Diferencias en el tratamiento antitrombótico y pronóstico en función del sexo en pacientes con síndrome coronario agudo tratados con stent / Sex-specific differences in antithrombotic therapy and prognosis in patients with acute coronary syndrome treated with stent

Resumen Antecedentes y objetivo: El interés sobre la influencia del sexo en pacientes con síndrome coronario agudo (SCA) tratados con stent y nuevos antiagregantes inhibidores de P2Y12 en la práctica clínica es creciente. Se analizan las diferencias en función del sexo en el tratamiento con doble antiagregación plaquetaria (DAPT) y los eventos adversos isquémicos y hemorrágicos Materiales y métodos: Estudio prospectivo de pacientes consecutivos con diagnóstico de SCA tratados con stent coronario desde julio de 2015 hasta enero de 2016. Resultados: De un total de 283 pacientes incluidos, 75 (26.5%) correspondió a mujeres y 208 (73.5%) a hombres. La edad media fue de 71 ± 13 y 66.5 ± 13 años, respectivamente. Un 44% de mujeres se presentó como SCA con elevación del segmento ST contra un 52.4 de los hombres, p = 0.21. Las mujeres mostraron un mayor riesgo de sangrado (CRUSADE), sin diferencias en el riesgo isquémico (GRACE y TIMI). Se usaron stents farmacoactivos con más frecuencia en mujeres (88.9 vs. 75.5%, p = 0.04). Se observó una tendencia de menor prescripción del ticagrelor en mujeres (42.6 vs. 50.9%, p = 0.29) en favor de un mayor uso del clopidogrel. No se identificaron diferencias en cuanto a la prescripción del prasugrel. Las mujeres presentaron al año una menor mortalidad (1.4 vs. 6.7%, p = 0.19), aunque mayor sangrado (23.3 vs. 17.4%, p = 0.27). Conclusiones: En este estudio de pacientes consecutivos con SCA tratados con stent se registró una mayor prescripción de clopidogrel en las mujeres que en los hombres. Las mujeres presentaron una menor incidencia anual de mortalidad, pero mayor sangrado en comparación con los hombres, no significativo.

Abstract Aims and objective: Impact of sex-related differences in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention and treated with new P2Y12 inhibitors is not adequately characterised. We aimed to analyse gender-based differences in dual antiplatelet therapy, and adverse cardiovascular events and bleeding. Materials and methods: Prospective-observational study of the consecutive ACS patients treated with stent from July 2016 to January 2016, with a follow-up of 1 year. Results: We examined 283 patients, 75 (26.5%) women and 208 (73.5%) men. Women were older than men (71 ± 13 vs. 66,5 ± 13 years). There were 44% of women and 52% of men presenting with ST-elevation ACS (p = 0.21). Women had a higher bleeding risk (CRUSADE), without differences in the ischaemic risk (GRACE and TIMI). More women were treated with drug-eluting stent (88.9 vs. 75.5%, p = 0.04). There was a lower rate of ticagrelor prescription in women (42.6 vs. 50.9%, p = 0.29), in favour of clopidogrel. No differences were observed in prasugrel prescription. No significant differences were observed after a year of follow up, but women had a tendency towards lower mortality (1.4 vs. 6.7%, p = 0.19) and higher bleeding rates (23.3 vs. 17.4%, p = 0.27). Conclusions: In our study of patients presenting with ACS treated with stent, clopidogrel was preferred in women, whereas ticagrelor was the most frequent prescription in men. No significant differences were noted in clinical outcomes, but women experienced a tendency towards less mortality and more bleeding events.

Evidencias para el uso combinado de ácido acetilsalicílico (aspirina) y clopidogrel en síndromes coronarios agudos / Evidences about combination use of acetylsalicylic acid (aspirin) and clopidogrel in acute coronary syndrome

Las enfermedades tromboembólicas siguen siendo una de las causas más importantes de morbilidad y mortalidad en todo el mundo. El mecanismo fisiopatológico subyacente en los síndromes coronarios agudos es la trombosis coronaria. Por eso, la base de su tratamiento se ha centrado en los fármacos antiplaquetarios, fibrinolíticos y anticoagulantes. En un número importante de individuos deben emplearse medidas adicionales como, por ejemplo, el intervencionismo percutáneo coronario (angioplastia y la colocación de los llamados stentsintracoronarios). La aspirina se ha considerado como el fármaco de primera elección en la prevención de las afecciones tromboembólicas. La combinación aspirina-clopidogrel ha representado una terapéutica sumamente eficiente en el tratamiento de los eventos tromboembólicos. La introducción de tabletas de combinación fija representa un avance para facilitar el cumplimiento de la terapia.

Thromboembolic diseases remain one of the most important causes of morbidity and mortality worldwide. The pathophysiologic mechanism underlying the acute coronary syndromes is coronary thrombosis. That is why the basis of its treatment has focused on antiplatelet, fibrinolytic and anticoagulant drugs. In a significant number of individuals, additional measures must be used, such as, for example, the coronary percutaneous intervention (angioplasty and placement of the so-called intracoronary stents). Aspirin has been regarded as the drug of first choice in the prevention of thromboembolic diseases. The combination aspirin-clopidogrel has represented a highly efficient therapeutic measure for thromboembolic events. The introduction of fixed combination tablets represents a step forward in order to facilitate therapeutic compliance.

Time-To-Treatment of Acute Coronary Syndrome and Unit of First Contact in the ERICO Study / Tempo para Tratamento durante Síndrome Coronariana Aguda e Unidade de Primeiro Contato no Estudo ERICO

Abstract Background: To the best of our knowledge, there are no studies evaluating the influence of the unit of the first contact on the frequency and time of pharmacological treatment during an acute coronary syndrome (ACS) event. Objectives: The main objective was to investigate if the unit of first contact influenced the frequency and time of aspirin treatment in the Strategy of Registry of Acute Coronary Syndrome (ERICO) study. Methods: We analyzed the pharmacological treatment time in 830 ERICO participants - 700 individuals for whom the hospital was the unit of first contact and 130 who initially sought primary care units. We built logistic regression models to study whether the unit of first contact was associated with a treatment time of less than three hours. Results: Individuals who went to primary care units received the first aspirin dose in those units in 75.6% of the cases. The remaining 24.4% received aspirin at the hospital. Despite this finding, individuals from primary care still had aspirin administered within three hours more frequently than those who went to the hospital (76.8% vs 52.6%; p<0.001 and 100% vs. 70.7%; p=0.001 for non ST-elevation ACS and ST-elevation myocardial infarction, respectively). In adjusted models, individuals coming from primary care were more likely to receive aspirin more quickly (odds ratio: 3.66; 95% confidence interval: 2.06-6.51). Conclusions: In our setting, individuals from primary care were more likely to receive aspirin earlier. Enhancing the ability of primary care units to provide early treatment and safe transportation may be beneficial in similar settings.

Resumo Fundamento: Em nosso conhecimento, não há estudos que avaliam a influência da unidade de primeiro contato na frequência e tempo para o tratamento farmacológico durante um evento de síndrome coronariana aguda (SCA). Objetivos: O principal objetivo foi investigar se a unidade de primeiro contato influencia a frequência e o tempo para tratamento com aspirina no estudo "Estratégia de Registro de Insuficiência Coronariana" (ERICO). Métodos: Analisamos o tempo para o tratamento farmacológico em 830 participantes do estudo ERICO - 700 indivíduos cuja primeira unidade de contato foi o hospital, e 130 que procuraram, num primeiro momento, unidades de atenção primária. Construímos modelos de regressão logística para estudar se a unidade de primeiro contato estava associada a um tempo de tratamento de menos de três horas. Resultados: Indivíduos que buscaram unidades de atenção primária receberam a primeira dose de aspirina nestas unidades em 75,6% dos casos. Os outros 24,4% receberam a aspirina no hospital. Apesar deste achado, indivíduos de unidades de atenção primária receberam aspirina em três horas mais frequentemente do que aqueles que foram ao hospital (76,8% vs 52,6%; p<0,001 e 100% vs, 70,7%; p=0,001 para SCA sem elevação do segmento ST e infarto agudo do miocárdio com elevação do ST, respectivamente). Em modelos ajustados, indivíduos vindos de unidades de atenção primária tinham mais probabilidade de receber aspirina mais rapidamente (razão de chances: 3,66; 95% intervalo de confiança: 2,06-6,51). Conclusões: Neste contexto, indivíduos provenientes de unidades de atenção primária tinham maior chance de receber aspirina mais rapidamente. O aprimoramento da capacidade das unidades de atenção primária para proporcionar tratamento precoce e transporte seguro pode ser benéfico em contextos similares.

Efficacy and safety of antiplatelet-combination therapy after drug-eluting stent implantation

BACKGROUND/AIMS: Combination single-pill therapy can improve cost-effectiveness in a typical medical therapy. However, there is a little evidence about the efficacy and tolerability of combination single-pill antiplatelet therapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: From June to November 2012, in total, 142 patients who met the following criteria were enrolled: at least 18 years old; successful PCI with DES at least 3 months earlier; and regular medication of aspirin and clopidogrel with no side effects. After VerifyNow P2Y12 and aspirin assays, the combination single pill of aspirin and clopidogrel was given and laboratory tests were repeated 6 weeks later. RESULTS: At baseline, the incidence of aspirin resistance, defined as aspirin reaction unit (ARU) > or = 550, was 9.2%, that of clopidogrel resistance, defined as P2Y12 reaction unit (PRU) > or = 230, was 46.5%, and that of percent inhibition of PRU < 20% was 32.4%. At follow-up, the incidence of resistance by ARU value was 7.0%, 50.0% by PRU value, and 35.9% by percentage inhibition of PRU, respectively. The mean values of ARU (431.5 +/- 63.6 vs. 439.8 +/- 55.2; p = 0.216) and PRU (227.5 +/- 71.4 vs. 223.3 +/- 76.0; p = 0.350) were not significantly different before versus after antiplatelet-combination single-pill therapy. Five adverse events (3.5%) were observed during the study period. CONCLUSIONS: Combination single-pill antiplatelet therapy, which may reduce daily pill burden for patients after PCI with DES, demonstrated similar efficacy to separate dual-pill antiplatelet therapy.

Desensibilización rápida en pacientes con hipersensibilidad a aspirina sometidos a angioplastía coronaria: Reporte de cuatro casos / Rapid aspirin desensitization in patients with a history of aspirin hypersensitivity requiring coronary angioplasty: Report of four cases

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.

Adjunctive Cilostazol versus High Maintenance Dose of Clopidogrel in Patients with Hyporesponsiveness to Chronic Clopidogrel Therapy

PURPOSE: Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown. MATERIALS AND METHODS: We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35). RESULTS: Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0+/-10.2% versus 11.8+/-9.7%, p=0.61, and 286.3+/-54.7 versus 295.7+/-53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5+/-17.9% versus 28.3+/-16.6%, p=0.02, and 207.3+/-68.2 versus 241.3+/-76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7+/-8.7% to 15.8+/-18.4%, p=0.08, and from -18.6+/-58.0 to -61.9+/-84.3, p=0.08). CONCLUSION: Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy.

Optimal Anticoagulation during Off Pump Coronary Artery Bypass in Patients Recently Exposed to Clopidogrel

PURPOSE: The aim of this study was to find an optimal range of activated clotting time (ACT) during off-pump coronary artery bypass surgery (OPCAB) yielding ischemic protection without the risk of hemorrhagic complications in patients with recent exposure to dual antiplatelet therapy. MATERIALS AND METHODS: Three hundred and five patients who received aspirin and clopidogrel within 7 days of isolated multi-vessel OPCAB were retrospectively studied. Combined hemorrhagic and ischemic outcome was defined as the occurrence of 1 of the following: significant perioperative bleeding (>30% of estimated blood volume), transfusion of packed red blood cell (pRBC) > or =2 U, or myocardial infarction (MI). This was compared in relation to the tertile distribution of the time-weighted average ACT-212-291 sec (first tertile), 292-334 sec (second tertile), 335-485 sec (third tertile). RESULTS: The amount of perioperative blood loss was 937+/-313 mL, 1014+/-340 mL, and 1076+/-383 mL, respectively (p=0.022). Significantly more patients in the third tertile developed MI (4%, 4%, and 12%, respectively, p=0.034). The incidence of significant perioperative blood loss and transfusion of pRBC > or =2 U were lower in the first tertile than those of other tertiles without statistical significance. In the multivariate analysis, the first tertile was associated with a 52% risk reduction of combined hemorrhagic and ischemic outcomes (95% confidence interval: 0.25-0.92, p=0.027). CONCLUSION: A lower degree of anticoagulation with a reduced initial heparin loading dose should be carefully considered for patients undergoing OPCAB who have recently been exposed to clopidogrel.

Detection of Clopidogrel Hyporesponsiveness Using a Point-of-Care Assay and the Impact of Additional Cilostazol Administration after Coronary Stent Implantation in Diabetic Patients

BACKGROUND/AIMS: Impaired responsiveness to clopidogrel is common in patients with type 2 diabetes mellitus (DM). The aim of this study was to evaluate the clinical application of a point-of-care assay to detect impaired responsiveness to clopidogrel after coronary stent implantation in patients with type 2 DM. METHODS: We measured P2Y12 reaction units (PRU) with the VerifyNow point-of-care assay in 544 consecutive patients undergoing dual or triple (i.e., dual plus cilostazol) anti-platelet therapy after coronary stent implantation. High platelet reactivity (HPR) was defined as a PRU value > or = 240. RESULTS: The mean PRU values were 233.5 +/- 83.2 and 190.3 +/- 85.5 in patients undergoing dual or triple anti-platelet therapy, respectively (p < 0.001). Patients with DM manifested higher post treatment PRU values (238.3 +/- 82.4 vs. 210.8 +/- 86.8, p = 0.001) and a higher frequency of HPR (44.8% vs. 31.0%, p = 0.003) as compared to patients without DM. We also found that higher PRU values and a higher frequency of HPR were present in patients with DM who were undergoing both triple and dual anti-platelet therapy. However, the higher post-treatment PRU values observed in patients with DM decreased with triple anti-platelet therapy (219.4 +/- 82.5 vs. 247.9 +/- 81.1, p = 0.044). CONCLUSIONS: A point-of-care assay can detect elevated platelet reactivity and impaired responsiveness to clopidogrel in patients with type 2 DM. The addition of cilostazol to dual anti-platelet therapy may decrease post-treatment PRU values in patients with type 2 DM.

Similar observed CABG related bleeding complications in patients with and without clopidogrel loading doses / Complicaciones hemorrágicas asociadas a cirugía de revascularización miocárdica en pacientes con o sin dosis de carga de clopidogrel

Objective: Pretreatment with clopidogrel before percutaneous coronary intervention improves cardiovascular outcomes. However, some patients require elective coronary artery bypass graft (CABG) surgery instead, possibly increasing bleeding complications. We sought to assess the hemorrhagic complications and the length of hospital stay of stable patients receiving clopidogrel pretreatment that are referred for CABG. Methods: Between March and August 2007, 493 patients underwent diagnostic catheterization; 54 patients underwent elective CABG and were stratified according to clopidogrel loading dose (n = 20) or not (n = 34). Incidences of major hemorrhagic events and median post-surgical hospital stay were compared between groups. Results: TIMI Bleeding Index was not significantly different between the clopidogrel and no-clopidogrel groups (mean difference 0.46; 95% CI -0.89 to 1.82; p = 0.5). The incidence of major TIMI bleeding (70% vs. 73.5%; p > 0.9), peak hemoglobin loss > 5 g/dL (60% vs. 38.2%; p = 0.2), and blood transfusion > 4 units (20% vs. 26.5%; p = 0.7) in clopidogrel vs. no-clopidogrel group were not statistically different. Interestingly, the post-surgical length of stay was longer for the no-clopidogrel group (median of 5 vs. 7 days; p = 0.006). Conclusion: There was no significant evidence of increased bleeding or need for blood transfusion during CABG in patients pretreated with clopidogrel. The current practice of clopidogrel pretreatment before percutaneous coronary intervention does not significantly increase the risk of hemorrhagic complications in stable patients provided they can wait for at least 7 days before CABG. In a single center retrospective study, clopidogrel pretreatment was not found to be associated with increased bleeding or need for blood transfusion during coronary artery bypass graft surgery, suggesting that clopidogrel pretreatment before percutaneous coronary intervention does not significantly increase the risk of hemorrhagic complications in stable patients provided they can wait for 7 days before the surgery.

Objetivo: El pretratamiento con clopidogrel antes de la intervención precutánea coronaria, mejora los resultados cardiovasculares. Sin embargo, algunos pacientes que requieren cirugía programada de puente aortocoronario (CABG), posiblemente incrementan las complicaciones de sangrado. Nosotros buscamos valorar las complicaciones hemorrágicas y la duración de la estancia hospitalaria de los pacientes estables que reciben el pretratamiento de clopidogrel y que son enviados a CABG. Métodos: Entre los meses de marzo y agosto de 2007, 493 pacientes tuvieron diagnóstico de cateterización; 54 pacientes tuvieron una CABG programada y fueron estratificados con base en la dosis cargada de clopidogrel (n = 20) o no cargada (n = 34), y se compararon las incidencias de mayores eventos hemorrágicos y la media de estancia post operatoria entre ambos grupos. Resultados: El Indice de Sangrado TIMI no arrojó una diferencia significativa entre los grupos con clopidogrel y sin clopidogrel (la diferencia principal 0.46; 95% CI - 0.89 a 1.82; p = 0.5). La incidencia de mayor sangrado TIMI (70 % vs. 73.5%; p > 0.9) máxima pérdida de hemoglobina > 5 g/dL (60% vs. 38.2%; p = 0.2) y transfusión de sangre > 4 unidades (20% vs. 26.5%; p = 0.7) entre los grupos con clopidogrel y sin clopidogrel no fue estadísticamente diferente. Pero es interesante que el periodo de permanencia post operatoria fue más largo en el grupo que no fue tratado con clopidogrel (media de cinco vs. siete días: p = 0.006). Conclusión: No hay una evidencia significativa de incremento de sangrado o necesidad de transfusión sanguínea durante la CABG en pacientes pretratados con clopidogrel. La práctica actual del pretratamiento clopidogrel antes de la intervención precutánea coronaria no incrementa significativamente el riesgo de complicaciones hemorrágicas en pacientes estables siempre y cuando puedan esperar al menos siete días antes de la CABG. En un estudio simple de retrospectiva, no se encontró que el pretratamiento con clopidogrel se asociara con el incremento de sangrado o la necesidad de transfusión sanguínea durante la cirugía de puente aortocoronario, sugiriendo que el pretratamiento con clopidogrel antes de la intervención precutánea coronaria, no incrementa significativamente el riesgo de complicaciones hemorrágicas en pacientes estables siempre y cuando puedan esperar siete días antes de la cirugía.

Aspirina, ticlopidina e clopidogrel nas síndromes isquêmicas miocárdicas instáveis com e sem supradesnível do segmento ST / Aspirin, ticlopidine and clopidogrel in acute coronary syndromes

Os antiplaquetários representam importante estratégia de tratamento para pacientes com síndromes coronárias agudas.Em decorrência do importante papel da aspirina e das robustas evidências de benefício na doença isquêmica do coração, seu emprego passou a abranger praticamente todas as modalidades de tratamento clínico, procedimentos percutâneos invasivos e intervenções cirúrgicas relacionadas à doença arterial coronária. Porém, apesar dos benefícios decorrentes do uso de aspirina, pacientes com síndrome coronáriana aguda ainda apresentam risco considerável de eventos cardiovasculares indesejáveis a curto prazo, como morte, reinfarto e acidente vascular cerebral. Derivados tienopiridínicos como ticlopidina e clopidogrel agregaram benefícios ao tratamento desses pacientes, agindo de maneira sinérgica à aspirina. Com perfil mais seguro e menos efeitos adversos comparativamente à ticlopidina, o clopidogrel foi testado em estudos clínicos controlados, randopmizados conduzidos internacionalmente, envolvendo grande número de pacientes com síndromes coronárias agudas com indiscutível demonstração de benefícios em ampla gama de situações clínicas. Características farmacológicas...

Antiplatelet agents represent an important treatment strategy for patients with acute coronary syndromes. Due to the important role of aspirin and robust evidence of benefit in ischemic heart disease, its use was expanded to include virtually all forms of medical treatment, invasive percutaneous procedures and surgical interventions related to coronary artery disease. But despite the benefits of aspirin, patients with acute coronary syndromes still present considerable risk of short and long-term adverse cardiovascular events, such as death, reinfarction and stroke. Thienopyridine derivatives like ticlopidine and clopidogrel have added benefits to the treatment of these patients acting in synergism with aspirin. With a safer profile and less adverse effects as compared to ticlopidine, clopidogrel has been tested in controlled, randomized, international clinical trials involving a large number of patients with acute coronary syndromes clearly showing to be beneficial in a wide range of clinical situations. Pharmacological characteristics of clopidogrel as time of onset, need of metabolization for a therapeutic effect and irreversible platelet receptors blockade still limit its use, as well as the possibility of gene polymorphism of cytochrome P450, drug interactions and resistance to its effect and to aspirin. This review briefly addresses the main scientific studies evaluating the effects of these drugs in acute coronary syndromes with emphasis on new knowledge about aspirin and clopidogrel, drug interaction, use of genetic and platelet adhesiveness tests and the impact of recent scientific studies in the daily practice.

Farmacovigilancia activa en pacientes afiliados al sistema general de seguridad social en salud / Active pharmacosurveillance of patients affiliated to the Colombian general social security/health system

Objetivos Determinar los posibles resultados negativos asociados a la medicación mediante la metodología de búsqueda activa de posibles interacciones medicamentosas en bases de datos de pacientes afiliados al Sistema General de Seguridad Social en Salud. Métodos A partir de las bases de datos de dispensación de medicamentos de Audifarma S.A a unos 4 millones de usuarios del país, se hizo una revisión sistemática de estadísticas de una serie de medicamentos identificados por presentar interacciones de riesgo, dosis diferentes a las recomendadas o dispensación irregular. Los casos son socializados con las EPS responsables. Resultados Se encontró un caso de nefrotoxicidad por ácido zoledrónico; el 37,0 por ciento de los usuarios de clopidogrel recibían concomitantemente omeprazol, que reduce la efectividad del primero; el 29,9 por ciento de los pacientes que toman losartan están recibiendo dosis superiores a las recomendadas para su indicación; el 2,0 por ciento de los pacientes que toman metoprolol o verapamilo, los recibe simultáneamente, con riesgo de generar bradicardia sinusal, bloqueos auriculoventriculares o disfunción sistólica. Todos los casos fueron notificados a los responsables en la EPS que atienden estos pacientes. Discusión La farmacovigilancia activa permite optimizar recursos, prevenir eventos adversos que puedan potencialmente causar morbilidad importante o incluso letalidad o determinar problemas que podrían ser responsables del fracaso terapéutico. Este tipo de estrategia se anticipa a la aparición de posibles riesgos para el paciente por lo que se recomienda considerarla para reforzar los programas de vigilancia de uso de medicamentos en el país.

Objectives Determining negative results associated with medication through an active search of possible drug interactions in databases for patients affiliated to the Colombian general social security/health system. Methods Statistics related to Audifarma S.A. dispensation drug databases for about 4 million Colombian users were systematically reviewed for identifying drugs having known interactions involving risk, doses different from recommended ones or irregular dispensation. The pertinent health-care providing services were made aware of the above. Results There was one case of nephrotoxicity being caused by zoledronic acid. 37 percent of clopidogrel users concomitantly received omeprazole which reduces the former's effectiveness. 29.9 percent of patients who were taking losartan were receiving doses higher than the recommended ones. 2.0 percent of patients who were taking metoprolol or verapamil were simultaneously receiving them, at the risk of generating first-degree heart block, bradycardia, or systolic dysfunction. All these cases were notified to the pertinent health-care services. Conclusions Active pharmacosurveillance leads to resources being optimised, adverse events which can potentially cause morbidity or lethality being prevented or even determining problems which could be responsible for therapeutic failure. This type of strategy anticipates the appearance of possible risks for patients, meaning that drug use monitoring programmes in Colombia should be reinforced.

Influência dos stents farmacológicos na seleção de pacientes diabéticos tratados por meio de intervenção coronária percutânea / Influence of drug-eluting stents in the selection of diabetic pacients treated by percutaneous coronary intervention

Introdução: Os diabéticos representam um desafio para as intervenções coronárias percutâneas (ICP) em decorrência das elevadas taxas de reestenose, limitando a utilização desse procedimento em situações com grande perspectiva de recidiva, restringindo o emprego da técnica e predispondo à revascularização incompleta. Os stents farmacológicos contribuíram para a atenuação expressiva dessas limitações, podendo ter causado mudanças nas características dos casos tratados contemporaneamente. Assim, nosso objetivo foi comparar o perfil dos diabéticos tratados por ICP em dois momentos distintos desta década. Método: Estudo de coorte envolvendo 2.530 pacientes diabéticos revascularizados de forma consecutiva, divididos em dois grupos: grupo A, 1.309 pacientes revascularizados no período de 2006 a 2008; e grupo B, 1.221 pacientes tratados entre 2003 e 2005. Excluíram-se apenas os pacientes em que foram utilizados stents farmacológicos não disponíveis para uso comercial...

Background: Diabetic patients represent a challenge for percutaneous coronary interventions (PCI) due to the highrestenosis rates, which limit the use of the procedure in cases prone to recurrences, predisposing patients to incomplete revascularization. Drug-eluting stents (DES) have contributed for a significant improvement of these limitations and may have caused changes in the characteristics of patients treated contemporaneously. Thus, our objective was to compare the profile of diabetic patients treated intwo different periods of this decade. Method: This was a consecutive cohort study including 2,530 diabetic patientswho were divided into two groups: group A, 1,309 patients revascularized from 2006 to 2008; and group B, 1,221patients treated from 2003 to 2005. Only patients using DES not commercially available were excluded. Results: DES were more frequently used in group A (23% vs. 9%; P < 0.0001), which has a higher prevalence of insulin requiring patients (14% vs. 10%; P = 0.0001), chronic renal failure (20% vs. 10.1%; P < 0.0001), B2/C lesions(68% vs. 63%; P = 0.003), total occlusions (17% vs. 10%; P < 0.0001), stent diameter < 2.5 mm (26% vs. 22%; P = 0.01) and stent length > 24 mm (31% vs. 22%; P < 0.0001).Multivessel interventions (12% vs. 6%; P < 0.001) and complete revascularization (65% vs. 59%; P = 0.002) also prevailed in group A. Clinical hospital results were not different between groups. Conclusion: The greater availability of DES has led to significant changes in the profile ofdiabetic patients treated currently, expanding the indications for more complex patients and providing a more complete myocardial revascularization.

Anticoagulantes y antiplaquetarios en cirugía dermatológica / Anticoagulants and antiplatelet in cutaneous surgery

Introducción: Un porcentaje importante de pacientes sometidos a cirugía cutánea están en tratamiento anticoagulante o antiplaquetario. Las cirugías cutáneas tienen bajo riesgo de sangrado, pero los tratamientos antitrombóticos podrían causar mayor riesgo, lo que ha llevado a los cirujanos dermatólogos a suspender estas terapias antes de la cirugía. Por otro lado, un inadecuado manejo de estas terapias puede tener graves consecuencias tromboembólicas. Objetivo: Establecer los riesgos y beneficios de continuar o suspender el tratamiento antitrombótico antes de una cirugía dermatológica, con el fin de establecer una conducta preoperatoria segura. Materiales y métodos: Se realizó una revisión de la literatura médica bajo los términos anticoagulants, anticoagulation y anticoagulation therapy in dermatologic surgery o in cutaneous surgery. Se seleccionaron los 20 artículos que mejor respondían al objetivo del estudio, dando prioridad a los más recientes. Resultados: En los estudios analizados no se observó evidencia que sustente la suspensión de lo warfarina, clopidogrel o ácido acetilsalicilico antes de una cirugía cutánea, pero sí se reportan casos de complicaciones tromboembólicas asociadas a la suspensión de la terapia antitrombótica. No existe consenso respecto al valor del INR sobre el cual existe mayor riesgo de sangrado perioperatorio en la cirugía cutánea ni del mejor momento para controlarla. Conclusiones: La cirugía cutánea con anticoagulantes y antiplaquetarios es segura, pero la suspensión de estas terapias se puede asociar a complicaciones vasculares con riesgo vital. Sugerimos tomar un INR de control dentro de las 24 horas previos a la cirugía; en caso de valores mayores a 4, derivar al médico tratante para ajustar los niveles.

Introduction: A significant percentage of patients undergoing cutaneous surgery are on anticoagulants or antiplatelet therapy. Cutaneous surgery are at low risk of bleeding but antithrombotic treatments may cause increased risk which has led to dermatologic surgeons to discontinue these therapies before surgery. Moreover, inadequate management of these therapies can have serious thromboembolic consequences Objective: To establish the risks and benefits to continue or suspend the therapy prior to a dermatologic surgery in order to have o reliable preoperative behavior. Materials and methods: A search was conducted by the authors on medical literature under the terms anticoagulants, anticoagulation and anticoagulation therapy in dermatologic surgery or in cutaneous surgery. A total of 20 articles were selected giving priority to the most recent ones. Results: In the studies reviewed there was no evidence to support the suspension of warfarin, clopidogrel or aspirin before skin surgery but reported cases of thromboembolic complications associated with the suspension of antithrombotic therapy were found. There is no consensus on the INR value related with increased risk of perioperative bleeding in cutaneous surgery or the best time to control it Conclusions: Perform o cutaneous surgery under anticoagulant and antiplatelet treatment is safe; the suspension of these therapies may be associated with life-threatening vascular complications. An INR control within 24 hours prior to surgery is suggested. In case of an INR over 4 o recommendation of control with the physician to adjust levels seem reasonable.

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests / 대한진단검사의학회지

BACKGROUND: Dual therapy with aspirin and clopidogrel has emerged as the gold standard therapy for patients treated with drug-eluting stents (DES). However, there is variability in patients' responses to this antiplatelet therapy, and some patients continue to show ischemic recurrences after therapy. The purpose of the study was to compare the simultaneously obtained results of various platelet-function tests for assessing the prevalence of antiplatelet resistance in coronary artery disease patients undergoing DES therapy. METHODS: A total of 66 patients were administered a loading dose of aspirin, clopidogrel, and cilostazol at least 12 hr before stenting. The results of VerifyNow (Accumetrics, USA), multiplate analyzer (Dynabyte Medical, Germany), and vasodilator-stimulated phosphoprotein/P2Y12 (Biocytex, France) assays were compared with those of light transmission aggregometry (LTA) analysis. RESULTS: The P2Y12 reaction units and P2Y12% inhibition values obtained using the VerifyNow assay showed strong correlation (r) with the results of the LTA analysis. All tests results showed low concordance in defining the antiplatelet resistance in patients, and the degrees of agreement were as follows: 0 for aspirin reaction units; 0.25, P2Y12% inhibition; 0, aspirin-sensitive patients' identification test; 0.21, ADPtest; and 0.14, platelet reactivity index, expressed as the kappa statistics. The prevalence of aspirin and clopidogrel resistances in patients resulted in remarkable variations, from 0% to 22.7% and from 9.1% to 48.5%, respectively. CONCLUSIONS: The clinical usefulness of the different assays for the correct classification of patients in terms of antiplatelet resistance remains unclear. Further studies are required to determine the best method for correlating the occurrences of adverse ischemic events.

The Impact of Generic Clopidogrel Bisulfate on Platelet Inhibition in Patients with Coronary Artery Stents: Results of the ACCEL-GENERIC Study

BACKGROUND/AIMS: In patients with coronary artery stents, the cost of clopidogrel has been cited as a factor in the premature discontinuation of therapy. Thus, the introduction of lower-cost generic clopidogrel may increase patient compliance. However, platelet inhibition by generic clopidogrel has not been compared to the original clopidogrel formulation in patients with coronary artery stents. METHODS: We prospectively enrolled 20 patients receiving chronic therapy with the original clopidogrel bisulfate (Plavix(R)). After assessing patient compliance with Plavix(R), maintenance therapy was switched to generic clopidogrel bisulfate (Plavitor(R)). Platelet reactivity was assessed at baseline and 30-day after the switch using conventional aggregometry and the VerifyNow P2Y12 assay. RESULTS: All patients completed maintenance therapy with Plavitor(R). Before and after switching therapy maximal (36.5 +/- 7.9% vs. 39.8 +/- 16.2%, p = 0.280) and late platelet aggregation (23.5 +/- 10.9% vs. 29.1 +/- 18.3%, p = 0.156) with 5 micromol/L adenosine diphosphate (ADP) stimulus did not differ. Likewise, 20 micromol/L ADP-induced platelet aggregation and P2Y12 reaction unit in patients on Plavitor(R) therapy was comparable to that in patients on Plavix(R) therapy. However, Bland-Altman analysis showed wide limits of agreement between measured platelet reactivity on Plavix(R) vs. Plavitor(R) therapies. CONCLUSIONS: Among patients on Plavix(R) maintenance therapy with coronary stents, replacement with Plavitor(R) shows a comparable inhibition of ADP-induced platelet aggregation. However, due to poor inter-therapy agreement, between two regimens, physicians may be cautious when introducing generic clopidogrel bisulfate.

Stents libertadores de sirolimus com e sem cobertura polimérica: análise seriada com angiografia e ultrassom intracoronariano tridimensional / Sirolimus-eluting stents with and without polymeric coating: serial angiography and three-dimensional intravascular ultrasound analysis

Introdução: A presença de polímeros sintéticos em contato com a parede vascular tem sido associada a intensaresposta inflamatória local e a eventos adversos tardios. Entretanto, sua ausência pode comprometer a eficácia dos stents farmacológicos em suprimir a hiperplasia intimal. Avaliamos, com angiografia coronariana quantitativa (ACQ) e ultrassom intracoronariano (USIC), a eficácia do stent Vestasync™ (VES), liberador não-polimérico de sirolimus em baixa dose (55 µg), e do stent CypherTM (CYP), liberador de sirolimus polimérico em alta dose (140 µg). Método: Quinze pacientes com lesões primárias < 14 mm, em artérias coronárias nativas de 2,5 mm a 3,5 mm, foram tratados com VES e comparados a uma coorte histórica de 15 pacientes tratados com CYP. ACQ e USIC foram realizados pós-procedimento, aos 4 e 12 meses. Desfechos primários foram: perda tardia intrastent e porcentual de obstrução volumétrica intrastent. Resultados: As características clínicas eram semelhantes. O grupo VES tinha vasos menores (2,67 ± 0,32 mm vs. 2,98 ± 0,4 mm; P = 0,02). Aos 4 meses, o grupo VES mostrou tendência a maior perda tardia intrastent (0,30 ± 0,25 mm vs. 0,10 ± 0,3 mm; P = 0,06), mas porcentual de obstrução volumétrica intrastent similar ao do grupo CYP (2,8 ± 2,2% vs. 2,2 ± 3,8%; P = 0,60). Aos 12 meses, a perda tardia intrastent foi de 0,37 ± 0,24 mm no grupo submetido a implante de stent VES vs. 0,16 ± 0,36 mm no grupo submetido a implante de stent CYP (P = 0,074), e o porcentual de obstrução volumétrica intrastent foi de 4,0 ± 2,2% no grupo que recebeu stent VES vs. 2,4 ± 3,9% no grupo que recebeu stent CYP (P = 0,17). Não houve casos de reestenose binária...

Background: The long-term presence of the stent polymer in contact with the vessel wall has been associated to intense inflammatory response and late adverse events. However, absence of the stent polymer may compromise drug dose and drug delivery kinetics, leading to some efficacy issues. We aimed to compare, by means of serial quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), the efficacy of the novel nonpolymeric low-dose (55 µg) VESTAsync™ (VES) sirolimus-eluting stent, with the permanent polymer, high-dose (140 µg) Cypher™ sirolimus-eluting stent (CYP). Methods: Fifteen patients with single, de novo lesions < 14 mm, in native vessels of 2.5 mm to 3.5 mm diameter, were treated with VES and compared to a paired historical cohort of 15 patients treated with CYP. QCA and IVUS data were obtained post-procedure and at 4 and 12-month follow-up. Primary endpoints were the comparison of in-stent late luminal loss and percentage of intimal hyperplasia obstruction. Results: Clinical characteristics were similar between groups. The VES group had smaller vessels (2.67 ± 0.32 mm vs. 2.98 ± 0.4 mm; P = 0.02). At 4 months, the VES group had a tendency towards a higher in-stent late luminal loss (0.30 ± 0.25 mm vs. 0.10 ± 0.3 mm; P = 0.06) but similar IVUS % of intimal hyperplasia obstruction (2.8 ± 2.2% vs. 2.2 ± 3.8%; P = 0.60). At 12-months, in-stent late luminal loss was 0.37 ± 0.24 mm (VES) vs. 0.16 ± 0.36 mm (CYP), P = 0.074, and the IVUS % of intimal hyperplasia obstruction was 4.0 ± 2.2% (VES) vs. 2.4 ± 3.9% (CYP), P = 0.17. There were no cases of binary restenosis...

Nonresponders to clopidogrel therapy among Indian patients undergoing elective/adhoc angioplasty.

BACKGROUND: Clopidogrel has become the standard antiplatelet drug along with aspirin in patients undergoing coronary angioplasty; however, data regarding the nonresponse rate to clopidogrel therapy in Indian patients are limited. METHODS AND RESULTS: Platelet aggregation was measured at baseline and 2 and 24 hours post administration of bolus dose of 300 mg clopidogrel, followed by 75 mg once daily in patients undergoing elective or adhoc coronary angioplasty. Baseline platelet aggregation with 2.5 and 10 micromol/L ADP was 27.91 +/- 20.9% and 53.45 +/- 22.44%. Platelet aggregation at 2 hours and 24 hours with 2.5 micromol/L of ADP was 19.65 +/- 16.9% and 10.44 +/- 11.9%. The corresponding values with 10 micromol of ADP were 48.81 +/- 25.3% and 27.04 +/- 22.4%. Platelet aggregation was maximally inhibited at 24 hours with both 2.5 and 10 micromol/L of ADP. Marked interpatient variability in platelet aggregation in response to clopidogrel administration was observed and varied from -43 to 65%, -32 to 85% with 2.5 micromol/L at 2 hours and 24 hours and -65 to 53%, -35 to 97% with 10 micromol/L ADP at 2 hours and 24 hours. Nonresponse rate 2 hours after clopidogrel administration was 47.7%, and decreased to 29.2% at 24 hours post drug administration. CONCLUSION: Clopidogrel nonresponse is prevalent among Indian patients, and there is wide interpatient variability in platelet inhibition among individual patients. However, the clinical implications of these findings need to be substantiated in larger studies with clinical end points.

Anti-atherosclerotic effect of atorvastatin and clopidogrel alone and in combination in rats.

Atherosclerosis is a disease affecting arterial blood vessels due to the accumulation of macrophage white blood cells and low density lipoproteins. Effects of atorvastatin, a recently introduced lipid lowering statin was studied alone and in combination with clopidogrel in high fat diet fed atherosclerotic rats orally. Results showed significant reduction in total serum cholesterol and malondialdehyde levels and significant improvement in urine creatinine levels. Aortic cross sections of rats treated with clopidogrel alone showed reversal of atherosclerotic calcification. The same effect was observed with the combined treatment of clopidogrel and atorvastatin. Only atorvastatin treatment did not show any histological atheroprotective effect. Atorvastatin and clopidogrel alone and in combination have offered significant atheroprotective effect. No specific advantage was seen with combined treatment of atorvastatin and clopidogrel, moreover the advantages seen with independent drug administration also reduced with combined treatment.

Stents auto-expansíveis versus balão-expansível para tratamento de lesões em vasos de fino calibre: estudo com ultra-som intracoronário tridimensional / Self-expanding versus balloon-expandable stents for the treatment of small coronary vessels: a three-dimensional intracoronary ultrasound study

Introdução: Intervenção coronária pecutânea em vasos de fino calibre (VF) está associada a piores resultados imediatos e tardios, com elevadas taxas de reestenose. Estudos prévios têm sugerido que stents auto-expansíveis causam menos injúria vascular no momento do implante, com expansão de seus volumes com o tempo, gerando maiores áreas luminais que stents balão-expansíveis. A influência desses fenômenos em VF ainda é desconhecida. Objetivos: Avaliar as propriedades mecânicas e a eficácia do novo stent CardioMind no tratamento de lesões em VF em comparação ao stent balão-expansível Multi-link Pixel (Pixel). Método: Treze pacientes portadores de lesões únicas primárias < 14 mm de extensão, em artérias coronárias nativas < 2,5 mm de diâmetro, foram tratados com o stent CardioMind e comparados a uma corte histórica de 25 pacientes, com os mesmos critérios de inclusão, tratados com o stent Pixel. Ultrasom intracoronário (USIC) seriado foi realizado pós-procedimento e aos 7,3 +/- 1,0 meses. Resultados: A média das idades foi de 58,1 +/- 9,9 anos, com 60,5 por cento do sexo masculino e 39,4 por cento diabéticos. Ambos os stents produziram volumes de hiperplasia neo-intimal (HNI) smelhantes...

Background: Percutaneous coronary intervention in small vessels (SV) is associated with poor short- and long-term outcomes, with high rates of restenosis. Previous studies have suggested that self-expanding stents can cause less vessel injury at implantation, expanding their volumes over time, and leading to larger luminal areas than those of balloon-expandable stents. The influence of these phenomena on SV remains unknown. Objectives: To assess the mechanical properties and efficacy of the novel CardioMind™ stent in comparison with the balloon-expandable Multi-Link Pixel™ (Pixel) stent in the treatment of SV. Methods: Thirteen patients with single, de novo, < 14 mm length lesions in native coronary arteries < 2.5 mm in diameter were treated with the CardioMind™ stent and compared with a historical cohort of 25 patients, with the same inclusion criteria, treated with the Pixel™ stent. Intravascular ultrasound (IVUS) was performed serially after the procedure and at 7.3 ± 1.0 months of follow-up. Results: Mean age was 58.1 ± 9.9 years; 60.5% were male and 39.4% were diabetic. Both stents produced similar neointimal hyperplasia (NIH) volumes (indexed NIH volume: 1.45 ± 0.46 mm³/mm for CardioMind™ versus 1.66 ± 1.02 mm³/mm for Pixel™; p = 0.48). However, the CardioMind™ stentpresented a 12% expansion of its volume, leading to a...

Preditores e incidência de complicações vasculares após a realização de intervenções coronárias percutâneas: achados do registro IC-FUC / Predictors and incidence of vascular complications after percutaneous coronary interventions: findings from the IC-FUC registry

Introdução: As complicações vasculares (CV) são uma das principais causas de morbidade e mortalidade em pacientes submetidos a intervenções coronárias percutâneas (ICPs), porém estudos anteriores não refletem a prática atual. Objetivos: Avaliar a incidência de CV e seus preditores, em uma população de pacientes tratada com ICP contemporaneamente. Método: Estudo observacional de corte transversal, com implantes de stents coronários, de janeiro de 2000 a dezembro de 2007. As características clínicas e angiográficas e a evolução intra-hospitalar foram avaliadas e registradas em banco de dados informatizados. Foram excluídos aqueles com óbito hospitalar ou cirurgia cardíaca de urgência. CV foram definidas como sangramento maior, cirurgia vascular ou hematoma > 10 cm. Os dados foram analisados com SPSS 11,0, e as características dos pacientes com e sem CV foram comparadas com teste t de Student e teste do qui-quadrado. Os preditores independentes de CV foram identificados por análise de regressão logística múltipla. Resultados: Total de 4.595 pacientes com 5.485 stents implantados, com média de idade de 60,64 + - 10,65 anos e 32 por cento de mulheres. As ICPs foram realizadas pela via femoral...

Background: Vascular complications (VC) following percutaneous coronary intervention (PCI) are an important cause of morbidity and mortality. However, available data do not reflect current interventional cardiology practice. Objective: To determinate the incidence of VC and its predictors in a population treated with PCI in contemporary practice. Methods: Cross-sectional study with coronary stent implantation conducted from January/2000 to December/2007. Clinical and angiographic characteristics, as well as in-hospital evolution, were evaluated and recorded in a database. Exclusion criteria included in-hospital death and urgent heart surgery. VC were defined as major bleeding, vascular surgery or hematoma > 10 cm. Data were analyzed using SPSS 11.0 and the characteristics of patients with and without VC were compared using the Student's t test and chi-square test. Multiple Logistic Regression Analysis was performed to determinate the independent predictors of VC. Results: A total of 4,595 patients with 5,485 stents were included in this analysis. Mean age was 60.64 ± 10.65 years and 32% of the patients were female. The transfemoral approach was used in 95% of the PCIs and the transradial approach in 5%. Six French and 7 French introducers were used in 85% and 15% of the PCIs, respectively. A total of 162 (3.3%) patients experienced VC. The multivariate analysis determined that the only predictor for VC was the use of 7 French introducers (odds ratio = 3.05, 95% confidence interval = 1.2-7.8; p = 0.02)...