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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:

Roza Getachew,1 Tamrat Assefa Tadesse,1 Bekele Alemayehu Shashu,2 Amsalu Degu,3 Getachew Alemkere1 1Department of Pharmacology and Clinical Pharmacy School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Internal Medicine School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 3Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy & Health Sciences, United States International University Africa, Nairobi, KenyaCorrespondence: Tamrat Assefa Tadesse, Email tamrat.assefa@aau.edu.etIntroduction: 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.Objective: The study aimed to assess anticoagulation management with warfarin among adult outpatients at two selected private cardiac centers in Addis Ababa, Ethiopia.Methods: 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.Results: 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.Conclusion: 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.Keywords: warfarin, anticoagulation, time in the therapeutic range, international normalization ratio, Ethiopia

Introduction: Vitamin K Antagonists (VKAs) have been in use for more than 50 years. They have remained as mainstay therapy in the prevention of thromboembolic events in atrial fibrillation, mechanical heart valves and venous thromboembolism. Despite many years of clinical experience with VKAs, the quality of anticoagulation achieved in routine clinical practice is suboptimal. Aim: To study the effects of structured Anticoagulation Clinic (ACC) interventions on patient centred outcomes in subjects taking VKAs. Materials and Methods: A retrospective study was conducted among patients taking VKAs enrolled in ACC. A total of 169 patients receiving VKAs for at least six months with 4 INR (International Normalised Ratio) values and completed 12 months of follow-up were analysed. Anticoagulation related quality measures like Time in the Therapeutic Range (TTR), Percentage of International Normalised Ratios in the therapeutic Range (PINRR) and clinical outcomes like stroke, systemic embolic events and bleeding was analysed at the time of enrolment and compared with those during ACC care. Results: Among 352 patients enrolled in ACC, 169 patients were eligible for analysis. The mean age of the study population was 55.62±13.77 years. Atrial fibrillation (59%) was the most common indication for VKA therapy. Hypertension (66.3%) was the most common co-morbidity. Mean TTRs were significantly higher in the ACC care when compared with the pre-ACC care at 12 months follow-up (77.58±8.85% vs 51.01±16.7%, p70% which increased to 70.4% at 12 months of followup. INR testing was done more frequently in ACC care. Adverse clinical events were higher in pre-ACC care than ACC care (4.7% vs 2.4%, p>0.05). Major bleeding and thromboembolic events were higher in pre-ACC care than ACC care (1.8% vs. 0.6% and 2.4% vs. 0.6% respectively). Conclusion: ACC services helps in achieving better quality of anticoagulation control as measured by time in therapeutic range translating into better clinical outcomes.

BackgroundWarfarin is the most common oral anticoagulant drug, especially in low-income and emerging countries, because of the high cost of direct oral anticoagulant (DOACs), or when warfarin is the only proven therapy (mechanical prosthetic valve and kidney dysfunction). The quality of warfarin therapy is directly associated with dose management. Evidence shows that pharmaceutical care achieves a better quality of therapy with warfarin. However, there are no studies showing this intervention in a specific patient group with poor quality of anticoagulation in a long period after the end of the follow-up by a pharmacist. Thus, the aim of this study was to evaluate whether the quality of warfarin therapy driven by a pharmacist remains stable in the long term after the end of follow up with a pharmacist, in AF patients with poor quality of anticoagulation.MethodsThis is a prospective study, which evaluated about 2,620 patients and selected 262 patients with AF and poor quality of anticoagulation therapy with warfarin (TTR

Introduction: Vitamin K Antagonists (VKAs) have been in use for more than 50 years. They have remained as mainstay therapy in the prevention of thromboembolic events in atrial fibrillation, mechanical heart valves and venous thromboembolism. Despite many years of clinical experience with VKAs, the quality of anticoagulation achieved in routine clinical practice is suboptimal. Aim: To study the effects of structured Anticoagulation Clinic (ACC) interventions on patient centred outcomes in subjects taking VKAs. Materials and Methods: A retrospective study was conducted among patients taking VKAs enrolled in ACC. A total of 169 patients receiving VKAs for at least six months with 4 INR (International Normalised Ratio) values and completed 12 months of follow-up were analysed. Anticoagulation related quality measures like Time in the Therapeutic Range (TTR), Percentage of International Normalised Ratios in the therapeutic Range (PINRR) and clinical outcomes like stroke, systemic embolic events and bleeding was analysed at the time of enrolment and compared with those during ACC care. Results: Among 352 patients enrolled in ACC, 169 patients were eligible for analysis. The mean age of the study population was 55.62±13.77 years. Atrial fibrillation (59%) was the most common indication for VKA therapy. Hypertension (66.3%) was the most common co-morbidity. Mean TTRs were significantly higher in the ACC care when compared with the pre-ACC care at 12 months follow-up (77.58±8.85% vs 51.01±16.7%, p<0.0001). There was a significant improvement in TTRs as early as three months of ACC intervention (73.18±13.56%). At the time of enrolment, 21.9% of patients had individual TTRs (i-TTR) >70% which increased to 70.4% at 12 months of followup. INR testing was done more frequently in ACC care. Adverse clinical events were higher in pre-ACC care than ACC care (4.7% vs 2.4%, p>0.05). Major bleeding and thromboembolic events were higher in pre-ACC care than ACC care (1.8% vs. 0.6% and 2.4% vs. 0.6% respectively). Conclusion: ACC services helps in achieving better quality of anticoagulation control as measured by time in therapeutic range translating into better clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Warfarin is the most common oral anticoagulant drug, especially in low-income and emerging countries, because of the high cost of direct oral anticoagulant (DOACs), or when warfarin is the only proven therapy (mechanical prosthetic valve and kidney dysfunction). The quality of warfarin therapy is directly associated with dose management. Evidence shows that pharmaceutical care achieves a better quality of therapy with warfarin. However, there are no studies showing this intervention in a specific patient group with poor quality of anticoagulation in a long period after the end of the follow-up by a pharmacist. Thus, the aim of this study was to evaluate whether the quality of warfarin therapy driven by a pharmacist remains stable in the long term after the end of follow up with a pharmacist, in AF patients with poor quality of anticoagulation. Methods: This is a prospective study, which evaluated about 2,620 patients and selected 262 patients with AF and poor quality of anticoagulation therapy with warfarin (TTR<50% - based on the last three values of international normalized ratio). Pharmacist-driven therapy management was performed up to 12 weeks. Data from patients were evaluated 1 year after the end of the follow-up with pharmacist. Results: Comparison between mean TTR after 12 weeks of pharmaceutical care (54.1%) and mean TTR one year after the end of the pharmaceutical care (56.5%; p=0.081) did not achieve statistical difference, demonstrating that the increment of quality due to intervention of 12 weeks was maintained for 1 year after intervention. Conclusion: The long-term impact of pharmaceutical care was beneficial for patients with AF and poor quality of warfarin anticoagulation. This design might be an important strategy to treat a subgroup of patients without proven effectiveness of warfarin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Thromboembolic events are associated with high mortality and morbidity indexes. In this context, warfarin is the most widely prescribed oral anticoagulant agent for preventing and treating these events. This medication has a narrow therapeutic range and, consequently, patients usually have difficulty in achieving and maintaining stable target therapeutics. Some studies on the literature about oral anticoagulant management showed that pharmacists could improve the efficiency of anticoagulant therapy. However, the majority of these studies included general patients retrospectively. The aim of this study was to prospectively evaluate a pharmacist’s warfarin management in patients with poor quality of anticoagulation therapy (Time in the Therapeutic Range- TTR < 50%). We included 268 patients with atrial fibrillation (AF) and without stable dose of warfarin (TTR < 50%, based on the last three values of International Normalized Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when necessary, the dose adjustments were performed. During the first four visits, patient’s INR was measured every 7 days. Then, if INR was within the target therapeutic range (INR: 2–3), the patient was asked to return in 30 days. However, if INR was out the therapeutic target, the patient was asked to return in 7 days. Adherence evaluation was measured through questionnaires and by counting the pills taken. Comparison between basal TTR (which was calculated based on the three last INR values before prospective phase) and TTR of 4 weeks (calculated by considering the INR tests from visits 0 to 4, in the prospective phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the INR tests from visits 0 to 12, in the prospective phase of the study) revealed significant statistical differences (0.144 ± 0.010 vs. 0.382 ± 0.016; and 0.144 ± 0.010 vs. 0.543 ± 0.014, p < 0.001, respectively). We also observed that the mean TTR of 1 year before (retrospective phase) was lower than TTR value after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 ± 0.015; 0.540 ± 0.015, p < 0.001). In conclusion, pharmaceutical care was able to improve TTR values in patients with AF and poor quality of anticoagulation with warfarin.

Background Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention (PCI) compared with dual anti-platelet therapy (DAPT). However, whether warfarin control is associated with reduced cardiovascular events and major bleeding events in patients undergoing PCI with triple antithrombotic therapy is uncertain. Methods We investigated 1207 consecutive patients who underwent PCI between 2004 and 2011. Major bleeding complications and major adverse cardiac and cerebrovascular events (MACCE) defined as all-cause death, acute coronary syndrome, target vessel revascularization, and stroke were compared between groups of patients who received either triple antithrombotic therapy or DAPT. Results Triple antithrombotic therapy was administered to 95 (7.9%) patients. The mean international normalized ratio of prothrombin time (PT-INR) was 1.8. The target PT-INR level was set between 1.6 and 2.6 and the ratio (%) of time in the therapeutic range (TTR) was calculated. The median TTR was 78.4% (interquartile range, 67.4–87.6%). Kaplan–Meier survival curves showed that warfarin therapy was not associated with MACCE ( p = 0.89) and major bleeding ( p = 0.80). Multivariable Cox regression analysis revealed that triple antithrombotic therapy was not an independent predictor of MACCE and major bleeding. Conclusions Triple antithrombotic therapy does not increase the occurrence of MACCE and major bleeding complications, if the warfarin dose is tightly controlled with a lower INR. [ABSTRACT FROM AUTHOR]

In recent clinical trials, the \“quality\“ of warfarin management has been characterized by the time in therapeutic range (TTR) - with the therapeutic range being an INR between 2.0 and 3.0. In many reviews of recent clinical trials, differences in the TTR have been used comparatively to critique and contrast the trials. However, TTR is a more complex measurement than is commonly appreciated, and many factors that underlie the TTR calculation, which can differ from trial to trial, have not been adequately addressed. This manuscript attempts to explain these issues so as to help the reader understand the factors that contribute to TTR and to understand the limitations of TTR so as to better understand anticoagulation trial results. It also addresses the issue of INRs below or above the therapeutic range, that can differ among trials, that are not provided simply by presenting a TTR value, but that can in a substantial way affect the bleeding risk and embolismprevention likelihood of anticoagulation in a trial. [ABSTRACT FROM AUTHOR]

In the era of drug-eluting stents (DES), a long-term dual antiplatelet therapy is required to prevent late stent thrombosis. However, in patients with atrial fibrillation (AF), there is a concern that combining warfarin with dual antiplatelet therapy may increase the risk of bleeding. We analyzed 1274 consecutive patients with coronary artery disease who were treated with coronary intervention from January 2006 through January 2009. Of these, we enrolled 74 AF patients treated with DES and dual antiplatelet therapy as well as warfarin. The primary endpoint was the incidence of major bleeding within 3 years; the predictive factor of major bleeding was also analyzed. To evaluate the efficacy of anticoagulant therapy, time in therapeutic range (TTR) was also measured. The 3-year incidence of major bleeding was 12.2 % (nine of 74 patients). The average observation period was 25.7 ± 20.2 months. Mean TTR value was 44.6 ± 33.0 % and was maintained at a relatively low level. Multivariate analysis revealed that a higher CHADS2 score (2-point more) was an independent predictor of increased risk of major bleeding. Major bleeding in the patients with triple antithrombotic therapy including warfarin occurred at a relatively high rate. Although the higher CHADS2-score indicates a high risk of thrombotic events, it was strongly associated with bleeding complications. [ABSTRACT FROM AUTHOR]

Oral vitamin K antagonists are highly efficacious in the prevention and treatment of thromboembolic disease. Optimal use of these agents in clinical practice is challenged by their narrow therapeutic window. The proportion of time spent in the International Normalized Ratio (INR) range of 2.0-3.0 [time in the therapeutic range (TTR)] has been closely associated with adverse outcomes, i.e., stroke, hemorrhage, mortality. Although TTR is a validated marker, it has several limitations. TTR does not capture short-term risks associated with highly variable periods or periods characterized by extreme deviations in INR. Because TTR measurement is limited to consecutive periods of warfarin exposure, it does not inform the risks associated with gap periods of 56 days or greater as these time intervals are excluded from end-point rate calculations. Because individuals with gaps in monitoring represent a different patient population than those without gaps, e.g., less adherent, more acutely ill, more frequent transitions in health status, TTR analyses are likely most valid and informative for individuals with uninterrupted monitoring of the INR. Duration of warfarin therapy and patient-specific factors have also been shown to influence TTR. Younger age, female sex, lower income, black race, frequent hospitalizations, polypharmacy, active cancer, decompensated heart failure, substance abuse, psychiatric disorders, dementia, and chronic liver disease have all been associated with lower TTR. Targeted strategies to improve TTR are urgently needed. [ABSTRACT FROM AUTHOR]