A aterotrombose e suas complicações correspondem, hoje, à principal causa de mortalidade no mundo todo, e sua incidência encontra-se em franca expansão. As plaquetas desempenham um papel essencial na patogênese dos eventos aterotrombóticos, justificando a utilização dos antiagregantes plaquetários na prevenção dos mesmos. Desse modo, é essencial que se conheça o perfil de eficácia e segurança desses fármacos em prevenção primária e secundária de eventos aterotrombóticos. Dentro desse contexto, a presente revisão foi realizada com o objetivo de descrever e sintetizar os resultados dos principais ensaios, envolvendo a utilização de antiagregantes nos dois níveis de prevenção, e avaliando a eficácia e os principais eventos adversos relacionados à terapia.
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG - Brasil
A aterotrombose e suas complicações correspondem, hoje, à principal causa de mortalidade no mundo todo, e sua incidência encontra-se em franca expansão. As plaquetas desempenham um papel essencial na patogênese dos eventos aterotrombóticos, justificando a utilização dos antiagregantes plaquetários na prevenção dos mesmos. Desse modo, é essencial que se conheça o perfil de eficácia e segurança desses fármacos em prevenção primária e secundária de eventos aterotrombóticos. Dentro desse contexto, a presente revisão foi realizada com o objetivo de descrever e sintetizar os resultados dos principais ensaios, envolvendo a utilização de antiagregantes nos dois níveis de prevenção, e avaliando a eficácia e os principais eventos adversos relacionados à terapia.
A aterotrombose associa-se a uma série de complicações, sendo as mais importantes a Doença Arterial Coronariana (DAC), cujas principais manifestações são a angina instável e o Infarto Agudo do Miocárdio (IM), com ou sem elevação do segmento ST; o Acidente Vascular Encefálico Isquêmico (AVEi) e o ataque isquêmico transitório, além da Doença ARterial Obstrutiva Periférica (DAOP)1. Tais complicações correspondem, hoje, à principal causa de mortalidade no mundo todo, estimando-se que tenham sido responsáveis por 17,3 milhões de óbitos em 2008, sendo 80% dessas mortes em países de baixa e média renda. Segundo projeções da Organização Mundial da Saúde, em 2030, cerca de 23,6 milhões de pessoas morrerão anualmente, somente devido a complicações cardiovasculares2. Devido ao papel chave desempenhado pelas plaquetas na patogênese de eventos aterotrombóticos, a utilização de antiagregantes plaquetários é essencial na prevenção primária e secundária de tais eventos. Os fatores de risco associados ao desenvolvimento desses eventos estão intimamente associados à exacerbação da ativação plaquetária que, por sua vez, favorece a formação de agregados plaquetários e geração de trombina, resultando em trombos ricos em plaquetas (trombos brancos). Dessa forma, o uso de antiagregantes plaquetários tem sido benéfico na prevenção primária e secundária de eventos mediados por trombos.
As características dos principais antiagregantes plaquetários utilizados na prática clínica e em fase de estudos estão descritos na
O Ácido Acetilsalicílico (AAS) é o antiplaquetário mais comumente utilizado na prevenção primária de eventos cardiovasculares decorrentes da aterotrombose, e seu uso em indivíduos com moderado risco de doença cardíaca coronariana e como prevenção primária em indivíduos idosos é recomendado por diversas diretrizes. No entanto, a eficácia e a segurança da terapia com AAS, para prevenção primária, ainda geram controvérsias, pois os dados da literatura não demonstram eficácia tão pronunciada quanto na prevenção secundária11.
Seis ensaios clínicos randomizados avaliaram os benefícios e os riscos da utilização de AAS em doses baixas na prevenção de DCV. As descrições e os resultados desses ensaios estão resumidos na
Meta-análise de seis ensaios clínicos realizada pela
Segundo a meta-análise da
Em uma meta-análise realizada por Berger e cols. 13 envolvendo os seis ensaios clínicos, há indícios de que homens e mulheres respondam de maneira diferente à terapia com AAS. Em indivíduos do gênero feminino, foi observada uma redução de 12% (p = 0,03) na ocorrência de eventos cardiovasculares e de 17% na ocorrência de AVE (p = 0,02), devido principalmente à redução da ocorrência de AVE isquêmico. Não houve efeito pronunciado na redução de IM ou na redução da mortalidade por DCV. Em indivíduos do gênero masculino, observou-se redução na incidência de 14% nos eventos cardiovasculares (p = 0,01) e de 32% na incidência de IM (p = 0,001), não sendo observadas diferenças significativas quanto à ocorrência de AVE ou mortalidade por DCV.
A
O estudo
No ensaio
Como existem diferentes processos que levam à agregação plaquetária, imagina-se que a terapia com associação de antiplaquetários seja benéfica na prevenção de eventos cardiovasculares. Com o objetivo de se testar essa hipótese, diversos ensaios clínicos foram elaborados testando a eficácia de outros antiagregantes plaquetários junto ao AAS.
No estudo
Uma meta-análise realizada por Helton e cols.18 investigou a eficácia e a segurança da terapia combinada de AAS e clopidogrel utilizando os resultados de cinco ensaios clínicos randomizados, envolvendo um total de 79.624 pacientes. Os estudos utilizados foram: CURE,
Já a meta-análise realizada por Berger e cols.13, utilizando os mesmos ensaios, clínicos comparou a eficácia e a segurança da terapia combinada em homens e mulheres. Segundo essa meta-análise, a terapia conjunta proporcionou uma redução relativa no risco de eventos cardiovasculares de 14% (OR: 0,86 IC95%: 0,80-0,93), comparando-se com a monoterapia com o AAS. Aparentemente, embora o risco relativo total nas mulheres seja menor, não atinge significância estatística (11,0% contra 11,8%; OR: 0,93; IC95%: 0,86-1,1). Observa-se, nas mulheres, que o efeito é significativo em relação à prevenção do IM (OR: 0,81; IC95%: 0,70-0,93), sendo os efeitos em AVE (OR: 0,91; IC95%: 0,69-1,21) e mortalidade (OR: 0,99; IC95%: 0,90-1,08) não estatisticamente significativos. Em homens, verifica-se que a terapia combinada proporciona um menor risco de eventos cardiovasculares (7,8% contra 9,0%; OR: 0,84; IC95%: 0,78-0,91), sendo essa redução significativa para IM (OR: 0,83; IC95%: 0,76-0,92), AVE (OR: 0,83; IC95%: 0,71-0,96) e mortalidade total (OR: 0,91; IC95%: 0,84-0,97). A incidência de sangramentos maiores foi maior com a terapia combinada, tanto em mulheres (OR: 1,43 IC95%: 1,15-1,79) quanto em homens (OR: 1,22; IC95%: 0,1,05-1,42).
O ensaio TRITON-TIMI 38, um ensaio clínico randomizado, duplo-cego, de fase III, revelou redução significativa no risco dos desfechos primários do estudo (IM não fatal, AVE não fatal e morte cardiovascular) nos pacientes tratados com prasugrel (10 mg ao dia) em relação aos tratados com clopidogrel (75 mg ao dia) (9,9% contra 12,1%, p < 0,001). O prasugrel também foi associado a uma redução em tromboses ligadas à prótese expansível instalada no interior de vasos sanguíneos (
A utilização do dipiridamol em prevenção secundária de eventos cardiovasculares ainda é controversa, visto que diversos ensaios clínicos não demonstram eficácia adequada do dipiridamol ou da associação entre ele e o AAS na prevenção de eventos cardiovasculares. Após o desenvolvimento de formulações de liberação controlada do dipiridamol, novos estudos, como o ESPS-2 e o
Os inibidores da GPIIb/IIIa têm eficácia estabelecida em redução de eventos isquêmicos, tanto no manejo das síndromes coronarianas agudas quanto como terapia adjunta durante a angioplastia coronariana. O ensaio
Os estudos a respeito da eficácia da utilização de inibidores da GPIIb/IIIa ainda não são conclusivos, visto que, embora a maioria dos ensaios demonstre um efeito benéfico significativo da utilização desses fármacos na prevenção secundária, alguns ensaios, como o
Vários fármacos antiplaquetários encontram-se atualmente em fases de teste, alguns com ensaios clínicos concluídos e outros com ensaios ainda em andamento.
A eficácia do ticagrelor foi avaliada pelo ensaio
Estudos de fase I demonstram que o elinogrel inibe a agregação plaquetária dentro de 20 minutos após a administração, em uma relação dose-dependente, e que apresenta efeito sinérgico com o AAS. Segundo o ensaio
Em um ensaio clínico randomizado envolvendo pacientes com infarto miocárdico, em que a terapia combinada de cangrelor e alteplase (um fármaco trombolítico) foi comparada à terapia com cada fármaco isoladamente, verificou-se que a terapia combinada foi melhor que com qualquer um dos fármacos isoladamente. Já os estudos CHAMPION PLATFORM e CHAMPION PCI, que buscaram verificar a eficácia da terapia combinada de cangrelor e clopidogrel comparando-a à terapia com apenas clopidogrel, foram cancelados por falta de eficácia da terapia combinada24.
O atopaxar e o vorapaxar, inibidores do receptor PAR-1, encontram-se em fase de estudo clínico (o atopaxar em fase II e o vorapaxar em fase III), cujos resultados devem ser publicados em breve. No estudo
As informações referentes à participação das plaquetas nas doenças aterotrombóticas permitem inferir que a terapia antiplaquetária desempenha um papel crucial na prevenção de eventos cardiovasculares. A utilização de antiplaquetários, principalmente na prevenção secundária, apoia-se em vários estudos que avaliaram a eficácia e a segurança dos mesmos. Na prevenção primária, deve-se avaliar criteriosamente e de maneira individualizada o potencial benefício proveniente da utilização preventiva de AAS.
O avanço na compreensão dos mecanismos que levam as plaquetas a participarem do processo aterotrombótico levou à busca pelo desenvolvimento de novos fármacos, com capacidade de inibir a atividade plaquetária consistentemente e com o máximo de segurança. Diversos estudos em andamento levam a crer que, nos próximos anos, serão otimizadas as estratégias atualmente disponíveis para prevenção das doenças cardiovasculares e que novas opções farmacológicas estarão disponíveis para uso clínico.
CNPq e FAPEMIG. LMSD e MGC agradecem ao CNPq pela bolsa de produtividade em pesquisa.
Concepção e desenho da pesquisa, Obtenção de dados, Análise e interpretação dos dados, Análise estatística, Redação do manuscrito e Revisão crítica do manuscrito quanto ao conteúdo intelectual: Silva MVF, Dusse LMS, Vieira LM, Carvalho MG.
Declaro não haver conflito de interesses pertinentes.
O presente estudo não teve fontes de financiamento externas.
Não há vinculação deste estudo a programas de pós-graduação.
Marcos Vinícius Ferreira Silva Rua Ciro Vaz de Melo, 514, casa 4 - Dona Clara CEP 31255-840, Belo Horizonte, MG - Brasil E-mail:
Artigo recebido em 13/7/12, revisado em 18/01/13, aceito em 8/2/13.
Atherothrombosis and its complications are currently the leading cause of worldwide mortality and its incidence is increasing . Platelets play an essential role in the pathogenesis of atherothrombotic events, justifying the use of antiplatelet agents in their prevention. Thus, it is essential to know the efficacy and safety profile of these drugs in primary and secondary prevention of atherothrombotic events. In this context, this review was performed with the aim of describing and summarizing the outcomes of the main trials involving the use of antiplatelet agents in the two levels of prevention, and evaluating the effectiveness and major adverse events related to therapy.
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG - Brazil
Mailing Address
Atherothrombosis and its complications are currently the leading cause of worldwide mortality and its incidence is increasing . Platelets play an essential role in the pathogenesis of atherothrombotic events, justifying the use of antiplatelet agents in their prevention. Thus, it is essential to know the efficacy and safety profile of these drugs in primary and secondary prevention of atherothrombotic events. In this context, this review was performed with the aim of describing and summarizing the outcomes of the main trials involving the use of antiplatelet agents in the two levels of prevention, and evaluating the effectiveness and major adverse events related to therapy.
Atherothrombosis and its complications are currently the leading cause of worldwide mortality and its incidence is increasing. Platelets play an essential role in the pathogenesis of atherothrombotic events, justifying the use of antiplatelet agents in their prevention. Thus, it is essential to know the efficacy and safety profile of these drugs in primary and secondary prevention of atherothrombotic events. In this context, this review was performed with the aim of describing and summarizing the outcomes of the main trials involving the use of antiplatelet agents in the two levels of prevention, and evaluating the effectiveness and major adverse events related to therapy.
Atherothrombosis is associated with a number of complications and the most important are Coronary Artery Disease (CAD), of which main manifestations are unstable angina and acute myocardial infarction (MI), with or without ST-segment elevation; ischemic cerebrovascular disease (CVA) and transient ischemic attack, in addition to Peripheral Obstructive Arterial Disease (POAD)1. Such complications currently correspond to the leading cause of mortality worldwide and it has been estimated that they were responsible for 17.3 million deaths in 2008, with 80% of these deaths in low and middle-income countries.
According to projections of the World Health Organization (WHO), in 2030, approximately 23.6 million people will die every year only due to cardiovascular complications2. Due to the key role played by platelets in the pathogenesis of atherothrombotic events, the use of platelet antiaggregants is essential in primary and secondary prevention of such events. Risk factors associated with the development of these events are closely associated with the exacerbation of platelet activation which, in turn, favors the formation of platelet aggregates and thrombin generation, resulting in platelet-rich thrombi (white thrombi). Thus, the use of platelet antiaggregants has shown to be beneficial in primary and secondary prevention of thrombus-mediated events.
The characteristics of the main platelet antiaggregants used in clinical practice and undergoing study are described in
Acetylsalicylic Acid (ASA) or aspirin is the most commonly used platelet antiaggregant in the primary prevention of cardiovascular events caused by atherothrombosis and its use in patients with moderate risk of coronary heart disease and as primary prevention in elderly individuals has been recommended by several guidelines. However, the efficacy and safety of ASA therapy for primary prevention are still controversial, as the literature data have not demonstrated that such efficacy is as marked as in secondary prevention11.
Six randomized controlled trials have evaluated the benefits and risks of using low-dose ASA in CVD prevention. The description and results of these trials are summarized in
A meta-analysis of six clinical trials performed by the Antithrombotic Trialists' (ATT) Collaboration12 reported that the use of ASA in primary prevention resulted in a 12% reduction in the occurrence of severe cardiovascular events (0.51% in patients treated with ASA vs. 0.57% in the control group, per year, p = 0.0001), mainly due to a decrease in myocardial infarction (MI) incidence (0.18% vs. 0.23% per year, p <0.0001). The reduction in CVA incidence (0.20% vs. 0.21% per year, p = 0.4) was not significant, nor was the increase in hemorrhagic CVA incidence (0.04% vs. 0.03% per year; p = 0.05). CVD mortality as a whole did not change (0.19% vs. 0.19% per year, p = 0.7)12.
According to the ATT Collaboration12 meta-analysis, as a result of the studies, there is no solid evidence to justify the use of ASA in primary prevention, mainly due to the fact that risk of adverse effects (mostly gastrointestinal bleeding) offsets the benefit of ASA therapy. Thus, the choice of therapy should be individualized, and ASA use is indicated or not according to each patient's characteristics. Additional studies should be performed to assess which factors influence the success of ASA therapy and to define risk thresholds below which its use is indicated.
In a meta-analysis by Berger et al13 involving six clinical trials, there is evidence that men and women respond differently to ASA therapy. In female subjects, there was a 12% reduction (p = 0.03) in the occurrence of cardiovascular events and 17% in the occurrence of CVA (p = 0.02), mainly due to the reduction in the occurrence of ischemic CVA. There was no significant effect on the reduction of MI or in CVD mortality. In male subjects, there was a 14% reduction in the incidence of cardiovascular events (p = 0.01) and 32% in the incidence of MI (p = 0.001), and there were no significant differences regarding the occurrence of CVA or CVD mortality.
The Antithrombotic Trialists' Collaboration developed a meta-analysis involving 16 randomized controlled trials, which sought to evaluate the efficacy of aspirin in secondary prevention. The occurrence of cardiovascular events was significantly reduced (6.7% vs. 8.2% per year, p < 0.0001), with a 20% reduction in the risk of CVA (2.08%
The "Clopidogrel versus Aspirin in Patients at Risk of Ischemic Event" (CAPRIE) trial compared the efficacy of aspirin and clopidogrel in secondary prevention of atherothrombotic events. In patients treated with clopidogrel (75 mg daily), there was a relative reduction of 8.7% (p = 0.0043) in the occurrence of ischemic events (CVA, MI or CVD death) compared to patients treated with aspirin (325 mg daily), with a lower incidence of gastrointestinal bleeding in clopidogrel users15.
The "Ticlopidine Versus Aspirin After Myocardial Infarction (STAMI)" trial showed no evidence of differences in the efficacy of ticlopidine (325 mg/day) and ASA (160 mg /day), whereas the "Ticlopidine Aspirin Stroke Study (TASS)" trial showed that, in one year, the incidence of ischemic CVA in patients treated with ticlopidine (500 mg/day) was 17%,
As there are different processes that lead to platelet aggregation, it is supposed that therapy combined with platelet antiaggregants is beneficial in cardiovascular event prevention. In order to test this hypothesis, several clinical trials have been developed to test the efficacy of other platelet antiaggregants combined with ASA.
In the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial, patients with CVD or multiple risk factors were randomly assigned to therapies with ASA (75-162 mg daily) + clopidogrel (75 mg daily) or ASA (7-162 mg daily) + placebo. The events tested in this study were CVA, MI and death from cardiovascular disease. As a result, cardiovascular events occurred in 6.8% of individuals in the group receiving ASA + clopidogrel
The "Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE)" trial evaluated dual antiplatelet therapy in patients with acute coronary syndrome without ST-segment elevation, and its results showed that therapy with ASA (75-325 mg daily) + clopidogrel (75 mg daily) led to a lower incidence of myocardial infarction and CVD death than ASA alone (9.3% vs. 11.4%, p <0.001), with most of the beneficial effects related to the reduction in nonfatal myocardial infarction (5.2%
A meta-analysis performed by Helton et al18 assessed the efficacy and safety of combined therapy with aspirin and clopidogrel using the results of five randomized controlled trials, involving a total of 79 624 patients. The analyzed studies were: CURE, Clopidogrel for the Reduction of Events During Observation (CREDO), Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28), Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) and CHARISMA. All studies compared dual antiplatelet therapy with efficacy and safety of aspirin alone.
It was observed that, in patients undergoing adjuvant therapy, mortality was 6.3% against 6.7% in ASA users alone (OR: 0.94, 95% CI: 0.89 - 0.99, p = 0.026). The incidence of myocardial infarction and CVA were 2.7%
The meta-analysis by Berger et al13, using the same trials, compared the clinical efficacy and safety of combined therapy in men and women. According to this meta-analysis, the combined therapy resulted in a relative decrease of 14% in the risk of cardiovascular events (OR: 0.86 95%CI: 0.80-0.93), when compared with monotherapy with ASA. Apparently, although the relative risk in women is lower, it does not reach statistical significance (11.0%
It was observed that, in women, the effect was significant in relation to MI prevention (OR: 0.81, 95%CI: 0.70-0.93), whereas the effects on CVA (OR: 0.91, 95%CI: 0.69-1.21) and mortality (OR: 0.99, 95%CI: 0.90-1.08) were not statistically significant. In men, it was observed that combined therapy resulted in a lower risk of cardiovascular events (7.8% versus 9.0%, OR: 0.84, 95%CI: 0.78-0.91), with this reduction being significant for MI (OR: 0.83, 95% CI: 0.76-0.92), CVA (OR: 0.83, 95% CI: 0.71-0.96) and overall mortality (OR: 0.91; 95% CI: 0.84-0.97). The incidence of major bleeding was higher with the combined therapy, both in women (OR: 1.43 95%CI: 1.15-1.79) and in men (OR: 1.22, 95%CI: 1.05 -1.42).
The TRITON-TIMI 38 trial, a randomized, double-blind, phase III study, showed significant risk reduction in the study primary endpoints (nonfatal MI, nonfatal CVA and cardiovascular death) in patients treated with Prasugrel (10 mg daily) when compared to those treated with clopidogrel (75 mg daily) (9.9%
The use of dipyridamole in the secondary prevention of cardiovascular events remains controversial, as several clinical trials did not demonstrate adequate efficacy of dipyridamole or its association with ASA in preventing cardiovascular events. After the development of controlled-release formulations of dipyridamole, new studies, such as the ESPS-2 and the European Stroke Prevention Reversible Ischemia Trials (ESPRIT) evaluated the efficacy and safety of dipyridamole in the secondary prevention of cardiovascular events. The ESPS-2 concluded that the dipyridamole + ASA association (50 mg daily + 400 mg daily) is associated with a 22% reduction in cardiovascular events compared with ASA monotherapy. This study, concluded that dipyridamole results in 16% reduction (p = 0.039) in the risk of CVA, when compared to placebo, and a 24% reduction (p <0.001) when associated with ASA. Dipyridamole alone led to a reduction of CVA in patients with a history of ischemic brain disease, when compared to placebo (OR: 0.82, 95% CI: 0.68-1.0), and that there was an even greater benefit when ASA was added to therapy (OR: 0.61, 95% CI: 0.51-0.71). There is no evidence to suggest that dipyridamole may be useful in the treatment of CAD, being indicated for the prevention of CVA and transient ischemic attack19-21.
GPIIb/ IIIa inhibitors have established efficacy in reducing ischemic events, both in the management of acute coronary syndromes and as adjunctive therapy during coronary angioplasty. The "Abciximab Before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long Term Follow-Up (ADMIRAL)" trial concluded that patients undergoing coronary angioplasty, together with abciximab therapy (bolus of 0.25 mg/kg, followed by infusion of 0.125 µg / kg / min for 12 hours), showed a 59% reduction in the incidence of death, myocardial infarction or urgent revascularization, when compared to patients only submitted to angioplasty (6% vs. 14.6%, p = 0, 01)21.
The studies on the efficacy of GPIIb / IIIa receptors are not yet conclusive, as even though most of the trials have shown a significant beneficial effect of using these drugs in secondary prevention, others, such as the "Controlled Abciximab Device Investigation to Lower Late Angioplasty Complications (CADILLAC)" have shown no such benefits. The "Intracoronary Stenting and Atherothrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT2) trial showed that in patients with acute coronary syndrome without ST segment elevation, the use of abciximab had a benefit restricted to patients with high plasma levels of troponin22.
Several antiplatelet drugs are currently undergoing testing, some with completed clinical trials and with others with ongoing.
The efficacy of ticagrelor was evaluated by the "Platelet Inhibition and Patient Outcomes (PLATO)" trial, a multicenter, randomized, double-blind phase III trial comparing the efficacy of ticagrelor (loading dose of 180 mg followed by administration of 90 mg twice daily) compared to clopidogrel (loading dose of 300 mg followed by daily administration of 75 mg). The study results showed that the primary outcome (a compound rate of death from cardiovascular disease, CVA and MI) occurred in 9.8% of patients in the group using ticagrelor
The incidence of major bleeding was higher in ticagrelor users, but there was no statistically significant difference between the groups (11.6% vs. 11.2%, p = 0.43)23.
Phase I studies demonstrate that elinogrel inhibits platelet aggregation within 20 minutes after administration, in a dose-dependent form and shows synergistic effect with ASA. According to the "
In a randomized clinical trial involving patients with myocardial infarction, in which the combined therapy with Cangrelor and Alteplase (a thrombolytic agent) was compared to therapy with each drug alone, it was observed that the combined therapy was better than with either drug alone. The CHAMPION PLATFORM and CHAMPION PCI studies, which sought to determine the efficacy of combined therapy with Cangrelor and Clopidogrel compared to therapy with Clopidogrel alone, were canceled due to lack of efficacy of the combined therapy24.
Atopaxar and Vorapaxar, PAR-1 receptor inhibitors, are undergoing clinical trials (Atopaxar at phase II and Vorapaxar at phase III), of which results should be published soon. The "Thrombin Receptor Antagonist for Clinical Event Reduction in Coronary Syndrome (TRA-CER)" trial, which involves Vorapaxar, recommended the exclusion of individuals with a history of CVA, due to excess risk of intracranial hemorrhage. In the phase-II Atopaxar trial "Japanese-Lesson from Antagonizing the Cellular Effect of Thrombin" (J-LANCELOT), it was observed that this drug does not lead to significant risk of bleeding25.
Information related to the participation of platelets in atherothrombotic diseases allows us to imply that antiplatelet therapy plays a crucial role in the prevention of cardiovascular events. The use of antiplatelet agents, especially in secondary prevention is supported by several studies that evaluated their efficacy and safety. In primary prevention, the potential benefit of the preventive use of ASA should be carefully assessed and individualized.
Advances in understanding of mechanisms by which platelets participate in atherothrombotic processes have led to the search for the development of new drugs capable of consistently inhibiting platelet activity with maximum safety. Several ongoing studies suggest that, in the coming years, currently available strategies for the prevention of cardiovascular disease will be optimized and new pharmacological options will be available for clinical use.
CNPq and FAPEMIG/Brazil. LMSD and MGC are grateful to CNPq Research Fellowship (PQ).
Conception and design of the research, Acquisition of data, Analysis and interpretation of the data, Statistical analysis, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Silva MVF, Dusse LMS, Vieira LM, Carvalho MG.
No potential conflict of interest relevant to this article was reported.
There were no external funding sources for this study.
This study is not associated with any post-graduation program.