Safety of early surgery for geriatric hip fracture patients taking clopidogrel: a retrospective case-control study of 120 patients in China / 中华医学杂志(英文版)

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.

Clopidogrel versus prasugrel en síndrome coronario agudo tratado con angioplastia / Clopidogrel versus prasugrel in acute coronary syndrome treated with coronary angioplasty

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.

Alta reatividade plaquetária durante tratamento é preditora de eventos cardíacos em pacientes com stents farmacológicos / High on-treatment platelet reactivity predicts cardiac events in patients with drug-eluting stents

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.

Photoselective vaporization of the prostate in men taking clopidogrel

To evaluate the peri-operative morbidity of men taking clopidogrel who underwent photoselective vaporisation of the prostate [PVP]. A prospective database was collected. Between March 2005 and July 2010, 480 men underwent PVP. Of these, 18 men underwent PVP treatment while on clopidogrel. The surgery was carried out with either an 80W KTP laser or a 120W lithium triborate laser. In the peri-operative period there were no complications related to PVP. There were no urinary tract infections, nor did any patient require bladder re-catheterisation. No cardiovascular events were reported within 3 months of the procedure. At 3 months post operatively, the International Prostate Symptom Score +/- standard deviation had improved from was 17.5 +/- 10.6 to 9.2 +/- 6.1 P<0.05. While the Quality of Life +/- standard deviation improved from 4.7 +/- 1.2 to 2.2 +/- 1.5 P<0.01. The maximum flow rate [Qmax], and post void residual volume [PVR] improved from 6.2 +/- 3.0 mL/s to 19.7 +/- 9.1 mL/s [P<0.01], and 140 +/- 102 mL to 59 +/- 77 mL [P<0.05], respectively. PVP is a safe and efficacious in the treatment of high risk patients with bladder outlet obstruction. Further, the ability to continue therapeutic anticoagulation and anti-platelet agents, is a significant advantage over Holmium enucleation of the prostate and conventional transurethral resection of the prostate. Larger studies with greater numbers of patients are required prior to PVP becoming the gold standard for high-risk patients with bladder outlet obstruction

The Effect of Aspirin Alone or Aspirin Plus Additional Antiplatelets Therapy on Upper Gastrointestinal Hemorrhage / 대한소화기학회지

BACKGROUND/AIMS: The increasing incidence of cardiovascular disease has led to an increase in the frequency of upper gastrointestinal (GI) hemorrhage due to the use of antiplatelet agents. This study examined the clinical characteristics of patients with upper GI hemorrhage who were administered aspirin alone or a combination treatment of antiplatelet agents. METHODS: A 656 patients who underwent drug-eluting coronary stenting at Ewha Mokdong Hospital in 2008 were divided into three groups according to the antiplatetlet agents used after the intervention; groups of aspirin alone, aspirin plus clopidogrel, and aspirin, and clopidogrel plus another antiplatelet agent, respectively. Patients admitted with GI hemorrhage in the same period without a medication history of antiplatelet or nonsteroidal anti-inflammatory drugs were used as the control hemorrhage group. The medical records were reviewed. RESULTS: Significant GI symptoms were observed in 21.1% of total patients, of whom 48.2% had ulcers. The upper GI hemorrhage rate was 3.8%. There was no significant difference in the hemorrhage rate between three groups. Compared to the control hemorrhage group, the endoscopic variables of the antiplatelet-related hemorrhage group were not significantly different. However, the Helicobacter pylori infection rate was lower, the admission period was longer, and the mortality rate was higher in the antiplatelet-related hemorrhage group (p<0.05, respectively). There was no direct association between restarting or discontinuance of antiplatelets after the hemorrhage event and mortality. CONCLUSIONS: Adding other antiplatelet agents to aspirin did not increase the hemorrhage rate. However, active diagnostic and therapeutic efforts are recommended in patients with GI symptoms during antiplatelet therapy.

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.

GastrointentinaI bleed with clopidogrel and aspirin.

Anti-platelet drugs have been used to prevent thrombosis of systemic to pulmonary artery shunts. Aspirin has traditionally been used. Clopidogrel is being studied as an alternative and in combination with aspirin for shunt patients. We report a near fatal gastro-intestinal bleed in a patient with shunt and on aspirin and clopidogrel. This combination has been known to produce similar bleeds. The authors recommend caution in combining them. Prospective studies currently underway should evaluate this aspect of the antiplatelet drugs.

Timing of coronary artery bypass grafting in patients on clopidogrel therapy, a review

Clopidogrel in addition to aspirin is important pharmacological treatment of patients with severe coronary artery disease or recent coronary artery stenting. However, due to fear for preoperative bleeding, cardiac surgeons routinely tend to hold clopidogrel before cardiac surgery. The goal of this manuscript is to review current literature on this issue

A case of ticlopidine induced acute cholestatic hepatitis and pure red cell aplasia / 대한간학회지

Ticlopidine inhibits platelet aggregation and provides beneficial secondary prevention of cerebrovascular and coronary artery disease. Frequently reported adverse effects of ticlopidine include diarrhea, nausea, and rash. However, to our knowledge, there are only a few published reports of the simultaneous occurrence of cholestatic hepatitis and pure red cell aplasia. Here we report a patient with simultaneous severe cholestatic hepatitis and pure red cell aplasia associated with ticlopidine. Although these adverse effects are rare, periodic hematological and liver function tests are recommended after starting ticlopidine.

Clopidogrel-induced Spontaneous Spinal Epidural Hematoma

The hemorrhagic side effects associated with the use of clopidogrel are within the acceptable range and occur mainly at skin or gastrointestinal sites. We report a case of spontaneous spinal epidural hematoma (SSEH) in a 60-yr-old woman who was treated with clopidogrel for frequent transient ischemic attacks. To our knowledge, this is the second reported case of clopidogrel-induced SSEH. The patient's symptoms and past history of clopidogrel use suggested the diagnosis and made the procedure proceed quickly to operate SSEH 9 hr after the onset of paraplegia. The outcome was excellent. Therefore, with the popularity of antiplatelet prescription, physicians should keep in mind and urgently treat this unusual but critical side effect.

Bleeding post coronary artery bypass surgery: Clopidogrel-Cure or culprit?

Clopidogrel, in addition to aspirin, has become a common treatment of acute coronary syndrome and for stent thrombosis prevetion, when given before precutaneous transluminal coronary angioplasty. However, some patients turn out to have surgical coronary artery disease and are sent for coronary artery bypass grafting [CABG] where the irreversible effect of aspirin and clopidogrel on platelet function becomes a concern. This study was conducted to evaluate the role of preoperrative use of clopidogrel in bleeding complications after CABG. A total of 462 patients who underwent CABG between 2001 and 2003 were studied as a retrospective cohort. Comparison was made between patients who had taken clopidogoral within 7 days of surgery [n=162], and those who were not exposed to clopidogeral [n=300]. Chest tube output and bleeding index [a modified TIMI criteria], were primary outcomes measured. Our data showed that patients taking clopidogrel within 7 days of surgery have a higher bleeding index than those who were not exposed to the drug [p=0.024]. Similarlly, chest tube output was significantly higher in those who were exposed to clopidogrel within 7 days compared to those not taking clopidogrel [p=0.01]. To further dissect this rela tionship, we divided our population into three categories. We found that patients taking clopidogrel within 3 days prior to CABG [immediate exposure] have a higher bleeding index and TIMI major bleeding than either patients taking the drug between 3 and 7 days [recent exposure] or patients not exposed to clopidogrel at all [p=0.009] and 0.03 respectively for inter-groups comparsion]. The same was true for chest tube output [p=0.05 and 0.01 respectively]. Clopidogrel increased the risk of post-CABG bleeding if taken within three days prior to surgery but not if taken before that

Oral anti platelet drugs in dermatology

An up-to-date overview of antithrombotic drugs, with their currently reported beneficial cutaneous effects and skin side effect, is presented. Attempts to balance traditional pharmacodynamic concepts with the newly described empiric benefits are made. A concise, current and useful reference for dermatologists with an interest in dermatopharmacology and the practicing physician in the field of wound care, vasculitides and skin involvement of internal diseases is tried to be achieved

Fibroelastoma de valva mitral como causa de acidente vascular isquêmico transitório / Fibroelastoma of the mitral valve as a cause of transient ischemic stroke

A 44-year-old woman had a transient ischemic stroke, fibroelastoma of the mitral valve being the source of the embolus. The patient evolved with neutropenia induced by ticlopidine after 10 days of treatment. We report the major clinical features, therapeutical options, and medicamentous toxicity resulting from the use of antiplatelet drugs

Prevención de recurrencias en pacientes con ACV isquémico: estudio clínico con ticlopidina en Argentina (ECTA) / Prevention of recurrence in ischemic stroke: a clinical study with ticlopidine in Argentina (ECTA)

En 567 pacientes seleccionados prospectivamente, que padecieron una lesión encefalovascular isquémica reciente se evaluó la eficacia y seguridad de la ticlopidina en la prevención de recurrencias de ACV, IAM y muerte vascular. Los pacientes fueron controlados durante tres meses, período estimado para evaluar las recurrencias y la máxima incidencia de efectos adversos serios, que en su gran mayoría ocurren en los primeros meses después del ACV. Por razones éticas no se diseñó un grupo de placebo y los resultados obtenidos fueron comparados con los del grupo de control de estudios CATS (4), por meta-análisis. El índice de reducción de riesgo alcanzó el 28,2 por ciento (con un intervalo de confianza del 95 por ciento ), siendo efectiva en los dos sexos. En algún momento a lo largo del estudio, se registraron reacciones adversas en un 16 por ciento considerándose causa de interrupción definitiva en un 4 por ciento