Venous thromboembolism management in people with cystic fibrosis.

BACKGROUND: Rates of venous thromboembolism (VTE) are increasing in people with cystic fibrosis (PwCF). Providers treating VTE in PwCF have reported low confidence concerning anticoagulant drug selection, dose, duration, and drug-drug interactions. As there are currently no published reports regarding management of VTE in PwCF, our objective was to describe the management of VTE in PwCF. METHODS: PwCF and VTE at the University of Utah Health were identified through electronic medical record searches. Patients were categorized into one of three treatment groups: warfarin, direct oral anticoagulant (DOAC), and low molecular weight heparin (LMWH). The primary outcome was episodes of major bleeding. Secondary outcomes included clinically relevant nonmajor (CRNM) bleeding. RESULTS: Nine PwCF with a total of 12 unique VTE episodes were included in the study, with all but one episode associated with a peripherally inserted central catheter (PICC). Of the 12 VTE cases, 25% were treated with warfarin, 50% with a DOAC, and 25% with LMWH. There were no episodes of major bleeding and only one episode of CRNM bleeding (Hemoptysis) in the LMWH group. All anticoagulant doses and durations generally followed guidelines for persons without CF. DOACs were the most common VTE treatment, at doses and duration consistent with guidelines for persons without CF, with no major or CRNM bleeding. CONCLUSION: VTE treatment in PwCF is generally consistent with guidelines for persons without CF with low rates of bleeding. DOACs are a potential option for treatment of VTE in PwCF, but more research is needed.

Clinical outcomes associated with anti-Xa-monitored enoxaparin for venous thromboembolism prophylaxis.

STUDY OBJECTIVE: The objective of the study was to assess clinical outcomes (composite of any venous thromboembolism [VTE], any bleeding, and mortality) associated with anti-Xa monitoring in the 30 days following enoxaparin initiation for VTE prophylaxis. DESIGN: Retrospective cohort study. SETTING: Hospital within an academic healthcare system. PATIENTS: Propensity score-matched hospitalized adults receiving enoxaparin for VTE prophylaxis. INTERVENTION: Low-molecular-weight heparin anti-Xa monitoring. MEASUREMENTS AND MAIN RESULTS: During the 13-month study period, a total of 6611 patients received enoxaparin for VTE prophylaxis, 301 in the anti-Xa monitored group and 6310 in the unmonitored group (4.6% received monitoring). The mean age was 52.9 years and 52% of patients were male. The mean body mass index was 31 kg/m2 and the mean creatinine clearance was 109 mL/min. Twenty percent of patients had active cancer. The most common indication for enoxaparin prophylaxis was hospitalization for medical illness (52%) followed by nonorthopedic surgery (37%). The adjusted odds ratio for the primary outcome comparing monitored to unmonitored patients was 1.26 (95% confidence interval, 0.75-2.11). None of the between-group differences in the individual components of the composite outcome were statistically significant. CONCLUSIONS: Thirty-day clinical outcomes in patients receiving enoxaparin for VTE prophylaxis were not improved by anti-Xa monitoring. Our results support current evidence-based guideline recommendations against anti-Xa monitoring for patients receiving enoxaparin for VTE prophylaxis.

Implementation and evaluation of a warfarin patient self-management (PSM) program among experienced patients in a U.S. academic health system.

Warfarin patient self-management (PSM) is when a patient independently manages their warfarin therapy using a decision-support tool provided by their anticoagulation provider. Clinical trials of PSM, conducted predominantly in Europe, have consistently demonstrated superior efficacy without compromising safety. However, the evidence-based practice of PSM is rarely utilized in the United States (U.S.). We describe initiatives completed to implement a successful PSM program among experienced warfarin-taking patients in a U.S. academic health system by overcoming perceived barriers. The results showed PSM resulted in similar or improved INR control, and an estimated 68% reduction in pharmacist workload.

Impact of type of anticoagulant on clinical outcomes in cancer patients who had atrial fibrillation.

To date, evidence on optimal anticoagulant options in patients with AF who concurrently have active cancer remains elusive. To describe anticoagulant patterns and clinical outcomes among patients with a concomitant diagnosis of AF and cancer. Data were obtained from the University of Utah and Huntsman Cancer Institute (HCI) Hospitals. Patients were included if they had diagnosis of AF and cancer. Outcome was type and pattern of anticoagulant. Clinical outcomes were stroke, bleeding and all-cause mortality. From October 1999 to December 2020, there were 566 AF patients who concurrently had active cancer. Mean age ± standard deviation was 76.2 ± 10.7 and 57.6% were males. Comparing to warfarin, patients who received direct oral anticoagulant (DOACs) were associated with similar risk of stroke (adjusted hazard ratio, aHR 0.8, 95% confidence interval [CI] 0.2-2.7, P = 0.67). On contrary, those who received low-molecular-weight heparin (LMWH) were associated with significantly higher risk of stroke comparing to warfarin (aHR 2.4, 95% CI 1.0-5.6, P = 0.04). Comparing to warfarin, DOACs and LMWH was associated with similar risk of overall bleeding with aHR 1.1 (95% CI 0.7-1.6, P = 0.73) and aHR 1.1 (95% CI 0.6-1.7, P = 0.83), respectively. Patients who received LMWH but not DOACs were associated with increased risk of death as compared to warfarin, aHR 4.5 (95% CI 2.8-7.2, P < 0.001) and 1.2 (95% CI 0.7-2.2, P = 0.47). In patients with active cancer and AF, LMWH, compared to warfarin, was associated with an increased risk of stroke and all-cause mortality. Furthermore, DOACs was associated with similar risk of stroke, bleeding and death as compared to warfarin.

Association of Direct Oral Anticoagulation Management Strategies With Clinical Outcomes for Adults With Atrial Fibrillation.

Importance: Anticoagulation management services (AMSs; ie, warfarin clinics) have evolved to include patients treated with direct oral anticoagulants (DOACs), but it is unknown whether DOAC therapy management services improve outcomes for patients with atrial fibrillation (AF). Objective: To compare outcomes associated with 3 DOAC care models for preventing adverse anticoagulation-related outcomes among patients with AF. Design, Setting, and Participants: This retrospective cohort study included 44 746 adult patients with a diagnosis of AF who initiated oral anticoagulation (DOAC or warfarin) between August 1, 2016, and December 31, 2019, in 3 Kaiser Permanente (KP) regions. Statistical analysis was conducted from August 2021 through May 2023. Exposures: Each KP region used an AMS to manage warfarin but used distinct approaches to DOAC care: (1) usual care (UC) by the prescribing clinician, (2) UC plus an automated population management tool (PMT), or (3) pharmacist-managed AMS care. Propensity scores and inverse probability of treatment weights (IPTWs) were estimated. Direct oral anticoagulant care models were first indirectly compared using warfarin as a common comparator within each region and then directly compared across regions. Main Outcomes and Measures: Patients were followed up until the first occurrence of an outcome (composite of thromboembolic stroke, intracranial hemorrhage, other major bleeding, or death), discontinuation of KP membership, or December 31, 2020. Results: Overall, 44 746 patients were included: 6182 in the UC care model (3297 DOAC; 2885 warfarin), 33 625 in the UC plus PMT care model (21 891 DOAC; 11 734 warfarin), and 4939 in the AMS care model (2089 DOAC; 2850 warfarin). Baseline characteristics (mean [SD] age, 73.1 [10.6] years, 56.1% male, 67.2% non-Hispanic White, median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex] score of 3 [IQR, 2-5]) were well balanced after IPTW. Over a median follow-up of 2 years, patients who received the UC plus PMT or AMS care model did not have significantly better outcomes than those who received UC. The incidence rate of the composite outcome was 5.4% per year for DOAC and 9.1% per year for warfarin for those in the UC group, 6.1% per year for DOAC and 10.5% per year for those in the UC plus PMT group, and 5.1% per year for DOAC and 8.0% per year for those in the AMS group. The IPTW-adjusted hazard ratios (HRs) for the composite outcome comparing DOAC vs warfarin were 0.91 (95% CI, 0.79-1.05) in the UC group, 0.85 (95% CI, 0.79-0.90) in the UC plus PMT group, and 0.84 (95% CI, 0.72-0.99) in the AMS group (P = .62 for heterogeneity across care models). When directly comparing patients receiving DOAC, the IPTW-adjusted HR was 1.06 (95% CI, 0.85-1.34) for the UC plus PMT group vs the UC group and 0.85 (95% CI, 0.71-1.02) for the AMS group vs the UC group. Conclusions and Relevance: This cohort study did not find appreciably better outcomes for patients receiving DOAC who were managed by either a UC plus PMT or AMS care model compared with UC.

Trends in antiplatelet strategies 12-months following coronary stent placement in anticoagulated patients.

BACKGROUND: Antithrombotic guidelines for patients undergoing percutaneous coronary interventions (PCIs) and also requiring anticoagulant medications are evolving. This study describes changes to antithrombotic therapy and associated outcomes 12-months following PCI in patients requiring ongoing anticoagulation therapy. METHODS: Records of patients identified from queries of electronic medical records were manually reviewed to verify changes to antithrombotic therapy from discharge to 12-months and at 12-months following PCI, and episodes of major bleeding, clinically relevant non-major bleeding (CRNMB), major adverse cardiovascular or neurological events (MACNE), and all-cause mortality outcomes during an additional 6-months follow-up. RESULTS: Patients (n = 120) receiving anticoagulation therapy at 12-months post PCI were classified into the following groups according to antiplatelet therapy status: no antiplatelet therapy (n = 16), single antiplatelet therapy (SAPT) (n = 85), and dual antiplatelet therapy (DAPT) (n = 19). Between 12- and 18-months following PCI there were 2 major bleeds, 7 CRNMB, 6 MACNE, 2 venous thromboembolisms, and 5 deaths. All but one bleeding episode occurred in the SAPT group. The odds of remaining on DAPT at 12-months were higher in patients who had PCI for acute coronary syndrome (odds ratio [OR] 2.91, 95% confidence interval [CI] 0.96, 8.77), and in those experiencing MACNE in the 12-months following PCI (OR 1.95, 95% CI 0.67, 5.66), but these associations were not statistically significant. CONCLUSION: Most anticoagulated patients were continued on antiplatelet therapy 12-months post PCI. Bleeding was numerically more common in anticoagulated patients continuing SAPT therapy beyond 12 months. There was significant variability in antithrombotic prescribing patterns 12-months post PCI suggesting a potential opportunity for standardizing care in this patient population.

A scoping review of direct oral anticoagulant ambulatory management practices.

Models of care for managing direct oral anticoagulant (DOAC) therapy are evolving. Little is known of what services are provided by anticoagulation managements services (AMS) for DOACs, or what necessitates comprehensive DOAC management and what differentiates it from usual care. The purpose of this scoping review was to describe services, management, or monitoring of DOACs distinct from prescriber-managed or usual care of DOACs. This scoping review reported followed the 2018 Preferred Reporting Items for Systematic Review and Meta-Analyses extension for scoping reviews (PRISMA-ScR). We searched PubMed, CINAHL, and EMBASE from inception to November 2020 to identify articles of interest. No language restriction was applied. Articles were included if they provided a description of DOAC management services, and described longitudinal anticoagulation follow-up that occurred in ambulatory care, community, or outpatient-related settings. Data was extracted from a total of 23 articles. The specific types of DOAC management interventions provided varied across the included studies. Nearly all studies described some form of DOAC therapy appropriateness assessment. Other common interventions included assessments of DOAC therapy compliance, adverse event triage and management, assessment of DOAC dosing appropriateness, periprocedural management of DOAC therapy, educational interventions, and renal function monitoring. A variety of DOAC management interventions were identified, but additional studies are needed to help health systems decide whether specific interventions performed by dedicated services are preferred over the usual care provided by clinicians prescribing DOAC therapy.

Direct Oral Anticoagulants in Obese Patients with Venous Thromboembolism: Results of an Expert Consensus Panel.

In clinical practice, direct oral anticoagulants (DOACs) are increasingly used for venous thromboembolism treatment and prevention. A substantial proportion of patients with venous thromboembolism are also obese. International guidance published in 2016 stated that DOACs could be used in standard doses in patients with obesity up to a body mass index (BMI) of 40 kg/m2, but should not be used in those with severe obesity (BMI >40 kg/m2) owing to limited supporting data at the time. Although updated guidance in 2021 removed this limitation, some health care providers still avoid DOACs even in patients with lower levels of obesity. Furthermore, there are still evidence gaps regarding treatment of severe obesity, the role of peak and trough DOAC levels in these patients, use of DOACs after bariatric surgery, and appropriateness of DOAC dose reduction in the setting of secondary venous thromboembolism prevention. This document describes proceedings and outcomes of a multidisciplinary panel convened to review these and other key issues regarding DOAC use for treatment or prevention of venous thromboembolism in individuals with obesity.

Prevalence of antiphospholipid antibody syndrome misclassification in an academic health system.

PURPOSE: Antiphospholipid Antibody Syndrome (APS) is a complex autoimmune disorder that includes a combination of laboratory criteria and clinical events (thrombosis, pregnancy complications). Accurate classification is essential, as APS patients may have limited oral anticoagulant options and requires indefinite anticoagulation. The prevalence of inaccurate APS misclassification is unknown. This study sought to determine the proportion of patients in an academic health-system who formally met APS criteria. METHODS: This retrospective cohort study included any patient within the University of Utah Health system who had an International Classification of Diseases-10 code for APS, between January 1, 2016 and June 30, 2020. Manual chart review was performed to assess the appropriateness of the APS classification by laboratory and clinical criteria. RESULTS: Of the 184 patients identified, 59 (32.1 %) formally met APS criteria, while 69 (37.5 %) did not meet criteria. The remaining 56 (30.4 %) patients lacked enough information in their medical records to decide on appropriateness of APS classification. The most prevalent reason for inappropriate APS classification in the 69 patients identified was incorrect interpretation of lab values as positive (62; 89.9 %), followed by lack of repeat confirmation testing (32; 46.4 %). CONCLUSION: The results of this single-center study indicate that only one-third of patients with presumed APS met classification criteria. This was predominantly due to incorrect collection or interpretation of APS laboratory data. One-third had insufficient medical record data to determine APS classification, which impairs clinical decision-making. This suggests more education or implementation of anticoagulation stewardship is needed to ensure accurate APS classification and proper management of anticoagulation therapy.

Effectiveness and safety of direct oral anticoagulants in patients with venous thromboembolism and creatinine clearance < 30 mL/min.

The few studies that compared direct oral anticoagulants (DOAC) vs. warfarin in the setting of advanced renal insufficiency have focused on patients with atrial fibrillation. The purpose of this observational, matched, cohort study of patients was to assess the effectiveness and safety of DOAC vs. warfarin for the treatment of venous thromboembolism (VTE) among patients with a creatinine clearance (CrCl) < 30 mL/min. This observational, cohort study included patients with VTE and CrCl < 30 mL/min who were newly initiated on a DOAC or warfarin between January 1, 2016 and December 31, 2020. DOAC patients were matched up to 1:2 to warfarin patients. Primary outcome was a composite of recurrent VTE, clinically-relevant bleeding, ischemic stroke, and all-cause mortality. Adjusted conditional, multivariate Cox proportional hazards modeling was used to assess outcomes. 626 DOAC patients were matched to 1071 warfarin patients. DOAC patients had a higher mean age, higher mean baseline CrCl, and were less likely to have been receiving dialysis. There was no statistically significant difference in the composite outcome between groups (adjusted hazard ratio [aHR] 1.13, 95% confidence interval [CI] 0.87-1.47) or in the individual components of the composite (all HR 95% CI crossed 1.00). Identification of statistically non-significant rates of bleeding and thromboembolic outcomes suggest that the use of DOAC or warfarin is reasonable in patients with VTE and CrCl < 30 mL/min.

Antiplatelet therapy indication in patients also prescribed direct oral anticoagulants.

Direct oral anticoagulants (DOACs) are standard of care for venous thromboembolism (VTE) treatment and stroke prevention in atrial fibrillation (AF). Adding antiplatelet therapy (APT) to an oral anticoagulant (OAC) causes a 2-fold increase in major bleeding. As such, recent guidelines recommend limiting the duration and indication of combined therapy in patients already on an OAC. Despite these recommendations, approximately one-third of anticoagulated patients are prescribed concomitant APT. University of Utah Health patients receiving DOAC + APT between August 1, 2019 and November 30, 2019 were included. These were categorized into four groups by APT indication: primary atherosclerotic cardiovascular disease (ASCVD) prevention, ASCVD-no percutaneous coronary intervention (PCI), ASCVD-PCI ≤ 12 months prior, ASCVD-PCI > 12 months prior. The primary outcome was the proportion of DOAC patients receiving concomitant APT for each indication. During the study period, 347 patients received DOAC + APT, primarily for AF (59.1%) or VTE (33.1%), and the most common DOAC was apixaban (76.7%).The most common indication for APT was ASCVD-no PCI (47.3%), followed by ASCVD-PCI > 12 months prior (30.8%), primary ASCVD prevention (18.7%), and ASCVD-PCI ≤ 12 months prior (1.7%). Five patients (1.4%) were on APT with unclear indication. Based on recent guidelines limiting indications and duration of APT added to anticoagulation, over 95% of patients in this single-center study warranted re-assessment of APT indication, with stable ASCVD and primary prevention being prime targets for APT de-prescribing. This study highlights the tremendous potential to improve patient safety and reduce bleeding harm.

Incremental net monetary benefit of direct oral anticoagulants for the prevention of venous thromboembolism after total knee or hip replacement: A systematic review and meta-analysis.

INTRODUCTION: This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using direct oral anticoagulants (DOACs) for the prevention of venous thromboembolism (VTE) in patients undergoing total knee or hip replacements (TKR or THR). MATERIALS AND METHODS: We performed a comprehensive search in several databases published before June 2021. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year of DOACs compared to low molecular-weight heparins (LMWHs) or other anticoagulant agents for the prevention of VTE after TKR or THR. Risk of bias was also assessed using the biases in economic studies (ECOBIAS) checklist. Various monetary units were converted to purchasing power parity, adjusted to 2020 US dollars. The INBs were pooled across studies using a random-effects model, stratified by high-income countries (HICs) and low- and middle-income countries (LMICs). Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 49 comparisons (TKR = 25 and THR = 24) from 16 studies was included. In HICs, DOACs were cost-effective compared to LMWHs from the health care system/payer perspective for the prevention of VTE after both TKR and THR with corresponding INBs (95 % CI; I2) of $231.91 ($178.71, $285.11; 0 %) and $254.99 ($159.20, $350.77; 27.79 %), respectively. In LMICs, DOACs were not cost-effective compared to LMWHs for both TKR and THR with the INBs of $94.13 (-$40.21, $228.47; 97.04 %) and $80.55 (-$157.37, $318.47; 99.78 %), respectively. No evidence of small-study effects was identified in any analyses. The cost-effectiveness of using DOACs for TKR and THR in HICs was robust across a series of sensitivity analyses. CONCLUSIONS: DOACs were cost-effective as compared to LMWHs for VTE prophylaxis following TKR and THR surgeries in HICs. Further studies from LMICs are warranted.

Randomized evaluation of decision support interventions for atrial fibrillation: Rationale and design of the RED-AF study.

BACKGROUND: Shared decision making (SDM) improves the likelihood that patients will receive care in a manner consistent with their priorities. To facilitate SDM, decision aids (DA) are commonly used, both to prepare a patient before their clinician visit, as well as to facilitate discussion during the visit. However, the relative efficacy of patient-focused or encounter-based DAs on SDM and patient outcomes remains largely unknown. We aim to directly estimate the comparative effectiveness of two DA's on SDM observed in encounters to discuss stroke prevention strategies in patients with atrial fibrillation (AF). METHODS: The study aims to recruit 1200 adult patients with non-valvular AF who qualify for anticoagulation therapy, and their clinicians who manage stroke prevention strategies, in a 2x2 cluster randomized multi-center trial at six sites. Two DA's were developed as interactive, online, non-linear tools: a patient decision aid (PDA) to be used by patients before the encounter, and an encounter decision aid (EDA) to be used by clinicians with their patients during the encounter. Patients will be randomized to PDA or usual care; clinicians will be randomized to EDA or usual care. RESULTS: Primary outcomes are quality of SDM, patient decision making, and patient knowledge. Secondary outcomes include anticoagulation choice, adherence, and clinical events. CONCLUSION: This trial is the first randomized, head-to-head comparison of the effects of an EDA versus a PDA on SDM. Our results will help to inform future SDM interventions to improve patients' AF outcomes and experiences with stroke prevention strategies.

Exploring clinician perspectives on patients with atrial fibrillation who are not prescribed anticoagulation therapy.

Objective: To explore themes underlying why anticoagulants are under-prescribed for stroke prevention in atrial fibrillation (AF) patients from the clinician's perspective and characteristics of those patients. Methods: Clinicians at the University of Utah Health system were recruited for semi-structured 15-minute interviews. An interview guide focused on anticoagulant prescribing practices for patients with AF. Interviews were transcribed verbatim. Two reviewers independently coded passages corresponding with key themes. Results: Eleven practitioners were interviewed from cardiology, internal medicine, and family practice. Five themes were found: the role of compliance in anticoagulation decision making, the role of pharmacists in supporting clinicians, the use of shared decision making and risk communication, risk of bleeding as the main barrier to taking anticoagulants, and the variety of reasons patients have for not starting or discontinuing anticoagulants. Conclusion: Fear of bleeding was the foremost reason underlying anticoagulant underutilization in patients with AF followed by compliance, and patient worries. Communication between patients and clinicians as well as interdisciplinary teamwork are key to understanding and improving anticoagulant prescribing in AF. Innovation: Our study was the first to assess the role pharmacists play in prescribing clinician's decisions surrounding anticoagulant use in AF. Pharmacists could play an important collaborative role in SDM.

Replacement of traditional prothrombin time monitoring with the new Fiix prothrombin time increases the efficacy of warfarin without increasing bleeding. A review article.

The antithrombotic effect of vitamin K antagonists (VKA) depends on controlled lowering of the activity of factors (F) II and X whereas reductions in FVII and FIX play little role. PT-INR based monitoring, however, is highly influenced by FVII, which has the shortest half-life of vitamin K-dependent coagulation factors. Hence, variability in the anticoagulant effect of VKA may be partly secondary to an inherent flaw of the traditional monitoring test itself. The Fiix prothrombin time (Fiix-PT) is a novel test that is only sensitive to reductions in FII and FX and is intended to stabilize the VKA effect. Two clinical studies have now demonstrated that when warfarin is monitored with the Fiix-PT based normalized ratio (Fiix-NR) instead of PT-INR, anticoagulation is stabilized and less testing and fewer dose adjustments are needed. Furthermore, the relative risk of thromboembolism was reduced by 50-56% in these studies without an increase in major bleeding.

Outcomes of isolated distal thrombosis managed with serial compression ultrasonography.

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT) is a common subtype of deep vein thrombosis (DVT). Consensus guidelines provide conflicting recommendations for IDDVT management; some recommend anticoagulant treatment, while others suggest serial compression ultrasonography (CUS) monitoring for patients not at "high risk" of proximal extension. The purpose of this study was to describe outcomes of serial CUS-monitored IDDVT and identify risk factors for proximal thrombus extension or anticoagulant treatment initiation. METHODS: A retrospective descriptive study was conducted using electronic data from University of Utah Health. Adult subjects with objectively confirmed, serial CUS-monitored IDDVT were included. Subjects were followed for 30 days for occurrence of a composite outcome of proximal thrombus extension or anticoagulant treatment initiation. Descriptive statistics were used to summarize characteristics of the study population. Characteristics were compared across outcome groups using inferential statistics. RESULTS: A total of 182 subjects were included, with 53 subjects (29.1%) experiencing the composite outcome. Of these, 12 (22.6%) experienced proximal thrombus extension and 41 (77.4%) initiated anticoagulant treatment. A prior history of venous thromboembolism (VTE) was significantly higher in those who experienced the composite outcome than in those who did not. CONCLUSIONS: Our results suggest that 70% of patients with serial CUS-monitored IDDVT did not experience thrombus extension or require anticoagulant treatment within 30 days of diagnosis, regardless of risk factors for proximal extension. Serial CUS monitoring may be a useful management strategy for IDDVT. A history of VTE may identify patients more likely to experience proximal thrombus extension or require anticoagulation.