Brian Haymart

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.

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.

Bridging Anticoagulation Before Colonoscopy: Results of a Multispecialty Clinician Survey.

Bridging Anticoagulation Before Colonoscopy: Results of a Multispecialty Clinician Survey Long-term anticoagulant therapy is essential for stroke prevention among patients with atrial fibrillation, but increasing evidence also points to substantial risk for adverse events, especially when anticoagulation is temporarily interrupted.1,2 The recently published Effectiveness of Bridging Anticoagulation for Surgery Trial confirmed prior observational evidence that using short-acting anticoagulants periprocedurally increases bleeding risk without any reduction in stroke risk.3 Little is known about how medical specialists coordinate the complex decision of which patients to bridge. To investigate this question, we conducted a regional multispecialty, multicenter survey study regarding bridging practices.

SAMe-TT2R2 predicts quality of anticoagulation in patients with acute venous thromboembolism: The MAQI2 experience

A high SAMe-TT2R2 score predicted poor warfarin control and adverse events among atrial fibrillation patients. However, the SAMe-TT2R2 score has not been well validated in venous thromboembolism (VTE) patients. A cohort of 1943 warfarin-treated patients with acute VTE was analyzed to correlate the SAMe-TT2R2 score with time in therapeutic range (TTR) and clinical adverse events. A TTR <60% was more frequent among patients with a high (>2) versus low (0–1) SAMe-TT2R2 score (63.4% vs 52.3%, p<0.0001). A high SAMe-TT2R2 score (>2) correlated with increased overall adverse events (7.9 vs 4.5 overall adverse events/100 patient years, p=0.002), driven primarily by increased recurrent VTE rates (4.2 vs 1.5 recurrent VTE/100 patient years, p=0.0003). The SAMe-TT2R2 score had a modest predictive ability for international normalized ratio (INR) quality and adverse clinical events among warfarin-treated VTE patients. The utility of the SAMe-TT2R2 score to guide clinical decision-making remains to be investigated.

AREDS Formula, Warfarin, and Bleeding: A Case Report from the Michigan Anticoagulation Quality Improvement Initiative

Importance. The anticoagulant warfarin has been shown to interact with other medications, vitamin K containing foods, and over-the-counter products. These interactions may inhibit or potentiate the effect of warfarin, resulting in serious clotting or bleeding events. Observations. We report the case of an 84-year-old woman with atrial fibrillation, prescribed warfarin in May 2010 for stroke prevention. Her international normalized ratio (INR) was stable until April 2013, when she was prescribed AREDS (Age Related Eye Disease Study) formula pills, an eye vitamin compound, to slow the progression of age-related macular degeneration. This change was not reported to the Anticoagulation Service. Eighteen days later, she presented to the ED with groin and back pain and an INR of 10.4. An abdominal CT revealed a retroperitoneal hemorrhage with extension in multiple muscles. Both warfarin and AREDS were discontinued and the patient was discharged to subacute rehabilitation. This case was reviewed by the Anticoagulation Service and actions were taken to prevent similar adverse events. Conclusions. This report provides an example of the potential danger of supplement use, in this case, AREDS formula, in patients prescribed warfarin, and the importance of communicating medication changes to the providers responsible for warfarin management.

Extended International Normalized Ratio testing intervals for warfarin-treated patients

Essentials Warfarin typically requires International Normalized Ratio (INR) testing at least every 4 weeks. We implemented extended INR testing for stable warfarin patients in six anticoagulation clinics. Use of extended INR testing increased from 41.8% to 69.3% over the 3 year study. Use of extended INR testing appeared safe and effective.

Periprocedural Bridging Anticoagulation: Measuring the Impact of a Clinical Trial on Care Delivery

Use of bridging anticoagulation has been shown to be harmful and without benefit in warfarin-treated patients with atrial fibrillation. We performed a quasi-experimental interrupted time series analysis between 2010 and 2017 in the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) collaborative before and after the BRIDGE trial publication (July 2015). Predicted use of bridging at the end of the study period was calculated with and without the effect of the BRIDGE trial after adjustment for patient-level clustering. Predictors of bridging anticoagulation use in the post-BRIDGE trial period were analyzed. In adjusted analyses, the use of bridging anticoagulation declined from a predicted 27.8% (95% confidence interval, 20.5%-35.1%) to 13.6% (95% confidence interval, 9.0%-18.2%) at the end of 2017 (P = .001) in response to the BRIDGE trial. Use of bridging anticoagulation declined similarly among atrial fibrillation patients at low risk for stroke (29.0% to 14.4%) and intermediate or high risk for stroke (38.0%-20.3%). Younger age and a prior history of stroke were independent predictors of bridging anticoagulation use following the BRIDGE trial publication. The BRIDGE trial publication is associated with a rapid and significant decline in the use of periprocedural bridging anticoagulation.

Mind the gap: results of a multispecialty survey on coordination of care for peri-procedural anticoagulation

To understand how physicians from various specialties perceive coordination of care when managing peri-procedural anticoagulation. Cross-sectional survey of cardiologists, gastroenterologists, and primary care physicians (PCPs) in an integrated health system (N = 251). The survey began with a vignette of a patient with atrial fibrillation co-managed by his PCP, cardiologist, and an anticoagulation clinic who must hold warfarin for a colonoscopy. Respondents’ experiences and opinions around responsibilities and institutional support for managing peri-procedural anticoagulation were elicited using multiple choice questions. We examined differences in responses across specialties using Chi square analysis. The response rate was 51% (n = 127). 52% were PCPs, 28% cardiologists, and 21% gastroenterologists. Nearly half (47.2%) of respondents believed that the cardiologist should be primarily responsible for managing peri-procedural anticoagulation, while fewer identified the PCP (25.2%), anticoagulation clinic (21.3%), or gastroenterologist (6.3%; p = 0.09). Respondents across specialties had significantly different approaches to deciding how to manage the clinical case presented (p < 0.001). Most cardiologists (60.0%) would decide whether to offer bridging without consulting with other providers or clinical resources, while most PCPs would decide after consulting clinical resources (57.6%). Gastroenterologists would most often (46.2%) defer the decision to another provider. A majority of all three specialties agreed that their institution could do more to help manage peri-procedural anticoagulation, and there was broad support (88.1%) for anticoagulation clinics’ managing all aspects of peri-procedural anticoagulation. Providers across specialties agree that their institution could do more to help manage peri-procedural anticoagulation, and overwhelmingly support anticoagulation clinics’ taking responsibility.

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the “Real-World” Michigan Anticoagulation Quality Improvement Initiative (MAQI 2 ) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI2 registry taking warfarin, approximately 40–60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

Sociodemographic factors in patients continuing warfarin vs those transitioning to direct oral anticoagulants

Clinical factors and patient preferences are important for selecting oral anticoagulants for venous thromboembolism (VTE) and atrial fibrillation (AF). The relative association of sociodemographic factors with anticoagulant use is unknown. We evaluated a prospective cohort to compare sociodemographic variables in patients who continued on warfarin for AF or VTE to those who transitioned to 1 of the direct oral anticoagulants (DOACs). Adult patients, newly started on warfarin, were enrolled through 6 anticoagulation clinics across Michigan. Of 8468 patients, 53.3% had AF, 45.6% had VTE, and 1.1% had both. Of these, 696 (8.2%) switched from warfarin to a DOAC. There were no significant differences between switchers and nonswitchers for percentage of time with a therapeutic international normalized ratio on warfarin, urban-rural residence status, or health insurance. Switchers were more often white (83.3% vs 77.7%; P < .001), partnered (67.3% vs 59.2%; P < .001), or resided in a zip code with a higher median household income (P < .001). The results show that sociodemographic factors, such as race, partnered status, and income are associated with a patients likelihood of switching to a DOAC vs remaining on warfarin therapy. Although clinical factors predominate, the reason for, and impact of, these observed variations in care requires further investigation.