Background: Platelets provide the initial haemostatic plug at sites of vascular injury. They also participate in pathological thrombosis that leads to myocardial infarction, stroke and peripheral vascular disease. The outcome of an acute myocardial infarction depends not only on the formation and stability of an occlusive thrombus, but also on the efficacy of the endogenous thrombolytic process, which allows reperfusion of the infarct related artery and prevents recurrent ischaemic episodes. Various platelet function tests are available to measure the thrombogenic potential of an individual, but the sensitivity of these tests remain questionable as most of these tests use citrated blood and measure response to a particular agonist. Endogenous thrombolysis has been a neglected entity, and its beneficial effects on cardiovascular outcomes has not been studied in depth in the past, possibly as until recently there has been no available technique to measure spontaneous thrombolytic activity in native blood. The Global Thrombosis Test (GTT) is a new point of care tests that allows us to measure time to thrombus formation (Occlusion time: OT) using native blood, avoiding the use of agonists and making the test results more physiological. The GTT also measures the time to lyse this formed thrombi without use of any lytic agents (Lysis time: LT), allowing us to measure the patient’s endogenous thrombolytic potential. Aim: Our aim in this study was to detect patients who are at risk of future thrombotic events despite dual antiplatelet therapy, either due to prothrombotic tendency or due to impaired endogenous thrombolysis, and to determine if these two parameters were correlated. Methods: GTT was used to assess the thrombotic and thrombolytic activity in healthy volunteers, and in different patient populations. 100 healthy volunteers were tested using the GTT, and a normal range was established. 300 patients admitted to hospital with a diagnosis of acute coronary syndrome (ACS) were included in the study, and tested using the GTT after they had been stabilized on dual antiplatelet therapy (Aspirin and Clopidogrel). All these patients were followed up for a year, to determine if their baseline GTT results were a predictor of recurrent cardiac events. The primary endpoint of the study was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, nonfatal myocardial infarction, or stroke at 12 months. Results: All results were analysed using statistical package SPSS version 16.0 (SPSS Inc., Chicago, Illinois). The 100 healthy volunteers were all non-smokers, and were not taking any medications. There were 55 males and 45 females, and mean age was 38±11 years (range 22-76, IQR 11). OT was normally distributed with mean OT 377.80s, and using mean ± 2SD, we derived a normal range of 185-569s (200-550s). LT demonstrated a skewed distribution with values ranging between 457 – 2934s. Using log transformation, a normal range of 592 – 1923 (600- 2000s) was established for LT. OT and LT were both prolonged in ACS patients compared to normal volunteers (p< 0.001). No association was observed between OT and risk of major adverse cardiovascular events. LT was noted to be a significant and independent predictor of MACE in a multivariate model adjusted for cardiovascular risk factors. LT ≥ 3000 s was the optimal cutoff value for predicting 6 month MACE [hazard ratio (HR): 2.48, 95% CI: 1.2-4.8, P= 0.008] and cardiovascular death [HR: 4.04, 95% CI : 1.3-12.0, P= 0.012 ] and 12 month MACE [HR:1.9, 95% CI: 1.04- 3.5,P= 0.03] and cardiovascular death [HR: 3.9,95% CI: 1.34-11.9, P= 0.013 ]. LT ≥ 3000 s was observed in 23% of ACS patients. Conclusions: Our study suggests that endogenous thrombolytic activity based on lysis of platelet rich thrombi can be assessed by the point of care GTT assay, which can help in identification of ACS patients at high risk of future cardiac events. Prolongation of OT may be explained by the antiplatelet effects of Aspirin and Clopidogrel, as both these drugs prolong time to thrombus formation and hence increase OT. Further large studies are required to study factors which can reduce thrombogenic potential, and improve endogenous thrombolytic activity, which can be monitored using the GTT to improve cardiovascular outcomes.

En inhibant la formation de caillots dans le sang, les médicaments antiplaquettaires diminuent de façon importante le risque d’événements ischémiques aigus. Cependant, une sous-population de patients souffrant de maladie coronarienne présente une inhibition inadéquate de la fonction plaquettaire malgré la prise quotidienne d’acide acétylsalicylique (AAS). Le premier volet de cette thèse démontre qu’une régénération plaquettaire accélérée pourrait expliquer en partie la variabilité dans la persistance de l’effet antiplaquettaire de l’AAS chez certains sujets souffrant de maladie coronarienne. Ces données suggèrent qu’une augmentation de la fréquence d’administration d’AAS d’une à deux fois par jour pourrait être bénéfique chez ces sujets. Des méta-analyses ont suggéré qu’une réponse plaquettaire inadéquate à l’AAS pourrait augmenter le risque d’événements ischémiques récurrents. La nature rétrospective de ces analyses ne permet pas d’établir la causalité. Dans le deuxième volet de cette thèse, les résultats d’une étude prospective visant à comparer la pertinence clinique de 6 tests de fonction plaquettaire fréquemment utilisés pour évaluer la réponse plaquettaire à l’AAS est présentée. Les résultats démontrent qu’aucun des tests de fonction plaquettaire couramment employés ne prédit la survenue d’événements ischémiques aigus chez des patients souffrant de maladie coronarienne stable. Toutefois, la cessation de la prise d’AAS est un prédicteur important d’événements thrombotiques. La cessation de médicaments antiplaquettaires a souvent été associée à la survenue d’événements thrombotiques dans les jours suivant l’interruption. À savoir si la survenue de ces événements est attribuable uniquement au retrait d’un médicament protecteur ou plutôt à une sensibilisation plaquettaire, constitue un débat d’actualité. Dans le troisième volet de cette thèse, des données sont présentées démontrant que la cessation de clopidogrel après la période recommandée par les lignes directrices actuelles provoque une sensibilisation des plaquettes nouvellement formées aux stimuli plaquettaires physiologiques. Ces résultats encouragent la recherche sur différentes modalités pour atténuer le risque thrombotique accru chez ces patients souffrant de maladie coronarienne. En conclusion, cet ouvrage présente des études visant à identifier les sous-populations de patients qui sont plus à risque de complications cardiovasculaires récurrentes. Dans ce contexte, la personnalisation de traitement est une avenue thérapeutique prometteuse, où chaque patient pourra recevoir un traitement ciblé en fonction de ses besoins et de ses contre-indications. Ce changement de paradigme d’une thérapie empirique issue d’études de grande envergure sur des données populationnelles à une thérapie ajustée aux besoins individuels représente un vaste champ de recherche, où la majorité des découvertes sont à faire. / By inhibiting the formation of blood clots, antiplatelet drugs significantly reduce the risk of acute ischemic events. However, a subpopulation of patients suffering from coronary artery disease presents with an inadequate inhibition of platelet function despite taking acetylsalicylic acid (ASA) daily. The first part of this thesis demonstrates that accelerated platelet turnover could partly explain the variability in the persistence of the antiplatelet effect of ASA in some coronary artery disease patients. These results suggest that increasing the frequency of administration of ASA from once to twice daily may be beneficial in selected patients. Meta-analyses have suggested that an inadequate platelet response to ASA may increase the risk of recurrent ischemic events. The retrospective nature of these analyses forbids the inference of causality. In the second part of this thesis, the results of a prospective study comparing the clinical relevance of 6 platelet function tests commonly used to assess platelet response to ASA are presented. The results show that none of the commonly used platelet function tests predict the occurrence of acute ischemic events in stable coronary artery disease patients. However, discontinuation of ASA is an important predictor of thrombotic events. Discontinuation of antiplatelet drugs has often been associated with thrombotic events in the days following cessation. If the occurrence of these events is due solely to the withdrawal of a protective drug or rather platelet sensitization is a topic of some debate. In the third part of this thesis, data are presented demonstrating that clopidogrel discontinuation, after the period recommended by current guidelines, leads to sensitization of newly formed platelets to physiological platelet stimuli. These results encourage research on different ways to mitigate the increased risk of thrombosis in coronary artery disease patients scheduled to discontinue clopidogrel therapy. In conclusion, this dissertation presents studies aiming to identify subpopulations of patients who are at increased risk of recurrent cardiovascular events. In this context, the personalization of treatment is a promising therapeutic avenue, where each patient can receive a targeted therapy according to his needs and contraindications. This shift in paradigm from empirical therapy based on population data retrieved from large clinical studies to therapy tailored to individual needs opens a vast field of research, where the majority of discoveries remain to be made.

Introdução: O antecedente de AVCI e/ou AIT está presente em 5% dos pacientes com coronariopatia aguda e em até 17% dos pacientes com coronariopatia crônica. Esta população apresenta elevado risco para eventos cardiovasculares, assim como para desfechos hemorrágicos maiores (principalmente quando em uso de tratamento antitrombótico). A agregabilidade plaquetária apresenta papel fundamental no balanço isquêmico/hemorrágico; entretanto, esse mecanismo é pouco estudado em pacientes com evento cérebro vascular isquêmico prévio. O principal objetivo desse estudo é avaliar se pacientes com DAC e AVCI/ AIT prévio exibem alterações na agregabilidade plaquetária que justifiquem o risco aumentado para sangramento nesses indivíduos. Casuística e Métodos: Entre janeiro de 2013 e abril de 2015, 140 pacientes foram selecionados nos bancos de dados da unidade coronária e do serviço de cirurgia cardíaca do InCor- HCFMUSP. Critérios de inclusão: coronariopatia aguda prévia (há mais de 12 meses), antecedente de AVCI/AIT (anterior ao episódio de coronariopatia aguda), uso crônico de AAS e assinatura do Termo de Consentimento Livre e Esclarecido. Critérios de exclusão: AVCH prévio, uso de antiagregação plaquetária dupla ou anti-inflamatórios não esteroidais, trombofilia ou coagulopatia conhecida, trombocitopenia ou trombocitose, angioplastia ou cirurgia cardíaca nos últimos 6 meses, disfunção renal grave ou qualquer doença terminal. Desenho do estudo: Estudo de caso e controle (1:1), com os grupos caso (AVCI/AIT prévio) e controle (sem AVCI/AIT prévio) pareados por sexo, idade, tipo de coronariopatia aguda e tempo entre a coronariopatia aguda e a inclusão no estudo. A agregabilidade plaquetária foi mensurada pelo VerifyNow Aspirin®, VerifyNow P2Y12®, Agregometria óptica com agonista ADP, Agregometria óptica com agonista adrenalina e tromboelastrografia (Reorox®). Resultados: Os grupos controle (n=70) e caso (n=70), estavam bem pareados em relação à maioria das variáveis analisadas. A idade média da população global foi de 66 anos, 73% apresentavam IAM prévio, e o tempo médio entre o episódio de coronariopatia aguda e a inclusão no presente estudo foi de 5,31 anos. No momento da avaliação os pacientes do grupo caso apresentavam valores mais elevados de pressão arterial sistólica (135,84 ± 16,09 vs 123,68 ± 16,11mmHg, p < 0,001), embora esse grupo utilizasse maior número de antihipertensivos (2,37 ± 1,09 vs 3,0 ± 1,23, p=0,006). Em relação a variáveis metabólicas, o perfil lipídico não presentou diferença significativa entre os grupos, entretanto o grupo caso apresentou maiores valores de creatinina (1,24 ± 0,35 vs 1,11 ± 0,27 mg/dL, p=0,037) e também de glicemia de jejum (116,16 ± 32,03 vs 134,88 ± 57,58 mg/dL, p=0,031). No que se refere à meta principal do estudo, a agregabilidade plaquetária foi similar nos dois grupos por todos os métodos utilizados: VerifyNow Aspirin® (525,00 ± 79,78 vs 530,35 ± 83,81 ARU nos grupos caso e controle, respectivamente, p=0,7), VerifyNow P2Y12® (262,14 ± 43,03 vs 251,74 ± 43,72 PRU, p=0,21), Agregometria óptica com agonista ADP (78,34 ± 9,02 vs 77,55 ± 9,70%, p=0,82), Agregometria óptica com agonista adrenalina (49,01± 23,93% vs 49,34 ± 21,7, p=0,77), e tromboelastografia (Firmeza máxima do coágulo: 2,136,00 ± 569,97 vs 2.001,27 ± 635,68 Pa, p=0,19). Conclusão: Em pacientes com doença arterial coronária crônica a agregabilidade plaquetária foi similar nos indivíduos com ou sem AVCI/AIT. Esses resultados apontam para que outros mecanismos sejam responsáveis pelo elevado risco hemorrágico dessa população / Background: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 5% of patients with acute coronary syndrome (ACS) and in 17% of patients with stable atherosclerotic disease (CAD). This population has a higher risk for major cardiovascular events and an increased incidence of major hemorrhagic outcomes when subjected to modern antithrombotic regimens, Platelet aggregability have key role in \"ischemic-hemorrhagic\" balance, however, these factors are little known in the population with prior cerebrovascular event. The aim of this study is to evaluate whether patients with coronary artery disease and previous IS/ TIA exhibit alterations in platelet aggregation, justifying the increased bleeding risk of these individuals. Methods: Between January 2013 and April 2015, 140 participants were selected in the coronary care unit and cardiac surgery service databank. Inclusion criteria: prior ACS (over 12 months), history of IS/ TIA previous to ACS, chronic use of aspirin since ACS and agreement to the consent form. Exclusion criteria: prior hemorrhagic stroke, current dual antiplatelet therapy or anti-inflammatory non-steroidal, any thrombophilia or coagulopathy, thrombocytopenia, thrombocytosis, PCI or CABG in the last 6 months, severe renal impairment and any terminal illness. Study design: Case-control study (1:1), case group (previous IS/TIA) and control group (without previous IS/TIA) matched for sex, age, type of previous ACS, time between ACS and inclusion in the study. Platelet aggregation was assessed by VerifyNow Aspirin®, VerifyNow P2Y12®, Light transmission aggregometry aggonist with agonists adrenaline, Light transmission aggregometry aggonist with ADP, and thromboelastography (Reorox®). Results: The control group (n=70) and case group (n=70), were well matched. The mean age was 63 years, about 73% presented previous AMI and the index ACS occurred 5,31 years before study inclusion. At the evaluation day patients in the case group presented higher SBP levels (135.84 ± 16.09 vs 123.68 ± 16.11 mmHg, p < 0,001), although this group were using more antihypertensive medications (2.37 ± 1.09 vs 3.0 ± 1.23, p=0,006). In relation to metabolic profile, lipid profile did not presented diferences, however, case group presented higher values for creatinine (1.24 ± 0.35 vs 1.11 ± 0.27 mg/dL, p=0.037) and also presented higher values for fasting glucose.(116.16 ± 32.03 vs 134.88 ± 57.58 mg/dL, p=0.031) Platelet aggregation was statistically similar in both groups: VerifyNow Aspirin® (525.00 ± 79.78 vs 530.35 ± 83.81 ARU, p=0.7), VerifyNow P2Y12® (262.14 ± 43.03 vs 251.74 ± 43.72 PRU, p=0.21), Light transmission aggregometry aggonist with agonists ADP (78,34 ± 9,02 vs 77,55 ± 9,70%, p=0,82), Light transmission aggregometry aggonist with adrenaline (49,01 ± 23,93% vs 49,34 ± 21,7, p=0,77) and thromboelastography (maximum clot firmness: 2.136,00 ± 569,97 vs 2.001,27 ± 635,68 Pa, p=0,19). Conclusion: Platlet aggregability is similar in CAD patients with or without previous IS/TIA and this results point at other reasons to justify the high risk for bleeding in this patients

En inhibant la formation de caillots dans le sang, les médicaments antiplaquettaires diminuent de façon importante le risque d’événements ischémiques aigus. Cependant, une sous-population de patients souffrant de maladie coronarienne présente une inhibition inadéquate de la fonction plaquettaire malgré la prise quotidienne d’acide acétylsalicylique (AAS). Le premier volet de cette thèse démontre qu’une régénération plaquettaire accélérée pourrait expliquer en partie la variabilité dans la persistance de l’effet antiplaquettaire de l’AAS chez certains sujets souffrant de maladie coronarienne. Ces données suggèrent qu’une augmentation de la fréquence d’administration d’AAS d’une à deux fois par jour pourrait être bénéfique chez ces sujets. Des méta-analyses ont suggéré qu’une réponse plaquettaire inadéquate à l’AAS pourrait augmenter le risque d’événements ischémiques récurrents. La nature rétrospective de ces analyses ne permet pas d’établir la causalité. Dans le deuxième volet de cette thèse, les résultats d’une étude prospective visant à comparer la pertinence clinique de 6 tests de fonction plaquettaire fréquemment utilisés pour évaluer la réponse plaquettaire à l’AAS est présentée. Les résultats démontrent qu’aucun des tests de fonction plaquettaire couramment employés ne prédit la survenue d’événements ischémiques aigus chez des patients souffrant de maladie coronarienne stable. Toutefois, la cessation de la prise d’AAS est un prédicteur important d’événements thrombotiques. La cessation de médicaments antiplaquettaires a souvent été associée à la survenue d’événements thrombotiques dans les jours suivant l’interruption. À savoir si la survenue de ces événements est attribuable uniquement au retrait d’un médicament protecteur ou plutôt à une sensibilisation plaquettaire, constitue un débat d’actualité. Dans le troisième volet de cette thèse, des données sont présentées démontrant que la cessation de clopidogrel après la période recommandée par les lignes directrices actuelles provoque une sensibilisation des plaquettes nouvellement formées aux stimuli plaquettaires physiologiques. Ces résultats encouragent la recherche sur différentes modalités pour atténuer le risque thrombotique accru chez ces patients souffrant de maladie coronarienne. En conclusion, cet ouvrage présente des études visant à identifier les sous-populations de patients qui sont plus à risque de complications cardiovasculaires récurrentes. Dans ce contexte, la personnalisation de traitement est une avenue thérapeutique prometteuse, où chaque patient pourra recevoir un traitement ciblé en fonction de ses besoins et de ses contre-indications. Ce changement de paradigme d’une thérapie empirique issue d’études de grande envergure sur des données populationnelles à une thérapie ajustée aux besoins individuels représente un vaste champ de recherche, où la majorité des découvertes sont à faire. / By inhibiting the formation of blood clots, antiplatelet drugs significantly reduce the risk of acute ischemic events. However, a subpopulation of patients suffering from coronary artery disease presents with an inadequate inhibition of platelet function despite taking acetylsalicylic acid (ASA) daily. The first part of this thesis demonstrates that accelerated platelet turnover could partly explain the variability in the persistence of the antiplatelet effect of ASA in some coronary artery disease patients. These results suggest that increasing the frequency of administration of ASA from once to twice daily may be beneficial in selected patients. Meta-analyses have suggested that an inadequate platelet response to ASA may increase the risk of recurrent ischemic events. The retrospective nature of these analyses forbids the inference of causality. In the second part of this thesis, the results of a prospective study comparing the clinical relevance of 6 platelet function tests commonly used to assess platelet response to ASA are presented. The results show that none of the commonly used platelet function tests predict the occurrence of acute ischemic events in stable coronary artery disease patients. However, discontinuation of ASA is an important predictor of thrombotic events. Discontinuation of antiplatelet drugs has often been associated with thrombotic events in the days following cessation. If the occurrence of these events is due solely to the withdrawal of a protective drug or rather platelet sensitization is a topic of some debate. In the third part of this thesis, data are presented demonstrating that clopidogrel discontinuation, after the period recommended by current guidelines, leads to sensitization of newly formed platelets to physiological platelet stimuli. These results encourage research on different ways to mitigate the increased risk of thrombosis in coronary artery disease patients scheduled to discontinue clopidogrel therapy. In conclusion, this dissertation presents studies aiming to identify subpopulations of patients who are at increased risk of recurrent cardiovascular events. In this context, the personalization of treatment is a promising therapeutic avenue, where each patient can receive a targeted therapy according to his needs and contraindications. This shift in paradigm from empirical therapy based on population data retrieved from large clinical studies to therapy tailored to individual needs opens a vast field of research, where the majority of discoveries remain to be made.

Introdução: O antecedente de AVCI e/ou AIT está presente em 5% dos pacientes com coronariopatia aguda e em até 17% dos pacientes com coronariopatia crônica. Esta população apresenta elevado risco para eventos cardiovasculares, assim como para desfechos hemorrágicos maiores (principalmente quando em uso de tratamento antitrombótico). A agregabilidade plaquetária apresenta papel fundamental no balanço isquêmico/hemorrágico; entretanto, esse mecanismo é pouco estudado em pacientes com evento cérebro vascular isquêmico prévio. O principal objetivo desse estudo é avaliar se pacientes com DAC e AVCI/ AIT prévio exibem alterações na agregabilidade plaquetária que justifiquem o risco aumentado para sangramento nesses indivíduos. Casuística e Métodos: Entre janeiro de 2013 e abril de 2015, 140 pacientes foram selecionados nos bancos de dados da unidade coronária e do serviço de cirurgia cardíaca do InCor- HCFMUSP. Critérios de inclusão: coronariopatia aguda prévia (há mais de 12 meses), antecedente de AVCI/AIT (anterior ao episódio de coronariopatia aguda), uso crônico de AAS e assinatura do Termo de Consentimento Livre e Esclarecido. Critérios de exclusão: AVCH prévio, uso de antiagregação plaquetária dupla ou anti-inflamatórios não esteroidais, trombofilia ou coagulopatia conhecida, trombocitopenia ou trombocitose, angioplastia ou cirurgia cardíaca nos últimos 6 meses, disfunção renal grave ou qualquer doença terminal. Desenho do estudo: Estudo de caso e controle (1:1), com os grupos caso (AVCI/AIT prévio) e controle (sem AVCI/AIT prévio) pareados por sexo, idade, tipo de coronariopatia aguda e tempo entre a coronariopatia aguda e a inclusão no estudo. A agregabilidade plaquetária foi mensurada pelo VerifyNow Aspirin®, VerifyNow P2Y12®, Agregometria óptica com agonista ADP, Agregometria óptica com agonista adrenalina e tromboelastrografia (Reorox®). Resultados: Os grupos controle (n=70) e caso (n=70), estavam bem pareados em relação à maioria das variáveis analisadas. A idade média da população global foi de 66 anos, 73% apresentavam IAM prévio, e o tempo médio entre o episódio de coronariopatia aguda e a inclusão no presente estudo foi de 5,31 anos. No momento da avaliação os pacientes do grupo caso apresentavam valores mais elevados de pressão arterial sistólica (135,84 ± 16,09 vs 123,68 ± 16,11mmHg, p < 0,001), embora esse grupo utilizasse maior número de antihipertensivos (2,37 ± 1,09 vs 3,0 ± 1,23, p=0,006). Em relação a variáveis metabólicas, o perfil lipídico não presentou diferença significativa entre os grupos, entretanto o grupo caso apresentou maiores valores de creatinina (1,24 ± 0,35 vs 1,11 ± 0,27 mg/dL, p=0,037) e também de glicemia de jejum (116,16 ± 32,03 vs 134,88 ± 57,58 mg/dL, p=0,031). No que se refere à meta principal do estudo, a agregabilidade plaquetária foi similar nos dois grupos por todos os métodos utilizados: VerifyNow Aspirin® (525,00 ± 79,78 vs 530,35 ± 83,81 ARU nos grupos caso e controle, respectivamente, p=0,7), VerifyNow P2Y12® (262,14 ± 43,03 vs 251,74 ± 43,72 PRU, p=0,21), Agregometria óptica com agonista ADP (78,34 ± 9,02 vs 77,55 ± 9,70%, p=0,82), Agregometria óptica com agonista adrenalina (49,01± 23,93% vs 49,34 ± 21,7, p=0,77), e tromboelastografia (Firmeza máxima do coágulo: 2,136,00 ± 569,97 vs 2.001,27 ± 635,68 Pa, p=0,19). Conclusão: Em pacientes com doença arterial coronária crônica a agregabilidade plaquetária foi similar nos indivíduos com ou sem AVCI/AIT. Esses resultados apontam para que outros mecanismos sejam responsáveis pelo elevado risco hemorrágico dessa população / Background: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 5% of patients with acute coronary syndrome (ACS) and in 17% of patients with stable atherosclerotic disease (CAD). This population has a higher risk for major cardiovascular events and an increased incidence of major hemorrhagic outcomes when subjected to modern antithrombotic regimens, Platelet aggregability have key role in \"ischemic-hemorrhagic\" balance, however, these factors are little known in the population with prior cerebrovascular event. The aim of this study is to evaluate whether patients with coronary artery disease and previous IS/ TIA exhibit alterations in platelet aggregation, justifying the increased bleeding risk of these individuals. Methods: Between January 2013 and April 2015, 140 participants were selected in the coronary care unit and cardiac surgery service databank. Inclusion criteria: prior ACS (over 12 months), history of IS/ TIA previous to ACS, chronic use of aspirin since ACS and agreement to the consent form. Exclusion criteria: prior hemorrhagic stroke, current dual antiplatelet therapy or anti-inflammatory non-steroidal, any thrombophilia or coagulopathy, thrombocytopenia, thrombocytosis, PCI or CABG in the last 6 months, severe renal impairment and any terminal illness. Study design: Case-control study (1:1), case group (previous IS/TIA) and control group (without previous IS/TIA) matched for sex, age, type of previous ACS, time between ACS and inclusion in the study. Platelet aggregation was assessed by VerifyNow Aspirin®, VerifyNow P2Y12®, Light transmission aggregometry aggonist with agonists adrenaline, Light transmission aggregometry aggonist with ADP, and thromboelastography (Reorox®). Results: The control group (n=70) and case group (n=70), were well matched. The mean age was 63 years, about 73% presented previous AMI and the index ACS occurred 5,31 years before study inclusion. At the evaluation day patients in the case group presented higher SBP levels (135.84 ± 16.09 vs 123.68 ± 16.11 mmHg, p < 0,001), although this group were using more antihypertensive medications (2.37 ± 1.09 vs 3.0 ± 1.23, p=0,006). In relation to metabolic profile, lipid profile did not presented diferences, however, case group presented higher values for creatinine (1.24 ± 0.35 vs 1.11 ± 0.27 mg/dL, p=0.037) and also presented higher values for fasting glucose.(116.16 ± 32.03 vs 134.88 ± 57.58 mg/dL, p=0.031) Platelet aggregation was statistically similar in both groups: VerifyNow Aspirin® (525.00 ± 79.78 vs 530.35 ± 83.81 ARU, p=0.7), VerifyNow P2Y12® (262.14 ± 43.03 vs 251.74 ± 43.72 PRU, p=0.21), Light transmission aggregometry aggonist with agonists ADP (78,34 ± 9,02 vs 77,55 ± 9,70%, p=0,82), Light transmission aggregometry aggonist with adrenaline (49,01 ± 23,93% vs 49,34 ± 21,7, p=0,77) and thromboelastography (maximum clot firmness: 2.136,00 ± 569,97 vs 2.001,27 ± 635,68 Pa, p=0,19). Conclusion: Platlet aggregability is similar in CAD patients with or without previous IS/TIA and this results point at other reasons to justify the high risk for bleeding in this patients