The Therapeutic Range Research Articles

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 < 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.

Effectiveness of Smartphone Applications vs Conventional Care in Warfarin Therapy: A Randomized Controlled Trial on the Time in the Therapeutic Range

Objective: Warfarin is extensively used as an oral anticoagulant; however, its clinical application is complicated by a narrow therapeutic index. This investigation evaluated the efficacy of a drug reminder application versus traditional care in facilitating patients’ maintenance of the therapeutic range, as well as in stabilizing the time in the therapeutic range (TTR). Material and Methods: A single-blind randomized controlled trial recruited 40 warfarin users (≥3 months) with stable INR for 6 months. The intervention group received a smartphone app reminder. All INR values were collected for 6 months. Primary outcomes were TTR, INR, TTR during drug-drug interactions, and warfarin complications. Results: Forty patients were recruited between January 2021 and August 2023. The mean TTR was 66.11%±9.8% for the intervention group and 67.31%±18.08% for the control group. With analysis of covariance, the results were slightly better in the intervention group, but the differences were not statistically significant (95%CI = -5.67 – 1.92, P-value = 0.323). For the 6-month INR monitoring, 6 out of 8 patients who could maintain the therapeutic INR range were in the intervention group. There were no statistically significant differences in warfarin-related complications between the two groups (20% vs 15%, RR 1.333, 95%CI = 0.3413 – 5.2086, P-value = 0.6790). Conclusion: The drug reminder application likely improved the TTR, although without statistical significance. Further studies are needed to identify technology assistance in improving treatment outcomes.

Mechanical valve replacement for patients with rheumatic heart disease: the reality of INR control in Africa and beyond.

The majority of patients requiring heart valve replacement in low- to middle-income countries (LMICs) need it for rheumatic heart disease (RHD). While the young age of such patients largely prescribes replacement with mechanical prostheses, reliable anticoagulation management is often unattainable under the prevailing socioeconomic circumstances. Cases of patients with clotted valves presenting for emergency surgery as a consequence of poor adherence to anticoagulation control are frequent. The operative mortality rates of reoperations for thrombosed mechanical valves are several times higher than those for tissue valves, and long-term results are also disappointing. Under-anticoagulation prevails in these regions that has clearly been linked to poor international normalised ratio (INR) monitoring. In industrialised countries, safe anticoagulation is defined as >60%-70% of the time in the therapeutic range (TTR). In LMICs, the TTR has been found to be in the range of twenty to forty percent. In this study, we analysed >20,000 INR test results of 552 consecutive patients receiving a mechanical valve for RHD. Only 27% of these test results were in the therapeutic range, with the vast majority (61%) being sub-therapeutic. Interestingly, the post-operative frequency of INR tests of one every 3-4 weeks in year 1 had dropped to less than 1 per year by year 7. LMICs need to use clinical judgement and assess the probability of insufficient INR monitoring prior to uncritically applying Western guidelines predominantly based on chronological age. The process of identification of high-risk subgroups in terms of non-adherence to anticoagulation control should take into account both the adherence history of >50% of patients with RHD who were in chronic atrial fibrillation prior to surgery as well as geographic and socioeconomic circumstances.

Appropriateness of anticoagulation level in older adult patients on Warfarin: A multicenter retrospective study

Warfarin is favored over newer direct oral anticoagulants (DOACs) for many older adults. However, its use necessitates rigorous monitoring due to the fine line between toxic and therapeutic doses. Few studies have evaluated the anticoagulation quality of warfarin among elderly patients in Saudi Arabia. This study aimed to assess and identify factors affecting the anticoagulation quality of warfarin using the time in the therapeutic range (TTR) among older adults attending two hospitals in Saudi Arabia. Additionally, we aimed to evaluate differences in the anticoagulation quality of warfarin when managed by pharmacists or physicians. This cross-sectional study was conducted at King Abdullah bin Abdulaziz University Hospital (KAAUH) and King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. After calculating the TTR of each patient, the anticoagulation control level was determined using these values: a) good control: >70 %; b) intermediate control: 50–70 %; c) poor control: <50 %. A total of 132 patients prescribed warfarin therapy for different indications were included. Most patients (45.5 %) had poor control with TTRs < 50 %, while 18.2 % had intermediate control, and 36.4 % had good control.Our exploratory findings suggest that having three or more comorbidities was a significant factor associated with a poor TTR [odds ratio (OR) = 3.36; (95 % confidence interval 1.28–8.81); P = 0.014]. Thus, the anticoagulation quality of warfarin among older adult patients was poor in two Saudi Arabian tertiary hospitals, and the number of comorbidities was a potentially poor TTR predictor.

Telemedicine-based medical care compared to in-person medical care for warfarin follow-up: A retrospective propensity score matching cohort study.

Telemedicine is underutilized in Saudi Arabia, which is a matter of concern, especially since previous literature has showed its equivalence with office visits in providing access to care and convenience for patients while reducing anticoagulation-related bleeding events when appropriate measures are followed. The purpose of this study is to analyze the efficacy of telehealth-based care compared to in-person visit care for warfarin follow-up. The authors conducted a retrospective chart review comparing the mean percentage of time in the therapeutic range (TTR) of international normalized ratio (INR) values among patients prescribed warfarin from July 2019 to November 2020 at King Faisal Specialist Hospital & Research Center - Jeddah Branch whose anticoagulant therapy was managed via telemedicine or through in-person clinic visits. A subcohort analysis of outcomes in the telemedicine and in-person groups was performed using propensity score matching, and descriptive analysis was done for the entire cohort. A total of 350 patient records were included in this retrospective study. Matched analysis for 148 patients using propensity score matching showed that the mean (SD) percentages of TTR were 62.82% (19.46%) and 70.61% (19.83%) in the telemedicine and in-person groups, respectively (P = 0.017). There was no statistical difference in the incidence of major or minor bleeding events, thromboembolic events, and hospital readmission between the two groups. The study results showed that patients on oral anticoagulation therapy managed through a telemedicine method had a lower overall TTR percentage than a matched group of patients managed through in-person anticoagulant clinic visits, thus demonstrating that using a telemedicine approach alone for warfarin follow-up may not help patients to maintain their INR target level.

Simulating clinical trials for model-informed precision dosing: using warfarin treatment as a use case

Treatment response variability across patients is a common phenomenon in clinical practice. For many drugs this inter-individual variability does not require much (if any) individualisation of dosing strategies. However, for some drugs, including chemotherapies and some monoclonal antibody treatments, individualisation of dosages are needed to avoid harmful adverse events. Model-informed precision dosing (MIPD) is an emerging approach to guide the individualisation of dosing regimens of otherwise difficult-to-administer drugs. Several MIPD approaches have been suggested to predict dosing strategies, including regression, reinforcement learning (RL) and pharmacokinetic and pharmacodynamic (PKPD) modelling. A unified framework to study the strengths and limitations of these approaches is missing. We develop a framework to simulate clinical MIPD trials, providing a cost and time efficient way to test different MIPD approaches. Central for our framework is a clinical trial model that emulates the complexities in clinical practice that challenge successful treatment individualisation. We demonstrate this framework using warfarin treatment as a use case and investigate three popular MIPD methods: 1. Neural network regression; 2. Deep RL; and 3. PKPD modelling. We find that the PKPD model individualises warfarin dosing regimens with the highest success rate and the highest efficiency: 75.1% of the individuals display INRs inside the therapeutic range at the end of the simulated trial; and the median time in the therapeutic range (TTR) is 74%. In comparison, the regression model and the deep RL model have success rates of 47.0% and 65.8%, and median TTRs of 45% and 68%. We also find that the MIPD models can attain different degrees of individualisation: the Regression model individualises dosing regimens up to variability explained by covariates; the Deep RL model and the PKPD model individualise dosing regimens accounting also for additional variation using monitoring data. However, the Deep RL model focusses on control of the treatment response, while the PKPD model uses the data also to further the individualisation of predictions.

Efficacy of an Anticoagulation Clinic in Low-Income Brazilian Patients with Heart Disease: A Randomized Clinical Trial

Anticoagulation clinics (ACs) have a greater impact on anticoagulation control than usual medical care (UMC). There is little evidence of the performance of AC in patients on warfarin living in low and middle-income countries. We sought to investigate the efficacy and safety of an AC in patients treated at a Brazilian public hospital. This was a randomized clinical trial that tested the efficacy of a recently implemented AC, compared to UMC, in outpatients with heart disease. The primary and secondary endpoints were time in the therapeutic range (TTR) and warfarin-related complications, respectively. Overall, 280 patients were enrolled and randomly assigned to Group A: one year at an AC (A1: first half-year; A2: second half-year); and Group B: first half-year receiving UMC (B1) and second half-year being assisted at the AC (B2). The mean age was 56.8 ± 13.1 years, and most patients were female (54.6%). Above 68% of patients had limited reading capability. A1 demonstrated greater TTR (62.4 ± 20.8%) than B1 (55.1 ± 28.5%) (p = 0.014). Group B improved TTR from 55.1 ± 28.5% (B1) to 62.2 ± 23.1% (B2) (p = 0.008). Despite the underpowered analysis of safety, A1 exhibited a lower incidence rate (IR) per patient-year (p-y) of total bleeding than B1 (incidence rate ratio (IRR): 0.78; p = 0.041) and a reduction in intra-group comparisons (both groups: IRR 0.58; p &lt; 0.001). AC care helped increase TTR in a low-income setting showing favorable performance in a distinct population of those evaluated by previous studies. Extending AC care to similar populations may improve the outcomes of warfarin use.

Pressure changes in the endotracheal tube cuff in otorhinolaryngologic surgery: a prospective observational study.

Inflation of the endotracheal tube cuff is needed for providing ventilation. Cuff pressure should be maintained inside the appropriate range to prevent critical airway complications. The purpose of this study is to evaluate the pressure changes in the endotracheal tube cuff during otorhinolaryngologic surgery. This single-center observational study was conducted at Severance Hospital in Korea between April 2020 and November 2020. Patients aged >20 years scheduled to undergo otorhinolaryngological surgical procedures were enrolled. Patients undergoing planned tracheostomy and those who were slated for uncuffed endotracheal tube use were excluded. Intubation was performed after the induction of general anesthesia. A pressure transducer was connected to the pilot balloon of the endotracheal tube, and cuff pressure was continuously monitored until extubation. If the cuff pressure was not appropriate for more than 5 min, it was adjusted to the appropriate range by injecting or removing air. The percentage of time for which the cuff pressure remained within the appropriate range was calculated and defined as the time in the therapeutic range (TTR). The presumed cause for the rise or fall in cuff pressure was identified. In total 199 patients, alterations in cuff pressure outside the appropriate range occurred in 191 patients (96.0%). The mean TTR was 79.7% (SD 25.0%), and head and neck surgery had the lowest mean TTR of 69.0% compared to ear and nose surgeries (94.2 and 82.1%, respectively). Sixty-eight patients (34.2%) demonstrated inadequate endotracheal tube cuff pressure for more than 20% of the total anesthesia time. Twenty-six patients (13.1%) demonstrated optimal endotracheal tube cuff pressure for less than 50% of the total anesthesia time. The causative factors inducing inappropriate cuff pressure were found to vary, including positional changes, surgical procedure, anatomical manipulation, and anesthetic procedure. In otorhinolaryngologic surgery, cuff pressure increased or decreased outside the appropriate range due to various factors. Therefore, we suggest close continuous monitoring of cuff pressure during anesthesia for otorhinolaryngologic surgery. clinicaltrials.gov, identifier NCT03938493.

Higher tacrolimus trough levels and time in the therapeutic range are associated with the risk of acute rejection in the first month after renal transplantation

BackgroundTacrolimus trough levels (C0) are used in most transplant centres for therapeutic drug monitoring (TDM) of tacrolimus (Tac). The target range of Tac C0 has been remarkably changed, with a target as low as 3–7 ng/ml in the 2009 European consensus conference and a target of 4–12 ng/ml (preferably to 7–12 ng/ml) following the second consensus report in 2019. Our aim was to investigate whether reaching early Tac therapeutic targets and maintaining time in the therapeutic range (TTR) according to the new recommendations may be necessary for preventing acute rejection (AR) during the first month after transplantation.MethodsA retrospective study including 160 adult renal transplant patients (113 men and 47 women) with a median age of 36.3 (20–44) years was conducted between January 2018 and December 2019 at 103 Military Hospital (Vietnam). Tac trough levels were recorded in the first month, and episodes of AR were confirmed by kidney biopsy. Tac TTR was calculated as the percentage of time within the target range of 7–12 ng/ml, according to the 2019 second consensus report. Multivariate Cox analysis was performed to identify the correlation between the Tac target range and TTR with AR.ResultsIn the first month after RT, 14 (8.8%) patients experienced AR. There was a significant difference in the incidence of AR between the Tac level groups of < 4, 4–7 and > 7 ng/ml (p = 0.0096). In the multivariate Cox analysis, after adjusting for related factors, a mean Tac level > 7 ng/ml was associated with an 86% decreased risk of AR compared with that of 4–7 ng/ml in the first month (HR, 0.14; 95% CI, 0.03–0.66; p = 0.0131). Every 10% increase in TTR was associated with a 28% lower risk of AR (HR, 0.72; 95% CI, 0.55–0.94; p = 0.014).ConclusionGaining and maintaining Tac C0 according to the 2019 second consensus report might reduce the risk of AR in the first month following transplantation.

PO-04-216 PATIENT ENABLED INR OPTIMIZATION : A MULTICENTER PROSPECTIVE STUDY

For patients using Vitamin K antagonists (VKA), maximizing time within the therapeutic range (TTR) reduces stroke, major hemorrhage, and death. Despite improvements in counselling and patient education, patients using Vitamin K antagonists have a poor TTR. The objective of this study was to evaluate the effectiveness and safety of a smartphone application for improvement in TTR with minimal physician interference. Content was customized on a smartphone based platform (INR Assist) for patients using VKA which included automated INR dosage adjustment, tracking, reminders, and education. A multicenter prospective open-label study was conducted at two tertiary care medical centers with patients using VKA for at least the previous 6 months. In order to tailor INR dose adjustment, patients were enrolled into either normal bleeding/thrombotic risk (Group A), high bleeding risk (Group B) or high thrombotic risk (Group C) at the discretion of the treating physician. The primary endpoint of the study was the change in TTR before and after 6 months of using INR Assist. Secondary endpoints included stroke, major bleeding, and red-alerts (INR not in TTR for 3 consecutive entries, INR>6.0, INR<1.5) by the application that required direct physician assistance. There were 184 patients (mean age 50.5 + 8.2, males 68.5%) using VKA for either AF stroke prevention (54.9%), metallic valve replacement (38.6%), or venous thromboembolism (6.5%) were included in the study between January 2019 and June 2022. The number of patients enrolled in Groups A, B, and C were 145 (90.2%), 10 (6.0%), and 7 (3.8%), respectively. After a minimum of 6 months of using INR Assist, TTR improved from 59.2 + 6.7% to 80.5 + 9.4% (p<0.001). The improvement in TTR was similar in all three groups (p<0.001). There were fewer bleeding(3.1% vs. 1.2%, p=0.105) and thrombotic events (2.5% vs. 0.6%, p=0.115) following utilization of INR Assist. Overall there were 27 red-alerts during the study period. These alerts included INRs not within therapeutic range for 3 consecutive entries (n=9, 33.3%), INR > 6.0 (n=11, 40.7%), and INR < 1.5 (n=7, 25.9%). Smart phone based mobile application (INR Assist) by patients using VKAs was safe and led to an improvement in TTR.

Clinical impact of plasma concentrations of first-line antituberculosis drugs.

The clinical significance of low antituberculosis (anti-TB) drug concentrations has not been fully elucidated. To investigate the clinical consequences of first-line drug concentrations in adult patients with drug-susceptible pulmonary TBin South Africa (SA). We conducted a pharmacokinetic study nested within the control arm of the Improving Treatment Success (IMPRESS) trial(NCT02114684) in Durban, SA. During the first 2 months of treatment, participants received weight-based dosing of first-line anti-TBdrugs (rifampicin, isoniazid, pyrazinamide and ethambutol), and had plasma drug concentrations measured at 2 and 6 hours after drugadministration during the 8th week of treatment. Intermediate (8 weeks), end-of-treatment (6 months) and follow-up TB outcomes wereassessed using World Health Organization criteria. We measured plasma drug concentrations on available samples in 43 participants. Peak drug concentrations were below thetherapeutic range in 39/43 (90.7%) for rifampicin, 32/43 (74.4%) for isoniazid, 27/42 (64.3%) for pyrazinamide and 5/41 (12.2%) forethambutol. At the end of the intensive phase of treatment (week 8), 20.9% (n=9/43) of participants remained culture positive. We did notfind a relationship between the concentrations of first-line drugs and treatment outcomes at week 8. All participants were cured at the endof treatment, and there were no relapses during the 12-month follow-up period. Treatment outcomes were favourable despite low drug concentrations as defined by current reference thresholds.

The Value of Anticoagulation Management Combining Telemedicine and Self-Testing in Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials.

No consensus has been established on the safety and effectiveness of out-of-hospital management of Vitamin K antagonists (VKA) therapy combining portable coagulometers and telemedicine. The present meta-analysis investigated the safety and effectiveness of this hybrid anticoagulants management model. The PubMed, Embase, Cochrane, and Web of Science databases were searched for papers published before May 1, 2022.To reduce bias, only randomized controlled trials were included. RevMan 5.3 (Cochrane) software was used to evaluate and analyze clinical outcomes, including the effectiveness and safety of patient management approaches, determined by the time in the therapeutic range (TTR) and occurrence of thrombotic and bleeding events. Eight studies, comprising 3853 patients, were selected. The meta-analysis showed that anticoagulant management combining portable coagulometers and telemedicine significantly improved frequency of testing (mean difference [MD]= 12.95 days; 95% CI, 8.77-17.12; I2= 92%; P< 0.01) and TTR (MD= 9.50%; 95% CI, 3.16-15.85; I2= 87%; P< 0.01). Thromboembolism events were reduced (RR= 0.72; 95% CI, 0.51-1.01; I2= 0%; P= 0.05), but the results were not statistically significant. And no significant differences in major bleeding events, rehospitalization rate, mortality, or overall treatment cost existed between the two groups. Although the safety of remote cardiovascular disease management is not superior to that of conventional outpatient anticoagulant management, it provides a more stable monitoring of coagulation status.

Anticoagulation Management in Patients Receiving Warfarin at Private Cardiac Centers in Addis Ababa, Ethiopia.

Anticoagulants are the cornerstone therapy for thromboembolism prevention and treatment. Warfarin is the frequently prescribed drug and remains the oral anticoagulant of choice in low- and middle-income countries, including Ethiopia. It is a narrow therapeutic index drug that needs high-quality anticoagulation monitoring with frequent international normalization ratio (INR) testing. The study aimed to assess anticoagulation management with warfarin among adult outpatients at two selected private cardiac centers in Addis Ababa, Ethiopia. A hospital-based retrospective study design that enrolled 374 patients receiving warfarin was employed at two private cardiac centres in Addis Ababa, Ethiopia. The time in the therapeutic range (TTR) was calculated using the Rosendaal method. The data were analyzed using Statistical Package for Social Science version 25. The mean age of the patients was 57 years, and 218 (58.3%) participants were females. Out of 3384 INR tests, 1562 (46.5%) were within the therapeutic range and the mean percentage of TTR was 47.24%. Only 25.67% of the patients spent their TTR ≥ 65%. The present study revealed that dose adjustments were required 1764 times. In non-therapeutic INR values of 1764 that required warfarin dose adjustment, 59.7% of the doses were adjusted. About 262 (70.1%) of co-prescribed medications had interaction with warfarin. Sixty-four patients (17.11%) experienced bleeding events. Anticoagulation management with warfarin was suboptimal in private cardiac Addis Ababa, Ethiopia, private cardiac centers. Warfarin adjustment practice for nontherapeutic INR values was not minimal, and many patients encountered bleeding during their course of therapy.

Quality of anticoagulation with the use of warfarin in long-term care in a tertiary care hospital using time spent in therapeutic range as a predictive parameter

ABSTRACT Background: Warfarin was a frequently prescribed long-term anticoagulant before the advent of novel oral anticoagulants or direct oral anticoagulants. These drugs are used for the primary or secondary prevention of stroke in patients with atrial fibrillation or for the treatment and prophylactic prevention of venous thromboembolism. This study aimed to assess the anticoagulation control of patients receiving warfarin at a tertiary care hospital. Methods: This retrospective cohort study was conducted in an anticoagulation clinic at a tertiary care hospital in Saudi Arabia and included 113 patients who had been treated with warfarin for at least 3 months. Thereafter, the international normalized ratio results were collected for 3 years. Anticoagulation control was assessed by calculating time within the therapeutic range (TTR) as per the Rosendaal method. Results: A total of 113 patients (mean age, 56 ± 17.6 years; 64.6% of females) were included. The mean TTR was 48.1%. Almost one-third of the patients (31.3%) had poor anticoagulation control defined as a TTR of &lt;50%. Poor anticoagulation control was significantly associated with a higher CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke/transient ischemic attack) score (P = 0.043). TTR did not differ significantly between men and women, and it was not associated with age or anticoagulation therapy duration. Conclusion: Anticoagulation quality was suboptimal in patients receiving warfarin in a tertiary care hospital, with nearly 41% of time spent outside the therapeutic range. Methods should be implemented to improve anticoagulation control in appropriate patient groups.

Evaluation of anticoagulation control in elderly patients

Warfarin is the most prescribed oral anticoagulant in clinical practice to prevent thrombosis. Time in the therapeutic range (TTR) is the best method to evaluate the quality of warfarin therapy. Despite the overwhelming evidence of its effectiveness, elderly patients had higher risk of bleeding.

Use of SAMe-TT2R2 in a racially diverse anticoagulation clinic: prediction of optimal anticoagulation.

The SAMe-TT2R2 score predicts optimal long-term oral Vitamin K Antagonist (VKA) anticoagulation for homogenous Caucasian and homogenous Asian populations for non-valvular atrial fibrillation but at different score thresholds. The score that predicts optimal VKA anticoagulation in significantly diverse populations for multiple indications for systemic anticoagulation has not been reported. We determined whether optimal VKA anticoagulation is predicted by SAMe-TT2R2 score in a diverse inner-city population for non-valvular atrial fibrillation (NVAF), unprovoked venous and pulmonary thromboembolic disease (VTE), mechanical prosthetic heart valves and all other indications. All patients on long term VKA's that attended an inner-city anticoagulation clinic between February 2016 and October 2017 were included in this study. Eligible patients were grouped according to oral anticoagulation indication: (1) NVAF, (2) VTE, (3) prosthetic valves and (4) other indications. Each patient's SAMe-TT2R2 score and percent time of INR in the therapeutic range (TTR) was calculated with optimal international normalized ratio (INR) control defined as TTR ≥ 65%. The correlation between SAMe-TT2R2 score and TTR was determined by logistic regression for each oral anticoagulant indication. Receiver operating characteristic curves were then used to identify the best cutoff for prediction of ≥ 65% TTR. Of 316 patients meeting study criteria, 54% were non-Caucasian and there was a significant negative correlation between the SAMe-TT2R2 score and TTR (coefficient - 0.35, P < 0.0001) for all patients. A SAMe-TT2R2 score < 4 was identified as the best threshold for predicting optimal TTR (Youden's J-statistics = 0.238) with accuracy and positive likelihood ratio of 63.4% and 1.73, respectively. The SAMe-TT2R2 score predicts optimal VKA anticoagulation for systemic anticoagulation for multiple indications in a diverse urban population at a higher score than the original report for non-valvular atrial fibrillation of a cohort where < 10% non-Caucasians.

Medical Treatment for Rheumatic Heart Disease: A Narrative Review.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are rare in high-income countries; however, in Aotearoa New Zealand ARF and RHD disproportionately affect Indigenous Māori and Pacific Peoples. This narrative review explores the evidence regarding non-surgical management of patients with clinically significant valve disease or heart failure due to RHD. Medline, EMBASE and Scopus databases were searched, and additional publications were identified through cross-referencing. Included were 28 publications from 1980 onwards. Of the available interventions, improved anticoagulation management and a national RHD register could improve RHD outcomes in New Zealand. Where community pharmacy anticoagulant management services (CPAMS) are available good anticoagulation control can be achieved with a time in the therapeutic range (TTR) of more than 70%, which is above the internationally recommended level of 60%. The use of pharmacists in anticoagulation control is cost-effective, acceptable to patients, pharmacists, and primary care practitioners. There is a lack of local data available to fully assess other interventions; including optimal therapy for heart failure, equitable access to specialist RHD care, prevention, and management of endocarditis. As RHD continues to disproportionately affect Indigenous and minority groups, pro-equity tertiary prevention interventions should be fully evaluated to ensure they are reducing disease burden and improving outcomes in patients with RHD.

The treatment indication affects the time in therapeutic range

Objectives: This study aimed to compare the efficacy and safety of the treatment in patients with deep vein thrombosis (DVT) and mechanical mitral valve replacement (MVR) who were treated with warfarin for different indications. Patients and methods: A total of 536 patients (314 males, 222 females; mean age: 55.6±10.8 years; range, 18 to 89 years) were retrospectively reviewed between January 2016 and January 2020. The patients were evaluated in two groups: 273 DVT patients (149 males, 124 females; mean age: 56.7±11.3 years) who received long-term therapy (six months) and 263 mechanical MVR patients (165 males, 98 females; mean age: 56.2±9.4 years). Both groups were compared in terms of the percentage of time in the therapeutic range (TTR), the time to reach the target international normalized ratio (INR), and warfarin related complications. Results: The number of total hospital visits and total INR measurements for six months in the MVR group was statistically significantly higher than in the DVT group (p&lt;0.001). The duration and percentage of TTR in the first three and six months of the MVR group were statistically significantly higher than the DVT group (p&lt;0.05). Conclusion: More MVR patients remained in the therapeutic range than DVT patients due to the frequent hospital visits of these patients for various reasons; thus, it may be beneficial to increase the frequency of follow-up examinations or measurements of INR in patients who have started warfarin treatment for an indication other than valve replacement.

Predictive value of the adjusted Global Anti-Phospholipid Syndrome Score on clinical recurrence in APS patients: a longitudinal study.

To assess the effect of the average adjusted global APS score (aGAPSS) over time on recurrence of clinical manifestations in APS patients through a retrospective longitudinal study. The study included 200 patients with APS. The aGAPSS was calculated for each patient at baseline and on a yearly basis for either up to 6 years (minimum 3 years) or just before the clinical event in patients who experienced clinical recurrence. The mean score per patient was computed. In patients under vitamin K antagonists (VKA) the percentage of time spent within the therapeutic range (TTR) was calculated. Cox regression analysis was performed to determine the cut-off value of the aGAPSS with the strongest association with clinical recurrence. Higher average aGAPSS values were found in patients who experienced clinical recurrence in comparison to patients who did not [8.81 (95% CI 7.53, 10.08) vs 6.38 (95% CI 5.64, 7.12), P = 0.001], patients with thrombotic recurrence compared with patients with obstetric recurrence [9.48 (95% CI 8.14, 10.82) vs 4.25 (95% CI 0.85, 7.65), P = 0.006] and patients with arterial thrombosis compared with patients with venous thrombosis [10.66 (S.D. 5.48) vs 6.63 (S.D. 4.42), P = 0.01]. aGAPSS values >13 points were associated with the highest risk of recurrence in multivariate analysis [HR = 3.25 (95% CI 1.93, 5.45), P < 0.0001]. TTR was not statistically different between patients who had thrombosis recurrence and patients who had not. Our data support the role of periodic (annual) monitoring of the aGAPSS score in predicting clinical recurrence in patients with APS.

Cost-Effectiveness of the Pharmacist-Managed Warfarin Therapy vs. Standard Care for Patients With Mechanical Mitral Valve Prostheses: An Egyptian Healthcare Perspective.

BackgroundDespite warfarin therapy had been used for decades for patients with mechanical mitral valve prostheses (MMVPs), serious and life-threatening complications are still reported worldwide with a significant economic burden. This study is aimed at assessing the clinical and the cost-effectiveness of adopting pharmacist-managed warfarin therapy (PMWT) services for optimizing warfarin treatment in Egypt.MethodsA prospective randomized trial in which 59 patients with MMVPs were randomly assigned to receive the PMWT services or the standard care and followed up for 1 year. The primary outcome was percentage time in the therapeutic range (TTR). For the cost-effectiveness analysis, a Markov cohort process model with nine mutually exclusive health states was developed from a medical provider’s perspective. A lifetime horizon was applied. All costs and outcomes were discounted at 3.5% annually.ResultsThe study results revealed a significantly higher median TTR in the intervention group as compared to the control group; 96.8% [interquartile range (IQR) 77.9–100%] vs. 73.1% (52.7–95.1%), respectively, p = 0.008. A significant association between standard care and poor anticoagulation control (p = 0.021) was demonstrated by the multivariate regression analysis. For the cost-effectiveness analysis, the total cumulative quality-adjusted life-years (QALYs) and total costs per patient were 21.53 and 10.43; 436.38 and 1,242.25 United States dollar (USD) in the intervention and the control groups, respectively, with an incremental cost-effectiveness ratio (ICER) of −72.5796 for the intervention group.ConclusionThe PMWT strategy was proven to provide a significantly better anticoagulation control and to be a cost-saving approach in Egyptian patients with MMVPs. Nevertheless, the dominance of this strategy is sustained by maintaining the therapeutic International Normalized Ratio (INR) control within the recommended range. Our findings will benefit Egyptian policy-makers who may seek novel health strategies for better resource allocation.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT04409613].