Renal Function Protection as an Important Component of a Comprehensive Approach to the Management of Patients with Atrial Fibrillation

The increase in the life expectancy of the population is accompanied by an increase in the prevalence of diseases for which old and senile age are risk factors. Atrial fibrillation (AF) and chronic kidney disease (CKD) are two diseases that can coexist in a patient. The risk of ac thromboembolic and hemorrhagic events in this case increases due to the mutual aggravating influence of these diseases. In addition, these patients have a high incidence of coronary events, and cardiovascular complications are the main cause of death in patients with AF and CKD. Consequently, such patients require an integrated approach to treatment, and their management is a complex clinical task. The direct oral anticoagulant rivaroxaban has been most studied in a population of comorbid AF and CKD patients and has proven a high efficacy and safety profile in these patients in randomized controlled trials. In addition, rivaroxaban has shown a significant reduction in the risk of myocardial infarction in various patients, as well as the possibility of preserving renal function to a greater extent compared with warfarin therapy, and a possible positive effect on reducing the risk of cognitive impairment. A single dosing regimen can improve adherence to treatment, which is one of the key conditions for achieving the above effects. Thus, these factors make it possible to achieve comprehensive protection of comorbid patients with AF and CKD.

Evaluation of the Modified SAMe-TT2R2 Score to Predict Good Anticoagulation Control with Warfarin Among non-valvular Atrial Fibrillation Patients

Background: The SAMe-TT2 R2 Score was developed to identify vitamin K antagonists control outliers before non-valvular atrial fibrillation (AF) patients start treatment. SAMe-TT2 R2 Score was derived and validated using a primarily white Caucasian population to predict TTR. Given that non-Caucasian race already confers 2 points in this score, the SAMe-TT2 R2 score requires validation and/or re-calibration despite race of population. Method: We conducted a cohort retrospective study that included all non-valvular atrial fibrillation patients who were on warfarin therapy from January to December 2019. Then we calculated the modified SAMe-TT2 R2 and SAMe-TT2 R2 for all study populations and we correlated the result with patients' TTR. The TTR was calculated through the Rosendaal's method. Results: We had 662 patient using warfarin therapy, among those 662, 60.9% were under cardiology and using it for cardiac indication, and only 18.1% diagnosed to have non-valvular AF. Modified SAMe-TT2 R2 score has good relation to original SAMe-TT2 R2 score as showed 75.71% (95% CI. 63.99 to 85.17%), 100% (95% CI. 92.89 to 100%) and 15% (95% CI. 3.21 to 77.95%); accuracy, sensitivity and specificity in relation to SAMe-TT2 R2 respectively. In addition to that in this small cohort we found that there is universal relationship between SAMe-TT2 R2 score, Modified SAMe-TT2 R2 score and TTR; TTR >=65% associate with low score (<2) of both SAMe-TT2 R2 , Modified SAMe-TT2 R2 score. Conclusion: The use of Modified SAMe-TT2 R2 score allows clinicians to make an informed decision on whether to start vitamin K antagonist or other non-vitamin K antagonist oral anticoagulant despite the race of the patients.

Risk of Bleeding after Colorectal Endoscopic Resection in Patients with Continued Warfarin Use Compared to Heparin Replacement: A Propensity Score Matching Analysis

The Japan Gastroenterological Endoscopy Society (JGES) guidelines recommend continued warfarin treatment during gastroenterological endoscopic procedures with a high risk of bleeding as an alternative to heparin replacement in patients on warfarin therapy. However, there is insufficient evidence to support the use of warfarin in colorectal endoscopic resection (ER). The present study is aimed at verifying the risk of bleeding after ER for colorectal neoplasia (CRN) in patients with continued warfarin use. This was a single-center retrospective cohort study using clinical records. We assessed 126 consecutive patients with 159 CRNs who underwent ER (endoscopic mucosal resection, 146 cases; endoscopic submucosal dissection, 13 cases) at Hiroshima University Hospital between January 2014 and December 2019. Patients were divided into two groups: the heparin replacement group (79 patients with 79 CRNs) and the continued warfarin group (47 patients with 80 CRNs). One-to-one propensity score matching was performed to compare the bleeding rate after ER between the groups. The rate of bleeding after ER was significantly higher in the heparin replacement group than in the continued warfarin group for both before (10.1% vs. 1.3%, respectively; P = 0.0178 ) and after (11.9% vs. 0%, respectively; P = 0.0211 ) propensity score matching. None of the patients experienced thromboembolic events during the perioperative period. The risk of bleeding after colorectal ER was significantly lower in patients with continued warfarin use than in those with heparin replacement. Our data supports the recommendations of the latest JGES guidelines for patients receiving warfarin therapy.

Loss of engagement in controlling chronic anticoagulation therapy during Covid-19 stringency measures. A single center experience of disproportioned increase of stuck mechanical valves

Stuck valve is a very rare and severe complication that occurs in mechanical valve replacement patients with ineffective anticoagulation. However, with COVID-19 restriction measures, it became challenging to regularly assess INR to make sure it falls within the target therapeutic range to prevent this complication. We present a series of 10 patients who either underwent transthoracic echocardiography for a suspected stuck valve or were seen at the outpatient valve clinic with the residual consequences of a stuck valve during the COVID-19 restriction measures in our institute. Stuck prosthetic valves incident has increased significantly during this period, particularly those in the mitral position for which urgent replacement and prolonged hospitalization were necessary. Particularly with the COVID-19 restrictions in place, these cases highlight the need for physicians to be aware of the dramatic increase in the incidence of stuck prosthetic valves in patients on chronic warfarin therapy.

Patient-specific and healthcare real-world costs of atrial fibrillation in individuals treated with direct oral anticoagulant agents or warfarin

Background Anticoagulant therapies are used to prevent atrial fibrillation-related strokes, with warfarin and direct oral anticoagulant (DOAC) the most common. In this study, we incorporate direct health care costs, drug costs, travel costs, and lost working and leisure time costs to estimate the total costs of the two therapies. Methods This retrospective study used individual-level patient data from 4000 atrial fibrillation (AF) patients from North Karelia, Finland. Real-world data on healthcare use was obtained from the regional patient information system and data on reimbursed travel costs from the database of the Social Insurance Institution of Finland. The costs of the therapies were estimated between June 2017 and May 2018. Using a Geographical Information System (GIS), we estimated travel time and costs for each journey related to anticoagulant therapies. We ultimately applied therapy and travel costs to a cost model to reflect real-world expenditures. Results The costs of anticoagulant therapies were calculated from the standpoint of patient and the healthcare service when considering all costs from AF-related healthcare visits, including major complications arising from atrial fibrillation. On average, the annual cost per patient for healthcare in the form of public expenditure was higher when using DOAC therapy than warfarin therapy (average cost = € 927 vs. € 805). Additionally, the average annual cost for patients was also higher with DOAC therapy (average cost = € 406.5 vs. € 296.7). In warfarin therapy, patients had considerable more travel and time costs due the different implementation practices of therapies. Conclusion The results indicated that DOAC therapy had higher costs over warfarin from the perspectives of the patient and healthcare service in the study area on average. Currently, the cost of the DOAC drug is the largest determinator of total therapy costs from both perspectives. Despite slightly higher costs, the patients on DOAC therapy experienced less AF-related complications during the study period.

DO VKORC1 AND CYP2C9 MUTATIONS LEAD TO WARFARIN RESISTANCE?

The objective of this study was to determine the influence of VKORC1 and CYP2C9 polymorphisms on warfarin resistant patients. Warfarin resistance is described as the inability to prolong the prothrombin time or raise the INR up to the 2 therapeutic range when the drug is given at typically doses. Polymorphisms may play a role as some VKORC1 and CYP2C9 variant alleles are known to be associated with these circumstances. 28 patients who were taking warfarin more than 15 mg/day and had INR values below 2.1 and had thromboembolic events while using warfarin were enrolled in this study. Heterozygote mutation in the VKORC1 gene was identified in 15 of 28 patients. Seven patients had heterozygote mutation of the CYP2C9 gene, and that may correspond to the ultrarapid metabolism of warfarin. VKORC1 and CYP2C9 polymorphism contribute to the difference in dose requirement amongst the patients, but other additional possible factors may play a role in different races. We suggest that medicians may use this tests before starting warfarin therapy and shape the treatment course according to this results.

Anticoagulation Control in Different Ethnic Groups Receiving Vitamin K Antagonist for Stroke Prevention in Atrial Fibrillation

Vitamin K antagonist such as warfarin reduces the risk of stroke in atrial fibrillation (AF) patients. Since warfarin has a narrow therapeutic index, its administration needs to be regularly monitored to avoid any adverse clinical outcomes such as stroke and bleeding. The quality of anticoagulation control with warfarin therapy can be measured by using time in therapeutic range (TTR). This review focuses on the prevalence of AF, quality of anticoagulation control (TTR) and adverse clinical outcome in AF patients within different ethnic groups receiving warfarin therapy for stroke prevention. A literature search was conducted in Embase and PubMed using keywords of “prevalence,” “atrial fibrillation,” “stroke prevention,” “oral anticoagulants,” “warfarin,” “ethnicities,” “race” “time in therapeutic range,” “adverse clinical outcome,” “stroke, bleeding.” Articles published by 1st February 2020 were included. Forty-one studies were included in the final review consisting of AF prevalence (n = 14 studies), time in therapeutic range (n = 18 studies), adverse clinical outcome (n = 9 studies) within different ethnic groups. Findings indicate that higher prevalence of AF but better anticoagulation control among the Whites as compared to other ethnicities. Of note, non-whites had higher risk of strokes and bleeding outcomes while on warfarin therapy. Addressing disparities in prevention and healthcare resource allocation could potentially improve AF-related outcomes in minorities.

Pharmacists’ interventions improve health-related quality of life of rural older person on warfarin: a randomized controlled trial

Warfarin therapy can significantly affect patients’ quality of life and cause therapy discontinuation. This study aimed to investigate the effect of the pharmacists’ interventions on the health-related quality of life (HRQoL) in older rural patients on warfarin therapy. Eligible older patients from rural area of Croatian province Slavonia were randomized into the intervention and control groups and followed for six months. Repeated education and a follow-up plan were provided to the participants in the intervention group, and if needed, the pharmacist intervened to optimize warfarin therapy. Secondary analysis on HRQoL data are presented here. Main outcome measure was Duke anticoagulation satisfactions scale questionnaire score. In total, 131 participants finished the study (median age 73 years; 51.1% male). Participants in the intervention group scored significantly lower (median being 86.5 and 66.0 in the control and intervention groups, respectively; p < 0,001), indicating higher HRQoL. Adverse drug reactions and pharmacist’s intervention were identified as predictive factors for patients’ HRQoL (r2 = 65.5%, P < 0.001). The study demonstrated that community pharmacist’s interventions can improve HRQoL of older patients taking warfarin what is of particular significance for patients living in rural areas with less accessible healthcare and lower socio-economic status.Clinicaltrials.gov (ID: NCT03212898), 11/07/2017, retrospectively registered.