Time In Therapeutic Range Research Articles

Abstract 12981: Digital Health for the Management of Oral Anticoagulation Therapy: A Systematic Review and Meta-Analysis

Background: Direct oral anticoagulants (DOACs) have progressively replaced vitamin K antagonists (VKAs). However, in certain conditions, especially antiphospholipid syndrome, mechanical heart valves and rheumatic mitral stenosis, VKAs remain the only drugs with established safety and efficacy. In low-income contexts, they are frequently the preferred option due to the high costs of DOACs. Its management is often challenging, and different digital health strategies have been implemented to support it. Aims: To systematically review the evidence on the impact of digital health strategies to support anticoagulation management compared to usual care on thromboembolic and bleeding events. Methods: Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection, data extraction, and quality assessment using the Cochrane risk of bias tool (RoB2). Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models. Results: In total, 25 randomized controlled trials were included (25,746 patients) and classified as moderate to high risk of bias. Telemedicine resulted in a trend of reduced risk of thromboembolic events (13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07; I2=42%), comparable rates of major bleeding (11 studies, RR 0.94, 95% CI 0.82-1.07; I2=0%) and mortality (12 studies, RR 0.96, 95% CI 0.78-1.20; I2=11%), and an improved time in therapeutic range (16 studies, mean difference 3.38, 95% CI 1.12-5.65; I2=90%). In the subgroup of multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48). Conclusions: Digital health strategies resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events and better anticoagulation quality compared to standard care. Given the potential benefits of digital health-based care, such as greater access to remote populations, these findings may encourage further implementation of these strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases.

Antiphospholipid Antibody Syndrome (APS) Pediatric Patient Outcomes on Warfarin

Background: Antiphospholipid antibody syndrome (APS) is an acquired thromboembolism (TE) risk factor and places patients at very high risk of recurrent TE. APS diagnosis requires venous (deep vein thrombosis (DVT) or pulmonary embolism (PE)) or arterial thromboembolism and laboratory diagnosis including persistently positive lupus anticoagulant (LA) or elevated anticardiolipin (aCL) and/or beta 2 glycoprotein I (B2GPI) antibodies tested 12 weeks apart. Vitamin K antagonist (warfarin) is the standard of care anticoagulant to reduce risk of TE recurrence in APS patients. Warfarin is dosed based on the International Normalized Ratio (INR) with established therapeutic ranges for optimal efficacy and safety. The reported time in therapeutic range (TTR) varies greatly across specialties with an average TTR of 50-55%. However, it is often difficult to maintain target INR in APS. Furthermore, there is limited data evaluating pediatric patients with APS and their TTR on warfarin and outcomes. Aim: To evaluate the relationship of APS status to TTR and outcomes of patients < 21 years of age with APS who are on warfarin anticoagulation. Methods: This was a single center analysis of APS patients between July 2019 and May 2022 who were enrolled in a multi-center prospective study of pediatric patients on warfarin therapy, eKITE (electronic KidClot Thrombophilia Education). The study included an online learning series regarding warfarin management. Home INR meters and test strips were provided to all patients to perform INR testing. INR values were reported by patients and recorded. Demographic and clinical data was extracted from the electronic medical record, target INR was set by the treating provider, and TTR was calculated as a surrogate for safe, effective warfarin management. Results: Nine patients (n=9) with APS were identified for this analysis, mean age 16.7 years (range 12-19 years). Demographic and laboratory findings are summarized in Table 1. Most patients had secondary APS due to systemic lupus erythematous (SLE) 78% (n=7) and 22% (n=2) had other primary diagnoses. APS antibody status included single positive in 67% (n=6), double positive in 22% (n=2), and triple positive in 11% (n=1). More specifically, APS criteria were met by persistently elevated LA in 78% (n=7), aCL IgM in 22% (n=2) with overall mean aCL IgM of 34.4 MPL^ (range 9.9-127.9), B2GPI IgG in 11% (n=1) with overall mean B2GPI IgG SGU* of 13.1 (range 0.9-63.3), and B2GPI IgM in 22% (n=2) with overall B2GPI IgM mean of 32.5 SGU (range 3.3-190.9). At time of presentation 67% (n=6) of patients had DVT, 44% (n=4) had PE, 11% (n=1) had arterial TE, and 22% (n=2) presented with DVT & PE. Mean TTR for all patients was 56%. TTR for single positive APS was 66%, double positive APS 39%, and triple positive APS 33%. TTR for secondary APS (SLE) and non-SLE diagnoses was 53% and 68% respectively. Mean dose changes were 11 (range 0-48) with one single positive LA patient requiring 48 dose changes, and two patients with single positive LA not requiring any dose changes. Two patients (22%) developed recurrent clot. One triple positive APS patient developed two DVTs and one non-SLE patient developed recurrent arterial TE. Three patients (33%) had minor bleeding events including mild epistaxis and hematemesis not requiring intervention. One patient (11%) had a major bleeding event, hemoperitoneum from pseudoaneurysm extravasation, while resuming warfarin during post-operative period, and required takeback surgery with sub-therapeutic INR 1.5 at the time of event. Conclusion: The mean TTR for pediatric patients with APS is similar to what is reported in other populations despite the challenge of managing warfarin in this group where the INR may be affected by primary disease modifying medications or disease flares. The risk of recurrent TE remains high in APS patients. Home INR monitors are a safe and effective strategy in managing warfarin anticoagulation in APS patients, reducing time and laboratory monitoring burden for frequent dose changes, which ultimately improves quality of life.Optimizing TTR is important to decrease risk of recurrent TE or bleeding in these high risk APS patients.

Apixaban Vs Vitamin K Antagonist As Anticoagulant Therapy in Patients with End-Stage Kidney Disease on Hemodialysis and with Atrial Fibrillation

BACKGROUND Evidence of net safety and benefit of anticoagulation for stroke prevention in patients with end-stage kidney disease (ESKD) on hemodialysis and with atrial fibrillation (AF) is lacking because patients with advanced CKD and those with end-stage kidney disease (ESKD) have been excluded from randomized clinical trials of stroke prevention in AF. In Europe, apixaban is not approved for the indication of prevention of stroke and systemic embolism in adult patients with ESKD on hemodialysis and AF. AIM To assess the effectiveness and safety according to Apixaban or VKA treatment. The effectiveness outcome was defined by ischemic stroke, all-cause death and myocardial infarction. The safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. METHODS Unicenter, observational and retrospective study. Data was collected between January 2018 and July 2022. We included adult patients with ESKD on hemodialysis and AF and a CHA2DS2-VASc score ≥2 treated with low dose of Apixaban (2.5 mg twice daily) or VKA from the beginning of treatment. Patients in the VKA group received Acenocoumarol. Demographic, laboratory data and clinical presentation of AF were collected. Patients had a minimum follow-up (FU) of 6 months. Apixaban plasma drug concentrations were measured during the FU (week 1 and month 3). Blood samples were draw just before the next dose (Ctrough) and at 2-3 hours (Cpeak) after of drug intake using the Technoclone anti-Xa assay from Technoclone (Vienna-Austria). Bleeding events were classified according to ISTH criteria. RESULTS A total of 302 patients with NVAF and ESKD on hemodialysis were included. Among all patients, 192 (63.5%) were treated with Apixaban and 110 VKA. Mean FU was 14.8 and 12.5 months (DOAC vs VKA; p:0.53). Demographic characteristics are summarised in table 1. In Apixaban group, 100% of patients received reduce-dose, according to the care protocol established in our center and showed predictable pharmacokinetic, Ctrough (94.5- 180 μg/L) and Cmax (150-419 μg/L). In VKA group, Time in therapeutic range (international normalized ratio, 2.0-3.0) for Acenocumarol treated patients was 42% (interquartile range, 19%-60%). Stroke or systemic embolism occurred in three patients in the Apixaban group (1.04 %/year) and seven patients in the VKA group (7.2 %/year) [DOAC vs LMWH; p<0.05]. The apixaban group experienced fewer overall bleeding events than the VKA group (17.3% vs 39.7%; P = .01); this significant difference persisted in adjusted analysis (OR = 0.13; 95% CI = 0.04-0.42; P = .001). Major bleeding events were less frequent in the apixaban group compared with patients on VKA (4.7% vs 25%; P = .01). There were no significant differences regarding in all-cause mortality, 18.8% versus 21.5% respectively. CONCLUSIONS Compared to VKA, our findings suggest that low dose of apixaban is a safe and effective alternative in patients with AF and ESKD on hemodialysisis and low dose of apixaban showed predictable pharmacokinetic.

Which Factors Determine the Success of Anticoagulation with Warfarin

Background: Warfarin is a drug most commonly used for anticoagulation. Its efficiency depends on remaining in the demanded therapeutic range. Objectives: In this study, the relation between the time in therapeutic range (TTR) and sociodemographic characteristics, comorbidities, and drugs used was investigated for the patient’s use of warfarin. Methods: Among patients admitted to the Internal Diseases Polyclinic or taking inpatient treatment in internal diseases service, 50 female and 50 male patients using warfarin were selected starting from the closest date based on their admittance dates. Using patient files and hospital automation system data, TTR levels were calculated with the Rosendaal method, and sociodemographic characteristics, comorbidities, and drugs used were recorded. Patients were separated into 2 groups, TTR > 60% and TTR < 60%, and relations between sociodemographic characteristics, comorbidities, and drugs used were investigated among these groups. Results: Time in therapeutic range was found to be over 60% in 34% of the patients. It was observed that gender, occupation and education level, body mass index, smoking ratios, comorbid diseases, drugs used, serum creatinine, and alanine aminotransferase (ALT) levels were similar among TTR groups. The use of drugs lowering the warfarin effect was found to be similar among TTR groups. Conclusions: It was observed that sociodemographic characteristics, comorbid diseases, used drugs, serum creatinine, and ALT levels of the patients didn't affect the time in the therapeutic range.

Chinese stroke patients with atrial fibrillation used Robert's age-adjusted warfarin loading protocol obtained good INR results within therapeutic range

To assess whether Roberts’ age-adjusted warfarin loading protocol is effective in Chinese patients and whether the SAMeTT2R2 score can predict international normalized ratio (INR) control. Roberts’ protocol for warfarin titration was applied to patients with non-valvular atrial fibrillation (NVAF) complicated with ischemic stroke at the Department of Neurology between 2014 and 2019. Clinical and sociodemographic variables were recorded. A minimum of 1-year follow-up was used to calculate the time in therapeutic range (TTR) of the INR. A total of 94 acute ischemic stroke patients with NVAF were included in the study. Seventy-seven (81.9%) of the patients had attained stable INR (2.0–3.0) at the fifth dose, and 90.0% of the patients had achieved stable INR on the ninth day. Seventeen (18.1%) of the patients had an INR > 4 during dose-adjustment period. Patients with INR > 4 had significantly lower body weight (53.8 vs. 63.1 kg, P = 0.014), lower rate of achievement of stable INR (35.3% vs. 92.2%, P = 0.000), and lower rate of TTR ≥ 65% (23.5% vs. 70.1%, P = 0.001), but with no significant increase in bleeding risk. A total of 89 patients underwent long-term INR follow-up, of which 58 (65.2%) patients achieved TTR ≥ 65%. Patients with poor TTR had significantly lower body weight (56.3 vs. 63.7 kg, P = 0.020) and lower rate of stable INR achievement (64.5% vs. 89.7%, P = 0.002). All 94 patients had SAMeTT2R2 score ≥ 2. There was no linear association between SAMeTT2R2 score and the rate of TTR ≥ 65% (Ptrend = 0.095). Chinese ischemic stroke patients with NVAF on warfarin can safely and quickly achieve therapeutic INR using Roberts’ age-adjusted protocol and can obtain a good TTR. Lower body weight may be a predictor of poor TTR and INR > 4. Patients who have not attained stable INR after adjusting the dose five times are at high risk for poor TTR. SAMeTT2R2 score may not predict TTR in Chinese ischemic stroke patients with NVAF.

Evaluation of antithrombotic treatment in institutionalized geriatric patients with nonvalvular atrial fibrillation

ObjectiveThe goals of this study were to analyze the type of antithrombotic treatment administered to institutionalized patients with nonvalvular atrial fibrillation (and any ensuing complications) and to evaluate the degree of anticoagulation control achieved with vitamin K antagonists. MethodThis was a prospective observational follow-up study carried out in seven elderly care facilities during 2016. Patients with nonvalvular atrial fibrillation were evaluated for their antithrombotic therapy and any embolic or hemorrhagic events, as well as for mortality. Subjects on anticoagulation treatment with VKAs were evaluated for anticoagulation control, with control considered poor if the mean time in therapeutic range was < 65% when measured with Rosendaal's method or < 60% when determined by the direct method. ResultsOf the 699 residents evaluated, 20.6% had a diagnosis of NVAF. Average age was 85.83 years. Both the cardioembolic (mean CHA2DS2-VASc score: 4.79), and the hemorrhagic (mean HAS-BLED score: 3.04) risk were high. Fifty percent received anticoagulation treatment, mainly with vitamin K antagonists, of whom at least 56% were not within the therapeutic range. Sixteen percent of the residents, the oldest and most functionally and cognitively dependent ones, had not been prescribed any antithrombotic therapy. A higher frequency of hospital admissions induced by cardiovascular and bleeding events was found in these residents, although differences were not statistically significant. ConclusionsHalf of institutionalized geriatric patients with nonvalvular atrial fibrillation are anticoagulated, a third on antiplatelet therapy, and some without any antithrombotic treatment. This study showed that as functionality decreases, treatment strategies are increasingly aimed at therapeutic deintensification. Given that the degree of anticoagulation control with vitamin K antagonists is inadequate in 56% of cases, it is essential to monitor the time in therapeutic range to optimize treatment as needed.

Effect of Previous INR Control during VKA Therapy on Subsequent DOAC Adherence and Persistence, in Patients Switched from VKA to DOAC.

Current guideline suggests a switch from vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) in patients with low time in therapeutic range (TTR < 70%). Poor international normalized ratio (INR) control may be the result of poor compliance, and might therefore be associated with subsequent DOAC intake. Therefore, this study evaluates the effect of previous TTR and other measures of INR control on DOAC nonadherence and nonpersistence, in patients who switched from VKA to DOAC. A total of 437 patients who switched from VKA to DOAC between 2012 and 2019 were included using data from Certe Thrombosis Service, IADB.nl pharmacy community database University Groningen, and Statistics Netherlands. DOAC prescriptions were used to determine nonadherence and nonpersistence. INR control (i.e., TTR, time under therapeutic range [TUR], and INR variability) was assessed during the last 180 days of VKA use. Multivariable regression models were applied to determine the association between INR control and DOAC nonpersistence/nonadherence. On VKA, 67.7% of the patients had a TTR below 70%. DOAC nonpersistence was 39.8% (95% confidence interval [CI]: 33.4-45.5%) during a median follow-up of 34.4 months (interquartile range: 19.1-49.2). Approximately 80% of persistent patients were DOAC-adherent. Low TTR was not associated with DOAC nonpersistence (hazard ratio: 1.14, 95% CI: 0.69-1.87) and DOAC nonadherence (odds ratio: 1.38, 95% CI: 0.67-2.84), nor were TUR and INR variability. Previous INR control during VKA therapy is not associated with subsequent DOAC nonadherence and nonpersistence. This study suggests that INR control on VKA cannot, and therefore should not, be used for predicting DOAC adherence or persistence.

Impact of obesity on the conversion of immediate-release tacrolimus to extended-release tacrolimus in kidney transplant recipients.

Outcomes analyzing conversion from IR-tacrolimus (IR) to LCP-tacrolimus (LCP) in obesity are limited. This was a retrospective longitudinal cohort study of patients converted from IR to LCP from June 2019 to October 2020. Primary outcomes were conversion ratios for weight-based dose at a steady-state therapeutic level and identification of appropriate dosing weight. Other outcomes included tacrolimus coefficient of variation (CV), time in therapeutic range (TITR), adverse events, infections, donor specific antibodies (DSAs), and acute rejection. A total of 292 patients were included; 156 and 136 patients with a BMI<30 and BMI≥30kg/m2 , respectively. Baseline characteristics were similar, except for pancreas transplant, diabetes, and HLA mismatch. IR to LCP conversion ratio ranged from .73 to .79. Mean LCP dose was similar (.08 vs. .07mg/kg/day for BMI<30 and BMI≥30kg/m2 , respectively); there was a significant difference in IR and LCP mg/kg dosing at steady state with TBW (.11mg/kg vs.09mg/kg and .08mg/kg vs. .06mg/kg, respectively). The most appropriate dosing weight was adjusted body weight (AdjBW), consistent across IR and LCP steady-state doses, and might yield more accurate steady-state dosing requirements. In multivariable modeling, BMI was a significant predictor of steady state mg/kg dosing at therapeutic goal for total body weight (TBW), but not ideal body weight (IBW) or AdjBW.

A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial

BackgroundAtrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF.MethodsThe study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction.DiscussionThis study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries.Trial registrationChiCTR ChiCTR2200062123. Registered on 23 July 2022.

PB1086 Time in Therapeutic Range after an Event: Where We Started from and Where Are We Going?

PB1086 Time in Therapeutic Range after an Event: Where We Started from and Where Are We Going?

Challenges in Achieving Optimal Warfarin Anticoagulation Control: A Comprehensive Exploration and Proposed Holistic Approaches

In Indonesia warfarin remains the most widely oral anticoagulation prescribed. However, the time in therapeutic range remain low in Indonesia and also in some countries in throughout the world. This study aimed to analyse the challenges of optimal warfarin control from the perspectives of healthcare professionals, patients, health system, and to propose strategies to address these challenges. This research consists of two stages. The first stage was a prospective observational study aiming to analyse the challenges and the second stage of the research was focus group discussion to propose strategies to overcome the challenges. The result of this study showed that the average of TTR was 49.4 ± 32.1, where only 37.5% patients had TTR ≥ 65%. The average dosing consistency obtained was 62.33 ± 32.42%. With regard to INR monitoring interval, almost all patient who had supraterapeutic INR had their INR monitoring interval set to 1 month after the dose adjustment. There were also identified that only 43.8% patients classified as adherent and only 39.5 % patients had good knowledge of warfarin, indicating that the level of medication adherence and knowledge was not optimal. In this study, 14.6% of patients received other drugs that potentially interacted with warfarin that cause fluctuate INR. In conclusion, this study's results showed that there were multiple challenges for optimal warfarin control including barrier for dosing consistency, INR monitoring, patients’ adherence and knowledge, as well as drug interactions. However, there will be still room for improvement. The proposed strategy that likely will achieve optimal benefit was a holistic approach that combine multifaceted strategies to address each barrier.

Home systolic blood pressure time in therapeutic range and cardiovascular risk: the practitioner-based nationwide J-HOP study extended.

Time in therapeutic range (TTR) for office systolic blood pressure (SBP) is an independent predictor of major cardiovascular events. However, the clinical implications of TTR for home SBP have not yet been investigated. This study determined the association between TTR of home SBP and cardiovascular events in individuals with ≥1 cardiovascular risk factor who were enrolled in The Japan Morning Surge-Home Blood Pressure (J-HOP) study. The therapeutic range for home SBP was defined as home SBP of 100-135 mmHg during the 13-day baseline period of the J-HOP study. Participants were divided into subgroups based on quartiles of TTR for home SBP, and the risk of cardiovascular events was determined in each quartile. During a mean 6.3 years of follow-up in 4070 participants (mean age 65 years), cardiovascular events included stroke in 92, coronary artery disease in 119, heart failure in 41 and aortic dissection in 8. The adjusted hazard ratio (95% confidence interval) for the risk of total cardiovascular events in participants with home SBP TTR in the lowest (100%) versus highest quartile (<15.3%) was 1.74 (1.16-2.61); the corresponding hazard ratio for stroke events was 2.11 (1.06-4.21). A 10% decrease in home SBP TTR was associated with a 4% increase in the risk of total cardiovascular events (p = 0.033) and a 9% increase in the risk of stroke (p = 0.004). The significant association seen between home SBP TTR and the occurrence of cardio- and cerebrovascular events highlights the importance of achieving stable reductions in home SBP and minimizing day-by-day home BP variability.Clinical Trial Registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000000894 (J-HOP study).

Real-world evidence that among atrial fibrillation patients warfarin is associated with reduced nonelective admissions compared with those on DOACs.

Randomized trials show inconsistent estimates on risks of direct-acting oral anticoagulants (DOACs) versus warfarin in bleeding and mortality for atrial fibrillation (AF) patients. Trials are confounded by additional DOAC adherence support, while warfarin has a low time in therapeutic range. Few real-world studies compared emergency hospitalization risk between DOAC and warfarin users in AF. This study aimed to determine emergency hospitalization risk for AF patients on DOACs or warfarin in real-world settings. A tapered-matched real-world cohort extracted data from 412 English general practices' primary care records linked with emergency department (ED) and hospitalization data from the ECLIPSE database. AF patients with new DOAC or warfarin prescriptions were included. The primary outcome was all-cause ED attendance; the secondary outcomes were ED re-attendance, nonelective hospitalization, and rehospitalization within 12 months. Weighted Cox regression estimated relative risk difference. 39 201 DOAC patients were matched with 13 145 warfarin patients. DOAC patients had a 25% higher likelihood of attending ED (odds ratio 1.25; 95% confidence interval [CI] 1.01-1.55). DOAC use also associated with higher ED re-attendance, nonelective hospitalization, and rehospitalization within 12 months: 1.41 (95% CI 1.00-1.98), 1.26 (1.00-1.57), and 1.54 (1.01-2.34), respectively, with p-values < .05. DOACs for AF thromboprophylaxis are associated with the increased risk of ED attendance, recurrent hospitalization, and numerical rise in ED re-attendance and first nonelective hospitalization compared to warfarin. However, these real-world data cannot establish if this difference results from medication adherence, lack of regular warfarin clinic monitoring, unmeasured confounders, or fundamental agent efficacy disparities.

Decentralization and Virtualization of INR-based Anticoagulation Control During the COVID-19 Pandemic.

To investigate the effectiveness of the decentralization and virtualization of anticoagulation clinics just before and during the coronavirus disease 2019 (COVID-19) pandemic. We conducted a cohort study investigation at Prince Sultan Cardiac Clinics PSCC Qassim region, Saudi Arabia. To evaluate the effectiveness of the virtual coagulation clinic, we calculated the time in therapeutic range (TTR), Morisky score for adherence, and satisfaction. Demographics of the patients were analyzed to group patients based on their regions or districts to facilitate the visits. Thirteen different PHCs/Hospitals were allocated for decentralization based on patient density in that region. Intensive courses were provided for all general practitioners (GPs) regarding warfarin anticoagulation and point of care testing (POCT) using iSTAT. All appointments were scheduled by WhatsApp, with no more actual visits to the main center. Among the included participants (n = 5616), 61.1% were females, 38.9% were males, and the mean age was 60.5 (18-85) years. The total number of clinic visits was 7303 per month, with an average of 1.3 visits per patient. Approximately 95% of the participants had a valvular indication to receive anticoagulation; of them, 55% underwent mitral valve replacement. Moreover, after the virtualization of the INR clinic, keeping INR levels within a therapeutic range was reported in 80% of patients. Regarding patient satisfaction, 90% of the total population was satisfied by the new experience. Decentralization and virtualization of the INR clinic have similar TTR results if conducted properly.

Clinical, economic, and humanistic impact of a multidisciplinary medication review with follow-up for anticoagulated patients treated with vitamin K antagonists in primary care: A cluster randomised controlled trial

BackgroundInterdisciplinary collaboration between general practitioner, nurses and pharmacists can favour the control of patients treated with vitamin K antagonists (VKA), increasing their safety and effectiveness. The aim of the study was to evaluate the impact of pharmaceutical interventions on patients treated with VKA within the framework of a Pharmacotherapeutic Follow-up service on clinical, economic and humanistic outcomes. MethodsControlled and randomized study in patients from two health areas of Zaragoza in treatment with VKA with Time in Therapeutic Range (TTR) according to the Rosendaal method less than 70% in the last 6 months. Patients were recruited at the pharmacy and assigned to two groups: control and intervention. A Pharmacotherapeutic Follow-up Program was established for the intervention group for 6 months. The outcome variables were INR stability, pharmacological adherence, vitamin K intake, knowledge about the use of acenocoumarol, quality of life, satisfaction with treatment, associated costs and avoided costs. A descriptive analysis was performed, and the Students' T test or Mann-Whitney U test was used for the association between quantitative variables and Chi-square or Fisher's test for qualitative variables. ResultsA total of 123 patients were included, 65 in the intervention group (IG) and 58 in the control group (CG). A total of 108 interventions were conducted (1.7 interventions/patient) and the most common were those related to the proper taking of medications (41.0%). In IG, TTR (p = 0.019), adherence to treatment (p = 0.038) and knowledge about acenocoumarol (p = 0.031) improved, compared to CG. A higher proportion of patients in IG achieved a TTR>65% (p = 0.024). In addition, patients whose interventions were accepted by the physician (p = 0.027) and those who received vitamin K optimization interventions (p = 0.003) achieved TTR>65% in greater proportion. ConclusionsCommunity pharmacist medication review, in collaboration with general practitioners improve knowledge and adherence of patients treated with oral anti-vitamin K agents and enhances the achievement of their therapeutic INR ranges. Investment needed to achieve this clinical impact is low and patient satisfaction is high. Trial registrationThis study has been registered with Clinical Trials.gov dated 25/05/2017: NCT03154489.

Application of a warfarin dosing calculator to guide individualized dosing versus empirical adjustment after fixed dosing: a pilot study.

Background: Warfarin has a narrow therapeutic window and individual variation, and patients require regular follow-up and monitoring of the International Normalized Ratio (INR) for dose adjustment. The calculation method of Warfarin Dosing Calculator (WDC) software is based on the European and American populations, and its accuracy in the Chinese population is yet to be verified. Objective: This study was to evaluate the feasibility of applying Warfarin Dosing Calculator software intervention in a real-world clinical research setting in China. Methods: The pilot study divided the included patients after valve replacement into an experimental group and a control group, with 38 cases in each group. In the control group, the initial dose was fixed at 2.5mg/d and the dose was adjusted empirically during the study period; in the experimental group, the Warfarin Dosing Calculator software was applied to guide the dosing, and patients in both groups were followed up for 3months. Analysis of the incidence anticoagulation outcomes and excessive anticoagulation events in both groups. Kaplan-Meier survival curves were used to analyze the correlation between different dosing regimens and first International Normalized Ratio attainment, and Logrank tests were performed. Results: The mean time required for first International Normalized Ratio compliance in the experimental group was 4.38days less than in the control group, and the mean number of tests was 1.43 less (p < 05). Time in therapeutic range (TTR) was significantly higher in the experimental group than in the control group (p < 05). Kaplan-Meier survival curve analysis showed that the first International Normalized Ratio attainment rate was significantly higher in the experimental group than in the control group (p = 01). No major bleeding events occurred in either group, but other excessive anticoagulation events (INR>3.5 and minor bleeding) were significantly reduced in the experimental group compared with the control group (p < 05). Conclusion: Application of Warfarin Dosing Calculator software to guide individualized warfarin dosing may be better than a fixed dose of 2.5mg/d. It may be shorten the time to first International Normalized Ratio attainment, and the attainment rate in the same time, and can better improve the mean Time in therapeutic range level value and reduce excessive anticoagulation events, which improves the safety of warfarin anticoagulation therapy in clinical practice. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=52793, ChiCTR2000032393.

Assessment of the relationship between the level of patient knowledge on warfarin therapy and the quality of oral anticoagulation: A systematic review and meta-analysis.

The present study aimed to investigate the relationship between the level of patient knowledge on warfarin therapy and the quality of oral anticoagulation. This is a systematic review and meta-analysis written on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Searches at MEDLINE, EMBASE, Scopus and LILACS electronic databases were carried out on February 13, 2023, using the descriptors "Patient Medication Knowledge", "Patient Education as Topic", "Health Education", "Patient Education" and Warfarin. The steps of selection, data extraction and quality analysis of articles were performed independently by two reviewers. The analysis was performed considering patient knowledge as a possible modifier of time in therapeutic range (TTR). The meta-analysis included studies that reported the correlation coefficient (Pearson or Spearman) between patient knowledge and TTR. A subgroup analysis was performed according to questionnaires employed to measure patient knowledge. Twelve studies were selected with an overall sample size of 7634 participants and mean age 58.2 (standard deviation (SD)±12,8) years. Eleven (92.0%) cross-sectional studies. The mean TTR was 57.8% (SD±11,3%) and the average level of knowledge was 60.4%. The meta-analysis indicated that patient level of knowledge on warfarin therapy was moderately associated with TTR (rs = 0.435; 95% confidence interval (CI) = 0.163-0.645; I2 = 96%). Subgroup analysis indicated association between knowledge level and TTR in studies employing the OAK test (rs = 0.617; 95% CI = 0.192-0.847; I2 = 97%) and the AKA (rs = 0.269; 95% CI = 0.002 to 0.501; I2 = 94%). However, the subgroup analysis presented no significant difference between them (p = 0.14). The meta-regression showed a non-significant negative effect of age on the correlation (estimate = -0.028, 95% CI = -0.073 to 0.016, p = 0.207). No publication bias was noted (p = 0.881). To our knowledge, this is the first systematic review and meta-analysis gathering evidence about the relationship between the level of patient knowledge on oral anticoagulation with warfarin and TTR. The implementation of structured and patient-centered educational interventions is essential to effectively increase the level of patient knowledge and, thus, to improve the quality and safety of warfarin therapy. Systematic review registration number: PROSPERO CRD42023398030.

DOES THE TIMING OF WARFARIN INGESTION AFFECT THE TIME IN THERAPEUTIC RANGE IN PATIENTS WITH METALLIC PROSTHETIC VALVE?

Aim: Warfarin , a vitamin K antagonist, is the only approved oral agent to provide anticoagulation in patients with metallic prosthetic valves. Since effectively initiating and maintaining anticoagulation is challenging due to various factors , those patients undergo frequent periodic INR testing. The aim of this study was to investigate the effect of the timing of warfarin ingestion on the stability of anticoagulation.&#x0D; Materials and Methods: A total of 60 patients with metallic prosthetic valves were included in the study. First, all the patients were informed to take warfarin between 19:30 and 20:00 during the first month, then to take warfarin between 09:30 and 10:00 during the second month. All the patients underwent INR monitoring once every 15 days during the follow-up period. The time in therapeutic range (TTR) values for the first month and second month ( referred to as ‘first TTR’ and ‘second TTR’, respectively) were calculated separately using the Rosendaal method. &#x0D; Results: The mean age ( ± SD) of the patients was 59.6 ± 9.6 years and 36.7% (n=22) were male. There was no significant difference between the first TTR and second TTR values of the patients (66.23 ± 40.7% vs 64.12 ± 41.13%, p=0.783). The mean INR value in the first month was found to be significantly lower than in the second month (2.73 ± 0.53 vs 3.06 ± 0.47, p=0.001). &#x0D; Conclusion:.The study results showed that the timing of warfarin ingestion did not affect the stability of anticoagulation although taking the warfarin in the morning provided higher INR values.

Evaluation of Bivalirudin During Adult Extracorporeal Membrane Oxygenation: A Retrospective Characterization of Dosing, Efficacy and Bleeding.

Objective: Although heparin is the current standard anticoagulant during venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO), factors including heparin-induced thrombocytopenia, heparin resistance and drug shortages necessitate alternative anticoagulants such as direct thrombin inhibitors. The aim was to characterize dosing, safety, and efficacy of bivalirudin during ECMO support. Methods: This retrospective single-center study included 24 adults on ECMO support who received ≥6 hours of bivalirudin. The primary endpoint was dose to first therapeutic activated partial thromboplastin time (aPTT). Secondary endpoints included evaluating dosing between ECMO modes, incidence of bleeding and thrombotic events, and time in therapeutic range (TTR). Results: The dose at time of first therapeutic aPTT was bivalirudin 0.05 [0.05-0.1] mg/kg/hour. Bivalirudin dosing requirements were lower in VAECMO compared to VV-ECMO patients and were not impacted by continuous venovenous hemofiltration. Time to therapeutic aPTT was 5.5 [2-13] hours for VA-ECMO and 4.5 [2-8.6] hours for VV-ECMO patients. During any mode of ECMO TTR was 58.3% [39.6-73.1]. Thrombotic events occurred in 3 (13%) patients and major bleeding occurred in 12 (50%) patients. Conclusions: Our findings demonstrated variable bivalirudin dosing requirements based on mode of ECMO and dosing modifications may not be required during CVVH. Factors including mode of ECMO, indication for bivalirudin and concomitant antiplatelet therapy may impact hematologic events. Application of this data can assist with developing a bivalirudin ECMO protocol which provides less variability in initial dosing and TTR.

A "Bundle of Care" to Improve Anticoagulation Control in Patients Receiving Warfarin in Uganda and South Africa: Protocol for an Implementation Study.

The quality of warfarin anticoagulation among Sub-Saharan African patients is suboptimal. This is due to several factors, including a lack of standardized dosing algorithms, difficulty in providing timely international normalized ratio (INR) results, a lack of patient feedback on their experiences with treatment, a lack of education on adherence, and inadequate knowledge and training of health care workers. Low quality of warfarin anticoagulation, expressed as time in therapeutic range (TTR), is associated with higher adverse event rates, including bleeding and thrombosis, and ultimately, increased morbidity and mortality. Processes and interventions that improve this situation are urgently needed. This study aims to evaluate the implementation of the "warfarin bundle," a package of interventions to improve the quality of anticoagulation and thereby clinical outcomes. The primary outcome for this study is TTR over the initial 3 months of warfarin therapy. Patients aged 18 years or older who are newly initiated on warfarin for venous thromboembolism, atrial fibrillation, or valvular heart disease will be enrolled and followed up for 3 months at clinics in Cape Town, South Africa, and Kampala, Uganda, where the warfarin bundle is implemented. A retrospective review of the clinical records of patients on warfarin treatment before implementation (controls) will be used for comparison. This study uses a mixed methods approach of the implementation of patient- and process-centered activities to improve the quality of anticoagulation. Patient-centered activities include the use of clinical dosing algorithms, adherence support, and root cause analysis, whereas process-centered activities include point-of-care INR testing, staff training, and patient education and training. We will assess the impact of these interventions by comparing the TTR and safety outcomes across the 2 groups, as well as the cost-effectiveness and acceptability of the package. We started recruitment in June 2021 and stopped in August 2022, having recruited 167 participants. We obtained ethics approval from the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee, the Provincial Health Research Committees in South Africa, the Joint Clinical Research Centre Institutional Review Board, Kampala, and the University of Liverpool Research Ethics Committee. As of February 2023, data cleaning and formal analysis are underway. We expect to publish the full results by December 2023. We anticipate that the "bundle of care," which includes a clinical algorithm to guide individualized dosing of warfarin, will improve INR control and TTR of patients in Uganda and South Africa. We will use these findings to design a larger, multisite clinical trial across several Sub-Saharan African countries. DERR1-10.2196/46710.