Warfarin Dose Research Articles

Impact of Antibacterials on the Quality of Anticoagulation Control in Patients Initiating Warfarin Therapy.

Warfarin interacts with antibacterials to prolong the prothrombin time international normalized ratio (PT-INR) and increase the risk of bleeding. Patients initiating warfarin therapy often undergo precise dosage adjustments; however, the clinical implications of these interactions with antibacterials remain unclear. This study aimed to clarify the effect of antibacterials on PT-INR during the warfarin induction phase. This was a retrospective, observational study. Patients who were newly treated with warfarin after cardiovascular surgery were included. The primary endpoint was the comparison of the maximum PT-INR and time in therapeutic range (TTR) after warfarin initiation between the antibacterial-treated (ABx) and non-treated (non-ABx) groups. The maximum PT-INR was significantly higher in the ABx group (which included β-lactams, glycopeptides, quinolones, tetracyclines, and aminoglycosides) than in the non-ABx group (median [interquartile range] 2.37 [2.03-2.71] vs. 2.08 [1.93-2.33]; P = 0.005); however, the TTR did not differ significantly (65% [44-76] vs. 71% [43-85]; P = 0.150). The odds ratio for maximum PT-INR >2.6 with antimicrobial therapy was 2.51 (95% confidence interval 1.21-5.21). Antibacterial therapy was a risk factor for a maximum PT-INR >2.6. However, there was no association with the TTR, which is a marker of good outcomes. This was due to the strict warfarin dosing regimen according to the algorithm, which immediately and appropriately adjusted for PT-INR overexpansion. Antibacterials have been suggested to increase PT-INR during the induction phase of warfarin. However, with strict dose adjustments, the clinical impact on the PT-INR and TTR is likely limited.

Extracranial systemic embolic events in patients with atrial fibrillation: an individual patient-level meta-analysis of 71 683 patients randomized to NOAC vs warfarin from the COMBINE-AF study

Abstract Background Atrial Fibrillation (AF) poses a significant risk for both ischemic stroke and systemic embolic events (SEE). While the effectiveness of NOAC in preventing ischemic stroke is well-established, there is a lack of detailed analyses specifically characterizing SEE, which constitutes 5- 10% of all embolic events. Purpose To study the clinical characteristics, procedural management, and outcomes by randomized treatment (NOAC vs warfarin) of patients with SEE. Methods Using the COMBINE AF dataset, we conducted an individual patient level meta-analysis of 4 global RCTs (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48) of warfarin vs. NOAC in AF to assess risks of SEE. Outcomes were analyzed as time-to-first-event using a Cox proportional hazards model. Two authors independently reviewed deaths within 30 days after SEE to identify fatal SEE. Moreover, we independently assessed post SEE procedures to determined relatedness to SEE. Results There were 188 total SEEs, 9 patients (5%) had SEE then developed ischemic stroke; 16 patients (9%) had ischemic stroke then developed SEE; 1 patient had SEE and ischemic stroke simultaneously. Among the 171 patients with SEEs as first event, the median (IQR) age was 75 (68-80) years, 49.7% were female, median (IQR) of BMI was 27.5 (23.5-30.7) kg/m2, mean (SD) of CHADS2-VASC score was 4.7 (1.5). As compared with ischemic stroke (n=1789), SEE patients were more likely to have, PAD (16.5% vs. 5.4%, p <0.001), prior MI (24% vs. 17%, p = 0.02), be Vitamin K Antagonist experienced (57% vs 46%; p=0.007), have worse renal function (median CrCl mL/min; 58 vs 62, p = 0.02) and less likely to have paroxysmal AF (14% vs. 20%, p = 0.05). Of the total of 188 SEEs, 33 (18%) were fatal, 62 (31%) patients underwent surgical or percutaneous intervention (Fig). Standard dose (SD) NOAC significantly reduced the risk of SEE by 29% (95% CI 1-49%, p=0.04) compared with warfarin, However, no significant difference in the risk of SEE was observed between low dose (LD) NOAC and warfarin (Fig). Conclusion Standard dose NOAC was superior to warfarin in preventing SEE in AF patients. This benefit trends to be more pronounced for fatal cases. While SEE were about 1/10th as frequent as ischemic stroke in patients with AF, they were associated with significant morbidity and mortality and often required surgical or percutaneous intervention to restore blood flow.

Volumetric printing and non-destructive drug quantification of water-soluble supramolecular hydrogels.

Vat photopolymerisation 3D printing is being actively explored for manufacturing personalised medicines due to its high dimensional accuracy and lack of heat application. However, several challenges have hindered its clinical translation, including the inadequate printing speeds, the lack of resins that give soluble matrices, and the need for non-destructive quality control measures. In this study, for the first time, a rapid approach to producing water-soluble vat photopolymerised matrices and a means of non-destructively verifying their drug content were investigated. Volumetric printing, a novel form of vat photopolymerisation, was used to fabricate personalised warfarin-loaded 3D-printed tablets (printlets). Eight different formulations containing varying amounts of warfarin (0.5-6.0% w/w) were used to print two different sized torus-shaped printlets within 6.5 to 11.1s. Nuclear magnetic resonance (NMR) spectroscopy revealed the presence of only trace amounts of unreacted acrylate monomers, suggesting that the photopolymerisation reaction had occurred to near completion. All printlets completely solubilised and released their entire drug load within 2.5 to 7h. NIR spectroscopy (NIRS) was used to non-destructively verify the dose of warfarin loaded into the vat photopolymerised printlets. The partial least square regression model built showed strong linearity (R2 = 0.980), and high accuracy in predicting the drug loading of the test sample (RMSEP = 0.205%). Therefore, this study advances pharmaceutical vat photopolymerisation by demonstrating the feasibility of producing water-soluble printlets via volumetric printing and quantifying the drug load of vat photopolymerised printlets with NIRS.

Clinical predictors of warfarin-associated bleeding: A case-control study.

Despite the advent of directly acting oral anticoagulants, warfarin is still widely used in resource-poor settings. Bleeding as a result of warfarin overdosage is common and risk factors seem to vary between patient populations. Predictors of bleeding in patients using warfarin were studied using a case-control design. We calculated the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol (HAS-BLED) score (a bleeding risk prediction tool). Cases chosen were adults prescribed warfarin presenting with bleeding and controls were likewise taking warfarin but had no bleeding in the previous six months. The most common indication for warfarin use was venous thromboembolism. Recent decrease in food intake was strongly associated with bleeding. Older age, higher warfarin doses, recent illness in the past fortnight and prior bleeding were also independent predictors. A higher HAS-BLED score was not predictive independently. Closer monitoring of international normalised ratio is therefore advisable during acute illnesses and in those with decreased food intake.

Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population

PurposeTo identify the impact of CYP2C9*2, *3, VKORC1−1639 G>A and CYP4F2*3 on warfarin dose in an Arab population. To compare the accuracy of a clinical warfarin dosing (CWD) versus genetic warfarin dosing algorithms (GWD) during warfarin initiation. MethodsA cohort of Arab patients newly starting on warfarin had their dose calculated using CWD published in www.warfarindosing.org and were followed for 1 month. Each patient provided a saliva sample. DNA was extracted, purified and genotyped for VKORC−1639 G>A, CYP2C9*2, CYP2C9*3 and CYP4F2*3. After reaching warfarin maintenance dose, the dose was recalculated using the GWD and median absolute error (MAE) and the percentage of warfarin doses within 20% of the actual dose were calculated and compared for the two algorithms. ResultsThe study enrolled 130 patients from 12 Arabian countries. Compared to those with wild type, carriers of reduced function alleles in CYP2C9 required significantly lower median (IQR) warfarin weekly dose [24.5 (15.3) vs. 35 (29.8) mg/week, p=0.006]. With regards to VKORC, patients with AA genotype had a significantly lower median (IQR) weekly warfarin dose compared to AG and GG [21(10.5) vs 29.4 (21), p<0.001 for AA vs AG, p<0.001 for AA vs GG]. The MAE (IQR) for the weekly dose of the GWD was significantly lower compared to CWD [8.1 (10.5) vs 12.4 (12.6) (p<0.001)]. ConclusionCYP2C9 and VKORC1 variants are important determinants of warfarin dose in the Arab population. The use of the genetic and clinical factors led to better warfarin dose estimation when compared to clinical factors alone.

Pharmacogenetics of warfarin: A literature review

Warfarin is an oral indirect anticoagulant that is widely used for the prevention of thromboembolic events. Pharmacogenetic testing is the most promising approach to personalizing warfarin treatment. In this review, we aimed to summarize how the patients’ genetic predispositions affect the pharmacokinetics of warfarin, which determines the different dosing regimens for patients. To correctly interpret data in clinical settings, algorithms for selecting the optimal dosing regimen need to be developed that consider the patient’s age, sex, weight, height, health status, and genetic characteristics. These algorithms could help determine the optimal dose, enhance patient adherence to treatment, and increase the physician’s confidence in the treatment safety. Furthermore, although algorithms that consider SNPs in the CYP2C9, VKORC1, and CYP4F2 genes are more effective in predicting warfarin doses, their effectiveness varies according to race.

Applying a Computer-based Warfarin Management System at a Large Tertiary Cardiovascular Center in Iran.

Regarding adjustments to warfarin dosage, numerous studies have shown that computerized methods are superior to those based on personal experience. To report the efficacy of a computer-based warfarin management system (WMS) in the Iranian population. By utilizing the existing dosing algorithms and obtaining expert opinions, we developed a computer-based WMS at a large tertiary cardiovascular center. The time in therapeutic range and the number of international normalized ratio (INR) tests of clinic patients were compared before and after the implementation of WMS. Overall, 803 patients with 5407 INR tests were included in the before phase and 679 patients with 4189 INR tests in the after phase. The mean time in therapeutic range was 57.3% before and 59% after WMS implementation [mean difference, 1.64; 95% confidence interval (CI), -1.12-4.40]. In the before phase, the mean number of INR tests was 6.7, which dropped to 6.1 tests in the after phase (mean difference, -0.61; 95% CI, -0.97 to -0.24). Only 54.5% of the warfarin dosing prescriptions were consistent with the dosing recommendations of the WMS, and adherence to the WMS was poorest in the highest INR target range. For the first time in Iran, we demonstrated that a computerized system was as effective as a traditional experience-based method to monitor INR in VKA-anticoagulated patients. Furthermore, it could reduce both the number of INR tests and that of visits.

Warfarin Adherence and Its Associated Factors in Thai Older Adults with Atrial Fibrillation.

Older people mostly found unable to adhere with warfarin treatment guidelines. The health service system is challenged in order to improve medication adherence in older population under limited health resources. The purpose of this study was to explore health systems factors on warfarin adherence in older population, particularly in resources constraint setting. This study was a cross-sectional predictive study that enrolled older people who experienced atrial fibrillation (AF) and treated by warfarin, aged 60 years and over, and followed up at the warfarin clinic. A total of 197 participants with the mean age of 72.03 years (SD = 8.84) was recruited. Almost of them (85.8%) reported adhered to warfarin prescription. More than a half (60.5%) were able to report their targeted INR. Participants who stayed with the family had 5.54 times (95% CI 1.79-19.33), took regular daily dose warfarin had 5.07 times (95% CI 1.05-24.49), perceived targeted INR had 2.94 times (95% CI 1.04-8.29), and received family support had 1.33 times (95% CI 1.11-1.60) increased odds of warfarin adherence than those who did not. Participants who perceived a barrier to taking medication had 0.93 times decreased odds of warfarin adherence than those who did not (95% CI 0.86-0.99). Healthcare system should encourage family to support the older population with AF in order to increase warfarin adherence. Future research should develop intervention combining family support to promote warfarin adherence.

Effects of Switching Dose, Dose Variation, and Warfarin Interaction on the Incidence of Stroke Recurrence in Stroke Patients with Atrial Fibrillation

Atrial fibrillation (AF) significantly increases the risk of stroke, necessitating anticoagulation therapy. Warfarin, a commonly prescribed anticoagulant regimen, requires careful monitoring to ensure patient safety. This study aimed to assess the impact of dose switching, dose variation, and potential interactions with warfarin on the incidence of stroke recurrence in stroke patients with AF. The study retrospectively analyzed the treatment records of stroke patients with AF in outpatient settings over one year. The subjects comprised 314 patients who received warfarin prescriptions at two Indonesian Hospitals from January 1, 2015, to December 31, 2019. Out of these patients, 50 had recorded data regarding dose adjustments, variations, and interactions. They were divided into two groups: a case group (n=11) with stroke recurrence and a control group (n=39) without recurrence. Statistical analysis, including chi-square tests and odds ratio calculations, revealed that both warfarin dose switching (OR=7.6) and dose variation (OR=6.6) significantly influenced the incidence of stroke recurrence. It implies that inconsistencies or alterations in warfarin dosing substantially elevate the likelihood of experiencing another stroke, potentially due to inadequate anticoagulation leading to clot formation. Interestingly, the analysis of drug interactions did not significantly impact stroke recurrence. In summary, the recurrence of stroke in patients with AF is notably influenced by warfarin dose adjustments and variations rather than drug interactions. This study highlights the critical importance of precise dosing strategies and vigilant monitoring to enhance the efficacy of anticoagulant therapy in this high-risk population.

Meta-analysis of genome-wide association studies of stable warfarin dose in patients of African ancestry

AbstractWarfarin dose requirements are highly variable because of clinical and genetic factors. Although genetic variants influencing warfarin dose have been identified in European and East Asian populations, more work is needed to identify African-specific genetic variants to help optimize warfarin dosing. We performed genome-wide association studies (GWASs) in 4 African cohorts from Uganda, South Africa, and Zimbabwe, totaling 989 warfarin-treated participants who reached stable dose and had international normalized ratios within therapeutic ranges. We also included 2 African American cohorts recruited by the International Warfarin Pharmacogenetics Consortium (n = 316) and the University of Alabama at Birmingham (n = 199). After the GWAS, we performed standard error-weighted meta-analyses and then conducted stepwise conditional analyses to account for known loci in chromosomes 10 and 16. The genome-wide significance threshold was set at P < 5 × 10−8. The meta-analysis, comprising 1504 participants, identified 242 significant SNPs across 3 genomic loci, with 99.6% of these located within known loci on chromosomes 10 (top SNP: rs58800757, P = 4.27 × 10−13) and 16 (top SNP: rs9925964, P = 9.97 × 10−16). Adjustment for the VKORC1 SNP -1639G>A revealed an additional locus on chromosome 2 (top SNPs rs116057875/rs115254730/rs115240773, P = 3.64 × 10−8), implicating the MALL gene, that could indirectly influence warfarin response through interactions with caveolin-1. In conclusion, we reaffirmed the importance of CYP2C9 and VKORC1 in influencing warfarin dose requirements, and identified a new locus (MALL), that still requires direct evidence of biological plausibility.

Retrospective Evaluation of Inpatient Warfarin Management Practices in Patients Immediately Following Left Ventricular Assist Device Implantation.

Background: The International Society for Heart and Lung Transplantation recommends patients receive warfarin and aspirin following left ventricular assist device (LVAD) placement. Optimal warfarin management in this population has not been well established. Objectives: The objectives of this study were to evaluate warfarin practices in patients immediately post-LVAD implantation. Methods: This single-center, retrospective cohort study included patients 18 years and older following LVAD placement from August 1, 2012 to April 1, 2020. The primary outcome was to assess patient-specific risk factors affecting time to therapeutic range. Secondary outcomes included bleeding events, thrombotic events, and warfarin dosing patterns. Results: Of 104 included patients, 91% reached the therapeutic range at a median of 8 days. A higher proportion of patients started on 3.5 mg or higher reached therapeutic international normalized ratio (INR) and faster (96% vs 90%; 8 vs 5 days) compared to lower doses. Univariate analysis of associations with reaching therapeutic INR range included initial warfarin dose, cumulative warfarin, and warfarin dosing changes, whereas HAS-BLED and CHA2DS2VAC were associated with slower time to therapeutic INR. Overall, 44% of patients met Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) bleeding criteria. There were a total of 12 thrombotic events and no pump thrombotic events. Total weekly warfarin dosing was significantly lower post-LVAD (24.3 mg vs 35 mg, P = 0.0009). In addition, warfarin requirements were statistically higher after the first week of therapy (4.0 mg vs 2.89 mg, P < 0.0001). Conclusion: Based on the results, consider warfarin starting dose between 2.5 and 4 mg for patients on LVAD therapy, while balancing patient-specific risks for bleeding.

PharmVar GeneFocus: CYP4F2.

The Pharmacogene Variation Consortium (PharmVar) serves as a global repository providing star (*) allele nomenclature for the polymorphic human CYP4F2 gene. CYP4F2 genetic variation impacts the metabolism of vitamin K, which is associated with warfarin dose requirements, and the metabolism of drugs, such as imatinib or fingolimod, and certain endogenous compounds including vitamin E and eicosanoids. This GeneFocus provides a comprehensive overview and summary of CYP4F2 genetic variation including the characterization of 14 novel star alleles, CYP4F2*4 through *17. A description of how haplotype information cataloged by PharmVar is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) is also provided.

Effect of Vascular Senescence on the Efficacy and Safety of Warfarin: Insights from Rat Models and a Prospective Cohort Study.

Warfarin, with its narrow therapeutic range, requires the understanding of various influencing factors for personalized medication. Vascular senescence, marked by vascular stiffening and endothelial dysfunction, has an unclear effect on the efficacy and safety of warfarin. Based on previous studies, we hypothesized that vascular senescence increases the risk of bleeding during warfarin therapy. This study aimed to explore these effects using animal models and clinical cohorts. We established rat models of vascular senescence and calcification using d-galactose, vitamin D, and nicotine. After validating the models, we examined changes in the international normalized ratio (INR) at fixed warfarin doses (0.20 and 0.35 mg/kg). We found that vascular senescence caused significantly elevated INR values and increased bleeding risk. In the prospective clinical cohort study (NCT06428110), hospitalized warfarin patients with standard dose adjustments were divided into vascular senescence and control groups based on ultrasound and computed tomography diagnosis. Using propensity score matching to exclude the influence of confounding factors, we found that the vascular senescence group had lower steady-state warfarin doses and larger dose adjustments, with a higher probability of INR exceeding the therapeutic range. The vascular senescence group tended to experience more bleeding or thromboembolic/ischemic events during 1 year of follow-up, while there was no statistical difference. In conclusion, vascular senescence leads to unstable INR values and increases higher bleeding risk during warfarin therapy, highlighting the importance of considering vascular senescence in future precision warfarin therapies. SIGNIFICANCE STATEMENT: Many factors influence warfarin efficacy; however, the effect of vascular senescence remains unclear. This study aimed to investigate the effects of vascular senescence on the efficacy and safety of warfarin. Through both rat models and clinical cohort studies, our findings indicated that vascular senescence may compromise the stability of warfarin, presenting challenges in maintaining its efficacy and safety.

Effect of genetic factors on the interindividual variability of warfarin dosage requirements in Japanese patients after adjusting for renal function.

Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (β = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and β = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.

Dose Reduction of Edoxaban in Patients 80 Years and Older With Atrial Fibrillation

In older patients with atrial fibrillation who take anticoagulants for stroke prevention, bleeding is increased compared with younger patients, thus, clinicians frequently prescribe lower than recommended doses in older patients despite limited randomized data. To evaluate ischemic and bleeding outcomes in patients 80 years and older with atrial fibrillation receiving edoxaban, 60 mg vs 30 mg, and edoxaban, 30 mg vs warfarin. The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a parallel-design, double-blind, global clinical trial that randomized patients with atrial fibrillation to either one of 2 edoxaban dosing regimens or warfarin. This secondary analysis focused on patients 80 years or older without dose-reduction criteria receiving edoxaban, 60 mg vs 30 mg, as well as patients with or without dose-reduction criteria receiving edoxaban, 30 mg, vs warfarin. Study data were analyzed between October 2022 and December 2023. Oral edoxaban, 30 mg once daily; edoxaban, 60 mg once daily; or warfarin. Primary net clinical outcome of death, stroke or systemic embolism, and major bleeding and each individual component. The current analysis included 2966 patients 80 years and older (mean [SD] age, 83 [2.7] years; 1671 male [56%]). Among 1138 patients 80 years and older without dose-reduction criteria, those receiving edoxaban, 60 mg vs 30 mg, had more major bleeding events (hazard ratio [HR], 1.57; 95% CI, 1.04-2.38; P = .03), particularly gastrointestinal hemorrhage (HR, 2.24; 95% CI, 1.29-3.90; P = .004), with no significant difference in efficacy end points. Findings were supported by analyses of endogenous factor Xa inhibition, a marker of anticoagulant effect, which was comparable between younger patients receiving edoxaban, 60 mg, and older patients receiving edoxaban, 30 mg. In 2406 patients 80 years and older with or without dose-reduction criteria, patients receiving edoxaban, 30 mg, vs warfarin had lower rates of the primary net clinical outcome (HR, 0.78; 95% CI, 0.68-0.91; P = .001), major bleeding (HR, 0.59; 95% CI, 0.45-0.77; P < .001), and death (HR, 0.83; 95% CI, 0.70-1.00; P = .046), whereas rates of stroke or systemic embolism were comparable. In this post hoc analysis of the ENGAGE AF-TIMI 48 randomized clinical trial, in patients 80 years and older with atrial fibrillation, major bleeding events were lower in patients randomized to receive edoxaban, 30 mg per day, compared with either edoxaban, 60 mg per day (in patients without dose-reduction criteria), or warfarin (irrespective of dose-reduction status), without an offsetting increase in ischemic events. These data support the concept that lower-dose anticoagulants, such as edoxaban, 30 mg, may be considered in older patients with atrial fibrillation even in the absence of dose-reduction criteria. ClinicalTrials.gov Identifier: NCT00781391.

Comparative effectiveness of warfarin management strategies: a systematic review and network meta-analysis

The management of warfarin therapy presents clinical challenges due to its narrow therapeutic index. We aimed to evaluate the comparative effectiveness of different management strategies in patients using warfarin. PubMed, Embase, Cochrane CENTRAL, CINAHL, and EBSCO Open Dissertation were searched from inception to 8 May 2024. Randomized controlled trials that compared the following interventions: patient self-management (PSM), patient self-testing (PST), anticoagulation management services (AMS), and usual care in patients prescribed warfarin for any indication were included. Risk ratios (RR) with 95% confidence interval (CI) were estimated using a random-effects model. Surface under the cumulative ranking curves (SUCRA) were used to rank different interventions. The certainty of evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) online platform. This study is registered with PROSPERO (CRD42023491978). Twenty-eight trials involving 8100 participants were included, with follow-up periods of 1-24 months. Mean warfarin dosages were 4.9-7.2mg/day. Only PSM showed a significant reduction of major TE risk compared with usual care (RR=0.41; 95% CI: 0.24, 0.71; I2=0.0%) with moderate certainty of evidence. The 97.6% SUCRA also supported the beneficial effects of PSM over other interventions. The combined direct and indirect evidence showed significantly higher TTR in PSM compared with usual care (MD=7.39; 95% CI: 2.39, 12.39), with very low certainty. However, direct evidence showed non-significant TTR improvement (MD=6.49; 95% CI:-3.09, 16.07, I2=96.1%). No differences across various strategies were observed in all-cause mortality, major bleeding, stroke, transient ischemic attack, and hospitalization. PSM reduces the risk of major TE events compared with usual care, tends to improve anticoagulation control, and should be considered where appropriate. Agency for Healthcare Research and Quality (grant ID 5R18HS027960).

Implementation and Outcome of Clinical Pharmacist-led Anticoagulation Clinic at Cardiac Center: A Retrospective Cohort Study

Abstract Context: Managing patients on anticoagulant therapy, such as warfarin, can be challenging due to various factors. Implementing a specialized care model can be a useful strategy to address this issue. Studies have demonstrated that pharmacist-led anticoagulation therapy leads to improved outcomes. Aims: We aimed to assess the anticoagulation quality of warfarin therapy achieved by the implementation of a Clinical Pharmacist-led Anticoagulation Clinic at a cardiac center. Materials and Methods: In conjunction with the cardiac center, the hospital’s pharmaceutical care department established a clinic. The anticoagulation quality was evaluated by determining the time in the therapeutic range (TTR), which was calculated using the Rosendaal method. Data were collected from February 1, 2021, to July 31, 2022, in a retrospective manner. Statistical Analysis Used: Both descriptive and inferential analyses were performed and are presented as counts, percentages, and means ± standard deviation, as appropriate. A paired t test was used to compare the mean TTR, and the outcomes were logistically regressed against candidate factors. Statistical significance was set at P &lt; 0.05. Results: A total of 66 patients were eligible for inclusion in the study. The mean TTR was 73.4% ± 21.1%, compared to 46.9% ± 29.5% before clinic implementation. After clinic implementation, the proportion of patients who were able to reach a TTR of ≥70% increased from 28.8% to 60.6%. During clinical pharmacist care, there was one major bleeding event (0.7%/year), nine minor bleeding events (6%/year), and one thromboembolic event (0.7%/year). Age, comorbidities, and warfarin dose were not found to affect the TTR. However, females had a reduced likelihood of a TTR ≥70% (95% confidence interval, 0.11–0.89; P = 0.029). Conclusions: A clinical pharmacist-led anticoagulation clinic was implemented successfully, which resulted in positive outcomes in patient care by achieving a good TTR (≥70%) and low warfarin-related adverse events.

The Influence of Genetic Polymorphisms on Warfarin Dosage Requirements in Cardiac Valve Surgery Patients

Aim: Warfarin, a widely prescribed anticoagulant, exhibits considerable variability in patient response, making its clinical use challenging due to a narrow therapeutic window. This study aimed to evaluate the prevalence of CYP2C9 and VKORC1 gene polymorphisms in a cohort of 87 Turkish patients who underwent cardiac valve surgery and received warfarin therapy, as well as to assess their impact on warfarin dosage requirements. Methods: The frequencies of CYP2C9 and VKORC1 polymorphisms were analyzed, and patients were stratified based on the presence or absence of mutations affecting warfarin dosing. Results: Revealed that patients carrying at least one CYP2C9 or VKORC1 polymorphism required a significantly lower weekly warfarin dose to achieve the optimal international normalized ratio (INR). Conclusion: This study highlights the critical role of genetic factors in determining warfarin dosage and supports the integration of pharmacogenetic testing into clinical practice to personalize warfarin therapy. Such an approach has the potential to enhance treatment outcomes and minimize the risk of adverse events. Further research involving larger sample sizes and diverse patient populations is warranted to validate these findings and refine the current understanding of the genetic determinants of warfarin dosing.

Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method

The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.

Prediction of Warfarin Dosage Based on Genotype (VKORC1) – 1639 G&gt;A – rs9923231 In South Indian Populations

Background: Venous thromboembolism (VTE), characterized by thrombus formation in veins, ranks as the third most prevalent vascular disease globally after myocardial infarction (MI) and stroke. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common clinical manifestations of VTE, with potentially fatal consequences. In this study, the mean daily warfarin dose using VKORC1 (-1639 G&gt;A) rs9923231 genotyping will be established in order to categorize warfarin treatment into high, moderate, and low-dose groups within the South Indian population. Methods and Materials: A cohort of 192 patients was enrolled, and genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: In our study sample, the A allele frequency was 23.9%, and the AA genotype frequency was 12.5%. The mean daily doses required by AA homozygous (1.54 ± 1.05 mg/day) and GA heterozygous (2.93 ± 2.03 mg/day) genotype carriers were considerably lower to attain the optimal international normalized ratio (INR) than those of GG genotype carriers (4.07 ± 1.75 mg/day), with a p-value of 0.866. Conclusion: Our findings strongly advocate for incorporating VKORC1 polymorphism analysis in South Indian patients with DVT to guide the initial warfarin dosage genetically.