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Antithrombotic therapy for prophylaxis and treatment of venous thromboembolism in patients with cancer: review of the literature on current practice and emerging options.

ABSTRACT: The treatment of cancer-associated venous thromboembolism (VTE) is difficult because cancer patients with VTE on anticoagulation are at an increased risk of bleeding compared with patients without VTE. This review summarises the evidence supporting the current standard of care and emerging treatment options. In difficult-to-treat subpopulations, where clinical data are often lacking, this review also provides the best clinical practice strategies based on the available data. The use of therapeutic doses of parenteral anticoagulants in patients with cancer-associated VTE for at least 3 to 6 months is supported by the current clinical data. After major cancer surgery, extended thromboprophylaxis for approximately 1?month following hospital discharge is also supported. In select populations of ambulatory cancer patients with solid tumours, or in patients with myeloma receiving immunomodulatory agents in combination with chemotherapy and/or corticosteroids, pharmacological prophylaxis could be considered. Although parenteral anticoagulants may not be tolerated by some patients, the data pertaining to the use of direct oral anticoagulants (DOACs) in cancer patients with VTE at this point can only be considered hypothesis generating. Clarity of the use of DOACs is awaiting the results of head-to-head trials between DOACs and parenteral anticoagulants. In addition, because of the lack of clinical trials, there are still unanswered questions on the optimal treatment regimens in subpopulations at increased risk of bleeding, including cancer patients with thrombocytopenia and those with brain metastases. For clinicians to balance the risk of recurrent thrombosis with the chance of bleeding, they need to assess the relevant clinical data. Current data support the use of parenteral anticoagulants in cancer patients with VTE, but many unanswered questions pertaining to the optimal regimens in special subpopulations and regarding the efficacy and safety of DOACs remain. To address this need, there are currently several clinical trials under way.

SUBMITTER: Ay C

PROVIDER: S-EPMC5519804 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Antithrombotic therapy for prophylaxis and treatment of venous thromboembolism in patients with cancer: review of the literature on current practice and emerging options.

Ay Cihan C Kamphuisen Pieter Willem PW Agnelli Giancarlo G

ESMO open 20170608 2

The treatment of cancer-associated venous thromboembolism (VTE) is difficult because cancer patients with VTE on anticoagulation are at an increased risk of bleeding compared with patients without VTE. This review summarises the evidence supporting the current standard of care and emerging treatment options. In difficult-to-treat subpopulations, where clinical data are often lacking, this review also provides the best clinical practice strategies based on the available data. The use of therapeut ...[more]

PMID: 28761749

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Project description:Essentials Despite trial data, guidelines have not endorsed direct oral Xa inhibitors above other options. We provide profiles of venous thromboembolism and hemorrhage risk for 12 options. Direct oral Xa inhibitors had a favorable profile compared with low-molecular-weight heparin. Other options did not have favorable profiles compared with low-molecular-weight heparin.Background There are numerous trials and several meta-analyses comparing venous thromboembolism (VTE) prophylaxis options after total hip and knee replacement (THR and TKR). None have included simultaneous comparison of new with older options. Objective To measure simultaneously the relative risk of VTE and hemorrhage for 12 prophylaxis options. Methods We abstracted VTE and hemorrhage information from randomized controlled trials published between January 1990 and June 2016 comparing 12 prophylaxis options. We then constructed networks to compute the relative risk for each option, relative to once-daily dosing with low-molecular-weight heparin (LMWH) Low. Results Main: Relative to LMWH Low, direct oral Xa inhibitors had the lowest risk of total deep vein thrombosis (DVT)-asymptomatic and symptomatic- (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.35-0.57), translating to 53-139 fewer DVTs per 1000 patients. Vitamin K antagonists (VKAs) titrated to International Normalized Ratio [INR] 2-3 predicted 56% more DVT events (OR, 1.56; 95% CI, 1.14-2.14). Aspirin performed similarly (OR, 0.80; 95% CI, 0.34-1.86), although small numbers prohibit firm conclusions. Direct oral Xa inhibitors did not lead to significantly more bleeding (OR, 1.21; 95% CI, 0.79-1.90). Secondary: Relative to LMWH Low, direct oral Xa inhibitors prevented 4-fold more symptomatic DVTs (OR, 0.25; 95% CI, 0.13-0.47). Conclusions Relative to LMWH Low, direct oral Xa inhibitors had a more favorable profile of VTE and hemorrhage risk, whereas VKAs had a less favorable profile. The profile of other agents was not more or less favorable. Clinicians should consider these profiles when selecting prophylaxis options.

Project description:ObjectiveTo study the impact of multiphase quality improvement efforts to enhance appropriate use of chemical and mechanical venous thromboembolism (VTE) prophylaxis (VTEP) on the rate of hospital-acquired VTE and determine whether efforts have been associated with increased bleeding complications.Patients and methodsAll adult inpatients discharged between January 1, 2005, and December 31, 2015, were included in the study. Retrospective interrupted time series analysis compared VTEP performance, VTE outcomes, and unintended consequences (derived from linked administrative and clinical data) across 5 improvement phases: baseline (January 1, 2005-December 31, 2006), paper order set phase (January 1, 2007-February 9, 2009), electronic order set phase (February 10, 2009-December 16, 2009), active reminder phase (December 17, 2009-May 31, 2012), and maintenance phase (June 1, 2012-September 30, 2015).ResultsGuideline VTEP plan adherence at the end of the study period (including documenting contraindications) reached 88.8% (654,138 of 736,384 patient days). Delivery of pharmacological VTEP increased from 43.9% (49,155 of 111,906 patients) to 60.8% (75,784 of 124,676 patients); delivery of mechanical or pharmacological VTEP increased less (65.0% [431,791 of 664,087 patient days] to 67.4% [496,625 of 736,384 patient days]). Mean VTE rates decreased from 4.6 per 1000 hospitalizations (21.7 VTEs per month) at baseline to 4.3 per 1000 hospitalizations (18.0 VTEs per month) during the maintenance phase (P<.001). More than 97% of patients who had development of VTE (534 of 548) received VTEP, but 65.7% (360 of 548) experienced gaps of 1 or more days in VTEP delivery. Measured in-hospital bleeding rates were fairly consistent over the study (4.6% [5,198 of 111,906 patients] at baseline to 5.3% [6,662 of 124,676 patients] during the reminder phase). There was little change in rates of 7-day readmission with bleeding or VTE.ConclusionOur VTEP project improved guideline compliance, increased the proportion of patients receiving VTEP, and was associated with a decrease in VTE. Gaps in VTEP delivery occurred despite protocoled order sets and electronic feedback. Further improvements in VTE may require new approaches.

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Antithrombotic therapy for prophylaxis and treatment of venous thromboembolism in patients with cancer: review of the literature on current practice and emerging options.

Publications

Antithrombotic therapy for prophylaxis and treatment of venous thromboembolism in patients with cancer: review of the literature on current practice and emerging options.

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