Dabigatran and Warfarin for Stroke Prevention in Atrial Fibrillation: Use, Switching, and Clinical Effects Following New Market Entry in Real-World Patients

Patients with atrial fibrillation frequently benefit from anticoagulation to prevent stroke and systemic embolism. For decades, warfarin was the primary oral anticoagulant option despite its narrow therapeutic index requiring monitoring and drug-drug interactions. Dabigatran’s recent availability provides practical advantages including no monitoring and fewer interactions; however, it lacks a convenient reversal agent for bleeding events. Currently, it is unclear what factors have driven anticoagulant utilization since dabigatran’s introduction, and little real-world evidence on the agents’ comparative effectiveness and safety is available. The objectives were to describe dabigatran and warfarin’s utilization and switching patterns and assess their comparative effectiveness and safety. A cohort of non-valvular atrial fibrillation patients initiating anticoagulation from a large US database of commercial and Medicare supplement claims from 2009-2012 was extracted. We first examined factors associated with anticoagulant selection using a retrospective cohort design and multivariable regression. We then evaluated the effectiveness and safety of dabigatran compared with warfarin using multivariable Cox proportional hazards regression and propensity score weighting. Finally, we evaluated the clinical effects of switching anticoagulants compared with non-switching using a time-varying exposure design and multivariable Cox proportional hazards regression. Of the 64,935 patients included in the cohort, 32.5% used dabigatran. Dabigatran users were less likely to have high ischemic stroke or bleeding risk or other clinical comorbidities. Switching anticoagulation was also less frequent among patients with higher ischemic stroke or bleeding risk. Dabigatran was associated with a lower risk of ischemic stroke or venous thromboembolism, and no relation was seen between anticoagulant and harmful outcomes including bleeding events or acute myocardial infarction. However, dabigatran was also associated with a higher risk of gastrointestinal bleeding. Compared with non-switchers, no relation was seen between switching anticoagulants and an increased risk of stroke, systemic embolism, bleeding events, or myocardial infarction. Despite the rapid uptake of dabigatran, these results highlight that patients initiating dabigatran were generally healthier than those initiating warfarin. Dabigatran may be considered a safe and possibly more effective alternative to warfarin in patients with atrial fibrillation; despite encouraging results from the observed lack of increased adverse outcomes from switching anticoagulants, caution is still recommended

Racial/Ethnic and Gender Gaps in the Use of and Adherence to Evidence-Based Preventive Therapies Among Elderly Medicare Part D Beneficiaries After Acute Myocardial Infarction

It is unclear whether gender and racial/ethnic gaps in the use of and patient adherence to β-blockers, angiotensin-converting-enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and HMG-CoA reductase inhibitors (statins) post-acute myocardial infarction (AMI) have persisted following establishment of the Medicare Part D prescription program

Predictors of Gastrointestinal Bleeding Among Patients with Atrial Fibrillation After Initiating Dabigatran Therapy

To identify demographic and clinical risk factors associated with gastrointestinal (GI) bleeding among a large cohort of patients with atrial fibrillation (AF) who initiated dabigatran therapy for stroke prevention, and to describe patterns of subsequent anticoagulant use after occurrence of the GI bleeding event

The Effect of Community Pharmacy–Based Interventions on Patient Health Outcomes: A Systematic Review

Many studies have demonstrated the beneficial effects that pharmacist-provided patient care services can have on patient health outcomes. However, the effectiveness of patient care services delivered by pharmacists in community pharmacy settings, where organizational barriers may affect service implementation or limit effectiveness, remains unclear. The authors systematically reviewed the literature on the effectiveness of pharmacist-delivered patient care services in community pharmacy settings in the United States. Of the 749 articles retrieved, 21 were eligible for inclusion in the review. Information concerning 134 outcomes was extracted from the included articles. Of these, 50 (37.3%) demonstrated statistically significant, beneficial intervention effects. The percentage of studies reporting favorable findings ranged from 50% for blood pressure to 0% for lipids, safety outcomes, and quality of life. Our findings suggest that evidence supporting the effectiveness of pharmacist-provided direct patient care services delivered in the community pharmacy setting is more limited than in other settings

Design of a Medication Therapy Management Program for Medicare Beneficiaries: Qualitative Findings From Patients and Physicians

The quality of pharmacologic care provided to older adults is less than optimal. Medication therapy management (MTM) programs delivered to older adults in the ambulatory care setting may improve the quality of medication use for these individuals

Factors Driving Anticoagulant Selection in Patients With Atrial Fibrillation in the United States

With the introduction of novel oral anticoagulants (NOACs), the factors driving anticoagulant selection in atrial fibrillation (AF) in real-world practice are unclear. The goal was to examine whether and to what extent utilization has been driven by predictions of stroke risk (treatment benefit), bleeding risk (treatment harm), or prescription benefits’ coverage. We extracted a cohort of non-valvular AF patients initiating anticoagulation from Oct 2010-Dec 2012 from a large US database of commercial and Medicare supplement claims. Multivariable regression examined associations between ischemic stroke (CHA2DS2-VASc) and bleeding (ATRIA) risk scores and benefits’ generosity (proportion of costs covered by patients relative to total) with warfarin and NOAC selection and also between dabigatran and rivaroxaban. C-statistics and partial chi-square statistics were used to assess the variation explained. Of 70,498 patients initiating anticoagulation, 29.9% and 7.9% used dabigatran and rivaroxaban, respectively. Compared with warfarin, patients were less likely to receive a NOAC with high ischemic stroke risk (CHA2DS2-VASc ≥2) (Adjusted Relative Risk [aRR]: 0.75, 95% CI: 0.72-0.77) and high bleeding risk (ATRIA≥5) (aRR: 0.66, 95% CI: 0.64-0.69) but more likely with good benefits’ generosity (≤20% of costs borne by patient) (aRR: 2.03, 95% CI: 1.92-2.16). Prescription generosity explained almost twice the model variation as either risk score. Compared with dabigatran, patients were more likely to fill rivaroxaban with high bleeding risk (aRR: 1.16, 95% CI: 1.09-1.24). In conclusion, patients with higher bleeding and ischemic stroke risk were more likely to initiate warfarin, but generous benefits more strongly predicted NOAC usage and drove more selection

Medication use and medical comorbidity in patients with chronic hepatitis C from a US commercial claims database: high utilization of drugs with interaction potential

With the advent of the direct-acting antiviral agents (DAAs), significant drug-drug interaction (DDI) potential now exists for patients treated for chronic hepatitis C virus (HCV) infection. However, little is known about how often patients with HCV use medications that may interact with newer HCV treatments, especially those with CYP3A DDI potential

Completeness of prescription information in US commercial claims databases

Pharmacy commercial claims databases are widely used for pharmacoepidemiologic research. However, concerns have been raised that these databases may not fully capture claims for generic medication as a result of patients filling outside the context of their insurance. This has implications for many research activities and quality improvement programs. We sought to estimate the percentage of missing drug claims in US commercial claims data using a novel design

Rationale and design of the Novel Uses of adaptive Designs to Guide provider Engagement in Electronic Health Records (NUDGE-EHR) pragmatic adaptive randomized trial: a trial protocol

Background: The prescribing of high-risk medications to older adults remains extremely common and results in potentially avoidable health consequences. Efforts to reduce prescribing have had limited success, in part because they have been sub-optimally timed, poorly designed, or not provided actionable information. Electronic health record (EHR)-based tools are commonly used but have had limited application in facilitating deprescribing in older adults. The objective is to determine whether designing EHR tools using behavioral science principles reduces inappropriate prescribing and clinical outcomes in older adults. Methods: The Novel Uses of Designs to Guide provider Engagement in Electronic Health Records (NUDGE-EHR) project uses a two-stage, 16-arm adaptive randomized pragmatic trial with a “pick-the-winner” design to identify the most effective of many potential EHR tools among primary care providers and their patients ≥ 65 years chronically using benzodiazepines, sedative hypnotic (“Z-drugs”), or anticholinergics in a large integrated delivery system. In stage 1, we randomized providers and their patients to usual care (n = 81 providers) or one of 15 EHR tools (n = 8 providers per arm) designed using behavioral principles including salience, choice architecture, or defaulting. After 6 months of follow-up, we will rank order the arms based upon their impact on the trial’s primary outcome (for both stages): reduction in inappropriate prescribing (via discontinuation or tapering). In stage 2, we will randomize (a) stage 1 usual care providers in a 1:1 ratio to one of the up to 5 most promising stage 1 interventions or continue usual care and (b) stage 1 providers in the unselected arms in a 1:1 ratio to one of the 5 most promising interventions or usual care. Secondary and tertiary outcomes include quantities of medication prescribed and utilized and clinically significant adverse outcomes. Discussion: Stage 1 launched in October 2020. We plan to complete stage 2 follow-up in December 2021. These results will advance understanding about how behavioral science can optimize EHR decision support to improve prescribing and health outcomes. Adaptive trials have rarely been used in implementation science, so these findings also provide insight into how trials in this field could be more efficiently conducted. Trial registration: Clinicaltrials.gov (NCT04284553, registered: February 26, 2020

Utilization and Spending on Potentially Inappropriate Medications by US Older Adults with Multiple Chronic Conditions using Multiple Medications.

BACKGROUND The utilization of potentially inappropriate medications (PIMs) in older adults can lead to adverse events and increased healthcare costs. Polypharmacy, the concurrent utilization of multiple medications, is common in older adults with multiple chronic conditions. OBJECTIVE To investigate the utilization and costs of PIMs in multimorbid older adults with polypharmacy over time. METHODS This retrospective cross-sectional study used linked Medicare claims and electronic health records from seven hospitals/medical centers in Massachusetts (2007-2014). Participants were ≥65 years old, had ≥2 chronic conditions (to define multimorbidity), and used drugs from ≥5 pharmaceutical classes for ≥90 days (to define polypharmacy). Chronic conditions were defined using the Chronic Conditions Indicator from the Agency for Health Research and Quality. PIMs were defined using the American Geriatrics Society 2019 version of the Beers criteria. We calculated the percentage of patients with ≥1 PIMs and the percentages of patients using different types of PIMs. We used logistic regression analyses to test the odds of taking ≥1 PIMs. We calculated mean costs spent on PIMs by dividing the costs spent on PIMs by the total medication cost. RESULTS ≥69% of patients used ≥1 PIM. After adjusting for healthcare utilization, chronic conditions, medication intake, and demographic factors, female sex (2014: Odds ratio (OR)=1.27, 95%CI 1.25-1.30), age (2014: OR=0.92, 95%CI 0.90-0.93), and Hispanic ethnicity (2014: OR=1.41, 95%CI 1.27-1.56) were associated with PIM use. Gastrointestinal drugs and central nervous system drugs were the most commonly-used PIMs. In patients using ≥1 PIM, >10% of medication costs were spent on PIMs. CONCLUSION The utilization of PIMs in US older adults with multimorbidity and polypharmacy is high