Risk of Venous Thromboembolism by Cancer Type: A Network Meta-Analysis.

Patients with cancer have an increased risk of venous thromboembolism (VTE). Comparing tumor-specific VTE risk is complicated by factors such as surgery, disease stage, and chemotherapy. Network meta-analysis (NMA) using cancer types as network nodes enabled us to estimate VTE rates by leveraging comparisons across cancer types while adjusting for baseline VTE risk in individual studies. This study was conducted to estimate the risk of VTE by cancer type and factors influencing VTE risk. The Embase, MEDLINE, and Cochrane Library repositories were systematically searched to identify clinical trials and observational studies published from 2005 to 2022 that assessed the risk of primary cancer-related VTE among two or more distinct cancer types. Studies with similar cancer populations and study methods reporting VTE occurring within 1 year of diagnosis were included in the NMA. Relative VTE rates across cancer types were estimated with random-effects Bayesian NMAs. Absolute VTE rates were calculated from these estimates using the average VTE incidence in lung cancer (the most frequently reported type) as the "anchor." From 2,603 records reviewed, 30 studies were included in this NMA. The general network described 3,948,752 patients and 18 cancer types: 3.1% experienced VTE within 1 year of diagnosis, with cancer-specific rates ranging from 0.7 to 7.4%. Consistent with existing VTE risk prediction tools, pancreatic cancer was associated with higher-than-average VTE risk. Other cancer types with high VTE risk were brain and ovarian cancers. The relative rankings of VTE risk for certain cancers changed based on disease stage and/or receipt of chemotherapy or surgery.

Effectiveness and Safety of Extended Treatment Apixaban Versus Low-Molecular-Weight Heparin in Cancer-Associated Venous Thromboembolism.

BACKGROUND: Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months. METHODS: A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB). RESULTS: A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH. CONCLUSIONS: Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.

Effectiveness and safety of anticoagulants among patients with venous thromboembolism and common cancers or cancers with high venous thromboembolism risk.

Aim: Treatment effects among anticoagulant-treated patients with venous thromboembolism (VTE) and cancer across tumor types were evaluated. Methods: Patients initiating an anticoagulant within 30 days after VTE were identified. After inverse probability treatment weighting, patients were stratified by tumor type. Interactions between treatment and tumor type on recurrent VTE, major bleeding and clinically relevant non-major bleeding were assessed using Cox proportional hazard models. Results: Treatment effects were generally not significantly different among patients with or without the following cancer types: prostate, breast, lung, pancreatic or multiple myeloma. Few significant interactions were observed for lung and pancreatic cancer. Conclusion: Anticoagulant treatment effects were generally consistent across tumor types. The significant interactions may indicate tumor-specific effects of anticoagulants, but further research is needed.

Comparative clinical outcomes between direct oral anticoagulants and warfarin among elderly patients with non-valvular atrial fibrillation in the CMS medicare population.

Atrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) VS warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban-warfarin, 18,131 dabigatran-warfarin, and 55,359 rivaroxaban-warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59-0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73-0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72-1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57-0.67; NCO: HR: 0.64; 95% CI 0.60-0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71-0.89; NCO: HR: 0.84; 95% CI 0.76-0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02-1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99-1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.

Clinical and economic burden of COPD in a medicaid population.

OBJECTIVE: To evaluate the clinical and economic burden of COPD patients to Medicaid. STUDY DESIGN: Retrospective, observational matched cohort design. METHODS: We calculated the incremental costs incurred and medical resources used by COPD patients relative to those without COPD. Data were obtained from 8 Medicaid states during 2003-2007. COPD patients were defined as Medicaid beneficiaries ≥40 years with a COPD diagnosis (ICD-9 CM: 491.xx, 492.xx, 496.xx) and treated with maintenance drugs for COPD. Patients were matched (1:3) to Medicaid beneficiaries without a COPD diagnosis on age, gender, race, index year, Medicare/Medicaid dual eligibility, and use of long-term care. Results were stratified by Medicare/Medicaid dual eligibility status and race. RESULTS: A total of 10,221 COPD and 30,663 non-COPD patients were included. Cohorts were on average 65 years of age, 80% White, and 64.8% having Medicare/Medicaid dual eligibility. Inpatient hospitalizations and home healthcare visits/durable medical equipment were primary drivers of incremental medical costs. COPD patients were more than twice as likely to have a hospitalization (odds ratio [95% confidence interval] = 2.32 [2.19, 2.45]) or home healthcare visit/durable medical equipment (2.95 [2.82, 3.08]) compared to non-COPD patients. Medicaid incurred $2118/year in incremental costs due to COPD. On average, incremental costs were 7 times greater for non-dual-eligible patients ($4917) compared to dual-eligible patients ($667), and were more than double for Blacks compared to Whites ($4141 vs $1593). CONCLUSION: COPD imposes a substantial economic and clinical burden on the Medicaid program; this burden differs by dual eligibility status and race.

Delayed treatment initiation of oral anticoagulants among Medicare patients with atrial fibrillation.

Study objective: This study aimed to identify factors associated with delayed oral anticoagulant (OAC) treatment initiation among atrial fibrillation (AF) patients in United States (US) clinical practice. Participants: Medicare beneficiaries newly diagnosed with AF without moderate-to-severe mitral stenosis or a mechanical heart valve, were aged ≥65 years and prescribed OAC on or after 10/1/2015 through 2019 were included. Delayed and early OAC initiation were defined as >3 months and 0-3 months initiation from first AF diagnosis, respectively. Main outcome measures: Association between delayed OAC initiation and patient demographics, clinical and index OAC coverage and formulary characteristics was examined using multivariable logistic regression. Results: A total of 446,441 patients met the inclusion criteria; 30.0 % (N = 131,969) were identified as delayed and 70.0 % (N = 314,472) as early OAC initiation. Median age for both cohorts was 78 years. In the early and delayed OAC cohorts, 47.1 % and 47.6 % were male and 88.8 % and 86.6 %, were White, respectively. Factors associated with delayed OAC initiation (odds ratio; 95 % confidence interval) included Black race (1.29; 1.25 to 1.33), west region (1.29; 1.26 to 1.32), comorbidities such as dementia (1.27; 1.23 to 1.30), recent bleeding hospitalization (1.22; 1.18 to 1.27), prior authorization (1.69; 1.66 to 1.71), tier 4 formulary for index OAC at AF diagnosis (1.26; 1.22 to 1.30). Conclusion: Our study revealed that nearly one-third of Medicare patients with AF experienced delayed OAC initiation. Key patient characteristics found to be associated with delayed OAC initiation included race and ethnicity, comorbidities, and formulary restrictions.

Effectiveness and safety of anticoagulants among patients with venous thromboembolism and active cancer who also had prior bleed or prior renal disease.

OBJECTIVE: Patients with active cancer and venous thromboembolism (VTE) have elevated risk of recurrent VTE (rVTE) and major bleeding (MB). The risk is even higher within those with a prior bleeding event or renal disease. There is a need to understand the risk of rVTE and MB of commonly used anticoagulants among these high-risk patients. METHODS: VTE patients with active cancer and treated with apixaban, warfarin, or low molecular weight heparin (LMWH) within 30 days of VTE were identified from five claims databases in the United States. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. The post-IPTW population was stratified by prior bleed or renal disease status. Cox proportional hazards models were used to evaluate interactions between treatment and prior bleed or renal disease on risk of rVTE and MB, with p value <.1 considered significant. RESULTS: Study criteria were met by 30,586 VTE cancer patients: 35.0% had prior bleed and 29.0% had renal disease. For apixaban, LMWH, and warfarin cohorts, the incidence (events per 100 person-years) of MB was higher in patients with prior bleed (17.48 vs 7.58, 25.61 vs 13.11, and 20.38 vs 8.97) or renal disease (15.79 vs 8.71, 22.11 vs 15.90, and 18.49 vs 10.39) vs those without the conditions. Generally, there were no significant interactions between anticoagulant use and prior bleed or renal disease on rVTE and MB (p for interaction >.1). CONCLUSION: The incidence of MB was higher among those with prior bleed or renal disease. Effects of apixaban, warfarin, or LMWH were generally consistent regardless of prior bleed or renal disease status.

Payer formulary tier increases of apixaban: how patients respond and potential implications.

OBJECTIVE: To assess potential impacts of formulary tier increases of apixaban-an efficacious oral anticoagulant (OAC) for preventing stroke in patients with atrial fibrillation (AF)-on patients' prescription drug plan (PDP) switching and OAC treatment patterns. METHODS: Nationwide claims data for Medicare beneficiaries with Parts A, B, and D (100% sample) were used to assess apixaban-treated AF patients who faced a formulary tier increase for apixaban in 2017 by their Part D PDP. Patients' out-of-pocket (OOP) costs for apixaban were described, along with PDP switching and OAC treatment patterns. RESULTS: Among 1845 included patients, 97.7% had apixaban on tier 3 of their plan's formulary in 2016 and faced its increase to tier 4 for 2017. Approximately 4% (N = 81) of patients pre-emptively switched to a different PDP for 2017 with almost all switching to plans with apixaban on a lower formulary tier and 85.2% continuing apixaban treatment. Among the 96% (N = 1764) of patients who remained on the same PDP for 2017, over half (57.5%) continued apixaban treatment, despite increased OOP costs ($54 vs. $135 for a 30-day supply in 2016 vs. 2017). Only 12.4% of those who remained on the same plan for 2017 switched to another OAC, while as much as 30.1% discontinued OACs. These discontinuers exhibited higher comorbidity burdens than patients continuing on any OAC. CONCLUSION: The majority of patients continued on apixaban despite higher OOP cost, suggesting patients' reluctance to change treatment for non-medical reasons; however, 30% of patients discontinued OAC treatment after higher apixaban tier placement.

Effectiveness and Safety of Apixaban vs Warfarin in Patients with Venous Thromboembolism with Risk Factors for Bleeding or for Recurrences.

INTRODUCTION: Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences. METHODS: Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders). RESULTS: A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR [95% confidence interval (CI) 0.72 [0.67-0.78]), major bleeding (MB) (HR [95% CI] 0.70 [0.64-0.76]), and clinically relevant non-major (CRNM) bleeding (HR [95% CI] 0.83 [0.80-0.86]). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNM bleeding. CONCLUSION: Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences.

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

INTRODUCTION: 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). METHODS: Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 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. RESULTS: 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. CONCLUSION: 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.

Trends and factors associated with outpatient anticoagulant treatment initiation among VTE patients with active cancer.

BACKGROUND: Patients with venous thromboembolism (VTE) and cancer are at higher risk of recurrent VTE and mortality. Clinical guidelines recommend anticoagulant treatment for these patients. This study assessed trends in outpatient anticoagulant treatment and factors associated with this treatment initiation in outpatient setting among this high-risk patient population. OBJECTIVE: To study trends and factors associated with anticoagulant treatment initiation among patients with VTE and cancer. METHODS: VTE cancer patients age ≥65 were identified from the SEER-Medicare database from 01JAN2014-31DEC2019. Patients were enrolled for ≥6 months prior to their first VTE (i.e. index event) and without evidence of other reasons for anticoagulation (i.e., atrial fibrillation). Patients were also required to be enrolled for ≥30 days after index. Cancer status was identified from SEER or Medicare database in the 6 months pre- through 30 days post-VTE. Patients were classified into treated or untreated cohorts depending on whether they initiated outpatient anticoagulant treatment within 30 days post-index. The trends of treated vs. untreated were evaluated by quarter. Logistic regression was used to identify demographic-, VTE-, cancer- and comorbid-related factors associated with anticoagulant treatment initiation. RESULTS: A total of 28,468 VTE-cancer patients met all study criteria. Of these, ~46 % initiated outpatient anticoagulant treatment within 30 days, and ~54 % did not. The above rates were stable from 2014 to 2019. Factors such as VTE diagnosis in inpatient setting, pulmonary embolism (PE) diagnosis, and pancreatic cancer were associated with increased odds whereas bleeding history and some comorbid factors were associated with decreased odds of initiating anticoagulant treatment. CONCLUSION: Over half of VTE patients with cancer did not initiate outpatient anticoagulant treatment within the first 30-days after VTE diagnosis. This trend was stable from 2014 to 2019. A range of cancer-, VTE-, and comorbid-related factors were associated with the likelihood of the treatment initiation.

Cost-effectiveness of atrial fibrillation screening in Canadian community practice.

Background: Contemporary guidelines recommend opportunistic screening for atrial fibrillation (AF). Objective: The objective of this study was to assess the cost-effectiveness of single time point opportunistic AF screening for patients 65 years and older by using the single-lead electrocardiogram. Methods: An established Markov cohort model was adapted by updating the background mortality estimates, epidemiology, screening efficacy, treatment patterns, resource use, and cost inputs to reflect a Canadian health care setting. Inputs were derived from a contemporary prospective screening study performed in Canadian primary care settings (screening efficacy and epidemiology) and the published literature (unit costs, epidemiology, mortality, utility, and treatment efficacy). The impact of screening and oral anticoagulant treatment on the cost and clinical outcomes was analyzed. A Canadian payer perspective over lifetime was used for analysis, with costs expressed in 2019 Canadian dollars. Results: Among the estimated screening-eligible population of 2,929,301 patients, the screening cohort identified an additional 127,670 AF cases compared with the usual care cohort. The model estimated avoidance of 12,236 strokes and incremental quality-adjusted life-years of 59,577 (0.02 per patient) over lifetime in the screening cohort. Cost savings were substantial because of improved health outcomes, reflecting screening being the dominant strategy (affordable and effective). Model results were robust across sensitivity and scenario analyses. Conclusion: Single time point opportunistic screening of AF using a single-lead electrocardiogram device in Canadian patients 65 years and older without known AF may provide improved health outcomes with cost savings from the perspective of a single payer health care environment.

Effectiveness and safety of anticoagulants among venous thromboembolism cancer patients with and without brain cancer.

INTRODUCTION: Patients with brain cancer are at a high risk of developing venous thromboembolism (VTE) and are underrepresented in clinical trials. This study compared the risk of recurrent VTE (rVTE), major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among VTE cancer patients initiating apixaban, low molecular weight heparin (LMWH), or warfarin stratified by patients with brain vs other cancer types. MATERIALS AND METHODS: Active cancer patients initiating apixaban, LMWH, or warfarin within 30 days after VTE diagnosis were identified from 4 US commercial and the Medicare databases. Inverse probability of treatment weights (IPTW) was used to balance patient characteristics. Cox proportional hazards models were used to evaluate the interaction between brain cancer status and treatment on outcomes (rVTE, MB, and CRNMB), with a p-value <0.1 indicating a significant interaction. RESULTS: Of 30,586 patients with active cancer (5 % had brain cancer), apixaban (vs. LMWH and warfarin) was associated with lower risk of rVTE, MB, and CRNMB. Generally, no significant interactions (P > 0.1) were found between brain cancer status and anticoagulant treatment across outcomes. The exception was MB for apixaban [vs LMWH (p-value for interaction = 0.091)] with a higher reduction among those with brain cancer (HR = 0.32) than those with (HR = 0.72) other cancer. CONCLUSIONS: Among VTE patients with all types of cancer, apixaban (vs LMWH and warfarin) was associated with a lower risk of rVTE, MB, and CRNMB. In general, anticoagulant treatment effects were not significantly different between VTE patients with brain cancer and those with other cancer.

Short-acting ß-agonist use and its ability to predict future asthma-related outcomes.

BACKGROUND: Short-acting ß-agonist (SABA) use is well established in predicting asthma events in adults. However, this predictive ability has yet to be established in a pediatric population together with an assessment of amount of use. OBJECTIVE: To identify the number of SABA canisters that best predicts future asthma-related exacerbations and the optimal length of time for measurement of SABA use in pediatric and adult asthma patients. METHODS: Asthma patients were identified from a Medicaid and a commercially insured database (January 1, 2004, through December 31, 2005, and January 1, 2004, through June 30, 2006, respectively). Following the date of first asthma medication, an assessment period (3, 6, or 12 months) was used to measure SABA use. Asthma-related exacerbations were identified in the subsequent 12-month period. Receiver operating characteristic curve analyses and logistic regression were used to select the critical values of SABA use and optimal assessment periods and to conduct incremental analysis, respectively. RESULTS: A total of 33,793 Medicaid and 101,437 commercial patients met the study criteria. Use of 3 or more SABA canisters during 12 months was identified in both pediatric Medicaid and commercial populations to best predict an increased risk of an asthma-related exacerbation. For adults, use of 2 or more SABA canisters was found as the critical value with shorter optimal assessment periods of 3 and 6 months. Each additional SABA canister resulted in an 8% to 14% and 14% to 18% increase in risk of an asthma-related exacerbation in children and adults, respectively. CONCLUSION: The study identified critical values of SABA use that predict future asthma events. Each additional SABA canister predicted increases in exacerbation risk in children and adults.

Effectiveness and safety of apixaban vs warfarin among venous thromboembolism patients at high-risk of bleeding.

This study evaluated effectiveness and safety of apixaban versus warfarin among venous thromboembolism patients at high-risk of bleeding (defined as having at least one of the following bleeding risk factors: ≥75 years; used antiplatelet, NSAIDs, or corticosteroids; had prior gastrointestinal bleeding or gastrointestinal-related conditions; late stage chronic kidney disease). Adult venous thromboembolism patients initiating apixaban or warfarin with ≥1 bleeding risk factor were identified from Medicare and four commercial claims databases in the United States. To balance characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting was conducted. Cox proportional hazards models were used to estimate the risk of recurrent venous thromboembolism, major bleeding, and clinically relevant non-major bleeding. In total, 88,281 patients were identified. After inverse probability treatment weighting, the baseline patient characteristics were well-balanced between the two cohorts. Among venous thromboembolism patients at high-risk of bleeding, apixaban was associated with significantly lower risk of recurrent venous thromboembolism, major bleeding and clinically relevant non-major bleeding. No significant interactions were observed between treatment and number of risk factors on major bleeding and clinically relevant non-major bleeding or between treatment and type of bleeding risk factors on any of the outcomes. In conclusion, apixaban was associated with significantly lower risk of recurrent venous thromboembolism and bleeding among venous thromboembolism patients at high-risk of bleeding. Effects were generally consistent across subgroups of patients with different number or type of bleeding risk factors.

Impact of apixaban treatment discontinuation on the risk of hospitalization among patients with nonvalvular atrial fibrillation and COVID-19.

INTRODUCTION: This study evaluated the risk of hospitalization among nonvalvular atrial fibrillation (NVAF) patients with an outpatient COVID-19 diagnosis who discontinued vs continued apixaban treatment. METHODS: Adult patients with NVAF with an apixaban prescription prior to an outpatient COVID-19 diagnosis were identified from Optum Clinformatics claims database (1 April 2020-31 March 2021). Continuers were those who continued apixaban as of the index date (date of initial outpatient COVID-19 diagnosis) and discontinuers were those who had the last day of apixaban supply on or before index. Patients were followed from COVID-19 diagnosis to change of continuation/discontinuation status, switch, death, end of continuous coverage or study end, whichever occurred first. Inverse probability treatment weighting (IPTW) was performed to balance cohorts. Cox proportional hazard models were used to compare the risk of all-cause hospitalization and hospitalization for ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), bleeding and mortality. RESULTS: A total of 7869 apixaban patients with COVID-19 were included: 6676 continuers (84.8%) and 1193 discontinuers (15.2%). Compared with continuers, discontinuers had a higher risk of all-cause hospitalization (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.08-1.40), IS (HR: 2.00; 95% CI: 1.03-3.87), VTE (HR: 2.37; 95% CI: 1.06-5.27) and mortality (HR: 2.28; 95% CI: 1.85-2.80). There were no significant differences in the risk of MI (HR: 1.01; 95% CI: 0.54-1.90) or bleeding-related hospitalization (HR: 1.13; 95% CI: 0.73-1.76). CONCLUSION: NVAF patients with COVID-19 who discontinued apixaban had a higher risk of hospitalization and thrombotic events vs those who continued apixaban, with no significant difference in bleeding-related hospitalization.

Non-persistence to Oral Anticoagulation Treatment in Patients with Non-valvular Atrial Fibrillation in the USA.

BACKGROUND: Studies have shown that patients with non-valvular atrial fibrillation (NVAF) who discontinue oral anticoagulants (OACs) are at higher risk of complications such as stroke. OBJECTIVE: This analysis compared the risk of non-persistence with OACs among patients with NVAF. METHODS: Adult patients with NVAF who initiated apixaban, dabigatran, rivaroxaban, or warfarin were identified using 01JAN2013-30JUN2019 data from Centers for Medicare and Medicaid Services and four US commercial claims databases. Non-persistence was defined as discontinuation (no evidence of index OAC use for ≥ 60 days from the last days' supply) or switch to another OAC. Kaplan-Meier curves were generated to illustrate time to non-persistence along with cumulative incidences of non-persistence. Baseline and time-varying covariates were evaluated, and adjusted Cox proportional hazards models were used to evaluate non-persistence risk. RESULTS: In total, 363,823 patients receiving apixaban, 57,121 receiving dabigatran, 282,831 receiving rivaroxaban, and 317,337 receiving warfarin were included. Of these, 47-72% discontinued/switched OAC therapy within an average 9-month follow-up. Apixaban was associated with a lower risk of non-persistence than were dabigatran (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.61-0.62), rivaroxaban (HR 0.76; 95% CI 0.75-0.76), and warfarin (HR 0.74; 95% CI 0.74-0.75). Dabigatran was associated with a higher risk of non-persistence than were warfarin (HR 1.21; 95% CI 1.19-1.22) and rivaroxaban (HR 1.23; 95% CI 1.22-1.25), and rivaroxaban was associated with a lower risk of non-persistence than was warfarin (HR 0.98; 95% CI 0.97-0.98). Clinical events (stroke/systemic embolism and major bleeding [MB]) during follow-up were predictors of non-persistence (stroke HR 1.57; 95% CI 1.53-1.61; MB HR 2.96; 95% CI 2.92-3.00). CONCLUSION: In over one million patients with NVAF, our results suggest differences in anticoagulation treatment persistence across OAC agents, even after accounting for clinical events after OAC initiation. It is important for clinicians and patients to take these differences into consideration, especially as non-persistence to OAC therapy is associated with thromboembolic complications.

Effectiveness and Safety of Apixaban versus Warfarin in Venous Thromboembolism Patients with Chronic Kidney Disease.

There 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.

Effectiveness and Safety of Apixaban Versus Warfarin in Obese Patients with Nonvalvular Atrial Fibrillation Enrolled in Medicare and Veteran Affairs.

Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity. This retrospective study used body weight data of ≥100 kg or a body mass index of ≥30 kg/m2 to identify elderly (aged ≥65 years) NVAF patients with obesity in dually enrolled Veterans Affairs and fee-for-service Medicare patients. It evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that initiated apixaban versus warfarin. Stabilized inverse probability treatment weighting was used to balance the baseline characteristics between patients prescribed apixaban and warfarin in obese patients. Cox models were used to evaluate the relative risk of stroke/SE and MB. Overall, 35.9% (n = 26,522) of the NVAF population were obese, of which 13,604 apixaban and 12,918 warfarin patients were included. After inverse probability treatment weighting, patient characteristics were balanced. The mean age was 75 years, the mean CHA2DS2-VASc score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) was 3.8, the mean HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score was ∼2.6, and >98% of patients were males. Obese apixaban patients were associated with a similar risk of stroke/SE (hazard ratio: 0.82; 95% confidence interval: 0.66 to 1.03) and a significantly lower risk of MB (hazard ratio: 0.62; 95% confidence interval: 0.54 to 0.70) versus warfarin. No significant interaction was observed between treatment and obesity status (nonobese, obese/nonmorbid, obese/morbid) for stroke/SE (interaction p = 0.602) or MB (interaction p = 0.385). In obese patients with NVAF, apixaban was associated with a similar risk of stroke/SE and a significantly lower risk of MB versus warfarin.