Thromboprophylaxis In Ambulatory Patients Research Articles

Preventative and curative treatment of venous thromboembolic disease in cancer patients

Cancer-associated venous thromboembolism (CAT) is common in patients with cancer and associated with significant morbidity and mortality. The incidence of CAT continues to rise, complicating patient care and burdening healthcare systems. Patients with cancer experiencing VTE face poorer prognoses, making prevention and effective management imperative. This narrative review synthesizes evidence on thromboprophylaxis in ambulatory patients with cancer receiving systemic therapy and acute treatment strategies for CAT. Risk assessment models (e.g., Khorana score) aid in identifying high-risk patients who may benefit from thromboprophylaxis. Pharmacological thromboprophylaxis with low molecular weight heparins (LMWHs) direct oral anticoagulants (DOACs) has been shown to reduce the risk of CAT without significantly increasing the risk of bleeding complications. However, implementation of risk-based strategies remains limited in clinical practice. For acute CAT management, LMWHs have been the standard of care, but DOACs are increasingly favored due to their convenience and efficacy. However, challenges persist, including bleeding risks and drug interactions. Emerging therapies targeting Factor XI inhibitors present promising alternatives, potentially addressing current limitations in anticoagulation management for CAT.

Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers

Thromboprophylaxis for individuals receiving systemic anticancer therapies has proven to be effective. Potential to maximize benefits relies on improved risk-directed strategies, but existing risk models underperform in cohorts with lung and gastrointestinal cancers. To assess clinical benefits and safety of biomarker-driven thromboprophylaxis and to externally validate a biomarker thrombosis risk assessment model for individuals with lung and gastrointestinal cancers. This open-label, phase 3 randomized clinical trial (Targeted Thromboprophylaxis in Ambulatory Patients Receiving Anticancer Therapies [TARGET-TP]) conducted from June 2018 to July 2021 (with 6-month primary follow-up) included adults aged 18 years or older commencing systemic anticancer therapies for lung or gastrointestinal cancers at 1 metropolitan and 4 regional hospitals in Australia. Thromboembolism risk assessment based on fibrinogen and d-dimer levels stratified individuals into low-risk (observation) and high-risk (randomized) cohorts. High-risk patients were randomized 1:1 to receive enoxaparin, 40 mg, subcutaneously daily for 90 days (extending up to 180 days according to ongoing risk) or no thromboprophylaxis (control). The primary outcome was objectively confirmed thromboembolism at 180 days. Key secondary outcomes included bleeding, survival, and risk model validation. Of 782 eligible adults, 328 (42%) were enrolled in the trial (median age, 65 years [range, 30-88 years]; 176 male [54%]). Of these participants, 201 (61%) had gastrointestinal cancer, 127 (39%) had lung cancer, and 132 (40%) had metastatic disease; 200 (61%) were high risk (100 in each group), and 128 (39%) were low risk. In the high-risk cohort, thromboembolism occurred in 8 individuals randomized to enoxaparin (8%) and 23 control individuals (23%) (hazard ratio [HR], 0.31; 95% CI, 0.15-0.70; P = .005; number needed to treat, 6.7). Thromboembolism occurred in 10 low-risk individuals (8%) (high-risk control vs low risk: HR, 3.33; 95% CI, 1.58-6.99; P = .002). Risk model sensitivity was 70%, and specificity was 61%. The rate of major bleeding was low, occurring in 1 participant randomized to enoxaparin (1%), 2 in the high-risk control group (2%), and 3 in the low-risk group (2%) (P = .88). Six-month mortality was 13% in the enoxaparin group vs 26% in the high-risk control group (HR, 0.48; 95% CI, 0.24-0.93; P = .03) and 7% in the low-risk group (vs high-risk control: HR, 4.71; 95% CI, 2.13-10.42; P < .001). In this randomized clinical trial of individuals with lung and gastrointestinal cancers who were stratified by risk score according to thrombosis risk, risk-directed thromboprophylaxis reduced thromboembolism with a desirable number needed to treat, without safety concerns, and with reduced mortality. Individuals at low risk avoided unnecessary intervention. The findings suggest that biomarker-driven, risk-directed primary thromboprophylaxis is an appropriate approach in this population. ANZCTR Identifier: ACTRN12618000811202.

OC-15: Targeted thromboprophylaxis in ambulatory patients receiving anticancer therapies for lung or gastrointestinal cancers (TARGET-TP); a randomized trial

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Cost-utility analysis of apixaban compared with usual care for primary thromboprophylaxis in ambulatory patients with cancer.

Background:Apixaban (2.5 mg) taken twice daily has been shown to substantially reduce the risk of venous thromboembolism (VTE) compared with placebo for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE. We aimed to compare the health system costs and health benefits associated with primary thromboprophylaxis using apixaban with those associated with the current standard of care (where no primary thromboprophylaxis is given), from the perspective of Canada’s publicly funded health care system in this subpopulation of patients with cancer over a lifetime horizon.Methods:We performed a cost–utility analysis to estimate the incremental cost per quality-adjusted life-year (QALY) gained with primary thromboprophylaxis using apixaban. We obtained baseline event rates and the efficacy of apixaban from the Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) trial on apixaban prophylaxis. We estimated relative risk for bleeding, risk of complications associated with VTE treatment, mortality rates, costs and utilities from other published sources.Results:Over a lifetime horizon, apixaban resulted in lower costs to the health system (Can$7902.98 v. Can$14 875.82) and an improvement in QALYs (9.089 v. 9.006). The key driver of cost–effectiveness results was the relative risk of VTE as a result of apixaban. Results from the probabilistic analysis showed that at a willingness to pay of Can$50 000 per QALY, the strategy with the highest probability of being most cost-effective was apixaban, with a probability of 99.87%.Interpretation:We found that apixaban is a cost-saving option for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE.

Risk Factors and Prediction Models for Venous Thromboembolism in Ambulatory Patients with Lung Cancer.

Venous thromboembolism (VTE) is a significant cause of mortality in patients with lung cancer. Despite the availability of a wide range of anticoagulants to help prevent thrombosis, thromboprophylaxis in ambulatory patients is a challenge due to its associated risk of haemorrhage. As a result, anticoagulation is only recommended in patients with a relatively high risk of VTE. Efforts have been made to develop predictive models for VTE risk assessment in cancer patients, but the availability of a reliable predictive model for ambulate patients with lung cancer is unclear. We have analysed the latest information on this topic, with a focus on the lung cancer-related risk factors for VTE, and risk prediction models developed and validated in this group of patients. The existing risk models, such as the Khorana score, the PROTECHT score and the CONKO score, have shown poor performance in external validations, failing to identify many high-risk individuals. Some of the newly developed and updated models may be promising, but their further validation is needed.

The Clinical Applicability of Primary Thromboprophylaxis in Ambulatory Patients With Pancreatic Cancer.

Thromboembolism is a leading cause of death in ambulatory patients with cancer. Patients with pancreatic adenocarcinoma have a very high risk of developing venous thromboembolism, especially within the first 6 months of diagnosis. Although primary thromboprophylaxis could reduce this risk, there are unresolved questions concerning choice of agents for anticoagulation, duration of anticoagulation treatment, and criteria for patient selection. Furthermore, the current clinical guidelines on primary thromboprophylaxis in ambulatory patients with pancreatic cancer are ambiguous. This review seeks out to understand and critically appraise the evidence supporting the use of primary thromboprophylaxis in patients with pancreatic cancer and its clinical applicability.

Success of Online CME at Improving Knowledge and Confidence Around Guideline-Directed Management of Cancer-Associated Thrombosis

Title:Success of Online CME at Improving Knowledge and Confidence Around Guideline-Directed Management of Cancer-Associated Thrombosis Study Objectives:Recent guidance statements recommend the use of direct oral anticoagulants (DOACs) as primary thromboprophylaxis in ambulatory patients with cancer who are starting chemotherapy and in patients with cancer and acute venous thromboembolism at low risk of bleeding and no drug-drug interactions.[Farge 2019; Key 2020] Yet, many clinicians lack knowledge and confidence with integrating DOACs into management strategies for patients with cancer in accordance to guideline recommendations.[Cushman 2015; Khorana 2016] We sought to determine if online continuing medical education (CME) could improve the knowledge and confidence of hematologists/oncologists regarding guideline-directed use of DOACs in the management of cancer-associated thrombosis. Methods:This CME intervention comprised of a 30-minute online video-based roundtable discussion among experts in the field of cancer-associated thrombosis management. Responses to 3 multiple-choice, knowledge questions and 1 self-efficacy, 5-point Likert scale confidence question were analyzed using a repeated pairs pre-/post-assessment study design. A chi-square test (P &amp;lt;.05 is considered significant) assessed pre- to post-activity change . The activity launched December 23, 2019, and data were collected through February 24, 2020. Results:In total, 71 Hematologists/Oncologists were included in this study. Overall, there were knowledge and confidence improvements seen among all groups from pre- to post-assessment: 27% of hematologists/oncologists (P&amp;lt;.01) improved at identifying guideline-directed therapy regarding recommended thromboprophylaxis in patients with cancer per guideline recommendations.27% of hematologists/oncologists (P&amp;lt;.01) improved at selecting guideline-appropriate treatment options for cancer-associated thrombosis.44% of hematologists/oncologists had an increase in confidence in managing thrombosis in patients with cancer. Continued educational gaps: 25% of hematologists/oncologists failed to select guideline recommended DOAC therapy for thromboprophylaxis in cancer patients.45% of hematologists/oncologists failed to select guideline recommended DOAC therapy for treatment of thrombosis in cancer patients.66% of hematologists/oncologists still remain at only a rating of 1 to 3 on a scale of 1 to 5 in their confidence managing thrombosis in patients with cancer. Conclusion:This study demonstrates the success of online, CME-accredited, video-based roundtable discussion with experts in the field on significantly improving knowledge and confidence of hematologists/oncologists related to the guideline-recommended use of DOACs in the management of cancer-associated thrombosis. Continued gaps were also identified for future educational targets. Sources of support: Developed through an independent educational grant from Janssen in partnership with the University of Chicago.

Patterns and predictors of thromboembolic events among patients with gastric cancer

Patients with gastric cancer are at higher risk for venous thromboembolic events (VTE). Majority of such patients are treated in ambulatory settings where thromboprophylaxis is not routinely offered. In this study, we report on VTE rates and search for predictors that may help identify patients at higher risk to justify VTE-prophylaxis in ambulatory settings. Patients with pathologically-confirmed gastric adenocarcinoma were retrospectively reviewed for VTE detected by imaging studies. Clinical and pathological features known to increase the risk of VTE were studied. Khorana risk assessment model was applied on patients receiving chemotherapy. A total of 671 patients; median age 55 years, were recruited. VTE were diagnosed in 150 (22.4%) patients, including 42 (28.0%) pulmonary embolism and 18 (12.0%) upper extremity deep vein thrombosis (DVT). Majority (> 80%) developed VTE while in ambulatory settings and none had been on thromboprophylaxis. Rate was higher (27.1%) among 365 patients with metastatic compared to 16.7% among 306 patients with nonmetastatic disease, p = 0.001. Patients with metastatic disease who received multiple lines of chemotherapy (n = 85) had significantly higher rate of VTE compared to those who received a single line; 48.2% versus 19.4%, p < 0.001. Among the whole group, Khorana risk score, age, gender, smoking and obesity had no impact on VTE rates. Patients with metastatic gastric cancer, especially when treated with multiple lines of chemotherapy, are at a significantly higher risk of VTE. Khorana risk score had no impact on VTE rates. Thromboprophylaxis in ambulatory patients with metastatic gastric cancer worth studying.

Humanitas COVID-19 Task Force Venous and Arterial Thromboembolic Complications in COVID-19 Patients Admitted to an Academic Hospital in Milan, Italy

The occurrence of arterial and venous thromboembolic events was unusually high in hospitalized patients with coronavirus disease 2019 (COVID-19) in a Milan hospital from February to April 2020, prompting a revision of the diagnostic strategies and the use of thromboprophylaxis in ambulatory patients with COVID-19.

D-Dimer Enhances Risk-Targeted Thromboprophylaxis in Ambulatory Patients with Cancer.

Thromboprophylaxis for ambulatory patients with cancer is effective, although uncertainties remain on who should be targeted. Using D-dimer values from individuals enrolled to the AVERT trial, we sought to identify and validate a more efficient venous thromboembolism (VTE) risk threshold for thromboprophylaxis. The AVERT trial compared thromboprophylaxis with apixaban with placebo among patients with cancer with a Khorana Risk Score ≥2. The D-dimer measured at randomization was used to calculate an individualized 6-month VTE risk using the validated CATScore. A modified intention-to-treat analysis was used to assess efficacy (VTE) and safety (major and overall bleeding) in the (a) complete cohort and (b) ≥8% and < 8% 6-month VTE risk thresholds. Five hundred seventy-four patients were randomized in the AVERT trial; 466 (81%) with baseline D-dimer were included in the study. Two hundred thirty-seven subjects received apixaban; 229 received placebo. In the complete cohort, there were 13 (5.5%) VTE events in the apixaban arm compared with 26 (11.4%) events in the placebo arm (adjusted hazard ratio [aHR] 0.49 [0.25-0.95], p < .05). Number needed to treat (NNT) to prevent one VTE = 17. Eighty-two (35%) and 72 (31%) patients in the apixaban and placebo arms, respectively, had a 6-month VTE risk ≥8%. In this subgroup, 7 (8.4%) VTE events occurred with apixaban and 19 (26.3%) events with placebo (aHR 0.33 [0.14-0.81], p < .05), NNT = 6. Individuals with a VTE risk <8% derived no benefit from apixaban thromboprophylaxis (aHR 0.89 [0.30-2.65), p = .84). Increased rates of overall bleeding were observed with apixaban in both the complete (aHR 2.11 [1.09-4.09], p < .05) and ≥ 8% predicted risk cohorts (aHR 2.87 [0.91-9.13], p = .07). A 6-month VTE risk threshold of ≥8% increases the efficiency of risk-targeted thromboprophylaxis in ambulatory patients with cancer. Ambulatory patients with cancer receiving chemotherapy have an increased risk of venous thromboembolism (VTE). A Khorana Risk Score (KRS) ≥2 is currently the suggested threshold for thromboprophylaxis. Using baseline D-dimer values from individuals enrolled to the AVERT trial, this retrospective validation study identifies a 6-month VTE risk of ≥8% as a more efficient threshold for thromboprophylaxis. At this threshold, the number needed to treat to prevent one VTE is 6, compared with 17 when using a KRS ≥2. Conversely, individuals with a predicted risk of <8% derive no clinical benefit from thromboprophylaxis. Future prospective studies should validate this threshold for outpatient thromboprophylaxis.

Rivaroxaban thromboprophylaxis in ambulatory patients with pancreatic cancer: Results from a pre-specified subgroup analysis of the randomized CASSINI study.

BackgroundPancreatic cancer patients are at risk for venous thromboembolism (VTE); the value of thromboprophylaxis has not been definitively established.MethodsThis trial randomized cancer patients initiating a new regimen and at high risk for VTE (Khorana score ≥2) to rivaroxaban 10 mg or placebo up to day 180. This analysis examined the subset of pancreatic cancer patients. The primary efficacy endpoint was the composite of symptomatic deep‐vein thrombosis (DVT), asymptomatic proximal DVT, any pulmonary embolism, and VTE‐related death. The primary safety endpoint was International Society on Thrombosis and Haemostasis–defined major bleeding.ResultsIn total, 49/1080 (4.5%) patients enrolled had baseline VTE on screening, with higher rates (24/362 [6.6%]) in pancreatic cancer and they were not randomized. Of 841 randomized patients, 273 (32.5%) had pancreatic cancer; 155/273 (57% in each arm) completed the double‐blind period. The primary endpoint occurred in 13/135 (9.6%) patients in the rivaroxaban group and in 18/138 (13.0%) in the placebo group (hazard ratio [HR] = 0.70; 95% CI, 0.34‐1.43; P = .328) in up‐to‐day‐180 period and 5/135 (3.7%) patients receiving rivaroxaban and 14/138 (10.1%) receiving placebo in the intervention period (HR = 0.35; 95% CI, 0.13‐0.97; P = .034). Major bleeding was similar (2 [1.5%] receiving rivaroxaban and 3 [2.3%] receiving placebo). Correlative biomarker studies demonstrated significant decline in D‐dimer (weeks 8 and 16) in patients randomized to rivaroxaban compared to placebo (P < .01).ConclusionsIn ambulatory pancreatic cancer patients, rivaroxaban did not result in significantly lower incidence of VTE or VTE‐related death in the 180‐day period. During the intervention period, however, rivaroxaban substantially reduced VTE without increasing major bleeding, suggesting benefit of rivaroxaban prophylaxis in this setting.Trial registration: ClinicalTrials.gov identifier, NCT02555878.

Increased dose primary thromboprophylaxis in ambulatory patients with advanced pancreatic ductal adenocarcinoma, a single centre cohort study

BackgroundAdvanced pancreatic ductal adenocarcinoma (aPDAC) patients have a lifetime all type thromboembolic event (ATTE) rate of 25–35%. Efficacy and safety of increased dose primary thromboprophylaxis (IDPTP) with low molecular heparin (LMWH) given for 3 months has been shown in two prospective randomized trials.ObjectivesTo report on efficacy -reduction of all type thromboembolic events (ATTE)-, safety -incidence of Major Bleeding (MB)- and compliance in a single-centre cohort of aPDAC patients receiving first line chemotherapy and LMWH-IDPTP.MethodsFrom May 2009 to October 2016, 82 patients received IDPTP –LMWH with dalteparin. Schedule: 55 kg and below: 7500 IU, between 55 and 80 kg: 10,000 IU, above 80 kg: 12,500 IU. MB is reported using the International Society of Thrombosis and Haemostasis (ISTH) criteria. ATTE was defined as any arterial or venous event, incidental or clinically symptomatic, including visceral VTE.ResultsMean and median time on dalteparin was 10.2 (95%CI 8.1, 12.4) and 8.0 (95%CI 6.2, 9.7) months respectively. ATTE was observed in 7 (8.5%) of patients, with a median time on IDPTP of 6.2 months (95% CI 10.0, 13.2). MB was seen in 10 (12.2%) patients with a median time on IDPTP of 4.5 months (95% CI 1.6, 7.4). Six major bleeds (60%) were the direct or indirect result of aPDAC. Eighty-one patients had died at the time of data collection with a median overall survival time of 8.7 months (95%CI 6.4, 11.0). Thromboembolism and bleeding were late events. No impact of thromboembolism or bleeding on overall survival was observed.ConclusionsIDPTP-dalteparin was associated with lower ATTE occurrence rates than expected and comparable major bleeding rates. ATTE and MB were late events, the majority of MB was from direct or indirect result of locally progressing aPDAC. Since these conditions can frequently arise in aPDAC, IDPTP should be regularly reviewed beyond 3 months.

Direct oral anticoagulants for thromboprophylaxis in ambulatory patients with cancer

ABSTRACT Background: Venous thromboembolism (VTE) is a common complication in cancer patients. We aim to evaluate the effect and safety of direct oral anticoagulants (DOACs) as primary prophylaxis in ambulatory cancer patients. Methods: We conducted a literature search in PubMed, EMBASE and ClinicalTrials for studies that evaluated DOACs for thromboprophylaxis in cancer patients. RevMan 5.3 software was used for this meta-analysis. Results: Three randomized controlled trials (RCTs) with a total of 1465 patients were pooled in the meta-analysis. DOACs significantly reduced the symptomatic VTE incidence during intervention period (RR 0.23, CI 0.11-0.47, P<0.0001, I2 =9%). Significantly lower total VTE incidence (RR 0.53, CI 0.36-0.78, P = 0.001, I2 =30%) and PE incidence (RR 0.50, CI 0.28-0.89, P = 0.02, I2 =5%) were found during the observation period, and a trend for less symptomatic DVT events was found in the DOACs group (RR 0.62, CI 0.37-1.04, P = 0.07, I2 =5%). No differences for all-cause mortality were found between groups (RR 0.92, CI 0.74-1.15, P = 0.47, I2 =14%). DOACs did not significantly increase major bleeding risks (RR 1.66, CI 0.72-3.83, P = 0.24, I2 =0%) during the intervention period or clinically relevant non-major bleeding events (RR 1.50, CI 0.90-2.49, P = 0.12, I2 =0%) and total bleeding events during the observation period (RR 1.50, CI 0.98-2.29, P = 0.06, I2 =0%). Conclusion: DOACs are effective for thromboprophylaxis in ambulatory cancer patients, but there is a potential risk of bleeding. DOACs may be recommended in selected patients at high risk of VTE. More high-quality studies are needed to further validate our results. Abbreviations: CAT: cancer-associated thrombosis; CI: confidence interval; DOAC: direct oral anticoagulant; DVT: deep vein thrombosis; LMWH: low molecular weight heparin; NNH: number needed to harm; NNT: number needed to treat; PE: pulmonary embolism; RCT: randomized controlled trials; RR: risk ratio; RD: rate difference; VTE: venous thromboembolism.

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update.

To provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs published from August 1, 2014, through December 4, 2018. ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed. The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment. Two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin (LMWH) in patients with GI and potentially genitourinary cancers. Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE. Changes to previous recommendations: Clinicians may offer thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer; rivaroxaban and edoxaban have been added as options for VTE treatment; patients with brain metastases are now addressed in the VTE treatment section; and the recommendation regarding long-term postoperative LMWH has been expanded. Re-affirmed recommendations: Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for all outpatients with cancer. Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE.Additional information is available at www.asco.org/supportive-care-guidelines.

Apixaban to Prevent Venous Thromboembolism in Patients with Cancer

BackgroundPatients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis.MethodsWe conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode.ResultsOf the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P=0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24).ConclusionsApixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.)

Benefit and risk of primary thromboprophylaxis in ambulatory patients with advanced pancreatic cancer receiving chemotherapy: a systematic review and meta-analysis of randomized controlled trials.

As vascular thromboembolism (VTE) is a leading cause of death in cancer patients, it has been postulated that primary thromboprophylaxis (PTP) in cancer patients might improve survival by reducing VTE occurrence. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) to investigate the benefit and risk of PTP with low-molecular-weight heparins (LMWHs) in ambulatory advanced pancreatic cancer (APC) patients receiving chemotherapy. We undertook a literature search using MEDLINE and EMBASE databases through May 2015. RCTs with reduction in symptomatic VTE as a primary or secondary endpoints were included. Mantel-Haenszel method was used to estimate the pooled event-based risk ratio as well as the pooled absolute risk difference with 95% confidence interval (CI). Seven hundred and thirty-eight APC patients were eligible for analysis. PTP lasted 3-6 months. The crude VTE incidence was 2.1 and 11.2% in LMWH and in control groups, respectively (risk ratio, 0.18; 95% CI, 0.083-0.39; P < 0.0001). The absolute risk difference in VTE was -0.092 (95% CI, -0.127 to -0.057; P < 0.0001), with an estimated number needed to treat of 11 patients to prevent one symptomatic VTE event. The pooled risk ratio for major bleeding was 1.25 (95% CI, 0.48-3.3, P = 0.65). Although these findings are encouraging to deploy PTP in APC patients receiving chemotherapy, uncertainties remain as to its survival benefit, optimal PTP duration, type and dose of LMWH, and costs of care. Therefore, adequately powered randomized phase III studies are warranted to address these questions.

Benefit and Risk of Primary Thromboprophylaxis in Ambulatory Patients with Advanced Pancreatic Cancer Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Vascular thromboembolism (VTE) is the second leading cause of death in patients with cancer. Despite the fact that mortality is increased in cancer patients who developed VTE compared to those without VTE, empirical prophylaxis against VTE in ambulatory patients with cancer remains controversial. The risk of VTE is higher for certain types of cancer such as pancreatic and hematologic malignancies, in patients with advanced cancer, and in those who are undergoing chemotherapy or radiotherapy. We carried out a systematic review and meta-analysis of randomized controlled trials (RCT) to investigate the benefit and risk of primary thromboprophylaxis (PTP) with low-molecular weight heparins (LMWH) in ambulatory patients with advanced pancreatic cancer receiving chemotherapy.Methods: We undertook an extensive literature search using MEDLINE and EMBASE databases through July 13, 2014. References of the potential studies were also reviewed for any additional relevant studies. RCTs with reduction in symptomatic VTE as a primary endpoint were included. Mantel-Haenszel method was used to estimate the pooled event-based risk ratio (RR) as well as the pooled absolute risk difference (RD) with 95% confidence interval (CI). Fixed effects model was applied because there was homogeneity among the included studies (I2 = 0.00).Results: Two RCTs and a subgroup of another two RCTs, comprising a total of 738 patients with advanced pancreatic cancer, were eligible for analysis. Antithrombotics used in these trials were nadroparin (prophylactic dose), semuloparin (prophylactic dose), enoxaparin (semi-therapeutic dose), and dalteparin (therapeutic dose). The duration of PTP lasted from three to six months. The crude incidence of VTE was 5.51% and 15.12% in those receiving anticoagulants and in control patients, respectively, with a risk ratio of 0.36 (CI: 0.22 – 0.59, p < 0.0001). The absolute risk difference in VTE was 9.5% (CI: 5.3 – 13.8 %, p < 0.0001), with an estimate of the number needed to treat (NNT) of 10.5 to prevent one symptomatic VTE event. Major bleeding events were reported in 5.48% of patients on thromboprophylaxis compared to 7.94% in control patients according to an analysis of two RCTs. The pooled relative risk for major bleeding was statistically nonsignificant at 0.68 (CI: 0.33 – 1.39, p = 0.29).Conclusions: A previous meta-analysis reported that approximately 60 patients were required to be treated with LMWH to prevent one symptomatic VTE among unselected cancer patients receiving chemotherapy. Our meta-analysis revealed that thromboprophylaxis resulted in a significant reduction in symptomatic VTE events with NNT of 10.5 without an increase in major bleeding events, indicating that PTP with anticoagulants in advanced pancreatic cancer patients receiving chemotherapy may be beneficial. Further large randomized phase III studies are recommended to evaluate the effects of such targeted thromboprophylaxis on morbidity, mortality and the costs of care. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Thromboprophylaxis for medical patients with cancer: what do the guidelines say?

Venous thromboembolism (VTE) is frequent in cancer patients and is one of the leading causes of death in this population. Hospitalized cancer patients and those receiving chemotherapy are at the greatest risk of developing VTE. Many randomized controlled trials in a variety of patient populations have demonstrated that primary prophylaxis is effective in reducing the risk of VTE among cancer patients. Pharmacological thromboprophylaxis is recommended in all hospitalized medically ill cancer patients without a contraindication to anticoagulant therapy. Thromboprophylaxis in ambulatory patients undergoing chemotherapy is only considered in those at high risk of VTE. In this article, we evaluate the different clinical practice guideline recommendations for primary VTE prophylaxis in hospitalized medically ill patients with cancer and ambulatory patients undergoing chemotherapy.

Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Venous thromboembolism (VTE), a common complication in patients with cancer, is associated with increased risk of morbidity, mortality, and recurrent VTE. Risk factors for VTE in cancer patients include the type and stage of cancer, comorbidities, age, major surgery, and active chemotherapy. Evidence-based guidelines for thromboprophylaxis in cancer patients have been published: the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines recommend thromboprophylaxis for hospitalized cancer patients, while the American College of Chest Physician guidelines recommend thromboprophylaxis for surgical patients with cancer and bedridden cancer patients with an acute medical illness. Guidelines do not generally recommend routine thromboprophylaxis in ambulatory patients during chemotherapy, but there is evidence that some of these patients are at risk of VTE; some may be at higher risk while on active chemotherapy. Approaches are needed to identify those patients most likely to benefit from thromboprophylaxis, and, to this end, a risk assessment model has been developed and validated. Despite the benefits, many at-risk patients do not receive any thromboprophylaxis, or receive prophylaxis that is not compliant with guideline recommendations. Quality improvement initiatives have been developed by the Centers for Medicare and Medicaid Services, National Quality Forum, and Joint Commission to encourage closure of the gap between guideline recommendations and clinical practice for prevention, diagnosis, and treatment of VTE in hospitalized patients. Health-care institutions and providers need to take seriously the burden of VTE, improve prophylaxis rates in patients with cancer, and address the need for prophylaxis across the patient continuum.

Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

Venous thromboembolism (VTE), a common complication in patients with cancer, is associated with increased risk of morbidity, mortality, and recurrent VTE. Risk factors for VTE in cancer patients include the type and stage of cancer, comorbidities, age, major surgery, and active chemotherapy. Evidence-based guidelines for thromboprophylaxis in cancer patients have been published: the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines recommend thromboprophylaxis for hospitalized cancer patients, while the American College of Chest Physician guidelines recommend thromboprophylaxis for surgical patients with cancer and bedridden cancer patients with an acute medical illness. Guidelines do not generally recommend routine thromboprophylaxis in ambulatory patients during chemotherapy, but there is evidence that some of these patients are at risk of VTE; some may be at higher risk while on active chemotherapy. Approaches are needed to identify those patients most likely to benefit from thromboprophylaxis, and, to this end, a risk assessment model has been developed and validated. Despite the benefits, many at-risk patients do not receive any thromboprophylaxis, or receive prophylaxis that is not compliant with guideline recommendations. Quality improvement initiatives have been developed by the Centers for Medicare and Medicaid Services, National Quality Forum, and Joint Commission to encourage closure of the gap between guideline recommendations and clinical practice for prevention, diagnosis, and treatment of VTE in hospitalized patients. Health-care institutions and providers need to take seriously the burden of VTE, improve prophylaxis rates in patients with cancer, and address the need for prophylaxis across the patient continuum.