Background For more than a decade, guidelines have recommended a limited 3 months of anticoagulation for the treatment of provoked venous thromboembolism (VTE). How closely real-world practice ...follows guideline recommendations is not well described. Methods and Results In our multicenter, retrospective cohort study, we evaluated trends in anticoagulation duration for patients enrolled in the MAQI
(Michigan Anticoagulation Quality Improvement Initiative) registry who were receiving anticoagulation for a provoked VTE. The MAQI
registry comprises 6 centers in Michigan that manage patients' long-term anticoagulation. We identified 474 patients on warfarin and 302 patients on direct oral anticoagulants who were receiving anticoagulation for a primary indication of provoked VTE between 2008 and 2020. Using a predefined threshold of 120 days (3 months plus a buffer period), predictors of extended anticoagulant use were identified using multivariable logistic regression. Most patients received >120 days of anticoagulation, regardless of which medication was used. The median (25th-75th percentile) length of treatment for patients taking warfarin was 142 (91-234) days and for direct oral anticoagulants was 180 (101-360) days. Recurrent VTE (odds ratio OR, 2.75 95% CI, 1.67-4.53), history of myocardial infarction (OR, 3.92 95% CI, 1.32-11.7), and direct oral anticoagulant rather than warfarin use (OR, 2.22 95% CI, 1.59-3.08) were independently associated with prolonged anticoagulation. Conclusions In our cohort of patients with provoked VTE, most patients received anticoagulation for longer than the guideline-recommended 3 months. This demonstrates a potential opportunity to improve care delivery and reduce anticoagulant-associated bleeding risk.
Patients on chronic warfarin therapy require regular laboratory monitoring to safely manage warfarin. Recent studies have challenged the need for routine monthly blood draws in the most stable ...warfarin-treated patients, suggesting the safety of less frequent laboratory testing (up to every 12 weeks). De-implementation efforts aim to reduce the use of low-value clinical practices. To explore barriers and facilitators of a de-implementation effort to reduce the use of frequent laboratory tests for patients with stable warfarin management in nurse/pharmacist-run anticoagulation clinics, we performed a mixed-methods study conducted within a state-wide collaborative quality improvement collaborative.
Using a mixed-methods approach, we conducted post-implementation semi-structured interviews with a total of eight anticoagulation nurse or pharmacist staff members at five participating clinic sites to assess barriers and facilitators to de-implementing frequent international normalized ratio (INR) laboratory testing among patients with stable warfarin control. Interview guides were based on the Tailored Implementation for Chronic Disease (TICD) framework. Informed by interview themes, a survey was developed and administered to all anticoagulation clinical staff (n = 62) about their self-reported utilization of less frequent INR testing and specific barriers to de-implementing the standard (more frequent) INR testing practice.
From the interviews, four themes emerged congruent with TICD domains: (1) staff overestimating their actual use of less frequent INR testing (individual health professional factors), (2) barriers to appropriate patient engagement (incentives and resources), (3) broad support for an electronic medical record flag to identify potentially eligible patients (incentives and resources), and (4) the importance of personalized nurse/pharmacist feedback (individual health professional factors). In the survey (65% response rate), staff report offering less frequent INR testing to 56% (46-66%) of eligible patients. Most survey responders (n = 24; 60%) agreed that an eligibility flag in the electronic medical record would be very helpful. Twenty-four (60%) respondents agreed that periodic, personalized feedback on use of less frequent INR testing would also be helpful.
Leveraging information system notifications, reducing additional work load burden for participating patients and providers, and providing personalized feedback are strategies that may improve adoption and utilization new policies in anticoagulation clinics that focus on de-implementation.
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.
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.
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.
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.
Abstract only
Introduction:
Direct Oral Anticoagulants (DOACs) have overtaken warfarin in the treatment of non-valvular Atrial Fibrillation (AF) and venous thromboembolism (VTE). However, there is ...very limited data that explores the safety of DOACs for patients that are morbidly obese (BMI >40).
Methods:
In this multi-center retrospective study, we sought to use the Michigan Anticoagulation Quality Improvement registry (MAQI) to see how treatment of non-valvular AF or VTE with DOAC vs. warfarin affects bleeding in morbidly obese patients. Specifically, we compared average major, clinically relevant non-major (CRNM), and minor bleeding events per 100 patient years that were adjusted for statistically significant baseline characteristics (p<0.05).
Results:
There were a total of 1028 patients with BMI >40 included in the registry between June 2015 and September 2019. 434 patients were treated with DOACs, while 594 patients were treated with warfarin. Baseline characteristics between the two groups included age (61.5 vs 57.8, p<0.001), gender (63.6% vs 61.1% female, p=0.42), race (76.5% vs 64.3% white, p<0.001), and HAS-BLED score (2.3 vs 2.3, p=0.96). The DOAC treated group had a higher event rate of major (4.3 vs 3.7, p=0.006), CRNM (10.7 vs. 7.4, p=0.002), and minor bleeding (19.1 vs. 13.2 p<0.001) compared to the warfarin treated group.
Conclusions:
There is a higher rate of major, CRNM, and minor bleeding in morbidly obese patients treated with DOAC compared to warfarin. Further studies to compare the two anticoagulants and understand bleeding drivers in this population are needed.
Introduction Apixaban and rivaroxaban are the most commonly used direct oral anticoagulants (DOACs) for atrial fibrillation (AF) and venous thromboembolism (VTE). Both have been compared to warfarin ...in landmark clinical trials. However, there are limited comparative efficacy data between these drugs in a real-world setting. We sought to assess patient characteristics and outcomes of apixaban, rivaroxaban, and warfarin in a non-trial based study cohort. Methods Retrospective registry-based cohort of adults starting apixaban, rivaroxaban, or warfarin therapy or switching between these anticoagulants for the indications of VTE and/or non-valvular AF. Through the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2) collaborative of six anticoagulation clinics, warfarin treated patients were followed from January 2009 to June 2023. Four of these clinics contributed DOAC patient data from June 2011 to June 2023. Patients treated with other anticoagulants, with valvular AF, or with less than 3 months of follow-up were excluded. Propensity matched cohorts (apixaban versus warfarin 1:1, rivaroxaban versus warfarin 1:3, and apixaban versus rivaroxaban 1:1) of patients were analyzed based on DOAC use at study enrollment, using 1:1-3:1 matching ratios. Patients were matched based on demographics, social history, comorbidities, medications, bleeding/thrombotic history, indication for anticoagulation, and follow-up. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room (ER) visits, hospitalizations, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression. Results Of 13,435 patients on OAC who met the study inclusion criteria (3,536 on apixaban, 1,395 on rivaroxaban, and 8,504 on warfarin), the average age was 66.7 years (standard deviation SD 14.9 years), 51.1% identified as male, most (58.0%) were on anticoagulation for AF, and the average follow-up was 28.2 months (SD 30.7 months). After propensity matching, 3,527 patients on apixaban were compared to 3,527 patients on warfarin. Any bleeding was similar between groups, but major bleeding was higher with warfarin (3.4 versus 4.7 events/100 patient years, p<0.001). Thrombotic event rates were higher with apixaban (2.6 versus 2.1 events/100 patient years, p=0.026), including the thrombotic subtype of other thrombosis (1.0 versus 0.5 events/100 patient years, p<0.001). Rates of ER visits and hospitalizations for bleeding were higher with warfarin. Mortality was higher with warfarin (3.7 versus 4.4 deaths/100 patient years, p=0.027). After propensity matching, 1,395 patients on rivaroxaban were compared to 4,185 patients on warfarin. Any bleeding and major bleeding were higher with rivaroxaban (37.9 versus 24.9 events/100 patient years, p<0.001; 4.7 versus 3.6 events/100 patient years, p=0.041 respectively). Thrombotic event rates were similar, aside from a higher rate of the thrombotic subtype of other thrombosis with rivaroxaban (1.0 versus 0.3 events/100 patient years, p=0.002). ER visits, hospitalizations, and mortality were similar between rivaroxaban and warfarin. After propensity matching, 1,395 patients on apixaban were compared to 1,395 patients on rivaroxaban. Any bleeding and major bleeding were higher with rivaroxaban (37.9 versus 25.7 events/100 patient years, p<0.001; 4.7 versus 2.6 events/100 patient years, p<0.001). Thrombotic event rates were similar. ER visits occurred more frequently on rivaroxaban (12.8 versus 10.1 events/100 patient years, p=0.003) as did patient mortality (3.5 versus 2.6 deaths/100 patient years, p=0.047). Conclusions For patients on oral anticoagulation for AF and/or VTE we observed that bleeding was highest with rivaroxaban, followed by warfarin, and then apixaban. Rates of thrombosis were higher with apixaban compared to warfarin, seemingly largely driven by “other” thrombotic events. Thrombotic event rates were otherwise similar between apixaban, rivaroxaban, and warfarin. We observed apixaban to be associated with lower mortality than rivaroxaban and warfarin. While these findings should be confirmed with randomized studies, they may have implications for anticoagulant selection.
Clinical trials comparing direct oral anticoagulants (DOAC) to warfarin excluded patients with a history of bariatric surgery. The anatomic changes from bariatric procedures have several effects on ...drug absorption which can have serious consequences for these patients. We sought to describe real-world use of DOACs among adults that had a history of bariatric surgery or underwent a bariatric surgery while receiving a DOAC. We conducted a retrospective case series of adult patients, at a large academic medical center, who initiated any DOAC in 2016 thru 2019 and had a history of bariatric surgery or underwent a bariatric surgery while receiving a DOAC. Thrombotic and bleeding events were described using summary statistics and bleeding severity was described using the International Society on Thrombosis and Haemostasis criteria. Twenty-eight patients met the inclusion criteria of having bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy or gastric band) and receiving a DOAC. Twenty (71.4%) were prescribed apixaban and eight (28.6%) were prescribed rivaroxaban. Seven patients (25%) experienced at least one clinically relevant non-major bleeding event, including one patient (3.6%) that had a major bleeding event. Two patients (7.1%) had a thromboembolic event. Coagulation laboratory studies were infrequently performed at the time of the bleeding or clotting events. Among patients with a history of bariatric surgery, use of DOACs were commonly associated with clinically relevant non-major bleeding events and less commonly associated with major bleeding and thromboembolic events. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in patients that have undergone bariatric surgery. The specific role of coagulation laboratory studies warrants further evaluation.
Background While direct oral anticoagulants (DOACs) may be viewed as simpler to manage then warfarin, they present their own unique management challenges resulting in frequent off-label dosing. It is ...unknown to what extent off-label dosing occurs when a patient is started on a DOAC versus later in their treatment. Objectives We aimed to better characterize when off-label DOAC dosing is occurring and to evaluate the effectiveness of prescribing oversight using a registry-based intervention. Methods We evaluated data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry, a retrospective quality-improvement process using data abstractors, from 2018 to 2022 on the number of “alerts” that are generated in response to dosing deviating from the U.S. Food and Drug Administration instructions for atrial fibrillation (AF) and venous thromboembolism (VTE). Results Among a sample of 789 to 1,022 annual AF patients and 381 to 484 annual VTE patients prescribed a DOAC in the MAQI2 registry, off-label dosing was relatively common. Over the 5-year period (2018–2022), there were 569 alerts for AF patients and 162 alerts for VTE patients. Alerts occurred more frequently during follow-up than at the time of initial prescribing in AF patients (78.2 vs. 21.8%), but more commonly at initial prescribing in VTE patients (59.9 vs. 40.1%). After initial review by quality-improvement abstractors, 19.3% of AF alerts and 14.8% of VTE alerts resulted in contact to the prescriber. When the prescriber was contacted, it led to an intervention about 75% of the time for both populations. The most common intervention was a change in DOAC dosing. Conclusion This study demonstrates the benefit of DOAC prescribing oversight using a registry-based intervention to monitor for off-label dosing for the entirety of the time period a patient is prescribed DOAC, particularly for patients with AF, as off-label prescribing occurs frequently during the follow-up period.
For patients on warfarin for mechanical heart valve replacement, the 2020 American College of Cardiology and American Heart Association Guidelines recommend only adding aspirin in patients with a ...specific indication for antiplatelet therapy. This contrasts with prior guidelines, which recommended concomitant aspirin therapy. We sought to assess the prevalence of guideline-discordant aspirin use among patients on warfarin for mechanical heart valve replacement and to compare adverse event rates among patients with and without concomitant aspirin.
Patients on warfarin for mechanical heart valve replacement were identified from the Michigan Anticoagulation Quality Improvement Initiative registry. Patients with myocardial infarction, percutaneous coronary intervention, or coronary artery bypass within the past 12 months were excluded. Patients were divided into 2 groups based on aspirin use. Patient characteristics and bleeding and thromboembolic outcomes were compared.
Four hundred forty-four patients met the inclusion criteria, with 341 (76.8%) on concomitant aspirin. The aspirin group was older (50.6 vs 46.3 years, P = .028) and had more hypertension (57.8% vs 46.6%, P = .046) but other patient characteristics were similar. The aspirin group had a higher rate of bleeding events (28.3 vs 13.3 per 100 patient-years, P < .001) and bleed-related emergency department visits (11.8 vs 2.9 per 100 patient-years, P = .001) compared with the non-aspirin group. There was no observed difference in rates of ischemic stroke (0.56 vs 0.48 per 100 patient-years, P = .89).
A significant proportion of patients on warfarin for mechanical heart valve replacement are on guideline-discordant aspirin. Aspirin deprescribing in select patients may safely reduce bleeding events.
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