Time In Therapeutic Range Levels Research Articles

Appropriate Use of Anticoagulants among Nonvalvular Atrial Fibrillation Patients at a University Hospital in Thailand

OBJECTIVE: Warfarin is primarily used for stroke prevention in atrial fibrillation (AF) patients in Thailand. Novel oral anticoagulants (NOACs) are used less commonly due to their high cost. This study aimed to evaluate the appropriate use of anticoagulants and clinical outcomes among nonvalvular AF (NVAF) patients. METHODS: This retrospective study collected data from the electronic medical records of patients who were diagnosed with NVAF between January 2014 and December 2019 at the Faculty of Medicine, Vajira Hospital. Baseline characteristics, prescribed indication, types and doses of anticoagulant, and ischemic and hemorrhagic outcomes were recorded and analyzed. RESULTS: We analyzed 783 patients with NVAF in this study. Of these, 539 (68.90%) were treated with oral anticoagulants (OAC), including 344 patients (43.90%) with warfarin therapy and 195 (24.90%) with NOACs. Meanwhile, 492 (73.10%) patients with CHA2DS2VASC score ≥ 2 received OAC therapy that was suitable for their indication. Of the 344 patients who received warfarin, 112 patients (32.60%) had an optimal time in therapeutic range (TTR) level of ≥ 65%. Of the 195 NOAC patients, only 98 (50.30%) received appropriate doses of NOACs. There was no statistically significant difference in the overall incidence rates of ischemic stroke/systemic embolism, bleeding, cardiovascular death, and all-cause death between the warfarin and NOACS groups. Appropriate TTR levels in the warfarin group was associated with significantly lower incidence rates of cardiovascular death (hazard ratio: 0.14; 95% CI: 0.02–0.79; p = 0.02) and all-cause death (hazard ratio: 0.36; 95% CI: 0.12–0.87; p = 0.01), than inappropriate TTR levels. CONCLUSION: Most NVAF patients received oral anticoagulants with the appropriate indication. Warfarin is the most prescribed oral anticoagulant for patients with NVAF. About half of the patients received inappropriate doses of oral anticoagulants that potentially adversely affected the study outcomes of cardiovascular and all-cause deaths.

Which Factors Determine the Success of Anticoagulation with Warfarin

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

Comparison of the real-life clinical outcomes of warfarin with effective time in therapeutic range and non-vitamin K antagonist oral anticoagulants: Insight from the AFTER-2 trial.

It is unclear whether warfarin treatment with high time in therapeutic range (TTR) is as effective and safe as non-vitamin K antagonist oral anticoagulants (NOACs). It is crucial to compare warfarin with effective TTR and NOACs to predict long-term adverse events in patients with atrial fibrillation. We aimed to compare the long-term follow-up results of patients with atrial fibrillation (AF) who use vitamin K antagonists (VKAs) with effective TTR and NOACs. A total of 1140 patients were followed at 35 different centers for five years. During the follow-up period, the international normalized ratio (INR) values were studied at least 4 times a year, and the TTR values were calculated according to the Roosendaal method. The effective TTR level was accepted as >60% as recommended by the guidelines. There were 254 patients in the effective TTR group and 886 patients in the NOAC group. Ischemic cerebrovascular disease/transient ischemic attack (CVD/TIA), intracranial bleeding, and mortality were considered primary endpoints based on one-year and five-year follow-ups. Ischemic CVD/TIA (3.9% vs. 6.2%; P = 0.17) and intracranial bleeding (0.4% vs. 0.5%; P = 0.69), the one-year mortality rate (7.1% vs. 8.1%; P = 0.59), the five-year mortality rate (24% vs. 26.3%; P = 0.46) were not different between the effective TTR and NOACs groups during the follow-up, respectively. The CHA2DS2-VASC score was similar between the warfarin with effective TTR group and the NOAC group (3 [2-4] vs. 3 [2-4]; P = 0.17, respectively). Additionally, survival free-time did not differ between the warfarin with effective TTR group and each NOAC in the Kaplan-Meier analysis (dabigatran; P = 0.59, rivaroxaban; P = 0.34, apixaban; P = 0.26, and edoxaban; P = 0.14). There was no significant difference in primary outcomes between the effective TTR and NOAC groups in AF patients.

Switching from vitamin K antagonists to direct oral anticoagulants in non‐valvular atrial fibrillation patients: Does low time in therapeutic range affect persistence?

BackgroundNon‐valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low. ObjectiveTo examine if pre‐switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC. Patients/MethodsAdult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre‐switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100‐day prescription gap. Cumulative incidences of non‐persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre‐switch TTR levels with DOAC non‐persistence was evaluated by Cox regression models. ResultsA total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre‐switch TTR ≤ 45%. After switching from VKA to DOAC, 14.0% (95% confidence interval [CI] 11.3–17.0%) of the patients with a pre‐switch TTR ≤ 45% became non‐persistent to DOAC within 1 year, while 9.8% (95% CI 8.7–11.0%) did in those with a pre‐switch TTR > 45%. In a multivariable model, a pre‐switch TTR ≤ 45% was associated with a higher risk of non‐persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22–1.97). Results were similar when using other cut‐off points (60% or 70%) to define a low TTR. ConclusionNVAF patients switching from VKA to DOAC due to a low pre‐switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre‐switch TTR.

Anticoagulation Quality of Warfarin and the Role of Physician-Pharmacist Collaborative Clinics in the Treatment of Patients Receiving Warfarin: A Retrospective, Observational, Single-Center Study.

Background: The management of patients receiving warfarin is complicated. This study evaluated the anticoagulation quality of warfarin, explored potential predictors associated with poor anticoagulation quality, and elucidated the role of clinical pharmacists in the management of warfarin treatment. Methods: We retrospectively collected data on patients who either initially received warfarin or returned to warfarin after withdrawal between January 1, 2015 and January 1, 2020. The primary outcome was time in therapeutic range (TTR), and a TTR of ≥60% was considered as good anticoagulation quality. The secondary outcomes included thromboembolic and bleeding events during the follow-up. We assessed the TTR of each participant and investigated the potential predictors of poor anticoagulation quality (TTR < 60%) using logistic regression analysis. Additionally, we compared the warfarin anticoagulant quality and the incidence of clinical adverse events between atrial fibrillation patients in physician–pharmacist collaborative clinics (PPCCs) and general clinics. Results: Totally, 378 patients were included. The mean TTR of patients was 42.6 ± 29.8%, with only 32% of patients having achieved good anticoagulation quality. During a mean follow-up period of 192 ± 92 days, we found no significant differences in the incidences of thromboembolic events (5.0% vs. 5.1%, p = 0.967) and bleeding events (1.7% vs. 4.7%, p = 0.241) between patients with good and those with poor anticoagulation quality. The presence of PPCCs (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.25–0.90, p = 0.022) was an independent protective factor of poor anticoagulation quality, while the presence of more than four comorbidities (OR: 1.98, 95% CI: 1.22–3.24, p = 0.006) and an average interval of international normalized ratio monitoring of >30 days (OR: 1.74, 95% CI: 1.10–2.76, p = 0.019) were independent risk factors of poor anticoagulation quality. Compared with atrial fibrillation patients in general clinics, patients in PPCCs were found to have a significantly increased mean TTR level (48.4% ± 25.7% vs. 38.0% ± 27.6%, p = 0.014). Conclusion: The anticoagulation quality of warfarin was relatively low at our institution. The presence of more than four comorbidities and an average interval of international normalized ratio monitoring of >30 days independently contributed to poor anticoagulation quality. Meanwhile, the use of PPCC model improved the anticoagulation quality of warfarin.

Anticoagulation Control of Warfarin in Pharmacist-Led Clinics Versus Physician-Led Clinics: A Prospective Observational Study.

PurposeWarfarin is an affordable drug used for numerous indications, and still a favorable choice for patients with a history of bleeding from direct oral anticoagulants or presence of valvular heart diseases. However, warfarin requires regular international normalized ratio (INR) monitoring for safety and efficacy. Warfarin’s efficacy and safety is correlated with actual time spent within the therapeutic INR. Time in therapeutic range (TTR) is an estimate that measures the percentage of actual time spent within the therapeutic INR. Our aim was to investigate differences in anticoagulation control of warfarin using TTR between pharmacists and other health-care providers.MethodsThis prospective observational study was conducted in an ambulatory-care setting of a tertiary hospital to compare anticoagulation management using TTR between clinics run by pharmacists versus other health-care providers.ResultsA total of 62 patients were enrolled: 33 in the pharmacist-led clinic and 29 in the physician-led clinic. TTR levels were statistically higher among patients in the pharmacist-led clinic than than the physician-led clinic (87.27%±3.82% and 52.48%±5.49%, respectively; p<0.001). For 27 patients followed retrospectively by physicians and prospectively by clinical pharmacists, TTR was statistically higher during clinical pharmacists’ care (91.70%±2.93% versus 61.39%±5.11%, respectively; p<0.001). During the study, approximately 82% of patients reached their target INR in the pharmacist-led clinic compared to 24% in the physician-led clinic.ConclusionThe findings of our study found that patients followed in the pharmacist-led clinic had higher TTR levels than those followed in the physician-led clinic.

Non-genetic factors and polymorphisms in genes CYP2C9 and VKORC1: predictive algorithms for TTR in Brazilian patients on warfarin.

This study was designed to evaluate the association of non-genetic factors and polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) with time in therapeutic range (TTR), and to build a regression model to predict the quality of oral anticoagulation control in a sample of Brazilian patients. This is a retrospective cohort study developed at an anticoagulation clinic of a university hospital. Overall, 312 patients were included. The quality of oral anticoagulation control was evaluated by TTR. TTR was dichotomized for analysis, using two cutoff points for classification as inadequate (TTR ≤ 60.0%) and optimal (TTR ≥ 75.0%) control. The average age was 60.4 ± 13.5 years, with a predominance of women (187; 59.9%). The -G1639A polymorphism of the VKORC1 gene, when evaluated, based on the recessive inheritance pattern [AA × (GA + GG)], patients with AA genotype exhibited a higher TTR (68.2% versus 62.8%, p = 0.017). TTR ≤ 60.0% was associated with number of drugs in chronic use, assistance for warfarin administration, reports of not taking warfarin, absenteeism, sex (female), and target INR (International Normalized Ratio; 2.00-3.00). TTR ≥ 75.0% was associated with sex (male), target INR (2.00-3.00), assistance for warfarin administration, reports of not taking warfarin, and absenteeism. The two algorithms proposed showed adequate ability to predict TTR presenting good sensitivity and specificity. Our findings provided useful information for risk stratification depending on TTR level and for future investigations on the quality of oral anticoagulation control in Brazilian anticoagulation clinics.

Maintenance dose of warfarin beyond time in therapeutic range for preventing vascular events

BackgroundThe quality of anticoagulation is closely associated with efficacy and safety in warfarin users. Although genetic polymorphisms have been related to warfarin dosages and vascular events(VE), genetic evaluations have not been recommended for all warfarin users. The aim is to evaluate the significance of the maintenance dose of warfarin (MDW) on VE, considering the time in therapeutic range (TTR). MethodsThis retrospective study analyzed the data of patients who received warfarin for any reasons. A total of 11,835 patients with warfarin were divided into quartiles by MDW. We assessed TTR using the Rosendaal method and VE. ResultsVE occurred in 9.1% of the warfarin users. The mean TTR level was 34.0 ± 25.7%, and the MDW was 3.38 ± 1.06 mg per day. Patients with VE were more likely to have a lower MDW and lower TTR levels. In moderate- or well-controlled TTR status, a lower MDW was significantly related to under-controlled anticoagulation and associated with higher risks of VE. Lower MDW had a higher risk of stroke or arterial/venous thromboembolism (Q1: OR, 1.57; 95% CI 1.25 to 1.96; Q2: OR, 1.40; 95% CI 1.12 to 1.75; Q3: OR, 1.35; 95% CI 1.08 to 1.68). ConclusionsWe suggest that patients with very low MDW might be at risk when using warfarin. Therefore, we propose that patients with a very low MDW might be alternatively considered for novel oral anticoagulants rather than warfarin.

The Prevalence and Risks of Inappropriate Combination of Aspirin and Warfarin in Clinical Practice: Results From WARFARIN-TR Study

Background:The use of warfarin and aspirin in combination is restricted to limited patients under relevant guidelines.Aims:To evaluate the prevalence of the inappropriate combination of aspirin and warfarin therapy in daily practice and its risks.Study Design:Cross-sectional study.Methods:The awareness, efficacy, safety, and time in the therapeutic range of warfarin in the Turkish population study is a multi-center observational study that includes 4987 patients using warfarin for any reason between January 1, 2014, and December 31, 2014. To determine the prevalence of inappropriate combination use in daily practice, all patients who had a history of atherosclerotic disease (ischemic heart disease, peripheral artery disease) or cerebrovascular disease (n=1498) were excluded. The data of 3489 patients were analyzed. We defined inappropriate combination as all patients who received aspirin and warfarin regardless of the indication for warfarin use, under the direction of the European Society of Cardiology guideline recommendation.Results:The mean age of patients was 59.2±13.8 years (41.8% male). The prevalence of the inappropriate use of warfarin and aspirin combination was 20.0%. The prevalence of combination therapy in patients with a primary indication for mechanical heart valve, non-valvular atrial fibrillation, and other reasons was 20.5%, 18.7%, and 21.0%, respectively. Multivariate logistic regression analysis revealed that age (odds ratio, 1.009; 95% confidence interval, 1.002-1.015; p=0.010), heart failure (odds ratio, 1.765; 95% confidence interval, 1.448-2.151; p<0.001), smoking (odds ratio, 1.762; 95% confidence interval, 1.441-1.153; p<0.010), chronic kidney disease (odds ratio, 2.057; 95% confidence interval, 1.494-2.833; p<0.001), and deep vein thrombosis (odds ratio, 0.463; 95% confidence interval, 0.229-0.718; p=0.001) were independent predictors of combination therapy (r2=0.66). The mean time in therapeutic range of patients receiving combination therapy was significantly lower than in those on warfarin monotherapy (51.6±27.05 vs. 54.7±23.93; p=0.006). Overall, 19.4% (n=677) of patients had a bleeding event (major bleeding 13.0%, n=88) within a year. Percentages of patients with combination therapy were significantly higher in patients with major bleeding than in patients without major bleeding (29.5% vs. 19.7%; p=0.023).Conclusion:Our study demonstrated that 20.0% of patients taking warfarin use concomitant aspirin inappropriately in daily practice. Patients receiving aspirin with warfarin were demonstrated to have more comorbidities, lower time in therapeutic range levels, and higher bleeding rates.

Effect of Standardized Warfarin Treatment Protocol on Anticoagulant Effect: Comparison of a Warfarin Medication Therapy Adherence Clinic with Usual Medical Care.

Objective: To evaluate the impact of pharmacist-led warfarin management and standardized treatment protocol.Methods: A retrospective cohort study was carried out in a cardiology referral hospital located in central Kuala Lumpur, Malaysia, from 2009 to 2014. The inclusion criteria were: adult patients who were diagnosed and treated for atrial fibrillation (AF) with warfarin, attended the warfarin medication therapy adherence clinic (WMTAC) for at least 12 weeks, and with at least four international normalized ratio (INR) readings. The electronic medical records were reviewed for demographics, type of AF, warfarin dose, INRs, adverse events, co-morbidities, and drug–drug interactions. The outcome measures included the mean time to therapeutic INR, the mean percentage of time in therapeutic range (TTR), bleeding events, and common drug interactions.Results: Out of 473 patients, 151 patients fulfilled the inclusion criteria. The findings revealed that there were significant associations between the usual medical care (UMC) group and pharmacist-led WMTAC in terms of TTR (p = 0.01) and INR (p = 0.02) levels. A positive impact of pharmacists’ involvement in the WMTAC clinic was where the “pharmacist’s recommendation accepted” (p = 0.01) and “expanded therapeutic INR range” (p = 0.04) were statistically significantly higher in the WMTAC group.Conclusion: There was a significant positive association between the pharmacist-led WMTAC and anticoagulation effect (therapeutic TTR, INR). The identified findings revealed that expanded role of pharmacist in pharmacist-managed warfarin therapy is beneficial to optimize the warfarin therapy. This study also highlighted the critical roles that pharmacists can actively play to ensure optimal anticoagulation pharmaceutical care.Key messages:What is already known on this subject?• Pharmacist-managed warfarin therapy is beneficial for optimizing warfarin therapy. In such therapy, recommendations such as dose adjustment and safer alternative drugs (given drug–drug interactions and/or food–drug interactions) are made.• The active involvement of pharmacists in warfarin adherence clinics could significantly improve adherence.• However, the warfarin treatment outcomes from UMC, pharmacist-and-physician-led care and pharmacist-led care have not been studied.• The impact of the implementation of the standardized protocol for the warfarin adherence clinic has not been assessed.What this study adds?• INR levels among UMC group and WMTAC group were significantly different.• Though the TTR level for the WMTAC group was not significantly different than the UMC group, it was higher and close to the targeted 60% level.• The identified findings show that pharmacists’ focus on intervention for missed doses, adherence and dose adjustment provide positive impact on patients’ warfarin therapy.

Patient-Specific Tailored Intervention Improves INR Time in Therapeutic Range and INR Variability in Heart Failure Patients

BackgroundMany patients with heart failure need anticoagulants, including warfarin. Good control is particularly challenging in heart failure patients, with <60% of international normalized ratio (INR) measurements in the therapeutic range, thereby increasing the risk of complications. This study aimed to evaluate the effect of a patient-specific tailored intervention on anticoagulation control in patients with heart failure. MethodsPatients with heart failure taking warfarin therapy (n = 145) were randomized to either standard care or a 1-time intervention assessing potential risk factors for lability of INR, in which they received patient-specific instructions. Time in therapeutic range (TTR) using Rosendaal's linear model was assessed 3 months before and after the intervention. ResultsThe patient-tailored intervention significantly increased anticoagulation control. The median TTR levels before intervention were suboptimal in the interventional and control groups (53% vs 45%, P = .14). After intervention the median TTR increased significantly in the interventional group compared with the control group (80% [interquartile range, 62%-93%] vs 44% [29%-61%], P <.0001). The intervention resulted in a significant improvement in the interventional group before versus after intervention (53% vs 80%, P <.0001) but not in the control group (45% vs 44%, P = .95). The percentage of patients with a TTR ≥60%, considered therapeutic, was substantially higher in the interventional group: 79% versus 25% (P <.0001). The INR variability (standard deviation of each patient's INR measurements) decreased significantly in the interventional group, from 0.53 to 0.32 (P <.0001) after intervention but not in the control group. ConclusionsPatient-specific tailored intervention significantly improves anticoagulation therapy in patients with heart failure.

Potential Causes and Implications of Low Target Therapeutic Ratio in Warfarin-Treated Patients for Thrombosis Prophylaxis: A Single-Center Experience.

Time in therapeutic range (TTR) of international normalized ratio is crucial for the safety and efficacy of anticoagulation with warfarin and it is influenced by many factors. There are limited data about the quality of warfarin therapy and its effects on clinical outcomes in Turkey. The aim of this study is to demonstrate the quality of anticoagulant therapy with warfarin and evaluate the parameters that affect the quality of warfarin therapy. A total of 170 patients with atrial fibrillation (AF; mean age: 62.2 ± 13.3; 69.2% female) treated with warfarin were included in this study. The mean follow-up period was 20 ± 8.4 months. The mean TTR levels of all patients were found to be 54.2% ± 21.4%. The TTR levels were similar in patients with valvular AF (VAF) and nonvalvular AF (NVAF). Logistic regression analysis revealed that elderly, heart failure (HF), and renal dysfunction were independent predictors of lower TTR. There were no significant differences between the VAF and NVAF subgroups regarding the incidence of mortality, stroke, and myocardial infarction. Cox regression analysis revealed that HF, coronary artery disease, and renal dysfunction were independent predictors of clinical outcomes in addition to lower TTR. Our results provide data regarding the quality of anticoagulation with warfarin from a single tertiary center in Istanbul, Turkey. The questions remain in seeking quality improvement in anticoagulation.

Improvement of time in therapeutic range with warfarin by pharmaceutical intervention.

Background Anticoagulation therapy with warfarin is highly effective for prevention and treatment of thromboembolic disorders. Nevertheless, its management is challenging especially in developing countries, where the medical access is difficult and patient education is poor. Objective To determine the effect of pharmaceutical intervention (PI) on the time in therapeutic range (TTR) of a group of anticoagulated patients from our referral center. Method A group of consecutive outpatients previously treated by usual medical care underwent PI. The intervention consisted in the identification and avoidance of food and drug interactions, the confection of medication schedule charts and education to patients regarding side effects and drug monitoring. Mean TTR before and after PI was compared through the Wilcoxon test for repeated measures. Regression analyses were performed to assess the relationship between a TTR level under 65% and potential explanatory variables. Results Mean TTR before PI was 37.4±23.5% and after PI it raised to 67.0±24.9%. Mean change in TTR was +29.5% (95% CI 14.5-44.6; p<0.001). Before PI only 4 patients had TTR values above 65%, in contrast to 18 patients after PI. Conclusion Our findings support the efficacy of PI to improve TTR values in patients treated with warfarin.

The awareness, efficacy, safety, and time in therapeutic range of warfarin in the Turkish population: WARFARIN-TR.

Objective:The awareness, time in therapeutic range (TTR), and safety of warfarin therapy were investigated in the adult Turkish population.Methods:This multicenter prospective study includes 4987 patients using warfarin and involved regular international normalized ratio (INR) monitoring between January 1, 2014 and December 31, 2014. TTR was calculated according to F.R. Roosendaal’s algorithm. Awareness was evaluated based on the patients’ knowledge of warfarin’s affect and food–drug interactions.Results:The mean TTR of patients was 49.52±22.93%. The patients with hypertension (55.3%), coronary artery disease (23.2%), congestive heart failure (24.5%), or smoking habit (20.8%) had significantly lower TTR levels than the others. Of the total number of patients, 42.6% had a mechanical valve, 38.4% had non-valvular atrial fibrillation (AF), and 19% had other indications for warfarin. Patients with other indications had lower TTR levels than those with mechanical valve and non-valvular AF (p=0.018). Warfarin awareness decreased in higher age groups. The knowledge of warfarin’s food–drug interactions was 55%. People with higher warfarin awareness had higher TTR levels. Patients with ≤8 INR monitoring/year had lower TTR levels (46.4±25.3 vs. 51.1±21.3, respectively, p<0.001) and lower awareness (44.6% vs. 60.6%, p<0.001) than patients with ≥8 INR monitoring/year. In this study, 20.1% of the patients had a bleeding event (major bleeding 15.8%, minor bleeding 84.2%) within a year.Conclusion:Both the mean TTR ratios and awareness of the Turkish population on warfarin therapy were found to be low. It was thought that low TTR levels of the Turkish population may be caused by the low awareness of warfarin, warfarin’s food–drug interactions, and high rates of concomitant diseases. (Anatol J Cardiol 2016; 16: 595-600)

Evaluation of the impact of warfarin time in therapeutic range on outcomes of patients with atrial fibrillation in Turkey: perspectives from the observational, prospective WATER Registry.

Warfarin is highly efficacious in reducing stroke risk in patients with atrial fibrillation (AF). However, its safety and efficacy in stroke prevention is markedly influenced by its time in therapeutic range (TTR). The quality of anticoagulant therapy varies considerably among countries. Representative data concerning the quality of anticoagulant therapy and its effects on clinical outcomes in Turkey are lacking. Warfarin in Therapeutic Range (WATER) registry is a prospective, observational study which followed 572 AF patients (mean age 67.3 ± 12 years; females 60%; 71% non-valvular AF) treated with warfarin. At a median of 22-month follow-up, the mean TTR value was 42.3 ± 18% (median: 40%) for the whole population and lower in non-valvular AF su group than valvular AF subgroup (40.3 ± 18 vs. 46.9 ± 19, respectively, p < 0.001). Death, cardiac hospital-ization and minor bleeding rates were higher in the group with TTR value < 40% than the group with > 40% (3.4% vs. 5.9%; 28.6% vs. 35.4%; 36.5% vs. 41.7%, respectively, all of them p < 0.001). A correlation analysis showed a negative correlation between age and TTR value (r = -0.178, p < 0.001). Mean CHA2DS2VASc score was 3.63 ± 1.5 and mean HASBLED score was 2.38 ± 1.01 in the non-valvular AF group. A negative correlation was observed between TTR levels and CHA2DS2VASc score. WATER provides insight into the anticoagulation control status of AF patients in Turkey. The quality of anticoagulation was poor. Strategies should be undertaken by clinicians and patients to improve TTR. New oral anticoagulant agents may be perfect alternatives for non-valvular AF patients.

Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL.

BackgroundThe majority of studies on quality of oral anticoagulation (OAC) therapy with vitamin K-antagonists are performed with short-acting warfarin. Data on long-acting phenprocoumon, which is frequently used in Europe for OAC therapy and is considered to enable more stable therapy adjustment, are scarce. In this study, we aimed to assess quality of OAC therapy with phenprocoumon in regular medical care and to evaluate its potential for optimization in a telemedicine-based coagulation service.MethodsIn the prospective observational cohort study program thrombEVAL we investigated 2,011 patients from regular medical care in a multi-center cohort study and 760 patients from a telemedicine-based coagulation service in a single-center cohort study. Data were obtained from self-reported data, computer-assisted personal interviews, and laboratory measurements according to standard operating procedures with detailed quality control. Time in therapeutic range (TTR) was calculated by linear interpolation method to assess quality of OAC therapy. Study monitoring was carried out by an independent institution.ResultsOverall, 15,377 treatment years and 48,955 international normalized ratio (INR) measurements were analyzed. Quality of anticoagulation, as measured by median TTR, was 66.3% (inte rquartile range (IQR) 47.8/81.9) in regular medical care and 75.5% (IQR 64.2/84.4) in the coagulation service (P <0.001). Stable anticoagulation control within therapeutic range was achieved in 63.8% of patients in regular medical care with TTR at 72.1% (IQR 58.3/84.7) as compared to 96.4% of patients in the coagulation service with TTR at 76.2% [(IQR 65.6/84.7); P = 0.001)]. Prospective follow-up of coagulation service patients with pretreatment in regular medical care showed an improvement of the TTR from 66.2% (IQR 49.0/83.6) to 74.5% (IQR 62.9/84.2; P <0.0001) in the coagulation service. Treatment in the coagulation service contributed to an optimization of the profile of time outside therapeutic range, a 2.2-fold increase of stabile INR adjustment and a significant decrease in TTR variability by 36% (P <0.001).ConclusionsQuality of anticoagulation with phenprocoumon was comparably high in this real-world sample of regular medical care. Treatment in a telemedicine-based coagulation service substantially improved quality of OAC therapy with regard to TTR level, frequency of stable anticoagulation control, and TTR variability.Trial registrationClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0268-9) contains supplementary material, which is available to authorized users.

Improving quality measurement for anticoagulation: adding international normalized ratio variability to percent time in therapeutic range.

Among patients receiving warfarin, percent time in therapeutic range (TTR) and international normalized ratio (INR) variability predict adverse events individually. Here, we examined what is added to the prediction of adverse events by using both measures together. We included 40 404 patients anticoagulated for atrial fibrillation, aged 65+, within the Veterans Health Administration. TTR and log-transformed INR variability were calculated for each patient. Our study outcomes were ischemic stroke and major bleeding, defined using International Classification of Diseases-9 codes. We estimated the hazard ratios (HRs) for the study outcomes using 3 nested Cox regression models, including (1) TTR or log INR variability separately; (2) TTR and log INR variability together; and (3) both predictors together plus an interaction term. We divided TTR into 3 categories (high, >70%; moderate, 50% to 70%; low, <50%) and log INR variability into 2 categories (stable and unstable). The reference groups high TTR and stable anticoagulation each denote good control. Higher log INR variability (ie, unstable control) predicted ischemic stroke (HR=1.45, P<0.001) and major bleeding (HR=1.57, P<0.001) independently, regardless of TTR levels. Our model with interaction terms showed that High log INR variability predicted a significantly higher risk for ischemic stroke and major bleeding compared with low log INR variability, at moderate TTR levels (HR= 1.27 and HR=1.29, respectively) and at high TTR levels (HR=1.55 and HR=1.56, respectively), but not at low TTR levels. Unstable anticoagulation predicts warfarin adverse effects independent of TTR. Moreover, knowledge about anticoagulation stability further stratifies the risk for adverse events at given levels of TTR.

Abstract 18820: Estimating Time In Therapeutic Range Using The Percentage of Visits in International Normalized Ratio Range Among Patients with Nonvalvular Atrial Fibrillation

OBJECTIVES: Time in therapeutic range (TTR) has been a quality indicator for level of anticoagulation even though it is not readily available for practitioners to estimate level of anticoagulation for patients. A simpler measure that is based on the number of visits, percentage of visits in international normalized ratio (INR) range (PVIR), may estimate the anticoagulant control. This measure is examined for correlation with TTR levels achieved among patients with nonvalvular atrial fibrillation (NVAF) in a large retrospective database. METHODS: We analyzed longitudinal patient-level anticoagulation management records collected between 2006 and 2010 by decision support software, CoagClinic™. Adult patients with NVAF with at least 2 anticoagulation clinic visits and no gap &gt;180 days between visits were identified. The Rosendaal method was used to calculate TTR. Anticoagulation visits with 2.0≤ INR≤3.0 was defined as visits within INR range. PVIR was calculated by dividing the number of visits within INR range by the total number of visits. PVIR was stratified by the increment of 10%, and then compared to corresponding TTR. Pearson correlation coefficient between TTR and PVIR was calculated. RESULTS: We identified 36,978 patients who met all inclusion criteria. The mean (±SD) age was 72.3±10.6 years, with 78.4% ≥65 years. The mean (±SD) TTR was 62.2±20.7. On average, patients had 39 visits, of which 23 were in INR range. The average PVIR was 59%. A substantial proportion of patients (79%) had PVIR ≤70%; 18% of patients had PVIR between ≤71% and ≤90%; only about 3% had PVIR ≥91%. PVIR and TTR showed a strong linear relationship (Table 1; Pearson correlation coefficient=0.87). CONCLUSIONS: Percentage of visits in INR range (PVIR) offers a simplified measure for daily practitioners to estimate level of anticoagulation control and help identify patients with poor control.