Extended treatment of venous thromboembolism: a systematic review and network meta-analysis

Heart ◽  
2018 ◽  
Vol 105 (7) ◽  
pp. 545-552 ◽  
Author(s):  
Kang-Ling Wang ◽  
Nick van Es ◽  
Chris Cameron ◽  
Lana A Castellucci ◽  
Harry R Büller ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Dose ◽  
Meta Analysis ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Efficacy And Safety ◽  
Standard Intensity ◽  
All Cause Mortality ◽  
Dose Factor

ObjectiveTo evaluate efficacy and safety of oral anticoagulant regimens and aspirin for extended venous thromboembolism (VTE) treatment.MethodsWe searched MEDLINE, Embase, CENTRAL and conference proceedings for randomised controlled trials studying vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or aspirin for secondary prevention of VTE beyond 3 months. ORs (95% credible intervals) between treatments were estimated using random-effects Bayesian network meta-analysis.ResultsSixteen studies, totaling more than 22 000 patients, were included. Compared with placebo or observation and with aspirin, respectively, the risk of recurrent VTE was lower with standard-intensity VKAs (0.15 (0.08 to 0.24) and 0.23 (0.09 to 0.54)), low-dose factor Xa inhibitors (0.16 (0.06 to 0.38) and 0.25 (0.09 to 0.66)), standard-dose factor Xa inhibitors (0.17 (0.08 to 0.33) and 0.27 (0.11 to 0.65)) and the direct thrombin inhibitor (0.15 (0.04 to 0.37) and 0.23 (0.06 to 0.74)) although the risk of major bleeding was higher with standard-intensity VKAs (4.42 (1.99 to 12.24) and 4.14 (1.17 to 18.86)). Effect estimates were consistent in male patients and those with index pulmonary embolism or with unprovoked VTE and in sensitivity analyses. In addition, compared with placebo or observation, the risk of all-cause mortality was reduced with standard-intensity VKAs (0.44 (0.20 to 0.87)) and low-dose factor Xa inhibitors (0.38 (0.12 to 0.995)).ConclusionsStandard-intensity VKAs and DOACs are more efficacious than aspirin for extended VTE treatment. Despite a higher risk of major bleeding, standard-intensity VKAs was associated with a lower risk of all-cause mortality. Since overall efficacy and safety of standard-intensity VKAs and DOACs are in equipoise, patient factors, costs and patient preferences should be considered when recommending extending anticoagulation treatment.

Direct oral factor Xa inhibitors for the treatment of acute cancer-associated venous thromboembolism: A systematic review and network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23156-e23156
Author(s):  
Harry E Fuentes ◽  
Robert McBane ◽  
Waldemar Wysokinski ◽  
Alfonso Javier Tafur ◽  
Charles L. Loprinzi ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Indirect Comparison ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Efficacy And Safety ◽  
Patients With Cancer

e23156 Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thromboembolism (VTE). Also, the comparative efficacy and safety of apixaban, rivaroxaban, and edoxaban was assessed with a network meta-analysis. Methods: MEDLINE, CENTRAL, and EMBASE were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer associated acute VTE. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence, major and clinically relevant non-major bleeding (CRNMB). Results: Three randomized control trials, at low risk of bias, enrolled 1,739 patients with cancer associated VTE. Direct comparison showed a lower rate of VTE recurrence in DOAC compared to dalteparin groups (odds Ratio [OR]:0.48, 95% Confidence interval [CI]:0.24-0.96; I2:46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared to dalteparin (OR: 0.10; 95% CI: 0.01–0.82), but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared to dalteparin (OR: 1.70; 95% CI: 1.04–2.78). CRNMB did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding whereas estimates in urothelial cancer were imprecise. Conclusions: DOACs appear to lower the risk of VTE recurrence compared to daltaparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared to the other DOACs.

3054Efficacy and safety of non-vitamin K oral anticoagulants in patients with atrial fibrillation and cancer

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Cavallari ◽  
G Verolino ◽  
G Patti
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Intracranial Hemorrhage ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Patients With Cancer ◽  
All Cause Mortality

Abstract Background Anticoagulation in patients with cancer and atrial fibrillation (AF) is particularly challenging given the higher risk of both thrombotic and bleeding complications in this setting. Data regarding the efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in AF patients with malignancy remain unclear. Purpose In the present meta-analysis we further investigate the efficacy and safety of NOACs compared to warfarin in patients with AF and cancer assuming that available studies may be individually underpowered for endpoints at low incidence, i.e. stroke, major and intracranial bleeding. Methods We performed a systematic review and meta-analysis of studies comparing the use of NOACs vs. warfarin in AF patients with cancer. Efficacy outcome measures included stroke or systemic embolism, venous thromboembolism and mortality. Safety outcome measures were major bleeding and intracranial hemorrhage. Results We pooled data from 6 identified studies enrolling a total of 31,756 AF patients with cancer. Mean follow-up was 1.7 years. Patients with cancer had significantly increased annualized rates of venous thromboembolism (1.38% vs. 0.74%), major bleeding (9.01% vs. 5.13%), in particular major gastrointestinal bleeding (2.38% vs. 1.60%), and all-cause mortality (17.73% vs. 8.50%) vs. those without (all P values <0.001), whereas the incidence of stroke or systemic embolism and intracranial hemorrhage did not differ. Compared with warfarin, treatment with NOACs nominally decreased the risk of stroke or systemic embolism (5.41% vs. 2.70%; odds ratio, OR; 95% confidence intervals, CI 0.51, 0.26–1.01; P=0.05; Figure), mainly of ischemic stroke (OR 0.56; 95% CI 0.35–0.89; P=0.01), and the risk of venous thromboembolism (OR 0.51; 95% CI 0.42–0.61; P<0.001). In cancer patients receiving NOACs there was a significant reduction of major bleeding (3.95% vs. 4.66%; OR 0.66, 95% CI 0.46–0.94; P=0.02; Figure) and intracranial hemorrhage (0.26% vs. 0.66%; OR 0.25, 95% CI 0.08–0.82; P=0.02) vs. warfarin, with no difference in gastrointestinal major bleeding rates. Conclusion AF patients on oral anticoagulation and concomitant cancer are at higher risk of venous thromboembolism, major bleeding and all-cause mortality. NOACs may represent a safer and more effective alternative to warfarin also in this setting of patients.

scholarly journals Factor Xa inhibitor for venous thromboembolism management in patient with cancer: a systematic review and meta-analysis

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1257
Author(s):  
Johanes Nugroho Eko Putranto ◽  
Ardyan Wardhana ◽  
Yoga Alfian Noor ◽  
Pirhot Lambok Marnala Yosua Siahaan ◽  
Makhyan Jibril Al Farabi
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Cochrane Library ◽  
Factor Xa Inhibitor ◽  
Patients With Cancer

Background: An earlier systematic review reported no differences in the incidence of recurrent venous thromboembolism and major bleeding between factor Xa inhibitors and standard anticoagulation. The present meta-analysis aimed to assess the effectiveness of factor Xa inhibitors for the management of venous thromboembolism (VTE), specifically in patients with cancer, as there were more randomized clinical trials (RCTs) available. Methods: The PubMed and Cochrane Library databases were systematically screened for all RCTs assessing factor Xa inhibitor efficacy for VTE management in cancer patients. Using RevMan 5.3, we performed a Mantel–Haenszel fixed-effects meta-analysis of the following outcomes: recurrent VTE, VTE events, and major bleeding rates. Results: We identified 11 studies involving 7,965 patients. Factor Xa inhibitors were superior in preventing VTE recurrence, compared to low-molecular-weight heparin (LMWH) (OR 0.60; 95% CI 0.45–0.80; P < 0.01) and vitamin K antagonists (VKA) (OR 0.51; 95% CI 0.33–0.78; P < 0.01). As prophylaxis, factor Xa inhibitors had a similar rate of VTE compared to VKAs (OR 1.08 [95% CI 0.31–3.77]; P = 0.90) and a lower rate compared to placebo (OR 0.54 [95% CI 0.35–0.81]; P < 0.01). Major bleeding rates were higher with factor Xa inhibitors than with LMWHs (OR 1.34 [95% CI 0.83–2.18]; P = 0.23), but significantly lower than VKAs (OR 0.71 [95% CI 0.55–0.92]; P < 0.01). Conclusions: Factor Xa inhibitors are effective for VTE management in patients with cancer; however, they are also associated with an increased bleeding risk compared to LMWH, but decreased when compared to VKA.

Abstract 6048: An Indirect Comparison of the Efficacy and Safety of Factor Xa Inhibitors with Thrombin Inhibitors nn Preventing Venous Thromboembolism after Hip or Knee Surgery

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ganesan Karthikeyan ◽  
John W Eikelboom ◽  
Salim Yusuf ◽  
Jack Hirsh
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Indirect Comparison ◽  
Factor Xa ◽  
Knee Surgery ◽  
Phase Iii ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Controlled Trials ◽  
Efficacy And Safety

Introduction Selective factor Xa inhibitors and thrombin inhibitors are effective in the prevention of venous thromboembolism (VTE) after hip or knee surgery, but they have not been compared directly against each other. We performed an indirect comparison of the relative efficacy and safety of these two classes of inhibitors, from meta-analyses of randomized controlled trials (RCTs) of these agents, in which a low molecular heparin (LMWH) was used as a common comparator. Methods Relevant RCTs were identified by searching MEDLINE (Ovid MEDLINE® 1950 to March week 1, 2008), EMBASE (1980 to 2008, week 10) and the Cochrane Central Register of Controlled Trials (1 st quarter 2008), supplemented by hand searching and screening meeting websites. We restricted our search to the five agents (ximelagatran, dabigatran, fondaparinux, idraparinux and rivaroxaban) that have been evaluated in phase III trials. Trials were included if the study drug was compared against a LMWH and was administered in the pre- and/or postoperative (12–24hrs from surgery) period, to patients undergoing elective, hip or knee replacement surgery. The outcomes assessed were total VTE, symptomatic VTE, major bleeding and the need for blood transfusions. We obtained summary estimates (RR and 95% CI) for each outcome for the Xa and thrombin inhibitor studies, using a random-effects model. We then performed indirect comparisons between these estimates using standard statistical methods. Results We included 12 trials (18110 patients) of factor Xa inhibitors (fondaparinux, rivaroxaban) and 10 trials (17777 patients) of thrombin inhibitors (ximelagatran, dabigatran). These agents were compared with enoxaparin, except in two studies where dalteparin was the control agent. On indirect comparison, factor Xa inhibitors were significantly better than thrombin inhibitors in preventing total VTE (RR 0.54, 95% CI 0.40 – 0.75) and symptomatic VTE (RR 0.49, 95% CI 0.25– 0.97). There was no difference in the risk of major bleeding (RR 1.17, 95% CI 0.71–1.93) or the number of transfusions (RR 1.02, 95% CI 0.94–1.11). Conclusion Based on this indirect comparison, selective factor Xa inhibitors appear to be more effective than thrombin inhibitors, for the prevention of VTE after elective hip or knee surgery.

Abstract 12901: Novel Oral Anticoagulants Are Associated With Decreased Recurrence of Venous Thromboembolism in Patients With Cancer: An Updated Meta-Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sunil Upadhaya ◽  
Seetharamprasad Madala ◽  
Sunil Badami
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
P Value ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Recurrent Vte

Introduction: Patients with cancer are at high risk for recurrent thromboembolic phenomenon. Use of novel oral anticoagulants (NOAC) for treatment of venous thromboembolism (VTE) in such patients is controversial. We conducted this updated meta-analysis to evaluate the pooled efficacy and safety of NOAC in patients with cancer. Methods: We did systematic search of PubMed and Cochrane library databases for randomized controlled trials comparing NOAC with low molecular weight heparin (LMWH) for VTE treatment in cancer patients till April 2020. The efficacy outcomes were recurrent VTE and all-cause mortality rates, and the primary safety outcome was incidence of major bleeding rate. Results: Four randomized controlled studies comparing NOAC with LMWH (1446 patients in NOAC group and 1448 patients in LMWH group) were included in our study. Use of NOAC lead to significant reduction in recurrent VTE rate (odds ratio (OR): 0.55 [0.36-0.84], I 2 = 45 %, p value = 0.006) (Figure 1). However, we did not find any significant difference in rate of major bleeding (OR: 1.30 [0.76-2.23], I 2 = 35%, p value = 0.34) (Figure 2) and all-cause mortality (OR: 1 [0.80 - 1.26], I 2 = 33%, p value = 0.98). Conclusions: This updated meta-analysis showed comparatively lower pooled recurrent VTE rate in patient being treated with NOAC, whereas similar rates of major bleeding and all-cause death. NOAC are more efficacious and has similar safety profile compared with LMWH.

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

2020 ◽  
Vol 120 (07) ◽  
pp. 1128-1136 ◽  
Author(s):  
Michela Giustozzi ◽  
Giancarlo Agnelli ◽  
Jorge del Toro-Cervera ◽  
Frederikus A. Klok ◽  
Rachel P. Rosovsky ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
Recurrent Vte ◽  
Acute Venous Thromboembolism

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.

Direct Oral Factor Xa Inhibitors for the Treatment of Acute Cancer-Associated Venous Thromboembolism: A Systematic Review and Network Meta-analysis

2019 ◽  
Vol 94 (12) ◽  
pp. 2444-2454 ◽  
Author(s):  
Harry E. Fuentes ◽  
Robert D. McBane ◽  
Waldemar E. Wysokinski ◽  
Alfonso J. Tafur ◽  
Charles L. Loprinzi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Meta Analysis ◽  
Factor Xa ◽  
Factor Xa Inhibitors

scholarly journals Management of direct factor Xa inhibitor–related major bleeding with prothrombin complex concentrate: a meta-analysis

2019 ◽  
Vol 3 (2) ◽  
pp. 158-167 ◽  
Author(s):  
Siavash Piran ◽  
Rasha Khatib ◽  
Sam Schulman ◽  
Ammar Majeed ◽  
Anne Holbrook ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Prothrombin Complex Concentrate ◽  
Meta Analysis ◽  
Case Series ◽  
Factor Xa ◽  
The United States ◽  
Effective Management ◽  
Direct Factor ◽  
All Cause Mortality ◽  
Fxa Inhibitor

Abstract A targeted antidote for reversal of direct factor Xa (FXa) inhibitors is now available for clinical use in the United States, but it is costly and has limited availability. In a systematic review, we evaluated the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) as an alternative for managing direct FXa inhibitor–related major bleeding. A systematic literature search was conducted using Medline, Embase, and the Cochrane Register of Controlled Trials up to September 2018. No comparative studies were found. Ten case series with 340 patients who received PCC for direct FXa inhibitor–related major bleeding were included. The pooled proportion of patients with effective management of major bleeding was 0.69 (95% confidence interval [CI], 0.61-0.76) in 2 studies using the International Society on Thrombosis and Haemostasis (ISTH) criteria and 0.77 (95% CI, 0.63-0.92) in 8 studies that did not use the ISTH criteria; all-cause mortality was 0.16 (95% CI, 0.07-0.26), and thromboembolism rate was 0.04 (95% CI, 0.01-0.08). On the basis of evidence with very low certainty from single-arm case series, it is difficult to determine whether 4F-PCC in addition to cessation of direct oral FXa inhibitor is more effective than cessation of direct oral FXa inhibitor alone in patients with direct FXa inhibitor–related major bleeding.

scholarly journals Efficacy and Safety of Low-Dose Prasugrel Versus Clopidogrel in Patients With Acute Coronary Syndrome or Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Yuttana Wonngsalap ◽  
Supakorn Ungsriwong ◽  
Wanalee Kumtepm ◽  
Surasak Saokaew ◽  
Vichai Senthong ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Observational Studies ◽  
Low Dose ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Percutaneous Coronary

Abstract Purpose To assess the efficacy and safety of prasugrel at low doses compared to clopidogrel by looking at the occurrence of major adverse cardiac events (MACE) and major bleeding in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Methods We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for eligible randomized controlled trials (RCTs) and observational studies assessing efficacy and safety of low-dose prasugrel versus clopidogrel in patients with ACS or undergoing PCI up to May 22, 2020. We did a meta-analysis using a random-effects model to estimate relative risks (RRs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively. Results Six RCTs (n = 6,131) and six observational studies (n = 31,426) were included. There was no MACE reduction in patients receiving low-dose prasugrel compared with those receiving clopidogrel (RR 1.02, 95%CI 0.91 to 1.14), but there was an increased risk of major bleeding (RR 1.35, 95%CI 1.10 to 1.67). Conclusions Low-dose prasugrel yields no increase in efficacy when compared with clopidogrel, but it does expose patients to an increased risk of bleeding. Most studies considered here were conducted in Japan. Studies conducted with non-Asian patients may find that low-dose prasugrel offers a more favorable efficacy and risk profile. Considering the results of this analysis we believe low-dose prasugrel should be prescribed with extreme caution as it may result in bleeding events without any additional benefit over clopidogrel.

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