Alexander, G. Caleb

Introduction: Medicines don’t work in those who don’t take them. Although novel oral anticoagulants (NOACs) are more convenient than warfarin due to fewer drug-drug interactions and less need for laboratory monitoring, their considerable costs and lack of regular interactions with the healthcare system may also contribute to poor adherence. Little is known about the persistence and adherence in the era of NOACs, nor how such behaviors are associated with the risk of ischemic stroke and transient ischemic attack (TIA) among patients of varying baseline risk. Methods: We conducted a retrospective analysis using a large U.S. commercial insurance database, and identified 61,646 patients with atrial fibrillation who initiated one of OACs (warfarin, dabigatran, rivaroxaban and apixaban) between October 2010 and September 2014. We defined discontinuation as being off OACs for at least 3 months and adherence as the proportion of days covered of at least 80%. Cox proportional hazard models was used to examine whether the time that patients were off OACs, including both the gaps between medication fills and the time of discontinuation, increased the risk of ischemic stroke and TIA. Results: Approximately 1 in 3 patients discontinued OACs within one year after initiation and 1 in 10 switched to another OAC. The estimated likelihood of adherence was 0.77 during the time when patients were on their first-line medications. Apixaban had the highest continuation rate (65% at 1 year), while rivaroxaban had the best adherence (predicted probability of adherence 0.83). The event rate of stroke was 1.6 per 100 person years. Patients with high baseline risk (CHA2DS2-VASc ≥2) were more likely to have a stroke when they were off OACs for 1-3 months (HR=1.47, p<0.01), 3-6 months (HR=1.78, p<0.001) and ≥6 months (HR=2.16, p<0.001), compared to off OACs for less than a week. No significant effect was found among low-risk patients (CHA2DS2-VASc 0 or 1). Switching to another OAC was related to 22% increased risk of stroke (p=0.05). Conclusions: Despite their greater convenience relative to warfarin, discontinuation and nonadherence to NOACs is high. Lack of persistence and adherence was associated with increased risk of ischemic stroke and TIA among patients with elevated baseline risk.

Background In comparison to warfarin, non–vitamin K antagonist oral anticoagulants ( NOAC s) have the advantages of ease of dosing, fewer drug interactions, and lack of need for ongoing monitoring. We sought to evaluate whether these advantages translate to improved adherence and whether adherence is associated with improved outcomes in patients with atrial fibrillation. Methods and Results We performed a retrospective cohort analysis by using a large US commercial insurance database to identify 64 661 patients with atrial fibrillation who initiated warfarin, dabigatran, rivaroxaban, or apixaban treatment between November 1, 2010, and December 31, 2014. During a median of 1.1 y of follow‐up, 47.5% of NOAC patients had a proportion of days covered of ≥80%, compared with 40.2% in warfarin patients ( P <0.001). Patients with CHA 2 DS 2 ‐ VAS c (risk based on the presence of congestive heart failure, hypertension age 65–74 y, age ≥75 y, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, sex category) score ≥4 were at increased risk of stroke when they were not taking anticoagulation ≥1 month versus <1 week (1–3 months: hazard ratio [ HR ] 1.96, 3–6 months: HR 2.64, ≥6 months: HR 3.66; all P <0.001). Patients with CHA 2 DS 2 ‐ VAS c score 2 or 3 were at increased risk of stroke when they were not taking anticoagulation ≥6 months ( HR 2.73, P <0.001). In these patients with CHA 2 DS 2 ‐ VAS c score ≥2, nonadherence was not associated with intracranial hemorrhage. Among patients with CHA 2 DS 2 ‐ VAS c score 0 or 1, time not taking anticoagulation was not associated with stroke, but not taking anticoagulation ≥3 months was associated with a significant reduction of bleeding. Conclusions Adherence to anticoagulation is poor in practice and may be modestly improved with NOAC s. Adherence to therapy appears to be most important in patients with CHA 2 DS 2 ‐ VAS c score ≥2, whereas the benefits of anticoagulation may not outweigh the harms in patients with CHA 2 DS 2 ‐ VAS c score 0 or 1.

ABSTRACTBackgroundPrescription drug abuse has prompted considerable concern. We evaluated a retrospective drug utilization review program to reduce controlled substance use among individuals with high‐risk utilization.MethodsWe analyzed pharmacy claims from a large pharmaceutical benefits manager. For each eligible member, we calculated a controlled substance score based on the number and type of claims, prescribers and pharmacies, and utilization patterns over three months. Two state health plans sent controlled substance letters to prescribers of members meeting or exceeding a plan‐ and pre‐specified controlled substance score. Two different state health plans did not send such letters. We used a difference‐in‐difference design and generalized estimating equations to quantify the impact of the program on the mean difference in reduction of the controlled substance score over six months.ResultsEligible members in the intervention and comparison states had similar baseline mean controlled substance scores (19.0 vs. 18.6, p = 0.36). Adjusting for individuals' age, sex and pharmacy risk group score, reductions in the mean controlled substance score were greater in the intervention than comparison cohort (5.67 vs. 4.31, p = 0.01), corresponding with a 34.0% reduction in the intervention cohort compared to a 25.5% reduction in the comparison cohort. Changes were driven primarily by reductions in the number of controlled substance claims filled (30.5% vs. 23.1%, p = 0.01), as well as by a non‐statistically significant trend towards reductions in the number of prescribers and pharmacies used (26.9% vs. 20.1%, p = 0.07).ConclusionsRetrospective drug utilization review programs may reduce controlled substance scores and claims among individuals with patterns suggesting high‐risk utilization. Copyright © 2013 John Wiley & Sons, Ltd.

OBJECTIVE Little is known regarding recent changes in glitazone use. RESEARCH DESIGN AND METHODS Interrupted time series analyses of nationally representative office-visit data using IMS Health's National Disease and Therapeutic Index. RESULTS From 2003 through 2005, glitazone use increased steadily. From February 2005 to January 2007, rosiglitazone use decreased by 16% (95% CI −20 to −11) annually; pioglitazone use increased at an annual rate of 14% (9–18). During a period of Food and Drug Administration (FDA) advisories, rosiglitazone use declined sharply from 0.42 million monthly treatment visits (February 2007) to 0.13 million monthly visits (May 2008). Pioglitazone use remained stable, accounting for ∼5.8 million physician visits (77% of all glitazone use) where a treatment was used during the final 12 months of observation. CONCLUSIONS The combined effect of scientific publications, advisories, and media exposure was associated with a substantial decrease in rosiglitazone use. Despite a class-level FDA advisory, pioglitazone use was not similarly affected.