Direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis in cancer-related surgeries: A meta-analysis of efficacy and safety outcomes

Safety and Efficacy of Direct Oral Anticoagulants in Comparison to Low Molecular Weight Heparin in Hematological Malignancies

e24102 Background: Over the past decade, there has been an increase in the use of direct oral anticoagulants (DOACs) in the cancer population despite limited data comparing its use against low molecular weight heparin (LMWH), the standard of care in cancer patients. Increasing data supporting DOACs in cancer-associated thrombosis has emerged over the past few years. Nonetheless, this study will evaluate the relative safety and efficacy of DOACs versus LMWH in cancer-associated thrombosis within an urban setting associated with low socioeconomic status. Methods: This is a retrospective chart review of medical records from patients treated at an urban academic medical center from October 2010 through October 2018. Patients met study inclusion if they had a diagnosis of venous thromboembolism occurring after the date of diagnosis of active cancer and were prescribed a direct oral anticoagulant (rivaroxaban, apixaban, dabigatran, edoxaban) or a low molecular weight heparin (dalteparin, enoxaparin, or fondaparinux) as monotherapy for the treatment of venous thromboembolic disease. Patients were excluded if they had less than 6 months of follow up data for reasons other than death. The primary outcomes were recurrent venous thromboembolism, major bleeding and death. Results: Of the 914 patients who met inclusion criteria, 286 were excluded due to lack of follow up data. The remaining patients included 472 in the LMWH arm and 156 in the DOAC arm. At 6 months, recurrent thromboembolism occurred in 5 of the 472 patients (1.1%) in the LMWH group as compared with 4 of the 156 patients (2.6%) in the DOAC group (p = 0.170). Major bleeding occurred in 36 patients (7.6%) in the LMWH group and 11 patients (7.0%) in the DOAC group (p = 0.813). Death within 6 months of starting anticoagulation occurred in 76 patients (16.1%) in the LMWH group and 16 patients (9.6%) in the DOAC group (p = 0.046). Discontinuation before 6 months of treatment occurred in 241 patients (51.2%) in the LMWH group and 46 patients (29.5%) in the DOAC group. Conclusions: The LMWH and DOAC groups had similar rates of recurrent thromboembolism and major bleeding. The mortality rate within 6 months of starting anticoagulation was significantly higher in the LMWH group and this difference requires further evaluation. These results help support the continued use of DOACs for the treatment of cancer-associated thrombosis and demonstrate that DOACs are as safe and effective as LMWH in this patient population.

2015 Background: Glioblastoma (GBM) is associated with a high rate of venous thromboembolism (VTE), but there is little data to guide anticoagulation in GBM patients, in whom the risks of VTE must be balanced against the risk of intracranial hemorrhage (ICH). Methods: We performed a single-institution retrospective cohort study of patients with GBM diagnosed with VTE from 2014-2021 who were treated with low molecular weight heparin (LMWH) or a direct oral anticoagulant (DOAC). The cumulative incidence of ICH was compared between the LMWH and DOAC groups. The primary outcome was clinically relevant ICH within the first 30 days of anticoagulation, defined as any ICH that was fatal, symptomatic, required surgical intervention, and/or led to cessation of anticoagulation. Key secondary outcomes included clinically relevant ICH within 6 months, fatal ICH within 30 days and 6 months, any bleeding within 30 days and 6 months, and recurrent VTE within 6 months. Fisher’s exact test was used for comparison of primary and secondary endpoints between the two groups. Cumulative incidence curves were generated using the Kaplan-Meier method, and the cumulative incidence of clinically relevant ICH at both the 30-day timepoint and 6-month timepoint was compared between the DOAC and LMWH groups using the Gray test to account for death as a competing risk. Results: A total of 121 patients were identified in the primary cohort for 30-day outcome analyses (DOAC, n = 33; LMWH, n = 88). For 6-month outcome analyses, the cohort included only patients who were maintained on their initial anticoagulant (DOAC or LMWH) and did not switch anticoagulants during the 6 months following diagnosis of VTE (DOAC, n = 32; LMWH, n = 75). The cumulative incidence of clinically relevant ICH at 30 days was 0% (0/33) in the DOAC group and 9% (8/88) in the LMWH group (p = 0.11). The cumulative incidence of clinically relevant ICH at 6 months was 0% (0/32) in the DOAC group and 24% (18/75) in the LMWH group (p = 0.001), with 4 fatal ICHs in the LMWH group. Other outcomes are displayed in the Table. Conclusions: Our study suggests that DOACs are associated with a lower incidence of clinically relevant ICH in patients with GBM-associated VTE compared to LMWH. These data support the use of DOACs as a safe alternative to LMWH in patients with GBM.[Table: see text]

Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline

Introduction:Direct oral anticoagulants (DOACs) decrease the risk of venous thromboembolism (VTE) without increasing the risk of hemorrhage in elective lower limb orthopedic surgery. However, the role of DOACs in preventing VTE following hip fracture surgery in the older adults remains unclear. This study aims to evaluate the efficacy and safety of DOACs in older adults undergoing surgery for hip fracture.Materials and methods:Single-center, retrospective, population-based cohort study of patients receiving either a DOAC or low-molecular-weight heparin (LMWH) for VTE prophylaxis following hip fracture surgery. Data obtained included patient demographics, comorbidities, fracture classification, time to surgery, procedure performed, and length of stay. Main outcomes assessed were incidence of VTE, incidence of major hemorrhage, and death within 30 days of surgery.Results:A total of 321 patients were included. Incidence of VTE was 0% in the DOAC group and 3.4% in the LMWH group (risk ratio [RR]:0.26, 95% confidence interval [CI]: 0.02-4.34, P = .35). Hemorrhage occurred in 7.4% and 3.0% of patients in the DOAC and LMWH groups, respectively (RR: 2.47, 95% CI: 0.77-7.91, P = .13). Mortality from VTE was 0% in the DOAC group and 0.7% in the LMWH group (RR: 0.97, 95% CI: 0.05-20.02, P = .99). Mortality from hemorrhage was 1.9% in the DOAC group and 0.7% in the LMWH group (RR: 2.47, 95% CI: 0.23-26.78, P = .46).Discussion:The use of DOACs for VTE prophylaxis following surgery in older adults with hip fracture was associated with a similar rate of VTE compared to LMWH. However, there was a worrying trend toward an increased risk of hemorrhage.Conclusion:In the present study of a carefully selected cohort of patients, the effect of DOACs in reducing the risk of VTE following surgery for hip fracture in the older adults was comparable to LMWH. However, a trend toward increased risk of hemorrhage was noted. Larger prospective studies will be required to identify patients who will benefit the most from treatment.

Efficacy of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after gynecological cancer surgery: A systematic review and meta-analysis.

Bleeding Risk of Low-Molecular Weight Heparin Vs Direct Oral Anticoagulant in Patients with Intracranial Tumors

Introduction: Direct oral anticoagulants (DOACs) have been studied for treatment of venous thromboembolism (VTE) in patients with cancer. However, the trials have shown conflicting results when compared with low molecular weight heparin (LMWH). Therefore, we aimed to conduct an updated meta-analysis of the available studies. Methods: Randomized controlled trials (RCTs) comparing DOAC vs LMWH for VTE treatment in cancer patients were searched from multiple online databases. The primary endpoints of interest were recurrent VTE, major bleeding, clinically relevant non major bleeding (CRNB) and mortality at the longest available follow up. A random-effects model was used to estimate risk ratios (RR) with 95% confidence intervals (CI). Results: Six RCTs, with a total of 3,703 patients - 1,855 in the DOAC group and 1,848 in the LMWH group were included. Around 49% of patients were men and the mean age was 66 years. The follow up duration varied from 3 to 24 months. Patients treated with DOAC, when compared with the LMWH group, had lower risk of recurrent VTE (RR 0.66, 95% CI 0.52-0.83, p = 0.0005) (Figure 1), but a higher risk of CRNB (RR 1.63, 95% CI 1.19-2.23, p = 0.002). No significant differences were found between the two groups with regards to major bleeding (RR 1.19, 95% CI 0.82-1.71, p = 0.36) (Figure 2) or overall mortality (RR 1.02, 95% CI 0.90-1.14, p = 0.78). Conclusions: For treatment of VTE, DOACs as compared with LMWH are associated with significant reduction of recurrent VTE events but with a higher risk of CRNB.

Direct Oral Anticoagulants Compared to Low Molecular Weight Heparin in the Treatment of Cancer-Associated Thromboembolism: An Updated Meta-Analysis of Randomized Controlled Trails

Glioblastoma (GBM) is associated with a high incidence of venous thromboembolism (VTE), but there are little data to guide anticoagulation in patients with GBM, in whom the risks of VTE must be balanced against the risk of intracranial hemorrhage (ICH). We performed a single-institution retrospective cohort study of patients with GBM diagnosed with VTE from 2014 to 2021 who were treated with low molecular weight heparin (LMWH) or a direct oral anticoagulant (DOAC). The incidence of ICH was compared between the LMWH and DOAC groups. The primary outcome was clinically relevant ICH within the first 30 days of anticoagulation, defined as any ICH that was fatal, symptomatic, required surgical intervention, and/or led to cessation of anticoagulation. Secondary outcomes included clinically relevant ICH within 6 months, fatal ICH within 30 days and 6 months, and any bleeding within 30 days and 6 months. One hundred twenty-one patients were identified in the cohort for 30-day outcome analyses (DOAC, n = 33; LMWH, n = 88). For 6-month outcome analyses, the cohort included only patients who were maintained on their initial anticoagulant (DOAC, n = 32; LMWH, n = 75). The incidence of clinically relevant ICH at 30 days was 0% in the DOAC group and 9% in the LMWH group (P = .11). The cumulative incidence of clinically relevant ICH at 6 months was 0% in the DOAC group and 24% in the LMWH group (P = .001), with 4 fatal ICHs in the LMWH group. DOACs are associated with a lower incidence of clinically relevant ICH in patients with GBM-associated VTE compared to LMWH.

ABCL-104 Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Patients With Hematological Malignancies

Background: Cancer is well known to cause a pro-thrombotic state, however, the pharmacologic therapy for prevention of Venous Thromboembolism (VTE) remains under contention. Direct Oral Anticoagulants (DOACs) and Low Molecular Weight Heparins (LMWHs) remain the mainstay treatment to prevent VTE in active malignancy. The purpose of this pooled analysis is to clarify the safety and efficacy of DOACs and LMWHs in the prevention of VTE and the risk of bleeding. Methods: A systematic search of MEDLINE was conducted using PRISMA guidelines using the search terms “DOAC”, “VTE”, “LMWH” and “Cancer OR Malignancy”. Studies were only included if they were prospective and randomized with a control group. Clinical characteristics of patients and outcomes were aggregated according to the Cochrane Manual. A random effects model using clinical events as dichotomous variables and was utilized to calculate Odds Ratios with 95% confidence intervals. Revman 5.3 was used to aggregate outcomes and statistics. Results: A total of 3880 patients were included in this analysis. Solid organ tumors remained the most enrolled malignancies included in the trials, with gastrointestinal malignancies being the most common. Apixaban, Rivaroxaban, Edoxaban, and Dalteparin were compared in these trials. There was a significant reduction in VTE in favor of the DOACs (OR: 0.64 [0.49, 0.82], P=0.0004). There was no significant difference in major bleeding between DOACs and LMWH (OR: 1.22 [0.80, 1.86], P= 0.36). There was a significant increase in Clinically Relevant Non-Major Bleeding in the DOAC group (OR: 1.68 [1.3, 2.17], P<0.0001). There was no significant difference in All Cause Death (OR: 1.02 [0.88, 1.18], P=0.78). Conclusion: DOACs significantly reduced VTE as compared to LMWHs at the expense of an increase in Clinically relevant Non-Major Bleeding. Shared decision making should be utilized with the patient to balance the risks of VTE versus bleeding. Further trials are needed to confirm the safety and efficacy of anticoagulation with differing types of malignancies to guide VTE treatment.

Direct Oral Anticoagulants (DOACs) Vs. Low Molecular Weight Heparins (LMWH) for Venous Thromboembolism (VTE) in Patients with Primary Brain Tumors or Secondary Brain Metastases

In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain. To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event. Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020. Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses. The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin. Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death. Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer. ClinicalTrials.gov Identifier: NCT02744092.

Addressing the burden of hospital‐related venous thromboembolism: the role of extended anticoagulant prophylaxis