HVNI vs NIPPV in the treatment of acute decompensated heart failure: Is acute stabilization enough?
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Background Warfarin dosing varies due to individual genetic and clinical factors. The utility of genotype‐guided warfarin dosing to improve stable warfarin dose is not extensively studied in non-European populations.Research design and methods Retrospective cohort study of patients initiating warfarin receiving genotype (PGx)‐guided or clinically guided dosing. Primary outcomes included dose discordance between estimated dose at discharge and eventual stable dose.Results No significant difference in warfarin dose discordance was observed (PGx: 9.1 ± 8.8 mg/week difference vs. Clinical: 7.9 ± 8.9 mg/week difference; P = 0.446). PGx‐guided dosing did not reduce time to achieve stable dose (1.8 ± 2.5 months vs. 2.1 ± 2.6 months; P = 0.508). Vitamin K intake level did not alter prediction accuracy or time to stable dose (PGx‐predicted: dose difference P = 0.493, time to stable dose P = 0.336; Clinically predicted: dose difference P = 0.145, time to dose INR P = 0.095).Conclusions PGx‐guided warfarin dosing did not improve eventual stable dose discordance or reduce the time to achieve stable dose in this predominantly non‐European cohort. Dietary vitamin K intake level did not impact warfarin dose discordance or time to achieve stable warfarin dose. Additional study is needed to identify populations that best benefit from PGx‐guided warfarin dosing.
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Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation.Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDrFVIIa (1000 or 1200 mcg) for emergent warfarin reversal from August 2007 to October 2011. The primary end-points were achievement of an INR 1.5 or less for efficacy and thromboembolic events for safety.Seventy-four PCC3 and 32 LDrFVIIa patients were analyzed. Baseline demographics, reason for warfarin reversal, and initial INR were equivalent. There was no difference in the use of vitamin K or fresh frozen plasma. More LDrFVIIa patients achieved an INR of 1.5 or less (71.9% vs. 33.8%, p =0.001). The follow-up INR was lower after LDrFVIIa (1.25 vs. 1.75, p < 0.05) and the percent change in INR was larger after LDrFVIIa (54.1% vs. 38.8%, p = 0.002). There was no difference in the number of thromboembolic events (2 LDrFVIIa vs. 5 PCC3, p = 1.00), mortality, length of hospital stay, or cost.Based on achieving a goal INR of 1.5 or less, LDrFVIIa was more likely than PCC3 to reverse warfarin anticoagulation. Thromboembolic events were equivalent in patients receiving PCC3 and LDrFVIIa.
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Four‐factor prothrombin complex concentrate (4F‐PCC) has emerged as the preferred option for emergent reversal of vitamin K antagonists (VKAs); however, the optimal dosing strategy is unknown. Although several studies have attempted to determine the optimal dose of 4F‐PCC using a variety of dosing regimens, no dosing strategy has been found to be superior. Many of these studies have evaluated a low, fixed dose of 4F‐PCC rather than individualized dosing as recommended in product labeling. The purpose of this review was to evaluate the efficacy and safety of various fixed‐dose strategies of 4F‐PCC for emergent VKA reversal and to assess limitations of the existing literature. A search of the PubMed database was performed from the earliest available date through 2018 for relevant articles describing fixed‐dose 4F‐PCC for VKA reversal. Reference lists of relevant articles were also manually reviewed. Most currently available studies are primarily observational and heterogeneous in design. A very low fixed dose of 500 IU is likely inadequate for successful VKA reversal, but increased fixed doses of 1000–1500 IU have found some degree of success and may be considered for VKA reversal. However, many of these studies consistently identified a trend toward international normalized ratio (INR) reversal failure in patients presenting with high baseline INR values or intracranial hemorrhage, suggesting that higher 4F‐PCC doses are needed in these patients. Available studies are underpowered to determine whether a dose‐dependent association with thrombotic risk exists. Additional large, randomized studies are needed to determine the optimal dosing strategy and ascertain the role for fixed‐dose 4F‐PCC.
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Background: Warfarin-related bleeding occurred most commonly during the first three months of therapy, possibly due to an initiating overdose of warfarin. Previous small study reported that 3-mg initiating dose of warfarin appeared to be safe in Thai patients. Objective: To compare the performance of simplified warfarin dosing formula and 3-mg initiating dose to predict actual warfarin dose that achieved therapeutic range of target international normalized ratio (INR). Materials and Methods: The present study was a retrospective study including 640 patients who had been receiving warfarin with target INR of 2.0 to 3.0. The actual warfarin dose was defined as warfarin dose that resulted in INR of 2.0 to 3.0 for at least two consecutive follow-ups after initiation. The simplified warfarin dosing formula was 3.2 – (0.03×age(years)) + (0.02×body weight(kg)) (10% dose reduction if presence of heart failure (HF) and/or stroke). The optimal dosage was defined as difference from actual dose as being within 20%. Results: Mean age was 65±13 years. The mean actual dose of warfarin was 2.8±1.2 mg. The warfarin dosing formula resulted in optimal dosing in 41% and overdosing in 21% of cases, whereas 3-mg initiating dose resulted in optimal dosing in 39% and overdosing in 43% of patients. In patients with HF and/or stroke, using formula resulted in overdosing in 23% of cases, whereas 3-mg initiating dose led to overdosing in 53% of patients. Conclusion: A simplified warfarin dosing formula appeared to be safer than 3-mg initiating dose. Overdosing after using warfarin formula was less prevalent than using 3-mg initiating dose particularly in patients with HF and/or stroke. Keywords: Warfarin, Algorithms, Atrial fibrillation, Anticoagulant Received 15 May 2019 | Revised 4 Jul 2019 | Accepted 11 Jul 2019
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Abstract Background For decades, vitamin K antagonists and specifically warfarin, have been the sole agents used orally to manage thromboembolic conditions, including stroke and venous thromboembolism (VTE). Several factors lead to warfarin dose variability, including genetic and non-genetic factors which made warfarin management challenging especially at the initiation phase. To overcome the challenges with warfarin dosing at initiation, strategies other than conventional or fixed dosing were introduced and explored. Aim In this narrative review, we aim to discuss and critique the different dosing strategies for warfarin at initiation with more focus on genotype-guided warfarin dosing and the most recent supporting evidence for and against its use. Method Medline database was searched from 1965 to July 2021. Articles addressing different warfarin dosing methods were screened for inclusion. Results A number of methods exist for warfarin initiation. Studies comparing different dosing methods for initiation yielded conflicting outcomes due to differences in study design, population studied, comparator, and outcomes measured. Conclusions Looking at the big picture, the use of genetic dosing for warfarin initiation can lead to better outcomes. Whether these better outcomes are clinically or economically beneficial remains controversial.
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Abstract Background: Warfarin, a key anticoagulant medication, has a narrow therapeutic window and individual difference. Many warfarin dosing algorithms have been developed and been proved to have clinical benefits. However, the utilization of algorithms by medical professionals in China was unknown. We conducted an online survey to investigate the use and requirements of warfarin dosing algorithms among Chinese medical professionals. Method: A questionnaire survey was conducted via WeChat to investigate the utilization of warfarin dosing algorithms by medical professionals in seven regions of China. The content of questionnaire was included general characteristics of participants, condition of anticoagulant therapy, utilization of warfarin dosing algorithms and demand for function of an assistant warfarin dosing system we proposed.Results: A total of 399 participants completed the survey. Although most medical professionals use warfarin for anticoagulant therapy, some of them (15.04%) were not familiar with warfarin’s individual difference. As high as 32.97% of clinicians ruled out genotypes when using warfarin. The vast majority of anticoagulant medical professionals believed warfarin dosing algorithms can have clinical benefits, but only 20.80% of them usually use algorithms for anticoagulant therapy. Conclusion: Warfarin dosing algorithms have high evaluation while not good utilization among Chinese anticoagulant medical professionals. If warfarin dosing algorithms and assistant tools aimed to Chinese population were developed, to some extent can improve anticoagulant therapy in China.
Anticoagulant Therapy
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