Median Time In Therapeutic Range Research Articles

Comparison of anticoagulation control and outcomes between usual medical care and pharmacist-led anticoagulation service in ambulatory patients taking warfarin at tertiary hospital in Ethiopia: a quasi-experimental study

BackgroundWe aimed to compare anticoagulation control and outcomes between usual medical care (UMC) and pharmacist-led anticoagulation services (PLAS) in patients receiving warfarin at the Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia.MethodsA quasi-experimental study was conducted, including 350 (66.7%) and 175 (33.3%) patients from the UMC and PLAS groups, respectively, from 525 patients. The time in therapeutic range (TTR) was determined using the Rosendaal method, with a TTR ≥ 65% set as the cut-off for optimal anticoagulation. The two-sample Wilcoxon rank-sum (Mann–Whitney U) test was used to compare continuous variables between groups. Categorical variables were compared between groups using Pearson’s chi-square test or Fisher’s exact test. Logistic regression and negative binomial regression analyses were conducted to identify the factors associated with suboptimal TTR and secondary outcomes, respectively, at the p values < 0.05, and 95% confidence interval (CI).ResultsCompared with the UMC group, the patients in the PLAC group showed a significantly higher median (IQR) TTR [60.89% (43.5–74.69%) vs. 53.65% (33.92–69.14%), p < 0.001]. A significantly higher optimal TTR (≥ 65%) was achieved in the PLAC group (41.7% vs. 31.7%) than in the UMC group (p = 0.002). The odds of having a poor TTR were reduced by 43% (AOR = 0.57, 95% CI = 0.36–0.88, p = 0.01) among patients in the PLAC group compared to those in the UMC group. There were no statistically significant differences in the secondary outcomes between the groups, except for all-cause emergency visits (p = 0.003). The incidence of bleeding events decreased by 3% (IRR = 0.97, 95% CI = 0.96–0.99, p < 0.001) for every increase in INR monitoring frequency. The incidence of thromboembolic events increased by a factor of 15.13 (IRR = 15.13, 95% CI = 1.47–155.52, p = 0.02) among patients with a high-risk CHA2DS2-VASc score compared with those with a moderate score.ConclusionPatients in the PLAC group had a significantly higher median TTR than those in the UMC group did. There were no statistically significant differences in the secondary outcomes between the groups, except for fewer all-cause emergency department visits in the PLAC group.

Anticoagulation control among patients on vitamin K antagonists in nine countries in Sub-Saharan Africa.

Vitamin K antagonists (VKA) is the primary anticoagulant in most settings of Sub-Saharan Africa. Understanding the quality of anticoagulation services in the continent is vital in optimising the intended benefits. This study assessed the quality of anticoagulation and associated factors among VKA-treated patients in nine SSA countries. We conducted a retrospective cohort study of randomly selected patients on anticoagulation from 20 clinics in Botswana, the Democratic Republic of Congo, Ethiopia, Gambia, Ghana, Mozambique, Nigeria, Tanzania, and South Africa. Eligible participants were those on VKAs for at least three months and with at least four international normalised ratios (INR) results in 2019-2021. We report the proportion of INR values in the therapeutic range, time-in-therapeutic range (TTR) using the Rosendaal method, and the proportion of patients with TTR ≥ 65% (optimal anticoagulation). The mean age was 51.1(16.1) years, and 64.2% were women. The most common indications for VKA included venous thromboembolism (29.6%), prosthetic valves (26.7%) and atrial fibrillation/flutter (30.1%). We analysed 6743 INR tests from 1011 participants, and of these, 48.5% were sub-therapeutic, 34.1% therapeutic, and 17.4% were supratherapeutic relative to disease-specific reference ranges. TTR was calculated for 660 patients using 4927 INR measurements. The median (interquartile range [IQR]) TTR was 35.8(15.9,57.2) %. Optimal anticoagulation control was evident in 19.2% of participants, varying from 2.7% in Tanzania to 23.1% in Ethiopia. The proportion of patients with TTR ≥ 65% was 15,4% for prosthetic heart valves, 21.1% for venous thromboembolism and 23.7% for atrial fibrillation or flutter. Countries with universal health coverage had higher odds of optimal anticoagulation control (adjusted odds ratio (aOR) 1.79, 95% confidence interval [CI], 1.15- 2.81, p = 0.01). Patients on VKAs for different therapeutic indications in SSA had suboptimal TTR. Universal health coverage increased the odds of achieving TTR by 79%. The evidence calls for more intensive warfarin management strategies in SSA, including providing VKA services without out-of-pocket payments.

The quality of pharmacist-led community warfarin management across 2 provinces in Canada: A cross-sectional observational study.

Guidelines for anticoagulation management services recommend personnel be specially trained in warfarin management and suggest using tools such as decision-support software. To date, there have been no Canadian studies documenting the quality of warfarin management using a similar guideline recommended approach. A cross-sectional, retrospective observational study was conducted to measure the quality of pharmacist-led warfarin management using point-of-care international normalized ratio (INR) testing and decision-support software in various ambulatory settings in Canada. Settings included 4 family health teams in Ontario and 40 community pharmacies across Nova Scotia. Quality was measured using time in therapeutic range (TTR) and was reported in 3 manners: mean TTR, median TTR and time-weighted mean TTR. The primary outcome included 963 patients. The combined mean and median TTR for the 2019 Ontario family health teams and Nova Scotia pharmacies was 74.2% and 77.3% (interquartile range 64%-87.9%), respectively. The time-weighted mean TTR was 76.3%. To the best of our knowledge, the TTR achieved by this model of care is the highest reported in Canadian general practice. Since Thrombosis Canada defines good-quality warfarin management as a TTR of 60% or greater, and many studies have reported an association between higher TTR values and lower rates of thrombosis and hemorrhage, this model of care may have significant benefits for patients. This study demonstrates the high quality of anticoagulation management provided by specially trained pharmacists using point-of-care INR testing and decision-support software. These results support expanded access to this service for all Canadians. Can Pharm J (Ott) 2024;157:xx-xx.

Platelet Function Testing to Guide Cangrelor Dosing in Patients with Temporary Mechanical Circulatory Support or as a Bridge to Procedure.

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12-24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85-208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375-0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis.

Enhancing postoperative anticoagulation therapy with remote patient monitoring: A pilot crossover trial study to evaluate portable coagulometers and chatbots in cardiac surgery follow-up

Objective Prior research has not assessed the value of remote patient monitoring (RPM) systems for patients undergoing anticoagulation therapy after cardiac surgery. This study aims to assess whether the clinical follow-up through RPM yields comparable outcomes with the standard protocol. Methods A crossover trial assigned participants to SOC-RPM or RPM-SOC, starting with the standard of care (SOC) for the first 6 months after surgery and using RPM for the following 6 months, or vice-versa, respectively. During RPM, patients used the Coaguchek© to accurately measure International Normalized Ratio values and a mobile text-based chatbot to report PROs and adjust the therapeutic dosage. The study assessed patients’ and clinicians’ experience with RPM and compared direct costs. Results Twenty-seven patients participated. The median time in therapeutic range (TTR) levels during RPM were 72.2% and 50.6% for the SOC-RPM and RPM-SOC arms, respectively, and during SOC, they were 49.4% and 58.4% for SOC-RPM and RPM-SOC arms, respectively. Patients and the clinical team reported high trust and satisfaction with the proposed digital service. Statistically significant differences were only found in the cost of RPM in the RPM-SOC, which was higher than SOC in the SOC-RPM arm. Conclusions Portable coagulometers and chatbots can enhance the remote management of patients undergoing anticoagulation therapy, improving patient experience. This presents a promising alternative to the current standard procedure. The results of this study seem to suggest that RPM may have a higher value when initiated after a SOC period rather than starting RPM immediately after surgery. Trial registration: ClinicalTrials.gov NCT06423521.

Short versus long-term anticoagulation for left ventricular thrombosis resolution during vitamin k antagonist therapy

Abstract Background The optimal duration of anticoagulant therapy to achieve thrombus resolution and prevent cardioembolic events in left ventricular thrombosis (LVT) has not yet been established. Purpose The purpose of our study is to evaluate the incidence of LVT resolution at 3 versus 12 months of vitamin K antagonists (VKAs) therapy. Methods Consecutive patients diagnosed with LVT and treated with VKAs for at least 12 months at 5 anticoagulant outpatient clinics in Italy were retrospectively included. The primary effectiveness outcome was on-treatment thrombus resolution while the secondary was objectively documented on-treatment acute ischemic stroke, peripheral embolism, and myocardial infarction at 12-months follow-up. Safety outcomes were on-treatment major and clinically relevant non-major bleedings at 12-months follow-up as defined by the ISTH criteria. Cumulative incidences of thrombus resolution with 95% confidence intervals (CIs) were calculated while other outcomes were descriptively reported. Multivariable Cox hazards models were calculated using age, sex, reduced left ventricular ejection fraction (EF &amp;lt; 35%), VKAs monotherapy, and time in therapeutic range (TTR) below 60% as covariates for thrombus persistence at 12-months of follow-up. Results Out of 95 patients, 87 were finally included (Table) and 8 excluded due to the lack of relevant data. Median age was 67 years and 75.9% were men. A total of 64.4% of patients had acute myocardial infarction as risk factor for LVT development while 21.8% and 5.7% of patients had dilated and primary hypertrophic cardiomyopathy, respectively. A reduced EF and atrial fibrillation were present in 77.0% and 19.5% of patients, respectively. All but one patient received warfarin with a median TTR of 54%, and 35.5% of patients did not receive concomitant antiplatelet therapy. All included patients received VKAs for at least 12-months. The 3 and 12 month cumulative incidences (Figure) of thrombus resolution were 34.5% (95% CI, 24.7%-44.5%) and 68.3% (95% CI, 57.2%-77.1%), respectively. At multivariable Cox regression analysis, the presence of a reduced EF appeared to be associated with a higher risk of thrombus persistence at 12-months follow-up (Hazard Ratio 3.09; 95% CI 1.27-7.55; p=0.013). During 12-months follow-up, two patients (2.3%) had acute ischemic stroke at 4 and 7 months from the start of VKAs therapy. Three patients (3.4%) had a major and 5 (5.7%) a clinically relevant non-major bleeding that occurred within the first three months of VKAs. Conclusions A 12-month course of anticoagulant therapy with VKA appeared to be effective and safe in patients with LVT and appeared to be associated with a higher cumulative incidence of LVT resolution than a 3-month course. A reduced left ventricular EF was associated with a higher risk of LVT persistence. Whether anticoagulant agents with improved ease-of-use and safety profile are effective in this setting remains undefined.Baseline patients' characteristicsCumulative incidences of LVT resolution

Risk factors for serious adverse events related to vitamin K antagonists in children with congenital or acquired heart disease: a prospective cohort study

ObjectivesTo assess the occurrence of thrombosis and major bleeding in children with congenital or acquired heart disease (CAHD) treated with VKA and to identify risk factors for these serious adverse events (SAE). Study designAll children enrolled in our VKA dedicated educational program between 2008 and 2022 were prospectively included. The time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulation. Statistical analysis included Cox proportional hazard models. ResultsWe included 405 patients. Median follow-up was 18.7 (9.3–49.4) months. The median TTR was 83.1 % (74.4 %–95.3 %). No deaths occurred because of bleeding or thrombotic events. The incidences of thrombotic and major bleeding events were 0.9 % (CI95 % [0.1–1.8]) and 2.3 % (CI95 % [0.9–3.8]) per patient year, respectively. At 1 and 5 years, 98.3 % (CI95 % [96.2 %–99.2 %]) and 88.7 % (CI95 % [81.9 % 93.1 %]) of patients were free of any SAE, respectively. Although the mechanical mitral valve (MMV) was associated to major bleeding events (HR = 3.1 CI95 % [1.2–8.2], p = 0.02) in univariate analysis, only recurrent minor bleeding events (HR = 4.3 CI95 % [1.6–11.7], p < 0.01) and global TTR under 70 % (HR = 4.7 CI95 % [1.5–15.1], p < 0.01) were independent risk factors in multivariable analysis. In multivariable analysis, giant coronary aneurysms after Kawasaki disease (HR = 7.8 [1.9–32.0], p = 0.005) was the only risk factor for thrombotic events. ConclusionOverall, VKA therapy appears to be safe in children with CAHD. Suboptimal TTR, regardless of the indication for VKA initiation, was associated with bleeding events.

Lower dose direct oral anticoagulation or warfarin in atrial fibrillation. Which one is the best when time on therapeutic range information is available?

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District (TYH2019309) and The Finnish Foundation for Cardiovascular Research Background and aims Elderly patients with atrial fibrillation (AF) and patients with renal failure – for example – are recommended to use reduced doses of direct oral anticoagulants (DOACs) to minimize risk of ischemic stroke and hemorrhagic complications. However, it is not known whether DOACs used with reduced doses are better than warfarin when the quality of warfarin treatment is available by means of time in therapeutic range (TTR). Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients that combines data from several Finnish health care registers. Here all new-onset AF patients from 2011 to 2018 on reduced dose DOAC in Finland and patients on warfarin with TTR data were analyzed. Comorbidities, concomitant medications and CHA2DS2-VASc -scores were recorded until date of AF diagnosis. OAC purchases from diagnosis of AF to the end of study were analyzed. ICD-10 diagnoses for stroke (ischemic or hemorrhagic) or transient ischemic attack during OAC-use were analyzed until maximum follow-up of 730 days. Crude rates of stroke as well as weighted rates are provided. To avoid confounding by baseline characteristics as well as medications, an inverse probability of treatment weighted analysis was made. For warfarin users with sufficient laboratory data, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. Results Altogether, 52 204 new-onset AF patients with OAC therapy (46.1 % male, mean age 75.7 years, 43 549 on warfarin - with mean TTR 66%, median TTR 72%) were followed for 91 549 patient-years (py). Rate of stroke among patients on lower dose DOACs was 5.2/100 patient years (py) for dabigatran (n=2 672), 4.3/100 py for apixaban (n=3 936), 3.9 /100 py for rivaroxaban (n=1 866). In the TTR-quartiles of patients on warfarin, the rates of stroke were 9.3, 7.2, 5.5 and 4.3 /100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of stroke were 5.1, 3.5 and 3.1/100 py for dabigatran, apixaban and rivaroxaban, respectively and for warfarin from the lowest to the highest quartile: 8.7, 7.0, 5.4 and 4.1/100 py. Figure provides survival probabilities of the OAC groups with confidence limits. Conclusion In AF patients treated with OAC, the rates of stroke were highest among patients on warfarin at the lowest TTR quartiles, while the differences between high TTR groups and lower dose DOACs were only modest.

How good is time-in-therapeutic-range defined warfarin treatment compared to standard dose direct oral anticoagulants? Incidence of stroke in atrial fibrillation in a nationwide registry study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): The Finnish Foundation for Cardiovascular Research, and Helsinki and Uusimaa Hospital District research fund. Background and aims Direct oral anticoagulants (DOACs) have largely replaced warfarin in patients with atrial fibrillation (AF) to reduce risk of stroke. However, it is not known whether DOACs are more efficacious in preventing stroke or safer than good-quality warfarin treatment with high time in therapeutic range (TTR). Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients that combines data from several Finnish health care registers. We analyzed all new-onset AF patients in Finland from January 2011 to December 2018 with laboratory data available. Comorbidities, concomitant medications and CHA2DS2-VASc -scores were recorded until date of AF diagnosis. OAC purchases from diagnosis of AF to the end of study were analyzed. ICD-10 diagnoses for stroke (ischemic or hemorrhagic) or transient ischemic attack during OAC use were analyzed until maximum follow-up of 730 days. Confounding factors by baseline characteristics as well as medications were taken in account by use of an inverse probability of treatment weighted analysis. For warfarin users, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. Rate of stroke in different TTR quartiles for warfarin users were compared to standard dose dabigatran (150 mg bd.), apixaban (5mg bd.) and rivaroxaban (20mg od.). Results Altogether, 74 008 new-onset AF patients with OAC therapy (50.4 % male, mean age 73.0 years, 43 549 on warfarin, with mean TTR 66% and median TTR 72%) were followed for 109 143 patient years (py). Rate of stroke among patients with standard dose direct oral anticoagulants was 6.0/100 py for dabigatran (n=4545), 6.2/100 py for apixaban (n=12 426) and 4.0/100 py for rivaroxaban (n=12 950). In the TTR quartiles of patients on warfarin, rates of stroke were 9.3, 7.2, 5.5 and 4.3/100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of stroke were 6.3, 6.1 and 4.5/100 py for dabigatran, apixaban and rivaroxaban, respectively, and for warfarin from the lowest to the highest quartile: 8.8, 7.0, 5.5 and 4.2/100 py, respectively. The Figure provides survival probabilities (crude rates) of stroke with confidence intervals of the analysed OAC groups. Conclusion Rates of stroke were evidently the highest among patients on warfarin in the two lowest TTR quartiles, while the differences between high TTR groups and standard dose DOACs were only modest.

Implementation of point-of-care INR testing to improve effectiveness of anticoagulation clinic

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Oral Vitamin K antagonist (VKA) is still widely used for anticoagulation. Anticoagulation clinics are set up to monitor patients’ INR and adjust their VKA doses accordingly. Anticoagulation clinic in our centre introduced point-of-care (POC) INR testing in June 2021 to improve the effectiveness of the clinic. Purpose This audit was done to evaluate the effectiveness of anticoagulation since the introduction of the POC INR test into the clinic workflow. Methods This was a retrospective, cross-sectional, cohort audit study. The study period was from 1st June 2021 to 31st July 2022. List of patients who attended the clinic from 1st – 31st January 2022 was taken from the clinic log and their electronic medical records were reviewed for the study period. Only patients who have been established on VKA for at least 3 months were included in the audit. The data collected included their basic demographics, indication for VKA, any complications / death during the study period and if their VKA had been stopped and why and serial INRs from the POC INR test during the study period. The time in therapeutic range (TTR) is calculated by Rosendaal method and all the results analysed on Microsoft Excel. The audit standard for safe and effective anticoagulation was a TTR ≥ 70%. Results were compared to an audit done previously for the centre’s anticoagulation clinic done in 2020. Results 207 patients were included in this audit. Male patients accounted for 53.6% of the study population. Their ages ranged from 22 years to 102 years with a median age of 67 years. Majority of the patients were on VKA as stroke prevention for their atrial fibrillation (AF) (79.7%), followed by metallic valve replacement (13%). The median TTR for patients with AF had improved from 40.8% in 2020 to 51.05% in 2020-21 study period and this difference is significant (p = 0.017). Patients getting effective anticoagulation also improved from 23.26% in 2020 to 26.79% during this audit period. 13% of the study population developed complications on VKA in which 2.9% of patients developed gastrointestinal bleed and 1% developed intracranial haemorrhage. There were 4 fatalities, none were from gastrointestinal bleeding, intracranial haemorrhage or stroke. 10% of patients had their VKA changed to a novel oral anticoagulant (NOAC) as they were identified to have poor TTR during clinic review. Conclusions The introduction of POC INR test has proven to make significant improvement in patient’s median TTR for patients with AF. However, more efforts need to be made to further improve effectiveness of anticoagulation in our patients such as converting them to a NOAC if eligible or more thorough counselling and more frequent INR checks.

PS-C08-7: TIME IN THERAPEUTIC RANGE IS NOT A RISK FACTOR FOR CARDIOVASCULAR DISEASE WHEN ADJUSTED FOR MEAN SYSTOLIC BLOOD PRESSURE

Background: Time in therapeutic range (TTR) has been suggested as a novel metric to assess blood pressure (BP) control, the quality of antihypertensive therapy, and the risk of cardiovascular events in people with hypertension. Methods: We used a validated electronic health record dataset, including all BP recordings in primary care in two Swedish counties from 1993 to 2011. People were eligible if they were 18 years or older, had a diagnosis of hypertension, no previous cardiovascular events, and at least five BP recordings during the first five years from the date of hypertension diagnosis. TTR was defined as the percentage of BP readings with a systolic value less than 140 mmHg. Participants were followed until death, migration or the 31st of December 2019. The risk of myocardial infarction and stroke was assessed using Cox proportional hazards model with TTR as independent variable, with and without mean systolic BP as a covariate. All analyses were adjusted for age, sex, diabetes, county, income and educational level. Results: 72 724 participants (56% female, mean age 62 years) were included in the analyses. The mean BP level during the first five years after diagnosis was 151/85 mmHg, with a median TTR of 17.7% (interquartile range 0–40%). During an average 7.7 years of follow-up, 6551 participants experienced a first-ever stroke and 5513 a first-ever myocardial infarction. In the unadjusted analyses, the risk of stroke decreased by 7% (HR 0.93, 95%CI 0.92–0.94) and the risk of myocardial infarction decreased by 6% (0.94, 0.93–0.95) for each 10 percentage points increase in TTR. When including mean systolic BP as a covariate, however, TTR was not associated with either stroke (0.99, 0.97–1.01) or myocardial infarction (1.00, 0.99–1.02). Conclusion: TTR for systolic BP is not an independent risk factor for stroke and myocardial infarction in clinical practice and does not add importantly to mean systolic BP as a measure of BP control.

Oral anticoagulant management of patients with mechanical heart valves at the Salam Centre of Khartoum: Observations on quality of anticoagulation and thrombotic risk

IntroductionRheumatic heart disease with mechanical heart valve (MHV) replacement is common in Africa. However, MHV requires long-life anticoagulation and managing this can be challenging. Methods and resultsWe report data of a prospective observational study conducted between August 2018 and September 2019 in MHV patients in the Salam Centre for Cardiac Surgery built in Khartoum, by Emergency, an Italian Non-Governmental Organization, to evaluate the quality of anticoagulation control and the risk of thrombotic complications. ResultsWe studied 3647 patients (median age 25.1 years; 53.9 % female). Median Time in Therapeutic Range (TTR) was 53 % (interquartile range 37 % to 67 %) and 70 thrombotic events (rate 1.8 × 100 pt-years [95 % CI 1.38–2.23]) were recorded. Among patients in the first quartile of TTR (≤37 %), we recorded 34/70 (48.6 %) of all thrombotic events (rate 3.7 × 100 pt-years [95 % CI 2.5–5.1]), with a high mortality rate (2.2 × 100 pt-years [95 % CI 1.3–3.3]). In patients with guideline-recommended TTR (≥65 %) the event rate was 0.8 × 100 pt-years for thrombotic events [95 % CI 0.3–1.5] and 0.4 × 100 pt-years for mortality [95 % CI 0.1–0.9].Multivariable analysis showed that having a TTR in the lowest quartile (≤37 %) and being noncompliant are significantly associated with increased thrombotic risk. Aspirin use or different valve type did not influence the thrombotic risk. Almost 40 % of all thromboembolic complications could have been potentially prevented by further improving VKA management to obtain a TTR > 37 %. ConclusionThe thrombotic risk of MHV patients on VKAs living in a low-income country like Sudan is associated with low quality of anticoagulation control. Efforts should be made to decrease the number of non-compliant patients and to reach a guideline-recommended TTR of ≥65 %.

Oral anticoagulants, time in therapeutic range and renal function over time in real-life patients with atrial fibrillation and chronic kidney disease

AimsTo describe the use of warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD), to evaluate changes in renal function over time...

Severe adverse events related to vitamin K antagonists in children with congenital or acquired heart disease

Although increasingly used, vitamin K antagonists (VKA) remain difficult to manage for children with congenital or acquired heart disease (CAHD). To assess the occurrence of thrombosis and major bleeding events in children with CAHD treated with VKA and to determine associated risk factors. All children enrolled in the VKA dedicated educational program between 2008 and 2020 were prospectively included. Clinically suspected thrombotic events were confirmed by imaging, while major bleedings were defined according to the ISTH. Time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulant therapy. Statistical analysis included Cox proportional hazard models. We included 390 patients, median age at initiation was 6.6 (IQR: 12.8–3.2) years. Median follow-up was 17.7 months. The median TTR was 85.2% (IQR: 95.3%–74.4%). Thirteen thrombosis in 9 (2.3%) children and 24 major bleedings in 17 (4.4%) children were reported. At 6 years, 86.6% (CI95% [75.6%–92.4%]) and 95% (CI95% [89%–97.8%]) of patients were free of major bleeding and thrombotic events, respectively. In univariate analysis mitral valve replacement (MVR) was associated to major bleeding events (HR 3.32 [1.16–9.44], P = 0.025). In multivariable analysis, recurrent minor bleeding events (≥ 3) (HR 4.9 [1.7–13.8], P = 0.002) and global TTR under 70% (HR: 3.6 [1.1–10.9], P = 0.04) were risk factors associated to major bleeding events whereas MVR did not reach the level of significant association (HR: 1.92 [0.6; 5.9], P = 0.25). In multivariable analysis, Kawasaki disease (HR: 11.84 [2.7–52.6], P = 0.001) and global TTR under 80% (HR: 5.05 [1.2–20.7], P = 0.025) were main risk factors for thrombotic events. Overall, VKA use appears to be safe and effective in children with CAHD. Patients with Kawasaki disease and those with a TTR under 80% are at highest risk of thrombosis. A TTR under 70% and minor recurrent bleeding events are the main risk factors for major bleeding events.

Assessment of curbside anticoagulation pharmacy visits on clinical outcomes and patient satisfaction

AbstractIntroductionDuring the coronavirus disease 2019 (COVID‐19) pandemic, curbside international normalized ratio (INR) checks were implemented to monitor patients on warfarin therapy. Because of the lack of available data, clinical outcomes and patient satisfaction were assessed to determine if the implementation of curbside visits could be considered as an alternative to the standard of care.ObjectivesThe objectives were to assess clinical outcomes, safety, and patient satisfaction in a patient cohort whose anticoagulation was managed inside the clinic in 2019 compared with the same patients managed in the curbside setting in 2020.MethodsIn this retrospective study, INR time in therapeutic range (TTR) was used as a marker for clinical appropriateness of anticoagulation therapy. Data were also prospectively collected in the form of patient satisfaction surveys. Adverse events and hospitalizations were assessed to ensure patient safety was not omitted.ResultsThe median TTR in 2019 was significantly higher than in 2020, 95.7% (interquartile range [IQR] 33.3%) vs 84.3% (IQR 45.2%) (z = −3.99, P &lt; .001). Clinically, the mean TTR remained higher in 2019 than in 2020 (81.3% vs 74.7%). Less patients experienced bleeding events in 2020, and there was an average of 1 less visit per patient in 2020 compared with 2019. Surveys indicated that more patients would like their visits to occur inside the clinic if there were no concerns for a pandemic.ConclusionAnticoagulation management assessed by TTR was significantly lower in the 2020 time frame compared with 2019; however, the average TTR in both time frames was above the clinically accepted threshold of adequate anticoagulation control. Patients demonstrated favor toward in‐person visits unless there were concerns for a pandemic. If needed, curbside visits could be considered in the future at this site; however, more studies would need to be done to assess the impact of curbside visits at other institutions.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with hypertrophic cardiomyopathy with non-valvular atrial fibrillation.

Hypertrophic cardiomyopathy (HCM) patients with nonvalvular atrial fibrillation (AF) have an increased risk of suffering thromboembolic events. Vitamin K antagonists (VKA) are recommended as therapy but there is still limited data regarding the efficacy of prescribing non-vitamin K antagonist oral anticoagulants (NOACs). This retrospective study investigates the effectiveness and safety of NOAC administration in patients with HCM and AF. A total of 124 patients with HCM and AF on an oral anticoagulant therapy were recruited between January 2015 and December 2019; these patients were followed up until March 31, 2020. Kaplan-Meier analysis was used to compare the clinical outcomes in patients treated with NOACs versus warfarin. The Cox model was used to estimate the risk of clinically relevant bleeding. Our study included 124 patients, of which 48 (38.7%) received warfarin and 76 (61.3%) received NOACs. Survival analysis showed the patients undergoing NOACs had a lower risk of clinically relevant bleeding (log-rank P = 0.039) over a period of 53.6months. The median time in therapeutic range (TTR) score was 50% (interquartile range: 40.43 to 57.08%). A total of nine patients (18.75%) had a good TTR with a median score of 66.35% (interquartile range: 64.58 to 77.75%). The incidence of death by all causes, cardiovascular death and thromboembolism were similar between NOAC and warfarin-treated patients (log-rank P = 0.239, log-rank P = 0.386, and log-rank P = 0.257, respectively). Patients treated with NOACs showed a significant reduction in the risk of clinical (P = 0.011) and gastrointestinal bleeding (P = 0.032). Cox multiple regression analysis showed age (HR 1.13, 95% CI 1.03-1.24; P = 0.013) and warfarin therapy (HR 7.37, 95% CI 1.63-33.36; P = 0.010) were independent predictors of clinically relevant bleeding. Compared to warfarin, NOACs were associated with a lower incidence of clinically relevant bleeding in HCM patients with AF, as demonstrated by the similar incidence of death by all causes, cardiovascular death and thromboembolic events.

Étude comparative en soins primaires du taux d'INR dans la cible thérapeutique chez des patients traités par warfarine ou fluindione pour une fibrillation atriale. L’étude FLOWER (FLuindione Or WarfarinE – Result INR)

IntroductionThe aim of our study was to compare the time spent within the target INR or Time in Therapeutic Range (TTR) of patients treated with fluindione to that of patients treated with warfarin for non-valvular atrial fibrillation (NVAF) and followed in general practice, with the hypothesis of a better TTR with warfarin, which is the VKA most commonly prescribed in France. MethodLiberal nurses and general practitioners working in the Auvergne region recruited patients treated with fluindione or warfarin for NVAF. Patients' INRs (International Normalized Ratios) were recorded by medical analysis laboratories for 6 months. The primary endpoint was TTR, the secondary endpoint the number of hemorrhagic and/or thromboembolic events. ResultsOf the 342 participants with a mean age of 75.3 ± 9.8 years, 239 (70%) were treated with fluindione and 103 (30%) with warfarin. The mean number of INRs achieved per patient was 9.2 ± 4.0 in the fluindione group and 9.3 ± 4.0 in the warfarin group (p=0.73). The median TTR of fluindione was 81.9% [63.5; 94.1] and that of warfarin was 81.3% [65.6; 92.6] (p=0.98). Twenty-eight of 263 patients reported hemorrhage (10.6%) and 4 reported thromboembolic events (0.8%), with no significant difference between the groups. ConclusionThe TTRs of patients treated for NVAF with fluindione versus warfarin do not differ significantly over an observation period of 6 consecutive months in a patient population comparable to that of the publications in this field. However, these TTRs are significantly higher than those reported in the literature, with no difference between the two treatments.The TTRs of patients treated for VANF with fluindione versus warfarin do not differ significantly over a 6-month observation period in a patient population comparable to that of the publications in this indication.

Tacrolimus time in therapeutic range and long-term outcomes in heart transplant recipients.

Little is known about the association between tacrolimus time in therapeutic range (TTR) within the guideline-recommended targets and heart transplant (HT) patient outcomes. This study evaluated the association of early tacrolimus TTR with rejection and other clinical outcomes during an extended follow-up after HT. This was a single-center retrospective cohort study. The study was conducted at Michigan Medicine (1/1/2006-12/31/2017). HT recipients ≥18years of age were included. The primary end point was the effect of tacrolimus TTR on time to rejection over the entire follow-up period. A total of 137 patients were included with a median follow-up of 53months. Based on the median TTR of 58%, the patients were divided into the low tacrolimus TTR (n=68) and high tacrolimus TTR (n=69) cohort. The high tacrolimus TTR was associated with a significantly lower risk of rejection compared to the low tacrolimus TTR cohort (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.41-0.98; p=0.04). A post hoc analysis revealed associations between rejection and TTR when high and low TTR groups were created at different levels. TTR <30% was associated with a 7-fold higher risk of rejection (HR 7.56; 95% CI 1.76-37.6; p<0.01) and TTR >75% was associated with a 77% lower risk of rejection (HR 0.23; 95% CI 0.08-0.627; p<0.01). Patients in the higher tacrolimus TTR cohort had a lower risk of rejection. We observed correlations between higher risk of rejection with TTR <30% and lower risk of rejection with TTR >75%. Future studies should focus on validating the optimal TTR cutoff while also exploring a cutoff to delineate high-risk patients for which early interventions to improve tacrolimus TTR may be beneficial.

Abstract 13686: Variation in Time in Therapeutic Range for Cooling for Out-of-Hospital Cardiac Arrest

Introduction: For comatose survivors of out-of-hospital cardiac arrest (OHCA), targeted temperature management (TTM) is strongly recommended with a goal temperature of 32-36C for a period of at least 24 hours. However, adherence to this target in clinical practice remains unknown. We developed time-in-therapeutic range (TTR) as a treatment metric for patients receiving TTM and evaluated patient- and site-level variation in TTR. Methods: We used data from the Resuscitation Outcomes Consortium-CCC trial which included patients with OHCA across 10 North American sites during 2011-2015. We identified patients who underwent TTM for &gt;12 hours. Serial temperature measures were evaluated between hypothermia start and end times with temperatures between consecutive measures imputed using a linear interpolation method. TTR was defined as percent of time between 32C and 36C during TTM (Fig A). Site was defined based on trial clusters, which represented hospitals served by the same EMS agency. Site-level variation in TTR&lt;90% was evaluated in hierarchical logistic regression using median odds ratio (OR), after adjustment for patient-level factors. Results: A total of 2,695 patients across 49 clusters were included with a median of 45 (IQR: 34 - 52) patients per cluster. The median duration of hypothermia was 23 (IQR: 21 - 24) hours with a median time outside therapeutic range of 0.9 (IQR: 0.0 - 4.2) hours. The median TTR was 96.1% but 1,654 (61%) patients had at least one temperature outside the therapeutic range and 991 (37%) patients had a TTR &lt;90%. There was large variation across sites in the proportion of patients with TTR&lt;90%, ranging from 10% to 68%, with a median OR of 1.74 (Fig B). Conclusions: Within a large randomized controlled trial, more than 1 in 3 OHCA patients treated with TTM had a TTR &lt;90%, with large variation in TTR across sites. These findings highlight an urgent need to focus on improving quality of TTM in clinical practice.

International normalised ratio control in a non-metropolitan setting in Western Cape Province, South Africa.

The quality of international normalised ratio (INR) control determines the effectiveness and safety of warfarin therapy. Data on INR control in non-metropolitan settings of South Africa (SA) are sparse. To examine the time in therapeutic range (TTR) and its potential predictors in a sample of Garden Route District Municipality primary healthcare clinics (PHCs). INR records from eight PHCs were reviewed. The TTR and percentage of patients with a TTR &gt;65% were determined. A host of variables were analysed for association with TTR. The median (interquartile range (IQR)) age of the cohort (N=191) was 56 (44 - 69) years. The median (IQR) TTR was 37.2% (20.2- 58.8); only 17.8% of patients had a TTR ≥65%. Compared with patients aged &gt;50 years, those aged &lt;50 had worse INR control (median (IQR) TTR 26.6% (16.1 - 53.0) v. 43.5% (23.5 - 60.1); p=0.01). Patients hospitalised for any reason during the study period had worse INR control than patients not hospitalised (median (IQR) TTR 26.2% (16.2 - 50.2) v. 42.9% (23.5 - 62.0); p=0.02). On multivariable regression analysis, participants on warfarin for atrial fibrillation/flutter had better INR control than those with other indications for warfarin (odds ratio 2.21; 95% confidence interval 1.02 - 4.77; p=0.04), but the control was still very poor. INR control, as determined by TTR and proportion of TTR ≥65%, in these non-metropolitan clinics was poor. Age and hospitalisation as a marker of illness predicted poor control. There was a difference in control between groups, depending on the indication for warfarin. Evidence-based measures to improve the quality of INR control in patients on warfarin therapy need to be instituted as a matter of urgency.