Real-World Comparative Effectiveness, Safety, and Health Care Costs of Oral Anticoagulants in Nonvalvular Atrial Fibrillation Patients in the U.S. Department of Defense Population.

BACKGROUND: The ARISTOTLE trial demonstrated that apixaban had significantly lower rates of stroke/systemic embolism (SE) and major bleeding than warfarin; however, no direct clinical trials between apixaban and other direct oral anticoagulants (DOACs) are available. Few real-world studies comparing the effectiveness and safety between DOACs have been conducted. OBJECTIVE: To compare effectiveness, safety, and health care costs among oral anticoagulants (OACs) for nonvalvular atrial fibrillation (NVAF) patients in the U.S. Department of Defense (DoD) population. METHODS: Adult NVAF patients initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from U.S. DoD data from January 1, 2013, to September 30, 2015. The first OAC claim date was designated as the index date. Patients initiating another OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risk of stroke/SE and major bleeding for each OAC versus apixaban. Generalized linear and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE-related and major bleeding-related medical costs. RESULTS: Of the 41,001 eligible patients, 7,607 warfarin-apixaban, 4,129 dabigatran-apixaban, and 11,284 rivaroxaban-apixaban pairs were matched. Warfarin (HR = 1.84; 95% CI = 1.30-2.59; P < 0.001) and rivar-oxaban (HR = 1.46; 95% CI = 1.08-1.98; P = 0.015) were associated with a significantly higher risk of stroke/SE compared with apixaban. Dabigatran (HR = 1.17; 95% CI = 0.68-2.03; P = 0.573) was associated with a numerically higher risk of stroke/SE compared with apixaban. Warfarin (HR = 1.53; 95% CI = 1.24-1.89; P < 0.001), dabigatran (HR = 1.76; 95% CI = 1.27-2.43; P < 0.001), and rivaroxaban (HR = 1.59; 95% CI = 1.34-1.89; P < 0.001) were associated with higher risks of major bleeding compared with apixaban. Compared with apixaban, patients prescribed warfarin incurred numerically higher all-cause total health care costs per patient per month (PPPM) ($2,498 vs. $2,277; P = 0.148) and significantly higher stroke/SE-related ($118 vs. $46; P = 0.012) and major bleeding-related ($166 vs. $76; P = 0.003) medical costs. Dabigatran patients incurred numerically higher all-cause total health care PPPM costs ($2,372 vs. $2,143; P = 0.150) and stroke/SE-related medical costs ($61 vs. $32; P = 0.240) but significantly higher major bleeding-related costs ($114 vs. $58; P = 0.025). Rivaroxaban patients incurred significantly higher all-cause total health care costs ($2,546 vs. $2,200; P < 0.001) and major bleeding-related medical costs PPPM ($137 vs. $69; P < 0.001) but numerically higher stroke/SE-related medical costs PPPM ($58 vs. $38; P = 0.057). CONCLUSIONS: Among NVAF patients in the U.S. DoD population, warfarin and rivaroxaban were associated with a significantly higher risk of stroke/SE and major bleeding compared with apixaban. Dabigatran use was associated with a numerically higher risk of stroke/SE and a significantly higher risk of major bleeding compared with apixaban. Warfarin and dabigatran incurred numerically higher all-cause total health care costs compared with apixaban. Rivaroxaban was associated with significantly higher all-cause total health care costs compared with apixaban. DISCLOSURES This study was funded by Bristol-Myers Squibb and Pfizer, which were involved in the study design, as well as in the writing and revision of the manuscript. Keshishian and Zhang are paid employees of STATinMED Research, which was paid by Bristol-Myers Squibb and Pfizer to conduct this study and develop the manuscript. Gupta, Rosenblatt, Hede, and Nadkarni are paid employees of Bristol-Myers Squibb. Trocio, Dina, Mardekian, Liu, and Shank are paid employees of Pfizer.

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

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.

Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis C infection in the United States.

BACKGROUND: A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients. AIM: This study evaluated the cost-effectiveness of DCV + SOF vs SOF in combination with ribavirin (RBV) over a 20-year time horizon from the perspective of a United States (US) payer. METHODS: A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks. Clinical inputs came from the ALLY-3 and VALENCE trials. The primary outcome was the incremental cost-utility ratio. Life-years, incidence of complications, number of patients achieving sustained virological response (SVR), and the total cost per SVR were secondary outcomes. Costs (2014 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Deterministic, probabilistic, and scenario sensitivity analyses were conducted. RESULTS: DCV + SOF was associated with lower costs and better effectiveness than SOF + RBV in the base case and in almost all scenarios (i.e. treatment-experienced, non-cirrhotic, time horizons of 5, 10, and 80 years). DCV + SOF was less costly, but also slightly less effective than SOF + RBV in the cirrhotic and treatment-naïve population scenarios. Results were sensitive to variations in the probability of achieving SVR for both treatment arms. DCV + SOF costs less than $50,000 per QALY gained in 79% of all probabilistic iterations compared with SOF + RBV. CONCLUSION: DCV + SOF is a dominant option compared with SOF + RBV in the US for the overall GT 3 HCV patient population.