Reduction In Recurrent Venous Thromboembolism Research Articles

Direct Oral Anticoagulants for Treating Acute Venous Thromboembolism in Children: Meta-Analysis of Randomized Controlled Trials.

Acute venous thromboembolism (VTE) in children presents unique challenges due to the limitations of standard anticoagulation therapies. Herein, we aimed to systematically review randomized controlled trials (RCTs) evaluating the efficacy and safety of direct oral anticoagulants (DOACs) in pediatric patients with acute VTE. PubMed and Embase databases were searched for RCTs comparing DOACs to standard anticoagulation in pediatric VTE patients. Efficacy outcomes included VTE recurrence and all-cause mortality, while safety outcomes comprised major bleeding and other adverse events. Three RCTs with 790 participants were included. When compared with standard anticoagulation, DOACs demonstrated a reduced risk of VTE recurrence (risk difference[RD] = -3%, 95% confidence interval[CI]: -6% to 0%, P = 0.04) and an increased risk of any adverse event (RD = 8%, 95% CI: 1% to 14%, P = 0.02). No significant differences were found in all-cause mortality, major bleeding, clinically relevant non-major bleeding, or total bleeding between the DOAC and control groups. DOACs, primarily dabigatran and rivaroxaban, are non-inferior to standard anticoagulants in reducing VTE recurrence in pediatric patients, with comparable safety profiles. Further research is essential to confirm these findings.

Safety and efficacy of apixaban versus low-molecular weight heparin or vitamin-K antagonists for venous thromboembolism treatment in patients with severe renal failure: A systematic review and meta-analysis

IntroductionChronic kidney disease is an independent risk factor for venous thromboembolism (VTE). Traditionally, Low Molecular Weight Heparin (LMWH) followed by warfarin has been the conventional therapy for VTE treatment. Direct oral anticoagulants (DOACs), including apixaban, have shown several advantages over the traditional therapy in individuals with normal kidney function. This meta-analysis aims to review the safety and efficacy of apixaban compared to warfarin or LMWH for the treatment of VTE in severe renal failure. MethodWe conducted literature search in PubMed, Embase, and Cochrane databases. Retrospective observational studies involving clinical effectiveness and safety outcomes of apixaban compared to warfarin in adult patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/m2 or on dialysis were included. ResultsEight studies were included in the analysis. Significant reduction in VTE recurrence observed in apixaban compared to warfarin (RR, 0.65; 95 % CI, 0.43–0.98; P = 0.04; I2 = 78 %). No significant difference in all-cause mortality between apixaban and warfarin (RR, 0.99; 95 % CI, 0.91–1.07; P = 0.74; I2 = 0 %). Apixaban showed a significantly lower rate of major bleeding (RR, 0.72; 95 % CI, 0.62–0.84; P < 0.0001; I2 = 34 %) and minor bleeding events (RR, 0.42; 95 % CI, 0.21–0.86; P = 0.02; I2 = 10 %) compared to warfarin. No significant difference observed in clinically relevant non-major bleeding between apixaban and warfarin (RR, 0.81; 95 % CI, 0.65–1.00; P = 0.05; I2 = 67 %). ConclusionApixaban was favored over warfarin for treating VTE in severe renal failure, reducing VTE recurrence and bleeding risk. No differences were observed in all-cause mortality and CRNMB events. More evidence is required due to limited RCTs and prospective studies.

Rivaroxaban Versus Low-Molecular-Weight Heparins in a Broad Cohort of Patients With Cancer-Associated Venous Thromboembolism: An Analysis of the OSCAR-US Program.

Cancer-associated venous thromboembolism (CAT) guidelines recommend direct oral anticoagulants as alternatives to low-molecular-weight heparin (LMWH) in most patients. This study compared the effectiveness and safety of rivaroxaban versus LMWH for a broad CAT cohort. The cohort study used electronic health data from January 2012 to December 2020 to evaluate patients with active cancer experiencing acute venous thromboembolism (VTE) and treated with rivaroxaban or LMWH. Propensity score-overlap weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE, bleeding-related hospitalization, and all-cause mortality were calculated. In total, 4935 patients were identified (27.9% on rivaroxaban and 72.1% on LMWH). The cancer types included gastrointestinal (29.4%), genitourinary (26.2%), lung (24.0%), breast (19.7%), and hematologic (14.4%). Rivaroxaban was associated with a reduction in recurrent VTE versus LMWH among all patients with cancer (HR = 0.78; 95%CI = 0.61-0.99) at 3 months. No differences in bleeding-related hospitalization or all-cause mortality were observed. Directionally similar results to those at 3 months were observed at 6 months for all outcomes. In conclusion, we observed fewer recurrent VTE cases and no increase in bleeding-related hospitalizations with rivaroxaban versus LMWH at 3 months in this patient cohort with various cancer types.

Comparison of Rivaroxaban and Low Molecular Weight Heparin in the Treatment of Cancer-Associated Venous Thromboembolism

BACKGROUND: Cancer associated thrombosis (CAT) guidelines recommend direct oral anticoagulants as alternatives to low molecular weight heparin (LMWHs) in most patients. We sought to compare the effectiveness and safety of rivaroxaban versus LMWH in a broad CAT cohort. METHODS: This retrospective cohort analysis used US Optum De-Identified electronic health data from January 1, 2012 through December 31, 2020 to identify patients with any active cancer type, who were admitted to the hospital, emergency department or observation unit for venous thromboembolism (VTE) and treated with rivaroxaban or LMWH. We used propensity score overlap weighting to balance anticoagulant cohorts on baseline covariates. Hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE, bleeding related hospitalization and all-cause mortality were calculated using Cox regression. RESULTS: We identified 4935 patients treated with rivaroxaban or LMWH (Table). Of these patients, 26.5% were ≥75 years of age, 55.9% were female, 19.0% had a body mass index ≥35 kg/m2 and 18.2% had a GFR <60 mL/minute at baseline. The CAT event was a pulmonary embolism ± deep vein thrombosis in 52.0% of patients, 46.3% had metastatic disease and 60% received active cancer treatment within 4 weeks of the CAT event. Cancer types included gastrointestinal (29.4%), genitourinary (26.2%), lung (24.0%), breast (19.7%) and hematologic (14.4%). At 3 months, rivaroxaban was associated with a significant 22% relative hazard reduction in recurrent VTE versus LMWH among all cancer patients. No significant difference in bleeding related hospitalization or all-cause mortality were observed at 3 months. Directionally similar results to those at 3 months were observed at 6 months for all outcomes. CONCLUSIONS: We observed less recurrent VTE and no increase in bleeding related hospitalizations associated with rivaroxaban compared to LMWH at 3 months in a broad cohort of patients with various cancer types. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A ten-year review of the impact of the transition from warfarin to direct oral anticoagulant – Has venous thromboembolism treatment become safer?

BackgroundThe introduction of direct oral anticoagulants (DOAC) has resulted in a paradigm shift in the management of venous thromboembolism (VTE). We evaluate the impact of the transition to DOAC, over the last decade, on overall VTE clinical outcomes including in first unprovoked major VTEs. MethodA retrospective analysis of all VTE admissions in non-cancer patients from January 2011 to December 2020 at Northern Health, Victoria, Australia. “Warfarin era” included events that occurred between January 2011 and December 2014 and “DOAC era” from January 2016. ResultsThere were 2687 cases involving 2508 patients (45.9 % males; median age 63 years). 98 % were symptomatic and 1261 events (47 %) were unprovoked. 1003 events occurred during the warfarin era (79 % warfarin, 6 % DOAC) and 1479 during the DOAC era (18 % warfarin, 70 % DOAC). While recurrent thrombosis during the acute phase of treatment was comparable, there were fewer recurrences during the long-term preventative phase of treatment in the DOAC era compared to warfarin era (HR 0.602, 95 % CI: 0.393–0.924, p0.020). Clinically significant bleeding events were lower in the DOAC era (HR 0.623, 95 % CI: 0.395–0.985, p = 0.043). A subanalysis of first unprovoked major VTE events (n = 602) demonstrated a significant reduction in recurrent VTE during the long-term preventative phase of treatment in the DOAC era (HR 0.296, 95 % CI: 0.097–0.901, p = 0.032) with no difference in clinically significantly bleeding rates (HR 0.529, 95 % CI 0.219–1.280, p = 0.158) between the eras. ConclusionTreatment outcomes for VTE appear to have improved over time with reduced rate of thrombotic and clinically significant bleeding complications in the DOAC era.

Direct Oral Anticoagulants for the Prevention of Recurrent Venous Thromboembolism: A Systematic Review & Network Meta-Analysis

Background:Several studies have reported the superiority of extended anticoagulation with rivaroxaban, apixaban, dabigatran and aspirin as superior to placebo for the prevention of recurrent venous thromboembolism (VTE). However, it is unknown if this is a class effect applicable to all direct oral anticoagulants (DOACs) or if one agent is superior. Network meta-analysis allows for indirect comparisons of agents or interventions that have not been formally evaluated in head-to-head trials while preserving randomization of the original trials.Methods:We performed a systematic review and network meta-analysis of randomized controlled trials that compared extended anticoagulation with DOACs to other oral agents (e.g., another DOAC, aspirin or placebo) for the prevention of recurrent VTE. We excluded data on extended treatment with vitamin K antagonists or low-molecular-weight-heparin. Data extraction and assessment of methodological quality with the GRADE approach was assessed by two independent reviewers and verified by the primary investigator. Effect size estimates were calculated and pooled using techniques of network meta-analysis. Effect size was expressed as hazard ratios and 95% confidence intervals.Results:Six randomized trials with a total of 9,610 participants were analyzed. All trials were of high methodological quality. Prior to randomization, all participants had completed an initial period of anticoagulation for an index VTE event; the majority were treated for 6 to 18 months for an unprovoked event prior to starting extended treatment for VTE prevention. Two trials compared low-dose aspirin (100 mg daily) to placebo (ASPIRE and WARFASA), one compared rivaroxaban 10 mg or 20 mg daily to low-dose aspirin (EINSTEIN CHOICE), and the others evaluated rivaroxaban 20 mg daily (EINSTEIN-EXT), apixaban 2.5 mg or 5 mg twice-daily (AMPLIFY-EXT) and dabigatran 150 mg twice-daily (RE-SONATE) versus placebo for the prevention of recurrent VTE. The results are summarized in Figure 1b. Compared to placebo, aspirin and all DOACs effectively reduced VTE recurrence. Apixaban, rivaroxaban, and dabigatran were superior to aspirin and demonstrated comparable efficacy in preventing VTE recurrence. There was no statistically significant difference in bleeding rates between any agents compared to placebo.Conclusion:Our results demonstrate that all DOACs can be used interchangeably for secondary prophylaxis of VTE, likely due to a drug class effect. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for the treatment of cancer-associated thrombosis (which agent for which patient).

Venous thromboembolism (VTE) is a common complication among patients with cancer, associated with significant higher rate of mortality and morbidity. Low-molecular-weight heparin (LMWH) as a single therapeutic is considered as the standard of care for the treatment of acute cancer-associated thrombosis for many years, showing a significant 40% reduction of recurrent VTE (RR: 0.58; 95% CI, 0.43 - 0.77) without a significant increase of major bleeding complications compared to VKA (RR: 1.09; 95% CI 0.55 - 2.12). Based on results analysis studies only including patients with proximal DVT or PE the risk of recurrent VTE was similar in the DOAC and the LMWH (RR 0.68; 95% CI, 0.39 - 1.17) groups, without significantively increasing the risk of either major bleeding (RR = 1.32; 95% CI 0.7 - 2.47) or CRNMB (RR 1.6; 95% 0.99 - 2.6). Compared with LMWH, the risk of major bleeding and clinically relevant-non major bleeding was higher, although non-significantly, with DOACs than with LMWH, underlying that DOACs should be avoided in patients at high risk of bleeding. The higher risk of bleeding reported in DOACs-treated patients appears related to an excess of upper GI bleeding. In addition to GI cancer, other high-risk features associated with bleeding complications are an urothelial cancer, drug-drug interactions and use of anticancer drugs associated with GI toxicity. Overall, DOACs are an effective treatment option, and safe in most cancer patients with acute VTE. Nonetheless, DOACs should be used with caution in cancer patients at high risk for bleeding due to cancer site and stage per se or to cancer treatments.

Extended DOAC therapy in patients with VTE and potential risk of recurrence: A systematic review and meta‐analysis

BackgroundGuidelines recommend at least 3 months of anticoagulation for venous thromboembolism (VTE). Evidence supporting indefinite anticoagulation exists in certain conditions; however, for many patients, uncertainty regarding when to discontinue anticoagulation persists. ObjectiveWe aimed to investigate the efficacy and safety of extended direct oral anticoagulants (DOAC) therapy in patients with VTE and clinical uncertainty regarding extended anticoagulation. MethodsWe searched EMBASE, MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases for randomized control trials examining extended anticoagulation with DOACs as compared to non‐extended therapy for the treatment of VTE. ResultsOf 560 citations identified by the search, three studies were eligible. Extended anticoagulation reduced VTE recurrence (relative risk [RR] 0.18, 95% confidence interval [CI] 0.12 to 0.25), and mortality (RR 0.39, 95% CI 0.19 to 0.80) with a low total number of deaths in the DOAC group (n = 12) versus placebo (n = 18). Extended anticoagulation increased clinically relevant non‐major bleedings (RR 2.51, 95% CI 1.37 to 4.59). There was no difference in rates of major bleeding (RR 1.87, 95% CI 0.19 to 17.85); however, there was a low number of major bleeding events in both DOAC (n = 9) and placebo groups (n = 4). The results were mostly driven by one study (AMPLIFY‐EXT), with significant heterogeneity between studies noticed when assessing bleeding outcomes. ConclusionExtended DOAC therapy for 1 year in patients with clinical uncertainty for ongoing anticoagulation can reduce VTE recurrence and mortality; however, it could increase clinically relevant non‐major bleeding events.

Efficacy and safety of novel oral anticoagulants versus low molecular weight heparin in cancer patients with venous thromboembolism: A systematic review and meta-analysis.

Novel Oral Anticoagulants (NOACs) have been considered for treating cancer-related venous thromboembolism (VTE), but safety issues have been raised. We performed a systematic review and pairwise meta-analysis of the efficacy and safety of NOACs versus low molecular weight heparin (LMWH) in this setting. Four randomized controlled trials were included, providing data on 2894 patients. Compared to LMWH, NOACs were associated with a significantly lower risk of VTE recurrence and were not associated with an increased risk of major bleedings (MB). NOACs were non inferior to LMWH for a composite outcome of VTE recurrence and MB, pulmonary embolism recurrence and all-cause mortality; however, NOACs were associated with an increased risk of clinically relevant nonmajor bleedings (CRNMB) and gastrointestinal MB. In conclusion, in patients with cancer-related VTE, NOACs are effective and safe in reducing VTE recurrence compared to LMWH. An increased risk of CNRMB and GI MB should nonetheless be considered.

Anticoagulants for the treatment of venous thromboembolism in patients with cancer: A comprehensive systematic review, pairwise and network meta-analysis.

Cancer-associated venous thromboembolism (VTE) is associated with high VTE recurrence and bleeding. We included all randomized clinical trials that evaluated the efficacy and safety of various anticoagulants in cancer-associated VTE. Trial-level data were extracted from 13 trials. Aggregate odds ratios (ORs) were calculated using direct and network meta-analysis. The primary outcome was VTE (pulmonary embolism and/or deep vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. We identified 13 trials with 4869 patient-years of follow-up (6595 total patients; mean age 62.4 ± 12.2; 50.4 % female; 17.7 % hematological malignancies). The most common cancer type was colorectal and 48 % had metastatic cancer at baseline. Compared to vitamin-K-antagonists (VKAs), non-vitamin-K-antagonist-oral-anticoagulants (NOACs) were associated with significantly reduced VTE recurrence (OR, 0.58; 95 % CI, 0.40-0.83) and reduced major bleeding risks (OR, 0.56; 95 % CI, 0.35-0.91). However, no differences were observed in the subgroup analysis of patients with active cancer. Although NOACs were associated with reduced VTE recurrence compared with low-molecular-weight-heparin (LMWHs) (OR, 0.46; 95 % CI, 0.25- 0.85), there was a significant increased major bleeding in high-quality trials. LMWHs were associated with significantly reduced VTE recurrence compared with VKAs (OR, 0.52; 95 % CI, 0.39-0.71) and similar bleeding risks. Conclusions: Among patients with cancer-associated VTE, NOACs were associated with significantly reduced VTE recurrence and bleeding compared with VKAs, however, with similar outcomes in the active cancer population. NOACs were associated with reduced VTE recurrence but higher bleeding risks compared with LMWHs. LMWHs were associated with significantly reduced VTE recurrence and similar bleeding compared with VKAs.

Treatment of cancer‐associated venous thromboembolism: 12‐month outcomes of the placebo versus rivaroxaban randomization of the SELECT‐D Trial (SELECT‐D: 12m)

BackgroundThe Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT‐D) trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared with dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation. ObjectivesTo assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months. Patients/MethodsIn SELECT‐D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomization to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomization closed prematurely because of low recruitment when 92 of the planned 300 patients were recruited. ResultsNinety‐two of 136 eligible patients were randomized to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomization was 14% with placebo and 4% with rivaroxaban (hazard ratio, 0.32; 95% confidence interval [CI], 0.06‐1.58). The major and clinically relevant non‐major bleeding rates were 0% and 0% with placebo; and 5% (95% CI, 1‐18) and 4% (95% CI, 1‐17) with rivaroxaban. In an exploratory analysis, 7 (15%) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT‐negative cohort (P = .03). ConclusionThe SELECT‐D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence.

Comparative effectiveness and safety of direct-acting oral anticoagulants (DOACS) for the reduction of recurrent venous thromboembolism in cancer patients: A protocol for systematic review and network meta-analysis using a generalized pairwise modeling methodology.

Background:There has been a significant improvement in both our understanding and therapeutic choices available to clinicians for the management of cancer associated thrombosis (CAT). Even with the recent publication of a systematic review and landmark trials demonstrating the non-inferiority of DOACS-based anticoagulation strategy compared to the standard of care in patients with CAT, there is unresolved uncertainty regarding the exact hierarchy of risks and effectiveness of various DOAC analogues in these cohorts of patients.Method:We will carry out a network meta-analyses, utilizing a novel generalized pairwise methodology to generate direct and indirect comparisons between the various DOAC analogues. We will search the following databases for studies that satisfies pre-specified inclusions criteria; these include PubMed, EMBASE, Cochrane library, Clinicaltrials.gov, conference abstracts among other sources. The primary efficacy and safety outcomes are recurrent VTE and major hemorrhagic events, respectively. Two reviewers will Search the databases independently with the view to identify studies that meet eligibility criteria. The methodological quality of the included studies will be determined using a recently validated risk of bias assessment tool.Results:We expect that the result of this review will ascertain the hierarchy of risks and effectiveness of various DOAC analogues in patients with CAT.Conclusion:Results of this review will assist in informed decisions making regarding therapeutic guidelines of DOAC in CAT.

A randomised controlled trial of extended anticoagulation treatment versus standard treatment for the prevention of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (the ExACT study).

Venous thromboembolism (VTE) is prevalent and impactful, with a risk of death, morbidity and recurrence. Post-thrombotic syndrome (PTS) is a common consequence and associated with impaired quality of life (QoL). The ExACT study was a non-blinded, prospective, multicentred randomised controlled trial comparing extended versus limited duration anticoagulation following a first unprovoked VTE (proximal deep vein thrombosis or pulmonary embolism). Adults were eligible if they had completed ≥3months anticoagulation (remaining anticoagulated). The primary outcome was time to first recurrent VTE from randomisation. The secondary outcomes included PTS severity, bleeding, QoL and D-dimers. Two-hundred and eighty-one patients were recruited, randomised and followed up for 24months (mean age 63, male:female 2:1). There was a significant reduction in recurrent VTE for patients receiving extended anticoagulation [2·75 vs. 13·54 events/100 patient years, adjusted hazard ratio (aHR) 0·20 (95% confidence interval (CI): 0·09 to 0·46, P<0·001)] with a non-significant increase in major bleeding [3·54 vs. 1·18 events/100 patient years, aHR 2·99 (95% CI: 0·81-11·05, P=0·10)]. Outcomes of PTS and QoL were no different between groups. D-dimer results (on anticoagulation) did not predict VTE recurrence. In conclusion, extended anticoagulation reduced VTE recurrence but did not reduce PTS or improve QoL and was associated with a non-significant increase in bleeding. Results also suggest very limited clinical utility of D-dimer testing on anticoagulated patients.

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

ObjectiveTo explore the efficacy and safety of direct oral factor Xa inhibitors in the treatment of cancer-associated acute venous thromboembolism (VTE). Patients and MethodsMEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer-associated acute VTE. Databases were searched from inception to September 19, 2018. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence and major and clinically relevant nonmajor bleeding. ResultsWe identified 3 randomized controlled trials, at low risk of bias, that enrolled 1739 patients with cancer-associated VTE. Direct comparison revealed a lower rate of VTE recurrence in DOAC compared with dalteparin groups (odds ratio [OR], 0.48; 95% CI, 0.24-0.96; I2=46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared with 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 with dalteparin (OR, 1.70; 95% CI, 1.04-2.78). Clinically relevant nonmajor bleeding 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. ConclusionDirect oral anticoagulants appear to lower the risk of VTE recurrence compared with dalteparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared with the other DOACs.

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

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.

Anticoagulants for the treatment of venous thromboembolism in patients with cancer: An updated pairwise and network meta-analysis of randomized trials.

e14692 Background: Cancer-associated venous thromboembolism (VTE) is common. Although low molecular weight heparin (LMWH) is the standard therapy in this setting, little is known with regard to non-vitamin K antagonist oral anticoagulants (NOACs). Therefore, we thought about evaluating the safety and efficacy of various anticoagulants in this vulnerable population. Methods: Electronic database search was conducted to identify randomized clinical trials (RCTs) that compared LMWH, NOACs, and/or vitamin-K-antagonists (VKA) in cancer patients. We performed frequentist direct and Bayesian network meta-analysis using random-effects model to calculate odds ratios (ORs), 95% confidence intervals (CIs), and 95% credible intervals (CrIs). The primary outcome was VTE (pulmonary embolism and deep-vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. Results: We identified 13 RCTs with 6,595 total patients (mean age 62.4 ± 12.2; 50.4% female; 17.7% hematological malignancies; and 6 months median follow-up). The most common cancer type was colorectal and 48% of the population had metastatic cancer at baseline. NOACs were associated with significantly reduced VTE recurrence compared with VKA (OR = 0.58; 95% CI = 0.40-0.83; P &lt; 0.01; number needed to treat [NNT] = 40) and LMWH (OR = 0.46; 95% CI = 0.25-0.85; P = 0.01; NNT = 20). LMHW was associated with significantly reduced VTE recurrence compared with VKA (OR = 0.52; 95% CI = 0.39-0.71; P &lt; 0.01; NNT = 18). NOACs were associated with significantly reduced major bleeding compared with VKA (OR = 0.56; 95% CI = 0.35-0.91; P = 0.02; NNT = 64). There was no significant difference identified between the anticoagulant groups in regard to all-cause mortality. Conclusions: Among cancer patients with VTE, NOACs were associated with significantly reduced VTE recurrence compared to LMWH and VKA, and significantly reduced major bleeding compared with VKA. LMWH was associated with significantly reduced VTE recurrence compared with VKA.

Prevention of recurrent deep-vein thrombosis

The aim of this review is to outline recent randomized controlled trials and strategies that have tested various methods that aim to reduce the risk of recurrent venous thromboembolism (VTE) after the completion of anticoagulant therapy. Aspirin reduced VTE recurrence by approximately 30% (hazard ratio [HR], 0.68; 95% confidence interval [CI] 0.51–0.90) without any increase in bleeding. Dabigatran was effective in reducing VTE (HR, 0.08; 95% CI, 0.02–0.25) but carried a lower risk of major or nonmajor clinically relevant bleeding than warfarin but a higher risk than placebo: 5.3% in the dabigatran group and 1.8% in the placebo group (HR, 2.92; 95% CI, 1.52–5.60). Rivaroxaban was effective in reducing VTE (HR, 0.18; 95% CI, 0.09–0.39) but carried a higher risk of major or nonmajor clinically relevant bleeding than placebo: 6.0% in the rivaroxaban group and 1.2% in the placebo group (HR, 5.19; 95% CI, 2.3–11.7). Apixaban at either treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent VTE from 8.8% in the placebo group to 1.7% in the apixaban group (Relative risk reduction of 81%) (P < 0.001%) without increasing the rate of major bleeding. Sulodexide reduced the risk of recurrence (HR, 0.49; 95% CI 0.27–0.92), without any increase in bleeding risk. Residual thrombus and elevated D-dimer are markers for increased risk of recurrence. Their presence when combined with other risk factors enables one to stratify patients into high, intermediate, or low risk of recurrence of VTE. Other markers enable one to stratify patients into high, intermediate, and low risk for bleeding. On the basis of the balance of risks for recurrence and bleeding, one can advise patients on the need for secondary prevention and the most suitable medication.

Impact of Prolonged Anticoagulation with Rivaroxaban on Provoked Venous Thromboembolism Recurrence: IMPROVE-VTE

BackgroundWe sought to evaluate the real-world effectiveness and safety of prolonged anticoagulation with rivaroxaban following a provoked venous thromboembolism. MethodsUsing US MarketScan claims from November 2012 to March 2017, we identified adults with ≥1 primary hospitalization or emergency department diagnosis code for venous thromboembolism, a provoking (major or minor, persistent or transient) risk factor, at least 3 months of continuous rivaroxaban treatment, and ≥12 months of continuous insurance benefits prior to their qualifying venous thromboembolism. Patients were categorized as either continuing rivaroxaban or discontinuing anticoagulation (no anticoagulation or nonaspirin antiplatelet agents but may have received aspirin) after the initial 3 months of rivaroxaban treatment (index date). Differences in baseline covariates between cohorts were adjusted for using inverse probability-of-treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Twelve month incidences of recurrent venous thromboembolism or major bleeding were compared between cohorts using Cox regression (according to an intention-to-treat methodology) and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). ResultsAmong patients experiencing a provoked venous thromboembolism and treated with rivaroxaban for the first 3 months (N=4,990), continued rivaroxaban use beyond 3 months (median [25%, 75% range duration of additional rivaroxaban use = 3 [2, 5] months) was associated with a 44% (95% CI of 9%-66%) lower hazard of recurrent venous thromboembolism without altering major bleeding risk [HR of 0.87, 95% CI of 0.51-1.49] versus anticoagulation discontinuation (with or without aspirin use). ConclusionsOur study suggests continuing rivaroxaban after the initial 3 month period was associated with a decreased risk of recurrent venous thromboembolism. The observed reduction in recurrent venous thromboembolism with prolonged rivaroxaban use was not associated with a significant change in major bleeding risk.

Impact of Prolonged Anticoagulation with Rivaroxaban on Provoked Venous Thromboembolism Recurrence: The Improve-VTE Study

Background: The optimal duration of anticoagulation following an incident provoked venous thromboembolism (VTE) remains unclear. Two randomized trials have shown extended duration rivaroxaban use in patients experiencing an unprovoked or provoked VTE can reduce patients' risk of recurrent thrombosis without a significant increased risk of major bleeding compared to placebo or aspirin.Objectives: We sought to evaluate the real-world effectiveness and safety of prolonged anticoagulation with rivaroxaban following an incident provoked VTE.Methods: Using claims data from the US Truven MarketScan databases from November 1, 2012 through March 31, 2017, we identified adult patients with a primary discharge diagnosis of VTE (deep vein thrombosis and/or pulmonary embolism) during a hospitalization or emergency department visit, who had a provoking (major or minor, persistent or transient) risk factor, at least 3-months of continuous rivaroxaban treatment and ≥12-months of continuous medical and prescription insurance benefits prior to their incident VTE. Patients were categorized as either continuing rivaroxaban or discontinuing anticoagulation (no anticoagulation or antiplatelet agents, with or without aspirin) after the initial 3-months of rivaroxaban treatment (index date). Differences in baseline covariates between cohorts were adjusted for using inverse probability-of-treatment weights (IPTW) based on propensity-scores (residual standardized differences <0.1 achieved for all covariates after adjustment). Study endpoints included recurrent VTE and major bleeding (per the Cunningham algorithm). Patients were followed until occurrence of an endpoint, insurance disenrollment or up to 12-months post-index date. The incidences of recurrent VTE or major bleeding were compared between cohorts using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analyses were performed for each endpoint according to whether patients had a major persisting (i.e. cancer), minor persisting (i.e. inflammatory bowel disease, lower extremity paralysis, heart failure, stage III or worse chronic kidney disease, hereditary or acquired thrombophilia), minor transient (i.e. admitted to hospital for ≥3-consecutive days in past 3-months, hormonal therapy, pregnancy or puerperium, leg injury with impaired mobility) or major transient risk factor (i.e. major surgery or trauma).Results: Among patients experiencing an incident provoked VTE and treated with rivaroxaban for the first 3-months (N=4,990), continued rivaroxaban use beyond 3-months [median (25%, 75% range) duration of additional rivaroxaban use = 3 (2, 5) months] was associated with a 44% lower hazard of recurrent VTE without significantly altering major bleeding risk when compared to anticoagulation discontinuation with or without aspirin use (Table). The highest risk of recurrent thrombosis following provoked VTE (3.1% in the discontinued anticoagulation cohort) appeared to occur in patients with a minor persisting risk factor; with continued rivaroxaban use associated with a significant 73% reduction in recurrent VTE.Conclusions: Although the absolute incidence of recurrence was low, our study suggests continuing rivaroxaban after the initial 3-month period was associated with a decreased risk of recurrent VTE, particularly in those with a minor persisting risk factor. The observed reduction in recurrent VTE with prolonged rivaroxaban use was not associated with a significantly increased risk of major bleeding. [Display omitted] DisclosuresColeman:Bayer AG: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs LLC: Consultancy, Honoraria, Research Funding. Turpie:Bayer AG: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs LLC: Consultancy, Speakers Bureau. Beyer-Westendorf:Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bayer: Honoraria, Research Funding.

Extended Treatment with Apixaban for Venous Thromboembolism Prevention in the Netherlands: Clinical and Economic Effects.

Background Dutch guidelines advise extended anticoagulant treatment with direct oral anticoagulants or vitamin K antagonists for patients with idiopathic venous thromboembolism (VTE) who do not have high bleeding risk. Objectives The aim of this study was to analyze the economic effects of extended treatment of apixaban in the Netherlands, based on an updated and adapted previously published model. Methods We performed a cost-effectiveness analysis simulating a population of 1,000 VTE patients. The base-case analysis compared extended apixaban treatment to no treatment after the first 6 months. Five additional scenarios were conducted to evaluate the effect of different bleeding risks and health care payers' perspective. The primary outcome of the model is the incremental cost-effectiveness ratio (ICER) in costs (€) per quality-adjusted life-year (QALY), with one QALY defined as 1 year in perfect health. To account for any influence of the uncertainties in the model, probabilistic and univariate sensitivity analyses were conducted. The treatment was considered cost-effective with an ICER less than €20,000/QALY, which is the most commonly used willingness-to-pay (WTP) threshold for preventive drugs in the Netherlands. Results The model showed a reduction in recurrent VTE and no increase in major bleeding events for extended treatment in all scenarios. The base-case analysis showed an ICER of €9,653/QALY. The probability of being cost-effective for apixaban in the base-case was 70.0% and 91.4% at a WTP threshold of €20,000/QALY and €50,000/QALY, respectively. Conclusion Extended treatment with apixaban is cost-effective for the prevention of recurrent VTE in Dutch patients.