Ruslan Horblyuk

Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in "real-world" clinical practice: a propensity-matched analysis of 76,940 patients

Summary The ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA 2 DS 2 -VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59–0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54–0.65) than warfarin initiators. Different types of stroke/SE and major bleeding – including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding – were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA 2 DS 2 -VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest “real-world” study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard-and low-dose apixaban dose regimens. Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief. Supplementary Material to this article is available online at www.thrombosis-online.com .

Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis

Background Historically, warfarin or aspirin have been the recommended therapeutic options for the extended treatment (>3 months) of VTE. Data from Phase III randomised controlled trials (RCTs) are now available for non-VKA oral anticoagulants (NOACs) in this indication. The current systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of anticoagulants for the extended treatment of VTE. Methods Electronic databases (accessed July 2014 and updated April 2016) were systematically searched to identify RCTs evaluating apixaban, aspirin, dabigatran, edoxaban, rivaroxaban, and warfarin for the extended treatment of VTE. Eligible studies included adults with an objectively confirmed deep vein thrombosis, pulmonary embolism or both. A fixed-effect Bayesian NMA was conducted, and results were presented as relative risks (RRs). Sensitivity analyses examining (i) the dataset employed according to the time frame for outcome assessment (ii) the model used for the NMA were conducted. Results Eleven Phase III RCTs (examining apixaban, aspirin, dabigatran, rivaroxaban, warfarin and placebo) were included. The risk of the composite efficacy outcome (VTE and VTE-related death) was statistically significantly lower with the NOACs and warfarin INR 2.0–3.0 compared with aspirin, with no significant differences between the NOACs. Treatment with apixaban (RR 0.23, 95% CrI 0.10, 0.55) or dabigatran (RR 0.55, 95% Crl 0.43, 0.71) was associated with a statistically significantly reduced risk of ‘major or clinically relevant non-major bleed’ compared with warfarin INR 2.0–3.0. Apixaban also showed a significantly reduced risk compared with dabigatran (RR 0.42, 95% Crl 0.18, 0.97) and rivaroxaban (RR 0.23, 95% Crl 0.09, 0.59). Sensitivity analyses indicate that results were dependent on the dataset, but not on the type of NMA model employed. Conclusions Results from the NMA indicate that NOACs are an effective treatment for prevention of VTE or VTE-related death) in the extended treatment setting. However, bleeding risk differs between potential treatments, with apixaban reporting the most favourable profile compared with other NOACs, warfarin INR 2.0–3.0, and aspirin.

Risk of major bleeding in patients with non-valvular atrial fibrillation treated with oral anticoagulants: a systematic review of real-world observational studies

Abstract Objective: To conduct a systematic review of real-world (RWD) studies comparing the risk of major bleeding (MB) among patients with non-valvular atrial fibrillation (NVAF) on direct oral anticoagulants (DOACs) or warfarin. Methods: MEDLINE, Embase, NHS-EED, and EconLit were searched for RWD studies published between January 2003 and November 2016 comparing MB risk among DOACs and warfarin. Proceedings of clinical conferences from 2012 to 2016 were reviewed. Results: A total of 4218 citations were identified, 26 of which met eligibility criteria. Most studies were retrospective analyses of administrative claims databases and patient registries (n = 23 of 26); about half were based in the United States (n = 15). Apixaban showed a significantly lower risk of MB versus warfarin in all eight included studies. MB risk was either significantly lower (n = 9 of 16) or not significantly different (n = 7 of 16) between dabigatran and warfarin; there was no significant difference between rivaroxaban and warfarin in all seven included studies. The risk was significantly lower with apixaban versus rivaroxaban (n = 7 of 7) but not significantly different from dabigatran (n = 6 of 7). MB risk was significantly lower (n = 3 of 4) or not significantly different (n = 1 of 4) with dabigatran versus rivaroxaban. No evidence was identified for edoxaban. Conclusion: DOACs were associated with similar or lower risks of MB versus warfarin. A lower MB risk was consistently observed for apixaban, but less consistently for dabigatran; MB risk was similar between rivaroxaban and warfarin. Among DOACs, the risk of MB with apixaban was consistently lower than with rivaroxaban, but similar to dabigatran.

Outcomes associated with warfarin time in therapeutic range among US veterans with nonvalvular atrial fibrillation.

Abstract Background: Poor quality of warfarin control (time in therapeutic range [TTR] < 65%) can lead to increased risk of adverse events. The objective of this study was to examine the overall quality of international normalized ratio (INR) control and the association of TTR with clinical outcomes including stroke, major bleeding, and all-cause mortality among US warfarin users. Methods and results: This retrospective observational cohort study utilized the US Veterans Affairs electronic medical records database (VA EMR). Patients with NVAF who newly initiated warfarin from 1 January 2005 to 31 December 2015 were grouped into two cohorts based on TTR <65% or ≥65%. TTR was computed from INR test results. Clinical outcomes assessed were stroke/systemic embolism (SE), hemorrhagic stroke, ischemic stroke, and major bleeding, defined based on hospitalization with those conditions as primary diagnosis, as well as all-cause mortality. Patients were followed from warfarin initiation to the first occurrence of an outcome or censoring. Propensity score weighted time-varying Cox regression was used to evaluate the risk of the clinical events. A total of 127,385 NVAF patients with mean TTR of 51% were included. TTR <65% was observed in 65% of patients. Mean CHA2DS2-VASC score (SD) was 2.9 (1.5) in the low TTR cohort and 2.7 (1.4) in the high TTR cohort. Patients with TTR <65% had a higher risk for any stroke/SE (HR: 1.57; 95% CI: 1.41–1.75), major bleeding (HR: 2.78; 95% CI: 2.55–3.03) and all-cause mortality (HR: 1.73; 95% CI: 1.67–1.79). Conclusions: The observed quality of warfarin control in VA EMR suggests room for improvement given the association with elevated risk of adverse clinical outcomes.

Clinical and economic outcomes by first-line treatment among women with HR+/HER2– metastatic breast cancer in a large US health plan database

Abstract Background: Guidelines recommend that women with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (mBC) initiate hormonal therapy before chemotherapy. This study compared outcomes of women with mBC who received chemotherapy first vs hormonal therapy. Methods: A retrospective cohort study of women with mBC was conducted using a large US commercial health plan database between January 1, 2008–April 30, 2013. Subjects had evidence of a HR+/HER2– tumor sub-type in a cancer registry and use of chemotherapy or hormonal therapy in claims. Subjects were continuously enrolled for ≥6 months after metastasis and assigned to cohorts for receiving chemotherapy only or hormonal therapy only during first-line (CT-1L vs HT-1L). Adjusted incidence rates of clinically significant events were compared using a negative binomial model, and adjusted healthcare costs were compared using a generalized linear model. Results: Three hundred and twenty-four women with HR+/HER2– mBC met the selection criteria; 179 (55%) received CT-1L and 145 (45%) received HT-1L. Mortality rates did not differ between cohorts (unadjusted incidence rate ratio (IRR) = 1.67, 95% CI = 0.82–3.46; adjusted IRR = 0.64, 95% CI = 0.32–1.27). Adjusted average total all-cause healthcare costs were

Association Between Breast Cancer Disease Progression and Workplace Productivity in the United States

11 090 for women with CT-1L and

Correction: Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis.

6743 for women with HT-1L (cost ratio =1.64, 95% CI =1.36–1.99). Conclusions: Observed use of first-line chemotherapy (>50%) was higher than expected given the HR + molecular profile of the tumors. Chemotherapy use during first-line did not appear to be associated with a survival benefit, but was associated with significantly higher costs compared with the use of hormonal therapy during first-line; however, this comparison is limited by demographic and baseline characteristic differences between the two cohorts. This study contributes to understanding real-world treatment patterns and the associated clinical and economic outcomes of using chemotherapy vs hormonal therapy as a first-line treatment option for the HR+/HER2– mBC population.

REAL-WORLD COMPARISON OF INPATIENT BLEEDING RISK, BLEEDING-RELATED HOSPITALIZATION RATES AND COSTS AMONG NON-VALVULAR ATRIAL FIBRILLATION PATIENTS ON APIXABAN, DABIGATRAN, RIVAROXABAN: COHORTS COMPRISING NEW INITIATORS AND/OR SWITCHERS FROM WARFARIN

Objective: Determine workplace productivity losses attributable to breast cancer progression. Methods: Longitudinal analysis linking 2005 to 2012 medical and pharmacy claims and workplace absence data in the US patients were commercially insured women aged 18 to 64 diagnosed with breast cancer. Productivity was measured as employment status and total quarterly workplace hours missed, and valued using average US wages. Results: Six thousand four hundred and nine women were included. Breast cancer progression was associated with a lower probability of employment (hazard ratio [HR] = 0.65, P < 0.01) and increased workplace hours missed. The annual value of missed work was

Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: Comparative effectiveness and safety evaluated using a propensity-score-matched approach

24,166 for non-metastatic and

Abstract P1-11-07: The relationship between breast cancer progression and workplace productivity in the US

30,666 for metastatic patients. Thus, progression to metastatic disease is associated with an additional