of first period and then again at the beginning and end of the second period. The main outcome measure is the change in mean blood pressure over 24 h, and as secondary outcomes we will also assess changes in systolic and diastolic blood pressure, during the day and night, and the relationship between them. Lastly, we will explore whether non-dipper patients convert into dippers with the intervention.

Discussion: The goal of this research is to provide the scientific basis for indicating a change in the time of aspirin administration from morning to evening, by primary health practitioners, to improve the patient control of blood pressure and more effectively reduce their cardiovascular risk, by combining this hypotensive effect with the well-known anti-platelet effect of low-dose aspirin.

Trial registration: ClinicalTrials.gov NCT01741922.

Figures

Figure 1
Figure 1
Flow of the study.

References

    1. Hermida RC, Ayala DE, Calvo C, López JE. Aspirin administered at bedtime, but not on awakening, has an effect on ambulatory blood pressure in hypertensive patients. J Am Coll Cardiol. 2005;46:975–983. doi: 10.1016/j.jacc.2004.08.071.
    1. Hermida RC, Ayala DE, Calvo C, López JE, Mojón A, Rodríguez M, Fernández JR. Differing administration time-dependent effects of aspirin on blood pressure in dipper and non-dipper hypertensives. Hypertension. 2005;46:1060–1068. doi: 10.1161/01.HYP.0000172623.36098.4e.
    1. Hermida RC, Ayala DE, Mojón A, Fernández JR. Ambulatory blood pressure control with bedtime aspirin administration in subjects with prehypertension. Am J Hypertens. 2009;22:896–903. doi: 10.1038/ajh.2009.83.
    1. Hermida RC, Ayala DE, Calvo C, López JE, Fernández JR, Mojón A, Dominguez MJ, Covelo M. Administration time-dependent effects of aspirin on blood pressure in untreated hypertensive patients. Hypertension. 2003;41:1259–1267. doi: 10.1161/01.HYP.0000072335.73748.0D.
    1. Collaboration AT. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86. doi: 10.1136/bmj.324.7329.71.
    1. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–1860.
    1. Felmeden DC, Lip GY. Antithrombotic therapy in hypertension: a Cochrane Systematic review. J Hum Hypertens. 2005;19:185–196.
    1. Lip GY, Felmeden DC. Antiplatelet agents and anticoagulants for hypertension. Cochrane Database Syst Rev. 2004;3 CD003186.
    1. de la Sierra A, Gorostidi M, Marín R, Redón J, Banegas JR, Armario P, Garcia Puig J, Zarco J, Llisterri JL, Sanchis C, Abarca B, Palomo V, Gomis R, Otero A, Villar F, Honorato J, Tamargo J, Lobos JM, Macias-Nunez J, Sarria A, Aranda P, Ruilope LM. Evaluation and management of hypertension in Spain. A consensus guide. Med Clin (Barc) 2008;131:104–116. doi: 10.1157/13124015.
    1. del Campo Rotaeche R, Aguirrezabala Jaca J, Balagué Gea L. Guia de Practica Clinica sobre HTA. Osakidetza; 2007. .
    1. Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008;51:55–61. doi: 10.1161/HYPERTENSIONAHA.108.112979.
    1. Fagard RH, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J Hum Hypertens. 2009;23:645–653. doi: 10.1038/jhh.2009.9.
    1. Kikuya M, Ohkubo T, Asayama K, Metoki H, Obara T, Saito S, Hashimoto J, Totsune K, Hoshi H, Satoh H, Imai Y. Ambulatory blood pressure and 10-year risk of cardiovascular and noncardiovascular mortality: the Ohasama study. Hypertension. 2005;45:240–245. doi: 10.1161/01.HYP.0000152079.04553.2c.
    1. Ohkubo T, Hozawa A, Yamaguchi J, Kikuya M, Ohmori K, Michimata M, Matsubara M, Hashimoto J, Hoshi H, Araki T, Tsuji I, Satoh H, Hisamachi S, Imai Y. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens. 2002;20:2183–2189. doi: 10.1097/00004872-200211000-00017.
    1. Llisterri Caro JL, Rodríguez Roca GC, Alonso Moreno FJ, Prieto Díaz MA, Banegas Banegas JR, Gonzalez-Segura Alsina D, Lou Arnal S, Divison Garrote JA, Beato Fernandez P, Barrios Alonso V. en representacion del Grupo de Trabajo de Hipertension Arterial de la Sociedad Espanola de Atencion Primaria (Grupo HTA/SEMERGEN) y de los investigadores del Estudio PRESCAP 2010. Blood pressure control in hypertensive Spanish population attended in Primary Care setting. The PRESCAP 2010 study. Med Clin (Barc) 2012;139:653–661. doi: 10.1016/j.medcli.2011.10.023.
    1. Adiro 100 [Internet] .
    1. Staessen J, Fagard R, Lijnen P, Thijs L, van Hoof R, Amery A. Ambulatory blood pressure monitoring in clinical trials. J Hypertens Suppl. 1991;9:S13–S19. doi: 10.1097/00004872-199112007-00005.
    1. Donner A. Approaches to sample size estimation in the design of clinical trials–a review. Stat Med. 1984;3:199–214. doi: 10.1002/sim.4780030302.
    1. Llisterri Caro JL, Rodríguez Roca GC, Alonso Moreno FJ, Banegas Banegas JR, González-Segura Alsina D, Lou Arnal S, Prieto-Diaz MA, Sanchez-Ruiz T, Dura-Belinchon R, Santos-Rodriguez JA, Divison-Garrote JA, Gonzalez-Segura D, Banegas-Banegas JR. Working Group of Arterial Hypertension in the Spanish Society of Primary Care Physicians (group HTA/SEMERGEN); PRESCAP 2006 Investigators. Control of blood pressure in Spanish hypertensive population attended in primary health-care. PRESCAP 2006 Study. Med Clin (Barc) 2008;130:681–687. doi: 10.1157/13120766.
    1. Llisterri JL, Rodriguez-Roca GC, Escobar C, Alonso-Moreno FJ, Prieto MA, Barrios V, González-Alsina D, Divisón JA, Pallarés V, Beato P, on behalf of the Working Group of Arterial Hypertension of the Spanish Society of Primary Care Physicians (Group HTASEMERGEN), and the PRESCAP 2010 investigators Treatment and blood pressure control in Spain during 2002–2010. J Hypertens. 2012. pp. 2425–2431.
    1. Hermida RC, Ayala DE, Calvo C, López JE, Fernández JR, Mojón A. et al.Administration-time dependent effects of acetyl-salicylic acid on blood pressure in patients with mild essential hypertension. Med Clin (Barc) 2003;120:686–692.
    1. Zanchetti A, Hansson L, Dahlöf B, Julius S, Ménard J, Warnold I, Wedel H. HOT Study Group. Benefit and harm of low-dose aspirin in well-treated hypertensives at different baseline cardiovascular risk. J Hypertens. 2002;20:2301–2307. doi: 10.1097/00004872-200211000-00031.
    1. Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998;351:1755–1762. doi: 10.1016/S0140-6736(98)04311-6.
    1. Sierra C, De la Sierra A, Sobrino J, Segura J, Banegas JR, Gorostidi M, Ruilope LM. en representacion de los Investigadores del Registro Nacional de MAPA; Sociedad Espanola de Hipertension-Liga Espanola para la Lucha contra la Hipertension Arterial (SEH-LELHA) Ambulatory blood pressure monitoring (CABPM): clinical characteristics of 31,530 patients. Med Clin (Barc) 2007;129:1–5. doi: 10.1157/13106673.
    1. Guidelines for the management of Arterial Hypertension. The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) 2007. .
    1. Committee ESoH-ESoCG. European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003;2003(21):1011–1053.
    1. Moore JG, Goo RH. Day and night aspirin-induced gastric mucosal damage and protection by ranitidine in man. Chronobiol Int. 1987;4:111–116. doi: 10.3109/07420528709078514.

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