Quality Of International Normalized Ratio Control Research Articles

Anticoagulation Control in Older Atrial Fibrillation Patients Receiving Vitamin K Antagonist Therapy for Stroke Prevention.

Introduction Efficacy and safety of vitamin K antagonists (VKAs) among atrial fibrillation (AF) patients are enhanced when the International Normalised Ratio (INR) is 2.0–3.0. Anticoagulation control among older patients is perceived to be lower and contributes to poorer initiation and uptake. Objective To examine the quality of INR control, adverse clinical outcomes, and factors associated with bleeding in older AF patients (≥80 years). Methods Anticoagulation control assessed by time in therapeutic range (TTR) (Rosendaal method) and percentage INRs in range (PINRR). Among the 205 patients aged ≥80 years, 58.5% were female, with mean (SD) CHA2DS2-VASc 4.4 (1.3) and HAS-BLED 1.8 (0.8) scores. Results Mean (SD) TTR and PINRR were similar for those aged ≥80 vs. <80 years (66.7 (13.8) vs. 66.7 (13.1)) despite significantly lower INR monitoring intensity (51.2 (22.7) vs. 60.7 (25.8)) and shorter follow-up (4.4 (2.6–6.2) vs. 5.7 years (3.3–7.1)) in those ≥80 years of age. Good anticoagulation control (TTR and PINRR ≥70%) of 44% was seen in both age groups. No significant differences in composite major adverse clinical events were evident for those aged ≥80 vs. <80 years (p = 0.55). Cox regression analysis confirmed that age ≥80 years was associated with higher risk of bleeding (HR 1.90 (1.01–3.56); p = 0.047). Conclusions Suboptimal (TTR and PINRR <70%) anticoagulation control was evident in all patients. Risk of bleeding increased, but there was no difference in thromboembolic events and all-cause mortality in those aged ≥80 years. Improving TTR to ≥70% and enhancing anticoagulation monitoring of VKA use remain a clinical priority to prevent bleeding complications, particularly among those aged 80 years and above.

Differences in the quality of oral anticoagulation therapy with vitamin K antagonists in German GP practices \u2013 results of the cluster-randomized PICANT trial (Primary Care Management for Optimized Antithrombotic Treatment)

BackgroundIn Germany, patients receiving oral anticoagulation (OAC) are often treated by general practitioners (GPs), and large proportions of patients receive vitamin K antagonists (VKAs). The quality of OAC in German GP practices, differences between various practices, and improvement potential through implementation of case management, have not yet been investigated satisfactorily.Based on results of a cluster-randomized controlled trial, we aimed to assess whether OAC quality can be improved, any variations between practices exist and determine practice- and patient-level factors.MethodsThe PICANT trial (2012–2015) was performed in 52 GP practices in Hesse, Germany. Adult patients with long-term indication for OAC received best practice case management in the intervention group. International normalized ratio (INR) values were recorded from anticoagulation passes. The Rosendaal method was used to calculate Time in Therapeutic Range (TTR) at patient level, and mean pooling to obtain center-specific TTR (cTTR) at practice level. The quality of OAC was assessed by TTR and cTTR. Linear model analyses were used to investigate associations between practice−/ patient-level factors and TTR.ResultsInclusion of 736 patients (49.6% intervention and 50.4% control patients); 690 (93.8%) received phenprocoumon. Within 24 months, the TTR was 75.1% (SD 17.6) in the intervention versus 74.3% (SD 17.8) in the control group (p = 0.670). The cTTR averaged 75.1% (SD 6.5, range: 60.4 to 86.7%) in the intervention versus 74.3% (SD 7.2, range: 52.7 to 85.7%) in the control group (p = 0.668). At practice level, the TTR was significantly lower in practices with a male physician and certification in quality management. At patient level, the TTR was significantly higher in patients with moderate to high compliance, in men, and in patients that performed self-management. The TTR was significantly lower in patients with certain comorbidities, and who were hospitalized.ConclusionsThe intervention did not effectively improve OAC quality compared to routine care. Quality of INR control was generally good, but considerable variation existed between GP practices. The variability indicates optimization potential in some practices. The demonstrated association between patient-level factors and TTR highlights the importance of considering patient characteristics that may impede achieving high quality therapeutic outcomes.Trial registrationISRCTN registry, ISRCTN41847489, registered 27 February 2012.

Quality of INR control and switching to non-Vitamin K oral anticoagulants between women and men with atrial fibrillation treated with Vitamin K Antagonists in Spain. A population-based, real-world study.

BackgroundWorldwide, there is growing evidence that quality of international normalized ratio (INR) control in atrial fibrillation patients treated with Vitamin K Antagonists (VKA) is suboptimal. However, sex disparities in population-based real-world settings have been scarcely studied, as well as patterns of switching to second-line Non-VKA oral anticoagulants (NOAC). We aimed to assess the quality of INR control in atrial fibrillation patients treated with VKA in the region of Valencia, Spain, for the whole population and differencing by sex, and to identify factors associated with poor control. We also quantified switching to Non-VKA oral anticoagulants (NOAC) and we identified factors associated to switching.MethodsThis is a cross-sectional, population-based study. Information was obtained through linking different regional electronic databases. Outcome measures were Time in Therapeutic Range (TTR) and percentage of INR determinations in range (PINRR) in 2015, and percentage of switching to NOAC in 2016, for the whole population and stratified by sex.ResultsWe included 22,629 patients, 50.4% were women. Mean TTR was 62.3% for women and 63.7% for men, and PINNR was 58.3% for women and 60.1% for men (p<0.001). Considering the TTR<65% threshold, 53% of women and 49.3% of men had poor anticoagulation control (p<0.001). Women, long-term users antiplatelet users, and patients with comorbidities, visits to Emergency Department and use of alcohol were more likely to present poor INR control. 5.4% of poorly controlled patients during 2015 switched to a NOAC throughout 2016, with no sex differences.ConclusionThe quality of INR control of all AF patients treated with VKA in 2015 in our Southern European region was suboptimal, and women were at a higher risk of poor INR control. This reflects sex disparities in care, and programs for improving the quality of oral anticoagulation should incorporate the gender perspective. Clinical inertia may be lying behind the observed low rates of switching in patient with poor INR control.

Net clinical benefit of dabigatran vs. warfarin in venous thromboembolism: analyses from RE-COVER\xae, RE-COVER\u2122 II, and RE-MEDY\u2122

The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2.0–3.0]. Patients (≥18 years old) had symptomatic proximal deep vein thrombosis and/or pulmonary embolism. NCB was the composite of cardiovascular endpoints (non-fatal events of recurrent VTE, myocardial infarction, stroke or systemic embolism), all-cause death, and bleeding outcomes, all weighted equally. A broad definition of NCB included major bleeding events (MBE) and clinically relevant non-major bleeding events as bleeding outcomes, while a narrow definition included just MBE. The pooled dataset totalled 5107 patients from RE-COVER/RE-COVER II and 2856 patients from RE-MEDY. When NCB was narrowly defined, NCB was similar between DE and warfarin. When broadly defined, NCB was superior with DE vs. warfarin [RE-COVER/RE-COVER II, hazard ratio (HR) 0.80; 95% confidence interval (CI), 0.68–0.95 and RE-MEDY, HR 0.73; 95% CI 0.59–0.91]. These findings were unaffected by warfarin time in therapeutic range. The NCB of DE was similar or superior to warfarin, depending on the NCB definition used, regardless of the quality of INR control.

Feasibility of Warfarin Anticoagulation Management with a Patient Self-Testing Model in Korea

Warfarin is the main oral anticoagulant effective for the prevention of stroke in patients with atrial fibrillation, and for the prevention and treatment of venous thromboembolism. It has a narrow therapeutic window of effectiveness and safety, which may lead to underuse. Accordingly, dose adjustments are mandatory for its effective and safe treatment, which depends on the time spent in the therapeutic International Normalized Ratio (INR) range (TTR). Hence, TTR is a key determinant of outcomes for patients receiving anticoagulation with warfarin. It is well known that lower rates of TTR in warfarin patients leads to an increased risk of bleeding or thromboembolic complications. Many studies have reported on the accuracy and precision of point-of-care (POC) devices when used by patients for INR monitoring on warfarin anticoagulation, as well as their good correlations with conventional plasma INR measurements within therapeutic ranges. Previous studies have indicated that a patient self-testing model may be superior to usual care or an anticoagulation clinic model in the quality of INR control. Recently, there has been increasing demand for high-quality warfarin management in Korea. Nevertheless, no domestic data have been reported on warfarin anticoagulation management using a patient self-testing (PST) model. Here, we describe our experiences with warfarin management using a PST model where the warfarin dose was adjusted by the anticoagulation clinic staff on the basis of a validated algorithm with the INR values self-tested by patients at home using capillary blood on the POC device CoaguChek-XS (Roche Diagnostics, Mannheim, Germany).

Comorbidities against quality control of VKA therapy in non-valvular atrial fibrillation: a French national cross-sectional study.

BackgroundGiven the prevalence of non-valvular atrial fibrillation in the geriatric population, thromboembolic prevention by means of vitamin K antagonists (VKA) is one of the most frequent daily concerns of practitioners. The effectiveness and safety of treatment with VKA correlates directly with maximizing the time in therapeutic range, with an International Normalized Ratio (INR) of 2.0-3.0. The older population concentrates many of factors known to influence INR rate, particularly concomitant medications and concurrent medical conditions, also defined as comorbidities.ObjectiveDetermine whether a high burden on comorbidities, defined by a Charlson Comorbidity Index (CCI) of 3 or greater, is associated a lower quality of INR control.Study-DesignCross-sectional study.SettingsFrench geriatric care units nationwide.Participants2164 patients aged 80 and over and treated with vitamin K antagonists.MeasurementsComorbidities were assessed using the Charlson Comorbidity Index (CCI). The recorded data included age, sex, falls, kidney failure, hemorrhagic event, VKA treatment duration, and the number and type of concomitant medications. Quality of INR control, defined as time in therapeutic range (TTR), was assessed using the Rosendaal method.Results487 patients were identified the low-quality control of INR group. On multivariate logistic regression analysis, low-quality control of INR was independently associated with a CCI ≥3 (OR = 1.487; 95% CI [1.15; 1.91]). The other variables associated with low-quality control of INR were: hemorrhagic event (OR = 3.151; 95% CI [1.64; 6.07]), hospitalization (OR = 1.614, 95% CI [1.21; 2.14]).ConclusionAn elevated CCI score (≥3) was associated with low-quality control of INR in elderly patients treated with VKA. Further research is needed to corroborate this finding.

A Study of Elderly Adults Taking Warfarin Admitted with Prolonged International Normalized Ratio: A Community Hospital's Experience

To assess bleeding complications and outcome of individuals receiving oral anticoagulants who were admitted to the hospital with an international normalized ratio (INR) greater than 4 by comparing them according to age (≤ 80, >80). Retrospective cohort study. Community hospital. All individuals (N = 253) admitted to the Department of Internal Medicine over a period of 4 years with an INR greater than 4: Group I, aged 80 and younger (n = 127); Group II, older than 80 (n = 126). Data included bleeding complications, survival, and quality of INR control before admission and up to 48 months after admission. Atrial fibrillation was the most common indication for warfarin therapy. Its incidence was higher in the older group (88% vs 73%, P = .004). More elderly participants lived in nursing homes (23% vs 9.4%. P = .004) or received in-home assistance (38.9% vs 20.5%, P = .002). There was no difference in INR upon admission, duration of warfarin treatment, or frequency of INR tests before admission. The incidence of bleeding events was 18.1% in Group I and 12.7% in Group II (P = .30). Major bleeding events occurred in 1.6% of Group I and none of Group II (P = .50). During follow-up after the first admission, the incidence of INR greater than 4 was higher in Group II (87.3% vs 70%, P = .02), without a difference in the number of additional admissions or bleeding events. Primary care physicians can safely maintain warfarin treatment in elderly adults, even in those with a history of hospitalization for high INR, using frequent INR measurements.

Quality of INR Control and Outcomes Following Venous Thromboembolism

The objective of this study was to evaluate the pattern of anticoagulation after venous thromboembolism (VTE) in actual clinical practice. This study used the General Practice Research Database. Individuals aged 18+ years with VTE were matched to 3 controls. Of the 46 335 patients with VTE and 138 024 controls, 70.2% of cases and 86.6% of controls had no obvious risk factors. The mortality risk was increased substantially around the time of diagnosis (relative hazard rate [RR] around 21) but remained elevated for a further 4 years (RRs around 1.5-2.0). The mean percentage of time spent within the therapeutic range for international normalized ratio (INR) was 57.0%. The lowest rate of VTE recurrence occurred in patients with ≥70% time spent within therapeutic range (RR of 0.50, 95% CI 0.39-0.63 compared to <30%). Higher time spent within therapeutic INR range was associated with lower risks of VTE recurrence and death due to VTE.

Systematic Review to Identify Validated Manual Warfarin Maintenance Dosing Tools.

AbstractAbstract 3800 Rationale:Vitamin K antagonists, of which warfarin is the most widely used in North America, are some of the most difficult medications to control and require careful monitoring to keep the international normalized ratio (INR) in the therapeutic range. Anticoagulation clinics and computer-assisted decision support systems have been associated with an improved time patients spend in the therapeutic INR range, but these systems can be expensive. Also, patient self-management delivers the best INR control, but is only useful for patients who are capable to perform self testing and management. Simple, inexpensive and easy to use dosing algorithms have the potential to overcome some of these logistical barriers and offer a tool that could be used without the infrastructure of a formal anticoagulation clinic. We performed a systematic review to identify validated manual warfarin maintenance dosing algorithms that do not require computer support. Methods:MEDLINE was searched, without language restriction, by two independent reviewers for observational and experimental reports of warfarin dosing algorithms, nomograms or formulas. Studies that reported efficacy of anticoagulation clinics, patient self management and computer assisted warfarin dosing were reviewed for references for an underlying dosing process. Inclusion criteria for studies for this review were: 1) the tool needed to provide advice on maintenance dose adjustment and next INR testing, 2) the manual dosing tool needed to be compared to a control group, 3) time in therapeutic range or patient outcomes were reported, 4) the effect of the dosing method could be separated from other interventional aspects of warfarin management. Inter-rater agreement for inclusion of candidate studies was measured with the kappa statistic and disagreement was resolved by consensus. Results:Twenty-five studies were identified and 23 either did not report a manually useful tool (computer-based algorithm or complex formula), did not have a control comparator, did not report the time in therapeutic range or patient outcomes, or the effect of the tool could not be separated from other interventional aspects of anticoagulation clinics, computer systems or self-management. Only 2 studies fulfilled all of the inclusion criteria and there was 100% agreement between the two independent reviewers for their selection. Both studies were single center studies and used practice performance before implementation of the dosing tool as the comparator. One study (n=72) showed an improvement in the proportion of INRs in the therapeutic range from 32% to 46% (p < 0.05). The other study (n=1961) showed an improvement in the time in therapeutic range in patients with a target INR range of 2–3 from 67% to 73% (p < 0.001) and in patients with a range of 2.5–3.5, form 50% to 64% (p < 0.001). Data of the two studies were not pooled due to differences in the dosing tool, quality level of care and calculation of the primary outcome, and the negligible effect of the smaller study. Conclusion:We identified only 2 manually useful VKA maintenance dosing tools that have been compared with a control group. Both studies showed an improvement in the quality of INR control with a simple dosing algorithm, but the studies were limited by their pre/post interventional design. Our results stress the need for a randomized trial to validate the usefulness of a manual dosing algorithm which could yield a simple and inexpensive evidence-based method for many physicians managing patients taking a vitamin K antagonist. Disclosures:No relevant conflicts of interest to declare.

Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial

Effectiveness and safety of warfarin is associated with the time in therapeutic range (TTR) with an international normalised ratio (INR) of 2·0-3·0. In the Randomised Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, dabigatran versus warfarin reduced both stroke and haemorrhage. We aimed to investigate the primary and secondary outcomes of the RE-LY trial in relation to each centre's mean TTR (cTTR) in the warfarin population. In the RE-LY trial, 18 113 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to INR 2·0-3·0. Median follow-up was 2·0 years. For 18 024 patients at 906 sites, the cTTR was estimated by averaging TTR for individual warfarin-treated patients calculated by the Rosendaal method. We compared the outcomes of RE-LY across the three treatment groups within four groups defined by the quartiles of cTTR. RE-LY is registered with ClinicalTrials.gov, number NCT00262600. The quartiles of cTTR for patients in the warfarin group were: less than 57·1%, 57·1-65·5%, 65·5-72·6%, and greater than 72·6%. There were no significant interactions between cTTR and prevention of stroke and systemic embolism with either 110 mg dabigatran (interaction p=0·89) or 150 mg dabigatran (interaction p=0·20) versus warfarin. Neither were any significant interactions recorded with cTTR with regards to intracranial bleeding with 110 mg dabigatran (interaction p=0·71) or 150 mg dabigatran (interaction p=0·89) versus warfarin. There was a significant interaction between cTTR and major bleeding when comparing 150 mg dabigatran with warfarin (interaction p=0·03), with less bleeding events at lower cTTR but similar events at higher cTTR, whereas rates of major bleeding were lower with 110 mg dabigatran than with warfarin irrespective of cTTR. There were significant interactions between cTTR and effects of both 110 mg and 150 mg dabigatran versus warfarin on the composite of all cardiovascular events (interaction p=0·036 and p=0·0006, respectively) and total mortality (interaction p=0·066 and p=0·052, respectively) with reduced event rates at low cTTR, and similar rates at high cTTR. The benefits of 150 mg dabigatran at reducing stroke, 110 mg dabigatran at reducing bleeding, and both doses at reducing intracranial bleeding versus warfarin were consistent irrespective of centres' quality of INR control. For all vascular events, non-haemorrhagic events, and mortality, advantages of dabigatran were greater at sites with poor INR control than at those with good INR control. Overall, these results show that local standards of care affect the benefits of use of new treatment alternatives. Boehringer Ingelheim.