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

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.Doctor of Philosoph

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

MENA Confers Resistance to Paclitaxel in Triple-Negative Breast Cancer

Taxane therapy remains the standard of care for triple-negative breast cancer. However, high frequencies of recurrence and progression in treated patients indicate that metastatic breast cancer cells can acquire resistance to this drug. The actin regulatory protein MENA and particularly its invasive isoform, MENAINV , are established drivers of metastasis. MENAINV expression is significantly correlated with metastasis and poor outcome in human patients with breast cancer. We investigated whether MENA isoforms might play a role in driving resistance to chemotherapeutics. We find that both MENA and MENAINV confer resistance to the taxane paclitaxel, but not to the widely used DNA-damaging agents doxorubicin or cisplatin. Furthermore, paclitaxel treatment does not attenuate growth of MENAINV -driven metastatic lesions. Mechanistically, MENA isoform expression alters the ratio of dynamic and stable microtubule populations in paclitaxel-treated cells. MENA expression also increases MAPK signaling in response to paclitaxel treatment. Decreasing ERK phosphorylation by cotreatment with MEK inhibitor restored paclitaxel sensitivity by driving microtubule stabilization in MENA isoform-expressing cells. Our results reveal a novel mechanism of taxane resistance in highly metastatic breast cancer cells and identify a combination therapy to overcome such resistance

Prevalent But Moderate Variation Across Small Geographic Regions in Patient Nonadherence to Evidence-based Preventive Therapies in Older Adults After Acute Myocardial Infarction

Patient long-term adherence to β-blockers, HMG-CoA reductase inhibitors (statins), and angiotensin-converting-enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) after acute myocardial infarction (AMI) is alarmingly low. It is unclear how prevalent patient adherence may be across small geographic areas and whether this geographic prevalence may vary

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

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

Report of the 2011-2012 Standing Committee on Advocacy: The Relevance of Excellent Research: Strategies for Impacting Public Policy

According to the Bylaws of the American Association of Colleges of Pharmacy (AACP), the Advocacy Committee

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

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