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Journal of Integrative Medicine ; (12): 126-134, 2022.
Article in English | WPRIM | ID: wpr-929217


BACKGROUND@#High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.@*OBJECTIVE@#The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.@*DESIGN, PARTICIPANTS AND INTERVENTION@#This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.@*MAIN OUTCOME MEASURES@#The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.@*RESULTS@#A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.@*CONCLUSION@#STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.@*TRIAL REGISTRATION@#This study was registered on ChiCTR-IPR-16009785.

Adenosine Diphosphate , Angina, Unstable/chemically induced , Animals , Biomarkers , Clopidogrel , Cytochrome P-450 CYP2C19/genetics , Drugs, Chinese Herbal , Galectin 3 , Humans , Intercellular Adhesion Molecule-1 , Male , Mice , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Vascular Cell Adhesion Molecule-1/genetics
São Paulo; s.n; s.n; 2022. 202 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1378429


O infarto agudo do miocárdio (IAM) é a maior causa de mortalidade no mundo. A oclusão coronária determina a necrose completa de cardiomiócitos (células musculares cardíacas) durante as primeiras horas do IAM. Porém, mesmo após a perda de massa de miocárdio viável cessar, a região infartada pode se expandir ou contrair no decorrer das primeiras semanas, afetando o prognóstico dos pacientes. Alguns tratamentos podem auxiliar na recuperação e melhoria do prognóstico desses pacientes, como o uso de estatinas e antiplaquetários, que quando utilizados em conjunto, proporcionam efeitos sinérgicos. O presente estudo investigou e comparou, através da óptica da metabolômica global multiplataforma, tratamentos concomitantes de estatinas (sinvastatina ou rosuvastatina) e antiplaquetários bloqueadores do receptor de ADP (clopidogrel ou ticagrelor), em pacientes que sofreram IAM. Foram coletadas amostras de plasma e urina de cerca 40 pacientes tratados com clopidrogrel e sinvastatina ou ticagrelor e rosuvastatina no Hospital São Paulo em diferentes períodos (basal, 1 mês e 6 meses após IAM). Amostras de plasma (basal e 1 mês) foram analisadas por RPLC-MS nos modos de ionização positivo e negativo, GC-MS e CEMS. Amostras de urina (basal, 1 mês e 6 meses) foram analisadas por RPLC-MS no modo de ionização positivo e HILIC-MS nos modos de ionização positivo e negativo. A abordagem metabolomica global multiplataforma evidenciou alterações no metabolismo de diferentes vias pelos dois tratamentos. Os dois tratamentos proporcionaram um efeito pronunciado no metabolismo de diferentes lipídios, como glicerolipídios, esfingolipídios, glicerofosfolipídios e ácidos graxos, sendo que a combinação rosuvastatina e ticagrelor resultou num efeito mais acentuado. Já o tratamento com clopidogrel e sinvastatina alterou de maneira mais pronunciada o metabolismo de aminoácidos ramificados e de acilcarnitinas de cadeia curta. Observou-se ainda a alteração de possíveis biomarcadores relatados na literatura como associados a problemas cardiovasculares, como hipoxantina, ácido 2-hidroxibutírico, algumas espécies de ceramidas, fosfatidilcolinas e acilcarnitinas de cadeia curta

cute myocardium infarction (AMI) is the main mortality cause in the world. The coronary occlusion determines the complete necrosis of cardiomyocytes (cardiac muscle cells) during the first hours of AMI. However, even after the loss of viable myocardial mass ceases, the infarcted area may still expand or contract during the first weeks after AMI, affecting the patient prognosis. Some treatments may assist patient recovery and improve prognostic, such as statins and antiplatelets which, when combined, provide synergic effects. This study investigated and compared, by untargeted multiplatform metabolomics, simultaneous treatments of statins (simvastatin or rosuvastatin) and ADP receptor antagonist antiplatelets (clopidogrel or ticagrelor) in patients that suffered AMI. Plasma and urine samples from around 40 patients treated with clopidogrel and simvastatin or ticagrelor and rosuvastatin were collected in Hospital Sao Paulo at different time points (basal, 1 month, 6 months after AMI). Plasma samples (basal and 1 month) were analyzed by RPLC-MS in positive and negative ionization modes, GC-MS and CE-MS. Urine samples (basal, 1 month, 6 months) were analyzed by RPLC-MS in positive ionization mode and by HILIC-MS in positive and negative ionization modes. The untargeted multiplatform metabolomics approach has shown that different metabolic pathways have been altered by the two treatments. Both treatments had a profound impact on the metabolism of different lipids, such as glycerolipids, sphingolipids, glycerophospholipids, and fatty acids. However, the combined treatment using rosuvastatin and ticagrelor impacted the most the lipid pathways. On the other hand, clopidogrel and simvastatin treatment affected more intensily the branched chain amino acids and short chain acylcarnitines metabolisms. Reported biomarkers in the literature related to cardiovascular diseases were also observed in this study, such as hypoxanthine, 2-hydroxybutyric acid, some species of ceramides, phosphatidylcholines and short chain acylcarnitines

Humans , Male , Female , Platelet Aggregation Inhibitors/analysis , Platelet Aggregation Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/analysis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Simvastatin/analysis , Metabolomics/classification , Myocardial Infarction/pathology , Cardiovascular Diseases , Purinergic P2Y Receptor Antagonists , Rosuvastatin Calcium/analysis , Amino Acids/adverse effects
Chinese Medical Journal ; (24): 1720-1725, 2021.
Article in English | WPRIM | ID: wpr-887614


BACKGROUND@#Geriatric hip fracture patients receiving clopidogrel are a surgical challenge. In China, most of these patients undergo delayed surgical treatment after clopidogrel withdrawal for at least 5 to 7 days. However, delayed surgery is associated with increased complications and mortality in the older adults. This retrospective paralleled comparison study investigated the safety of early surgery for geriatric hip fracture patients within 5 days of clopidogrel withdrawal.@*METHODS@#Acute hip fracture patients (≥65 years) who were hospitalized in the orthogeriatric co-management ward of Beijing Jishuitan Hospital between November 2016 and April 2018 were retrospectively reviewed. Sixty patients taking clopidogrel before injury and discontinued  0.050). The percentages of patients with coronary heart disease (61.7% vs. 18.3%; P  0.050). There was no significant difference in perioperative complications, and 30-day and 1-year mortality rates between the groups.@*CONCLUSIONS@#Early hip fracture surgery is safe for elderly patients within 5 days of clopidogrel withdrawal, without increased perioperative blood loss, transfusion requirement, complications, and mortality compared with patients not taking antiplatelet drugs.

Aged , Case-Control Studies , Clopidogrel/therapeutic use , Hip Fractures/surgery , Humans , Platelet Aggregation Inhibitors/adverse effects , Retrospective Studies , Ticlopidine/adverse effects
Arch. cardiol. Méx ; 90(3): 293-299, Jul.-Sep. 2020. tab, graf
Article in Spanish | LILACS | ID: biblio-1131046


Resumen Introducción: La utilidad de la aspirina en la prevención primaria es todavía objeto de controversia. Los avances médicos y la variabilidad del riesgo cardiovascular podrían explicar la heterogeneidad de los estudios publicados, y las poblaciones de alto riesgo tendrían mayor beneficio. Objetivo: Analizar los efectos de la aspirina en pacientes sin antecedentes cardiovasculares y evaluar los resultados de acuerdo con el riesgo cardiovascular de las poblaciones. Métodos: Se incluyeron estudios que evaluaron el uso de la aspirina en comparación con placebo en la prevención primaria. Se analizó la combinación de muerte cardiovascular, infarto agudo de miocardio (IAM) y accidente cerebrovascular (ACV) isquémico. El punto final de seguridad fue la combinación de ACV hemorrágico y sangrado mayor. Se clasificaron los estudios en riesgo bajo y moderado/ alto, de acuerdo con el número de episodios en la rama de placebo. Resultados: Se evaluaron 13 estudios (n = 164,225), ocho de riesgo cardiovascular bajo (n = 118,455) y cinco de moderado/alto (n = 45,770). Se observó una reducción del punto final combinado en el grupo de aspirina (OR 0.90; IC 95%, 0.85-0.94), sin diferencias en mortalidad cardiovascular (OR 0.94; IC 95%, 0.86-1.04). No se identificaron diferencias entre los subgrupos de riesgo. Se reconocieron mayores complicaciones hemorrágicas en el grupo de aspirina (OR 1.45; IC 95%, 1.32-1.60), sin diferencias entre los subgrupos de riesgo. Conclusión: La aspirina se relacionó con una leve disminución de IAM y ACV isquémico en términos absolutos, sin diferencias en la mortalidad cardiovascular. Esto, junto con el aumento de las complicaciones hemorrágicas, se traduce en una ausencia de beneficio clínico neto. El riesgo cardiovascular basal de la población no modificó los resultados.

Abstract Background: The usefulness of aspirin in primary prevention continues to be the subject of debate. Medical advances and the variability of cardiovascular risk could explain the heterogeneity of the published studies. High risk populations would have greater benefit. Objective: Analyzing the effects of aspirin in patients without cardiovascular disease and evaluating the results according to the cardiovascular risk of the populations. Methods: Studies evaluating aspirin versus placebo in primary prevention were included. The primary endpoint was the combined cardiovascular death, acute myocardial infarction (AMI) and ischemic stroke. The final safety point was the combination of hemorrhagic stroke and major bleeding. The studies were classified into low and moderate/high risk, according to the number of events in the placebo arm. Results: Thirteen studies were evaluated (n = 164,225), eight of low cardiovascular risk (n = 118,455) and five of moderate/high risk (n = 45,770). There was a reduction of the combined endpoint in the aspirin group (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.85-0.94), without differences in cardiovascular mortality (OR 0.94; 95% CI, 0.86-1.04). No differences were observed when comparing the risk subgroups. Greater hemorrhagic complications were observed in the aspirin group (OR 1.45; 95% CI, 1.32-1.60), without differences between the risk subgroups. Conclusion: Aspirin was associated with a slight decrease in AMI and ischemic stroke in absolute terms, with no differences in cardiovascular mortality. This accompanied by the increase in hemorrhagic complications, results in an absence of net clinical benefit. The baseline cardiovascular risk of the population did not affect the results.

Humans , Platelet Aggregation Inhibitors/administration & dosage , Cardiovascular Diseases/prevention & control , Aspirin/administration & dosage , Primary Prevention/methods , Platelet Aggregation Inhibitors/adverse effects , Cardiovascular Diseases/mortality , Aspirin/adverse effects , Heart Disease Risk Factors , Ischemic Stroke/prevention & control , Hemorrhage/chemically induced , Myocardial Infarction/prevention & control
Arq. bras. oftalmol ; 81(4): 348-353, July-Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-950474


ABSTRACT Patients undergoing cataract surgery are generally elderly, and many take drugs with systemic effects. The surgeon must be aware of the risks of continuing or discontinuing such medications perioperatively. Antiplatelet drugs and anticoagulants, prescribed to reduce the incidence of thromboembolic events, are often used in this population. This paper aims to review the perioperative use of antiplatelet and anticoagulant drugs in the setting of cataract surgery. Topical or intracameral anesthesia is preferred over anesthesia injected with needles. Aspirin can be safely continued in patients undergoing cataract surgery. Warfarin has been extensively studied, and the risk of hemorrhage associated with cataract surgery is low if the international normalized ratio is in the therapeutic range. Only a few studies of direct oral anticoagulants are available, and therefore no definite recommendations regarding those agents can be made at this time. Anesthesia in cataract surgery carries a low risk, even for patients taking anticoagulant or antiplatelet drugs. The discontinuation of this class of drugs before cataract surgery may increase the risk of thromboembolism.

RESUMO Os pacientes submetidos à cirurgia de catarata são geralmente idosos e muitos deles usam drogas com efeitos sistêmicos. No entanto, o cirurgião deve estar ciente dos riscos em manter ou descontinuar medicamentos sistêmicos no pré-operatório da cirurgia de catarata, como os anticoagulantes e os antiplaquetários. Este artigo tem como objetivo revisar a classe de drogas antiplaquetárias e anticoagulantes e orientar o cirurgião de catarata. A classe de fármacos anticoagulantes e antiplaquetária reduz a incidência de eventos potencialmente tromboembólicos. A anestesia tópica ou intracameral nesses pacientes deve ser preferida em relação à anestesia com agulhas. Aspirina pode ser mantida com segurança nos pacientes submetidos à cirurgia de catarata. A varfarina foi amplamente estudada e os riscos na cirurgia de catarata são baixos, no entanto, o INR deve ser controlado. Mais estudos são necessários com anticoagulantes orais diretos. Anestesia na cirurgia de catarata tem baixo risco de complicações, mesmo em uso de anticoagulantes ou antiplaquetários sistêmicos. A descontinuação desta classe de medicamentos no pré-operatório da cirurgia de catarata pode aumentar os riscos sistêmicos tromboembólicos.

Humans , Platelet Aggregation Inhibitors/administration & dosage , Cataract Extraction/methods , Anticoagulants/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Cataract Extraction/adverse effects , Risk Factors , Venous Thromboembolism/prevention & control , Intraoperative Period , Anticoagulants/adverse effects
Rev. chil. cir ; 70(3): 291-299, 2018. tab
Article in Spanish | LILACS | ID: biblio-959386


Resumen El uso de fármacos antiagregantes plaquetarios para prevención primaria y secundaria de eventos cardiovasculares es una práctica común en clínica. La terapia antiagregante plaquetaria disminuye significativamente la incidencia de eventos cardiovasculares, incluyendo infarto agudo al miocardio y accidente cerebro-vascular. Cada vez es más frecuente enfrentarse a pacientes en terapia antiagregante plaquetaria que serán sometidos a algún procedimiento quirúrgico, por tanto es fundamental conocer el manejo perioperatorio de estos fármacos, para disminuir los riesgos y complicaciones asociados a la suspensión o mantención de estas drogas en el período perioperatorio. Los antiagregantes plaquetarios de mayor uso en Chile son la aspirina y las tienopiridinas, siendo el clopidogrel el fármaco más utilizado en este grupo. El enfrentamiento perioperatorio de estos fármacos está supeditado al riesgo trombótico individual de cada paciente y al riesgo hemorrágico de cada cirugía. En cirugías no cardiacas, se sugiere mantener la aspirina, excepto en pacientes con bajo-moderado riesgo trombótico que serán sometidos a cirugías con alto riesgo de sangrado, en los cuales se recomienda suspenderla 5-7 días previo a la intervención quirúrgica. El clopidogrel se sugiere suspenderlo 5 días antes de la cirugía, excepto en pacientes con alto riesgo trombótico que se someterán a procedimientos quirúrgicos con riesgo hemorrágico bajo-moderado. En cirugías de revascularización miocárdica, se recomienda mantener aspirina y suspender clopidogrel 5 días antes del procedimiento. En relación al reinicio postquirúrgico de estos fármacos, se sugiere reanudar aspirina 6 h posterior a la cirugía y clopidogrel durante las primeras 24 h postoperatorias, asegurando previamente una adecuada hemostasia quirúrgica.

The use of antiplatelet drugs for primary and secondary prevention of cardiovascular disease events is a common clinical practice. Antiplatelet therapy significantly decreases the incidence of cardiovascular disease events, including acute myocardial infarction and cerebrovascular accident. It is increasingly common to face patients on antiplatelet therapy who will undergo some surgical procedure, so it is essential to know the perioperative management of these drugs, to reduce the risks and complications associated with the suspension or maintenance of these therapies in the perioperative period. The most common antiplatelet agents used in Chile are acetylsalicylic acid and thienopyridines, of which clopidogrel is the most frequent one. The perioperative management of these drugs has to be based on the individual thrombotic risk of each patient and the risk of hemorrhage of each surgery. In noncardiac surgeries, it is suggested to maintain acetylsalicylic acid, except in patients with low to moderate thrombotic risk who will undergo surgeries with a high risk of bleeding, in which case it is recommended to suspend it 5 to 7 days before surgery. Clopidogrel is suggested to be discontinued 5 days before surgery, except in patients with high thrombotic risk who will undergo surgical procedures with low to moderate risk of hemorrhage. In myocardial revascularization surgeries, it is recommended to maintain acetylsalicylic acid and to suspend clopidogrel 5 days before the procedure. Once assuring adequate surgical hemostasis, it is suggested to reinitiate acetylsalicylic acid 6 hours after surgery and to reinitiate clopidogrel during the first 24 postoperative hours.

Humans , Surgical Procedures, Operative/methods , Platelet Aggregation Inhibitors/administration & dosage , Perioperative Care/methods , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/pharmacokinetics , Aspirin/administration & dosage , Aspirin/adverse effects , Risk Assessment , Postoperative Hemorrhage/chemically induced , Withholding Treatment , Thienopyridines/administration & dosage , Thienopyridines/adverse effects , Clopidogrel/administration & dosage , Clopidogrel/adverse effects
Rev. chil. cardiol ; 36(3): 200-208, dic. 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-899587


Resumen: Introducción: La terapia antiagregante dual (TAD) con aspirina más clopidogrel o ticagrelor es fundamental para prevenir trombosis de stent y nuevos eventos cardiovasculares (CV) en pacientes sometidos a angioplastía coronaria (AC). Sin embargo, TAD se asocia a un riesgo aumentado de hemorragias, en particular cuando su uso se prolonga. Recientemente se han creado puntajes (DAPT, PRECISE-DAPT) que buscan estimar el riesgo de sangrado en pacientes con TAD por tiempo prolongado, los que quisimos evaluar en nuestra población. Métodos: Se utilizó la base de datos prospectiva de Prevención Cardiovascular del Hospital Clínico U. Católica, seleccionando pacientes sometidos a AC el año 2015. Se realizó una encuesta telefónica estandarizada para identificar episodios de sangrado definidos según clasificación ISTH, tiempo de uso de TAD y nuevos eventos CV. Se calcularon los puntajes DAPT y PRECISE-DAPT. Se usó pruebas de t de Student, test exacto de Fisher y curva ROC, según correspondiese, considerando significativa una p<0,05. Resultados: Se incluyeron 227 pacientes (edad 64,2±12,3 años, 22,5% mujeres), de los cuales el 69,6% eran hipertensos, 28,6% diabéticos, 26,9% fumadores y 5,3% insuficientes renales crónicos. En el 63% de los pacientes la AC fue por síndrome coronario agudo, se implantaron 1,4±0,7 stents/paciente y el 37% de los pacientes recibió sólo stents metálicos. Al momento de la encuesta, el seguimiento fue de 26±3 meses. Se registró un tiempo promedio de duración de TAD de 12,6±7,4 meses, con 99,1% de los pacientes recibiendo aspirina, 93,4% clopidogrel, 6,6% ticagrelor y 9,3% anticoagulantes orales. Hubo 35 (15,4%) nuevos eventos CV (revascularización 14, infarto 12, accidente cerebrovascular 2 y muerte 7) y 31 (13,6%) episodios de sangrados (criterio ISTH). De acuerdo con el criterio TIMI de sangrado se registraron 5 (2,2%) episodios graves, 9 (3,9%) leves y 17 (7,4%) menores. En 10 (4,4%) pacientes se modificó la TAD debido al sangrado. PRECISE-DAPT se asoció de manera significativa a los episodios de sangrado (p<0,01); tener un puntaje de alto riesgo (>25) aumentó más de 3 veces el riesgo de sangrado (OR 3,1 IC 1,4-7,1, p<0,01) y una curva ROC estableció que en la población estudiada el mejor punto de corte fue de 18 puntos (C-statistic 0,69) (Figuras 1A y B). El uso de TACO aumentó el riesgo (OR 3,4 IC 1,2-9,5, p=0,02). Si bien miden distintos parámetros, los puntajes de riesgo DAPT y PRECISE-DAPT se correlacionaron significativamente en nuestra cohorte (p<0,01). Conclusiones: En esta cohorte de la vida real se demuestra que la ocurrencia de sangramientos es un evento frecuente en pacientes con TAD, similar a la tasa de nuevos eventos CV, y por tanto debe ser un factor relevante a considerar al momento de la AC y la selección de la TAD. El puntaje PRECISE-DAPT es una herramienta útil para predecir sangrados, aunque nuestros resultados sugieren que en población chilena los valores de corte pueden ser algo menores que lo previamente publicado .

Abstracts: Background: Dual antiplatelet therapy (DAT) with aspirin plus clopidogrel or ticagrelor is essential for the prevention of stent thrombosis and new cardiovascular events in patients undergoing PCI. However, DAT is associated with an increased risk of bleeding, more so when it is used for prolonged time periods. Scores (DAPT, PRECISE-DAPT) developed to predict bleeding risk were evaluated in this study. Method: The prospective Cardiovascular Prevention database at Catholic University Hospital was used to select patients who underwent PCI followed by DAT during 2015. By phone contact information on bleeding episodes - according to the ISTH classification -, new cardiovascular events and DAT duration were collected. DAPT and PRECISE- DAPT scores were calculated. Student's t test, Fisher exact test and ROC analysis were used. Significance was established at p< 0.05. Results: 277 patients were included (age 64.2±12.3 y-o, 22.5% women). Hypertension was present in 66.9%, diabetes in 28.6%, smoking habit in 26.9% and renal failure in 5.3%. The indication for PCI was acute coronary syndrome in 63%, 1.4±0.7 stents per patient were implanted and 37% of patients received bare metal stents exclusively. Follow-up extended for 26±3 months. DAT was active for 12.6±7.4 months and 9.3% of patients received oral anticoagulant therapy. There were 35 (15.4%) new cardiovascular events (14 revascularizations, 12 myocardial infarctions, 2 CVA and 7 deaths). Conversely, there were 31 (13.6%) bleeding episodes. According to the TIMI classification, bleeding episodes were severe in 2.2%, mild in 3.9% and minor in 7.4%. In 4% of patients DAT was modified due to bleeding. PRECISE-DAPT score was significantly associated to bleeding episodes (p<0.01). A high score (>25) was associated with a 3-fold risk of bleeding (OR 3.1, CI 1.4-7.1 (p<0.01). Through ROC analysis the best PRECISE-DAPT cutting point in this cohort was 18 (C=0.69). The use of oral anticoagulation increased bleeding risk (OR 3.4 CI 1.2 - 9.5, p=0.02). DAPT and PRECISE-DAPT were significantly correlated (p<0.01). Conclusion: Bleeding is a frequent complication of DAT, similar to the risk of new cardiovascular events. PRECISE-DAPT score is useful to estimate the risk of bleeding, although this study suggests that in the studied population the cutting point may be somewhat lower than previously published.

Humans , Male , Female , Middle Aged , Aged , Platelet Aggregation Inhibitors/adverse effects , Angioplasty, Balloon, Coronary/methods , Hemorrhage/chemically induced , Platelet Aggregation Inhibitors/therapeutic use , Cardiovascular Diseases/prevention & control , Aspirin/adverse effects , Prospective Studies , Surveys and Questionnaires , ROC Curve , Follow-Up Studies , Risk Assessment/methods , Clopidogrel/adverse effects , Ticagrelor/adverse effects , Hemorrhage/epidemiology
Lima; s.n; ago. 2016.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-848557


INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología sanitaria de la eficacia y seguridad de Ticagrelor en pacientes con re-infarto por trombosis de stent por falla a la terapia de doble antiagregación plaquetaria clopidogrel más aspirina. Aspectos Generales: El síndrome coronario agudo (SCA) es una condición en la que se manifestan síntomas de isquemia cardíaca y, clinicamente, se presentan de manera heterogénea. Los síndromes coronarios agudos como infarto agudo de miocardio con elevación del segmento ST (IAMCEST) y la angina inestable comparten una fisiopatología común: la rotura o erosión de una placa de ateroma con trombosis intracoronaria superpuesta (aterotrombosis). Tecnología Sanitaria de Interés: Dentro de los tratamientos farmacológicos para el síndrome coronario agudo el Ticagrelor: un derivado pirimidínico antiplaquetario oral de nueva generación, el cual se une reversiblemente al receptor adenosino difosfato P2Y inhibiendo así la activación y agregación plaquetaria. Tiene un mecanismo de iniciación, acción y finalización más rápido que su similar clopidogrel y es considerado un tratamiento de primera línea en algunos países del primer mundo. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una estrategia de búsqueda sistemática de la evidencia científica con respecto a Ticagrelor en pacientes con ref-infarto por trombosis de stent y falla a la terapia de doble antiagregación plaquetaria clopidogrel más aspirina. Para la búsqueda primaria se revisó la información disponible por entes reguladoras y normativas como la Food and Drug Administration (FDA), y la Dirección General de Medicamentos y Drogas (DIGEMID). Posteriormente se buscaron Guías de Práctica Clínica a través de los metabuscadores: Translating Research into Practice (TRIPDATABASE), National Library Systems Evidence. Finalmente, se realizó una búsqueda dentro de la información generada por grupos internacionales que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica, tales como The Cochrane Library, The National Institute for Health and Care Excellence (NICE), The Canadian Agency for Drugs and Technologies in Health (CADTH), The Scottish Medicines Consortium (SMC). Se realizó además una búsqueda manual con una estrategia de bola de nieve mediante la revisión de listas de referencias de las guías, evaluaciones de tecnologías estudios primarios y revisiones narrativas seleccionados. RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda y revisión de la evidencia científica actual para la evaluación de la eficacia y seguridad de Ticagrelor en pacientes con re-infarto por trombosis de stent y falla a la terapia de doble antiagregación plaquetaria clopidogrel más aspirina. La evidencia disponible a la actualidad sobre el uso de ticagrelor recae en un único ensayo clínico aleatorizado (ECA) fase III, el estudio PLATO 2009 de Wallentin et al., a partir del cual se emiten todas las recomendaciones en guías de práctica clínica, evaluaciones de tecnología sanitaria, y análisis exploratórios secundarios. CONCLUSIONES: En la actualidad, el Petitorio Farmacológico de Esalud cuenta con la terapia estándar de tratamiento para síndrome coronario agudo: clopidogrel en combinación con aspirina, terapia que es empleada como primera alternativa de elección para el manejo de pacientes con el diagnóstico mencionado. A la fecha, no existe alternativa de tratamiento a clopidogrel en el petitorio de ESSalud, por lo que es necesario contar con una alternativa para aquellos pacientes en alto riesgo de muerte al haber sufrido re-infarto al miocardio por trombosis de stent a pesar de encotrarse en terapia con clopidogrel más aspirina, a dosis tope y durante un tiempo de tratamiento adecuado. El Instituto de Evaluación de Tecnologías en Salud e Invstigación-IETSI, aprueba el uso de Ticagrelor en pacientes con re-infarto por trombosis de stent y falla a la terapia de doble antiagregación plaquetaria clopidogrel más aspirina.

Humans , Adenosine/administration & dosage , Adenosine/analogs & derivatives , Aspirin/administration & dosage , Coronary Thrombosis/drug therapy , Infarction/complications , Platelet Aggregation Inhibitors/adverse effects , Stents , Technology Assessment, Biomedical , Treatment Outcome
Medicina (B.Aires) ; 75(4): 207-212, Aug. 2015. graf, tab
Article in Spanish | LILACS | ID: biblio-841496


Al uso del clopidogrel se han agregado nuevos antiagregantes como prasugrel y ticagrelor. El objetivo de este estudio fue comparar la incidencia de eventos isquémicos y hemorrágicos en pacientes que han recibido clopidogrel o prasugrel.Se incluyeron de manera consecutiva todos los pacientes con angioplastia durante la internación por síndrome coronario agudo entre diciembre 2011 y diciembre 2012.Fueron incluidos 398 pacientes. No se observaron diferencias en la mortalidad de causa cardiovascular (clopidogrel 2.5% vs. prasugrel 2.9%, p = 0.48). El grupo prasugrel presentó una reducción en la tasa de infarto (1.9% vs. 6.8%, p = 0.01) con sangrado totales (18.5% vs. 8.5%, p = 0.001) a expensas de sangrados menores (12.4% vs. 3.4%, p < 0.001), sin diferencia en sangrados mayores (p = 0.27) y sangrados con peligro de vida (p =.0.20). Por análisis multivariado los predictores independientes de mortalidad cardiovascular fueron edad (odds ratio 1.08, intervalo de confianza, IC, 95% 1.02-1.16, p = 0.02) insuficiencia renal (odds ratio 6.98, IC 95% 1.23-39.71, p < 0.0001). En cuanto al sangrado total se identificaron la edad (odds ratio 1.06, IC 95% 1.02-1.09, p = 0.002), elevación del segmento ST (odds ratio 1.99, IC 95% 1.05-3.79, p = 0.02), insuficiencia renal (odds ratio 3.32, IC 95% 1.62-6.78, p = 0.002) y utilización de prasugrel (odds ratio 3.97, IC 95% 1.87-8.41, p < 0.0001). La utilización de prasugrel se asocia a una menor tasa de infarto agudo de miocardio al año de seguimiento, con incremento de hemorragias menores. No se observaron diferencias significativas en la mortalidad cardiovascular entre ambos grupos.

Greater antithrombotic potency new antiplatelet agents have been added such as prasugrel (PR) and ticagrelor to the traditional use of clopidogrel (CL) in the treatment of acute coronary syndrome (ACS). This study was aimed at comparing the incidence of long term ischemic and hemorrhagic events in patients treated with CL or PR during hospitalization. Retrospective ACS data base analysis performed by our cardiology service was completed prospectively. There were consecutively included all patients with percutaneous coronary intervention (PCI) during hospitalization due to ACS from December 2011 thru December 2012. A total of 398 ACS patients who underwent PCI with stent implantation were recruited. No differences in cardiovascular related deaths were observed in both groups (PR 2.9% vs. CL 2.5%, p = 0.48). PR group showed less re-infraction (1.9% vs. 6.8%, p = 0.01) with more total bleedings (18.5% vs. 8.5%, p = 0.001) and minor bleedings (12.4% vs. 3.4%, p < 0.001) with no differences in major and life threatening bleedings (p = ns). Multivariate analysis showed that independent predictors of cardiovascular mortality were age (OR 1.08, CI 95% 1.02-1.16) and renal failure (OR 6.98, CI 95% 1.23-39.71). Independent predictors for total bleeding were age (OR 1.06, CI 95% 1.02-1.09),ST segment elevation myocardial infarction (OR 1.99, CI 95% 1.05-3.79), renal failure (OR 3.32, CI 95% 1.62-6.78) and prasugrel use (OR 3.97, CI 95% 1.87-8.41). Use of prasugrel, in the ACS that requires PCI with stent, is associated with a lower myocardial infarction a year after follow-up, and it also leads to an increase of milder hemorrhage. No significant differences were observed in the cardiovascular mortality of both groups.

Humans , Male , Female , Middle Aged , Ticlopidine/analogs & derivatives , Platelet Aggregation Inhibitors/therapeutic use , Stents , Angioplasty/methods , Acute Coronary Syndrome/therapy , Prasugrel Hydrochloride/therapeutic use , Ticlopidine/adverse effects , Ticlopidine/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Retrospective Studies , Treatment Outcome , Angioplasty/adverse effects , Kaplan-Meier Estimate , Acute Coronary Syndrome/mortality , Prasugrel Hydrochloride/adverse effects , Clopidogrel , Hemorrhage/prevention & control
Arq. bras. cardiol ; 100(3): 221-228, mar. 2013. ilus, tab
Article in Portuguese | LILACS | ID: lil-670862


FUNDAMENTO: O papel dos testes de reatividade plaquetária (RP) na predição de eventos em longo prazo em pacientes latino-americanos tratados com stents farmacológicos (SF) não foi estabelecido. OBJETIVOS: Analisar o papel dos testes de RP na predição de eventos após a implantação de SF. MÉTODOS: De maio de 2006 a janeiro de 2008, foram incluídos 209 pacientes brasileiros que se submeteram a tratamento eletivo com SF. A RP foi avaliada 12 a 18 horas após o procedimento, por agregometria de transmitância de luz com 5µM de ADP. Os pacientes foram acompanhados prospectivamente por até 4,8 anos. Dezessete (8%) dos indivíduos foram perdidos durante o acompanhamento e a coorte final foi composta de 192 pacientes. A curva ROC foi utilizada para determinar o melhor ponto de corte de 5µM de ADP para prever eventos. O endpoint primário foi uma combinação de morte cardiovascular, infarto agudo do miocárdio, trombose definitiva de stent, e revascularização de artéria alvo.Modelos de risco proporcional de Cox foram utilizados para determinar as variáveis independentemente associadas com o tempo até o primeiro evento. RESULTADOS: O melhor ponto de corte de 5µM de ADP foi de 33%. Cento e sete (55,7%) pacientes apresentaram 5mM de ADP > 33%. A taxa de sobrevivência livre de eventos em 1.800 dias foi de 55% contra 70% para os indivíduos com ADP5 acima e abaixo desse ponto de corte, respectivamente (p = 0,001). Preditores de tempo independentes para o primeiro evento foram tabagismo atual (HR 3,49, IC95%: 1,76-6,9, p = 0,0003), ADP 5mM > 33% (HR 1,95, IC95%: 1,09-3,51, p = 0,025) e idade (HR 1,03 IC 95%: 1,0-1,06, p = 0,041). CONCLUSÕES: Neste estudo, 55,7% dos pacientes apresentaram alta reatividade plaquetária durante tratamento. 5µM de ADP > 33% foi um preditor independente de eventos em longo prazo.

BACKGROUND: The role of platelet reactivity (PR) tests in the prediction of long-term events in Latin-American patients treated with drug-eluting stents (DES) has not been established. OBJECTIVES: To assess the role of PR tests in the prediction of events after DES implantation. METHODS: From May 2006 through January 2008, 209 Brazilian patients who underwent elective treatment with DES were included. PR was assessed 12 to 18h after the procedure by light transmittance aggregometry with 5µM of ADP. Patients were prospectively followed for up to 4.8 years. Seventeen (8%) individuals were lost to follow-up and the final cohort comprised 192 patients. Receiver operating curve (ROC) was used to determine the best 5µM of ADP cutoff to predict events. The primary endpoint was a combination of cardiovascular death, acute myocardial infarction, definite stent thrombosis, and target-artery revascularization. Cox proportional hazard models were used to determine the variables independently associated with the time to the first event. RESULTS: The best ADP 5µM cutoff was 33%. One hundred and seven (55.7%) patients had ADP 5µM >33%. Event-free survival rate at 1,800 days was 55% vs. 70% for individuals with ADP5 above and below such cutoff, respectively (p=0.001). Independent predictors of time to first event were current smoking (HR 3.49; 95% CI 1.76-6.9; p=0.0003), ADP 5µM >33% (HR 1.95; 95% CI 1.09-3.51; p=0.025) and age (HR 1.03; 95% CI 1.0-1.06; p=0.041). CONCLUSIONS: In this study, 55.7% of the patients had high on-treatment platelet reactivity. ADP 5µM >33% was an independent predictor of long-term events.

Aged , Female , Humans , Male , Cardiovascular Diseases/prevention & control , Drug-Eluting Stents/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation/drug effects , Platelet Function Tests/standards , Ticlopidine/analogs & derivatives , Brazil/epidemiology , Cardiovascular Diseases/epidemiology , Epidemiologic Methods , Platelet Function Tests/methods , Reference Standards , Risk Factors , Ticlopidine/adverse effects
Rev. bras. cardiol. (Impr.) ; 26(1): 58-61, jan.-fev. 2013. ilus
Article in Portuguese | LILACS | ID: lil-679832


A síndrome coronariana aguda (SCA) é uma condição extremamente prevalente que impões às equipes médicas, acurácia diagnóstica e agilidade terapêutica. Dados da Organização Mundial da Saúde apontam a doença cardiovascular como principal causa de mortalidade mundial. O risco de doença arterial coronariana (DAC) está particularmente aumentado na presença de diabetes mellitus (DM). Essa enfermidade causa disfunção endotelial, aumentando o estado inflamatório sistêmico e ocasionando disfunção na agregação plaquetária. Os fármacos utilizados para o tratamento da SCA, principalmente os antiplaquetários, podem ter sua eficácia reduzida em vigência das alterações sistêmicas causadas pelo DM. Essas alterações podem ser responsáveis por um maior número de eventos tromboembólicos como a trombose intrastent em pacientes submetidos à angioplastia após infarto agudo do miocárdio (IAM). Os autores relatam um caso de trombose intrastent em paciente com diabetes mellitus descompensado em vigência de dose-padrão de clopidogrel e AAS.

Acute coronary syndrome (ACS) is an extremely prevalente condition that requires medical staff, diagnostic accuracy and fast treatment. data provided by the World Health Organization indicate cardiovascular disease as the main cause artery disease (CAD) rises particularly in the presence of diabetes mellitus (DM). This disease causes endothelial dysfunction by increasing the systemic inflammatory status, causing dysfunction in platelet aggregation. The efficacy of drugs used to treat ACS, especially antiplatelet agents, may reduced through systemic changes caused by DM. these changes may be responsible for an increased number of thromboembolic events such as intrastent thrombosis in angioplasty patients after acute myocardial infarction (AMI). the authors report a case of intra-stent thrombosis in a patient with decompensated diabetes mellitus while taking standard doses of clopidogrel and aspirin.

Humans , Male , Aged , Diabetes Mellitus/diagnosis , Coronary Artery Disease/complications , Coronary Artery Disease/diagnosis , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Angioplasty/methods , Angioplasty , Stents , Thrombosis/complications
Rev. méd. Chile ; 141(2): 255-259, feb. 2013. tab
Article in Spanish | LILACS | ID: lil-675066


Background: Aspirin use is necessary after a coronary angioplasty. It should not be used in patients with a history of hypersensitivity. However, rapid desensitization protocols have been reported to allow its use in such patients. One of these protocols consists in the administration of progressive doses of aspirin, from 1 to 100 mg in a period of 5.5 hours, in a controlled environment. We report four male patients aged 45,49, 59 and 73 years with a history of aspirin hypersensitivity, who were subjected to a coronary angioplasty. In all, the rapid aspirin desensitization protocol was successfully applied, allowing the use of the drug after the intervention without problems.

Aged , Humans , Male , Middle Aged , Angioplasty, Balloon, Coronary/methods , Aspirin/administration & dosage , Desensitization, Immunologic/methods , Drug Hypersensitivity/prevention & control , Platelet Aggregation Inhibitors/administration & dosage , Aspirin/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Treatment Outcome , Ticlopidine/administration & dosage , Ticlopidine/analogs & derivatives
Gastroenterol. latinoam ; 24(supl.1): S48-S51, 2013.
Article in Spanish | LILACS | ID: lil-763720


Currently the administration of antiplatelet and/or anticoagulant drugs for prophylaxis of thromboembolic events is frequent; thus increasing the risk of gastrointestinal bleeding. Approximately 10 percent of patients with gastrointestinal bleeding are on anticoagulation therapy. It is necessary to consider the indication for anticoagulation/antiplatelet therapy in patients with gastrointestinal bleeding, to decide on the importance of early reintroduction of such drugs, seeking a balance between the risk of recurrent bleeding and thromboembolic complications. Generally, in patients with gastrointestinal bleeding in anticoagulant therapy it is considered appropriate to make a quick correction of anticoagulation with intravenous vitamin K and fresh frozen plasma, prothrombin complex or recombinant factor VII, depending on the severity of the hemorrhage. The latter is considered only in life-threatening cases, where other methods have failed. The reduction of the internacional normalized ratio (INR) to 1.5 should be enough to control bleeding, and even with values < 2.5 there are no differences in bleeding control. Patients receiving aspirin should reintroduce it early. In patients with coronary stents placed uncoated < 1 month of the bleeding episode, or drug-eluting stents placed within < 1 year, no antiplatelet therapy should be withdrawn, and never without first consulting a cardiologist. Regardless of the value of INR, in most patients a lesion responsible for bleeding is identified at the time of endoscopy (often, this is a peptic lesion), therefore endoscopy should be performed even in patients with very high INR.

Actualmente, es frecuente la administración de fármacos antiagregantes y/o anticoagulantes para profilaxis de fenómenos tromboembólicos; con ello aumenta el riesgo de hemorragia digestiva. Aproximadamente 10 por ciento de los pacientes con hemorragia digestiva está en tratamiento anticoagulante. Es necesario considerar la indicación de la anticoagulación/ antiagregación en los pacientes con hemorragia digestiva, para poder decidir sobre la importancia de la reintroducción precoz de dichos fármacos, buscando un balance entre el riesgo de recidiva hemorrágica y de complicaciones tromboembólicas. En general, en los pacientes con hemorragia digestiva en terapia anticoagulante, se considera adecuado realizar una corrección rápida de la anticoagulación, con vitamina K endovenosa y plasma fresco congelado, complejo protrombínico, o factor VII recombinante, dependiendo de la gravedad de la hemorragia. El último se considerará sólo en casos de riesgo vital en que los otros métodos hayan fallado. La reducción del internacional normalized ratio (INR) hasta 1,5 debe ser suficiente para poder controlar la hemorragia, e incluso en valores < 2,5 no se observan diferencias en el control hemorrágico. Los pacientes que reciben aspirina deben reintroducirla precozmente; en pacientes con stents coronarios no recubiertos, colocados < 1 mes del episodio hemorrágico, o en stents liberadores de fármacos, colocados en un plazo de < 1 año, no debería retirarse la antiagregación, y en cualquier forma nunca sin antes consultar a un cardiólogo. Independientemente del valor de INR, en la mayoría de los pacientes se identifica en la endoscopia una lesión responsable del sangrado (con frecuencia se trata de una lesión péptica); por ello, no debe desestimarse la realización de una endoscopia incluso en pacientes con INR muy elevados.

Humans , Anticoagulants/adverse effects , Gastrointestinal Hemorrhage/chemically induced , Platelet Aggregation Inhibitors/adverse effects , Thromboembolism/drug therapy , Risk