{"id":36,"date":"2020-03-24T16:18:33","date_gmt":"2020-03-24T19:18:33","guid":{"rendered":"http:\/\/template1.bs2.com.br\/profissionais-saude\/?p=36"},"modified":"2020-03-24T16:18:35","modified_gmt":"2020-03-24T19:18:35","slug":"dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares","status":"publish","type":"post","link":"https:\/\/www.prcardio.org\/profissionais-saude\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\/","title":{"rendered":"DOSE DE ASPIRINA AJUSTADA AO PESO PARA PREVEN\u00c7\u00c3O DE EVENTOS CARDIOVASCULARES"},"content":{"rendered":"<!--themify_builder_content-->\n<div id=\"themify_builder_content-36\" data-postid=\"36\" class=\"themify_builder_content themify_builder_content-36 themify_builder tf_clear\">\n    <\/div>\n<!--\/themify_builder_content-->\n\n\n<h4 class=\"wp-block-heading\">diabetes, preven\u00e7\u00e3o, aspirina,&nbsp;\u00e1cido acetilsalic\u00edlico<\/h4>\n\n\n\n<h5 class=\"wp-block-heading\">Katherine N Theken<\/h5>\n\n\n\n<h3 class=\"wp-block-heading\">Abstract<\/h3>\n\n\n\n<p>Understanding the sources of variability in patients&#8217; responses to medications has the potential to improve<br>effectiveness and safety through personalization of treatment. Individual factors &#8211; that is, risk of patients&#8217; cardiovascular disease for events are already considered when deciding who is prescribed low dose aspirin for cardiovascular prevention. However, aspirin inhibits only one of several pathways of platelet activation, so it is not surprising that many patients still experience cardiovascular events.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Resumo<\/h3>\n\n\n\n<p>Aspirina com ajuste de peso para preven\u00e7\u00e3o cardiovascular Compreender as fontes de variabilidade em pacientes \u00e0s respostas aos medicamentos t\u00eam o potencial de melhorar a<\/p>\n\n\n\n<p>efic\u00e1cia e seguran\u00e7a atrav\u00e9s da personaliza\u00e7\u00e3o do tratamento. Fatores individuais &#8211; isto \u00e9, risco de doen\u00e7a cardiovascular dos paciente para eventos j\u00e1 s\u00e3o considerados ao decidir para quem \u00e9 prescrito aspirina em baixas doses para preven\u00e7\u00e3o cardiovascular. No entanto, a aspirina inibe apenas uma das v\u00e1rias vias de ativa\u00e7\u00e3o plaquet\u00e1ria, por isso n\u00e3o \u00e9 de surpreender que muitos os pacientes ainda experimentam eventos cardiovasculares.<\/p>\n\n\n\n<hr class=\"wp-block-separator\"\/>\n\n\n\n<p>Fatores que potencialmente contribuem para essas falhas de tratamento, \u00e0s vezes chamado de resist\u00eancia \u00e0 aspirina, foram estudados extensivamente, e v\u00e1rios mecanismos plaus\u00edveis t\u00eam sugerido, incluindo a n\u00e3o ades\u00e3o, turnover&nbsp;acelerado&nbsp; de plaquetas em pacientes com diabetes, &nbsp;intera\u00e7\u00f5es medicamentosas com anti-inflamat\u00f3rios n\u00e3o ester\u00f3ides, biodisponibilidade reduzida devido ao revestimento ent\u00e9rico, peso corporal&nbsp;Considerar esses fatores ao escolher a dose considerando frequ\u00eancia de dosagem, e talvez at\u00e9 tempo de dosagem de forma individualizada, pode&nbsp; ter substancial efeitos na sa\u00fade p\u00fablica Na revista The Lancet, Peter Rothwell e colegas relatam a sua investiga\u00e7\u00e3o dos efeitos da intera\u00e7\u00e3o entre peso corporal e dose de aspirina no risco de eventos vasculares, sangramento e c\u00e2ncer, combinando dados de pacientes individuais a partir de ensaios. Sua an\u00e1lise incluiu nove ensaios de aspirina em preven\u00e7\u00e3o prim\u00e1ria de eventos cardiovasculares e sangramento (incluindo aproximadamente 103.000 pacientes) e aspirina na preven\u00e7\u00e3o secund\u00e1ria de AVC (incluindo aproximadamente 13000 pacientes). Os autores descobriram que a dose baixa aspirina (\u2264100 mg \/ dia) preveniu o desenvolvimento<\/p>\n\n\n\n<p>eventos apenas em indiv\u00edduos com baixo peso corporal (&lt;70 kg),enquanto doses mais altas de aspirina (\u2265 300mg \/ dia) foram eficaz apenas em indiv\u00edduos com 70 kg ou mais.Uma intera\u00e7\u00e3o semelhante foi observada para o c\u00e2ncer colorretale sangramento, embora com um peso aparentemente maior ponto de corte (\u2265 80 kg para c\u00e2ncer colorretal e \u2265 90 kg para grandes hemorragias). Notavelmente, a an\u00e1lise implica que ajusar a dose&nbsp; para o peso corporal pode melhorar substancialmente a efic\u00e1cia da aspirina. Baixa dose de aspirina reduz eventos cardiovasculares em 23% (taxa de risco [HR] 0 \u00b7 77,IC95% 0,68-0,17; p &lt;0 \u00b7 0001) em indiv\u00edduos com peso menor 70 kg, contra uma redu\u00e7\u00e3o de apenas 12% (0,88,0 \u00b7 81 &#8211; 0 \u00b7 95; p = 0 \u00b7 0008) na preven\u00e7\u00e3o prim\u00e1ria geral popula\u00e7\u00e3o quando o peso n\u00e3o foi considerado. Tamb\u00e9m o autores sugerem que as diferen\u00e7as de sexo no peso corporal \u2013 por mais homens do que mulheres pesavam mais de 70 kg pode explicar a falta de efic\u00e1cia h\u00e1 muito reconhecida da aspirina na preven\u00e7\u00e3o de AVC em homens. A diferen\u00e7a no risco entre homens e mulheres j\u00e1 n\u00e3o era detect\u00e1vel quando o peso corporal foi contabilizado.O peso pode afetar a distribui\u00e7\u00e3o e o clearance de drogas,e \u00e9 conhecido por modular a inibi\u00e7\u00e3o plaquet\u00e1ria clopidogrel e prasugrel.9,10 Al\u00e9m disso, o dosagem ajustada ao peso \u00e9 comum para inibidores antagonistas da glicoprote\u00edna IIb \/ IIIa e cangrelor). Com em rela\u00e7\u00e3o \u00e0 aspirina, depura\u00e7\u00e3o extensa por esterases no intestino, plasma, c\u00e9lulas sangu\u00edneas e o f\u00edgado resulta em biodisponibilidade sist\u00eamica de apenas 50%. Parece plaus\u00edvel que indiv\u00edduos com maior massa corporal teriam um maior quantidade dessas esterases do que seria em indiv\u00edduos menores, resultando na redu\u00e7\u00e3o da biodisponibilidade da aspirina.Esta hip\u00f3tese \u00e9 apoiada pela observa\u00e7\u00e3o de que o<\/p>\n\n\n\n<p>intera\u00e7\u00e3o entre peso e risco de eventos&nbsp; cardiovascular&nbsp; foi acentuada com aspirina com revestimento ent\u00e9rico,que tem cerca de 40% de biodisponibilidade sist\u00eamica do que a aspirina n\u00e3o revestida.11O objetivo do uso de baixas doses de aspirina \u00e9 limitar a exposi\u00e7\u00e3o sist\u00eamica \u00e0 aspirina e o conseq\u00fcente depress\u00e3o da ciclooxigenase homeost\u00e1tica (COX)produtos na vasculatura e no est\u00f4mago. Aspirina Acetila de forma irrevers\u00edvel a COX-1 nas plaquetas que s\u00e3o incapazes para sintetizar nova enzima. Assim, baixas doses de aspirina pode inibir a fun\u00e7\u00e3o plaquet\u00e1ria, desde que haja mais inibidores plaquetarios do que os liberados recentemente dos megacari\u00f3citos.Esta inibi\u00e7\u00e3o pode ocorrer de forma pr\u00e9-sist\u00eamica antes da inativa\u00e7\u00e3o pelo f\u00edgado esterases.12 A prostaciclina, o Prostaciclina, produto vascular da COX destinado a ser poupado pelo uso de doses de aspirina, \u00e9 um potente inibidor de plaquetas e mol\u00e9cula central no importante feedback negativo,mecanismo que limita o crescimento de trombos em locais<\/p>\n\n\n\n<p>de les\u00e3o vascular.13 A aparente falta de efic\u00e1cia da dose intermedi\u00e1ria e dose alta de aspirina em indiv\u00edduos pesando menos de 70 kg levanta a quest\u00e3o de saber se essas falhas de tratamento podem refletir a inibi\u00e7\u00e3o prostaciclina vascular devido ao aumento sist\u00eamico biodisponibilidade da aspirina neste subgrupo. Como a dosagem ajustada ao peso da aspirina pode afetar risco de sangramento? Nos ensaios inclu\u00eddos na an\u00e1lise, 80% dos homens e quase 50% das mulheres pesavam 70 kg ou mais.<\/p>\n\n\n\n<p>Assim, a dosagem ajustada pelo peso resultaria em aumento doses di\u00e1rias de aspirina na maioria dos pacientes, o que seria esperado que afetasse o risco de sangramento. No entanto, essa associa\u00e7\u00e3o&nbsp; pode n\u00e3o ser linear porque os autores observaram que o risco de sangramento em baixas doses de aspirina foi elevada em pacientes com peso entre 70 e 90 kg, apesar da falha na preven\u00e7\u00e3o de eventos cardiovasculares. Como os autores observaram , o peso corporal deve ser considerado em curso e futuros ensaios cl\u00ednicos randomizados que abordam a dose de aspirina&nbsp; na preven\u00e7\u00e3o cardiovascular para esclarecer como a dosagem ajustada ao peso afetar\u00e1 tanto o benef\u00edcio quanto o risco.Rothwell e seus colegas apresentam resultados provocativos com o potencial de afetar substancialmente a sa\u00fade p\u00fablica.Claramente, mais pesquisas s\u00e3o necess\u00e1rias para estabelecer se a dose ajustada ao peso da aspirina deve ser incorporado em cuidados cl\u00ednicos.<\/p>\n\n\n\n<p>Katherine N Theken, *Tilo Grosser Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA tilo@pennmedicine.upenn.edu We declare no competing interests. Copyright \u00a9 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. 1 Antithrombotic Trialists\u2019 (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\u201360. 2 Hennekens CH, Schneider WR, Hebert PR, Tantry US, Gurbel PA. Hypothesis formulation from subgroup analyses: nonadherence or nonsteroidal anti-inflammatory drug use explains the lack of clinical benefit of aspirin on first myocardial infarction attributed to \u201caspirin resistance\u201d. Am Heart J 2010; 159: 744\u201348. 3 Pascale S, Petrucci G, Dragani A, et al. Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target. Blood 2012; 119: 3595\u2013603. 4 Li X, Fries S, Li R, et al. Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci USA 2014; 111: 16830\u201335. 5 Maree AO, Curtin RJ, Dooley M, et al. Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease. J Am Coll Cardiol 2005; 46: 1258\u201363. 6 Grosser T, Fries S, Lawson JA, Kapoor SC, Grant GR, FitzGerald GA. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation 2013; 127: 377\u201385. 7 Peace A, McCall M, Tedesco T, et al. The role of weight and enteric coating on aspirin response in cardiovascular patients. J Thromb Haemost 2010; 8: 2323\u201325. 8 Rothwell PM, Cook NR, Gaziano JM, et al. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet 2018; published online July 12. http:\/\/dx.doi.org\/10.1016\/S0140-6736(18)31133-4. 9 Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Platelet aggregation according to body mass index in patients undergoing coronary stenting: should clopidogrel loading-dose be weight adjusted? J Invasive Cardiol 2004; 16: 169\u201374. 10 Erlinge D, Ten Berg J, Foley D, et al. Reduction in platelet reactivity with prasugrel 5 mg in low-body-weight patients is noninferior to prasugrel 10 mg in higher-body-weight patients: results from the FEATHER trial. J Am Coll Cardiol 2012; 60: 2032\u201340. 11 Bochner F, Somogyi AA, Wilson KM. Bioinequivalence of four 100 mg oral aspirin formulations in healthy volunteers. Clin Pharmacokinet 1991; 21: 394\u201399. 12 Pedersen AK, FitzGerald GA. Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase. N Engl J Med 1984; 311: 1206\u201311. 13 Grosser T, Ricciotti E, FitzGerald GA. The cardiovascular pharmacology of nonsteroidal anti-inflammatory drugs. Trends Pharmacol Sci 2017<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"http:\/\/template1.bs2.com.br\/profissionais-saude\/wp-content\/uploads\/sites\/2\/2020\/03\/15335552125833.pdf\" target=\"_blank\" rel=\"noreferrer noopener\"><img loading=\"lazy\" decoding=\"async\" width=\"80\" height=\"88\" src=\"http:\/\/template1.bs2.com.br\/profissionais-saude\/wp-content\/uploads\/sites\/2\/2020\/03\/pdf.jpg\" alt=\"\" class=\"wp-image-20\"\/><\/a><\/figure>","protected":false},"excerpt":{"rendered":"<p>diabetes, preven\u00e7\u00e3o, aspirina,&nbsp;\u00e1cido acetilsalic\u00edlico Katherine N Theken Abstract Understanding the sources of variability in patients&#8217; responses to medications has the potential to improveeffectiveness and safety through personalization of treatment. Individual factors &#8211; that is, risk of patients&#8217; cardiovascular disease for events are already considered when deciding who is prescribed low dose aspirin for cardiovascular prevention. [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-36","post","type-post","status-publish","format-standard","hentry","category-artigos","has-post-title","has-post-date","has-post-category","has-post-tag","has-post-comment","has-post-author",""],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>SPC - Sociedade Paranaense de Cardiologia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.prcardio.org\/profissionais-saude\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\/\" \/>\n<meta property=\"og:locale\" content=\"pt_BR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"SPC - Sociedade Paranaense de Cardiologia\" \/>\n<meta property=\"og:description\" content=\"diabetes, preven\u00e7\u00e3o, aspirina,&nbsp;\u00e1cido acetilsalic\u00edlico Katherine N Theken Abstract Understanding the sources of variability in patients&#8217; responses to medications has the potential to improveeffectiveness and safety through personalization of treatment. Individual factors &#8211; that is, risk of patients&#8217; cardiovascular disease for events are already considered when deciding who is prescribed low dose aspirin for cardiovascular prevention. [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.prcardio.org\/profissionais-saude\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\/\" \/>\n<meta property=\"og:site_name\" content=\"SPC - Sociedade Paranaense de Cardiologia\" \/>\n<meta property=\"article:published_time\" content=\"2020-03-24T19:18:33+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-03-24T19:18:35+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.prcardio.org\/profissionais-saude\/wp-content\/uploads\/sites\/2\/2020\/03\/pdf.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"80\" \/>\n\t<meta property=\"og:image:height\" content=\"88\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Hospedagem\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Hospedagem\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"7 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.prcardio.org\\\/profissionais-saude\\\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.prcardio.org\\\/profissionais-saude\\\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\\\/\"},\"author\":{\"name\":\"Hospedagem\",\"@id\":\"https:\\\/\\\/www.prcardio.org\\\/profissionais-saude\\\/#\\\/schema\\\/person\\\/a9b1dff39e9c1d3ba41de0f3dd6e1104\"},\"headline\":\"DOSE DE ASPIRINA AJUSTADA AO PESO PARA PREVEN\u00c7\u00c3O DE EVENTOS CARDIOVASCULARES\",\"datePublished\":\"2020-03-24T19:18:33+00:00\",\"dateModified\":\"2020-03-24T19:18:35+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.prcardio.org\\\/profissionais-saude\\\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\\\/\"},\"wordCount\":1486,\"commentCount\":0,\"image\":{\"@id\":\"https:\\\/\\\/www.prcardio.org\\\/profissionais-saude\\\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\\\/#primaryimage\"},\"thumbnailUrl\":\"http:\\\/\\\/template1.bs2.com.br\\\/profissionais-saude\\\/wp-content\\\/uploads\\\/sites\\\/2\\\/2020\\\/03\\\/pdf.jpg\",\"articleSection\":[\"Artigos\"],\"inLanguage\":\"pt-BR\",\"potentialAction\":[{\"@type\":\"CommentAction\",\"name\":\"Comment\",\"target\":[\"https:\\\/\\\/www.prcardio.org\\\/profissionais-saude\\\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\\\/#respond\"]}]},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.prcardio.org\\\/profissionais-saude\\\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\\\/\",\"url\":\"https:\\\/\\\/www.prcardio.org\\\/profissionais-saude\\\/dose-de-aspirina-ajustada-ao-peso-para-prevencao-de-eventos-cardiovasculares\\\/\",\"name\":\"SPC - 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Individual factors &#8211; that is, risk of patients&#8217; cardiovascular disease for events are already considered when deciding who is prescribed low dose aspirin for cardiovascular prevention. 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