Geoffrey D. Barnes

National Trends in Ambulatory Oral Anticoagulant Use

BACKGROUND Four direct oral anticoagulants (DOACs) have been brought to market for the treatment of nonvalvular atrial fibrillation and venous thromboembolism. Many forces, including numerous positive trial results, emerging safety concerns, marketing, and promotion, may shape DOAC adoption by providers. However, relatively little is known regarding their ambulatory utilization compared with warfarin, as well as the degree to which they have decreased under-treatment of atrial fibrillation. METHODS We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of outpatient office visits, to estimate the use of warfarin and DOACs between 2009 and 2014. RESULTS Overall, visits with anticoagulation use increased from 2.05 (95% confidence interval [CI], 1.82-2.27) to 2.83 (95% CI, 2.49-3.17) million (M) quarterly visits (P < .001). Of these, DOAC use has grown to 4.21M (95% CI, 3.63M-4.79M; 38.2% of total) treatment visits in 2014 since their introduction in 2010. Use of all oral anticoagulants in treatment visits for atrial fibrillation has increased from 0.88M (95% CI, 0.74M-1.02M) to 1.72M (95% CI, 1.47M-1.97M; P < .001), with similar DOAC and warfarin use in 2014. Atrial fibrillation visits with anticoagulant use increased from 51.9% (95% CI, 50.4%-53.8%) to 66.9% (95% CI, 65.0%-69.3%) between 2009 and 2014 (P < .001). In 2014, rivaroxaban was the most commonly prescribed DOAC for atrial fibrillation (47.9% of office visits), followed by apixaban (26.5%) and dabigatran (25.5%). CONCLUSIONS Direct oral anticoagulants have been adopted rapidly, matching the use of warfarin, and are associated with increased use of oral anticoagulation for patients with atrial fibrillation.

Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH

G. D . BARNES ,* W. AGENO,† J . ANSELL‡ and S . KAATZ ,§ FOR THE SUBCOMMITTEE ON THE CONTROL OF ANT ICOAGULAT ION *Frankel Cardiovascular Center and Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; †Division of Internal Medicine, University of Insubria, Varese, Italy; ‡Department of Internal Medicine, Lenox Hill Hospital, New York, NY; and §Hurley Medical Center, Michigan State University, Flint, MI, USA

Reimagining Anticoagulation Clinics in the Era of Direct Oral Anticoagulants

Anticoagulation clinics were initially developed to provide safe and effective care for warfarin-treated patients with atrial fibrillation, venous thromboembolism, and mechanical valve replacement. Traditionally, these patients required ongoing laboratory monitoring and warfarin dose adjustment by expert providers. With the introduction of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban), many have questioned the need for anticoagulation clinic. However, we think that the growing number of oral anticoagulant choices creates an urgent need for expanding the traditional role of the anticoagulation clinic. We outline 3 key purposes that a reimagined anticoagulation clinic would serve: (1) to assist patients and clinicians with selecting the most appropriate drug and dose from a growing list of anticoagulant options (including warfarin), (2) to help patients minimize the risk of serious bleeding complications with careful long-term monitoring and peri-procedural management, and (3) to encourage ongoing adherence to these life-saving medications. We also describe how repurposing anticoagulation clinics as broader medication safety clinics would promote safe and effective care across a range of cardiovascular conditions for high-risk medications (eg, spironolactone, amiodarone). Finally, we highlight a few existing health systems that are overcoming key challenges to implementing a reimagined anticoagulation or medication safety clinic structure.

The Predictive Ability of the CHADS2 and CHA2DS2-VASc Scores for Bleeding Risk in Atrial Fibrillation: The MAQI2 Experience

INTRODUCTION Guidelines recommend the assessment of stroke and bleeding risk before initiating warfarin anticoagulation in patients with atrial fibrillation. Many of the elements used to predict stroke also overlap with bleeding risk in atrial fibrillation patients and it is tempting to use stroke risk scores to efficiently estimate bleeding risk. Comparison of stroke risk scores to bleeding risk scores to predict bleeding has not been thoroughly assessed. METHODS 2600 patients followed at seven anticoagulation clinics were followed from October 2009-May 2013. Five risk models (CHADS2, CHA2DS2-VASc, HEMORR2HAGES, HAS-BLED and ATRIA) were retrospectively applied to each patient. The primary outcome was the first major bleeding event. Area under the ROC curves were compared with C statistic and net reclassification improvement (NRI) analysis was performed. RESULTS 110 patients experienced a major bleeding event in 2581.6 patient-years (4.5%/year). Mean follow up was 1.0±0.8years. All of the formal bleeding risk scores had a modest predictive value for first major bleeding events (C statistic 0.66-0.69), performing better than CHADS2 and CHA2DS2-VASc scores (C statistic difference 0.10 - 0.16). NRI analysis demonstrated a 52-69% and 47-64% improvement of the formal bleeding risk scores over the CHADS2 score and CHA2DS2-VASc score, respectively. CONCLUSIONS The CHADS2 and CHA2DS2-VASc scores did not perform as well as formal bleeding risk scores for prediction of major bleeding in non-valvular atrial fibrillation patients treated with warfarin. All three bleeding risk scores (HAS-BLED, ATRIA and HEMORR2HAGES) performed moderately well.

National trends in venous disease

BACKGROUND The national burden of venous disease and use of ultrasound (US) in the outpatient and emergency department (ED) settings has not been well described. The objective of this study is to describe venous disease in the outpatient and ED settings nationally as well as to characterize the use of US for diagnosis of venous disease, including phlebitis. METHODS Data from the 1997 to 2006 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) were compiled, and complex sampling methods were used to describe the number of outpatient and ED visits for adults given a diagnosis of venous disease or phlebitis by ICD-9 coding. Logistic regression analysis with calculated odds ratios are used to examined patient visit characteristics and use of US. RESULTS During the 10 years studied, an office or ED visit for venous disease occurred over 46 million times, for an average of 4.6 million visits per year, with this rate increasing from 4.03 million to 5.71 million per year (odds ratio [OR] 1.01, confidence interval [CI] 1.00-1.01). The majority of these patients were seen by specialists, such as surgeons or cardiologists, but a significant number were also seen by primary care providers (PCP). There were 2 million office visits (PCP and specialists) on average per year with no significant increase. There were approximately 236,000 ED visits for deep vein thrombosis (DVT) on average per year, which showed a small increase (OR 1.01, CI 1.00-1.01). Visits for DVT and phlebitis were as likely to be seen by PCPs as ED physicians. Non-DVT venous disease is much more likely to be seen by a surgeon (OR 4.88, CI 3.53-6.74) than a PCP. DVT is much less likely to be diagnosed by a specialist (OR 0.27, CI 0.18-0.29) than a PCP. Insurance status and geographic region were not associated with DVT or non-DVT venous disease diagnosis. CONCLUSIONS Nationally, a significant and growing number of patients with venous disease are being seen in the outpatient setting by PCPs and specialists. A significant number of patients with DVT are being seen in the outpatient setting, but without a trend away from care in the ED over the 10-year study period. Additionally, the majority of patients with DVT diagnosis do not seem to be getting ultrasounds at the same visit. Many of these patients are being seen by PCPs who may require additional training and infrastructure for appropriate patient care.

Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score

Pulmonary embolism (PE) is a major cause of morbidity and mortality world-wide, and the use of thrombolytic therapy has been associated with favourable clinical outcomes in certain patient subsets. These potential benefits are counterbalanced by the risk of bleeding complications, the most devastating of which is intracranial haemorrhage (ICH). We retrospectively evaluated 9703 patients from the 2003-2012 nationwide in-patient sample database (NIS) who received thrombolytics for PE. All patients with ICH during the PE hospitalisation were identified and a clinical risk score model was developed utilizing demographics and comorbidities. The dataset was divided 1:1 into derivation and validation cohorts. During 2003-2012, 176/9705 (1.8 %) patients with PE experienced ICH after thrombolytic use. Four independent prognostic factors were identified in a backward logistic regression model, and each was assigned a number of points proportional to its regression coefficient: pre-existing Peripheral vascular disease (1 point), age greater than 65 years (Elderly) (1 point), prior Cerebrovascular accident with residual deficit (5 points), and prior myocardial infarction (Heart attack) (1 point). In the derivation cohort, scores of 0, 1, 2 and ≥ 5 points were associated with ICH risks of 1.2 %, 1.9 %, 2.4 % and 17.8 %, respectively. Rates of ICH were similar in the validation cohort. The C-statistic for the risk score was 0.65 (0.61-0.70) in the derivation cohort and 0.66 (0.60-0.72) in the validation cohort. A novel risk score, derived from simple clinical historical elements was developed to predict ICH in PE patients treated with thrombolytics.

Prescribing trends of atrial fibrillation patients who switched from warfarin to a direct oral anticoagulant

Direct oral anticoagulant (DOAC) agents offer several lifestyle and therapeutic advantages for patients relative to warfarin in the treatment of atrial fibrillation (AF). These alternative agents are increasingly used in the treatment of AF, however the adoption practices, patient profiles, and reasons for switching to a DOAC from warfarin have not been well studied. Through the Michigan Anticoagulation Quality Improvement Initiative, abstracted data from 3873 AF patients, enrolled between 2010 and 2015, were collected on demographics and comorbid conditions, stroke and bleeding risk scores, and reasons for anticoagulant switching. Over the study period, patients who switched from warfarin to a DOAC had similar baseline characteristics, risk scores, and insurance status but differed in baseline CrCl. The most common reasons for switching were patient related ease of use concerns (37.5%) as opposed to clinical reasons (16.5% of patients). Only 13% of patients that switched to a DOAC switched back to warfarin by the end of the study period.

Venous thromboembolism: Predicting recurrence and the need for extended anticoagulation

Initial treatment for venous thromboembolism (VTE) includes the acute and intermediate phases, usually lasting for 3 months. The choice to extend therapy beyond the initial 3-month window involves assessing a combination of risk factors for VTE recurrence and bleeding, along with weighing patient preferences. In some cases, such as VTE provoked by a reversible surgical risk factor, the recurrence risk is sufficiently low that most patients should not receive extended therapy. In other cases, such as VTE associated with malignancy, the recurrence risk is sufficiently high that treatment should be extended beyond the initial 3 months. However, a large number of patients fall into a grey zone where the decision on extended therapy is less clear-cut. In this review, we summarize the evidence for VTE recurrence risk and the role for extended anticoagulation given a variety of patient-specific factors and laboratory results. We also review the role of VTE risk prediction tools and provide a recommended algorithm for approaching the decision of extended anticoagulation therapy. Various agents available for extended VTE therapy, including warfarin, aspirin and the direct oral anticoagulant agents, are discussed.

Anticoagulation: where we are and where we need to go

Although a commonly prescribed medication, warfarin has unique pharmacologic properties that make dosing challenging for many primary care physicians. When a patient’s international normalized ratio (INR) is out of the therapeutic range, they are at increased risk for thrombotic or hemorrhagic complications. We have reviewed the current literature for quality improvement techniques to minimize adverse outcomes and improve anticoagulation care. The use of anticoagulation clinics, computer-guided dosing and patient self-monitoring have been demonstrated to reduce adverse events or improve patient and provider satisfaction. Additional techniques, including genetic-based dosing, concurrent vitamin K administration and development of risk-assessment tools, have been discussed, but not fully developed or assessed in the literature. We identify tools that can be implemented today as well as those currently under development for the improvement in anticoagulation care.

Evaluation of a pharmacist-led outpatient direct oral anticoagulant service

PURPOSE The impact of a pharmacist-led direct oral anticoagulant (DOAC) service on prescription appropriateness and patient adherence was simultaneously evaluated. METHODS In this retrospective analysis, patients age 18 years or older for whom a DOAC was prescribed from September 20, 2013, through December 31, 2014, were identified through electronic medical record review of all DOAC prescriptions within the University of Michigan Health System. Patients had their DOAC therapy managed by a pharmacist-led DOAC service or by their physician (usual care). Primary endpoints included the percentage of patients who had appropriate DOAC therapy prescribed at baseline and at follow-up appointments at 3-6 months. Secondary endpoints included mean medication possession ratios (MPRs). RESULTS A total of 258 patients were included in the study, with 129 in each group. Patients in the pharmacist-led DOAC service were significantly more likely to have an appropriate combination of DOAC and dosage prescribed for their indication at baseline compared with the usual care group (p = 0.009), a finding that persisted at follow up (p = 0.016). There was no significant difference between groups in the number of patients determined to have an appropriate DOAC prescribed for an approved indication (independent of dose) in the pharmacist-led service (95.3%) versus usual care (93.0%) at baseline. Patients in the pharmacist-led service had a greater mean adjusted MPR compared with the usual care group (p = 0.0014) over a median follow-up period of 248 days. CONCLUSION A pharmacist-led DOAC service increased appropriate dosing of DOACs at baseline and follow up as well as patient adherence to therapy.