recurrent vte
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Author(s):  
Laurent Bertoletti ◽  
Gaelle Gusto ◽  
Artak Khachatryan ◽  
Nadia Quignot ◽  
Jose Chaves ◽  
...  

Introduction: Data from clinical trials indicate that direct oral anticoagulants (DOACs) are non-inferior and safer than conventional therapy (low-molecular weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting. Materials and Methods: This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013–2018. Patients with active cancer were excluded. After propensity score matching for each DOAC-VKA comparison, risks of bleeding, recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional-hazards regression was used to estimate adjusted hazard ratios of the endpoints. Results: 58137 patients were included (10775 VKAs, 10440 apixaban, 36922 rivaroxaban). Propensity score-matched cohort sizes were 7503 for apixaban and 9179 for rivaroxaban. The hazard ratio (95% confidence interval) was significantly lower for apixaban than VKAs for bleeding requiring hospitalization (0.43 [0.32-0.59]), all-cause death (0.61 [0.51-0.74]), and first-recurrent VTE (0.67 [0.52-0.85]). The hazard ratio was also significantly lower for rivaroxaban than VKAs for all-cause death (0.63 [0.53-0.74]) but not for bleeding requiring hospitalization (0.86 [0.69-1.07]) or first-recurrent VTE (0.91 [0.74-1.13]). Conclusions: Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Olivier Nepveu ◽  
Charles Orione ◽  
Cécile Tromeur ◽  
Alexandre Fauché ◽  
Cecile L’heveder ◽  
...  

Abstract Background Growing evidence suggests the relationship between obstructive sleep apnea (OSA) and venous thromboembolism (VTE). Few studies focused on VTE recurrence risk associated with OSA after anticoagulation cessation. Methods In a prospective cohort study, patients with documented VTE, were followed for an indefinite length of time and VTE recurrence were documented and adjudicated. The primary outcome was recurrent VTE after anticoagulation discontinuation. Secondary outcomes included all-cause mortality and the clinical presentation of VTE. Univariable and multivariable analyses were performed to identify risk factors for recurrence and mortality. Results Among the 2109 patients with documented VTE included, 74 patients had moderate to severe OSA diagnosis confirmed by home sleep test or polysomnography. During a median follow-up of 4.8 (interquartile range 2.5–8.0) years recurrent VTE occurred in 252 patients (9 with OSA and 243 without OSA). The recurrence risk in the univariable and multivariable analysis was not increased in patients with OSA, regardless of the time of diagnosis (before or after index VTE or pooled). VTE phenotype was significantly more often PE with or without associated deep vein thrombosis in the first event and recurrence for OSA patients compared to non-OSA patients. The risk of death was not increased in the OSA population compared to non-OSA patients in multivariable analysis. Conclusions In patients with OSA and VTE, the risk of all-cause mortality and VTE recurrence after anticoagulation discontinuation was not increased compared to non-OSA patients.


Author(s):  
Alexander T. Cohen ◽  
Janvi Sah ◽  
Amol D. Dhamane ◽  
Theodore Lee ◽  
Lisa Rosenblatt ◽  
...  

AbstractThere has been limited evidence reported about the outcomes of oral anticoagulants among patients with venous thromboembolism (VTE) and chronic kidney disease (CKD), especially those with stage V/end-stage renal disease (ESRD). This retrospective cohort analysis of five U.S. claims databases evaluated the risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB) for apixaban versus warfarin among VTE patients diagnosed with CKD, including ESRD. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Hazard ratios (HRs) were calculated for recurrent VTE, MB, and CRNMB among patients with CKD who experienced an index VTE. An interaction analysis was conducted to evaluate treatment effects across different stages of CKD. A total of 29,790 VTE patients with CKD were selected for analyses, of whom 10,669 (35.8%) initiated apixaban and 19,121 (64.2%) initiated warfarin. Among IPTW-balanced patient cohorts, the apixaban group had significantly lower risk of recurrent VTE (HR: 0.78; 95% confidence interval [CI]: 0.66–0.92), MB (HR: 0.76; 95% CI: 0.65–0.88), and CRNMB (HR: 0.86; 95% CI: 0.80–0.93) than the warfarin group. When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.


Author(s):  
Jonas Florin ◽  
Odile Stalder ◽  
Christine Baumgartner ◽  
Marie Méan ◽  
Nicolas Rodondi ◽  
...  

Abstract Background A family (FH) and personal history (PH) of venous thromboembolism (VTE) are commonly evaluated risk factors for recurrence. We examined the association between FH/PH of VTE and the risk of recurrence and whether a stronger history status (i.e., both FH/PH vs. no FH/PH) carries an increased recurrence risk. Methods We prospectively followed 813 patients aged ≥ 65 years with acute VTE from 9 Swiss hospitals. We classified patients into four groups: no FH/PH, FH only, PH only, and both FH/PH. The primary outcome was recurrent VTE during the full observation period. We examined the association between FH/PH status and the time to VTE recurrence using competing risk regression, adjusting for confounders and periods of anticoagulation. Results Of 813 patients with VTE, 59% had no FH/PH, 11% a FH only, 24% a PH only, and 7% had both a FH and PH of VTE. Overall, 105 patients had recurrent VTE during the full observation period. After adjustment, patients with a FH only (subhazard ratio [SHR] 0.8, 95% confidence interval [CI] 0.4–1.7), PH only (SHR 1.5, 95% CI 0.9–2.5), and both FH/PH (SHR 1.4, 95% CI 0.6–3.1) did not have an increased risk of recurrent VTE compared with those without FH/PH. When we considered the period after the completion of initial anticoagulation only, the results were similar. Conclusion Our findings indicate that in patients with acute VTE, a FH and/or PH of VTE does not convey an increased risk of recurrent VTE. In particular, we did not find a “dose–effect” relationship between FH/PH status and VTE recurrence.


2021 ◽  
pp. 875512252110641
Author(s):  
Rachel M. Watson ◽  
Carmen B. Smith ◽  
Erica F. Crannage ◽  
Laura M. Challen

Background: While commonly prescribed today, direct oral anticoagulants (DOACs) have historically been avoided in patients with class III obesity or a weight >120 kg due to limited literature regarding the efficacy and safety in this population. Objective: The overall objective was to examine the effectiveness of DOACs compared to warfarin in a population with obesity. Methods: Patients with a diagnosis of venous thromboembolism (VTE) or atrial fibrillation and a body mass index (BMI) ≥35 kg/m2 from August 1, 2015, to August 1, 2020, were included in this retrospective cohort study. Patients receiving a DOAC were matched in a 1:2 ratio to warfarin. The primary outcome was a composite of stroke or recurrent VTE. Secondary outcomes included the individual components of the primary outcome, hospitalization for bleed, and the primary outcome in patients with a BMI ≥40 kg/m2. Results: A total of 162 patients were included, with 54 and 108 in the DOAC and warfarin groups, respectively. Baseline BMI was similar between groups (45.7 kg/m2 for DOACs vs 43.8 kg/m2 for warfarin), with approximately 70% of patients having a BMI ≥40 kg/m2. The primary outcome occurred in 1 patient (1.9%) in the DOAC group and 2 patients (1.9%) in the warfarin group. The DOAC group had a higher, nonsignificant incidence of bleeding (5.6% vs 0.9%, P = 0.11). There was no difference between groups in incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), or stroke in patients with a BMI ≥40 kg/m2. Conclusion: DOACs may be as efficacious as warfarin in the prevention of stroke or recurrent VTE in patients with a BMI of ≥35 kg/m2. Prospective, randomized trials are warranted to further assess the efficacy and safety of DOACs in this population.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 178-178
Author(s):  
Haesuk Park ◽  
Hye-Rim Kang ◽  
Pei-Lin Huang ◽  
Wei-Hsuan Lo-Ciganic ◽  
Eric A Dietrich ◽  
...  

Abstract Introduction: Approximately 30% of patients with venous thromboembolism (VTE) experience a recurrence within 10 years of the initial event with their recurrence risk peaking during the first 6-12 months. Two large randomized clinical trials AMPLIFY-EXT and PADIS-PE reported that extended treatment with apixaban and warfarin beyond 6 months of initial treatment reduced recurrent VTE without increasing the rate of major bleeding compared to placebo, respectively. Little is known about real-world effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment for Medicare beneficiaries with VTE, despite the fact that VTE disproportionately affects the elderly. We assessed the effectiveness and safety of extended use of apixaban and warfarin beyond 6 months of initial treatment for prevention of recurrent VTE and adverse major bleeding events among Medicare beneficiaries with newly diagnosed VTE. Methods: A retrospective cohort study using 2014-2018 Medicare data (5% samples in 2014-2016 and 15% samples of Medicare beneficiaries in 2017-2018) was conducted for patients aged ≥18 years with a diagnosis of deep vein thrombosis or pulmonary embolism ascertained from inpatient claims. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy defined as ≥83% proportion days covered with oral anticoagulants during the initial 6-month period, and received extended treatment with either apixaban or warfarin or no extended therapy. We compared the risks of recurrent VTE and major bleeding between apixaban, warfarin, and no treatment groups. To adjust for differences in baseline characteristics and clinical factors (e.g., HAS-BLED score, active cancer, and provoked VTE) between groups, we used the stabilized inverse probability treatment weighting (IPTW) method. Follow-up continued until the occurrence of the first event, switch to the comparator, disenrollment, death, or end of the study period. Multivariable Cox proportional hazards modeling with IPTW was used to obtain adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI). Results: The study cohort (mean age=74 ±12 years, 40% male, 76% White) consisted of 2,315 users of extended apixaban treatment (83% with 5 mg twice a day and 17% with 2.5 mg twice a day; mean duration=6.2 months), 2,757 users of extended warfarin treatment (mean duration=8.2 months), and 2,328 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The incidence rates of recurrent VTE were 0.42, 1.73, and 1.72 per 100 person-years, and those of major bleeding were 2.28, 3.62, and 1.43 per 100 person-years in the apixaban, warfarin, and no treatment groups, respectively (Table 1). Compared to no extended treatment, the use of apixaban was associated with an 80% decreased risk of recurrent VTE (aHR=0.19, 95%CI=0.06-0.55) without increasing the risk of major bleeding (aHR=1.19, 95%CI=0.65-2.19); the use of warfarin did not lower the risk of recurrent VTE (aHR=0.75, 95%CI=0.42-1.37) but increased the risk of major bleeding (aHR=1.92, 95%CI=1.13-3.25). Compared to the use of warfarin, the use of apixaban was associated with a decreased risk of recurrent VTE (aHR=0.26, 95% CI=0.09-0.76) and no difference in major bleeding risk (aHR=0.61, 95%CI=0.36-1.06). These findings remained consistent in subgroup (e.g., patients with provoked vs. unprovoked VTE, patients with active cancer vs. those without, and patients with chronic kidney diseases vs. those without) and sensitivity analyses (e.g., ≥92% proportion days covered with oral anticoagulants during the initial 6-month period). Conclusions: Compared to no extended therapy, extended anticoagulation with apixaban was associated with a reduced risk of recurrent VTE without increasing the risk of major bleeding, whereas warfarin did not lower risk of recurrent VTE but increased the risk of major bleeding among Medicare beneficiaries with VTE. In the head-to-head comparison, the use of apixaban was more effective than warfarin in preventing recurrent VTE, without increasing the risk of major bleeding events. Our findings suggest that apixaban is an effective and safer option for extended treatment of VTE when compared to warfarin or no treatment among Medicare beneficiaries with VTE. Figure 1 Figure 1. Disclosures Park: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Kang: BMS/Pfizer Alliance American Thrombosis InvestigatorInitiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: MERCK: Research Funding; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. DeRemer: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS advisory board attendee: Honoraria.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3231-3231
Author(s):  
Trine-Lise Hannevik ◽  
Herish Garresori ◽  
Jorunn Brekke ◽  
Tone Ronnaug Enden ◽  
Hege Froen ◽  
...  

Abstract Background: Apixaban is a treatment option for venous thromboembolism (VTE) in cancer patients. There are no data on the effect of low dose apixaban after 6 months treatment. We wanted to assess the efficacy and safety of apixaban 2.5 mg twice daily as prophylaxis for recurrent VTE after 6 months initial treatment with full-dose apixaban. Patients and methods: We included 298 patients with cancer and any type of VTE. All patients were treated with full dose apixaban for the first 6 months. After 6 months, all patients with active cancer continued with apixaban 2.5 mg twice daily and were followed for the next 30 months. The primary endpoint of efficacy was recurrent VTE, the primary safety endpoint was major bleedings. Clinically relevant non-major bleedings was a secondary endpoint. The endpoints are reported as incidence rates or fractions with 95% confidence intervals, and as Kaplan-Meier plots. Results: During the first 6 months of full-dose anticoagulation 12 of 298 patients had recurrent VTE (4.0%, 95% confidence interval 2.1-6.9), 16 experienced major bleeding (5.4%, 95% CI 2.8-7.9%), and 26 patients experienced one or more episodes of CRNMB (8.9%, 95% CI 5.5-12) as previously reported. 1 Of the 298 patients included, 196 continued with apixaban 2.5 mg twice daily after 6 months. During treatment from 6 to 36 months with low-dose apixaban 15 of 196 (7.6%, 95% CI: 4.4-12) patients had recurrent VTE, 7 (3.6%, CI: 1.5-7.2) patients experienced major bleeding and 16 (8.2%, 95% CI: 4.7-13) patients experienced CRNMB. The highest incidence rate of both recurrent VTE and major bleedings were seen during the first month of full-dose apixaban (Table 1). After the dose reduction of apixaban, the incidence rate of recurrent VTE increased slightly during 6 to 12 months while the incidence rate of major bleeding decreased during the same time-period. After 12 months the incidence rate of both recurrent VTE and major bleeding was low and remained low during the entire 30 months follow-up (Table 1 and Figure 1). The Kaplan-Meier plot of the composite endpoint of recurrent VTE or major bleeding did not change after dose-reduction. After about 9 months treatment (i.e. 3 months on low dose apixaban) the Kaplan-Meier curve of the composite endpoint flattened out. Conclusion: Dose reduction of apixaban to 2.5 mg twice daily after 6 months of full dose anticoagulation resulted in a small increase in recurrent VTE, but a marked decrease in major bleedings during the 6-12 months period. After approximately 9 months the frequency of recurrent VTE and major bleedings remained low compared with the first 6 months of full-dose treatment. Reducing the dose of apixaban to 2.5 mg twice daily after 6 months of full-dose treatment appears safe and effective. References 1. Hannevik TL, Brekke J, Enden T, et al: Thrombosis and bleedings in a cohort of cancer patients treated with apixaban for venous thromboembolism. Thromb Res, 2020 Figure 1 Figure 1. Disclosures Hannevik: Pfizer/Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Garresori: Pfizer: Honoraria; Amgen: Honoraria; Bayer: Honoraria. Froen: Bristol-Myers Squibb: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees. Porojnicu: Bristol-Myers Squibb: Honoraria. Ghanima: Bayer, BMS/Pfizer: Research Funding; Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Griffols, Sanofi: Honoraria; Amgen, Novartis, Pfizer, Principia Biopharma Inc- a Sanofi Company, Sanofi, SOBI, Griffols, UCB, Argenx: Consultancy. Dahm: Pfizer: Honoraria; Novartis: Honoraria; Pfizer/Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4297-4297
Author(s):  
Tamanna Haque ◽  
Arletta Lozanski ◽  
Tzyy-Jye Doong ◽  
Ying Huang ◽  
Rui Li ◽  
...  

Abstract Background Venous thromboembolism (VTE) is the third most common cardiovascular disease with an incidence over 1% in the elderly. About 50% of VTE is unprovoked, which is associated with higher rates of recurrent VTE and complications such as post-thrombotic syndrome. Clonal hematopoiesis (CH) refers to recurrent somatic mutations associated with hematologic malignancies that are present in otherwise healthy individuals. CH is more common with increased age, occurring in more than 10% of people over the age of 70 and has been associated with an increased risk of coronary artery disease. The rates of CH in patients with VTE or complications arising from this is not known. Methods Adult patients (age ≥ 18) with VTE were enrolled at the Ohio State University Thrombosis Clinic between 2017 and 2020. Clinical data was obtained at the time of routine clinic follow-up or ad hoc, and a research blood sample was collected with routine blood work. DNA extracted from peripheral blood mononuclear cells were analyzed for the presence of CH via error corrected next generation sequencing (NGS) using the Ion Gene Studio S5 System. A custom AmpliSeq panel IAH150087 was designed to detect CH, which included whole gene sequencing and hotspots in 25 common genes associated with myeloid malignancies, including DNMT3A, TET2, ASXL1, among others, with a sequencing depth of up to 50,000X. Data was collected and analyzed using Ion Torrent S5/GS-S5 Instrument with Torrent Suite 5.12.0 version. Final analysis of sequence data was performed using combination of software: Variant Caller v.5.12.10-1, IGV5.01 (0) and Ion Reporter v.5.12.3.0. The hg19 reference sequence was used to assess for deviation. CH was defined as a variable allele frequency ≥ 2%. Two sample t-test and chi-square test were used to compare patients with and without CH for continuous and categorical variables, respectively. Results A total of 167 patients are included the study. Median age is 60.3 years and 55% of patients are female. 80% of patients are white. The majority of patients have unprovoked VTE (81%); 23 patients (13.8%) have VTE associated with cancer. 84% of patients were treated with a direct oral anticoagulant. Over the median follow-up duration of 400 days, 7 patients had recurrent VTE and 19 patients had a total of 21 bleeding events (7 major bleeding and 14 clinically relevant non-major bleeding [CRNMB] by ISTH criteria). Overall, 22 patients (13.2%) have detectable CH. Patients with CH are significantly older than those without CH (mean age 70 vs 59, p <0.0001). There is a trend towards increased CH rate in male patients (17% of male patients vs 10% of female patients with CH). There are no other differences in baseline characteristics among patients with and without CH, including type or location of VTE or cancer status. Among the 144 VTE patients without cancer, the median age is 60 years old and the CH rate is also 13.2%. In this group, the mean age of patients with CH is 12 years older than those without CH (70.5 years vs 58.4 years, p <0.0001). No other significant baseline characteristics are noted. 30 distinct CH mutations are noted in these 22 patients. Most patients have a single gene mutation (77%). Gene mutations in DNMT3A are the most common (46%), followed by TET2 (13%), and PPM1D (10%) (see figure). Most mutations are missense (57%), followed by nonsense (30%) and insertion/deletion mutations (13%). One patient has a JAK2 V617F mutation without known history of myeloproliferative disease. 8 CH patients with serial samples collected over a median duration of 136 days (range 91 - 490 days) showed no significant change in CH clone size over time. Patients with CH have no differences in rates of recurrent VTE or arterial thrombosis compared to those without CH. Patients with CH have a trend towards increased rate of combined major bleeding and CRNMB events (23% vs 10%, p=0.14). Patients with CH also had a trend towards increased mean corpuscular volume (MCV) (mean 93.5 vs 90.7, p=0.13), although no other cytopenias or differences in complete blood count parameters were noted. Conclusion The CH rate in patients with VTE was not found to be much higher than what might be expected by age alone. We found no change in the CH rate after excluding cancer patients. A larger VTE population with age-matched controls will better determine the CH rate in patients with VTE. CH can be a consideration in designing future clinical VTE studies that assess bleeding risk. Figure 1 Figure 1. Disclosures Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Newave: Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria. Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4059-4059
Author(s):  
Hye-Rim Kang ◽  
Bobby L Jones ◽  
Wei-Hsuan Lo-Ciganic ◽  
Christina E DeRemer ◽  
Eric A Dietrich ◽  
...  

Abstract Introduction: The optimal duration of extended oral anticoagulant treatment for patients with venous thromboembolism (VTE) beyond the initial 3 to 6 months of the treatment remains undetermined. Group-based trajectory modeling (GBTM) is a data-driven method that can categorize patients with similar longitudinal adherence patterns over time into distinct subgroups. This study identified distinct patient subgroups with similar adherence trajectories of extended treatment of direct-acting oral anticoagulants (DOACs), and then examined the association between adherence trajectories and the risk of recurrent VTE and major bleeding among patients with VTE. Methods: We identified patients ≥18 years with a diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) from inpatient claims using 2013-2019 Truven Commercial and Medicare Supplemental database. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy-defined as ≥83% proportion days covered (PDC) with oral anticoagulants during the initial 6-month treatment period, and had extended treatment with any DOACs or no extended therapy. Based on the monthly PDC as the DOAC adherence measure, we used GBTM to identify DOAC adherence trajectories during 6 months of the extended treatment. The final trajectory model was chosen by assessing the Bayesian information criteria, Nagin's criteria, and having at least 10% of patients in each trajectory group for improving clinical utility. We compared recurrent VTE and major bleeding among adherence trajectory subgroups. Patients were followed up from the initiation of the extended treatment until the occurrence of the study outcomes, discontinuation of DOACs, switching to warfarin, end of study period, or end of enrollment, whichever occurred first. Cox proportional hazard modeling with inverse probability treatment weighting (IPTW) was used to obtain hazard ratios (HR) and 95% confidence intervals (95% CI). Results: The study cohort (mean age=58.7 years and 51.1% males) consisted of 10,960 patients with extended treatment of DOACs (4,294 apixaban, 6,409 rivaroxaban, 238 dabigatran, and 19 edoxaban users) with a mean treatment duration of 7.7 months and 5,133 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The final GBTM models identified four distinct adherence trajectories for extended therapy including (1) patients with consistent adherence (group 1, 40.7%), (2) patients with gradually declining adherence (group 2, 14.3%), (3) patients with rapidly declining adherence (group 3, 13.1%), and (4) patients with no extended treatment (reference group, 31.9%) (Figure 1). The incidence rates of recurrent VTE were 18.6, 46.9, 84.1, and 160.7 per 10,000 person-years, and those of major bleeding were 61.0, 125.1, 168.3, and 48.7 per 10,000 person-years in group 1, group 2, group 3, and the reference group, respectively. After IPTW, demographics and clinical characteristics (e.g., HAS-BLED bleeding risk score, provoked VTE) were comparable across the four trajectory groups with <0.1 of the standardized mean difference for each pairwise comparison. Compared to the reference group, group 1 (HR=0.09, 95% CI=0.05-0.17) and group 2 (HR=0.16, 95% CI=0.04-0.58) had decreased risk of recurrent VTE without increasing risk of major bleeding (HR=1.26, 95% CI=0.76-2.10 in group 1, HR=2.28, 95% CI=0.96-5.36 in group 2). There was no difference in the risk of recurrent VTE (HR=0.32, 95% CI=0.09-1.16) in group 3 but they had an increased risk of major bleeding (HR=2.69, 95% CI=1.00-7.23). The findings were consistent across different types of DOACs, suggesting a class effect of DOACs as extended therapy. Conclusions: We identified 4 distinct trajectories of DOAC adherence during the 6 months of extended therapy among patients who completed 6 months of initial treatment. Compared to no extended treatment, persistent use of DOACs during extended treatment was associated with a lower risk of recurrent VTE without increasing major bleeding risk, whereas a rapid decline in adherence was associated with an increased risk of major bleeding with no difference in the risk of recurrence. Our findings provide evidence on the benefits of continuing and being adherent to extended anticoagulant treatment in patients with VTE without increasing the risk of major bleeding. Figure 1 Figure 1. Disclosures Kang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Jones: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; MERCK: Research Funding. DeRemer: BMS advisory board attendee: Honoraria; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. Park: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 668-668
Author(s):  
Corinne Frere ◽  
Dominique Farge ◽  
Deborah Schrag ◽  
Pedro H. Prata ◽  
Jean M. Connors

Abstract Introduction: International clinical practice guidelines (ITAC, ASCO, NCCN and ASH) have progressively endorsed direct factor Xa inhibitors (edoxaban, rivaroxaban and apixaban) as an alternative to monotherapy with low-molecular-weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) in cancer patients. The results from new randomized controlled trials (RCT) which assessed the efficacy and the safety of direct oral anticoagulants (DOAC) compared to LMWH for the treatment of cancer-associated thrombosis (CAT) were released during the past months. We therefore performed an updated meta-analysis of all publicly available data from RCT comparing DOAC with LMWH for the treatment of CAT. Methods: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and conference proceedings from all languages were searched up to August 2, 2021. Search strategy, study selection, data extraction and statistical analysis were performed in accordance with the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Risk of bias was assessed by using the Cochrane risk-of-bias tool in randomized controlled trials version 2.0. Pooled relative risk (RR) and 95% confidence intervals (CIs) were estimated using the Mantel-Haenszel method of Der Simonian and Laird within a random-effect model. Heterogeneity of effect size across studies was assessed using the I 2 statistic. Publication bias was assessed by visual inspection of funnel plots. All the statistical analyses were performed with the RevMan 5.3 software. Results: Six RCT comparing the efficacy and safety of DOAC versus LMWH, which enrolled a total of 3,690 cancer patients with acute VTE (1850 randomized to the DOAC arms and 1840 randomized to the LMWH arms), were included in the pooled analysis. Main study characteristics are summarized in Table 1. During a follow-up of 3 to 6 months under anticoagulant treatment, recurrent VTE occurred in 99 of 1,850 (5.3%) patients receiving DOACs versus 152 of 1,840 (8.3%) patients receiving LMWH. The risk of recurrent VTE was significantly lower with DOAC than with LMWH (RR 0.67, 95% CI 0.52-0.85, p = 0.001, I 2 = 0%, Figure 1A). Major bleeding occurred in 78 (4.2%) patients with CAT treated with DOAC versus 65 (3.5%) patients treated with LMWH. The risk of major bleeding was non significantly higher with DOAC (RR 1.20, 95% CI 0.85-1.70, p = 0.31, I 2= 7%, Figure 1B). CRNMB was more frequent in cancer patients receiving DOAC compared to those receiving LMWH (10.3% versus 6.3%, RR 1.63, 95% CI 1.25-2.11, p = 0.0003, I²= 6%, Figure 1C). The rates of all-cause mortality did not differ between the two groups (23.6% in the DOAC arms versus 23.3% in the LMWH arms, RR 1.02, 95% CI 0.89-1.16, p = 0.80, I² = 13%, Figure 1D). Conclusions: In this August 2021 meta-analysis of 3,690 patients treated for CAT, DOAC significantly reduced the risk of recurrent VTE compared with LMWH, without increasing the risk of major bleeding. However, as previously highlighted, the use of DOAC was associated with an increased risk of CRNMB. Our results provide additional evidence for the use of DOAC as a safe and effective first-line option for the treatment of CAT in patients who are not at high risk of bleeding. These findings may increase the level of certainty for the evidence used in the national or international clinical practice guidelines supporting the use of DOAC in cancer patients with CAT. Figure 1 Figure 1. Disclosures Connors: CSL Behring: Research Funding; Pfizer: Honoraria; Alnylam: Consultancy; takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Abbott: Consultancy.


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