International Normalized Ratio Range Research Articles

Anticoagulation therapy: patients attitude, knowledge, and concerns regarding their effects on the international normalized ratio (INR) in Saudi Arabia

Introduction: Thoughtful evaluation of patients’ knowledge, satisfaction, and concerns in Anticoagulation clinics will help to understand areas of improvement. Our study aimed to examine patients’ drug knowledge, satisfaction and concerns with provided anticoagulation services. Patients and Methods: We designed our study as a cross-sectional survey that was developed and conducted in a regional anticoagulation clinic with good number of patients. Two hundred sixty eight were recruited in the survey. Patients’ warfarin refill records and time within the therapeutic INR range were retrieved from hospital databases. Results: Adequate knowledge of warfarin-food and warfarin-drug interactions was lacking in about 50% of patients. Satisfaction with provided service was not optimal, Concerns associated with warfarin was bothersome to many patients due to possible drug-drug interactions (41.42%), missed doses impact (29.10%), adverse drug reactions (29.85%). All of which might lead to unfavorable consequences. Higher satisfaction was associated with better knowledge (r=0.27, p=0.001) and fewer concerns (rs=-0.26, p=0.002). Improved drug related knowledge and higher satisfaction were positively reflected in these patients’ attitude toward drug use compliance in knowledge (rs=0.23, p=0.01) and satisfaction (rs=0.19, p=0.041). Eventually, good INR control was shown more with better knowledge, higher satisfaction, and better warfarin adherence (p=0.004, 0.03, 0.04 and 0.004, respectively). Conclusion: There is a deficit in patients’ knowledge and satisfaction with warfarin therapy. Such deficits lifted the threshold of concerns with warfarin use and negatively affected INR control.

Knowledge and information levels and adherence to oral anticoagulant therapy with warfarin in patients attending primary health care services.

Background Oral anticoagulation therapy with warfarin is widely used around the world and its safety and efficacy are well-established. Nevertheless, anticoagulants are among the drug classes most associated with fatal medication errors in primary health care. Objective To investigate patient knowledge, the level of information provided, and medication adherence in patients treated with warfarin at a primary health care service. Method A cross-sectional study of a prospective cohort of 60 patients on warfarin treatment in the town of Ijuí, Rio Grande do Sul, Brazil. A questionnaire was administered to test patients’ knowledge about their prescriptions and the level of information provided by the health team. The 8-item Morisky Medication Adherence Scale (MMAS-8) and International Normalized Ratio (INR) were used to verify adherence to treatment. Results The results were expressed in absolute and relative values and prevalence ratios were calculated, with respective 95% confidence intervals. It was found that 83.3% of the participants had been given insufficient information by the health team, 50% did not know how to use the medication correctly, 86.7% were not adherent to the treatment according to MMAS-8 and 63.3% were outside of the correct INR range. Conclusion In this study, we observed a need to improve the quality of information provided to users and to develop strategies to improve adherence to treatment, to ensure the safety of patients treated with warfarin in primary health care services.

Oral anticoagulation cost in primary antiphospholipid syndrome: comparison between warfarin and hypothetical rivaroxaban.

: The objective of the study is to perform a cost comparison of 1 year of oral anticoagulation management with warfarin vs. hypothetical rivaroxaban (RRX) in thrombotic primary antiphospholipid syndrome. Longitudinal study on 20 primary antiphospholipid syndrome patients followed-up for 1 year after anticoagulation stabilisation with warfarin: a dedicated software calculated number of clinic visits, time in therapeutic range and warfarin consumption for each patient; for RRX, we considered a visit every 3 months (baseline done in hospital before attending anticoagulant clinic); knowing the cost of both anticoagulants, the laboratory cost and the human cost we calculated and compared the yearly expenditure. Average time in therapeutic international normalized ratio range was 69 ± 11%: warfarin management required a total of 375 of visits compared with the 60 for RRX; the yearly cost of RRX was superior to that of warfarin (12 012 vs. 446.4 euros, P < 0.0001), and in spite of lower laboratory (738 vs. 1853 euros, P < 0.0001) and human costs (774.6 vs. 4841 euros), RRX thromboprophylaxis still yielded a hefty bill (13 525 vs. 7140 euros, P < 0.0001). Switching from warfarin to RRX will be 48% more expensive to our Healthcare Authority; unless ongoing clinical trials demonstrate improved long-term outcomes for RRX over warfarin, we feel that a 69% time in therapeutic range does not warrant a change to RRX at a 48% increased cost.

Predictors of International Normalized Ratio Variability in Patients With Atrial Fibrillation Under Warfarin Therapy.

Variability in the international normalized ratio (INR) of prothrombin time has been suggested to be related to outcome in patients with atrial fibrillation (AF) under warfarin therapy, but its determinants remain unclear.Methods and Results:The study population consisted of 626 AF patients under warfarin therapy in the Shinken Database (n=22,230). INR variability was calculated by Fihn's method. Determinants of high log INR variability (defined as over mean+standard deviation) were determined by logistic regression analyses. Symptomatic heart failure (odds ratio [OR] 3.974, 95% confidence interval [CI] 2.510-6.292), older age (≥75 years old; OR 2.984, 95% CI 1.844-4.826) and severe renal dysfunction (eGFR <30 mL/min/1.73 m2; OR 3.918, 95% CI 1.742-8.813) were identified as independent predictors of high INR variability on multivariate logistic regression analysis. The determinants of INR variability in AF patients under warfarin therapy could assist Japanese clinicians in identifying patients likely to show unstable warfarin control irrespective of the definition of the target INR range.

Association between satisfaction with and adherence to warfarin therapy on the control of international normalized ratio: A hospital-based study in Saudi Arabia

BackgroundHigh satisfaction with, and adherence to, warfarin therapy are linked to better international normalized ratio (INR) control and good therapeutic outcomes. ObjectiveThis study was conducted to identify the association between satisfaction with, and adherence to, warfarin therapy and the control of the INR within the target therapeutic range. MethodsA cross-sectional study was conducted from June 1 to August 31, 2016, at the Anticoagulation Clinic in the Cardiology Center at King Fahad Hospital, Qassim, Saudi Arabia. All adult patients included in the study were 18-years-old or older and were on warfarin therapy for 6 months or more. The data were collected through face-to-face interviews using a structured questionnaire. ResultsA total of 298 patients were included. Of them, 194 patients (65.1%) were males and 152 (51.0%) were classified as satisfied with their warfarin therapy. Secondary educational level and above (P = .001) and being non-Saudi (P = .026) were identified as determinants of a high level of satisfaction. Ninety-five (31.8%) participants were classified as adherent to the therapy, and satisfaction with treatment was the only predictor of adherence (P = .009). One hundred thirty-six patients (45.6%) achieved their target INR range. Satisfaction (P = .038) and adherence (P = .023) were significantly associated with better INR control. ConclusionSubstantial efforts are needed to improve patient satisfaction and adherence to treatment through different strategies in order to achieve the target therapeutic goal for warfarin treatment.

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.

Anticoagulation Control in Patients With Ventricular Assist Devices.

Anticoagulation control has been associated with risk of thromboembolism and hemorrhage. Herein, we explore the relationship between anticoagulation control achieved in left ventricular assist device (LVAD) patients and evaluate the association with risk of thromboembolism and hemorrhage. Patients (19 years old or older) with a continuous flow LVAD placed from 2006 to 2012. Percent time spent in target range (PTTR) for international normalized ratio (INR) was estimated with target range of 2.0-3.0. Proportion of time spent in target range was categorized into PTTR > 60%, PTTR ≥ 50 < 60%, and PTTR < 50%. The relationship between PTTR and thromboembolism and hemorrhage was assessed. One hundred fifteen participants contributed 624.5 months of follow-up time. Only 20% of patients achieved anticoagulation control (PTTR > 60% for INR range of 2-3). After adjusting for chronic kidney disease, history of diabetes, history of atrial fibrillation, and age at implant, compared with patients with PTTR < 50%, the relative risk of thromboembolism in patients with PTTR ≥ 60% (hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.14-0.96; p = 0.042) was significantly lower, but not for patients with a PTTR of ≥ 50 < 60% (HR: 0.21; 95% CI: 0.02-1.82; p = 0.16). The relative risk for hemorrhage was also significantly lower among patients with a PTTR ≥ 60% (HR: 0.45; 95% CI: 0.21-0.98; p = 0.045), but not among those with PTTR of ≥ 50 < 60% (HR: 0.47; 95% CI: 0.14-1.56; p = 0.22). This current study demonstrates that LVAD patients remain in the INR target range an average of 42.9% of the time. To our knowledge, this is the first report with regard to anticoagulation control as assessed by PTTR and its association with thromboembolism, hemorrhage, or death among patients with ventricular assist devices (VADs).

Renal function in patients receiving long-term warfarin therapy: A five-year prospective follow-up

To investigate the prognostic value of renal function and to estimate glomerular filtration rate (GFR) changes during a 5-year follow-up of patients receiving warfarin therapy. 200 patients (124 men, 76 women) mainly from a group at high risk for thromboembolic events (mean CHA2DS2-VASc scores, 3.25±1.89) were examined. The patients' mean age was 62.3±9.4 years; the follow-up period was 5 years. 74% of the patients received warfarin monotherapy (international normalized ratio (INR) 2.0 to 3.0); 36% took vitamin K antagonists in combination with one or two antiplatelet agents. The CKD-EPI formula was used to estimate GFR in all the patients at baseline and throughout the investigation once a year. GFR less than 70.9 ml/min/1.73 m2 was found to be a predictor of fatal and nonfatal thrombotic events. The decreased GFR was unassociated with the development of major and clinically relevant hemorrhagic complications within 5 years of warfarin therapy. The initial decline in renal function (GFR <70.9 ml/min/1.73 m2) was associated only with an increased rate of recurrent minor hemorrhagic complications. During 5-year warfarin therapy, there was a significant decrease in GFR from 97.1±24.85 to 91.9±28.9 ml/min/1.73 m2; at the same time, a rapidly progressive loss of renal function (GFR ≥3 ml/min/1.73 m2/year) was recorded in 25.9% of the patients. Discriminant analysis showed that a baseline left ventricular ejection fraction of <40% was a predictor for the rapidly progressive loss of kidney function. Long-term warfarin therapy achieved the therapeutic range for INR is safe in the environment of the created patronage system. The initial decrease in GFR is a predictor of thrombotic events and is unassociated with an increased risk of bleeding.

IMPACT OF PHARMACIST LED ANTICOAGULATION MONITORING AND PATIENT EDUCATION ON ORAL ANTICOAGULATION THERAPY WITH ACENOCOUMAROL

Objective: Acenocoumarol is anoral anticoagulant with narrow therapeutic index, and the ideal dose of anticoagulation lies between International normalized ratio (INR) values of 2.0 and 3.5. Lack of monitoring and knowledge on acenocoumarol therapy may compromise patient’s safety resulting in under- or over-anticoagulation. A study was conducted to monitor for the safety of anticoagulation therapy, achievement of goal INR levels and to assess the impact of pharmacist led anticoagulation monitoring and patient education on the rational use of acenocoumarol in patients admitted in cardiology wards with thromboembolic disorders.Methods: The study was conducted in 70 patients; data collection was done, prescriptions were analyzed for drug-drug interactions and adverse drug reactions (ADRs). Patients’ knowledge on acenocoumarol therapy was assessed using a self-developed questionnaire at the baseline, then were subjected to a detailed patient education and on an average each patient received three sessions of education. They were again made to answer the same questionnaire on the day of discharge. The mean score of the responses before and after education was compared statistically using Wilcoxon signed rank test and McNemar test.Results: There were 60% patients under anticoagulated with the INR range of &gt;2.0. 123 drug interactions were observed in 58 patients, on an average of 2 interactions per prescription, but no ADRs were observed. 59 patients (84.3%) showed significant overall improvement in knowledge on anticoagulation therapy following education.Conclusion: This study implies the role of clinical pharmacists in achieving better clinical outcomes in patients receiving oral anticoagulation therapy with acenocoumarol.

Assessment of the efficacy of a novel tailored vitamin K dosing regimen in lowering the International Normalised Ratio in over-anticoagulated patients: a randomised clinical trial.

Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24h. One hundred and eighty-one patients with an index INR>6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P=0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P<0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients.

Association Between Patient-Reported Medication Adherence and Anticoagulation Control

BackgroundThe prevention of thromboembolism events remains challenging in cases of poor medication adherence. Unfortunately, clinical prediction of future adherence has been suboptimal. The objective of this study was to examine the correlation between 2 measures of real-time, self-reported adherence and anticoagulation control. MethodsThe 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 percentage of pills taken since prior visit on a linear scale) and 7-day recall of pill-taking behavior. Anticoagulation control was measured by between-visit percent time in international normalized ratio range (BVTR), dichotomized at the cohort median. The longitudinal association between adherence and anticoagulation control was estimated using generalized estimating equations, controlling for clinical and demographic characteristics, prior BVTR, and warfarin dose changes. ResultsAmong 598 participants with 3204 (median 4) visits, the median BVTR was 36.8% (interquartile range 0%-73.9%). Participants reported ≤80% adherence in 182 visits (5.7%) and missed pills in the past 7 days in 377 visits (11.8%). Multivariable regression analysis found poorer anticoagulation control (BVTR <36.8%) in those with a VAS ≤80% (odds ratio 1.89; 95% confidence interval, 1.12-3.18; P = .02) and self-reported change in adherence since last visit (odds ratio 1.55; 95% confidence interval, 1.20-2.01; P = .001). ConclusionSelf-reported VAS medication adherence at a clinic visit and changes in reported adherence since the last visit are independently associated with BVTR. Clinicians may gain additional insight into patients' medication adherence by incorporating this information into patient management.

The Impact of Gene Polymorphisms on Anticoagulation Control With Warfarin.

Differences in warfarin maintenance dosages based on the presence of polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through dosage adjustment according to routine guidelines. Little is known about whether routine therapy could provide consensus anticoagulation control for patients with different genotypes. This study was carried out to compare anticoagulant control in patients with different genotypes. Six hundred seventy patients using warfarin according to Chinese guidelines were enrolled. Warfarin dosages and monitored international normalized ratios (INRs) were recorded. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622, CYP2C9 rs1057910, and ORM1 rs17650 polymorphisms were determined. Warfarin dosages and INR were compared between genotypes. Patients with the AGCC*F*F*1*1 polymorphism took longer than patients with the AACC*F*F*1*1 polymorphism (20 vs 5 days, P < .001) to achieve the targeted INR range. The INR values of patients with AACC*F*F*1*3 were unstable and did not enter the stable state control phase until after 35 days. The peak INR of patients with the AACC*F*F*1*3 polymorphism was exceedingly high, with some values exceeding the control range limit of 3.0. Patients with the AACC*F*S*1*1 or AACT*F*F*1*1 polymorphisms exhibited similar INR values as the patients with the AACC*F*F*1*1 polymorphism. This study found that routine medication with warfarin provides significantly different levels of anticoagulant control between patients with wild-type genotypes and patients with heterozygous polymorphism genotypes of VKORC1 rs9923231 or CYP2C9 rs1057910. Patients with heterozygous polymorphism genotypes of VKORC1 or CYP2C9 require genotype-directed therapy with warfarin to increase efficacy and safety in anticoagulant treatment.

Dosing algorithms for vitamin K antagonists across VKORC1 and CYP2C9 genotypes

Background The multicenter, single-blind, randomized EU-PACT trial compared the safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep vein thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. Objectives To explore possible reasons for the lack of differences between trial arms by performing a secondary analysis of EU-PACT data in order to evaluate the performance of both dosing algorithms across VKORC1-CYP2C9 genetic subgroups. Patients/Methods Anticoagulation control measured according to an International Normalized Ratio (INR) below (INR of < 2), within (INR of 2-3) and above (INR of > 3) the therapeutic range was compared across VKORC1-CYP2C9 subgroups. Owing to a low number of patients in each subgroup, trials for acenocoumarol and phenprocoumon were combined for analysis. Results Four weeks after therapy initiation, genotype-guided dosing increased the mean percentage of time in the therapeutic INR range (PTIR) in the VKORC1 GG-CYP2C9*1*1 subgroup as compared with the non-genetic dosing (difference of 14.68%, 95% confidence interval [CI] 5.38-23.98). For the VKORC1 AA-CYP2C9*1*1 subgroup, there was a higher risk of under-anticoagulation with the genotype-guided algorithm (difference of 19.9%; 95% CI 11.6-28.2). Twelve weeks after therapy initiation, no statistically significant differences in anticoagulation control between trial arms were noted across the VKORC1-CYP2C9 genetic subgroups. Conclusions EU-PACT genetic-guided dose initiation algorithms for acenocoumarol and phenprocoumon could have predicted the dose overcautiously in the VKORC1 AA-CYP2C9*1*1 subgroup. Adjustment of the genotype-guided algorithm could lead to a higher benefit of genotyping.

Major vessel occlusion may predict subtherapeutic anticoagulation intensity and feasibility of administration of intravenous thrombolytics.

ObjectiveWe investigated the association between the presence of major vessel occlusion (MVO) and the intensity of the International Normalized Ratio (INR) in cardioembolic high-risk patients taking warfarin. We also evaluated whether the presence of MVO could predict the subtherapeutic range of INR ≤1.7 ensuring safe administration of intravenous thrombolytics.MethodsThe medical records of 177 cardioembolic stroke patients who were taking warfarin between April, 2008 and March, 2015 were retrospectively analyzed. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between vessel occlusion and intensity of INR. To predict INR ≤1.7, decision tree analysis was performed.ResultsINR was inversely associated with MVO in an unadjusted model (OR, 0.36; 95% CI, 0.17–0.76), and in a model adjusted for initial NIHSS score and time from symptom onset to arrival (OR, 0.28; 95% CI, 0.11–0.73). Fifty-two of 58 (89.7%) patients with MVO had an INR ≤1.7, compared with 83 of 119 (69.7%) patients without MVO. Indication for anticoagulation agent use was dichotomized into NVAF and others, and applied to the subgroup of patients with MVO. All patients with NVAF (31/31, 100%) had INR ≤1.7, while 21 of 27 of the other patients (77.8%) had INR ≤1.7.ConclusionsLow INR at presentation in cardioembolic stroke patients during anticoagulation treatment was associated with occurrence of major vessel occlusive stroke. Presence of MVO and indications for anticoagulation may be utilized to ensure the feasibility of administration of intravenous thrombolytics.

Effects of Computerized Decision Support Systems on Management of Atrial Fibrillation: A Scoping Review.

Potential role of computerized decision support system on management of atrial fibrillation is not well understood. To systematically review studies that evaluate the effects of computerized decision support systems and decision aids on aspects pertaining to atrial fibrillation. We searched Medline, Scopus and Cochrane database. Last date of search was 2016, January 10. Computerized decision support systems that help manage atrial fibrillation and decision aids that provide useful knowledge for patients with atrial fibrillation and help them to self-care. Two reviewers extracted data and summarized findings. Due to heterogeneity, meta-analysis was not feasible; mean differences of outcomes and confidence intervals for a difference between two Means were reported. Seven eligible studies were included in the final review. There was one observational study without controls, three observational studies with controls, one Non-Randomized Controlled Trial and two Randomized Controlled Trials. The interventions were three decision aids that were used by patients and four computerized decision support systems. Main outcomes of studies were: stroke events and major bleeding (one article), Changing doctor-nurse behavior (three articles), Time in therapeutic International Normalized Ratio range (one article), decision conflict scale (two articles), patient knowledge and anxiety about stroke and bleeding (two articles). A computerized decision support system may decrease decision conflict and increase knowledge of patients with atrial fibrillation (AF) about risks of AF and AF treatments. Effect of computerized decision support system on outcomes such as changing doctor-nurse behavior, anxiety about stroke and bleeding and stroke events could not be shown.We need more studies to evaluate the role of computerized decision support system in patients with atrial fibrillation.

Incidence and Risk Factors for Venous Thromboembolism in Patients with Spinal Cord Injury: A Retrospective Study

Introduction: The true incidence of venous thromboembolism (VTE) in patients with acute spinal cord injury (SCI) is unclear. The management of thromboprophylaxis varies among clinicians and is challenging due to the balance against bleeding. There is limited data on the risk factors associated with VTE in patients with an acute SCI.Methods: We performed a retrospective chart review of consecutive adult patients with acute traumatic or non-traumatic SCI presenting within 1 week of injury from 2009 to 2015. We excluded patients who were already on therapeutic oral anticoagulation, those who had a short hospital admission (<7 days), and patients who had early transfer to a different hospital location (<30 days from the initial admission). The primary outcome was incidence of symptomatic, objectively verified deep vein thrombosis (DVT) and/or pulmonary embolism (PE) within 90 days. Secondary outcomes were major bleeding, all-cause mortality, and fatal PE. Step-wise cox modeling analyses were used to identify risk factors for VTE.Results: A total of 211 eligible patients were initially screened and 60 patients were excluded: 34 patients had short hospital admissions, 17 were transferred to a different hospital location (median time of 11 days, range 5 to 29 days), 3 had another reason for admission, and 6 patients were already on therapeutic anticoagulation. The remaining 151 patients with acute SCI were analyzed. Median age was 51 (range 17 to 91 years) and 106 (70%) were males. Patients were followed for a median of 90 days (range 1 to 90 days) and the median length of hospital stay was 79 days (range 1 to 90 days). Hundred and eleven patients (73.5%) had paraplegia or tetraplegia, 10 patients (6.6%) had no neurological impairment, and the degree of impairment was unspecified in 30 patients (19.9%). A total of 112 patients (74.2%) had a traumatic SCI with a fracture, 34 (22.5%) had a traumatic SCI without a fracture, and 5 (3.3%) had a non-traumatic SCI. Ninety four patients (62.2%) had a SCI alone versus 57 (37.8%) who had other sites of injury in addition to a SCI. The median duration of thromboprophylaxis was 65 days (range 2 to 90 days). Majority of the patients (59.6%) received low-dose low-molecular-weight heparin (LMWH) either alone (85 of 151, 56.3%) or sequentially with warfarin (5 of 151, 3.6%) with international normalized ratio range of 2 to 3 compared to 48 patients (31.8%) who received increased intensity LMWH either alone (9 of 151, 6%) or sequentially with low-dose LMWH (39 of 151, 25.8%). Thirteen patients (8.6%) had no thromboprophylaxis. Of the 151 patients included in the analysis, 17 patients (11%) had symptomatic VTE (9 PEs, 6 lower extremity DVT, 1 upper extremity DVT, and 1 with both a DVT and PE). The median time of VTE occurrence was 18 days (range 2 to 65 days) (Figure 1). There was no statistical difference in rate of VTE between the standard prophylactic LMWH group compared to those who received increased intensity LMWH (13.3% versus 8.3%, respectively; odds ratio [OR] 0.59, 95% confidence interval [CI], 0.13-2.1, p = 0.58). Six patients (4%) had major bleeding and none had a fatal PE. The median time of major bleeding occurrence was 17 days (range 8 to 40 days). The all-cause mortality rate was 13.9%. The median time of all-cause death was 6 days (range 1 to 61 days). In the univariate analyses, male sex (OR 14.95; 95% CI, 1.05-49.1, p = 0.003) and having other sites of injuries along with SCI (OR 2.6; 95% CI. 0.8- 8.7, p = 0.049) were significantly associated with the risk of VTE. In stepwise Cox modeling, independent contributors to risk for VTE were other sites of injuries (hazard ratio [HR] 6.07), age (HR 1.05 per year) and to some extent the presence of leg paresis/para- or tetraplegia (HR 2.7), whereas hypertension appeared to reduce the risk (HR 0.18). The gender variable could not be included due to zero events for females.Conclusions: Symptomatic VTE is still today a frequent complication in patients with acute SCI and can occur early after injury. Male sex, age and presence of other sites of injuries along with SCI were independent risk factors for symptomatic VTE. Future randomized trials assessing the role of direct oral anticoagulants versus the current standard of care using low-dose LMWH among these higher risk patients are needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Quality of Vitamin K Antagonist Control and 1-Year Outcomes in Patients with Atrial Fibrillation: A Global Perspective from the GARFIELD-AF Registry.

AimsVitamin K antagonists (VKAs) need to be individually dosed. International guidelines recommend a target range of international normalised ratio (INR) of 2.0–3.0 for stroke prevention in atrial fibrillation (AF). We analysed the time in this therapeutic range (TTR) of VKA-treated patients with newly diagnosed AF in the ongoing, global, observational registry GARFIELD-AF. Taking TTR as a measure of the quality of patient management, we analysed its relationship with 1-year outcomes, including stroke/systemic embolism (SE), major bleeding, and all-cause mortality.Methods and ResultsTTR was calculated for 9934 patients using 136,082 INR measurements during 1-year follow-up. The mean TTR was 55.0%; values were similar for different VKAs. 5851 (58.9%) patients had TTR<65%; 4083 (41.1%) TTR≥65%. The proportion of patients with TTR≥65% varied from 16.7% in Asia to 49.4% in Europe. There was a 2.6-fold increase in the risk of stroke/SE, 1.5-fold increase in the risk of major bleeding, and 2.4-fold increase in the risk of all-cause mortality with TTR<65% versus ≥65% after adjusting for potential confounders. The population attributable fraction, i.e. the proportion of events attributable to suboptimal anticoagulation among VKA users, was 47.7% for stroke/SE, 16.7% for major bleeding, and 45.4% for all-cause mortality. In patients with TTR<65%, the risk of first stroke/SE was highest in the first 4 months and decreased thereafter (test for trend, p = 0.021). In these patients, the risk of first major bleed declined during follow-up (p = 0.005), whereas in patients with TTR≥65%, the risk increased over time (p = 0.027).ConclusionA large proportion of patients with AF had poor VKA control and these patients had higher risks of stroke/SE, major bleeding, and all-cause mortality. Our data suggest that there is room for improvement of VKA control in routine clinical practice and that this could substantially reduce adverse outcomes.Trial RegistrationClinicalTrials.gov NCT01090362

Improving Warfarin Management Within the Medical Home: A Health-System Approach

BackgroundAnticoagulation clinics have been considered the optimal strategy for warfarin management with demonstrated improved patient outcomes through increased time in therapeutic international normalized ratio (INR) range, decreased critical INR values, and decreased anticoagulation-related adverse events. However, not all health systems are able to support a specialized anticoagulation clinic or may see patient volume exceed available anticoagulation clinic resources. The purpose of this study was to utilize an anticoagulation clinic model to standardize warfarin management in a primary care clinic setting. MethodsA warfarin management program was developed that included standardized patient assessment, protocolized warfarin-dosing algorithm, and electronic documentation and reporting tools. Primary care clinics were targeted for training and implementation of this program. ResultsThe warfarin management program was applied to over 2000 patients and implemented at 39 clinic sites. A total of 160 nurses and 15 pharmacists were trained on the program. Documentation of warfarin dose and date of the next INR increased from 70% to 90% (P <.0001), documentation occurring within 24 hours of the INR result increased from 75% to 87% (P <.0001), and monitoring the INR at least every 4 weeks increased from 71% to 83% (P <.0001) per patient encounter. Time in therapeutic INR range improved from 65% to 75%. ConclusionIncorporating a standardized approach to warfarin management in the primary care setting significantly improves warfarin-related documentation and time in therapeutic INR range.

Patient knowledge of anticoagulant treatment does not correlate with treatment quality

ObjectivesThe objectives of this study were to investigate whether patient knowledge is a predictor of treatment stability in anticoagulant clinic patients and to evaluate the correlation between the patients' subjective assessment of own knowledge and their score on a validated knowledge assessment instrument. Study designThis is a prospective study where international normalized ratio (INR) stability was followed up 6 months after knowledge assessment. MethodsWe analyzed data of 42 consecutive patients new to vitamin-K antagonist (VKA) treatment and 64 experienced patients from an anticoagulant clinic offering patient education. The patients filled out a VKA knowledge assessment questionnaire with 24 items under standardized conditions, and simultaneously, they were asked about their subjective knowledge. Subsequently, time in range of INR (TIR) was collected for each patient. ResultsOut of the 106 patients, 52 had 18 or more correct answers (>75%), defined as a ‘satisfactory level’ of objective knowledge. The average TIR was 73%, and treatment stability was significantly higher in experienced patients than new patients. We found no correlation between objective knowledge and TIR (Spearman rho = −0.03, P = 0.78). Most patients (77%) reported a high subjective knowledge of VKA, but no correlation was found between objective and subjective knowledge (Spearman rho = 0.129, P = 0.19). ConclusionWe observed that many patients had a low level of knowledge of VKA, despite high treatment stability and patient education. The patient's own assessment of knowledge was not found to predict objective knowledge, which could have implications for selection of patients for self-test or self-management of treatment.

Improving Transitions of Care for Hospitalized Patients on Warfarin

Transitions in care create challenges for warfarin management, including dosing errors, medication nonadherence, and/or insufficient monitoring. Adverse drug events from warfarin following transitions have been found to have serious consequences. Before the intervention, at the time of hospital discharge, individual physicians identified warfarin management plans on paper forms on the basis of their personal practice preferences. With the implementation of a computerized physician order entry in the electronic health record (EHR) in November 2010, the paper form became obsolete. A modification to the EHR created an order prompting physicians to include five key elements for warfarin management on discharge. A study was conducted to assess the impact of this intervention as a communication tool for patients and health care providers. Discharge documentation was retrospectively reviewed for warfarin patients discharged from University of Missouri (MU) Health Care (Columbia). Frequencies of documentation in the EHR of five key elements of warfarin management were calculated (indication for anticoagulation, target International Normalized Ratio (INR) range, anticipated duration of therapy, date of next INR, and posthospital provider to manage warfarin therapy) pre- and post-EHR modification. All five key elements were included in the discharge documents for 268 (42%) of the charts for 633 patients in the preintevention (baseline) period, for 297 (78%) of the 382 charts in the first postintervention period (September 15, 2013-March 15, 2014) and for 574 (61%) of the 943 charts in the second postintervention period (March 16, 2014-August 5, 2015). Although limited to one health care system's experience, this study demonstrates the EHR's potential value in assisting with anticoagulation therapy between outpatient and inpatient settings and across multiple providers.