Similar Risk Of Major Bleeding Research Articles

Clopidogrel Versus Aspirin as Monotherapy Following Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome Receiving a Drug-Eluting Stent: A Systematic Literature Review and Meta-Analysis.

This study aimed to evaluate the comparative effectiveness and safety of clopidogrel versus aspirin as monotherapy following adequate dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS). MEDLINE, Embase, and CENTRAL were searched from database inception to September 1, 2023. Randomized controlled trials (RCTs) and observational studies evaluating the effectiveness or safety of clopidogrel versus aspirin as monotherapy following DAPT in patients with ACS who received a drug-eluting stent were included. Random-effects meta-analyses were conducted to compare risks of major adverse cardiovascular events (MACE) and clinically relevant bleeding. Of 6242 abstracts identified, three unique studies were included: one RCT and two retrospective cohort studies. Studies included a total of 7081 post-percutaneous coronary intervention ACS patients, 4260 of whom received aspirin monotherapy and 2821 received clopidogrel monotherapy. Studies included variable proportions of patients with ST-elevation myocardial infarction (STEMI), non-STEMI, and unstable angina. From the meta-analysis, clopidogrel was associated with a 28% reduction in the risk of MACE compared with aspirin (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.54, 0.98), with no significant difference in clinically relevant bleeding (HR: 0.92; 95% CI: 0.68, 1.24). Despite the paucity of published evidence on the effectiveness and safety of clopidogrel versus aspirin in patients with ACS post-drug-eluting stent implantation, this meta-analysis suggests that clopidogrel versus aspirin may result in a lower risk of MACE, with a similar risk of major bleeding. The present results are hypothesis-generating and further large RCTs comparing antiplatelet monotherapy options in ACS patients are warranted.

Apixaban Versus Vitamin K Antagonists in Patients With Antiphospholipid Syndrome: A Cohort Study.

Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in patients with APS on apixaban versus vitamin K antagonists (VKA). We enrolled 152 patients with APS (aged 44 years [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target international normalized ratio [INR] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism, ischemic stroke, or myocardial infarction, along with major bleeding. We observed 4 thrombotic events (6.1%, 3 venous thromboembolism and 1 ischemic stroke) in patients on apixaban and 12 events (14%, 9 venous thromboembolism, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. Patients with APS on apixaban had similar risk of recurrent thromboembolism compared with those on warfarin (hazard ratio [HR] = 0.327, 95% confidence interval [CI]: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs. 50%, P = 0.01) and more frequently in triple-positive APS (50% vs. 22.1%, P = 0.028) and in patients with higher D-dimer at baseline ( P = 0.023); the latter difference was present in the apixaban group ( P = 0.02). Patients on apixaban had similar risk of major bleeding compared with warfarin (HR = 0.54, 95% CI: 0.201-1.448). In real-life patients with APS, apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some patients with APS could be treated with apixaban.

Comparison of different direct oral anticoagulant regimens in atrial fibrillation patients with high bleeding risk

BackgroundThe optimal dose of direct oral anticoagulants (DOACs) to prevent ischemic stroke (IS) and systemic thromboembolism (STE) in atrial fibrillation (AF) patients with a predisposing bleeding risk remains unclear. ObjectiveThe purpose of this study was to compare the effectiveness and safety of different DOAC dosage regimens in AF patients with high bleeding risk but low thrombosis risk. MethodsThis retrospective observational study was conducted with the National Health Insurance claims database in Taiwan to include AF patients aged 20 up to 75 years, under DOAC therapy, with CHA2DS2-VASc score of 1 for males and 2 for females and HAS-BLED score ≥3. Standard-dose regimen was defined as dabigatran 300 mg, rivaroxaban 20 mg, apixaban 10 mg, or edoxaban 60 mg per day. Any other lower-dose regimen were defined as the low-dose regimen. The primary outcomes were IS and major bleeding (MB). The secondary outcomes were STE, gastrointestinal bleeding, intracranial hemorrhage, and cardiovascular death. ResultsA total of 964 patients were included (52.1% standard-dose regimen). Median HAS-BLED score was 3 [interquartile range 3–3]. Compared with standard-dose group, patients in the low-dose group had a significantly increased risk of IS (adjusted hazard ratio [aHR] 5.13; 95% confidence interval 1.37–19.22) and STE (aHR 3.14 [1.05–9.37]) but similar risk of MB (aHR 0.45 [0.12–1.67]). The risks of other hemorrhage and cardiovascular death were similar between the 2 dose groups. ConclusionAmong patients with a predominant bleeding risk but relatively low thrombosis risk, the low-dose DOAC regimen is not a more appropriate selection than standard-dose regimen.

Thromboembolic and bleeding events after valvular intervention in patients with atrial fibrillation

AimTo assess outcomes after cardiac surgery with biological valve replacement, valve repair or transcatheter aortic valve implantation (TAVI) in patients with atrial fibrillation (AF) in accordance with oral anticoagulant (OAC)...

Risk of Major Bleeding Associated with Concomitant Direct-Acting Oral Anticoagulant and Clopidogrel Use: A Retrospective Cohort Study.

Combined anticoagulant-antiplatelet therapy is often indicated in adults with cardiovascular disease and atrial fibrillation or venous thromboembolism. The study aim was to assess the comparative risk of bleeding between rivaroxaban and apixaban when combined with clopidogrel. We conducted a retrospective cohort study of commercially insured US adults newly treated with a combination of rivaroxaban+clopidogrel or apixaban+clopidogrel (2015-2018) using Merative™ Marketscan Research Databases. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the treatment groups. Weighted Cox proportional hazards regression was used to estimate the risk of major bleeding. The study cohort included 2895 rivaroxaban+clopidogrel users and 3628 apixaban+clopidogrel users. The median (range) duration of follow up was 61 (73) days. Rivaroxaban+clopidogrel users had a similar risk of major bleeding compared with apixaban+clopidogrel users (IPTW incidence rate per 100 person-years 7.96 vs 7.38; IPTW hazard ratio [HR] 1.13 [95% CI 0.78-1.63]). In the subcohort of adults who were treated with DOAC or clopidogrel monotherapy prior to the combined therapy, the risk of major bleeding did not differ by the drug of monotherapy (IPTW HR for rivaroxaban+clopidogrel group: 0.66 [95% CI 0.33-1.32]; IPTW HR for apixaban+clopidogrel group: 1.10 [95% CI 0.55-2.23]) CONCLUSIONS: In our study of commercially insured US adults, the concomitant use of rivaroxaban+clopidogrel and apixaban+clopidogrel conferred a similar risk of major bleeding. DOAC versus clopidogrel monotherapy prior to the concomitant therapy did not influence the risk of major bleeding.

Abstract 19017: Peri-Operative Bridging Requirement for Patients Chronically Taking Direct Oral Anticoagulants (DOACS) or Vitamin-K Antagonists (VKA) Before Undergoing the Elective Procedure: A Systematic Review and Meta-Analysis

Introduction: Many patients undergo elective interventions/surgical procedures while being on direct oral anticoagulants (DOACs) or vitamin-K antagonists (VKA) chronically. There is limited data on peri-procedural management of DOACs in patients undergoing elective procedures. It is also unclear if there is any role of peri-procedural bridging in patients on chronic VKA therapy. We conducted this study to evaluate the efficacy and safety of DOACs (continued vs. interrupted)and VKAs (with vs. without bridging) among patients undergoing elective procedures. Methods: This systematic literature review was conducted according to PRISMA guidelines until 10 th June 2023. The following inclusion criteria were used: adults, chronic use of VKAs or DOACs, elective procedures, and clinical trials. Primary endpoints were major bleeding, stroke, MI, and VTE. A generic variance random effects model was used to estimate odds ratios using CMA III. Heterogeneity and quality of studies were quantified via I 2 statistic and GRADE score, respectively. Results: 14 clinical trials were included (n=15683). There was no difference in the risk of major bleeding (OR: 1.06, 95% CI: 0.65 -1.7, I2: 46%) or risk of stroke(OR: 1.10, 95% CI: 0.66 - 1.84, I2: 0%) whether DOACs were held or continued respectively. Among patients on VKA, there was no difference in risk of major bleeding in bridging vs. no bridging groups (OR: 2.02, 95% CI: 0.87 - 4.71, I2:75%). There was no difference in the rates of stroke (OR: 0.44, 95% CI: 0.12 -1.58, I2: 0%), MI (OR: 1.64, 95% CI: 0.76 - 3.53, I2: 0%), and VTE (OR: 1.26,95% CI: 0.31 - 5.01, I2: 0%). The quality of included studies was low to moderate. Conclusion: Patients undergoing elective procedures and chronically taking DOACs have a similar risk of major bleeding and stroke when DOACs are continued or interrupted peri procedurally. Similarly, among patients on VKA who were bridged or not bridged, there was no difference in risk of bleeding, stroke, MI or VTE.

Abstract 15183: Diabetes is Associated With Worse Postoperative Mortality and Morbidity in Bariatric Surgery, Regardless of the Procedure

Introduction: Bariatric surgery is an efficient treatment for obesity. Objectives: We aimed to assess the impact of diabetes on postoperative outcomes of bariatric surgery. Further, we compared the outcomes of different techniques in patients with diabetes. Methods: We used data from the National Inpatient Sample (2015-2019) to identify patients who underwent either sleeve gastrectomy, Roux-en-Y, or gastric banding. Outcomes included postoperative mortality (primary outcome), major bleeding, atrial fibrillation, and acute renal failure. Results: Patients with diabetes had an overall increased risk of perioperative complications when compared to non-diabetic ones for all three types of bariatric surgery. Among patients who underwent sleeve gastrectomy, diabetes was associated with a higher adjusted risk of mortality [aOR 2.07 (1.36-3.16)], atrial fibrillation [aOR 1.07 (1.02-1.11)], and acute renal failure [aOR 1.51 (1.39-1.64)] but a similar risk of major bleeding. Among patients who underwent Roux-en-Y, diabetes did not increase the risk of mortality and bleeding. Still, it was associated with a higher risk of atrial fibrillation [aOR 2.24 (1.25-4.02)] and acute renal failure [aOR 1.36 (1.21-1.62)]. Among patients who underwent gastric banding, diabetes was only associated with a higher risk of major bleeding [aOR 2.94 (1.42-5.88)]. When comparing the 3 techniques in diabetes patients, Roux-en-Y was significantly associated with a higher mortality rate (1.05%, 0.06%, 0%), atrial fibrillation (7.04%, 3.35%,3.48%), and acute renal failure (6.32%, 1.29%, 3.48%) (Roux-en-Y, sleeve, gastric banding; respectively). Major bleedings were more common in Roux-en-Y (1.05%) than in Sleeve (0.5%) (p<0.001). Conclusions: Diabetes is associated with worse postoperative outcomes regardless of the type of bariatric surgery performed. Among diabetes patients, Roux-En-Y was associated with higher mortality and morbidity.

Safety and Effectiveness of Rivaroxaban Versus Warfarin Across GFR Levels in Atrial Fibrillation: A Population-Based Study in Australia and Canada

The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Multicenter retrospective cohort. Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR≥60, 45-59, 30-44, and<30mL/min/1.73m2. Patients receiving dialysis and kidney transplant recipients were excluded. New dispensation of either rivaroxaban or warfarin. Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR<60mL/min/1.73m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR≥60, 45-59, 30-44, and<30mL/min/1.73m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Unmeasured treatment selection bias and residual confounding. In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate<30mL/min/1.73m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.

Impact of frailty on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a nationwide cohort study.

Data on non-vitamin K antagonist oral anticoagulants (NOACs) use in patients with atrial fibrillation (AF) and frailty are scarce. Therefore, the impact of frailty on AF-related outcomes and benefit-risk profiles of NOACs in patients with frailty were investigated. AF patients initiating anticoagulation between 2013 and 2019 were included using Belgian nationwide data. Frailty was assessed with the Claims-based Frailty Indicator. Among 254478 anticoagulated AF patients, 71638 (28.2%) had frailty. Frailty was associated with higher all-cause mortality risks [adjusted hazard ratio (aHR) 1.48, 95% confidence interval (CI) (1.43-1.54)], but not with thromboembolism or bleeding. Among subjects with frailty (78080 person-years of follow-up), NOACs were associated with lower risks of stroke or systemic embolism (stroke/SE) [aHR 0.77, 95%CI (0.70-0.86)], all-cause mortality [aHR 0.88, 95%CI (0.84-0.92)], and intracranial bleeding [aHR 0.78, 95%CI (0.66-0.91)], a similar major bleeding risk [aHR 1.01, 95%CI (0.93-1.09)], and higher gastrointestinal bleeding risk [aHR 1.19, 95%CI (1.06-1.33)] compared with VKAs. Major bleeding risks were lower with apixaban [aHR 0.84, 95%CI (0.76-0.93)], similar with edoxaban [aHR 0.91, 95%CI (0.73-1.14)], and higher with dabigatran [aHR 1.16, 95%CI (1.03-1.30)] and rivaroxaban [aHR 1.11, 95%CI (1.02-1.21)] compared with VKAs. Apixaban was associated with lower major bleeding risks compared with dabigatran [aHR 0.72, 95%CI (0.65-0.80)], rivaroxaban [aHR 0.78, 95%CI (0.72-0.84)] and edoxaban [aHR 0.74, 95%CI (0.65-0.84)], but mortality risk was higher compared with dabigatran and edoxaban. Frailty was an independent risk factor of death. Non-vitamin K antagonist oral anticoagulants had better benefit-risk profiles than VKAs in patients with frailty, especially apixaban, followed by edoxaban.

Clinical course and treatment of incidentally detected splanchnic vein thrombosis: an individual patient data meta-analysis

BackgroundThe clinical relevance and management of incidental splanchnic vein thrombosis (SVT) remain poorly defined. ObjectivesThe objectives of this study were to evaluate the clinical course of incidental SVT in comparison with symptomatic SVT and assess the safety and effectiveness of anticoagulant treatment in incidental SVT. MethodsIndividual patient data meta-analysis of randomized controlled trials or prospective studies published up to June 2021. Efficacy outcomes were recurrent venous thromboembolism (VTE) and all-cause mortality. The safety outcome was major bleeding. Incidence rate ratios and 95% CIs for incidental vs symptomatic SVT were estimated before and after propensity-score matching. Multivariable Cox models were used considering anticoagulant treatment as a time-varying covariate. ResultsIn total, 493 patients with incidental SVT and 493 propensity-matched patients with symptomatic SVT were analyzed. Patients with incidental SVT were less likely to receive anticoagulant treatment (72.4% vs 83.6%). Incidence rate ratios (95% CI) for major bleeding, recurrent VTE, and all-cause mortality in patients with incidental SVT compared with symptomatic SVT were 1.3 (0.8, 2.2), 2.0 (1.2, 3.3), and 0.5 (0.4, 0.7), respectively. In patients with incidental SVT, anticoagulant therapy was associated with a lower risk of major bleeding (hazard ratio [HR] 0.41; 95% CI, 0.21 to 0.71), recurrent VTE (HR 0.33; 95% CI, 0.18 to 0.61), and all-cause mortality (HR 0.23; 95% CI, 0.15 to 0.35). ConclusionPatients with incidental SVT appeared to have a similar risk of major bleeding, a higher risk of recurrent thrombosis, but lower all-cause mortality than patients with symptomatic SVT. Anticoagulant therapy seemed safe and effective in patients with incidental SVT.

Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity.

In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January1, 2012 to December31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

CYP2C19 genotype and platelet aggregation test-guided dual antiplatelet therapy after off-pump coronary artery bypass grafting: A retrospective cohort study.

Dual antiplatelet therapy (DAPT) is recommended in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB). Clopidogrel is less effective among patients with loss-of-function (LoF) of CYP2C19 alleles, while ticagrelor has direct effects on P2Y12 receptor. Whether a CYP2C19 genotype plus platelet aggregation test (PAgT)-guided DAPT after CABG could improve clinical outcomes remain uncertain. From August 2019 to December 2020, 1,134 consecutive patients who underwent OPCAB received DAPT for 1 year after surgery in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. According to the actual treatment they received in real-world, 382 (33.7%) of them received a traditional DAPT: aspirin 100 mg qd + clopidogrel 75 mg qd, no matter the CYP2C19 genotype and response in platelet aggregation test (PAgT). The other 752 (66.3%) patients received an individual DAPT based on CYP2C19 genotype and PAgT: aspirin 100 mg qd + clopidogrel 75 mg qd if CYP2C19 was extensive metabolizer, or moderate metabolizer but normal response in PAgT; aspirin 100 mg qd + ticagrelor 90 mg bid if CYP2C19 was poor metabolizer, or moderate metabolizer but no or low response in PAgT. One-year follow-up was achieved for all patients. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. The safety outcome was thrombolysis in myocardial infarction (TIMI) criteria major bleeding. Compared with the traditional DAPT group, the risk of MACE in the individual DAPT group was significantly lower (5.5 vs. 9.2%, HR 0.583; 95% CI, 0.371-0.915; P = 0.019), mainly due to the decreased risk of MI (1.7 vs. 4.2%, HR 0.407; 95% CI, 0.196-0.846; P = 0.016). The risk of TIMI major bleeding events was similar between the two groups (5.3 vs. 6.0%, RR 0.883; 95% CI, 0.537-1.453; P = 0.626). For patients who underwent OPCAB, individual DAPT (CYP2C19 genotype plus PAgT-guided strategy) was associated with a lower risk of MACE and a similar risk of major bleeding.

Impact of diabetes on outcomes of cardiogenic shock: A systematic review and meta-analysis.

To provide synthesized evidence on the association of diabetes with clinical outcomes of patients with acute myocardial infarction (AMI) and associated cardiogenic shock (CS). We analyzed observational studies on patients with AMI and CS, identified through a systematic search using PubMed and Scopus databases. The main outcome was mortality and other outcomes of interest were risk of major bleeding, re-infarction, cerebrovascular adverse events, and need for revascularization. We conducted the meta-analysis with data from 15 studies. Compared to patients without diabetes, those with diabetes had an increased risk of in-hospital mortality (OR, 1.34; 95% CI, 1.17–1.54) and cerebrovascular complications (OR, 1.28; 95% CI, 1.11–1.48). We found similar risk of major bleeding (OR, 0.68; 95% CI, 0.43–1.09), re-infarction (OR, 0.98; 95% CI, 0.48–1.98) and need for re-vascularization (OR, 0.96; 95% CI, 0.75–1.22) as well as hospital stay lengths (in days) (WMD 0.00; 95% CI, −0.27–0.28; n = 4; I2 = 99.7%) in the two groups of patients. Patients with diabetes, acute MI and associated cardiogenic shock have increased risks of mortality and adverse cerebrovascular events than those without diabetes.

Effectiveness, safety, and healthcare costs associated with rivaroxaban versus warfarin among venous thromboembolism patients with obesity: a real-world study in the United States

Prior observational studies suggest rivaroxaban is safe and effective among patients with morbid obesity who suffered a venous thromboembolism (VTE) event, but existing data are more limited in the broader population of VTE patients with obesity. This study assessed VTE recurrence, major bleeding, healthcare resource utilization, and healthcare costs among VTE patients with obesity who received rivaroxaban versus warfarin. VTE patients with obesity who initiated rivaroxaban or warfarin after a first VTE (index date) were identified from the IQVIA PharMetrics® Plus database (01/02/2011–09/30/2019). The follow-up period spanned from the index date until health plan disenrollment, end of data availability, cancer diagnosis/treatment, end of the 12 month post-index period, or (for the analysis of major bleeding) anticoagulant discontinuation or switch. Patient characteristics were balanced using inverse probability of treatment weighting. The weighted rivaroxaban (N = 8666) and warfarin cohorts (N = 5946) were well balanced (mean age = 51 years, females = 52%). Over a 9.6 months mean observation period, rivaroxaban users had a significantly lower risk of VTE recurrence [7.0% vs. 8.2%, HR(95% CI) = 0.85(0.75;0.97)] and a similar risk of major bleeding [4.1% vs. 3.6%, HR(95% CI) = 1.11(0.89;1.37)] relative to warfarin users at 12 months. Relative to warfarin users, rivaroxaban users had significantly fewer all-cause outpatient visits [RR(95% CI) = 0.71(0.70;0.74)]. The higher pharmacy costs incurred by rivaroxaban recipients (cost difference = $1252) were offset by lower medical costs (cost difference = − $2515, all p < 0.05) compared with warfarin recipients. Our findings suggest that rivaroxaban is safe and effective versus warfarin, and associated with lower medical costs among VTE patients with obesity.

Effectiveness and Safety of Rivaroxaban versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Polypharmacy.

BackgroundCurrent evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications.MethodsThis retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m2 and the presence of polypharmacy (1–4, 5–9, or ≥ 10 concurrent medications). Outcomes of stroke, systemic embolism, and major bleeding were compared between the rivaroxaban and warfarin cohorts after propensity score matching (PSM).ResultsA total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70–0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81–1.06; p = 0.2842), and results were consistent across the three polypharmacy groups.ConclusionsIn this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-021-00520-7.

Effectiveness and safety of rivaroxaban versus warfarin among nonvalvular atrial fibrillation patients with obesity and diabetes.

To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes. Patients aged ≥18years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09). In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants versus warfarin among nonvalvular atrial fibrillation patients with prior bleeding events

Abstract Background Patients with non-valvular atrial fibrillation (NVAF) use oral anticoagulants such as warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) for the prevention of stroke. However, the effectiveness and safety of warfarin and NOACs can be influenced by pre-existing patient comorbidities, such as a history of bleeding, and limited evidence are available to inform the choice of the most appropriate anticoagulant treatment for NVAF patients with bleeding history. Purpose This study used five United States insurance claims databases to evaluate the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among NVAF patients with prior bleeding events who were prescribed NOACs versus warfarin. Methods This retrospective observational study used data from 5 databases (CMS Medicare and four commercial databases, covering &amp;gt;180 million beneficiaries) to select adult NVAF patients who were treated with apixaban, dabigatran, rivaroxaban, or warfarin (01JAN2013–30JUN2019). Patients were required to have a prior bleeding event, defined as a hospitalization with a diagnosis for intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding or bleeding at other key sites prior to or during the index treatment episode. In each database, three 1:1 NOAC-warfarin propensity-score-matched (PSM) cohorts were created before pooling the results. Outcome measures were time to first stroke/SE, (ischemic stroke, hemorrhagic stroke, and SE), and time to first MB (gastrointestinal bleeding, intracranial hemorrhage, and MB at other key sites), and were measured from the index treatment episode to treatment discontinuation or switch, death, health plan disenrollment, or end of study period. Hazard ratios of S/SE and MB were calculated using Cox proportional hazards models. Results Among the eligible NVAF population, 8.2% of patients had a prior bleeding event (ICH: 12.3%; GI: 60.7%; Other: 27.0%). After PSM, a total of 43,092 apixaban-warfarin, 11,295 dabigatran-warfarin, and 32,723 rivaroxaban-warfarin patient pairs with prior bleeding were selected with a mean follow-up of 8–9 months. Apixaban and rivaroxaban were associated with a lower risk of S/SE, and dabigatran was associated with a similar risk of S/SE when compared to warfarin. Apixaban and dabigatran were associated with a lower risk of MB, and rivaroxaban was associated with a similar risk of MB, compared to warfarin (Figure). Conclusion Among NVAF patients with prior bleeding events, NOACs were associated with varying risks of S/SE and MB compared to warfarin. These results can help inform healthcare providers concerning the impact of OAC treatment in NVAF patients with history of bleeding. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer, Inc.

VTE Recurrence and Safety of Anticoagulants Among Patients with Cancer Treated for Venous Thromboembolism

Introduction:Anticoagulation (AC) is effective for the treatment of venous thromboembolism (VTE) in cancer patients, but is associated with an increased risk of bleeding. Currently, LMWH monotherapy is the recommended treatment for cancer patients with VTE; however, emerging data from Medicare patients suggests that rivaroxaban had a significantly lower risk of VTE recurrence and similar risk of major bleeding compared to LMWH or warfarin. In this study, we compared the effectiveness and risk of major bleeding associated with these anticoagulants in a younger cohort of patients from a commercial claims database.Methods: Truven Health Analytics MarketScan databases were used to find patients aged ≥18 newly diagnosed with cancer who then had their first VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE); excluding upper VTE) between 1/1/2013 - 9/30/2016 and AC start ≤ 7 days. Patients were categorized into LMWH, warfarin, or rivaroxaban cohorts based on index AC. The warfarin cohort included patients who started LMWH and warfarin ≤ 7 days of their first VTE. Inverse probability of treatment weights based on propensity score were used to adjust for treatment differences in the comparison of LMWH vs. rivaroxaban, warfarin vs. rivaroxaban, and LMWH vs. warfarin. Patients were observed until the earliest of end of eligibility or data end. VTE recurrences were defined conservatively as hospitalizations with a primary diagnosis of VTE ≥7 days after the first VTE. Major bleeding events were identified using validated criteria (Cunningham et al., 2011) and evaluated while patients were on treatment. Kaplan-Meier rates at 6 and 12 months were used to compare VTE recurrence between cohorts. Time on treatment was approximately 30-50% of total eligibility time, so rates at 3 and 6 months were used to compare major bleeding between cohorts. Cox proportional hazard models were used to compare VTE recurrence and major bleeding risk between cohorts.Results: A total of 12,457 patients (LMWH: N=4,313; warfarin; N=4,774; rivaroxaban: N=3,370) were included. After weighting the cohorts, baseline demographic and clinical characteristics were well balanced. Mean patient age ranged from 61.3 to 63.6 years. Median observation time with LMWH was shorter than with rivaroxaban (6.8 vs. 8.3 months, p<0.001) and with warfarin (7.4 vs. 9.8 months, p<0.001). Time on treatment was significantly shorter as well (Figures 1A-1C). VTE recurrence rates were significantly lower with rivaroxaban than with LMWH users at 6 months (8.7% vs. 11.7%; p=0.003) and 12 months (11.9% vs.14.7%; p=0.006), respectively, with a hazard ratio (HR [95%CI]) of 0.83 (0.73-0.96; p=0.010; Figure 1A). Major bleeding rates for rivaroxaban and LMWH users were similar at 3 months (3.2% vs. 3.5%; p=0.592) and 6 months (4.4% vs. 4.9%; p=0.438), respectively [HR 0.91 (0.71-1.17; p=0.455]. VTE recurrence rates for rivaroxaban and warfarin users were similar at 6 months (8.2% vs 8.8%; p=0.530) and 12 months (11.3% vs 11.6%; p=0.675), respectively [HR 0.95 (0.83-1.09; p=0.456; Figure 1B)]. Major bleeding rates for rivaroxaban and warfarin users were also similar at 3 months (3.2% vs. 2.8%; p=0.199) and 6 months (4.2% vs. 3.8%; p=0.362), respectively [HR 1.08 (0.86-1.37; p=0.500)]. Recurrence rates were significantly lower for warfarin users than for LMWH users at 6 months (10.2% vs. 12.4%; p=0.006) and 12 months (13.3% vs. 15.3%; p=0.011), respectively, but the rate of recurrence over the entire follow up was not significantly different between the two cohorts [HR of 0.91 (0.81-1.02; p=0.103; Figure 1C)]. Major bleeding rates for warfarin and LMWH users were similar at 3 months (3.1% vs. 3.7%; p=0.114) and 6 months (4.3% vs. 5.1%; p=0.109), respectively [HR of 0.86 (0.68-1.08; p=0.187)].Conclusion: In this large cohort of cancer patients treated for VTE, time on treatment was shorter for patients treated with LMWH than oral agents. Rivaroxaban was associated with a significantly lower rate of VTE recurrence than LMWH and a similar rate of VTE recurrence to warfarin; major bleed rates were similar for all. While LMWH has been associated with greater reductions in recurrent VTE compared to warfarin in trials, poor persistence on LMWH in real world settings may explain its lack of comparative effectiveness in this analysis. [Display omitted] DisclosuresKhorana:Bayer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding; Leo: Consultancy, Honoraria, Research Funding; Halozyme: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Milentijevic:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. McCormick:Janssen Scientific Affairs, LLC: Research Funding. Laliberté:Janssen Scientific Affairs, LLC: Research Funding. Crivera:Janssen Scientific Affairs, LLC: Employment, Equity Ownership. Lefebvre:Janssen Scientific Affairs, LLC: Research Funding. Lejeune:Janssen Scientific Affairs, LLC: Research Funding. Rozjabek:Janssen Scientific Affairs, LLC: Other: Fellowship supported by Janssen Scientific Affairs, LLC. Schein:Janssen Scientific Affairs, LLC: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Streiff:Roche: Research Funding; CSL Behring: Consultancy, Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Research Funding; Portola: Research Funding.

Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and DOACs in the management of malignancy induced VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November 28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p &amp;lt; 0.05. Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p &amp;gt; 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

A network meta-analysis of direct factor Xa inhibitors for the treatment of cancer-associated venous thromboembolism.

Treatment of cancer-associated venous thromboembolism (CAVTE) remains challenging. The aim of this study was to assess the outcomes of direct acting oral anticoagulants (DOAs) for the treatment of CAVTE. A network meta-analysis of randomized clinical trials comparing DOAs (Apixaban, Rivaroxaban, and Edoxaban) versus Dalteparin for the treatment of CAVTE was performed. Outcomes of interest included, VTE recurrence, all-cause mortality, event-free survival, major bleeding, and clinically relevant non-major bleeding (CRNMB). Analysis was based on a random effects model and Bayesian Markov-chain Monte Carlo method was used for indirect comparisons. Four RCTs involving 2894 patients were included. Overall certainty of evidence was moderate regarding all outcomes. DOAs exhibited lower risk of VTE (RR 0.62; 95% CI 0.44, 0.87; P = 0.007), similar risk of major bleeding (RR 1.33; 95% CI 0.84, 2.11; P = 0.23), and higher risk of CRNMB (RR 1.66, 95% CI 1.08, 2.56; P = 0.02), compared with Dalteparin. Risk of all-cause mortality and event-free survival were similar between groups with RR 0.99 (95% CI 0.84, 1.16) and RR 1.03 (95% CI 0.94, 1.13), respectively. Apixaban ranked first for recurrent VTE (42.4%) and major bleeding (62.3%) and Dalteparin ranked first for CRNMB (54.7%). Rivaroxaban ranked best considering all-cause mortality (58.7%); Apixaban ranked best for event-free survival (83.6%). DOAs presented a reduced risk of recurrent VTE with similar risk of major bleeding compared to Dalteparin. However, a higher risk of CRNMB is expected when this cohort of patients are treated with DOAs instead of Dalteparin.