Anticoagulation Changes Following Major and Clinically Relevant Nonmajor Bleeding Events in Non-valvular Atrial Fibrillation Patients

Background Bleeding events are common complications of oral anticoagulant drugs, including both warfarin and the direct oral anticoagulants (DOACs). Some patients have their anticoagulant changed or discontinued after experiencing a bleeding event, while others continue the same treatment. Differences in anticoagulation management between warfarin- and DOAC-treated patients following a bleeding event are unknown. Methods Patients with non-valvular atrial fibrillation from six anticoagulation clinics taking warfarin or DOAC therapy who experienced an International Society of Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant non-major (CRNM) bleeding event were identified between 2016 and 2020. The primary outcome was management of the anticoagulant following bleeding (discontinuation, change in drug class, and restarting of same drug class). DOAC- and warfarin-treated patients were propensity matched based on the individual elements of the CHA2DS2-VASc and HAS-BLED scores as well as the severity of the bleeding event. Results Of the 509 patients on warfarin therapy and 246 on DOAC therapy who experienced a major or CRNM bleeding event, the majority of patients continued anticoagulation therapy. The majority of warfarin (231, 62.6%) and DOAC patients (201, 81.7%) restarted their previous anticoagulation. Conclusion Following a bleeding event, most patients restarted anticoagulation therapy, most often with the same type of anticoagulant that they previously had been taking.

The Immediate Effect of COVID-19 Vaccination on Anticoagulation Control in Patients Using Vitamin K Antagonists

Background: In January 2021, the Dutch vaccination programme against SARS-CoV-2 was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications. Aims: To investigate whether the BNT162b2 vaccine affects anticoagulation control in outpatients using Vitamin K antagonists (VKAs). Methods: A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. INR results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination. Results: A total of 3148 outpatient VKA users were included, with a mean age (standard deviation (SD)) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic [OR=1.34 (95% CI 1.08-1.67)] and subtherapeutic levels [OR=1.40 (95% CI 1.08-1.83)] after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination [OR=2.29 (95% CI 1.22-4.28)] and 3.3 times higher after second vaccination [OR 3.25 (95% CI 1.06-9.97). Conclusion: BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with vitamin K antagonists, so it is advisable to monitor the INR short after vaccination, even in stable patients. Figure 1 Figure 1. Disclosures Kruip: Daiichi Sankyo: Research Funding; Bayer: Honoraria, Research Funding.

A systematic review of economic aspects of service interventions to increase anticoagulation use in atrial fibrillation

Objective: To systematically identify and appraise existing evidence surrounding economic aspects of anticoagulation service interventions for patients with atrial fibrillation. Methods: We searched the published and grey literature up to October 2019 to identify relevant economic evidence in any healthcare setting. A narrative synthesis approach was taken to summarise evidence by economic design and type of service intervention, with costs expressed in pound sterling and valued at 2017-2018 prices. Results: 13 studies met our inclusion criteria from 1,168 papers originally identified. Categories of interventions included anticoagulation clinics (n=4), complex interventions (n=4), decision support tools (n=3) and patient-centred approaches (n=2). Anticoagulation clinics were cost saving compared to usual care (range for mean cost difference: £188-£691 per-patient per-year) with equivalent health outcomes. Only one economic evaluation of a complex intervention was conducted; case management was more expensive than usual care (mean cost difference: £255 per-patient per-year) and the probability of its cost-effectiveness never exceeded 70%. There was limited economic evidence surrounding decision support tools or patient-centred approaches. Targeting service interventions at high-risk groups and those with suboptimal treatment was most likely to result in cost savings. Conclusion: This review revealed some evidence to support the cost-effectiveness of anticoagulation clinics. However, summative conclusions are constrained by a paucity of economic evidence, a lack of direct comparisons between interventions, and study heterogeneity in terms of intervention, comparator and study year. Further research is urgently needed to inform commissioning and service development. Data from this review can inform future economic evaluations of anticoagulation service interventions

Anticoagulation Clinical Pharmacist: Anticoagulation Care between the Headset and the Dial Pad

Anticoagulant is a class of medication that saves lives while carries an intrinsic risk of harm. The American College of Chest Physicians Consensus Conference on Antithrombotic Therapy for the first time in 1995 endorsed the setting of specialized anticoagulation clinics instead of usual medical care. Recently telemedicine is not a brand-new method of patient care, yet, telemedicine utilization has increased dramatically during the last year to comply with the curfew that most cities of the world had to apply to reduce the spread of COVID-19. Telemedicine and especially anticoagulation care need careful systems, the minimum infrastructure of patient records including telephone contact number, facility telephone, and clinic appointment system. The top three challenges when applying telehealth are payment, confidentiality, and un-updated patients’ information.

ANTICOAGULATION CONTROL AMONG PATIENTS WITH ATRIAL FIBRILLATION

Objective: To assess adequacy of anticoagulation in Warfarin treated patients with atrial fibrillation Study Design: Prospective observational study. Place and Duration of Study: Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi, from Nov 2019 to Apr 2020. Methodology: All individuals fulfilling the inclusion criteria were enrolled in the study after their consent. Based upon their serial International Normalized Ratio (INR) values, Time in Therapeutic Range (TTR) was calculated using Rosendaal method. A TTR>70% was a marker of adequate anticoagulation. Factors associated with TTR <70% were identified. Results: Total 70 participants were included in the study. Mean age (± SD) was 51.43 (± 11.27) years. Thirty four (48.6%) were males and 36 (51.4%) were females. Twenty four (34.3%) had valvular atrial fibrillation while 46 (65.7%) had non-valvular atrial fibrillation. Overall, TTR>70% was observed in 29 (41.4%) of study participants. Poly-pharmacy and multiple co-morbidities were identified as statistically significant factors associated with subtherapeutic anticoagulation (TTR<70%). Conclusion: Determined TTR of study population indicates poor anticoagulation control in majority of patients being anticoagulated with Warfar in highlighting the need for focused interventions such as dedicated anticoagulation clinics and patient education.

Oral anticoagulants in the prevention of thromboembolic complications in cardiac patients: analysis of use in the Russian Federation

In last years, special attention has been paid in the Russian Federation (RF) to improving medical care for patients with atrial fibrillation (AF) and the prevention of thromboembolic complications (TEC). The appearance on the Russian market of new oral anticoagulants (NOAC) has become a help for doctors, however, their cost imposes restrictions on the use. A humanitarian aid drugs to medical organizations of the RF, an active information program from manufacturers over the past 1.5 years have significantly increased the use of NOAC. In different regions, a different situation arises regarding the procurement and frequency of use of one or another anticoagulant. Analyzing the procurement of additional drug supplies for different regions of the Russian Federation, we see that dabigatran is preferred in a number of regions of the Central Federal District, and rivaroxaban in the Northern regions. The cost of warfarin is low. Data on the important role of the genotype in determining the individual dose and the development of bleeding, which is associated with the metabolism of warfarin, have been obtained. The pharmacogenetic approach allows you to quickly and efficiently choose its dose. The use of generics is highly relevant on the Russian market. Also, a number of regions are of great interest as a basis for conducting clinical trials of drugs. Aim. To analyze the current use of anticoagulant drugs taking into account personalized treatment approaches (the implementation of pharmacogenetic examinations and the work of anticoagulation clinics). Methods. Analysis of real clinical practice in the Russian Federation, patient registries, evaluation of adverse events in anticoagulation therapy and pharmacogenetic studies. Analysis of anticoagulant purchase under the Drug Reimbursement Program in several regions of the RF. Evaluation of the effect of anticoagulation clinics throughout the RF. Results. We analyzed the use of anticoagulants. To reduce the risk of thromboembolic complications and select the appropriate antithrombotic therapy, the entire range of antithrombotic agents is required, including NOACs and vitamin K antagonists (warfarin). Th e appearance of warfarin and NOACs on the Russian market has significantly improved the quality of medical care and treatment outcomes in these patients. Active awareness raising, the addition of anticoagulants to the national clinical guidelines and to clinical practice, and state support as part of the Drug Reimbursement Program have significantly increased the frequency of anticoagulant use. Nevertheless, the frequency of anticoagulant use varies slightly between regions. Warfarin is the most widely used anticoagulant and has high affordability (from 44 to 72.5 % out of all anticoagulants). The frequency of bleeding does not differ significantly between different anticoagulants, with an average of 2.8 %. A first INR value of ≥2.0 aft er 3-5 days is significantly associated with over coagulation during warfarin dose titration. The rapid achievement of an anticoagulation effect is often associated with a specific genotype (CYP2C9*2/*2, *3/*3 and 2/*3 variants and A/A of the VKORC1 gene, or CYP2C9 and VKORC1 polymorphism). Pharmacogenomics-guided warfarin dosing in clinical practice allows the warfarin dose to be selected in a faster and more effective way and for the risk of adverse reactions to be reduced. The creation of a network of anticoagulation clinics has proven to be highly effective. The most well-structured system of anticoagulation clinics is present in the Kursk Region. Rivaroxaban was the biggest selling anticoagulant out of the NOACs on the Russian sales market in 2018, but given the growth in apixaban sales, it is likely that this NOAC will move into first place in the near future.Conclusion. A personalized approach to anticoagulant use is crucial for the prevention of thromboembolic complications.

Hypertensive Complications of Pregnancy and Risk of Venous Thromboembolism

Hypertension during pregnancy and preeclampsia are associated with increased arterial thrombotic risk in later life. Whether these complications are associated with risk of venous thromboembolism (VTE) on the short term after pregnancy and on the long term, that is, outside pregnancy, is largely unknown. We conducted a nationwide cohort study in women with at least 1 pregnancy and their first VTE risk by linking the Dutch perinatal registry (Perined) to anticoagulation clinics. We used Cox proportional hazard models to estimate hazard ratios (HRs) and corresponding 95% CI for VTE risk in women with hypertension during pregnancy, women with preeclampsia, compared with women with uncomplicated pregnancies (reference). A total of 1 919 918 women were followed for a median of 13.7 (interquartile range, 7.6–19.2) years for a total of 24 531 118 person-years in which 5759 first VTEs occurred; incidence rate: 2.3 (95% CI, 2.3–2.4) per 10 000 person-years. In the first pregnancy and 3-month postpartum period, VTE risk was higher in women with hypertension, HR, 2.0 (95% CI, 1.7–2.4), and highest among women with preeclampsia, HR, 7.8 (95% CI, 5.4–11.3), versus the reference group. On the long term, women with hypertension during pregnancy and preeclampsia had a higher VTE risk: HR, 1.5 (95% CI, 1.4–1.6) and HR, 2.1 (95% CI, 1.8–2.4), respectively, versus the reference group. When excluding events during pregnancy and postpartum, these HRs were 1.4 (95% CI, 1.3–1.5) and 1.6 (95% CI, 1.4–2.0), respectively. In conclusion, hypertension during pregnancy and preeclampsia are associated with an increased VTE risk during pregnancy and postpartum period and in the 13 years after.

Drive-Through Model for Anticoagulation Clinics During the COVID-19 Pandemic

The coronavirus disease of 2019 (COVID-19) has posed a major challenge for providers and patients. A large number of patients with atrial fibrillation, venous thromboembolism, or valvular heart disease are chronically anticoagulated with vitamin K antagonists and rely on frequent follow ups at anticoagulation clinics for management of their anticoagulation therapy. The need for isolation during COVID-19 pandemic can potentially limit access to health care including anticoagulation clinics and directly affect the care of patients on chronic anticoagulation. Therefore, we created a drive-through clinic to bridge the gap of continuation of care and preservation of social distancing precautions. In this manuscript, we report the steps in implementing such initiative which can be applied to other clinics during a pandemic.

Evaluation of the potential impact of pharmacy technician performance of anticoagulation clinic tasks on operational efficiency

Purpose Results of a study to determine the proportion of anticoagulation clinic workload that could be performed by clinical pharmacy technicians (CPTs) and the potential impact on operational efficiency of pharmacist-managed anticoagulation clinics (ACCs) are reported. Methods In a quality improvement project involving 11 Veterans Affairs (VA) medical centers, investigators conducted a 3-day time study in pharmacist-managed ACCs followed by scoring of task appropriateness for CPTs via the RAND/UCLA appropriateness method by the VA Anticoagulation Subject Matter Expert (SME) Workgroup. The primary outcome was the percentage of tasks deemed appropriate for a CPT to perform. Results The Anticoagulation SME Workgroup determined that a wide variety of mainly administrative ACC tasks could be completed by a CPT. At the 11 VA ACCs, an average of 53.4% (range, 39.9–76.1%) of tasks being performed by pharmacists were deemed appropriate for CPTs. The average percentage of total clinic time associated with performing tasks appropriate for a CPT equated to an estimated 1,111 hours per year. Shifting that portion of the annual work hours to a CPT could potentially result in cost avoidance of $55,302. Conclusion At the ACCs evaluated, a significant proportion of tasks (53.4% on average) may be appropriate to assign to CPTs to improve the operational efficiency of these clinics. This finding supports development of business plans for the addition of CPTs in ACCs along with elements to inform crafting of an effective template for ACC structure, including clearly defined CPT roles.