Time In Therapeutic INR Range Research Articles

Warfarin Time in Therapeutic INR Range and Direct Oral Anticoagulant Adherence for Venous Thromboembolism Across the Spectrum of Weight and Body Mass Index: Findings from Veterans Health Administration.

The evidence of direct oral anticoagulants (DOACs) usage for venous thromboembolism (VTE) in patients at extremes of body weight or mass index is limited. In such situations, warfarin may be more frequently used. We investigated warfarin time in the therapeutic international normalized ratio range (TTR) and DOAC adherence based on the calculated proportion of days covered (PDC) by pill coverage from a DOAC prescription in patients with VTE across all body sizes. Using data from the Veterans Health Administration (VA), we identified first-time patients with VTE between 2013 and 2018 treated with warfarin or DOACs. We analyzed 28,245 patients with warfarin TTR (N = 10,167) or DOAC PDC(N = 18,078). For warfarin-treated patients after index VTE, mean TTR was lower over shorter treatment durations (TTR 30 vs TTR 180 [mean ± SD]: 43.8% ± 33.5% vs 58.8% ± 23.5%). Mean TTR over 180 days after VTE was lowest for patients <60 kg (TTR 180 [mean ± SD]: <60kg: 49.3% ± 24.2% vs ≥60 to <100 kg: 57.8% ± 23.4%; P < .0001). For DOAC-treated patients over 180 days after index VTE, mean PDC was lowest for patients <60 kg (PDC 180 [mean ± SD]: < 60kg: 76.9% ± 33.2% vs ≥ 60 to <100 kg: 83.6% ± 27.7%; P < .0001).Most DOAC-treated patients attained sufficient adherence across the body size spectrum while warfarin-treated patients <60kg were at risk for low TTR.

Impact of an electronic medium delivery of warfarin education in a low income, minority outpatient population: a pilot intervention study

BackgroundWarfarin is classified as a high-alert medication for ambulatory healthcare and safe guards for high-alert medications are necessary, including the practice of mandatory patient education. The high cost of hospitalizations related to adverse events combined with the average bleeding event rate of 7–8% in spite of routine patient education, suggests the importance of new approaches to standardized health education on warfarin. We sought to evaluate the impact of a warfarin educational video using an electronic tablet on patient knowledge and to determine patients’ satisfaction with the use of an electronic tablet for educational purposes in outpatient clinics serving a low income, minority population.MethodsA warfarin educational video delivered on an electronic tablet (iPad) was delivered at two pharmacist-managed anticoagulation clinics to uninsured patients whose annual income is equal or less than two hundred percent below the poverty level were offered. Patients (n = 18) completed a pre-video and post-video knowledge test on warfarin before and after viewing the warfarin educational video on an electronic tablet and a follow-up test to measure the retention of knowledge and a patient satisfaction survey at 60 days. The primary outcome was change in knowledge test scores. Other outcome measures included adherence rates, adverse events, time in therapeutic INR range, and patient-reported satisfaction scores.ResultsThe majority of patients were uninsured men taking warfarin for atrial fibrillation (n = 5). The median scores at post-video knowledge test and follow-up knowledge test were significantly higher than that for the pre-knowledge test (12 (11–12) vs. 10(8–11), p < 0.001). The study group had a ‘time in therapeutic INR’ range of 56.3%, a rate of adverse events of 24.5%, and a self-reported adherence rate to warfarin of 94.1%. The majority of patients also had positive responses to the patient satisfaction survey.ConclusionsPatient education delivered via iPad to facilitate knowledge of medication can serve as a useful tool for educating patients about warfarin and warfarin therapy. Use of an electronic medium may be a unique way to provide standard medication education to patients.Trial registrationThe study was retrospectively registered with: NCT03650777; 9/18/18.

Novel Oral Anticoagulants in Patients with Continuous Flow Left Ventricular Assist Devices

Purpose The gold standard for anticoagulation in patients with continuous flow left ventricular assist device (CF-LVADs) is warfarin. However, many patients fail warfarin therapy due to thromboembolic and bleeding events. Warfarin requires regular monitoring and dosage adjustments, and is associated with significant patient time outside recommended therapeutic INR range. Novel oral anticoagulation (NOAC) has been shown to be non-inferior compared to warfarin in stroke prevention with less intracranial hemorrhage in patients with atrial fibrillation. In this study, we sought to evaluate the safety and efficacy of NOACs in patients with CF-LVADs after failed warfarin therapy. Methods Patients who underwent CF-LVAD insertion between 2008 and 2018 were identified in a single-center database. 7 patients with either HeartMate II or HeartWare were switched from warfarin to a NOAC, either apixaban or rivaroxaban, were included. Occurrence of stroke, non-CNS embolism, pump thrombosis, and major GI bleeding or intracranial hemorrhage on warfarin and NOAC were evaluated. Results 5 of 7 patients were male, with an average BMI of 30. Common comorbidities were hypertension (100%), diabetes mellitus (57%) and ischemic cardiomyopathy (57%). There were a total of 3968 patient days on warfarin and 1459 patient days on a NOAC. Patients on warfarin therapy spent an average time of 30% within a therapeutic INR range. The rates of complications under warfarin versus NOAC therapy were: strokes 0.019 vs. 0 /patient-year, non-CNS embolism 0.019 vs. 0 /patient-year, pump thrombosis 0.01 vs. 0 /patient-year, major GI bleeding 0.02 vs. 0.07 /patient-year, and intracranial hemorrhage 0.019 vs. 0 /patient-year.(Table 1). Conclusion Increased complication rates and poor time in therapeutic INR range were present in patients receiving warfarin therapy after CF-LVAD insertion. NOAC therapy with apixaban or rivaroxaban may be a viable alternative. However, large prospective studies are necessary to confirm these results.

Association between insurance status, anticoagulation quality, and clinical outcomes in patients with acute venous thromboembolism

IntroductionA higher level of health insurance coverage may be related to better quality of care and outcomes. Whether insurance status is associated with anticoagulation quality and clinical outcomes in patients with venous thromboembolism (VTE) is unknown. MethodsWe studied 819 elderly patients treated with vitamin K antagonists for VTE in a Swiss prospective multicenter cohort (09/2009–12/2013). The study outcomes were the anticoagulation quality, defined as the time spent in the therapeutic INR range, and clinical events, i.e. the time to a first VTE recurrence, major bleeding, and mortality. We assessed the association between insurance status (private vs. general), anticoagulation quality, and clinical outcomes using regression models, adjusting for potential confounders. ResultsAlthough the unadjusted mean percentage of time spent in the therapeutic INR range (2.0–3.0) was slightly higher in patients with private vs. general insurance (65% vs. 61%; p = 0.030), the adjusted difference was not statistically significant (1.53%, 95% CI −1.97 to 5.04). Patients with private insurance had a lower 36-month cumulative incidence of major bleeding (9.7% vs. 15.7%; p = 0.018). After adjustment, privately insured patients had a lower risk of major bleeding compared to patients with general insurance (sub-hazard ratio 0.57, 95% CI 0.32 to 0.98). Insurance status was not associated with recurrent VTE or mortality. ConclusionPrivately insured patients spent somewhat more time in therapeutic INR range and had a lower rate of major bleeding than generally insured patients. Basic (general) health insurance may be a marker of lower anticoagulation quality and higher risk of major bleeding.

Characteristics and quality of oral anticoagulation treatment in pediatric patients in the Netherlands based on the CAPS cohort

Background The use of vitamin-K antagonists in pediatric patients is rare and information on the quality and safety of treatment with acenocoumarol and phenprocoumon is limited. Objectives To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. Methods The Children Anticoagulation and Pharmacogenetics Study (CAPS) was designed as a multicenter retrospective follow-up study. Patients who used acenocoumarol or phenprocoumon at an age of ≤ 18 years, were selected from four pediatric hospitals and one anticoagulation clinic in the Netherlands. The quality of treatment was assessed by calculating the percentage of time in therapeutic INR range (TTR) for the first month and for every 3 months of use during the first year of treatment. Effectiveness and safety were assessed by the number of thromboembolic and bleeding events. Results In total, 213 patients participated, of whom 187 (155 acenocoumarol; 32 phenprocoumon) were included in this analysis. The mean TTR was 47.0% and 51.4% in the first month of use for acenocoumarol and phenprocoumon, respectively. After the first 3 months the mean TTR for both VKAs was above 64%. In 14.6% (acenocoumarol) and 31.3% (phenprocoumon) of the patients a bleeding event occurred during the first year of treatment; no thromboembolic events were reported. Conclusions The quality of anticoagulation treatment was low during the first month of use and leaves room for improvement. After the first month it increased to an acceptable level. However, bleeding events occurred frequently during the first year.

Abstract 259: Two Readily Obtainable Measures of Patient-reported Adherence and Their Association With Anticoagulation Control

Introduction: Despite the emergence of new effective anticoagulation therapies, the prevention of thromboembolic events remains challenging in cases of poor medication adherence. Unfortunately, clinical prediction of future adherence has been suboptimal and electronic adherence measures are impractical. The inability of clinicians to easily and accurately identify poorly adherent patients has been an obstacle to the delivery of quality care. We examined two measures of real-time, self-reported adherence among warfarin treated patients to determine if these could be used to explain level of anticoagulation control. Methods: The IN-RANGE2 Cohort recruited patients initiating warfarin therapy in 3 urban anticoagulation clinics. At each study visit, participants reported adherence using a 100-point Visual Analogue Scale (VAS, marking % of pills taken since prior visit on a linear scale) and 7-day recall of pill taking behavior before their current INR was revealed. Anticoagulation control was measured by between visit time in therapeutic INR range (BVTR), dichotomized at the cohort median. The longitudinal association between these adherence measurements and anticoagulation control was estimated using generalized estimating equations, controlling for clinical and demographic characteristics, prior BVTR, and warfarin dose changes. Results: A total of 598 participants with 3204 (median 4) visits were studied. The median BVTR was 36.8% (interquartile range 0-73.9%). Mean VAS score was 96.6% (standard deviation 5.8), with participants reporting less than or equal to 80% adherence in 182 (5.7%) visits; missed pills in the past 7 days were reported in 308 (11.8%) visits. Multivariate regression analysis found poorer anticoagulation control (BVTR&lt;36.8%) in those with a VAS score less than or equal to 80% (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.12-3.18, p=0.02) and self-report of a change in adherence since last visit using 7-day recall (OR 1.55, 95% CI 1.20-2.01, p=0.001). Conclusion: Self-reported VAS medication adherence at a clinic visit and changes in reported adherence since the last visit are independently associated with BVTR. Incorporating information from both the VAS and changes in 7-day pill recall into clinical practice could improve the quality of anticoagulation management, by helping clinicians identify poorly adherent patients who might benefit from specialized interventions. Because the association is independent of knowing the prior BVTR, these findings may be translatable to direct oral anticoagulant, medications that are not easily monitored with laboratory testing.

Clinical impact of a pharmacist-led inpatient anticoagulation service: a review of the literature.

BackgroundAnticoagulant therapies provide management options for potentially life-threatening thromboembolic conditions. They also carry significant safety risks, requiring careful consideration of medication dose, close monitoring, and follow-up. Inpatients are particularly at risk, considering the widespread use of anticoagulants in hospitals. This has prompted the introduction of safety goals for anticoagulants in Canada and the USA, which recommend increased pharmacist involvement to reduce patient harm. The goal of this review is to evaluate the efficacy and safety of pharmacist-led inpatient anticoagulation services compared to usual or physician-managed care.MethodsThis narrative review includes articles identified through a literature search of PubMed, Embase, and International Pharmaceutical s databases, as well as hand searches of the references of relevant articles. Full publications of pharmacist-managed inpatient anticoagulation services were eligible if they were published in English and assessed clinical outcomes.ResultsTwenty-six studies were included and further divided into two categories: 1) autonomous pharmacist-managed anticoagulation programs (PMAPs) and 2) pharmacist recommendation. Pharmacist management of heparin and warfarin appears to result in improvements in some surrogate outcomes (international normalized ratio [INR] stability and time in INR goal range), while results for others are mixed (time to therapeutic INR, length of stay, and activated partial thromboplastin time [aPTT] measures). There is also some indication that PMAPs may be associated with reduced patient mortality. When direct thrombin inhibitors are managed by pharmacists, there seems to be a shorter time to therapeutic aPTT and a greater percentage of time in the therapeutic range, as well as a decrease in the frequency of medication errors. Pharmacist recommendation services have generally resulted in a greater time in therapeutic INR range, greater INR stability, decreased length of stay, and reduced major drug interactions, with no significant differences in safety outcomes.ConclusionPharmacist-led inpatient anticoagulation management seems to result in superior outcomes, as compared to usual or physician-managed care. This conclusion is limited by small, poorly designed studies lacking statistical power, focusing mainly on surrogate outcomes.

Ezetimibe enhances and stabilizes anticoagulant effect of warfarin.

Ezetimibe reduces plasma levels of low-density lipoprotein cholesterol by inhibiting Niemann-Pick C1-like protein 1 (NPC1L1). A recent study demonstrated that NPC1L1 plays an important role in absorption of fat-soluble vitamins including vitamin K. We evaluated whether the add-on treatment of ezetimibe affects anticoagulation in patients taking warfarin. Between October 2007 and March 2015, the administration of ezetimibe was started to a total of 101 outpatients who were already on oral anticoagulation with warfarin. We retrospectively analyzed blood lipid levels, prothrombin time international normalized ratio (PT-INR) and time in therapeutic INR range (TTR). Seventy-one patients (70%) showed increase in PT-INR after ezetimibe treatment (1.96±0.45 to 2.20±0.61, p<0.001). It was necessary to reduce the warfarin dose in 9 of 101 patients for clinical indication. There was a significant positive correlation between change in PT-INR and statin usage at baseline (p=0.03). The mean value of changes in PT-INR of patients with taking statin was significantly larger than that of patients without taking statin (0.34±0.54 vs. 0.06±0.36, p=0.03). There was an increase in the TTR (52±26 to 61±23%, p<0.0001) and a decrease in the frequency to change the dose of warfarin after the ezetimibe treatment [45 times of 735 examination days (6%) to 20 times of 695 examination days (3%), p=0.02]. Our data suggest possible drug interaction between warfarin and ezetimibe. Ezetimibe may increase and stabilize the anticoagulant effect of warfarin, especially in patients taking statins.

Adequate time in therapeutic INR range using triple antithrombotic therapy is not associated with long-term cardiovascular events and major bleeding complications after drug-eluting stent implantation

BackgroundTriple 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. MethodsWe 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. ResultsTriple 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. ConclusionsTriple antithrombotic therapy does not increase the occurrence of MACCE and major bleeding complications, if the warfarin dose is tightly controlled with a lower INR.

EVALUATION OF ATRIAL FIBRILLATION STROKE PREVENTION THERAPIES IN THE ERA OF NOACS AND EVOLVING ANTICOAGULATION GUIDELINES IN CANADA

EVALUATION OF ATRIAL FIBRILLATION STROKE PREVENTION THERAPIES IN THE ERA OF NOACS AND EVOLVING ANTICOAGULATION GUIDELINES IN CANADA

Abstract 19565: SAMeTT2R2 Scores Predict Stroke Risk After Initiation of Vitamin K Antagonist Therapy for Atrial Fibrillation: a Real-world Practice Study

Introduction: Quality and duration of anticoagulation reflected by high proportion of Time in Therapeutic INR range (TTR) is associated with reduced thrombo-embolic and bleeding events in atrial fibrillation (AF). SAMeTT2R2, a novel score incorporating age, sex, ethnicity, smoking, co-morbidities, and interacting drugs, predicts inadequate anticoagulation control (TTR &lt;0.6) after commencing Vitamin K Antagonist (VKA) for AF, with scores ≥2 suggested as a cut-off to predict inadequate control. Aims: To determine whether SAMeTT2R2 score ≥2 at VKA inception is associated with an increased stroke risk in real-world practice. Methods: A cohort of VKA-naïve patients with incident non-valvular AF between 2001 - 2010 was formed from a large UK primary care database (Clinical Practice Research Datalink, CPRD) with linkage to hospital discharges, and death registry. SAMeTT2R2 score was calculated in a subset of 4468 in whom VKA treatment was initiated within 90 days of AF diagnosis, and scores 0-1, ≥2 were related to 3-year stroke incidence. Competing risk analysis accounting for death was performed to compare the risk of stroke between the two groups in an intention-to-treat analysis. Results: Of 4468 patients with incident AF commenced on VKA (mean age 70.7, 41.2% female), 3422 (76.6%) had a SAMeTT2R2 score of 0-1, and 1046 (23.4%) a score of ≥2. During 3-years 138 patients had a stroke and 58 of these occurred in the year following AF. Cumulative risk estimates for stroke in patients with scores ≥2 compared to 0-1 were significantly increased at 1, 2 and 3 years (log rank test, p&lt;0.01)(Figure). The proportion with TTR≥0.6 was 37.1% for scores ≥2 compared to 44.1% for scores 0-1 (p&lt;0.01). Conclusions: SAMeTT2R2 scores ≥2 predict increased stroke risk in the 3 years following incident AF in patients commenced on VKA treatment. These findings suggest that patients with high SAMeTT2R2 scores may require intensified anticoagulation control or use of oral non-VKA anticoagulants.

Vitamin E Serum Levels and Bleeding Risk in Patients Receiving Oral Anticoagulant Therapy: a Retrospective Cohort Study

BackgroundHemorrhagic risk assessment is a crucial issue in patients with nonvalvular atrial fibrillation (NVAF) who are receiving oral anticoagulant therapy (OAT). Our aim was to analyze the relationship between vitamin E, which possesses anticoagulant properties, and bleeding events in NVAF patients.Methods and ResultsIn this retrospective observational study we analyzed baseline serum cholesterol‐adjusted vitamin E (vit E/chol) levels in 566 consecutive patients (59% males, mean age 73.6 years) receiving OAT followed up for a mean time of 22 months. Mean time in therapeutic INR range (TTR) was 64%. The overall incidence rate of any bleeding event was 9.2/100 person‐years. Compared to patients who did not bleed, those who experienced bleeding events (n=92, 73 minor and 15 major bleedings and 4 cerebral hemorrhages according to International Society on Thrombosis and Haemostasis [ISTH] ) classification) showed a significant difference for history of coronary heart disease (P=0.039), HAS‐BLED score (P=0.002), and vit E/chol levels (P<0.001). Higher vit E/chol serum levels were found in patients who bled compared to those who did not (5.27±1.93 versus 4.48±1.97 μmol/cholesterol; P<0.001), with a progressive increase from minor (5.16±1.91 μmol/mmol cholesterol, P=0.006) to major bleedings (5.72±2.0 μmol/mmol cholesterol, P=0.008). A Cox proportional hazard model demonstrated that serum vit E/chol quartiles (global P=0.0189) and HAS‐BLED scores (P=0.005) predicted bleeding events.ConclusionsIn a NVAF population being treated with warfarin, serum vitamin E predicted hemorrhagic events. Further study is necessary to see if the relationship between serum levels of vitamin E and bleeding is still maintained with the use of new anticoagulants.Clinical Trial RegistrationURL: ClinicalTrials.gov. Unique identifier NCT01882114.

Abstract P205: Anticoagulation Volume Does Not Predict Facility Performance of Time in Therapeutic INR Range of Patients With Atrial Fibrillation: A National VA Study

Introduction: Effectiveness of warfarin for stroke prevention in atrial fibrillation (AF) is proportional to the time in INR therapeutic range of 2.0-3.0. Time in therapeutic range (TTR) ≥ 58% is a validated threshold at which warfarin has benefit over aspirin, while TTR &lt; 40% may cause net harm due to hemorrhage. Variation of TTR across facilities may be due to systematic or facility-based factors, including patient volume. We evaluated the relationship of anticoagulation facility patient volume and TTR. Methods: We performed a national cohort study of Veterans Health Administration data using centralized medical and administrative records. We identified 48,192 patients with at least two outpatient ICD-9 diagnoses of AF who were prescribed warfarin from 94 VA anticoagulation facilities in FY 2003-04. The primary outcome was facility TTR, which was mean TTR calculated for FY04 from all patient-level TTRs of that facility. Patient-level TTR was calculated using the modified Rosendaal method, using linear imputation of INR values up to a maximum of 56 days. Results: Excluding two outliers with TTR &lt; 1%, the mean TTR across 92 facilities was 54.6% ± 6.1% (95% CI 43.7%-63.0%). Only 30 of 92 facilities (33%) had a mean TTR ≥ 58%, and 2 (2.2%) had a mean TTR &lt; 40%. Facility volume, as measured by the number of identified patients per facility, was not related to TTR (R-squared 2.6%) although facility INR test frequency was related to TTR (R-squared 29%). After multivariate adjustment for facility volume and facility prevalence of diabetes, heart failure, hypertension, coronary disease, stroke/TIA, and mean patient age, INR test frequency was significantly associated with TTR ≥ 58% (p &lt; 0.001), while facility volume remained insignificant (p=0.55). For every three additional INR tests per month, the adjusted odds of achieving TTR ≥ 58% increased 5.33 (p &lt; 0.001). Conclusions: We found systematic variation of facility TTR in a national health care system. Facility volume did not predict quality of anticoagulation. However, the facility's mean INR frequency is strongly associated with its overall quality of anticoagulation of patients with AF. Standardization and improvement of warfarin management across facilities may improve quality and prevent adverse outcomes.

Quality of Oral Anticoagulation Management in Pharmacist Vs Nurse Managed Models of Care

Systematic models of anticoagulation management result in better clinical outcomes than routine medical care. At the University of Illinois at Chicago Medical Center (UIMCC) systematic anticoagulation management is provided via 2 models of care: a pharmacist managed antithrombosis clinic (PMATC) and a nurse managed anticoagulation clinic (NMAC). The objective of this study was to evaluate the quality of oral anticoagulation management in these two models of care by assessing efficacy, safety, monitoring and resource utilization outcomes. A retrospective, observational cohort study was conducted between January 2005 and April 2007. A total of 200 patients, 100 in each group, were randomly selected and contributed 179.3 and 206.8 patient-years of therapy for the PMATC and NMAC respectively (p<0.0001). Venous thromboembolism and atrial fibrillation were the 2 most common indications for anticoagulation therapy, although the PMATC group managed a higher proportion of patients with shorter-term venous indications then the NMAC group (78% vs 4% respectively; p<0.0001). The PMATC group reached goal INR faster after initiating therapy then the NMAC group. (median of 9 days vs 22 days respectively; p=0.0003). The mean % of patients with INR controlled within the therapeutic range (TTR) was 65.8% in the PMATC group and 71.2% in the NMAC group (p=0.009). The PMATC group had a higher proportion of difficult to manage patients who were non-compliant with their clinic monitoring appointments and non-compliant with their warfarin therapy as compared to the NMAC group. (median number of missed appointments per year was 4.8 vs 1.0 respectively; p < 0.0001 and median number of deviations from prescribed warfarin dose was 16.6 vs 3.5 respectively; p < 0.0001). The percent of patients who developed thromboembolic events and major bleeding complications during therapy were similar in the PMATC and NMAC groups (1.2% vs 0.5% per patient-year of therapy, respectively; RR 2.40; 95% CI 0.096 to 4.26; and 4.7% vs. 4.9% per patient-year of therapy, respectively; RR 0.96; 95% CI, 0.28 to 3.30). Hospital admissions and emergency department visits due to non-therapeutic INRs were higher in the NMAC group compared to the PMATC group (9.2% vs 0.6% per patient-year of therapy, respectively; RR 0.06; 95% CI 0.004 to 0.79; and 1.5% vs 0 per patient-year of therapy, respectively.) Patients who spent > 60% of the time in therapeutic INR range had a lower median number of missed clinic monitoring appointments and a lower median number of deviations from the prescribed warfarin dose as compared to patients who spent < 60% of the time in the therapeutic INR range (1.8 vs 4.0, respectively; p=0.0002 and 9.1 vs. 12.8, respectively; p=0.02). In this study, the PMATC model showed better outcomes in attaining a faster therapeutic INR after initiating warfarin therapy and also demonstrated more judicious resource utilization by lower hospitalization rates and emergency room visits due to non-therapeutic INRs. Although the TTR was lower in the PMATC group, the 2 groups faired similarly with regards to clinical outcomes such as recurrent thromboembolism and major bleeding complications. The difference in TTR can be attributed to the higher proportion of more difficult to manage, non-compliant patients in the PMATC group. Both models of care were found to be well within acceptable limits of national benchmark quality data for systematic anticoagulation management, although the PMATC model had better resource utilization outcomes.

Abstract 3589: Warfarin Therapy, Anticoagulation Intensity and Outcomes in Older vs. Younger Patients with Atrial Fibrillation: The ATRIA Study

Background. Warfarin is highly efficacious for stroke prevention in atrial fibrillation (AF) in selected randomized trial populations. However, controversy exists about its effectiveness and safety and the target INR range in the old and oldest old AF patients in usual clinical care. Methods. We examined anticoagulation-related outcomes associated with older vs. younger age among 13,559 patients with AF within Kaiser Permanente of Northern California between July 1996 and September 2003. Longitudinal warfarin use was characterized using a validated algorithm from filled prescriptions and INR tests found in pharmacy and lab databases. Anticoagulation intensity was characterized using linear interpolation from outpatient INR tests. Risk factors for stroke and bleeding were obtained from clinical and administrative databases. Thromboembolic (TE) and intracranial hemorrhage (ICH) events were identified from hospitalization databases and confirmed by chart review. Results. During 66,754 person-years of follow-up, a large fraction was contributed by older patients: &lt;60 (12.3%), 60 – 69 (18.5%), 70 –79 (37.8%), 80+ (31.4%) years. Older patients were more likely to be women and have a higher prevalence of stroke and bleeding risk factors. Among warfarin users, the proportion of time in therapeutic INR range was similar across age groups (64 – 66%, P=NS). We validated 1041 TE and 279 ICH events. Absolute event rates were higher with older age, but the relative effectiveness of warfarin for preventing TE increased and relative harm due to ICH decreased between ages 60 – 69 and 80+ years (Table ). In separate multivariable analyses, INR 2.0 –3.0 provided the optimal risk-benefit ratio for TE and ICH events across each age category. Conclusion. Among persons with nonvalvular AF, the net clinical benefit of warfarin was greater at older ages. INR 2.0 –3.0 is the optimal target anticoagulation range across the spectrum of age to maximize TE prevention at an acceptable risk of ICH.

Health literacy and anticoagulation-related outcomes among patients taking warfarin

Little is known about whether health literacy affects anticoagulation-related outcomes. To assess how health literacy is associated with warfarin knowledge, adherence, and warfarin control (measured by the international normalized ratio [INR]). Survey. Patients taking warfarin through an anticoagulation clinic. Health literacy was measured using the short-form Test of Functional Health Literacy in Adults (s-TOFHLA), dichotomized as "limited" (score 0 to 22) and "adequate" (score 23 to 36). We asked patients to answer questions relating to their warfarin therapy and used multivariable logistic regression to assess whether health literacy was associated with incorrect answers. We also assessed whether health literacy was associated with nonadherence to warfarin as well as time in therapeutic INR range. Bilingual research assistants administered the survey and s-TOFHLA to 179 anticoagulated English- or Spanish-speaking patients. Limited health literacy was associated with incorrect answers to questions on warfarin's mechanism (adjusted odds ratio [OR] 4.8 [1.3 to 17.6]), side-effects (OR 6.4 [2.3 to 18.0]), medication interactions (OR 2.5 [1.1 to 5.5]), and frequency of monitoring (OR 2.7 [1.1 to 6.7]), after adjusting for age, sex, race/ethnicity, education, cognitive impairment, and years on warfarin. However, limited health literacy was not significantly associated with missing warfarin doses in 3 months (OR 0.9 [0.4 to 2.0]) nor with the proportion of person-time in therapeutic INR range (OR 1.0 [0.7 to 1.4]). Limited health literacy is associated with deficits in warfarin-related knowledge but not with self-reported adherence to warfarin or INR control. Efforts should concentrate on investigating alternative means of educating patients on the management and potential risks of anticoagulation.