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Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence.

ABSTRACT: Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions.

SUBMITTER: Garcia-Escobar I

PROVIDER: S-EPMC8084841 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence.

García-Escobar I I Brozos-Vázquez E E Gutierrez Abad D D Martínez-Marín V V Pachón V V Muñoz Martín A J AJ

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 20201118 6

Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety da ...[more]

PMID: 33206333

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Project description:Background: Direct oral anticoagulants (DOACs) are increasingly prescribed for the treatment of venous thromboembolism (VTE). However, little is known regarding pharmacists' practice patterns and preferences in clinical areas of contention, such as initiation dosing, obesity, and renal impairment. Objective: To determine pharmacist trends in practice regarding DOACs for the treatment of VTE overall and within areas of clinical controversy. Methods: An electronic survey was distributed to pharmacists in the United States through national and state pharmacy organizations. Responses were collected for 30 days. Results: One hundred fifty-three complete responses were submitted. The majority of pharmacists preferred apixaban (90.2%) for the oral treatment of venous thromboembolism. When initiating apixaban or rivaroxaban for a new VTE, 76% and 64% of pharmacists surveyed, respectively, state the duration of the initiation dose phases are reduced if the patient received parenteral anticoagulation. Fifty-eight percent of pharmacists used body mass index to evaluate the appropriateness of DOACs in obese patients whereas 42% used total body weight. Preference for rivaroxaban (31.4%) was higher in this population compared to the global population (10%). Apixaban was preferred for patients with renal impairment (92.2%). However, as creatinine clearance as calculated by the Cockcroft-Gault equation (CrCl) reduced to ≤15 milliliters/minute (mL/min), preference for warfarin increased (36%). Conclusion: This national survey of pharmacists demonstrated an overall preference for apixaban and significant variability in practice patterns regarding DOACs for patients with new VTE, patients with obesity, and patients with renal impairment. Further research is warranted to evaluate the efficacy and safety of DOAC initiation dosing phase modifications. Prospective evaluations of DOACs in obese and renal dysfunction populations would confirm the safety and efficacy of DOACs in these populations.

Project description:Anticoagulation for cancer-associated venous thromboembolism (VTE) can be challenging due to complications-including bleeding and potential drug-drug interactions with chemotherapy-associated with vitamin K antagonists and inconvenience of low-molecular-weight heparin (LMWH). Direct oral anticoagulants (DOACs) could partially overcome these issues, but until recently there were no large clinical trials assessing their efficacy and safety in cancer patients. This review summarizes clinical treatment guidelines, prior clinical and real-world evidence for anticoagulant choice, recent clinical trials assessing DOACs for cancer-associated VTE (i.e. Hokusai-VTE Cancer, SELECT-D, CARAVAGGIO, and ADAM VTE), and special considerations for DOAC use. Based on established data, clinical guidelines recommend patients with cancer-associated VTE receive LMWH treatment of at least 3-6 months. Nevertheless, LMWH is underused and associated with poor compliance and persistence in these patients relative to oral anticoagulants. Clinical data supporting DOAC use in cancer patients are becoming available. In Hokusai-VTE Cancer, edoxaban was noninferior to dalteparin for the composite of recurrent VTE and major bleeding (12.8% versus 13.5%), with numerically lower recurrent VTE (7.9% versus 11.3%) and significantly higher major bleeding (6.9% versus 4.0%); only patients with gastrointestinal cancer had significantly higher risk of bleeding with edoxaban. In SELECT-D, rivaroxaban had numerically lower VTE recurrence (4% versus 11%), comparable major bleeding (6% versus 4%), and numerically higher clinically relevant nonmajor bleeding (13% versus 4%) versus dalteparin. Most bleeding events were gastrointestinal or urologic; patients with esophageal/gastroesophageal cancer had higher rates of major bleeding with rivaroxaban (36% versus 11%). For comparison of apixaban versus dalteparin, CARAVAGGIO is ongoing, and preliminary results from ADAM VTE are favorable. This review concludes that DOACs appear to be reasonable alternatives to LMWH for treatment of cancer-associated VTE. In patients with gastrointestinal cancer, DOAC use should be considered on a case-by-case basis with consideration of the relative risks and benefits.

Project description:Pulmonary embolism (PE) is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT) are considered expressions of the same disease, termed as venous thromboembolism (VTE). In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41%) had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70-1.11) and index DVT (RR: 0.93; 95% CI: 0.75-1.16) (P for subgroup differences =0.76). VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83-5.03) and in patients with index DVT (RR: 1.11; 95% CI: 0.49-2.50) (P for subgroup differences =0.32). In trials that compared DOAC versus placebo for extended therapy, the reduction in recurrent VTE was consistent in patients with PE (RR: 0.15; 95% CI: 0.01-1.82) and in patients with DVT (RR: 0.25; 95% CI: 0.10-0.61) (P for subgroup differences =0.71). The DOAC were associated with a consistently lower risk of clinically relevant bleeding (CRB) than standard treatment of acute VTE and higher risk of CRB than placebo for extended therapy of VTE regardless of index event. In summary, the DOAC were as effective as, and safer than, standard treatment of (hemodynamically stable) PE. Their efficacy in preventing recurrent VTE seemed consistent regardless of anatomical extension of PE (extensive, intermediate, or limit) or presence/absence of right ventricular dysfunction although the data are limited. For extended therapy, the DOAC were more effective than placebo in preventing recurrent VTE but were associated with an increase in CRB regardless of index event.

Project description:ImportanceExtending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear whether clinical outcomes differ when using direct oral anticoagulants (DOACs) or warfarin.ObjectiveTo compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE.Design, setting, and participantsThis cohort study was conducted in 2 integrated health care delivery systems in California with adults aged 18 years or older who received a diagnosis of incident VTE between 2010 and 2018 and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. Patients were followed from the end of the initial 6-month treatment period until discontinuation of anticoagulation, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019). Data were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Data analysis was conducted from March 2022 to January 2023.ExposureDispensed prescriptions of DOACs or warfarin after a 6-month initial treatment for VTE.Main outcomes and measuresThe primary outcomes were rates per 100 person-years of recurrent VTE, hospitalizations for hemorrhage, and all-cause death. Comparison of DOAC and warfarin outcomes were performed using multivariable Cox proportional hazards regression.ResultsA total of 18 495 patients (5477 [29.6%] aged ≥75 years; 8973 women [48.5%]) with VTE who were treated with at least 6 months of anticoagulation were identified, of whom 2134 (11.5%) were receiving DOAC therapy and 16 361 (88.5%) were receiving warfarin therapy. Unadjusted event rates were lower for patients receiving DOAC therapy than warfarin therapy for recurrent VTE (event rate per 100 person-years, 2.92 [95% CI, 2.29-3.54] vs 4.14 [95% CI, 3.90-4.38]), hospitalizations for hemorrhage (event rate per 100 person-years, 1.02 [95% CI, 0.66-1.39] vs 1.81 [95% CI, 1.66-1.97]), and all-cause death (event rate per 100 person-years, 3.79 [95% CI, 3.09-4.49] vs 5.40 [95% CI, 5.13-5.66]). After multivariable adjustment, DOAC treatment was associated with a lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82). For patients prescribed DOAC treatment, the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those for patients prescribed warfarin treatment.Conclusions and relevanceIn this cohort study of patients with VTE who continued warfarin or DOAC anticoagulation beyond 6 months, DOAC treatment was associated with a lower risk of recurrent VTE, supporting the use of DOACs for the extended treatment of VTE in terms of clinical outcomes.

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Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence.

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Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence.

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