DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis

Mai, Vicky; Tanguay, Virginie F.; Guay, Charles-Antoine; Bertoletti, Laurent; Magnan, Sindy; Turgeon, Alexis F.; Lacasse, Yves; Lega, Jean‐Christophe; Provencher, Steeve

doi:10.1007/s11239-020-02055-1

Cited by 24 publications

(20 citation statements)

References 24 publications

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“…Strengths of our meta-analysis in comparison to previous ones, include the inclusion of the Caravaggio study, thereby increasing generalizability and power of the individual analyses. [27][28][29] Our findings indicate that the evaluated oral factor Xa inhibitors may replace LMWH in the majority of patients with cancer-associated VTE. Moreover, state-of-the-art methodology was used according to current guidelines for performing meta-analyses.…”

Section: Limitations and Strengthsmentioning

confidence: 68%

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis

et al. 2020

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Abstract Background International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE. Methods MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel–Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs). Results Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43–0.91; I 2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83–2.08; I 2, 23%). Conclusion In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH.

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Section: Limitations and Strengthsmentioning

confidence: 68%

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis

et al. 2020

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“…Superiority with respect to recurrent VTE has not been shown for a DOAC, neither in any of the single RCTs nor in aggregated results of previous meta‐analyses 16,17 . The improvement in efficacy of DOACs over LMWHs might be explained in part by better treatment adherence with an orally administered drug than with subcutaneous injections, which may be reflected by a lower preterm treatment discontinuation rate in patients treated with oral factor Xa inhibitors.…”

Section: Discussionmentioning

confidence: 88%

“…Previous meta‐analyses have been performed comparing DOACs to LMWHs for the treatment of cancer‐associated VTE aggregating data from 2 or 3 of the now 4 available randomized controlled trials (RCTs) and showed a nonsignificant decrease in risk of VTE accompanied by an increase in risk of bleeding in patients treated with a DOAC 16‐19 …”

Section: Introductionmentioning

confidence: 99%

Direct oral anticoagulants compared to low‐molecular‐weight heparin for the treatment of cancer‐associated thrombosis: Updated systematic review and meta‐analysis of randomized controlled trials

Moik

Posch

Zielinski

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Background Low‐molecular‐weight‐heparins (LMWHs) have been established for the treatment of cancer‐associated venous thromboembolism (VTE). Recently published randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) with LMWHs. The aim of this systematic review and meta‐analysis was to evaluate efficacy and safety of DOACs versus LMWHs and update the evidence for treatment of VTE in cancer. Methods Biomedical databases were screened for RCTs evaluating DOACs for cancer‐associated VTE. Primary efficacy and safety outcomes of this meta‐analysis were recurrent VTE and major bleeding at 6 months. Secondary outcomes comprised clinically relevant nonmajor bleeding (CRNMB), major gastrointestinal (GI) and genitourinary bleeding, mortality, fatal bleeding/pulmonary embolism, and treatment discontinuation rate. We performed prespecified subgroup analyses. Pooled relative risk (RR) and 95% confidence intervals (CIs) were obtained by the Mantel‐Haenszel method within a random‐effect model. Results We screened 759 articles and included 4 RCTs (n = 2894). DOACs significantly reduced recurrent VTEs compared to LMWHs (5.2% vs 8.2%; RR, 0.62 [95% CI, 0.43‐0.91]), but were associated with a nonsignificant increase in major bleedings (4.3% vs 3.3%; RR, 1.31 [95% CI, 0.83‐2.08]) and a significant increase in CRNMB (10.4% vs 6.4%; RR, 1.65 [95% CI, 1.19‐2.28]). Mortality risks were comparable between groups (RR, 0.99 [95% CI, 0.83‐1.18]). Preterm treatment discontinuation was less common with DOACs (RR, 0.88 [95% CI, 0.81‐0.96]). Major bleeding was more frequent in patients with GI cancer treated with DOACs (RR, 2.30 [95% CI, 1.08‐4.88]). Conclusion In patients with cancer‐associated VTE, DOACs are more effective in preventing recurrent VTE compared to LMWH. However, risk of bleeding is increased with DOACs, especially in patients with GI cancer.

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“…Third, although the current study had limited power to evaluate the risk of bleeding associated with concurrent TKIs and DOACs, the HR of 4.15 indicates a higher bleeding risk. A recent meta‐analysis demonstrated that DOACs were associated with a higher risk of major bleeding and CRNMB compared with LMWH in the treatment of patients with cancer‐associated thrombosis 30 . Therefore, further studies are needed to address the safety of concurrent TKIs and DOACs, especially in the current era, in which DOACs often are used as first‐line anticoagulants in patients with cancer.…”

Section: Discussionmentioning

confidence: 99%

Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low‐molecular‐weight heparin

Patel

George

Wang

et al. 2020

Cancer

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Background Some cancer patients who are diagnosed with thromboembolism may require dual treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors (low‐molecular‐weight heparin [LMWH] or direct oral anticoagulants [DOACs]). However, to the authors' knowledge, the safety of such combinations has not been well characterized. Methods Patients with advanced cancer who were treated with concurrent VEGFR TKIs and factor Xa inhibitors between 2010 and 2018 at The Ohio State University Comprehensive Cancer Center were included. Charts were reviewed retrospectively for clinically significant bleeding events occurring during concurrent treatment compared with those occurring during factor Xa inhibitor therapy alone, using each patient as their own control. The Fisher exact test was used to compare distribution of bleeding severities. The Cox proportional hazards model was used to compare bleeding risk between groups. Results Among 86 patients, there were 29 clinically significant bleeding events (including 8 major bleeding events) reported during concurrent treatment and 17 events (including 4 major bleeding events) reported during factor Xa inhibitor therapy alone over a median follow‐up of 63 days. Concurrent treatment was associated with significantly higher risks of overall bleeding (hazard ratio, 2.45; 95% confidence interval, 1.28‐4.69 [P = .007]) and first‐onset bleeding (hazard ratio, 2.23; 95% confidence interval, 1.13‐4.42 [P = .02]). Analysis of 6‐month bleeding risk and the subgroups of patients treated with concurrent TKIs and LMWH versus LMWH alone demonstrated a similar trend. The sample size was inadequate for comparisons between treatment with concurrent TKIs and DOACs versus DOACs alone. Conclusions Concurrent treatment with VEGFR TKIs and LMWH was found to be associated with a significantly increased risk of bleeding events when compared with LMWH therapy alone.

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DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis

Cited by 24 publications

References 24 publications

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis

Direct Oral Anticoagulants for the Treatment of Acute Venous Thromboembolism Associated with Cancer: A Systematic Review and Meta-Analysis

Direct oral anticoagulants compared to low‐molecular‐weight heparin for the treatment of cancer‐associated thrombosis: Updated systematic review and meta‐analysis of randomized controlled trials

Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low‐molecular‐weight heparin

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