Comparative outcomes associated with rivaroxaban versus warfarin use in elderly patients with atrial fibrillation or acute venous thromboembolism managed in the United States: a systematic review of observational studies.

BACKGROUND: Advancing age is a risk factor for developing non-valvular atrial fibrillation (NVAF) or acute venous thromboembolism (VTE). We assessed the comparative effectiveness, safety, costs, and healthcare utilization associated with rivaroxaban versus warfarin in patients of advanced age managed in the United States (US). METHODS: We conducted a systematic review of Medline and Embase through April 2023 to identify real-world evidence (RWE) studies of older adults (at least 65+ years of age) with either NVAF or VTE who received either rivaroxaban or warfarin in the US and reported an outcome of stroke or systemic embolism (SSE), ischemic stroke (IS), recurrent VTE, major bleeding, intracranial hemorrhage, costs, or healthcare resource utilization. We classified each outcome of interest per study as "positive" (lower risk), "negative" (higher risk), or "neutral" based upon the summary effect size of rivaroxaban versus warfarin. RESULTS: Twenty-nine RWE studies met inclusion criteria, mostly (83%) in NVAF populations. For SSE with rivaroxaban versus warfarin, 68.8% of studies showed positive effects and 31.2% showed neutral outcome. For major bleeding, 57.7% showed neutral effects, 38.5% showed negative effects, and 3.8% of studies showed positive effects with rivaroxaban versus warfarin. Of the two studies reporting cost data, both were positive, showing lower costs for SSE for rivaroxaban versus warfarin and neutral cost for major bleeding costs. CONCLUSIONS: This systematic review supports findings from subgroup analyses of randomized controlled trials that, compared with warfarin, rivaroxaban is associated with generally neutral or positive effects on thrombosis and a mixed picture on bleeding outcomes in older adults with either NVAF or VTE treated in the United States.

Impact of mobility impairment on indirect costs and health-related quality of life in multiple sclerosis.

This study was conducted to estimate the indirect costs and health-related quality of life (HRQoL) (utilities) of multiple sclerosis (MS) patients in the United States (US), and to determine the impact of worsening mobility on these parameters. In collaboration with the North American Research Committee on Multiple Sclerosis (NARCOMS) registry we conducted a cross-sectional study of participants who completed the biannual update and supplemental spring 2010 survey. Demographic, employment status, income, mobility impairment, and health utility data were collected from a sample of registry participants who met the study criteria and agreed to participate in the supplemental Mobility Study. Mean annual indirect costs per participant in 2011US$ and mean utilities for the population and for cohorts reporting different levels of mobility impairment were estimated. Analyses included 3,484 to 3,611 participants, based on survey completeness. Thirty-seven percent of registrants were not working or attending school and 46.7% of these reported retiring early. Indirect costs per participant per year, not including informal caregiver cost, were estimated at $30,601±31,184. The largest relative increase in indirect costs occurred at earlier mobility impairment stages, regardless of the measure used. Participants' mean utility score (0.73±0.18) was lower than that of a similarly aged sample from the general US population (0.87). As with indirect costs, larger decrements in utility were seen at earlier mobility impairment stages. These results suggest that mobility impairment may contribute to increases in indirect costs and declines in HRQoL in MS patients.

Dosing frequency and medication adherence in chronic disease.

BACKGROUND: Prior research has shown a decrease in medication adherence as dosing frequency increases; however, meta-analyses have not been able to demonstrate a significant inverse relationship between dosing frequency and adherence when comparing twice-daily versus once-daily dosing. OBJECTIVE: To determine the effect of scheduled dosing frequency on medication adherence in patients with chronic diseases. METHODS: A systematic literature search of Medline and Embase from January 1986 to December 2011 and a hand search of references were performed to identify eligible studies. Randomized and observational studies were included if they utilized a prospective design, assessed adult patients with chronic diseases, evaluated scheduled oral medications taken 1 to 4 times daily, and measured medication adherence for at least 1 month using an electronic monitoring device. Manual searches of reference sections of identified studies and systematic reviews were also performed to find other potentially relevant articles. Standard definitions for medication taking, regimen, and timing adherence were used and evaluated. Studies were pooled using a multivariate linear mixed-model method to conduct meta-regression accounting for both random and fixed effects, weighted by the inverse of the variance of medication adherence. RESULTS: Fifty-one studies, comprising 65, 76, and 47 dosing frequency arms for the taking, regimen, and timing adherence endpoints were included. Unadjusted adherence estimates were highest when the least stringent definition, taking adherence, was used (range for dosing frequencies: 80.1%-93.0%) and lowest when the most stringent definition, timing adherence, was used (range for dosing frequencies: 18.8%-76.9%). In multivariate meta-regression analyses, the adjusted weighted mean percentage adherence rates for all regimens dosed more frequently than once per day were significantly lower compared with once-daily regimens (for 2-times, 3-times, and 4-times daily regimens, respectively: differences for taking adherence: -6.7%, -13.5%, and -19.2%; regimen adherence: -13.1%, -24.9%, and -23.1%; and timing adherence: -26.7%, -39.0%, and -54.2%). CONCLUSION: Patients with chronic diseases appear to be more adherent with once-daily compared with more frequently scheduled medication regimens. The use of more stringent definitions of adherence magnified these findings.

Cost-effectiveness of fingolimod versus interferon beta-1a for relapsing remitting multiple sclerosis in the United States.

OBJECTIVE: Fingolimod has been shown to be more efficacious than interferon (IFN) beta-1a, but at a higher drug acquisition cost. The aim of this study was to assess the cost-effectiveness of fingolimod compared to IFN beta-1a in patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) in the US. METHODS: A Markov model comparing fingolimod to intramuscular IFN beta-1a using a US societal perspective and a 10-year time horizon was developed. A cohort of 37-year-old patients with RRMS and a Kurtzke Expanded Disability Status Scale score of 0-2.5 were assumed. Data sources included the Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS) and other published studies of MS. Outcomes included costs in 2011 US dollars, quality-adjusted life years (QALYs), number of relapses avoided, and incremental cost-effectiveness ratios (ICERs). RESULTS: Compared to IFN beta-1a, fingolimod was associated with fewer relapses (0.41 vs 0.73 per patient per year) and more QALYs gained (6.7663 vs 5.9503), but at a higher cost ($565,598 vs $505,234). This resulted in an ICER of $73,975 per QALY. Results were most sensitive to changes in drug costs and the disutility of receiving IFN beta-1a. Monte Carlo simulation demonstrated fingolimod was cost-effective in 35% and 70% of 10,000 iterations, assuming willingness-to-pay thresholds of $50,000 and $100,000 per QALY, respectively. LIMITATIONS: Event rates were primarily derived from a single randomized clinical trial with 1-year duration of follow-up and extrapolated to a 10-year time horizon. Comparison was made to only one disease-modifying drug-intramuscular IFN beta-1a. CONCLUSION: Fingolimod use is not likely to be cost-effective compared to IFN beta-1a unless fingolimod cost falls below $3476 per month or a higher than normal willingness-to-pay threshold is accepted by decision-makers.

Effect of dosing frequency on chronic cardiovascular disease medication adherence.

BACKGROUND: Many cardiovascular diseases (CVDs) require patients to take one or more long term medications, often administered multiple times a day. We sought to determine the effect of chronic CVD medication dosing frequency on medication adherence. METHODS: A search of Medline and Embase from 1986 to December 2011 was performed. Included studies used a prospective design, assessed adults with chronic CVDs, evaluated scheduled oral medications administered one to four times daily, and measured adherence for ≥1 month using an electronic monitoring device. Mixed linear model meta-regression was used to determine how dosing frequency affected adherence using three definitions of increasing strictness: taking, regimen and timing adherence. RESULTS: A total of 29 studies, comprising 41, 29, and 27 dosing frequency arms for the taking, regimen and timing adherence definitions were included. Crude pooled adherence estimates were highest when the lenient taking definition was assessed (range for dosing frequencies: 80.1%-93.1%), and lowest when the strictest timing definition was assessed (range: 57.1%-76.3%). Upon meta-regression, the adjusted weighted mean percentage adherence for twice and three times daily dosing regimens (no studies evaluated four times daily regimens), were 6.9% and 13.7% lower than once daily regimens for the taking, 14.0% and 27.5% lower for the regimen, and 22.9% and 30.4% lower for the timing adherence definition (p < 0.01 for all). LIMITATIONS: The presence of residual confounding and publication bias cannot be ruled out. CONCLUSION: Patients appear to be more adherent with once daily dosing compared with more frequently scheduled chronic CVD medication regimens. This finding is magnified when more stringent definitions of adherence are used.