Direct Oral Anticoagulants and Cancer-Associated Thrombosis Management. Where Do We Stand in 2019?
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ABSTRACT:
SUBMITTER: Ramacciotti E
PROVIDER: S-EPMC6714910 | biostudies-literature | 2019 Jan-Dec
REPOSITORIES: biostudies-literature
Publications
Direct Oral Anticoagulants and Cancer-Associated Thrombosis Management. Where Do We Stand in 2019?
Ramacciotti Eduardo E Agati Leandro B LB Caffaro Roberto Augusto RA Volpiani Giuliano G GG Lopes Renato D RD Comerota Anthony J AJ Fareed Jawed J
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20190101
Direct oral anticoagulants (DOACs) are now widely used for the management of venous thromboembolism (VTE) that now includes cancer-associated thrombosis. This review summarizes recent data on VTE prophylaxis and treatment, new challenges, guidelines, and updates as well as the current place for DOACs on the emerging cancer-associated VTE management landscape. ...[more]
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Project description:Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10-15% of patients on oral anticoagulants will undergo an invasive procedure and expert groups have issued several guidelines on perioperative management in such situations. The perioperative guidelines have undergone numerous updates as clinical experience of emergency management has increased and perioperative studies including measurement of residual anticoagulant levels have been published. The high inter-patient variability of DOAC plasma levels has challenged the traditional recommendation that perioperative DOAC interruption should be based only on the elimination half-life of DOACs, especially before invasive procedures carrying a high risk of bleeding. Furthermore, recent publications have highlighted the potential danger of heparin bridging use when DOACs are stopped before an invasive procedure. As antidotes are progressively becoming available to manage severe bleeding or urgent procedures in patients on DOACs, accurate laboratory tests have become the standard to guide their administration and their actions need to be well understood by clinicians. This review aims to provide a systematic approach to managing patients on DOACs, based on recent updates of various perioperative guidance, and highlighting the advantages and limits of recommendations based on pharmacokinetic properties and laboratory tests.
| S-EPMC5433145 | biostudies-literature
Project description:BackgroundRecently, direct oral anticoagulants (DOACs) have been included in guidelines for the treatment of cancer-associated thrombosis (CAT) to be extended to suitable cancer patients. The purpose of this study was to compare the cost-effectiveness of using DOACs and low molecular weight heparins (LMWHs) for treating CAT from the perspective of the Chinese healthcare system.MethodsA Markov model was constructed to estimate the cost-effectiveness of the two strategies with a 6-month and 5-year time horizon. Input parameters were either sourced from the clinical trial, published literature. The primary outcome of the model was reported as incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed to test model uncertainty.ResultsThe 6-month cost of DOACs was $ 654.65 with 0.40 quality adjusted life-years (QALYs) while the 6-month cost of LMWHs was $USD 1719.31 with 0.37 QALYs. Similarly, treatment with DOACs had a lower cost ($USD 657.85 vs. $USD 1716.56) and more health benefits (0.40 QALYs vs. 0.37 QALYs) than treatment with LMWHs in a subgroup of patients with gastrointestinal malignancy. We found treatment with DOACs would result in a large reduction in cost ($USD 1447.22 vs. $USD 3374.70) but a small reduction in QALYs (3.07 QALYs vs. 3.09 QALYs) compared with LMWHs over a 5-year time frame, resulting in an ICER of $USD 112895.50/QALYs. Sensitivity analysis confirmed the robustness of the results.ConclusionAs compared to LMWHs, DOACs can be a cost-saving anticoagulant choice for the treatment of CAT in the general oncology population and gastrointestinal malignancy population.
| S-EPMC8479897 | biostudies-literature
Project description:ObjectivesCurrent guidelines do not recommend direct oral anticoagulants (DOACs) to treat cerebral venous thrombosis (CVT) despite their benefits over standard therapy. We performed a systematic review to summarise the published experience of DOAC therapy in CVT.Data sourcesMEDLINE, Embase and COCHRANE databases up to 18 November 2020.Eligibility criteriaAll published articles of patients with CVT treated with DOAC were included. Studies without follow-up information were excluded.Data extraction and synthesisTwo independent reviewers screened articles and extracted data. A risk of bias analysis was performed.Primary and secondary outcome measuresSafety data included mortality, intracranial haemorrhage (ICH) or other adverse events. Efficacy data included recurrent CVT, recanalisation rates and disability by modified Rankin Scales (mRS).Results33 studies met inclusion criteria. One randomised controlled trial, 5 observational cohorts and 27 case series or studies reported 279 patients treated with DOAC for CVT: 41% dabigatran, 47% rivaroxaban, 10% apixaban and 2% edoxaban, in addition to 315 patients treated with standard therapy. The observational cohorts showed a similar risk of death in DOAC and standard therapy arms (RR 2.12, 95%?CI 0.29 to 15.59). New ICH was reported in 2 (0.7%) DOAC-treated patients and recurrent CVT occurred in 4 (1.5%). A favourable mRS between 0 and 2 was reported in 94% of DOAC-treated patients, more likely than standard therapy in observational cohorts (RR 1.13, 95%?CI 1.02 to 1.25).ConclusionThe evidence for DOAC use in CVT is limited although suggests sufficient safety and efficacy despite variability in timing and dose of treatment. This systematic review highlights that further rigorous trials are needed to validate these findings and to determine optimal treatment regimens.
| S-EPMC7888326 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Cerebral venous thrombosis causes disability from venous infarct and hemorrhage and potential mortality. Anticoagulation improves survival and disability outcomes, yet direct oral anticoagulants are currently not indicated in cerebral venous thrombosis due to lack of evidence, despite being on the market for nearly a decade. This systematic review will collate evidence of reported safety and efficacy of direct oral anticoagulant therapy in cerebral venous thrombosis. METHODS:A search strategy was developed with a research librarian and registered on a protocol database (PROSPERO CRD42017078398). All published studies from MEDLINE and EMBASE up to February 2019 containing patients diagnosed with cerebral venous thrombosis who were treated with a direct oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) will be included. A risk of bias analysis will be performed to evaluate quality of studies overall. DISCUSSION:Current guidelines in the treatment of cerebral vein thrombosis dating back to 2011 from the American Heart Association/American Stroke Association endorse the utility of anticoagulation for the treatment of cerebral vein thrombosis; however, they did not support the use of direct oral anticoagulants. Updated guidelines from the European Stroke Organization, endorsed by the European Academy of Neurology in 2017, also refute utilization of direct oral anticoagulants due to a lack of evidence. There have been nearly 10?years of experience with direct oral anticoagulants in the treatment of venous thrombosis and prevention of stroke in patients with atrial fibrillation, with purported efficacy and safety in comparison with heparins and vitamin K antagonists. Our goal is to undertake a systematic review to assess the effectiveness and safety of direct oral anticoagulants in patients with cerebral vein thrombosis to help guide clinical decision-making for patients unable to take heparins or vitamin K antagonists and to direct future studies to contribute further to an area of certain evidence-based needs. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42017078398.
| S-EPMC6474061 | biostudies-literature
Project description:BackgroundVenous thromboembolism (VTE) affects nearly 1 million Americans annually, and many benefit from continued anticoagulation after the initial 3- to 6-month treatment period (secondary prevention).ObjectivesTo determine whether warfarin, apixaban, or rivaroxaban is associated with reduced recurrent VTE hospitalization in the secondary prevention of VTE.Patients/methodsWe performed a retrospective cohort study of participants enrolled in the MarketScan Insurance Database between 2013 and 2017 in those with an incident VTE. In those individuals who continued oral anticoagulation (warfarin, apixaban, or rivaroxaban) beyond 6 months, we determined the relative rate of recurrent VTE hospitalization.ResultsAmong 119 964 individuals with VTE, 25 419 remained on anticoagulation after 6 months and were matched successfully by age, sex, and date. After adjusting for a propensity score, apixaban versus rivaroxaban (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.45-0.94) and apixaban versus warfarin (HR, 0.68; 95% CI, 0.47-1.00) had a reduced risk of recurrent VTE hospitalization, and rivaroxaban versus warfarin (HR, 1.12; 95% CI, 0.94-1.33) had equivalent rates. For the rivaroxaban versus warfarin comparison there was a significant interaction by renal function (P < .01) where rivaroxaban was associated with a lower risk of recurrent VTE hospitalization (HR, 0.65; 95% CI, 0.41-1.03) in those with kidney disease and increased risk in those without kidney disease (HR, 1.24; 95% CI, 1.02-1.50).ConclusionsThese data suggest that apixaban has a lower recurrent VTE hospitalization rate than rivaroxaban during the secondary prevention of VTE, and further study of diverse patient populations, especially by kidney function, is warranted.
| S-EPMC8371351 | biostudies-literature
Project description:Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect.
| S-EPMC5016308 | biostudies-other
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.
| S-EPMC6594460 | biostudies-literature
Project description:Reversal agents for direct oral anticoagulants (DOACs), including factor X inhibitors and direct thrombin inhibitors, are a major concern in clinical practice. After DOACs were introduced and became widely used as an alternative for vitamin K antagonists in the management of venous thromboembolism and nonvalvular atrial fibrillation, the need for effective reversal agents has increased, particularly for life-threatening bleeding episodes related to DOACs or to reverse medication effects during urgent interventions. In the absence of specific reversal agents, prothrombin complex concentrate (PCC) and activated PCC are reasonable options to reverse bleeding associated with DOACs. However, high-quality clinical evidence is lacking. Idarucizumab is the only agent approved by the US Food and Drug Administration to reverse the effects of dabigatran; andexanet alfa and ciraparantag are also under evaluation as reversal agents for DOACs. This review summarizes the current evidence for nonspecific and specific reversal of DOACs.
| S-EPMC5529093 | biostudies-other
Project description:Data on specific studies in cancer patients using direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE) are still scarce. For preventing VTE with DOACs, current experience is still very limited, so definite conclusions cannot yet be drawn. However, DOACs have so far been compared with vitamin K antagonists (VKAs) in patients with acute VTE in 5 studies, and several hundreds of patients included in these studies had either active cancer, a history of cancer, or a new occurrence of cancer during the course of disease. Meta-analyses have revealed an at least similar efficacy and safety profile of DOACs compared with VKAs. A number of studies of cancer patients investigating primary prevention and treatment are underway, and some will be finalized soon. Nevertheless, we might need further trials, specifically on the prevention of VTE in patients who are at particularly high risk. This article also includes a personal opinion on the use of DOACs in cancer patients. In conclusion, the currently available data show that DOACs might be safe and efficacious in the treatment of VTE, however, this has yet to be proven in specifically designed trials in patients with cancer. With regard to prevention, thus far, even less data exist, and the outcomes of the ongoing studies have to be evaluated before DOACs may be used for primary prevention.
| S-EPMC6142595 | biostudies-literature
Project description:Efficacy and safety of direct oral anticoagulants (DOACs) for preventing primary and recurrent venous thromboembolism (VTE) in patients with cancer remain unclear. In this study, we conducted a systematic review to summarize the most up-to-date evidence from randomized controlled trials (RCTs). Our primary outcomes included the benefit outcome (VTE) and safety outcome (major bleeding). A random-effects model was used to pool the relative risks (RRs) for data syntheses. The Grading of Recommendations Assessment, Development and Evaluation tool was used to evaluate the quality of the entire body of evidence across studies. We included 11 RCTs with a total of 3741 patients with cancer for analyses. The DOACs were significantly related with a reduced risk of VTE when compared with non-DOACs: RR = 0.77, 95% confidence interval [CI]: 0.61-0.99, P = .04. Nonsignificant trend towards a higher risk of major bleeding was found in DOACs: RR = 1.28 95% CI: 0.81-2.02, P = .29. The quality of the entire body of evidence was graded as moderate for risk of VTE, and low for risk of major bleeding. To summarize, DOACs were found to have a favorable effect on risk of VTE but a nonsignificant higher risk of major bleeding compared with non-DOACs in patients with cancer. The safety effect of DOACs in patients with cancer requires further evaluation in adequately powered and designed studies.
| S-EPMC6714916 | biostudies-literature