Evaluation of Perioperative Antithrombotic Management in Patients Undergoing Moderate to High Risk Surgery

OBJECTIVE: The perioperative management of antithrombotic therapy is often challenging and it requires a fine balance between the risk of hemorrhage and thrombosis. We aimed to evaluate the antithrombotic management for moderate to high risk patients in real world setting. METHODS: Among the patients who were consulted to the neurologist for the evaluation of perioperative risk from 2010 to 2012, patients undergoing moderate to high risk surgery and taking antithrombotics within 30 days were identified. We analyzed the timing of discontinuation and reinitiation of antithrombotic drugs before or after surgery as well as the status of bridging therapy. In addition, the conformity with the guideline suggested by American College of Chest Physicians was assessed. The rate of thromboembolic event and major hemorrhage were also investigated. RESULTS: A total of 329 patients were included. The concordance rate of warfarin stop and restart time with guideline was 23.4% and 10.3%, respectively. Continuing aspirin in patients undergoing coronary artery bypass surgery or non-cardiac surgery in patients with high risk for cardiovascular events were 59.2% and 2.6%, respectively. Bridging therapy was adopted in 92.9% and 81.2% in patients who had received anticoagulant before surgery and who were at high and low risk thromboembolism, respectively. In entire cohorts, 30-day incidence of major bleeding and thromboembolic event were 31.9% and 3.0%. Co-morbid renal disease were shown as independent predictor for major bleeding (adjusted OR 2.65. 95% CI 1.33-5.28). CONCLUSION: The concordance rate with guideline regarding perioperative antithrombotic use was low and bridging therapy was prevalent in patients undergoing moderate to high risk surgery.

Evaluation of bleeding following dental extraction in patients on long‑term antiplatelet therapy: A clinical trial.

Objective: The aim of this trial was to evaluate the bleeding after dental extractions among patients on uninterrupted antiplatelet therapy. Materials and Methods: A total of 190 patients under oral antiplatelet drugs requiring extraction of a single molar tooth were randomly assigned to two groups. Group A consisted of 95 patients on uninterrupted antiplatelet therapy and Group B consisted of 95 patients who have discontinued antiplatelet medication 5 days prior to extraction. The bleeding time of all patients was checked prior to extraction. The surgical procedure involved simple extraction of a single molar tooth under local anesthesia. The extraction socket was sutured with 3–0 silk. Pressure pack with gauze was given for 1 h. Bleeding after 1 h, 24 h, 48 h, and 5 days were compared between two groups. Chi‑square test was used to compare the variables. P <0.05 was taken as significant. Results: None of the patients in either group had any significant uncontrollable bleeding after extraction. Conclusion: Hence, we recommend routine single tooth extractions in patients on long‑term antiplatelet medication, without interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding.

Antiplatelet therapy: present status and its future directions.

Anti-platelets drugs play an important role in the prevention or treatment of cardiovascular diseases e.g. coronary artery disease, stroke, etc., which cause high mortality and morbidity in the present day world. These drugs either inhibit the platelet activation, aggregation or other signaling pathways, thereby inhibiting the clot formation. The anti-platelet drugs currently used are aspirin, ADP receptor inhibitors (ticlopidine and clopidogrel)and glycoprotein (GP)IIb/IIIa inhibitors (abciximab, tirofi ban and eptifi batide). Aspirin was and still continues to be the main anti-platelet therapy. A combination regimen of aspirin and clopidogrel is commonly used for the prevention of platelet activation, thrombosis and stroke. However, many of the current anti-platelet drugs face limitations due to narrow therapeutic window and limited effi cacy. The four possible targets for novel anti-platelet action are: Inhibition of agonist generation, receptor inhibition, G protein inhibition and inhibition of enzymatic cascades. Newer P2Y12 antagonists e.g. prasugrel, ticagrelor, cangrelor, etc., have better effi cacy and low bleeding risk. The thrombin receptor (PAR1 and 4) inhibitors are said to decrease the hemorrhagic complications. Drugs which inhibit TXA2 Synthase or TXA2 receptor are also promising in their anti-platelet action. Another novel group is of collagen receptor antagonists such as GPVI antagonists, GPIb receptor antagonists, etc. The other targets being explored are von Willebrand Factor antagonists, platelet Gq antagonists, etc. However, there still lies a bundle of unresolved issues regarding the effi cacy and safety, optimal dosage, administration requirements, combination therapy, clinical evaluation, cost-effectiveness, and the resistance phenomena of these drugs.

Doble antiagregación bajo la lupa: beneficio real y subgrupos de riesgo / Dual Antiplatelet Therapy Under Scrutiny: Real Benefit and Risk Subgroups

Los estudios CURE, TRITON-TIMI 38 y PLATO han demostrado beneficio clínico con el uso de doble antiagregación plaquetaria con clopidogrel, prasugrel o ticagrelor adicionados a la aspirina en pacientes con síndrome coronario agudo y han contribuido a incrementar exponencialmente su prescripción. La publicación de nuevos ensayos aleatorizados con hallazgos que contrastaron con los beneficios obtenidos en estos estudios y de algunos artículos de opinión que han cuestionado la validez de los resultados hace necesario, al menos, replantear su indicación generalizada y el real beneficio clínico de estas drogas. En este artículo se discuten los resultados de estos tres ensayos, como también los cuestionamientos metodológicos que se les han efectuado, focalizando en el real beneficio clínico de estas drogas. Asimismo, considerando que en determinados subgrupos puede existir perjuicio, se discute este punto y se propone un esquema sencillo que permita seleccionar a los pacientes que más se benefician con estos tratamientos.

CURE, TRITON-TIMI 38 and PLATO studies have demonstrated clinical benefit with the use of dual antiplatelet therapy with clopidogrel, prasugrel or ticagrelor in addition to aspirin in patients with acute coronary syndrome, and have contributed to exponentially increased prescription. The publication of new randomized trials with findings contrasting with the benefits obtained in these studies and of some opinion articles which have questioned the validity of the results, make it necessary, at least, to rethink the general indication and actual clinical benefit of these drugs. In this article we discuss the results of these three trials as well as the methodological objections that have been posed to them, focusing on the real clinical benefit of these drugs. Likewise, the probability of prejudice in certain subgroups is discussed and a simple scheme that allows the selection of patients most likely to benefit from these treatments is postulated.

Discontinuation of Anticoagulant or Antiplatelet Therapy for Transrectal Ultrasound-Guided Prostate Biopsies: A Single-Center Experience

PURPOSE: Historically, it was thought that hemorrhagic complications were increased with transrectal ultrasound-guided prostate biopsies (TRUS biopsy) of patients receiving anticoagulation/antiplatelet therapy. However, the current literature supports the continuation of anticoagulation/antiplatelet therapy without additional morbidity. We assessed our experience regarding the continuation of anticoagulation/antiplatelet therapy during TRUS biopsy. MATERIALS AND METHODS: A total of 91 and 98 patients were included in the anticoagulation/antiplatelet (group I) and control (group II) groups, respectively. Group I subgroups consisted of patients on monotherapy or dual therapy of aspirin, warfarin, clopidogrel, or low molecular weight heparin. The TRUS biopsy technique was standardized to 12 cores from the peripheral zones. Patients completed a questionnaire over the 7 days following TRUS biopsy. The questionnaire was designed to assess the presence of hematuria, rectal bleeding, and hematospermia. Development of rectal pain, fever, and emergency hospital admissions following TRUS biopsy were also recorded. RESULTS: The patients' mean age was 65 years (range, 52 to 74 years) and 63.5 years (range, 54 to 74 years) in groups I and II, respectively. The overall incidence of hematuria was 46% in group I compared with 63% in group II (p=0.018). The incidence of hematospermia was 6% and 10% in groups I and II, respectively. The incidence of rectal bleeding was similar in group I (40%) and group II (39%). Statistical analysis was conducted by using Fisher exact test. CONCLUSIONS: There were fewer hematuria episodes in anticoagulation/antiplatelet patients. This study suggests that it is not necessary to discontinue anticoagulation/antiplatelet treatment before TRUS biopsy.

Novas evidências em antitrombóticos na fibrilação atrial 2010 / New evidences in antithrombotics for atrial fibrillation 2010

JUSTIFICATIVA E OBJETIVOS: A principal arritmia cardíaca em pacientes acima dos 60 anos de idade é a fibrilação atrial (FA). Com o aumento da expectativa de vida, estima-se que 30% da população acima de 65 anos, apresentará FA, e esta é associada a um risco de eventos cardio embólicos anuais ao redor de 6% ao ano. Devido as complicações cardio embólicas, o tratamento de eleição é o uso de fármacos antitrombóticos, os quais estão incluídos, os antiplaquetários e os anticoagulantes, baseados na estratificação de risco do paciente. Até o momento, a terapia de eleição na prevenção de eventos cardio embólicos são os antagonistas de vitamina K (AVK); entretanto, devido sua janela terapêutica estreita, controle laboratorial rigoroso, interação com outros medicamentos e principalmente dificuldade de utilização em pacientes idosos, torna-se um fator limitador na prática clínica diária. Dentro deste cenário, novos antitrombóticos estão sendo desenvolvidos no intuito de melhorar o cuidado e a qualidade de vida dos portadores de FA e talvez substituir os AVK. CONTEÚDO Artigos publicados entre 1969 e 2009 foram selecionados no banco de publicações Medline, através das palavras-chaves fibrilação atrial, antitrombóticos, anticoagulantes e antiplaquetários, assim como diretrizes internacionais foram buscadas no link http://sumsearch.uthscsa.edu. CONCLUSÃO: O desenvolvimento de novos antitrombóticos, através de ensaios clínicos aleatórios, talvez em um futuro próximo possibilite a utilização e implementação de forma sistemática na pratica clinica destes novos medicamentos, como, por exemplo, os inibidores diretos da trombina, inibidores diretos e indiretos do fator Xa, superando as limitações dos AVK.(AU)

BACKGROUND AND OBJECTIVES: The main cardiac arrhythmia in patients over 60 years of age is atrial fibrillation (AF). With increasing life expectancy, it is estimated that 30% of the population over 65 years, will present FA, and this is associated with a risk of cardioembolic events annually around 6% per annum. Because of cardioembolic complications, the treatment of choice is the use of antithrombotic drugs, which are included, the antiplatelet agents and anticoagulants, based on risk stratification of patients. So far, the therapy of choice in the prevention of cardioembolic events are antagonists of vitamin K (AVK), however, due to its narrow therapeutic window, under strict control, interaction with other drugs and especially difficult to use in elderly patients, it is a limiting factor in clinical practice. Within this scenario, new antithrombotic agents are being developed in order to improve care and quality of life of patients with AF and perhaps replace the AVK. The development of new antithrombotic drugs through clinical trials, perhaps in the near future allow the use and implementation in a systematic manner in the clinical practice of these new drugs, such as the direct thrombin inhibitors, indirect and direct inhibitors of factor Xa, overcoming limitations of AVK.CONTENTS: Articles published from 1969 to 2009 were selected in the MedLine database, using the keywords Atrial Fibrillation, antithrombotics, anticoagulants, antiplatelets in the MedLine database as well as search for international guidelines in http://sumsearch.uthscsa.edu.CONCLUSION: The development of new antithrombotic drugs through clinical trials, perhaps in the near future allow the use and implementation in a systematic manner in the clinical practice of these new drugs, such as the direct thrombin inhibitors, indirect and direct inhibitors of factor Xa, overcoming limitations of AVK.(AU)

Prophylactic Antibiotics, Anticoagulants and Antiplatelets for GI Endoscopy / 대한소화기내시경학회지

This review provides general recommendations, based on the literature, on antibiotic prophylaxis, anticoagulants and antiplatelets for GI endoscopy. Antibiotic prophylaxis is recommended for patients at high risk of infection - ERCP with incomplete drainage, ERCP with sterile pancreatic fluid collection (which communicates with the pancreatic duct), pancreatic pseudocyst drainage, EUS-FNA of cystic lesions, percutaneous endoscopic feeding tube placement and cirrhosis with acute GI bleeding. Prophylactic antibiotics are no longer recommended for GI endoscopy to prevent infectious endocarditis. To decide how to manage anticoagulants and antiplatelets during endoscopic procedures, the risk of an adverse ischemic event or a thromboembolic complication and the risk of bleeding must be weighed. For a low-risk procedure, no adjustments in anticoagulation and antiplatelets need to be made. For a high risk procedure, it is recommended to discontinue warfarin 3 to 5 days before the procedure and clopidogrel 7 to 10 days before. Low molecular weight heparin may be used as a bridge before endoscopy in patients with a high risk of a thromboembolism. In the absence of a pre-existing bleeding disorder, endoscopic procedures may be done in patients taking aspirin or other NSAIDs. Further controlled clinical studies are needed to clarify aspects of these recommendations.

Tratamiento combinado con antitrombóticos en la prevención secundaria del ictus isquémico: [revisión] / Combined treatment with antithrombotics in secondary prevention of the isquemic stroke: [review]

El ictus isquémico constituye un problema sanitario de primer orden debido a su alto riesgo de recurrencia. La búsqueda de estrategias eficaces y seguras para la prevención de eventos vasculares en los pacientes con un ictus isquémico debe ser una prioridad, con el objetivo de disminuir la mortalidad y discapacidad asociada con el mismo. Diversos estudios han analizado el tratamiento combinado con antitrombóticos para intentar mejorar la eficacia de estos fármacos en la prevención secundaria de eventos vasculares tras un primer ictus isquémico. En este trabajo se revisa el estado actual de la evidencia científica en cuanto a la terapia combinada con antitrombóticos en pacientes con un primer ictus isquémico...

Ischemic stroke constitutes a fundamental health issue due to its high level of recurrence. Developing efficient and safe strategies to prevent vascular episodes in patients with ischemic stroke must be a top priority, with the purpose of diminishing associated mortality and disability. Several studies have examined combined antithrombotic therapy in depth, trying to improve its efficacy in secondary prevention of vascular events after a first ischemic stroke. This work reviews the current state of clinical evidence related to combined antithrombotic therapy in patients presenting a first ischemic stroke...

The Effect of Preoperative Clopidogrel on the Postoperative Bleeding after OPCAB / 대한흉부외과학회지

BACKGROUND: Clopidogrel is widely used just before coronary artery bypass surgery, yet its pharmacological effect can cause postoperative bleeding-related complications. The purpose of this study was to find the effect of preoperative clopidogrel exposure on the blood transfusion requirement and on the rate of reexploration for bleeding control and the rate of readmission caused by bleeding in patients who undergo off-pump coronary artery bypass surgery (OPCAB). MATERIAL AND METHOD: This study included 103 patients who had been on clopidogrel preoperatively and they underwent OPCAB by one surgeon from January, 2005 to November, 2007. We divided the patients into two groups. Group 1 consisted of 45 patients who stopped cloidogrel 5 days before surgery and group 2 consisted of 58 patients who were taking clopidogrel within 5 days before surgery. Two groups were compared in terms of the bleeding related reoperation rate and the readmission rate, the amount of postoperative bleeding and the required amount of transfusion. RESULT: There were no significant differences between the two groups concerning the demographic, echocardiographic and hematologic features. There were no significant differences in the postoperative bleeding amount, but the amount of required transfusion was greater in group 2 (p=0.018). While group 1 showed a 0% reoperation rate for hemostasis and a 0% readmission rate as related to postoperative bleeding, group 2 showed a 6.9% reoperation rate and a 5.2% readmission rate, but there were no statistically significant differences between the two groups. CONCLUSION: Continuous use of clopidogrel did not cause postoperative major bleeding, but it can increase the amount of bleeding and the amount of required transfusion postoperatively. We think that discontinuation of clopidogrel for a while before elective OPCAB can help the patient's postoperative recovery.

The Change of PAC-1 and P-selectin Expression after Initiation of Antiplatelets in Patients with Acute Ischemic Stroke

BACKGROUND: The purpose of this study was to evaluate the time course of PAC-1 and the P-selectin expression after the initiation of antiplatelets in acute ischemic stroke. METHODS: We serially measured PAC-1 and the P-selectin expression level using flow cytometry immediately before and at: one day, seven days, and one month after starting antiplatelets in 25 patients with acute cerebral infarctions. RESULTS: The P-selectin expression increased initially (p<0.05) and then from the seventh day, it began to decrease continually (post-hoc analysis, p<0.05). However, the PAC-1 expression did not reveal significant alterations during the follow-up period of one month. CONCLUSIONS: Although the P-selectin expression rapidly declined, the PAC-1 expression remained elevated for one month. Our results suggest that the P-selectin may be useful in monitoring platelet inhibition during the early period after cerebral infarction.

Secondary prevention of stroke with antiplatelets - An economics analysis

The burden of stroke therapy has been ameliorated to a great extent with the use of anti-platelet agent for secondary prevention. The cost of health care in general is rising. Economic factors play a significant role in the cost of hospitalization for stroke patients in general and in the choice of anti-platelet agents in particular. The goal of this study is (1) to compare the total costs associated with prescription of anti-platelet drugs, (2) to determine the number-needed-to-treat (NNT) with each of the different anti-platelet drugs in the market: aspirin, dipyridamole, ticlopidine, cilostazol and clipidogrel; and (3) determine the direct cost incurred with the use of each anti-platelet drug. To do this, a cost-minimization analysis of total costs was done. Data were collected from all randomized control trials published evaluating drug treatment vs. placebo. Event rates, absolute risk reduction and NNT were calculated. Cost computation was done from direct medication and additional expenses were included for treatment or monitoring of adverse effects. Transportation and professional fees were excluded. The results of the study showed the following: NNT for ASA: 33; DP: 50; DP-ASA: 17; Ticlopidine: 33; Cilostazol: 17 and Clopidogrel: 100. Direct cost for two years treatment for ASA: Php13,678.90; DP: Php18,615.00, DP-ASA: Php3l,615.00, Ticlopidine: Php77,060.00, Cilostazol: Php64,240.00 and Clopidogrel: Php64,240,00. Total costs to prevent 1 stroke in two years treatment for ASA: Php451,403.70, DP: Php930,750.00, DP-ASA: Php537,455.00, Ticlopidine: Php2,542,980.00, Cilostazol: Phpl,092,080.00 and Clopidogrel: Php6,424,000.00. We conclude that aspirin should be the mainstay of therapy in preventing secondary stroke. (Author)

The Effects of Therapeutic Duration of Combined Antiplatelets, Aspirin and Ticlopidine, on Coronary Stent Restenosis

BACKGROUND: One of most important mechanisms of coronary stent restenosis is neointimal hyperplasia. Although the process of neointima formation is not fully understood, a special role has been advocated for adherent platelets. Previous studies have shown a clear benefit with combined antiplatelet therapy such as aspirin plus ticlopidine in reducing the rate of thrombotic occlusions of stented vessels. The purpose of this study was to evaluate the effects of duration of antiplatelet regimens on coronary stent restenosis. METHODS: After successful placement of coronary artery stents in 222 patients, we performed follow-up coronary angiograms in 99 patients (42.3%). Forty-six patients were randomly assi-gned to receive aspirin and ticlopidine for four weeks (Group I: 54+/-9 years: M 38, F 8) and 48 patients for 6 months (Group II: 58+/-8 years: M 38, F 10). RESULTS: There were no significant differences in clinical and procedural variables or coronary lesion characteristics before and after stenting. At 6 months after stenting, minimal luminal diameter was 2.16+/-0.93mm in Group I and 2.04+/-1.07mm in Group II (p-0.57). Late lumen loss was 0.80+/-1.07mm in Group I and 0.92+/-1.11mm (p-0.58) in Group II. The stent restenosis rate of Group I at 28.3% and that of Group II at 29.2% were not statistically significant between the two groups (p-0.92). CONCLUSIONS: The therapeutic duration of combined antiplatelet regimen with aspirin and ticlopidine after coronary stent does not affect stent restenosis rate.

Initial Results after Implantation of Coronary Artery Stents with Antiplatelet Agents

Backgound: The placement of stents in coronary arteries has been shown to reduce acute closure and restenosis in comparison to balloon angioplasty. However, clinical use of intracoronary stents is impeded by the subacute stent thrombosis and hemorrhagic complications associated with the anticoagulant regimen. It's known that the complete stent deployment with high pressure inflation and new antiplatelet agents are effective in reduction of subacute thrombosis and hemorrhage. So we evaluated initial results (success and complication rate) after high pressure-stent deployment with new anticoagulation protocol. METHODS: One hundred and ninety one patients with 201 lesions were treated with 231 stents of various types. The high pressure balloon inflation and antiplatelets agents were used in all cases. Final high pressure balloon inflation guided by IVUS were performed in 23 consecutive cases with incomplete stent deployment according to angiographic findings. RESULTS: 1) The indications of stenting (n=210) were De novo in 124 (59%), bailout procedure in 57 (27%), suboptimal result after PTCA in 19 (8%), and restenosis after PTCA in 14 (6%). The location of lesions were LAD in 101, RCA in 67, circumflex in 28, ramus intermedius in 3, and LMT artery in 2 lesions. Angiographic morphologic characteristics were type A in 2, type B in 158 (B1: 57, B2: 101), and type C in 22 lesions. 2) The angiographic and clinical success rate was 96% (192/201) and 92% (186/201) respectively. 3) In angiographic analysis, the baseline average reference vessel dirmeter was 3.33+/-0.35 mm. Baseline minimum lumen diameter (MLD) was 0.58+/-0.29 mm, with baseline percent diameter stenosis of 82.86+/-8.64%. The final stent diameter was 3.37+/-0.29 mm, with mean final percent stenosis of 0.63+/-8.25. The mean MLD after stenting was significantly increased (p12atm) (p<0.001). The length of lesions in GR I (cook), GR II, and Micro II stents were significantly longer than ones in PS, Cordis, Wiktor, Nir (p<0.001). 4) In intravascular ultrasound analysis, the mean lumen CSA at the tightest point within stent increased 11%, from 8.4+/-2.4 mm2 at the intial intravascular ultrasound to 9.4+/-2.1 mm2 at the final intravascular ultrasound (p<0.001). 5) The procedural and postprocedural complications were 2 acute closures associated with AMI and emergent CABG, 1 subacute closure which was revascularized by bail out stenting, 5 major hemorrhage requiring transfusion associated with 1 CVA and 2 metabolic acidosis induced by acute renal failure, and 5 death. CONCLUSION: The high pressure stent deployment procedure and new anticoagulation protocol associating tidopidine and aspirin without coumadin or prolonged heparin infusion allow us to obtain an acceptably low subacute thrombosis or bleeding complication rate. These results are encouraging and allow a wide use of coronary stenting.