Significant Difference In Bleeding Events Research Articles

Red blood cell transfusion triggers in acute leukemia: a randomized pilot study.

Red blood cell (RBC) transfusion thresholds have yet to be examined in large randomized trials in hematologic malignancies. This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy. A randomized (2:1) study was conducted of restrictive (LOW) hemoglobin (Hb) trigger (7 g/dL) compared to higher (HIGH) Hb trigger (8 g/dL). The primary outcome was feasibility of conducting a larger trial. The four requirements for success required that more than 50% of the eligible patients could be consented, more than 75% of the patients randomized to the LOW arm tolerated the transfusion trigger, fewer than 15% of patients crossed over from the LOW arm to the HIGH arm, and no indication for the need to pause the study for safety concerns. Secondary outcomes included fatigue, bleeding, and RBCs and platelets transfused. Ninety patients were consented and randomly assigned to LOW to HIGH. The four criteria for the primary objective of feasibility were met. When the number of units transfused was compared, adjusting for baseline Hb, the LOW arm was transfused on average 8.0 (95% confidence interval [CI], 6.9-9.1) units/patient while the HIGH arm received 11.7 (95% CI, 10.1-13.2) units (p = 0.0003). There was no significant difference in bleeding events or neutropenic fevers between study arms. This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile. This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting.

Oral surgery during therapy with anticoagulants-a systematic review.

Oral anticoagulation therapy (OAT) with vitamin K inhibitors protects the patients from thromboembolic events. It may however lead to excessive hemorrhage during and after an oral surgery procedure. The aim of this systematic review was to evaluate the justifications to reduce, withdraw, or alter OATs prior to minor oral surgery procedures to manage bleeding events. A systematic MEDLINE search was conducted for clinical studies in English or German language from 1994 to 2014 comparing patients treated with OAT, without OAT, as well as patients with altered OAT for oral surgery purposes. Relevant outcome parameters were: postoperative local hemostasis, bleeding episodes, occurrence of thromboembolic events, and other complications due to the anticoagulation medication. A hand search for references cited in the identified publications completed the review. After screening of 1755 abstracts, 16 clinical studies were identified according to the selection criteria. Due to the heterogeneity of the obtained data, aggregation and synthesis were not possible. There was no significant difference in bleeding events comparing patients under continued OAT to those with reduced, altered, and/or discontinued OAT medications. Minor bleeding events in the test and control groups were successfully stopped with local measures. However, no superiority of a single hemostatic measure could be identified. Neither the international normalized ratio (INR), within the therapeutic range (2-4), nor the extent of the minor oral surgery procedure had an influence on postoperative bleeding episodes. There is strong evidence that OAT patients undergoing minor oral surgery should not discontinue their medication in order to prevent thromboembolic complications. Nonetheless, INR should be less than 4, local hemostatic measures are of high importance and patients need to be instructed and closely monitored as minor bleedings might occur more often in OAT patients.

Anticoagulation therapy and invasive management of acute non-ST elevation coronary syndromes: guidelines and everyday practice

Introduction and goal: The latest 2011 non-ST- segment elevation acute coronary syndromes (NSTE- ACS) management guidelines indicated that all patients should receive anticoagulation drugs irrespective of the treatment strategy. In this report, 2-year data on anticoagulation therapies for NSTE-ACS are presented, in relation to invasive management selection and treatment outcomes in a clinical setting without registered bivalirudin. Patients and Methods: Data for 374 patients with NSTEACS treated in the Coronary Care Unit in General Hospital Slavonski Brod, Croatia were analyzed from January 2012 to December 2013. Treatment strategies, outcomes and complications among patients treated with different anticoagulation agents (enoxaparine, fondaparinux or unfractionated heparin) were analyzed and compared. Results: In all, 72% of all NSTE-ACS patients were treated invasively, out of which 66% underwent angiography within 72 hours. Urgent and early angiography was performed in 44% of all invasively treated patients. Generally, 58% and 5% of patients received enoxaparine and unfractionated heparin (UFH), respectively, whereas fondaparinux was administered in 37% of patients. Median age of patients treated with enoxaparine was 66, compared to 76 in the fondaparinux group. There were significantly more patients treated with enoxaparine and UFH than with fondaparinux in the invasive strategy group. We observed that the number of patients treated with fondaparinux in the invasive group increased together with the period between symptom onset and angiography. The number of patients treated conservatively with either fondaparinux or enoxaparine was almost equal. There were no patients treated conservatively with UFH. In general, in-hospital mortality was low, 2.6% with no significant differences in bleeding events regarding the selection of anticoagulation therapy. Conclusions: Although the guidelines gave preference to fondaparinux, everyday practice in our hospital showed that enoxaparine was a preferred agent, particularly in younger patients selected for early invasive strategy, most probably because of the risk/benefit ratio and opportunity of avoiding the mixing of anticoagulation agents. Only 5% of patients were selected for urgent invasive approach with UFH, which should probably increase in the future. Considering a higher cost of bivalirudin, the introduction of this agent for non-ST segment elevation myocardial infarction management does not seem to be mandatory in our clinical setting, since this small group of patients was adequately managed with UFH.

Abstract T P236: Safety of Venous Thromboembolism Prophylaxis in Intracranial Hemorrhage Patients with External Ventricular Drains

Introduction: Despite high rates of venous thromboembolism (VTE) among critically ill patients with intracranial hemorrhage, there is a reluctance to use pharmacologic VTE prophylaxis in patients with external ventricular drains (EVD) due to concerns of procedure site hemorrhage. METHODS: In a prospective study of intracranial hemorrhage patients with an EVD (subarachnoid hemorrhage N=64; intracerebral hemorrhage N=41 and subdural hemorrhage N=5) conducted between 7/2008-11/2011, we compared bleeding complications, VTE rates and 3-month functional outcomes between patients who received pharmacologic VTE prophylaxis (either heparin or enoxaparin) plus compression boots versus mechanical prophylaxis (compression boots) alone. RESULTS: Of 110 patients with an EVD, 98 (89%) received pharmacologic prophylaxis (heparin BID N=3 [3%]; heparin TID N= 34 [31%]; enoxaparin N=61 [56%]) in addition to compression boots, while 11 (11%) received compression boots alone. The median time to initiation of pharmacological prophylaxis was 4 days post hemorrhage. Compared to mechanical prophylaxis alone, pharmacologic prophylaxis patients were more likely to have SAH (60% versus 22%, P=0.028), less likely to have SDH (2% versus 33%, P<0.0001) and less likely to be DNR/comfort care (19% versus 44%, P=0.035). Admission GCS and APACHE 2 scores did not differ between groups. There were no significant differences in bleeding events (EVD associated hemorrhage, ICH expansion, new ICH, new SDH, SDH reaccumulation, bleeding at the craniotomy site, GI bleeding or anemia requiring transfusion) or thombotic events (DVT or PE) between groups. At 3-months, fewer patients receiving pharmacologic prophylaxis were dead (25% versus 67%, P=0.012) or severely disabled (51% versus 89%, P=0.049). After adjusting for admission GCS, age, DNR status, and bleed type this trend for reduced 3-month mortality remained (adjust OR 0.1, 95%CI 0.004-1.2,P=0.065). CONCLUSIONS: In intracranial hemorrhage patients with EVDs, pharmacological VTE prophylaxis is not associated with higher bleeding risks and is associated with improved 3-month mortality rates compared to mechanical VTE prophylaxis alone.

CHANCE Trial

The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial tested the effect of early dual antiplatelet treatment for the prevention of secondary stroke within the first 90 days following a qualifying transient ischemic attack (TIA) or minor stroke in 5170 Chinese patients. The trial showed a significant reduction in secondary stroke in patients treated with dual antiplatelet therapy (hazard ratio, 0.68; 95% confidence interval, 0.57–0.81; P <0.001). There was no difference in the rate of moderate or severe hemorrhages (0.3% in both groups; P =0.73).1 CHANCE is critical support for early-onset and short-term intervention of antiplatelet therapy in patients with TIAs and mild strokes. The trial builds on knowledge gained during the past decade, beginning with observations that the risks of stroke early after a TIA or minor stroke are substantial,2–4 with a 2-day risk of stroke following TIA of ≈5%.2,4 Greater attention has since been paid to early evaluation, identification, and treatment of modifiable risk factors and the initiation of antiplatelet treatment for noncardioembolic events within 48 hours of the initial event.5 Previous lysis and recanalization studies have shown the importance of immediate medical management following ischemic events. More recently, studies have addressed the use of antiplatelet agents in an earlier time window, seeking to address the period of highest stroke recurrence risk. The Fast Assessment of Stroke and Transient Ischaemic Attack to Prevent Early Recurrence (FASTER) pilot trial randomized 392 patients with TIA/stroke presenting within 24 hours to aspirin plus clopidogrel or aspirin plus placebo. There was a reduction of stroke within 90 days seen with dual therapy (absolute risk reduction, 3.8%; 95% confidence interval, −9.4 to 1.9; P =0.19) and no significant difference in bleeding events between treatment arms.5 …

Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: A randomized control trial

The objective of this study is to compare personalized antiplatelet therapy according to CYP2C19 phenotype with conventional antiplatelet therapy in patients after percutaneous coronary intervention (PCI). A total of 600 patients with coronary artery disease (CAD) undergoing PCI randomly received a personalized antiplatelet therapy (group A; n=301) or conventional antiplatelet treatment (group B; n=299). For group A, antiplatelet therapy was performed according to CYP2C19 phenotype. For group B, the patients received conventional antiplatelet treatment without detected CYP2C19 genotype. The primary end point was compared between these two groups. This study is registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001807). The primary end point occurred in 27 patients assigned to conventional treatment as compared with 8 patients assigned to personalized therapy (cumulative event rate, 9.03% vs. 2.66%; P<0.01). The composite rate of death, myocardial infarction, or stroke at 180 days occurred in 3 and 18 patients in the two groups, respectively (cumulative event rate, 1.0% and 6.2%, P<0.01). The cumulative 180-day incidence of ST was significantly lower in group A than in group B (0.66% vs. 3.01%, P=0.032). The 180-day incidence of MI (0.33% vs. 3.01%, P=0.011) and death (0.33% vs. 2.34%, P=0.011) was fewer than that in control, respectively. We did not find the significant difference in bleeding events between the 2 groups. Personalized antiplatelet therapy according to CYP2C19 genotype after PCI can significantly decrease the incidence of major adverse cardiovascular events and the risk of 180-day ST in Chinese population.

PERSONALISED ANTIPLATELET THERAPY ACCORDING TO CYP2C19 GENOTYPE AFTER PERCUTANEOUS CORONARY INTERVENTION IN CHINESE POPULATION: A RANDOMISED CONTROL TRIAL

ObjectivesThe purpose of this study was to compare personalised antiplatelet therapy according to CYP2C19 phenotype with conventional antiplatelet therapy in patients after percutaneous coronary intervention (PCI).BackgroundRecent studies have demonstrated that...

Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (review of Technology Appraisal No. 90): a systematic review and economic analysis

Occlusive vascular events such as myocardial infarction (MI), ischaemic stroke and transient ischaemic attack (TIA) are the result of a reduction in blood flow associated with an artery becoming narrow or blocked through atherosclerosis and atherothrombosis. Peripheral arterial disease is the result of narrowing of the arteries that supply blood to the muscles and other tissues, usually in the lower extremities. The primary objective in the treatment of all patients with a history of occlusive vascular events and peripheral arterial disease is to prevent the occurrence of new occlusive vascular events. To assess the clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole (MRD) alone or with aspirin (ASA) compared with ASA (and each other where appropriate) in the prevention of occlusive vascular events in patients with a history of MI, ischaemic stroke/TIA or established peripheral arterial disease. To consider the clinical effectiveness and cost-effectiveness of clopidogrel in patients with multivascular disease. This review is an update of the evidence base for the National Institute for Health and Clinical Excellence (NICE) guidance Technology Appraisal No. 90 (TA90) entitled Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (2005). Four electronic databases (EMBASE, MEDLINE, Web of Science and The Cochrane Library) were searched for randomised controlled trials (RCTs) and economic evaluations. Submissions to NICE by the manufacturers of the interventions were also considered. A systematic review of clinical effectiveness and cost-effectiveness was conducted. To manage heterogeneity between trials, indirect analysis (using a mixed-treatment methodology) was performed on selected clinical outcomes. A new economic model was developed to assess incremental costs per life-year gained [quality-adjusted life-years (QALYs)]. For evidence of clinical effectiveness, four RCTs were identified: CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events), ESPRIT (European/Australasian Stroke Prevention in Reversible Ischaemia Trial), PRoFESS (Prevention Regimen For Effectively avoiding Second Strokes) and ESPS-2 (Second European Stroke Prevention Study). In CAPRIE (patients with MI, ischaemic stroke or peripheral arterial disease), statistically significant outcomes in favour of clopidogrel were noted for the primary outcome (first occurrence of ischaemic stroke, MI or vascular death) compared with ASA [relative risk reduction 8.7%; 95% confidence interval (CI) 0.3% to 16.5%; p = 0.043]. In ESPRIT (patients with ischaemic stroke/TIA) for the primary outcome (first occurrence of death from all vascular causes, non-fatal stroke, non-fatal MI or major bleeding complication), the risk of event occurrence was statistically significantly lower in the MRD + ASA arm than in the ASA arm [hazard ratio (HR) 0.80; 95% CI 0.66 to 0.98], with no statistically significant difference in bleeding events between the two arms. In PRoFESS (patients with ischaemic stroke) the rate of recurrent stroke of any type (primary outcome) was similar in the MRD + ASA and clopidogrel groups, and the null hypothesis (that MRD + ASA was inferior to clopidogrel) could not be rejected. In ESPS-2 (patients with ischaemic stroke/TIA), on the primary outcome of stroke, statistically significant differences in favour of MRD + ASA were observed compared with ASA and MRD alone (relative risk 0.76; 95% CI 0.63 to 0.93). The outcomes addressed in the mixed-treatment comparisons (limited by the available data) for the ischaemic stroke/TIA population confirmed the results of the direct comparisons. The 11 economic evaluations included in the review of cost-effectiveness indicated that for patients with previous peripheral arterial disease, ischaemic stroke or MI, clopidogrel is cost-effective compared with ASA, and for patients with previous ischaemic stroke/TIA, treatment with MRD + ASA is cost-effective compared with any other treatment in patients in the secondary prevention of occlusive vascular events. The relevance of the review was limited as the economic evaluations were not based on the most current clinical data. Cost-effectiveness results generated from the Assessment Group's de novo economic model suggested that the most cost-effective approach for patients with ischaemic stroke/TIA is clopidogrel followed by MRD + ASA then ASA. For patients with MI, the most cost-effective approach is ASA followed by clopidogrel. For patients with established peripheral arterial disease, the most cost-effective approach is clopidogrel followed by ASA. For patients with multivascular disease, clopidogrel followed by ASA is the most cost-effective approach. Incremental cost-effectiveness ratios (ICERs) were also calculated for patients who are intolerant to ASA. Assuming that the branded price for clopidogrel is used and TA90 guidance is not applied, all of the ICERs range between £2189 and £13,558 per QALY gained. Probabilistic sensitivity analyses were fully consistent with these findings. The evidence suggests that the most cost-effective treatment for patients with ischaemic stroke/TIA is clopidogrel followed by MRD + ASA followed by ASA; for patients with MI, ASA followed by clopidogrel; and for patients with established peripheral arterial disease or multivascular disease, clopidogrel followed by ASA. The National Institute for Health Research Health Technology Assessment programme.

Comparison of the 5‐Fluorouracil‐Warfarin and Capecitabine‐Warfarin Drug Interactions

To compare the differences between the 5-fluorouracil-warfarin and capecitabine-warfarin drug interactions in patients receiving therapeutic doses of warfarin. Retrospective medical record review. Large academic Veterans Affairs health care system. Twenty-four patients who received concomitant therapeutic doses of warfarin and at least one dose of a fluoropyrimidine--5-fluorouracil or capecitabine--between January 2004 and May 2008. The primary outcome was mean change in international normalized ratio (INR) from baseline to end of 90-day study period. Only patients who were taking warfarin before starting either fluoropyrimidine-based chemotherapy were included in the primary analysis. Of the 24 eligible patients, 15 (9 receiving 5-fluorouracil, 6 receiving capecitabine) were taking warfarin before receiving either fluoropyrimidine. No significant differences were noted in the average weekly warfarin dose or baseline INR between the 5-fluorouracil and capecitabine groups. The mean change in INR for patients taking warfarin before fluoropyrimidine use was 4.62 in the 5-fluorouracil group compared with 5.11 in the capecitabine group (p=0.87). The capecitabine group had a similar proportion of patients achieving an INR above 9 while taking warfarin compared with the 5-fluorouracil group (17% vs 22%). In those patients who required a warfarin dosage reduction, the dose was reduced by 38% and 41% in the 5-fluorouracil and capecitabine groups, respectively. No significant differences in bleeding events were reported within 90 days of concurrent use of either fluoropyrimidine with warfarin. Our study suggests that in patients receiving concomitant warfarin and a fluoropyrimidine, no significant differences in INR elevation or bleeding events were noted with 5-fluorouracil compared with capecitabine.

Economic and clinical evaluation of fondaparinux vs. enoxaparin for thromboprophylaxis following general surgery

ABSTRACTPurpose: Patients undergoing general surgical procedures are at increased risk for venous thromboembolism (VTE). Compliance rates with established guidelines for VTE thromboprophylaxis in patients at moderate-to-high risk are notably low. Recent literature has demonstrated that fondaparinux is associated with lower costs and fewer VTEs than enoxaparin in patients undergoing major orthopedic surgery (MOS), but data are limited in patients undergoing general surgery. This study was conducted to evaluate the cost implications and relative real-world effectiveness of fondaparinux vs. enoxaparin in general surgery patients.Methods: Data were obtained from inpatient billing records from over 500 hospitals using Premier's Perspective Comparative Database. Patients hospitalized for general surgery between July 1, 2003 and January 31, 2006 were eligible for inclusion. Eligible patients were included if they received fondaparinux or enoxaparin after their general surgery date. Patients were excluded if they received both anticoagulants on their first day of therapy, were <18 years of age on the surgery date, or did not have data 6 months prior and 1 month post hospitalization. Included patients were stratified into two cohorts based on their first anticoagulant, fondaparinux or enoxaparin. Patients were matched in each group on 1 : 1 case-control matching based on propensity scores.Results: A total of 5364 patients were included (n = 2682 for each cohort) from 326 unique hospitals. Average total costs per patient for the fondaparinux group were significantly lower than the enoxaparin group ($15 156 vs. 17 741, p < 0.0001). Patients receiving fondaparinux were significantly less likely to experience a VTE (2.80 vs. 3.77%, p = 0.046, a 35% relative risk reduction). No significant differences in bleeding events between the cohorts were observed (p = 0.6047), and no significant differences in all-cause inpatient death were noted (p = 0.3673).Conclusion: Fondaparinux was associated with significantly lower costs and fewer VTEs compared to enoxaparin without an increase in bleed rates or all-cause inpatient mortality. The findings from this study are limited by the retrospective study design and should only be generalized to a similar patient population.

The Safety and Efficacy of Thrombolysis for Strokes After Cardiac Catheterization

The purpose of this study was to systematically compare clinical outcomes of patients treated with thrombolysis with those without treatment in a multi-year, multicenter cohort of strokes after cardiac catheterization. Ischemic strokes after cardiac catheterization procedures, although uncommon, lead to the morbidity and mortality of thousands of patients each year. Despite the availability of Food and Drug Administration-approved thrombolytic therapy for acute ischemic stroke since 1996, thrombolysis remains unestablished in the setting of cardiac catheterization, owing to unique concerns regarding safety and efficacy. Consecutive cases of ischemic stroke after cardiac catheterization were abstracted retrospectively and reviewed by clinicians at 7 major North American academic centers with acute stroke teams. Safety and efficacy outcome measures were pre-defined. A total of 66 cases of ischemic strokes after cardiac catheterization were identified over 3 to 4 years; 12 (18%) were treated with thrombolysis, consisting of 7 intravenous and 5 intra-arterial recombinant tissue plasminogen activator cases. Improvement in stroke symptoms, as measured by the primary efficacy measure of median change in National Institutes of Health Stroke Scale score from baseline to 24 h, was greater in treated versus nontreated cases (p < 0.001). Additional secondary measures of efficacy also showed better outcomes in the treated group. There were no significant differences in bleeding events, defined as symptomatic intracerebral hemorrhage, hemopericardium, or other systemic bleeding resulting in hemodynamic instability or blood transfusions. Mortality rates were also similar. Thrombolysis might improve early outcomes after post-catheterization strokes and seems safe in this context. Emergent cerebral revascularization should be a routine consideration.

Increased Risk in Patients With High Platelet Aggregation Receiving Chronic Clopidogrel Therapy Undergoing Percutaneous Coronary Intervention: Is the Current Antiplatelet Therapy Adequate?

We sought to determine whether patients receiving chronic clopidogrel therapy undergoing nonemergent stenting who display high on-treatment preprocedural platelet aggregation measured by standard light transmittance aggregometry and thrombelastography (TEG) will be at increased risk for poststenting ischemic events. Patients exhibiting heightened platelet reactivity to adenosine diphosphate (ADP) might be at increased risk for recurrent ischemic events after coronary stenting. A total of 100 consecutive patients receiving chronic antiplatelet therapy consisting of aspirin (325 mg qd) and clopidogrel (75 mg qd) were studied before undergoing nonemergent stenting. Patients were followed for 1 year after coronary stenting for the occurrence of death, myocardial infarction, stent thrombosis, stroke, or ischemia requiring a hospital stay. All patients were aspirin responsive. Patients with ischemic events (23 of 100, 23%) within 1 year had greater on-treatment prestent ADP-induced platelet aggregation than patients without ischemic events by aggregometry and TEG (p < 0.001 for both measurements). Of patients with an ischemic event, 70% and 87% displayed high on-treatment platelet reactivity at baseline by aggregometry and TEG, respectively. High on-treatment platelet reactivity as measured by aggregometry and TEG were the only variables significantly related to ischemic events (p < 0.001 for both assays). The administration of eptifibatide reduced periprocedural elevation in platelet reactivity, with no significant differences in bleeding events. Patients receiving chronic clopidogrel therapy undergoing nonemergent percutaneous coronary intervention who exhibit high on-treatment ADP-induced platelet aggregation are at increased risk for postprocedural ischemic events. These findings might have implications for the alteration in clopidogrel maintenance dose and use of glycoprotein IIb/IIIa inhibitors in selected patients.

A prospective control study of the safety and cellular yield of EUS-guided FNA or Trucut biopsy in patients taking aspirin, nonsteroidal anti-inflammatory drugs, or prophylactic low molecular weight heparin

Although the ASGE recommends that high-risk endoscopic procedures can safely be performed on patients taking aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in standard doses, there is a paucity of data on EUS-FNA per se in this setting. We studied the safety and cellular yield of EUS-FNA and/or Trucut biopsy (TCB) in patients taking aspirin, NSAIDS, or prophylactic low molecular weight heparins (LMWH). Prospective control study. Consecutive patients undergoing EUS-FNA and/or TCB were recruited over an 18-month period. The usage of aspirin, NSAIDS, or LMWH were recorded and patients who were not taking these medications served as controls. The bleeding events (endosonographic findings of extraluminal bleeding, intraluminal bleeding requiring hemostatic procedures, hematemesis, or melena) and cellular yield were compared between patients and controls. Two hundred fourteen patients (8 had repeat procedures) underwent EUS-FNA and/or TCB on 241 lesions. Bleeding events occurred in none (0 of 26), 33.3% (2 of 6), and 3.7% (7 of 190) of the patients in the aspirin/NSAIDS, LMWH, and control groups, respectively (p = 0.023). The mean numbers of FNA passes, applications of suction, bloody specimens, and cellular yield were not significantly different between patients who were or were not receiving medications. No significant difference in bleeding events was noted between the FNA and TCB groups. EUS-FNA or TCB is safe in patients taking aspirin or NSAIDS. Consideration should be given to stopping LMWH before the procedure. The cellular yield and blood contamination of the specimen from FNA are similar to those in controls.

Selecting an anticoagulant for recurrent venous thromboembolism in cancer

Purpose. The thrombogenicity of newer anticancer agents and the challenges associated with managing cancer patients on warfarin have led to the evaluation of the low-molecular-weight heparins (LMWHs) for primary and secondary prophylaxis in this high-risk patient population. Summary. The first published trial of LMWH in cancer compared three months of warfarin therapy with enoxaparin in cancer patients with proximal deep venous thrombosis (DVT), pulmonary embolism (PE), or both. All patients received four days of enoxaparin 1.5 mg/kg and were then randomized to continue receiving enoxaparin or begin warfarin therapy. Due to inadequate patient enrollment, no statistically significant differences were detected between the two treatment groups. In a similar patient population, the Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) trial evaluated the use of long-term dalteparin for the prevention of recurrent venous thromboembolism (VTE) in patients with cancer. Cancer patients with proximal DVT, PE, or both were randomized to initial treatment with dalteparin followed by either six months of oral anticoagulant therapy or dalteparin monotherapy. The primary outcome was symptomatic, recurrent VTE, and secondary outcomes were bleeding events and survival time. The cumulative risk of recurrent VTE at six months was reduced from 17% in the oral anticoagulant group to 9% in the dalteparin group, a risk reduction of 52% (p=0.002). No significant differences in bleeding events or overall mortality occurred between the groups. Recent recommendations from the American College of Chest Physicians on the treatment of cancer-associated thrombosis are based in part on data from the CLOT trial and support the use of dalteparin and tinzaparin in the long-term treatment of patients with DVT and cancer. Finally, results of recent trials support the concept that antithrombotic therapy with dalteparin or nadroparin may have an antineoplastic effect, resulting in improved survival time. However, these results require further validation. Conclusion. Despite the absence of oncology-specific guidelines for cancer-associated thrombosis, pharmacists now have a number of new tools available for selecting an anticoagulant, including results from several clinical trials with LMWHs and recent reports from national meetings.

Clopidogrel Plus Aspirin in Patients With Acute Myocardial Infarction Treated With Fibrinolytic Therapy – CLARITY-TIMI 28

Evaluation of: Sabatine MS, Cannon CP, Gibson CM et al.: CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N. Engl. J. Med. 352, 1179-1789 (2005). The CLopiodogrel as Adjunctive ReperfusIon TherapY (CLARITY)--Thrombolysis In Myocardial Infarction (TIMI) 28 study was a double-blind, placebo-controlled trial designed to evaluate whether the addition of clopidogrel to aspirin would improve infarct artery patency and reduce ischemic complications in patients with acute myocardial infarction (MI) treated with fibrinolytic therapy. A total of 3491 patients presenting within 12 h of MI intended for treatment with a fibrinolytic agent were enrolled and randomized to receive either aspirin alone or aspirin plus clopidogrel (300 mg loading dose followed by 75 mg/day). The primary efficacy end point was the composite of the presence of an occluded infarct-related artery (TIMI flow grade 0 or 1) at follow-up angiography (performed 48-192 h after enrollment), or death or recurrent MI before angiography; this occurred in 21.7% of the placebo group and 15.0% of the clopidogrel group (p < 0.001). At 30 days, the composite of death, MI and recurrent ischemia requiring revascularization was 14.1% in the placebo group and 11.6% in the clopidogrel group (p = 0.03). The primary safety end point was the incidence of major bleeding (by TIMI criteria); other safety end points included intracranial hemorrhage and TIMI minor bleeding. There were no significant differences in bleeding events between groups.