Course Of Anticoagulation Research Articles

The Clinical Course of Venous Thromboembolism May Differ According to Cancer Site

BackgroundWe hypothesized that the clinical course of venous thromboembolism in patients with active cancer may differ according to the specificities of primary tumor site. Aim and MethodsWe used data from RIETE (international registry of patients with venous thromboembolism) to compare the clinical venous thromboembolism-related outcomes during the course of anticoagulation in patients with one of the 4 more frequent cancers (breast, prostate, colorectal, or lung cancer). ResultsAs of September 2014, 3947 cancer patients were recruited, of whom 938 had breast, 629 prostate, 1189 colorectal, and 1191 lung cancer. Overall, 55% had metastatic disease (42%, 36%, 53%, and 72%, respectively). During the course of anticoagulant therapy (mean duration, 139 days), the rate of thromboembolic recurrences was similar to the rate of major bleeding in patients with breast (5.6 [95% confidence interval (CI), 3.8-8.1] vs 4.1 [95% CI, 2.7-5.9] events per 100 patient-years) or colorectal cancer (10 [95% CI, 7.6-13] vs 12 [95% CI, 9.4-15] per 100 patient-years). In contrast, in patients with prostate cancer, the rate of venous thromboembolic recurrences was half the rate of major bleeding (6.9 [95% CI, 4.4-10] vs 13 [95% CI, 9.2-17] events per 100 patient-years), whereas in those with lung cancer, the rate of thromboembolic recurrences was twofold higher than the rate of major bleeding (27 [95% CI, 22-23] vs 11 [95% CI, 8.6-15] per 100 patient-years). ConclusionsSignificant differences in the clinical profile of venous thromboembolic-related outcomes were observed according to the site of cancer. These findings suggest the development of cancer-specific anticoagulant strategies as an area for further research.

Clinical presentation, management, follow-up, and outcomes of isolated celiac and superior mesenteric artery dissections

ObjectiveIsolated visceral artery dissections are rare entities with no current consensus guidelines for treatment and follow-up. This study aims to evaluate the presentation, management, outcomes, and follow-up practices for patients with isolated visceral artery dissections and to compare those with and without symptoms. MethodsIn this retrospective analysis, we identified all patients with isolated celiac artery and/or isolated superior mesenteric artery dissections at a single institution between September 2006 and December 2014. Patients with concomitant aortic dissections were excluded. Cases were stratified by symptom status. Presentation, anatomic findings, treatment, outcomes, and follow-up imaging were then compared between symptomatic and asymptomatic patients. ResultsWe identified 25 patients including 15 with symptoms and 10 without. There were no differences in patient comorbidities; however, symptomatic patients more frequently presented with thrombus (n = 10; 67% vs n = 1; 10%; P = .01) and inflammation (n = 8; 53% vs n = 1; 10%; P = .04), and trended toward increased stenosis (n = 12; 80% vs n = 4; 40%; P = .09) compared with asymptomatic patients. All asymptomatic patients were treated with observation alone with vessel diameter enlargement noted in 33% (n = 2) of patients on follow-up imaging. Among symptomatic patients, standard treatment included a short course of anticoagulation (mean, 4.5 months) with lifelong antiplatelet therapy. Three patients underwent operative intervention for persistent or worsening symptoms, two during the index admission and one 10 months after presentation for chronic abdominal pain. Approximately 70% (n = 17) of patients in each group had follow-up imaging (computed tomography angiography: n = 14; 56%; magnetic resonance angiography: n = 4; 16%; ultrasound: n = 13; 52%). Among patients treated nonoperatively, no patients complained of symptoms at follow-up, and 50% of those with inflammation on initial imaging had resolution. Twenty-five percent (n = 4) of patients had an increase in vessel size; however, all vessels remained less than 2 cm in maximal diameter. There were no ruptures or related deaths in either group. ConclusionsAmong patients with visceral artery dissection, no ruptures occurred but diameter enlargement was documented. This disease progression suggests that routine surveillance may be appropriate; however, transitioning early to ultrasound imaging should be considered to decrease radiation, contrast, and associated costs.

Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: a prospective cohort study

Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but no prior studies have been reported specifically evaluating the efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT and now report a validation analysis of our first 200 patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose full course of anticoagulation was with rivaroxaban, were accrued. In competing risk analysis, primary endpoints at 6 months included new or recurrent PE or symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. In competing risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4 % (95 % CI = 1.4–7.4 %), major bleeding was 2.2 % (95 % CI = 0−4.2 %) and all-cause mortality 17.6 % (95 % CI = 11.7–23.0 %). In this cohort of 200 patients with active cancer and CAT the rates of new or recurrent VTE and major bleeding were comparable to the cancer subgroup analysis from the EINSTEIN studies. The results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment of CAT, and suggest that safety and efficacy is preserved, compared with past-published experience with LMWH.

Outcome during and after anticoagulant therapy in cancer patients with incidentally found pulmonary embolism.

Current guidelines suggest treating cancer patients with incidental pulmonary embolism comparably to patients with symptomatic pulmonary embolism.We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry to compare the rate of major bleeding and symptomatic pulmonary embolism during the course of anticoagulation and after its discontinuation in cancer patients with incidental pulmonary embolism.As of March 2016, 715 cancer patients with incidental pulmonary embolism had been enrolled in RIETE. During the course of anticoagulant therapy (mean 235 days), the rate of major bleeding was higher than the rate of symptomatic pulmonary embolism (10.1 (95% CI 7.48-13.4) versus 3.17 (95% CI 1.80-5.19) events per 100 patient-years, respectively), and the rate of fatal bleeding was higher than the rate of fatal pulmonary embolism (2.66 (95% CI 1.44-4.52) versus 0.66 (95% CI 0.17-1.81) deaths per 100 patient-years, respectively). After discontinuing anticoagulation (mean follow-up 117 days), the rate of major bleeding was lower than the rate of symptomatic pulmonary embolism (3.00 (95% CI 1.10-6.65) versus 8.37 (95% CI 4.76-13.7) events per 100 patient-years, respectively); however, there were no differences in the rate of fatal events at one death each.The risk/benefit ratio of anticoagulant therapy in cancer patients with incidental pulmonary embolism is uncertain and must be evaluated in further studies.

Venous thromboembolism in centenarians: Findings from the RIETE registry

BackgroundThe balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain. MethodsWe used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years. ResultsOf 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported. ConclusionsAmong patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency.

Abdominal thrombotic complications following bariatric surgery

BackgroundThrombotic events involving the portal-splenic-mesenteric venous system (PSMVT) are rare but potentially lethal after bariatric surgery. ObjectivesTo investigate the incidence, clinical presentation, management, and outcome of thrombotic events after bariatric surgery. SettingTwo university hospitals. MethodsA retrospective review of individuals who underwent bariatric surgery between January 2006 and December 2015. ResultsOverall, 4386 patients underwent bariatric surgery (laparoscopic sleeve gastrectomy [LSG; n = 2886], laparoscopic Roux-en-Y gastric bypass [n = 762], laparoscopic adjustable gastric banding [n = 668], and biliopancreatic diversion [n = 70]). Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 hours after surgery until discharge) was provided for all patients. A minority of patients (n = 543, 12.4%) also received an extended course of enoxaparin for 1–4 weeks after discharge. We observed 16 cases of PSMVT, all after LSG, with an incidence of .55% (16/2886). Twelve additional patients experienced deep vein thrombosis and 6 had pulmonary embolism. Follow-up imaging indicated complete resolution in all cases, with no sequelae, recurrent thrombosis, or mortality. The overall thrombosis rate was significantly lower in patients who received an extended course of anticoagulation after LSG (P = .01) and after any type of bariatric surgery (P = .02). ConclusionsPSMVT was found to occur uncommonly after LSG. Prompt diagnosis and anticoagulation therapy led to favorable outcomes in most cases. Significantly lower rates of thrombosis were found in patients who received an extended course of anticoagulation. We support its use for at least 1 week after discharge.

OC-15 - Risk factors for cancer development after idiopathic venous thromboembolism

Idiopathic venous thromboembolism (VTE) is associated with the risk of cancer but the risk factors for cancer development in such patients are still uncertain. To assess risk factors for the development of cancer after a standard course of anticoagulation in patients with first episode of idiopathic VTE. Subjects were enrolled in the three large prospective multicentre studies: PROLONG (NEJM 2006) PROLONG II (Blood 2010) and DULCIS (Blood 2014). Women whose index event was hormone related were excluded from the analysis. The development of cancer was recorded during a 2-year follow-up. 1,805 patients were enrolled (M/F: 510/453), mean age: 62, median: 67; range:18-87 years). Cancer developed in 55 patients (3% ; 1.7% pt-years) of whom 15 (2.0%; 1.1% pt-years) had PE with or without DVT and 40 (3.8%; 2.1% pt-years) had DVT without PE (p=0.03). The development of cancer was associated with DVT without PE (HR:1.8; 95% CI: 1.1-3.3) and age >65 (HR: 2.5; 95%: 1.3-4.9). Among patients with DVT, with or without PE, the development of cancer was associated with the presence of residual vein obstruction>4mm (RVO) at compression ultrasound (HR: 1.8, 95% CI: 1.1-3.3) and age>65 (HR: 2.8; 95% CI: 1.3-6.2). Age>65 years, DVT without PE and the presence of RVO are significantly associated with the risk of developing cancer after a first episode of idiopathic VTE over a two-year follow-up.

Etiopathogenesis, Prevention, and Treatment of Thromboembolism in Inflammatory Bowel Disease

The close relationship between inflammation and thrombosis affects the progression and severity of inflammatory bowel disease (IBD). The prevalence of venous thromboembolism (VTE) varies between 1% and 7% among patients with IBD. The VTE risk in patients with IBD is at least 3 times higher than that in the normal general population. The absolute risk is very high during hospitalization, active disease, and surgery. The IBD-related VTE occurs at younger ages and recurs more frequently. The development of thrombosis in IBD is due to the interaction of many hereditary and acquired risk factors. Each patient diagnosed with IBD should be evaluated for a personal and family history of thrombosis and for prothrombotic drug use. Although procoagulant factors are increased during the natural course of inflammation, natural anticoagulants and fibrinolytic activity are decreased. Although IBD is accepted as a prothrombotic condition, there is no treatment that can remove this risk from daily practice. Patient training is required to control important factors, such as long-term immobilization and smoking. Oral contraceptives and hormone replacement therapy should be avoided. Inducing permanent disease remission must be the key approach for the prevention of thrombosis. Low-molecular-weight heparin (LMWH) is the basis of prophylactic treatment, which reduces the thrombosis risk by 50%. Prophylaxis with LMWH should be administered to all patients with IBD hospitalized due to disease attack or surgery. Long-term or even life-long anticoagulation therapy should be planned if there is insufficient disease control, recurrent VTE attacks, positive thrombophilia tests, or thrombosis in vital veins.

Extra-luminal sigmoid sinus granulation tissue resulting in otitic hydrocephalus

Summary A four-year-old male presented to the emergency department with bilateral cranial nerve VI palsy following a failed outpatient course of antibiotics for acute mastoiditis. Imaging revealed a right sigmoid sinus flow defect. Urgent mastoidectomy with removal of the right sigmoid sinus osseous plate was performed. Intraoperatively, extensive granulation tissue was encountered compressing the sinus. The cranial nerve deficit resolved overnight, and follow-up imaging revealed restoration of venous outflow. As a result, the flow void was determined to be a result of compression of the sinus rather than thrombosis, and a prolonged course of systemic anticoagulation was avoided.

Extended anticoagulation and mortality in venous thromboembolism. A meta-analysis of six randomized trials

Data on all-cause mortality in patients with venous thromboembolism (VTE) and prolonged anticoagulation are inconclusive. The aim of this study was to compare the incidence of all-cause mortality in patients with VTE at intermediate risk of recurrence, i.e. without transient risk factors or cancer, exposed to shorter (at least three months) or longer anticoagulation.We did a systematic revue and meta-analysis of randomized clinical trials searching MEDLINE and COCHRANE bibliographic databases. A random-effects model was used to pool study results. I2 testing was used to test for heterogeneity.Six studies (5920 patients) entered in the final analysis. Mean course of anticoagulation was 7.5months in the shorter and 18.6months in the longer treatment arm. Prolonged anticoagulation was associated with a statistically significant reduction in all-cause mortality (RR 0.47, 95% CI 0.29 to 0.75; 0.8% vs 1.8%). Pulmonary embolism-related death was also lowered in the longer anticoagulation arm (RR 0.32, 95% CI 0.12 to 0.83; 0.2% vs 0.6%).Longer compared with shorter anticoagulation significantly reduced all-cause mortality in patients with VTE at intermediate risk of recurrence.

Safe and Effective Use of Rivaroxaban for Treatment of Cancer-Associated Venous Thromboembolic Disease: A Quality Improvement Initiative

▪Background: Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. LMWH injections are painful and costly. Rivaroxaban, an oral direct factor Xa inhibitor, was FDA approved in 2012 for treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but there has been a knowledge gap for its use in patients with cancer-associated thrombosis (CAT). Under a Quality Assurance Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT, and began to offer rivaroxaban as an alternative to enoxaparin, in January 2014, for patients who met appropriate clinical criteria. We are tracking all cancer patients with PE or symptomatic proximal DVT, whose full course of anticoagulation is with rivaroxaban (allowing up to 3 days of initial parenteral anticoagulation). We now report the characteristics of the first 200 patients, and an outcome analysis of our first 100 patients, who have been treated for at least 6 months or otherwise reached an endpoint.Materials and Methods: The Clinical Pathway guidelines will be available on request, pending publication. Patients were not treated with rivaroxaban if they had active gastrointestinal or genitourinary lesions, or had undergone gastric resection due to anticipated excess bleeding risk or reduced absorption. This excluded under 5% of patients. The Pathway provided dosing guidelines in the setting of thrombocytopenia, advanced age, transient renal, or hepatic dysfunction. Primary endpoints include new or recurrent PE, symptomatic proximal lower extremity DVT, major bleeding (ISTH definition), clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. Considering those outcomes as competing risks, the cumulative incidence of each event type was calculated using R 3.2.0 for Windows and package "Survival".Results: The characteristics of our first 200 patients are in Table 1. 70% of the patients had PE. Of the solid tumor patients, 65.6% had metastatic disease. The first 100 patients have completed at least 6 months of rivaroxaban anticoagulation or otherwise reached a primary endpoint. At 6 months, the cumulative incidence of death was 14.4% (95% CI=6.8-21.4%), new or recurrent VTE was 4.3% (95% CI=0.1-8.4%), major bleeding was 1.1% (95% CI=0-3.1%), and clinically relevant non-major bleeding leading to rivaroxaban discontinuation was 7.9% (95% CI=2.1-13.3%).Conclusions: In the analysis of the first 100 patients entered into our QAI program, the rates of major bleeding, and new or recurrent VTE compare favorably to two published studies of LMWH for treatment of cancer associated thrombosis. In the CLOT study (Lee et al, NEJM, 2003) and the Daltecan study (Francis et al, JTH, 2015), the 6-month rates of new or recurrent VTE were approximately 9%, and the rates of major bleeding were 6% and 9.5% respectively. Our final analysis awaits the completion of 6 months follow-up on 200 patients, to be completed in December 2015. But the rates of major bleeding and recurrent VTE at this point suggest safety and efficacy to be at least non-inferior to LMWH, with the advantage of reduced patient burden, and support the ongoing use of our Clinical Pathway.Our low rate of major bleeding likely is influenced by the exclusion of patients with active GI or GU lesions, who would be expected to have a high bleeding risk with an oral direct anticoagulant. However, we estimate this excluded less than 5% of cancer patients with VTE. Further, we anticipated reduced drug clearance in the elderly, and used a reduced dose for patients greater than 75 years of age. This appeared to be associated with no loss in efficacy, and helped maintain a low rate of major bleeding.A randomized trial is the optimal approach to establish non-inferiority or superiority of rivaroxaban to LMWH for cancer associated thrombosis. However, our QAI Clinical Pathway provides guidance and reassurance for rivaroxaban use until a randomized trial is conducted.TableBaseline Characteristics of PatientsCharacteristicNumber of IndividualsGenderMale82Female118Event TypePE, with or without DVT140Proximal, Symptomatic Lower extremity DVT60Cancer TypeSolid Tumor186Hematologic Malignancy14Cancer Stage (Of Solid Tumors)No Evidence of Disease (Post-Cancer Surgery)11 (5.9%)11 (0.5%)24 (2.2%)316 (8.6%)4122 (65.6%)Unknown32 (17.2%) [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Thrombophylaxis in Patients Undergoing Bariatric Surgery

Background: Patients undergoing bariatric surgery are at increased risk for symptomatic venous thromboembolism (VTE). Although the incidence of clinical VTE is lower than in other general and orthopedic surgical procedures, pulmonary embolism is an independent predictor of death after gastric bypass surgery. The optimal strategy for postoperative thrombophylaxis in bariatric surgery has yet to be elucidated. In 2010 our institution proposed a guideline for postoperative thrombophylaxis for bariatric surgery based on risk stratification. Patients were considered high risk if they had history of VTE or a BMI >/= 60 kg/m2 or if they had two or more of the following: age > 50, BMI >/= 50 kg/m2, male sex, recent history of smoking, obstructive sleep apnea, varicose veins, or hormone therapy within 30 days. All patients undergoing bariatric surgery received enoxaparin 40 mg SC twice daily in addition to mechanical thrombophylaxis including venodynes and compression stockings during the hospital stay. Prophylactic IVC filter insertion was not recommended. High-risk patients received an extended course of anticoagulation for 10 days after discharge.Methods: We retrospectively reviewed the medical charts of 692 patients who underwent bariatric surgery at Dartmouth-Hitchcock Medical Center from 2009 to 2014. We analyzed the incidence of VTE and bleeding complications under two different institutional thrombophylaxis protocols: an earlier protocol of VTE prophylaxis based on surgeon's preference (n = 62) and our subsequent protocol based on risk stratification (n = 630).Results: Prior to implementing our protocol the incidence of VTE and bleeding complications in patients who underwent bariatric surgery was 1.6% (1 in 62) for each. After 2010, with the implementation of extended VTE prophylaxis for high-risk patients, the incidence of postoperative VTE was 0% (0 in 630) and the incidence of postoperative bleeding was 2.7% (17 in 630). Of 17 patients who developed postoperative bleeding, 14 (82%) developed bleeding before postoperative day 3 during the hospitalization and 3 (18%) experienced delayed bleeding after hospital discharge. Of 3 patients with delayed bleeding, only 1 was on the extended thrombophylaxis protocol. Severe bleeding, defined as the need for packed red blood cell transfusions or re-operation, occurred in 1.6% (10 in 630).Conclusion: Our study demonstrates that a protocol based on risk stratification is effective at reducing the risk of symptomatic VTE in patients undergoing bariatric surgery. Although the incidence of all postoperative bleeding appears to have increased slightly after implementation of the protocol, the incidence of severe bleeding appears unchanged. As most of the post-operative bleeding events occurred during the hospitalization period, extending the length of pharmacologic thromboprophylaxis was not associated with an increase in bleeding. This study is limited by its retrospective design and the small number of patients studied prior to implementing the extended VTE prophylaxis protocol. Nevertheless, the findings are promising with respect to VTE risk reduction after bariatric surgery and suggest that prospective evaluation of the thromboprophylaxis protocol is in order. DisclosuresNo relevant conflicts of interest to declare.

Critical Review and Update on the Treatment of Acute and Chronic Pulmonary Embolism

Pulmonary embolism (PE), can be life-threatening without rapid appropriate therapy and often leads to chronic disease and disability. The ambiguity of symptoms makes PE difficult to diagnose, and available imaging strategies have their limitations. Treatment options for acute PE include fibrinolytics, surgical embolectomy, catheter-directed treatment, or vena cava filter placement as well as traditional parenteral anticoagulants, used alone or as a bridge to a vitamin K antagonist (VKA). The direct oral anticoagulants (DOACs) rivaroxaban and apixaban allow for single drug therapy, eliminating the need for initial parenteral anticoagulation, while dabigatran and edoxaban are initiated after a short course of parenteral therapy. The DOACs serve as a viable alternative to warfarin for chronic management for PE. Pulmonary embolism provoked from transient risk factors often requires a short-term course of anticoagulation (3 months). Unprovoked events, and those that occur in the presence of continuing risk factors such as cancer, or clinical markers such as residual vein thrombosis and elevated d-dimers can predict a higher risk of recurrent events and warrant extended anticoagulation. This review evaluates current recommendations for the treatment of PE, including dosing strategies, duration of therapy, and special populations such as renal impairment, malignancy, and obesity.

Venous thromboembolism in patients with glioblastoma multiforme: Findings of the RIETE registry

BackgroundThere is uncertainty about the optimal therapy of venous thromboembolism (VTE) in patients with glioblastoma multiforme (GBM). MethodsWe used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in patients with GBM, other cancers and in patients without cancer. ResultsAs of September 2014, 53,546 patients have been recruited in RIETE. Of these, 72 (0.13%) had GBM and 11,811 (22%) had other cancers. Most patients in all 3 subgroups received initial therapy with low-molecular-weight heparin (LMWH), but those with GBM received slightly lower doses than those with other cancers or without cancer. Then, most patients with GBM continued on LMWH for long-term therapy, at similar doses than those in the other subgroups. During the course of anticoagulation (mean, 202days), 3 patients with GBM presented VTE recurrences (10.9 per 100 patient-years; 95% CI: 2.76–29.5) and 4 suffered major bleeding (one intracranial) (14.5 bleeds per 100 patient-years; 95%CI: 4.60–34.9). Compared with patients with other cancers, those with GBM had a similar rate of VTE recurrences and major bleeds, but had a higher rate of extracranial hematoma (p<0.05). Compared with VTE patients without cancer, those with GBM had a higher rate of PE recurrences (p<0.01) and major bleeding (p<0.001), particularly extracranial hematoma (p<0.001). ConclusionsPatients with GBM and VTE had a similar rate of VTE recurrences or major bleeds during the course of anticoagulant therapy than those with other cancers.

Indirect comparison and cost-utility of dabigatran etexilate and rivaroxaban in the treatment and extended anticoagulation of venous thromboembolism in a UK setting

Background: Acute venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is traditionally managed with a short course of parenteral anticoagulation followed by 3–6 months of a vitamin-K antagonist. Non-vitamin K oral anticoagulants (NOACs) do not require routine monitoring and dose adjustment, thus potentially provide an alternative treatment option. Methods and results: Because of the lack of head-to-head clinical studies, an indirect comparison was conducted of dabigatran etexilate and rivaroxaban based on the respective phase III clinical trial. The derived relative safety and efficacy estimates were used to evaluate the cost-utility of dabigatran compared with rivaroxaban in the treatment and secondary prevention of VTE. The results of the indirect comparison showed no significant difference between dabigatran and rivaroxaban in avoiding recurrent VTE following index PE, index DVT, or DVT/PE combined, in treatment and extended anticoagulation. Dabigatran has significantly less major or clinically relevant bleeds (MCRBE) compared to rivaroxaban in treatment after index DVT and treatment after DVT or PE combined, but was not significantly different from rivaroxaban after index PE or in extended anticoagulation. In cost-utility deterministic analyses, dabigatran was projected dominant in all analyzed settings, given its marginally lower total cost and marginally higher QALYs gained compared to rivaroxaban. Probabilistic analyses results showed a high likelihood of dabigatran being considered good value for money in the UK, in treatment and in secondary prevention of VTE. Conclusion: The cost-effectiveness evaluations showed that dabigatran can be considered the dominant treatment strategy compared to rivaroxaban in the patients’ sub-groups considered, given the projected marginally higher clinical benefits and lower treatment costs.

Evaluation of the Caprini Model for Venothromboembolism in Esophagectomy Patients

Patients undergoing esophagectomy for cancer are in the highest-risk group for venous thromboembolism, with a 7.3% incidence reported by the National Surgical Quality Improvement Program. Venothromboembolism (VTE) doubles esophagectomy mortality. The Caprini risk assessment model (RAM) is a method to stratify postoperative thromboembolism risk for consideration of prolonged preventive anticoagulation in higher-risk patients. Our aim was to examine the potential use of this model for reducing the VTE incidence in esophagectomy patients. The records of patients who underwent an esophagectomy by the thoracic surgery service at our institution between June 2005 and June 2013 were reviewed. The inclusion criteria were a diagnosis of esophageal cancer treated with esophagectomy (any approach) and with available 60-day postoperative follow-up. Exclusion criteria were the presence of an inferior vena cava filter or chronic anticoagulation therapy. The Caprini risk score and the number of VTE events were recorded retrospectively for each patient. Seventy patients satisfied eligibility criteria. The VTE incidence was 14.3%. Patients with esophageal thromboembolism had a higher Caprini score distribution than patients without thromboembolism (p < 0.001). Adjusted logistic regression analysis demonstrated increased odds of VTE with increasing score (p < 0.05), with good discrimination. In this first report examining the Caprini model categories in an esophagectomy population, the VTE incidence in true high-risk patients was high. From this retrospective calculation of risk and events, patients in the highest-risk Caprini group may benefit from an enhanced course of postoperative anticoagulation.

Subsequent arterial ischemic events in patients receiving anticoagulant therapy for venous thromboembolism.

Patients with acute venous thromboembolism (VTE) are at increased risk for the development of subsequent arterial ischemic events unrelated to the diagnosis of VTE. Accurate identification of VTE patients at increased risk for ischemic events during the course of anticoagulation may help to select those who would potentially benefit from concomitant therapy with anticoagulants and antiplatelets. We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry to assess the rate and severity of subsequent ischemic events (ie, stroke, myocardial infarction, lower limb amputation, or mesenteric ischemia) appearing during the course of anticoagulant therapy and tried to identify risk factors for these events. From February 2009 to March 2014, 23,370 patients were recruited: 12,397 initially presenting with pulmonary embolism (PE) and 10,973 with deep venous thrombosis. During the course of anticoagulation (mean, 9.2 months), 597 patients developed recurrent VTE, 652 bled, 162 had ischemic events (stroke, 86; myocardial infarction, 53; limb amputation, 13; mesenteric ischemia, 11), and 2063 died. Of these, 29 patients died of recurrent PE, 83 of bleeding, and 53 of the ischemic events. On multivariable analysis, cancer (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.21-2.61), chronic lung disease (HR, 1.54; 95% CI, 1.05-2.26), renal insufficiency (HR, 1.72; 95% CI, 1.25-2.36), anemia (HR, 1.54; 95% CI, 1.11-2.14), prior artery disease (HR, 1.84; 95% CI, 1.29-2.64), and diabetes (HR, 1.58; 95% CI, 1.10-2.27) independently predicted the risk for ischemic events. Most of these variables also predicted major bleeding (cancer, chronic lung disease, renal insufficiency, anemia, and prior artery disease) or recurrent PE (cancer, chronic lung disease, anemia, and prior artery disease). In patients receiving anticoagulation for VTE, the mortality due to PE recurrences was lower than the mortality due to ischemic events. Most independent predictors for ischemic events were also predictors for major bleeding and for recurrent PE.

Gender differences in cancer patients with acute venous thromboembolism

The outcome of cancer patients with acute venous thromboembolism (VTE) may differ according to gender. We used the RIETE database to compare the rate of VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) recurrences), major bleeding and mortality during the course of anticoagulation, according to gender. As of August 2014, 11,055 patients with active cancer were enrolled in RIETE, of whom 5,104 (46%) were women. During the course of anticoagulation (mean: 142 days), 505 patients developed recurrent VTE, 429 bled and 2730 died. Compared with men, women had a significantly lower rate of fatal bleeding (risk ratio [RR]: 0.69; 95% CI: 0.47-0.99) and death (RR: 0.90; 95% CI: 0.83-0.97), and a non-significantly lower rate of PE recurrences (RR 0.83; 95% CI: 0.65-1.06) and major bleeding (RR: 0.89; 95% CI: 0.74-1.08). During the course of anticoagulation, cancer women with VTE had a better outcome than men.

Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin - a model-based study.

PurposeDabigatran (D) is increasingly used for chronic anticoagulation in place of warfarin (W). These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation.Patients and methodsIn a retrospective study of patients treated with D, W, or neither drug (N) undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM) analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups.ResultsData for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P<0.05) to the initial heparin bolus than Group W (approximately 50%). Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the heparin effect in the model did not differ significantly among groups.ConclusionPatients on warfarin with an average INR of 1.5 or higher are more sensitive to heparin than patients not previously anticoagulated or patients who discontinued dabigatran 27 hours earlier (approximately two half-lives) warfarin.

Fragile Patients With Venous Thromboembolism, What did We Learn From RIETE

In recent years, a number of new anticoagulants have been developed for the treatment of venous thromboembolism (VTE), demonstrating significant reductions in major bleeding compared with standard therapy. Subgroup analyses showed favourable results for rivaroxaban in the so-called fragile patients (defined as those having creatinine clearance levels ≤50 mL/min, age ≥75 years or body weight ≤50 kg) compared with standard therapy. However, the prevalence of fragile patients with VTE in real life and their natural history during the course of anticoagulation has not been thoroughly investigated. We used the RIETE registry database to assess the proportion of fragile patients with VTE in real life, and their natural history during the course of anticoagulant therapy. We found that 43% of patients with VTE were fragile, and that they had an over 2-fold higher rate of major bleeding during the course of anticoagulant therapy compared with non-fragile patients.