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PURPOSE OF REVIEW: To examine the concept of time in target range for blood pressure (BP) management, exploring its calculation methods, implications for patient outcomes, and potential use in patient care. RECENT FINDINGS: Recent post-hoc analyses of clinical trials and observational studies highlight the importance of BP time in target range in predicting cardiovascular outcomes. Higher time in target range correlates with reduced risks of major adverse cardiovascular events including heart failure, stroke, myocardial infarction and all-cause mortality. Additionally, longer time in target range decreases the risk of incident atrial fibrillation and risk of developing dementia. BP time in target range is a novel metric offering valuable insights into BP control and its impact on clinical outcomes. Higher time in target range is consistently associated with better cardiovascular outcomes across various patient populations. However, the clinical application of BP time in target range requires further investigation through prospective clinical trials and real-world studies. Integrating wearable devices for continuous BP monitoring could enhance the practical utility of BP time in target range in hypertension management.

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Achieving clinical effectiveness with vitamin K antagonists (VKAs) requires a Time in Therapeutic Range (TTR) above 65%. TTR is influenced by genetics (CYP2C9, VKORC1, CYP4F2), treatment adherence, and knowledge. The SAMe-TT2R2 algorithm is used to assess VKA treatment suitability. In this case report, SAMe-TT2R2 and pharmacogenetic analysis were used to improve oral anticoagulant management in a patient with poor control of INR. An 84-year-old, obese male with atrial fibrillation, undergoing acenocoumarol therapy, had a suboptimal TTR. An assessment with the SAMe-TT2R2 algorithm indicated a favorable profile for VKA use. An educational intervention on vitamin K-rich foods was conducted, and his physician was informed about the interaction between omeprazole and acenocoumarol, recommending its replacement with pantoprazole. This intervention was accepted by the physician and, three months post-intervention, the patient's TTR improved to 100%. Poor adherence and limited knowledge contributed to treatment failures in patients with a good VKA profile. Pharmaceutical interventions significantly improved TTR management. Patients with favorable genetic and clinical profiles could achieve adequate control of their anticoagulant medication through these interventions. Predictive tools may help select patients who can effectively and safely use VKAs through pharmaceutical interventions.

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The proportion of time that blood pressure (BP) readings are at treatment target levels, commonly referred to as time at target or time in therapeutic range (BP-TTR), is emerging as a useful measure for evaluating hypertension management effectiveness and assessing longitudinal BP control. However, method of determination for BP-TTR differs across studies. This review identifies variations in BP-TTR determination methodologies and its potential prognostic value for cardiovascular outcomes. Following PRISMA extension for scoping reviews guidelines, literature was systematically searched in Embase, PubMed, Scopus, Web of Science, and CINAHL. Relevant clinical trials, observational studies, cohort studies, cross-sectional studies, and systematic reviews published in English were screened. Of 369 articles identified, 17 articles were included. Studies differed in the BP targets used (e.g., BP < 140/90 mmHg or 130/80 mmHg; systolic BP within 110-130 mmHg or 120-140 mmHg), BP-TTR measurement duration (range 24 h to 15 years), and calculation method (linear interpolation method, n = 12 [71%]; proportion of BP readings at target, n = 5 [29%]). Regardless of method, studies consistently demonstrated that higher BP-TTR was associated with reduced risk of cardiovascular outcomes. Six of eight studies found the association was independent of mean achieved BP or last measured BP. Despite variation in methods of BP-TTR determination, these studies demonstrated the potential prognostic value of BP-TTR for cardiovascular outcomes beyond current BP control measures. We recommend standardization of BP-TTR methodology, with preference for linear interpolation method when BP measurements are few or less frequent, and proportion of BP readings method when large number of BP readings are available.

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Warfarin remains the most prescribed oral anticoagulant of choice in atrial fibrillation (AF) patient in resource-limited settings. Despite evidence linking Time in Therapeutic Range (TTR) to patient outcomes, its use in clinical practice is not widespread. This prospective study explores the impact of a TTR-INR guided Warfarin adjustment protocol on TTR in AF patients. Conducted at the Warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated using the Rosendaal linear interpolation method at baseline, and then at 6 and 12 months post-protocol implementation. The primary outcome was the improvement in TTR following the protocol's implementation. The study analyzed 57 patients, with a mean age of 72 years and an even gender distribution. At baseline, 53% of patients had a TTR of less than 65%. However, TTR significantly improved from 65% at baseline to 80% after 12 months of protocol implementation (p < 0.001). Furthermore, there was a significant increase in the proportion of patients with a TTR of 65% or more, from 47 to 88% (p < 0.001). During the follow-up period in the first 12 months, three patients died, but no ischemic or major bleeding events occurred. The significant improvement in TTR after 12 months of protocol implementation suggests that this strategy could provide additional value in improving TTR and outcomes in AF patients receiving Warfarin.

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Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the therapeutic range and intrapatient variability in predicting rejection and de novo donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%, p = 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%, p = 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%, p = 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk.

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BACKGROUND: Warfarin management is associated with severe complications, highlighting the critical need to evaluate the quality of its administration. OBJECTIVES: To evaluate the quality of warfarin management for patients managed in primary healthcare centers by measuring the percentage of Time in Therapeutic Range (TTR) and the proportion of extreme out-of-range international normalized ratio (INR) values. METHODS: This is a cross-sectional study. Data was extracted from a national dataset retrieved from the largest primary healthcare provider in Qatar. TTR was calculated using the traditional method. Inferential and descriptive analyses were performed as appropriate. RESULTS: Four hundred ninety-four patients met the inclusion criteria. The mean (SD) TTR was 45.3 % (17.5). This was significantly lower than the recommended cutoff value (P<0.001). Extreme out-of-range INR accounted for 24.7 % of total INR readings. CONCLUSIONS: The management of patients taking warfarin in Qatar is inadequate. More effective strategies are warranted to ensure safe and effective therapy.

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This review provides an overview of the efficacy and safety of renal sympathetic denervation as a therapeutic approach for resistant hypertension. While the initial enthusiasm was sparked by the results of early clinical trials, it was dampened by the findings of the Symplicity HTN-3 study. However, recent advances in catheter technology and more refined patient selection criteria have yielded more promising results. Subsequent studies, such as SPYRAL HTN-OFF MED and RADIANCE II, demonstrated significant reductions in blood pressure, even in patients with mild to moderate hypertension. Despite the lack of robust data on major clinical outcomes, investigations into the time in therapeutic range for patients undergoing renal sympathetic denervation suggested potential cardiovascular benefits. Nevertheless, further research is needed to thoroughly understand the long-term impact, assess cost-effectiveness, and accurately identify which patient subgroups may derive the greatest benefits from this therapy.

Esta revisión brinda una síntesis de la eficacia y la seguridad de la denervación simpática renal como enfoque terapéutico para la hipertensión resistente. A pesar del entusiasmo inicial generado por los resultados de los primeros ensayos clínicos, la eficacia de esta terapia se vio comprometida por los hallazgos negativos del estudio Symplicity HTN-3. Sin embargo, recientes avances en la tecnología de catéteres y una refinada selección de los pacientes han proporcionado resultados más prometedores. Estudios posteriores, como SPYRAL HTN-OFF MED y RADIANCE II, demostraron reducciones significativas en la presión arterial, incluso en pacientes con hipertensión de leve a moderada. A pesar de la falta de datos sólidos sobre desenlaces clínicos importantes, las investigaciones sobre el tiempo en rango terapéutico de los pacientes sometidos a denervación simpática renal sugirieron posibles beneficios cardiovasculares. No obstante, se requiere una mayor investigación para comprender a fondo el impacto a largo plazo, evaluar la relación costo-efectividad y determinar con precisión qué subgrupos de pacientes podrían obtener los mayores beneficios de esta terapia.

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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).

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BACKGROUND: Tacrolimus 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. METHODS: A 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. RESULTS: In 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). CONCLUSION: Gaining and maintaining Tac C0 according to the 2019 second consensus report might reduce the risk of AR in the first month following transplantation.

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BACKGROUND: Evidence-based anticoagulation programs usually serve a local, adult patient population. Here we report outcomes for a regional combined pediatric-adult program. AIMS: The aims of this study were: (1) Compare the pre- vs. post-implementation quality of therapy (% time in therapeutic range (%TTR) and compliance). (2) Assess anticoagulant-relevant outcomes (bleeding and thrombotic complications). METHODS: Data were collected for the years 2014-2019. Rosendaal linear interpolation was used to calculate %TTR. Bleeding complications were categorized using ISTH-SSC standard nomenclature and new thrombotic events were reviewed. RESULTS: The patients were divided into a long-term warfarin group (N = 308), 80.2% of whom had cardiac-related therapeutic indications (median age 24y), and a second group (N = 114) comprised of short-term and non-warfarin long-term anticoagulation (median age 16y). Median %TTR for those on long-term warfarin was 78.9%. The incidence of major and clinically relevant non-major bleeding events was 1.65 and 2.43 /100 person-years of warfarin use, respectively. Thromboembolism (TE) incidence was 0.78/100 patient-years of warfarin use. Neither bleeding nor thrombosis was associated with %TTR (p = 0.48). Anticoagulant indication was the only variable associated with bleeding risk (p = 0.005). The second group had no on-therapy TE events but 7.9% experienced bleeding. Complete data were available for a randomly sampled pre-program warfarin group (N = 26). Median %TTR improved from 17.5 to 87% pre- vs. post-implementation. Similarly, compliance (defined as ≥ 1 INR/month) improved by 34.3%. CONCLUSIONS: In conclusion, this program significantly improved and sustained %TTR and compliance. The lack of association between bleeding and thrombosis events and %TTR may be related to the high median %TTR (> 70%) achieved by this approach.

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Background We aimed to determine the effect of integrating Atrial Fibrillation Better Care pathway compliance in relation to achievement of systolic blood pressure (SBP) targets and good control of time in therapeutic range (TTR) on clinical outcomes in patients with atrial fibrillation. Methods and Results We prospectively enrolled patients with nonvalvular atrial fibrillation  from 27 hospitals in Thailand. All clinical outcomes were recorded. Main outcomes were the composite of all-cause death or ischemic stroke/systemic embolism (SSE), as well as secondary outcomes of all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure. An SBP of 120 to 140 mm Hg was considered good blood pressure control. Target TTR was a TTR ≥65%. A total of 3405 patients were studied (mean age 67.8 years, 41.8% female). Full ABC pathway compliance was evident in 42.7%. For blood pressure control, 41.9% had SBP within target, whereas 35.9% of those on warfarin had TTR within target. The incidence rates of all-cause death/SSE, all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure were 5.29, 4.21, 1.51, 2.25, 0.78, and 2.84 per 100 person-years respectively. Adjusted hazard ratios and 95% CI of Atrial Fibrillation Better Care pathway compliance for all-cause death/SSE, all-cause death, and heart failure were 0.76 (0.62-0.94), 0.79 (0.62-0.99), and 0.69 (0.51-0.94), respectively, compared with noncompliance. Patients with Atrial Fibrillation Better Care compliance and SBP within target had a better outcome or TTR within target had better outcomes. Conclusions In COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Level in Patients With Non-Valvular Atrial Fibrillation in Thailand), a multicenter nationwide prospective cohort of patients with atrial fibrillation, achieving SBP within target and TTR ≥ 65% has added value to Atrial Fibrillation Better Care pathway compliance in the reduction of adverse clinical outcomes in patients with atrial fibrillation.

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BACKGROUND: The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fibrillation (AF) is still lacking. AIM: We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients. METHOD: Our study consisted of 508 newly recruited and 471 existing Chinese AF patients. Among the total 979 patients, 585 patients received their dose of warfarin determined by a genetic and clinical factor (gene group), while the remaining 394 patients whose dosing was determined empirically in control group. We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR during 12-month follow-up. Secondary safety outcome included bleeding and thrombotic events. RESULTS: Compared with the control group, the average TTR of the gene group was higher [68.4 ± 20.6% vs 48.5 ± 21.6%, P < 0.001]. The average INR monitoring times to reach the therapeutic time in the gene group was lower (P < 0.001). The risk ratios (RR) for cumulative incidence of total bleeding events, minor bleeding events, gastrointestinal bleeding, and intracerebral bleeding events were not significantly different between the two groups (P > 0.05). Comparing to the analysis using existing 471 patients, the analysis using total 979 patients showed that the gene group experienced a lower (RR 0.4 (95% CI 0.2 to 0.8), P = 0.008) incidence of cumulative ischemic stroke. CONCLUSION: Genotype-guided warfarin administration increases the average TTR, reaches higher TTR levels in the early anticoagulant phase, and significantly reduces the risk of ischemic stroke events.

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A lack in patient knowledge of warfarin therapy is associated with poor adherence. This knowledge gap may result in a lower INR Time in Therapeutic Range (TTR). To investigate association between patient anticoagulation knowledge and warfarin control. Michigan Anticoagulation Quality Improvement Initiative (MAQI2) is a Blue Cross Blue Shield of Michigan sponsored consortium of six anticoagulation management services. Patients prescribed warfarin at two MAQI2 sites completed a voluntary Oral Anticoagulation Knowledge (OAK) questionnaire at warfarin initiation and 6-month follow-up. The results of 20 OAK questions and TTRs (excluding 1st month post-initiation) were compared using chi-square tests, t-tests and multivariate analysis adjusting for SAMe-TT2R2 and days on warfarin. Of 1836 surveys distributed at warfarin initiation, 481 (26.2%) patients completed the baseline questionnaire (within 1 month post-initiation): mean OAK score: 14.6 ± 3.4. Of those, 147 (30.6%) completed 6-month follow-up surveys (OAK: 12.7 ± 5.8). Patients with TTR ≥ 70% at baseline scored higher on OAK tests than patients with TTR < 70% in unadjusted analyses (15.1 ± 3.2 v. 14.2 ± 3.5, p = 0.003) and adjusted analysis (p = 0.020). There was no unadjusted or adjusted difference in OAK scores at 6-month follow-up between patients with TTR ≥ 70% and TTR < 70%. For patients who completed baseline and follow-up surveys, there was a decrease of 2.4 points in OAK score between baseline and 6-month follow up (p < 0.001). Higher baseline, but not follow-up, OAK score is associated with better warfarin control and average OAK scores decreased between baseline and follow-up. Further studies are needed to determine what type of patient education may improve patient knowledge retention and warfarin control.

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Previous studies on solid organ transplantation have reported that a low time in therapeutic range (TTR) of tacrolimus increases the risk of poor outcomes. However, the reproducibility of the findings in liver transplantation has not yet been confirmed. The TTR, coefficient of variation (CV) and standard deviation (SD) were calculated for 207 adult liver transplant patients from the date of transplantation until the first episode of acute rejection (AR), graft loss, acute kidney injury (AKI), biliary complications, infection or the last follow-up. Kaplan-Meier curves, log-rank tests and Cox regression analyses were performed. Sixty-one (29.5%) patients reached the composite endpoint of AR, biliary complications and graft loss. The log-rank test indicated that the low TTR group had an increased risk of the composite endpoint (P < 0.001), AKI (P < 0.001) and infection (P < 0.001). Multivariate Cox regression analyses revealed that a 10% decrease in TTR was associated with an increased hazard for composite endpoint (hazard ratio [HR]: 1.185, P = 0.010), AKI (HR: 1.355, P < 0.001) and infection (HR: 1.357, P < 0.001). Unexpectedly, SD and CV demonstrated no association with the above-mentioned inferior outcomes. Compared with SD and CV, the TTR of tacrolimus was more correlated with inferior outcomes and may be a novel indicator for predicting the prognosis of liver transplantation.

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BACKGROUND: The effectiveness and safety of warfarin depend on maintaining an international normalized ratio (INR) within the therapeutic range. Time in Therapeutic Range (TTR) is defined as the percentage of time a patient's INR is within the therapeutic range. OBJECTIVE: We sought to determine the factors affecting good TTR in patients on warfarin therapy. METHODS: This was a descriptive cross-sectional study conducted in a single tertiary care center. Good anticoagulation control was defined as TTR ≥65%. RESULTS: The study population consisted of 518 patients. The mean age was 57.6 ± 12.3 (19-87) and 54.4% of the patients were female. 47.5% patients achieved good anticoagulation control (TTR ≥65%). The mean Medication Adherence Report Scale (MARS) score was significantly higher in patients with good TTR (23.5 ± 1.9 vs. 22.8 ± 2.1, p = .002). Only 40.2% of the patients received education on warfarin. In multivariable analyses, the duration of warfarin therapy >10 years (OR: 2.27, 95% CI: 1.34-3.84, p = .002) and MARS score (OR: 1.22, 95% CI: 1.09-1.35, p < .001) were found to be the independent predictors of the good anticoagulation control. CONCLUSION: Duration of warfarin therapy >10 years and MARS score were the independent predictors of good anticoagulation control.

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OBJECTIVE: For comatose survivors of out-of-hospital cardiac arrest (OHCA), current guidelines recommend targeted temperature management (TTM) with a goal temperature of 32 °C-36 °C for at least 24 h. We examined adherence to temperature targets, quantified as time-in-therapeutic range (TTR), and association of TTR with survival and neurologic outcomes. METHODS: We conducted a retrospective cohort study of the Resuscitation Outcomes Consortium-Continuous Chest Compressions trial, including adults with OHCA who underwent TTM for >12 h. We imputed continuous temperatures between consecutive temperature measurements using the linear interpolation method and calculated TTR for multiple target temperatures. The association of TTR with survival to hospital discharge and favorable neurological outcome was evaluated using hierarchical regression models. MAIN RESULTS: Among 2,637 patients (mean age 62.3 years, 29.9 % female), the median duration of TTR for TTM between 32 °C-36 °C was 23 (IQR: 21-24) hours with a median time outside therapeutic range of 0.9 (IQR: 0.0-4.2) hours. In risk-adjusted analyses, there was no association of TTR of 32 °C-36 °C with overall survival (OR 1.00 [95 % CI, 0.90-1.10]) or favorable neurologic outcome (1.02 [95 % CI, 0.90-1.14]). However, in assessments of TTR 33 °C-36 °C, there was a significant association with favorable neurologic survival (OR 1.12 [1.01-1.25]) but not overall survival (OR 1.04 [0.94-1.15]). CONCLUSIONS: Among patients with OHCA who underwent TTM, we found variability in adherence to guideline-recommended treatment targets. Higher TTR was not associated with overall survival, but for certain temperature thresholds, TTR was associated with favorable neurologic outcome.

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Background: The objective of this study was to evaluate the quality of anticoagulation by the time in therapeutic range (TTR) for patients with 12-week INR follow-up interval. Materials and methods: From January 2018 to December 2020, a selective group of patients who underwent mechanical valve replacement and followed up at our anticoagulation clinic for adjustment of warfarin dose were enrolled. The incidences of complications of anticoagulation therapy were reported by linearized rates. TTR was calculated by the Rosendaal linear interpolation method. Results: Two hundred and seventy-four patients were eligible for this study. The mean age of these patients was 52.8 ± 12.7 years, and 65.7% (180 cases) of them were females. The mean duration of warfarin therapy was 16.7 ± 28.1 months. A total of 1309 INR values were collected, representing 66789 patient days. In this study, the mean TTR was 63.7% ± 18.6%, weekly doses of warfarin were 20.6 ± 6.0 mg/weekly, and the mean monitoring interval for the patient was 53.6 ± 27.1 days. There were 153 cases in good TTR group (TTR ≥ 60%) and 121 cases in poor TTR group (TTR < 60%). The calculated mean TTR in both groups was 42.6% ± 22.1% and 74.8% ± 10.4%, respectively. Compared with the TTR ≥ 60% group, the TTR < 60% group exhibited a more prevalence of female gender (p = 0.001), atrial fibrillation (p < 0.001), NYHA ≥ III (p < 0.001), and lower preoperative left ventricular ejection fraction (LVEF, p = 0.032). In multivariate analysis, female gender (p = 0.023) and atrial fibrillation (p = 0.011) were associated with TTR < 60%. The incidence of major bleeding and thromboembolic events was 2.7% and 1.1% patient-years, respectively. There was one death which resulted from cerebral hemorrhage. The incidence of death was 0.5% patient-years. The difference in anticoagulation-related complications between the TTR < 60% group and the TTR ≥ 60% group was not statistically significant. Conclusion: For patients with stable international normalized ratio monitoring results who are follow-up at anticoagulation clinics, a 12-week monitoring interval has an acceptable quality of anticoagulation. The female gender and atrial fibrillation were associated with TTR < 60%.

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BACKGROUND: Tacrolimus is a key drug in immunosuppressive therapy following lung transplantation. The blood tacrolimus levels are likely to fluctuate in the early postoperative period, and failure to maintain the tacrolimus trough level in target ranges is a risk factor for rejection. However, there is little information about the relationship between the time in therapeutic range (TTR) of the tacrolimus trough level (tacrolimus TTR) and clinical outcomes. This study aimed to evaluate the association between tacrolimus TTR and acute rejection (AR) within the first three months after lung transplantation. METHODS: This was a retrospective study of patients who underwent lung transplantation at a single center. The target tacrolimus trough levels were 10-15 ng/mL, and tacrolimus TTR was calculated using the Rosendaal method. The cut-off value of the tacrolimus TTR was estimated by receiver operating characteristic analysis based on AR. RESULTS: The study included 90 patients. AR was observed in 26 patients. In this study, ''early-AR'' was defined as any AR within 2 weeks post-transplant (n = 22) and ''late-AR'' was defined as any AR after 1-month post-transplant (n = 4). For early AR, the relationship between tacrolimus TTR and the onset of AR was examined. There were no differences in the tacrolimus TTR between the early-AR group and non-AR group (35.7 ± 22.4 vs 31.5 ± 19.9%, P = 0.416). For late-AR, the relationship with tacrolimus TTR was examined every 10 d. The tacrolimus TTR during postoperative days (POD) 21-30 and POD 31-onset was significantly lower in the late-AR group than the no-AR group (50.0 ± 7.1 vs. 71.8 ± 18.0% and 37.0 ± 26.6 vs. 68.9 ± 31.5%, P < 0.05, respectively). The cutoff value of the tacrolimus TTR during POD 21-30 was estimated as 55.0%. CONCLUSIONS: Our findings suggest that a lower tacrolimus TTR is a predictor of late AR. A tacrolimus TTR of 55% or higher is necessary to reduce the risk of AR during this period after lung transplantation.

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PURPOSE: We investigated whether blood pressure (BP) control measures, visit-to-visit BP variability, and time in therapeutic range (TTR) are associated with future cardiovascular outcomes in hypertensive patients. MATERIALS AND METHODS: Among 1,408 hypertensive patients without cardiovascular disease, we prospectively evaluated the incident major cardiovascular events over 6 years. In newly diagnosed patients, antihypertensive drug treatment was initiated. We estimated two markers of on-treatment BP control, (1) visit-to-visit BPV as the coefficient of variation of office systolic BP (BP-CV), and (2) TTR calculated as the percentage of office systolic BP measurements within 120-140mmHg across visits. RESULTS: The hypertensive cohort (672 males, mean age 60 years, 31% newly diagnosed) had a mean systolic/diastolic BP of 142/87 mmHg. The mean number of visits was 4.9 ± 2.6, while the mean attained systolic/diastolic BP during follow-up was 137/79 mmHg using 2.7 ± 1.1 antihypertensive drugs. The BP-CV and TTR were 9.1 ± 4.1% and 45 ± 29%, respectively, and the incidence of the composite outcome was 8.3% (n = 117). After adjustment for relevant confounders and standardization to z-scores, BP-CV and TTR were associated with a 43% (95% CI, 27-62%) increase and a 33% (95% CI, 15-47%) reduction in the outcome. However, the joint evaluation of TTR and BP-CV in a common multivariable model indicated that a standardized change of TTR was associated with the outcome to a greater extent than BP-CV (mean hazard ratios of 30% vs. 24%, respectively). When combined with the higher BP standardized-CV quartile, the lower TTR quartile predicted the outcome by 2.3 times (95% CI, 1.1-5.4) compared to the inverse TTR and BP-CV quartile pattern. CONCLUSION: High BP-CV or low TTR was associated with future cardiovascular events in a cohort of treated hypertensive patients. As a determinant, the extent of TTR value appears greater than BP-CV when these measures are considered in the same multivariable model.

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Background: Despite 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. Methods: A 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. Results: The 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. Conclusion: The 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].