[Perioperative management for fracture in a child with homozygous congenital protein C deficiency].

Congenital protein C (PC) deficiency is one type of hereditary thrombosis. Patients with hereditary thrombosis are at high risk for thrombosis in the perioperative period, but a standard management strategy has not been established. Here we report a case of perioperative management of a fracture in a child with homozygous congenital PC deficiency. The patient was a 3-year-old boy who was diagnosed with congenital PC deficiency at birth. He sustained a traumatic supracondylar fracture of the right humerus and underwent emergency surgery. To prepare for open surgery for fixation of the fracture, warfarin was discontinued, and an activated PC (APC) concentrate was used in combination with vitamin K antagonism. However, warfarin was administered during the scheduled nail extraction because the operation was minimally invasive. No thrombotic or bleeding complications occurred in either operation. In emergency surgery in patients with congenital PC deficiency, the combination of vitamin K and APC concentrate is considered a maintenance option for PC deficiency. Postoperative PT-INR control was difficult in our patient due to the administration of vitamin K and withdrawal of warfarin, and this issue must be addressed in the future. Further case experience is desirable to standardize perioperative management.

Repeated Measurement of the Novel Atrial Biomarker BMP10 (Bone Morphogenetic Protein 10) Refines Risk Stratification in Anticoagulated Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial.

BACKGROUND: BMP10 (bone morphogenic protein 10) has emerged as a novel biomarker associated with the risk of ischemic stroke and other outcomes in patients with atrial fibrillation (AF). The study aimed to determine if repeated BMP10 measurements improve prognostication of cardiovascular events in patients with AF. METHODS AND RESULTS: BMP10 was measured using a prototype Elecsys immunoassay in plasma samples collected at randomization and after 2 months in patients with AF randomized to apixaban or warfarin in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial (n=2878). Adjusted Cox-regression models were used to evaluate the association between 2-month BMP10 levels and outcomes. BMP10 levels increased by 7.8% (P<0.001) over 2 months. The baseline variables most strongly associated with BMP10 levels at 2 months were baseline BMP10 levels, body mass index, sex, age, creatinine, diabetes, warfarin treatment, and AF-rhythm. During median 1.8 years follow-up, 34 ischemic strokes/systemic embolism, 155 deaths, and 99 heart failure hospitalizations occurred. Comparing the third with the first sample quartile, higher BMP10 levels at 2 months were associated with higher risk of ischemic stroke (hazard ratio [HR], 1.33 [95% CI, 0.67-2.63], P=0.037), heart failure (HR, 1.91 [95% CI, 1.17-3.12], P=0.012) and all-cause death (HR, 1.61 [95% CI, 1.17-2.21], P<0.001). Adding BMP10 levels at 2 months on top of established risk factors and baseline BMP10 levels improved the C-indices for ischemic stroke/systemic embolism (from 0.73 to 0.75), heart failure hospitalization (0.76-0.77), and all-cause mortality (0.70-0.72), all P<0.05. CONCLUSIONS: Elevated levels of BMP10 at 2 months strengthened the associations with the risk of ischemic stroke, hospitalization for heart failure, and all-cause mortality. Repeated measurements of BMP10 may further refine risk stratification in patients with AF.

Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.

BACKGROUND: Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery. METHODS: Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed. RESULTS: Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability. CONCLUSION: The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis-a nationwide cohort study.

BACKGROUND: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. METHODS: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. RESULTS: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. CONCLUSIONS: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Precision medicine in cardiovascular therapeutics: Evaluating the role of pharmacogenetic analysis prior to drug treatment.

Pharmacogenomics is the examination of how genetic variation influences drug metabolism and response, in terms of both efficacy and safety. In cardiovascular disease, patient-specific diplotypes determine phenotypes, thereby influencing the efficacy and safety of drug treatments, including statins, antiarrhythmics, anticoagulants and antiplatelets. Notably, polymorphisms in key genes, such as CYP2C9, CYP2C19, VKORC1 and SLCO1B1, significantly impact the outcomes of treatment with clopidogrel, warfarin and simvastatin. Furthermore, the CYP2C19 polymorphism influences the pharmacokinetics and safety of the novel hypertrophic cardiomyopathy inhibitor, mavacamten. In this review, we critically assess the clinical application of pharmacogenomics in cardiovascular disease and delineate present and future utilization of pharmacogenomics. This includes insights into identifying missing heritability, the integration of whole genome sequencing and the application of polygenic risk scores to enhance the precision of personalized drug therapy. Our discussion encompasses health economic analyses that underscore the cost benefits associated with pre-emptive genotyping for warfarin and clopidogrel treatments, albeit acknowledging the need for further research in this area. In summary, we contend that cardiovascular pharmacogenomic analyses are underpinned by a wealth of evidence, and implementation is already occurring for some of these gene-drug pairs, but as with any area of medicine, we need to continually gather more information to optimize the use of pharmacogenomics in clinical practice.

Pharmacogenetic considerations in therapy with novel antiplatelet and anticoagulant agents.

Antiplatelets and anticoagulants are extensively used in cardiovascular medicine for the prevention and treatment of thrombosis in the venous and arterial circulations. Wide inter-individual variability has been observed in response to antiplatelets and anticoagulants, which triggered researchers to investigate the genetic basis of this variability. Data from extensive pharmacogenetic studies pointed to strong evidence of association between polymorphisms in candidate genes and the pharmacokinetics and pharmacodynamic action and clinical response of the antiplatelets clopidogrel and the anticoagulant warfarin. In this review, we conducted an extensive search on Medline for the time period of 2009-2023. We also searched the PharmGKB website for levels of evidence of variant-drug combinations and for drug labels and clinical guidelines. We focus on the pharmacogenetics of novel antiplatelets and anticoagulants while excluding acetylsalicylic acid, warfarin and heparins, and discuss the current knowledge with emphasis on the level of evidence.

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial.

INTRODUCTION: Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit. METHODS AND ANALYSIS: The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient. ETHICS AND DISSEMINATION: The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.

Effects of sodium ferulate for injection on anticoagulation of warfarin in rats in vivo.

BACKGROUND: Herb-drug interactions may result in increased adverse drug reactions or diminished drug efficacy, especially for drugs with a narrow therapeutic index such as warfarin. The current study investigates the effects of sodium ferulate for injection (SFI) on anticoagulation of warfarin from aspects of pharmacodynamics and pharmacokinetics in rats and predicts the risk of the combination use. METHODS: Rats were randomly divided into different groups and administered single- or multiple-dose of warfarin (0.2 mg/kg) with or without SFI of low dose (8.93 mg/kg) or high dose (26.79 mg/kg). Prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected by a blood coagulation analyzer, and international normalized ratio (INR) values were calculated. UPLC-MS/MS was conducted to measure concentrations of warfarin enantiomers and pharmacokinetic parameters were calculated by DAS2.0 software. RESULTS: The single-dose study demonstrated that SFI alone had no effect on coagulation indices, but significantly decreased PT and INR values of warfarin when the two drugs were co-administered (P < 0.05 or P < 0.01), while APTT values unaffected (P > 0.05). Cmax and AUC of R/S-warfarin decreased but CL increased significantly in presence of SFI (P < 0.01). The multiple-dose study showed that PT, APTT, INR, and concentrations of R/S-warfarin decreased significantly when SFI was co-administered with warfarin (P < 0.01). Warfarin plasma protein binding rate was not significantly changed by SFI (P > 0.05). CONCLUSIONS: The present study implied that SFI could accelerate warfarin metabolism and weaken its anticoagulation intensity in rats.

Short-term antiplatelet versus anticoagulant therapy after left atrial appendage closure: a systematic review and meta-analysis.

This meta-analysis compared the efficacy and safety of different antithrombotic regimens after left atrial appendage closure (LAAC). PubMed, Embase, Medline, Cochrane Library databases were systematically searched from their inception to March 2023. Patients were divided into short-term oral anticoagulation (OAC) group and antiplatelet therapy (APT) group. The incidence of events were performed using RevMan 5.4. The events including device-related thrombus (DRT), ischemic stroke/systemic embolization (SE), major bleeding, any bleeding, any major adverse event and all-cause mortality. Subgroup analysis were based on OAC alone or OAC plus single antiplatelet therapy (SAPT) in OAC group. Oral anticoagulants include warfarin and direct oral anticoagulant (DOAC). Fourteen studies with 35,166 patients were included. We found that the incidence of DRT (OR = 0.49, 95% CI 0.36-0.66, P＜0.0001) and all-cause mortality (OR = 0.71, 95% CI 0.57-0.89, P = 0.002) were significantly lower in OAC group than APT group. However, there was no statistical differences in the incidence rates of ischemic stroke/SE (OR = 0.77, 95% CI 0.49-1.20, P = 0.25), major bleeding (OR = 0.84, 95% CI 0.55-1.27, P = 0.84), any bleeding (OR = 0.83, 95% CI 0.56-1.22, P = 0.34) and any major adverse event (OR = 0.56, 95% CI 0.30-1.03, P = 0.06) in the two groups. Subgroup analysis found that the incidence of DRT, all-cause mortality and any major adverse event in OAC monotherapy were lower than that in APT group (P＜0.05), but not statistically different from other outcome. The incidence of DRT, all-cause mortality, any major adverse event and any bleeding in DOAC were significantly better than APT group (P＜0.05). While warfarin only has better incidence of DRT than APT (P＜0.05), there was no statistical difference between the two groups in other outcome (P＞0.05). The incidence of DRT was significantly lower than APT group (P＜0.05), major bleeding were higher, and the rest of the outcome did not show any statistically significant differences(P＞0.05) when OAC plus SAPT. Based on the existing data, short-term OAC may be favored over APT for patients who undergo LAAC. DOAC monotherapy may be favored over warfarin monotherapy or OAC plus APT, when selecting anticoagulant therapies.

Oropharyngeal Hemorrhage and Difficult Airway Management: A Decision Not to Intubate.

BACKGROUND: Bleeding in the upper airways is an important cause of airway-related death. A higher incidence of airway management failure and complications after intubation attempts in the emergency department (ED) had been suggested. Airway management of patients with active oropharyngeal hemorrhage may be challenging, leading the clinician to modify the approach. CASE REPORT: A 57-year-old woman presented to the ED with oropharyngeal hemorrhage after an extensive invasive dental procedure. She was on long-term warfarin therapy due to aortic and mitral valve replacement, which she suspended 5 days prior and restarted the day after the procedure. Besides the active bleeding, swelling, and hematoma of the face, the patient had other signs of "difficult airway," so there were serious questions on when and how to manage the airway. Several strategies to address the airway were considered, the main point being an early versus later intubation. As the patient remained clinically stable, she was conservatively managed with local hemostasis and coagulopathy reversal. The patient was transferred to the intensive care unit, where she remained stable and was successfully discharged after restart on warfarin. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When faced with an oropharyngeal hemorrhage, emergency physicians may be compelled to secure and protect the airway. This could be achieved by planning several strategies. Nevertheless, in selected patients, and considering the circumstances, not addressing the airway is a reasonable and justifiable alternative.

Clinical outcomes and anticoagulation therapy in elderly non-valvular atrial fibrillation and heart failure patients.

AIMS: Atrial fibrillation (AF) and heart failure (HF) often coexist. Older age is strongly associated with stroke, HF, and mortality. The association between coexistence of HF and a risk of clinical outcomes and the effectiveness of anticoagulation therapy including direct oral anticoagulants (DOACs) in elderly patients with AF and HF have not been investigated. We aimed to evaluate 2 years of outcomes and to elucidate the efficacy of DOACs or warfarin in elderly AF patients in the All Nippon AF In the Elderly (ANAFIE) Registry with and without a history of HF. METHODS AND RESULTS: The ANAFIE Registry is a multicentre, prospective observational study following elderly non-valvular AF patients aged ≥75 years for 2 years. Hazard ratios (HRs) were calculated based on the presence or absence of an HF diagnosis and DOAC or warfarin use at enrolment. Among 32 275 eligible patients, 12 116 (37.5%) had been diagnosed with HF. Patients with HF had significantly higher rates of HF hospitalization or cardiovascular death (HR 1.94, P < 0.001), cardiovascular events (HR 1.59, P < 0.001), cardiovascular death (HR 1.49, P < 0.001), all-cause death (HR 1.32, P < 0.001), and net clinical outcome including stroke/systemic embolism, major bleeding, and all-cause death (HR 1.23, P < 0.001), compared with those without HF; however, HRs for stroke/systemic embolism (HR 0.96, P = 0.56) and major bleeding (HR 1.14, P = 0.13) were similar. DOAC use was associated with a low risk of stroke/systemic embolism (HR 0.86, P = 0.19 in HF; HR 0.79, P = 0.016 in non-HF; P for interaction = 0.56), major bleeding (HR 0.71, P = 0.008 in HF; HR 0.75, P = 0.016 in non-HF; P for interaction = 0.74), HF hospitalization or cardiovascular death (HR 0.81, P < 0.001 in HF; HR 0.78, P < 0.001 in non-HF; P for interaction = 0.26), cardiovascular events (HR 0.83, P < 0.001 in HF; HR 0.82, P = 0.001 in non-HF; P for interaction = 0.65), cardiovascular death (HR 0.84, P = 0.12 in HF; HR 0.75, P = 0.035 in non-HF; P for interaction = 0.18), all-cause death (HR 0.89, P = 0.082 in HF; HR 0.80, P = 0.001 in non-HF; P for interaction = 0.091), and net clinical outcome (HR 0.88, P = 0.019 in HF; HR 0.81, P < 0.001 in non-HF; P for interaction = 0.21) compared with warfarin, irrespective of the presence or absence of HF. Analysis using the propensity score matching method showed similar associations. CONCLUSIONS: Non-valvular AF patients aged ≥75 years with a history of HF had higher risks of cardiovascular events and mortality. DOACs were favourable to warfarin regardless of the coexistence of HF. These results might encourage the use of DOACs in elderly patients with non-valvular AF with or without HF.

A comprehensive comparison of the safety and efficacy of drugs in the treatment of idiopathic pulmonary fibrosis: a network meta-analysis based on randomized controlled trials.

OBJECTIVE: Randomized controlled trials(RCTs) of multiple drugs for Idiopathic pulmonary fibrosis(IPF) have been reported and achieved a certain degree of efficacy, however, the difference in safety and efficacy of them for IPF is not yet well understood. The aim of this network meta-analysis is to assess their safety and efficacy in the treatment of IPF and differences in this safety and efficacy comprehensively. METHODS: The PubMed, EMbase, CENTRAL and MEDLINE were retrieved to find out the RCTs of drugs in the treatment of IPF. The retrieval date is from construction to November 10, 2022. Stata 14.0 and RevMan 5.3 was used for statistical analysis. REGISTRATION NUMBER: CRD42023385689. RESULTS: Twenty-four studies with a total of 6208 patients were finally included, including RCTs of 13 drugs. The results of safety showed that there' s no difference in the incidence of SAEs of 13 drugs treated with IPF compared to placebo (P>0.05), and it's also found that Warfarin had a higher all-cause mortality for IPF than placebo (OR = 5.63, 95% CI [1.54 to 20.55]). SUCRA' s scatterplot showed that Pirfenidone, Nintedanib, Sildenafil and Imatinib were lower than placebo, and Warfarin, Ambrisentan and N-acetylcysteine were higher than placebo. The results of effectiveness showed that Nintedanib (MD = -0.08, 95% CI [-0.12 to -0.04]) improved FVC (L)absolute change from baseline in patients better than placebo, and Nintedanib (OR=1.81, 95% CI [1.23 to 2.66]), Pirfenidone (OR=1.85, 95%CI [1.26 to 2.71]) and Pamrevlumab (OR=4.11, 95% CI [1.25 to 13.58]) improved the proportion of patients with a decline in FVC ≥10% predicted better than placebo. SUCRA' s scatterplot showed that Pamrevlumab, Pirfenidone and Nintedanib were lower than placebo, and Warfarin and Ambrisentan were higher than placebo. CONCLUSION: Compared with other drugs, Nintedanib and Pirfenidone can significantly slow the decline of lung function in patients with IPF, and the safety is higher. Therefore, they can be further promoted in clinical practice. Warfarin and Ambrisentan shouldn't be used clinically for IPF as the safety and efficacy of them are poor compared to other drugs and placebo. Pamrevlumab may become important drugs for the treatment of IPF in the future.

Impact of frailty on the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a nationwide cohort study.

AIMS: Data on non-vitamin K antagonist oral anticoagulants (NOACs) use in patients with atrial fibrillation (AF) and frailty are scarce. Therefore, the impact of frailty on AF-related outcomes and benefit-risk profiles of NOACs in patients with frailty were investigated. METHODS AND RESULTS: AF patients initiating anticoagulation between 2013 and 2019 were included using Belgian nationwide data. Frailty was assessed with the Claims-based Frailty Indicator. Among 254 478 anticoagulated AF patients, 71 638 (28.2%) had frailty. Frailty was associated with higher all-cause mortality risks [adjusted hazard ratio (aHR) 1.48, 95% confidence interval (CI) (1.43-1.54)], but not with thromboembolism or bleeding. Among subjects with frailty (78 080 person-years of follow-up), NOACs were associated with lower risks of stroke or systemic embolism (stroke/SE) [aHR 0.77, 95%CI (0.70-0.86)], all-cause mortality [aHR 0.88, 95%CI (0.84-0.92)], and intracranial bleeding [aHR 0.78, 95%CI (0.66-0.91)], a similar major bleeding risk [aHR 1.01, 95%CI (0.93-1.09)], and higher gastrointestinal bleeding risk [aHR 1.19, 95%CI (1.06-1.33)] compared with VKAs. Major bleeding risks were lower with apixaban [aHR 0.84, 95%CI (0.76-0.93)], similar with edoxaban [aHR 0.91, 95%CI (0.73-1.14)], and higher with dabigatran [aHR 1.16, 95%CI (1.03-1.30)] and rivaroxaban [aHR 1.11, 95%CI (1.02-1.21)] compared with VKAs. Apixaban was associated with lower major bleeding risks compared with dabigatran [aHR 0.72, 95%CI (0.65-0.80)], rivaroxaban [aHR 0.78, 95%CI (0.72-0.84)] and edoxaban [aHR 0.74, 95%CI (0.65-0.84)], but mortality risk was higher compared with dabigatran and edoxaban. CONCLUSION: Frailty was an independent risk factor of death. Non-vitamin K antagonist oral anticoagulants had better benefit-risk profiles than VKAs in patients with frailty, especially apixaban, followed by edoxaban.

Trends in Drug Spending of Oral Anticoagulants for Atrial Fibrillation, 2014-2021.

INTRODUCTION: This study documents cost trends in oral anticoagulants (OAC) in patients with newly diagnosed atrial fibrillation. METHODS: Using MarketScan databases, the mean annual patients' out-of-pocket costs, insurance payments, and the proportion of patients initiating OAC within 90 days from atrial fibrillation diagnosis were calculated from July 2014 to June 2021. Costs of OACs (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) and the payments by three insurance types (commercial payers, Medicare, and Medicaid) were calculated. Patients' out-of-pocket costs and insurance payments were adjusted to 2021 prices. Joinpoint regression models were used to test trends of outcomes and average annual percent changes (AAPC) were reported. Data analyses were performed in 2022-2023. RESULTS: From July 2014 to June 2021, the mean annual out-of-pocket costs of any OAC increased for commercial insurance (AAPC 3.0%) and Medicare (AAPC 5.1%) but decreased for Medicaid (AAPC -3.3%). The mean annual insurance payments for any OAC significantly increased for all insurance groups (AAPC 13.1% [95% CI 11.3-15.0] for Medicare; AAPC 11.8% [95% CI 8.0-15.6] for commercial insurance; and AAPC 16.3% [95% CI 11.3-21.4] for Medicaid). The initiation of any OAC increased (AAPC 7.3% for commercial insurance; AAPC 10.2% for Medicare; AAPC 5.3% for Medicaid). CONCLUSIONS: There was a substantial increase in the overall cost burden of OACs and OAC initiation rates in patients with newly diagnosed atrial fibrillation in 2014-2021; these findings provide insights into the current and anticipated impact of rising drug prices on patients' and payers' financial burden.

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.

Anticoagulation Bridging in Patients With Left Ventricular Assist Device: A Regional Analysis of HeartMate 3 Recipients.

Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR < 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups.