Improvement of oral anticoagulation therapy by INR self-management

Thromboembolic complications after valve replacement are significantly reduced if the INR is increased from 1.0 to 2.0. Hemorrhagic events increase exponentially with more intensive oral anticoagulation. In INR (patient) self-testing (PST), patients self-check their INR after being appropriately educated and supplied with a coagulometer. Patients contact their home physician if the actual INR tends to run outside an individually defined target INR corridor for correction. For patient self-management (PSM), subjects are trained to self-test their INR and to adjust the anticoagulant dose according to their anticoagulation state. The median difference between self-tested and laboratory-tested INRs was < 5.0%, indicating no significant differences between the two methods. PSM resulted in a significantly more stable oral anticoagulation therapy (OAT), which was the strongest predictor for a low complication rate after valve replacement surgery. Lower rates of thromboembolism (0.9 versus 3.6% per patient-year; pt-yr) and bleeding (4.5 versus 10.9% per pt-yr) (p < 0.001) were seen in PSM subjects than with conventional INR management. A switch from conventional to PSM resulted in a 30% reduction in complication rates in the German Experience with Low Intensity Anticoagulation (GELIA) study. After appropriate education and provision with a handy coagulometer, the vast majority of patients after valve replacement can self-check INRs and adjust the anticoagulant dosage accordingly. PSM results in a significantly more stable oral anticoagulation treatment and consequently in lower incidences of thromboembolic and bleeding events.     

CoaguChek XS血凝仪检测国际标准化比值和凝血酶原时间的准确性和可靠性

目的比较罗氏CoaguChek XS快速凝血分析仪与标准实验室静脉血测定的国际标准化比值(INR)和凝血酶原时间之间的差异,判断CoaguChek XS测量INR的准确性。方法 80例患者同时抽取静脉血及指端毛细血管血,分别行标准实验室INR测定及罗氏CoaguChek XS快速凝血分析仪INR测定。结果 2种测量方法差异无统计学意义(P0.05)。CoaguChek XS INR与标准实验室测定的INR呈正相关(r=0.987,P0.05)。92.5%的患者更愿意接受CoaguChek XS测定INR。结论罗氏CoaguChek XS快速凝血分析仪测定INR结果可靠,具有快速、简便、准确、疼痛小、依从性好等特点,能很快提供可靠数据,便于临床医师及时调整抗凝药物剂量。     

Experience with INR self-management: patient selection and complication rates

BACKGROUND: INR self-management can reduce the risk of complications for patients with indication of long-term oral anticoagulation therapy. However, little is known about early indicators of complication risk. METHODS: In a prospective study on 330 consecutive patients all participants were informed about oral anticoagulation by a structured teaching program. The two groups were divided as to whether they received usual medical care provided by a family physician (n=220) or self-management (n=110) on a portable coagulation monitor (CoaguChek System). After a mean follow up of 13.3+/-4.4 months, the participants of the study were interviewed by a structured questionnaire to obtain information about hemorrhagic and thromboembolic complications as well as survival. RESULTS: In comparison to patients under usual care, patients with INR selfmanagement were significantly younger (58 vs 64 years) and had fewer comorbidities (diabetes and hypertension) as well as a higher ejection fraction (53.6 vs 51.1%). Indication for anticoagulation, age and heart rhythm explained 58% of the differences between the management groups. There was no significant difference in the overall complication rates between the two groups (usual care vs selfmanagement): major bleeding 0.5 vs 0.9%, cerebral embolism (TIA or stroke) 1.9 vs 0.9%, hospital admission 2.3 vs 1.8%. A high BMI (OR=1.5; 95% CI 1.06-1.25; p=0.001) or a high therapeutic INR range (OR=2.42; 95% CI 1.16-5.1; p=0.019) is associated with a higher complication rate. CONCLUSIONS: Complication rates for patients with long-term oral anticoagulant therapy did not differ significantly between usual care and self-management. Rather, the patient's body weight and the requirement of high anticoagulation intensity drive the complication risk under both management systems.     

A randomized trial comparing INR monitoring devices in patients with anticoagulation self-management: evaluation of a novel error-grid approach

BACKGROUND: In addition to the metrological quality of international normalized ratio (INR) monitoring devices used in patients' self-management of long-term anticoagulation, the effectiveness of self-monitoring with such devices has to be evaluated under real-life conditions with a focus on clinical implications. An approach to evaluate the clinical significance of inaccuracies is the error-grid analysis as already established in self-monitoring of blood glucose. Two anticoagulation monitors were compared in a real-life setting and a novel error-grid instrument for oral anticoagulation has been evaluated. METHODS: In a randomized crossover study 16 patients performed self-management of anticoagulation using the INRatio and the CoaguChek S system. Main outcome measures were clinically relevant INR differences according to established criteria and to the error-grid approach. RESULTS: A lower rate of clinically relevant disagreements according to Anderson's criteria was found with CoaguChek S than with INRatio without statistical significance (10.77% vs. 12.90%; P = 0.787). Using the error-grid we found principally consistent results: More measurement pairs with discrepancies of no or low clinical relevance were found with CoaguChek S, whereas with INRatio we found more differences with a moderate clinical relevance. A high rate of patients' satisfaction with both of the point of care devices was found with only marginal differences. CONCLUSIONS: A principal appropriateness of the investigated point-of-care devices to adequately monitor the INR is shown. The error-grid is useful for comparing monitoring methods with a focus on clinical relevance under real-life conditions beyond assessing the pure metrological quality, but we emphasize that additional trials using this instrument with larger patient populations are needed to detect differences in clinically relevant disagreements.     

A randomised control trial of patient self-management of oral anticoagulation compared with patient self-testing

Several studies suggest that patient self-management (PSM) may improve the quality of oral anticoagulation therapy as measured by time spent within the international normalised ratio (INR) target range. We performed a prospective randomised control trial to determine whether the improvement in quality of treatment afforded by PSM is greater than that achieved by patient self-testing (PST) alone. A total of 104 of 800 eligible patients aged 22-88 years (median = 59.8), attending our hospital anticoagulant clinic and receiving long-term warfarin for >8 months agreed to participate. Patients were randomised to PSM (n = 55) or PST (n = 49). Both groups measured their INR using the CoaguChek S every 2 weeks or more frequently if required, for a period of 6 months. Seventy-seven of 104 (74%) patients completed the study (PSM = 41 and PST = 36). The 'drop out' rates for both groups were similar. There was no significant difference between the percentage time in target therapeutic range for PSM (69.9%) and PST (71.8%). Both groups combined showed a significant improvement over the previous 6 months (71.0% vs. 62.5%; P = 0.04). Changes in time within the therapeutic range in individual patients (+5.86) also showed a significant difference. The quality of warfarin control in both PST and PSM may be superior to that achieved by conventional management in a specialised hospital anticoagulation clinic.     

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

Background

Many patients with heart failure need anticoagulants, including warfarin. Good control is particularly challenging in heart failure patients, with <60% of international normalized ratio (INR) measurements in the therapeutic range, thereby increasing the risk of complications. This study aimed to evaluate the effect of a patient-specific tailored intervention on anticoagulation control in patients with heart failure.

Performance of a point-of-care device in determining prothrombin time in an anticoagulation clinic

New portable devices for the measurement of the prothrombin time and the international normalized ratio (INR) from capillary blood samples have demonstrated to have good correlation with classic laboratory methods in multiple clinical settings. In this study, we evaluated the performance of the point-of-care device CoaguChek XS (CoaguChek XS; Roche Diagnostics, Basel, Switzerland), comparing the INR results with the standard laboratory method (automatic coagulometer) in an outpatient anticoagulation clinic. Results were compared by linear regression and Bland-Altman plot. Two hundred paired results were collected from 170 patients in a period of 90 days. The main indications for anticoagulation were prophylaxis of venous thromboembolic events, atrial fibrillation and prosthetic heart valves. Mean INR results obtained with the portable device and with the standard laboratory method were 2.22?±?0.70 and 2.30?±?0.77, respectively. The proportion of patients with supratherapeutic INRs was 13.5%. The CoaguChek XS monitor tended to underestimate the INR on average by 0.08?U. The correlation coefficient (R) between the two methods was 0.91 (P?相似文献   

The Bad Oeynhausen Concept of INR Self-Management

BACKGROUND: A significant number of patients depend on the intake of vitamin K antagonists for prevention and treatment of thromboembolic events. The development of portable anticoagulation monitors has enabled self-testing and self-adjustment of anticoagulation therapy. OBJECTIVE: To describe the principles of a training course to learn INR self-management and to illustrate reliability of our concept. DESCRIPTION: The training is divided into an early postoperative training, an ambulatory training six months later, and a 24 hours care and consultation. According to our concept, each patient who depends on long-term anticoagulation therapy is able to learn INR self-management. Reliability of our concept has been proved in two prospective, randomized clinical trials. STUDY RESULTS: A study with 1,155 patients has demonstrated that INR values lie more often in the predetermined target range in the INR self-management group if compared to the conventional group (79.2% vs. 64.9%; P < 0.001). Moreover, this study has demonstrated that self-management can lead to a reduction of thromboembolism (1.5% vs. 2.8%; P < 0.05), and to a lower lethality if compared to conventional INR management (3.5% vs 6.0%; P < 0.025). A second study with 1,816 patients has confirmed that INR self-management results in a high percentage of INR values in the target range (76%), even though target INR-range is reduced and narrowed. Thus, low dose INR self-management did not increase the risk of thromboembolism while avoiding the zone of higher risk for bleeding, beginning from INR > 3.5. CONCLUSIONS: The Bad Oeynhausen concept of INR self-management is a promising tool to achieve low hemorrhagic complications without increasing the risk of thromboembolic complications. It can thus be successfully applied to patients with an indication for permanent anticoagulation therapy.     

INR Self-Management Following Mechanical Heart Valve Replacement

INR self-management can reduce severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement. Beginning anticoagulation therapy immediately in the postoperative period further reduces anticoagulant-induced complications. Data were collected from the first 600 surviving patients (from a total study sample of 1200 patients) who completed follow-up of at least 2 years. Patients were randomly divided into a self-management group and a control group. INR self-management reduced severe hemorrhagic and thromboembolic complications (P=0.018). Nearly 80% of INR values recorded by patients themselves, regardless of educational level, were within the target therapeutic range of INR 2.5–4.5, compared with 62% of INR values monitored by family practitioners. Only 8.3% of patients trained in self-management immediately after surgery were unable to continue with INR self-management. The results differed slightly between patient groups with different levels of education. We conclude that all patients for whom anticoagulation is indicated are candidates for INR self-management regardless of education level.     

INR self-management following mechanical heart valve replacement

INR self-management can reduce severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement. Beginning anticoagulation therapy immediately in the postoperative period further reduces anticoagulant-induced complications. Data were collected from the first 600 surviving patients (from a total study sample of 1200 patients) who completed follow-up of at least 2 years. Patients were randomly divided into a self-management group and a control group. INR self-management reduced severe hemorrhagic and thromboembolic complications (P=0.018). Nearly 80% of INR values recorded by patients themselves, regardless of educational level, were within the target therapeutic range of INR 2.5-4.5, compared with 62% of INR values monitored by family practitioners. Only 8.3% of patients trained in self-management immediately after surgery were unable to continue with INR self-management. The results differed slightly between patient groups with different levels of education. We conclude that all patients for whom anticoagulation is indicated are candidates for INR self-management regardless of education level.     

Patient self-testing is a reliable and acceptable alternative to laboratory INR monitoring

SAn ageing population and the continuing expansion of clinical indications for coumadin therapy have increased pressure on hospital anticoagulant clinics. One solution is patient self-testing (PST) of the international normalized ratio (INR) using capillary blood samples on point-of-care coagulation monitors at home. We conducted a prospective study to determine whether patients can achieve accurate INR values through PST, using the CoaguChek S (Roche Diagnostics, Lewes, UK). The main outcome measurements were: comparability of INR values obtained by PST and the hospital laboratory, patient acceptability as assessed by a questionnaire and anticoagulant control. Eighty-four patients [53 men, 31 women; median age 59 years (range 26-83)], receiving long-term oral anticoagulation (warfarin), were recruited from our Anticoagulation Clinic. Patients were randomized to weekly self-testing or continuing 4-weekly hospital laboratory monitoring of INR. Comparison of INRs (n = 234) showed no significant differences between the CoaguChek (median INR 3.02) and laboratory testing (median INR 3.07). There was excellent correlation between the two methods (r = 0.95), with 85% of CoaguChek results within 0.5 INR units of the laboratory method. On four occasions, differences of >1 unit INR were obtained, but in each case the patient's anticoagulation was unstable (INR >4.5 by both methods) and the differences in INR would not have altered patient management. 87% of patients found self-testing straightforward, 87% were confident in the result they obtained and 77% preferred self-testing. We conclude that PST is a reliable alternative to hospital clinic attendance and is acceptable to the majority of suitably trained patients.     

Reliability of point-of-care prothrombin time testing in a community clinic: a randomized crossover comparison with hospital laboratory testing

The success in achieving therapeutic international normalized ratio (INR) targets in the control of warfarin using a whole-blood point-of-care testing (POCT) monitor (CoaguChek) in a community clinic was compared with hospital laboratory coagulometer prothrombin time (PT) testing in a randomized crossover study. Forty-six patients were randomized into two groups. At each visit, capillary blood was taken for the POCT monitor and venous blood for the laboratory coagulometer. In Group 1, for 6 months, dosage was based on the CoaguChek and for the second 6 months on the coagulometer. In the second group, the order was reversed. Dosages were determined using the dawn ac computer programme. Success was assessed by the percentage of time patients were maintained within the INR targets. Agreement between laboratory and monitor INR, and patient satisfaction were also assessed. Results with the POCT monitor compared well with the hospital coagulometer. Time in INR target range between the groups was similar, with 60.9% on the POCT monitor and 59.3% with the laboratory coagulometer in Group 1 and in Group 2, respectively, 64.3% and 63.4% with no significant difference in mean INR. An INR above 4.0 gave some discrepant results. International Sensitivity Index calibrations of the two test systems indicated that the INRs were dependable. Patient questionnaires showed greater satisfaction with community POCT monitoring.     

Validation of the international normalized ratio (INR) in a new point‐of‐care system designed for home monitoring of oral anticoagulation therapy

The new CoaguChek XS system is designed for use in patient self testing with a measuring range from 0.8 INR up to 8.0 INR, which has been calibrated against the mean INR of rTF/95 and ERM‐AD149. This study was performed to confirm the correct INR results received from two routinely manufactured lots of test strips when compared with the international reference preparations (IRP) rTF/95 and ERM‐AD149. At one study site capillary and noncitrated venous whole blood samples from 20 normal donors and 62 anticoagulated patients were applied to two test strip lots of the new system in duplicate. Additionally blood was collected in citrate tubes, processed to plasma, and PT results were obtained using rTF/95 and ERM‐AD149 by the manual tilt tube method. Method comparisons of the INR results of the CoaguChek XS system vs. the mean INR of the IRP demonstrated a mean relative bias of ?0.02% to ?0.4%, mean absolute relative deviations of 6.4–9.6%, and accuracy observing >95% of CoaguChek XS INR within limits of ±14% to ±21.5% to the mean INR of the IRP. The results of the study confirm the successful calibration of two lots of the new CoaguChek XS system, demonstrate the validity of the calibration concept and prove the accuracy of the new system in comparison with the IRP. Clinical decisions in oral anticoagulation therapy may be reliably made upon the INR results of the new system.     

INR variability in atrial fibrillation: A risk model for cerebrovascular events

BackgroundUse of vitamin K antagonists (VKAs) for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) necessitates frequent monitoring of the international normalized ratio (INR) to avoid the increased risk of hemorrhage associated with excess anticoagulation, or ischemic stroke due to insufficient anticoagulation. We therefore developed a model to estimate the excess morbidity attributable to inadequate INR control in NVAF populations.MethodsEquations expressing the risk of cerebrovascular events as a function of INR were generated using published data. Additional functions were developed to estimate the excess risk attributable to inferior INR control, using the clinical trial setting as the reference.ResultsThe derived risk functions were applied to French NVAF patients receiving anticoagulation in routine medical practice. This population achieved a time in therapeutic range (INR 2.0–3.0) of 59%, compared with 68% time in therapeutic range (TTR) in the SPORTIF III and V clinical trials. However, there was considerable variation in the TTR among patients in routine care, of whom 36% were in range for less than 50% of the time. Among this latter group, the relative risk, compared with the clinical trial setting, was 1.47 for ischemic stroke and 2.68 for intracranial hemorrhage. Conversely, for patients achieving a TTR greater than 50%, the relative risks for ischemic stroke and intracranial hemorrhage were 0.99 and 1.16, respectively.ConclusionsThis model permits estimation of the excess risk attributable to inferior INR control in NVAF populations receiving VKA anticoagulation, and has implications for public health planning and management.     

INR Control of Patients with Mechanical Heart Valve on Long-Term Warfarin Therapy

Background

Warfarin is an anticoagulant indicated for patients who had undergone mechanical heart valve(s) replacement (MHVR). In these patients, time in therapeutic range (TTR) is important in predicting the bleeding and thrombotic risks.

Relationship Between Test Frequency and Outcomes of Anticoagulation: A Literature Review and Commentary with Implications for the Design of Randomized Trials of Patient Self-Management

Background: Patient self-management (PSM) of anticoagulation, which is primarily based upon the premise that more frequent testing will lead to tighter anticoagulation control and thus to improved clinical outcomes, is a promising model of care. The goals of this paper are (1) to describe the strength of evidence correlating more frequent testing with improved outcomes; and (2) to discuss implications of these findings for the design of randomized controlled trials (RCTs) assessing the effectiveness and cost-effectiveness of PSM.Methods: We performed two literature reviews: one examining the strength of the relationship between time in target range (TTR) and the clinical outcomes of major bleeding and thromboembolism; and the second examining the strength of the relationship between frequency of testing and TTR.Results: We found that (1) the relationship between TTR and clinical outcomes is strong, thus supporting use of TTR as a primary outcome variable; and (2) more frequent testing seems to increase TTR, although the studies supporting this latter conclusion were relatively few and not definitive. Statistical analysis suggested that a study which uses clinical event rates as its primary outcome would need to be much larger than a comparable study which is based upon TTR.Conclusions: When designing randomized trials of PSM, the design should (1) use as its control group high quality anticoagulation management rather than usual care; (2) include the maximum possible amount of self-management in the intervention group; (3) include different testing intervals in the intervention group; (4) use TTR as the primary outcome variable and event rates as a secondary outcome; and (5) base the sample size calculations upon a 5–10% absolute improvement in TTR. Additional RCTs are needed in order to determine how the promise of PSM can best be fulfilled.     

Cluster randomized controlled trial of a simple warfarin maintenance dosing algorithm versus usual care among primary care practices

Many patients using warfarin are being managed in primary care and typically achieve a lower time in therapeutic range (TTR) for the international normalized ratio (INR) than patients in specialized care. A simple warfarin maintenance dosing tool could assist primary care physicians with improving TTR. We tested whether a simple warfarin maintenance dosing algorithm can improve TTR compared with usual care among Canadian primary care physicians. Primary care practices managing warfarin therapy without an anticoagulation clinic, computer decision support system or patient self-management tools enrolled 10–30 patients with target INR range 2–3. Practices were randomized to manage warfarin maintenance with the algorithm, or as usual in 2009–2010. Primary outcome was the mean individual patient TTR, and was compared between groups with adjustment for clustering within practices. There were 13 practices randomized to the Algorithm and 15 practices to Control, enrolling 240 and 297 patients respectively, with a mean follow-up of 280 days. Mean (standard deviation; SD) TTR before the study was comparable between groups [68 % (SD 26) for usual care vs. 70 % (SD 27) for the algorithm; p = 0.49]. Dosing decisions during the study in the algorithm group were more often in agreement with the algorithm’s recommendations than with usual care (81 vs. 91 %; p < 0.0001). Mean study TTR of the algorithm group was not superior to usual care: [72.1 (SE 1.7) vs. 71.4 % (SE 1.5) respectively; p = 0.73]. The simple warfarin maintenance dosing algorithm did not improve TTR compared with usual care among Canadian primary care practices.     

Qualidade da Anticoagulação Oral em Pacientes com Fibrilação Atrial em um Hospital Terciário no Brasil

BackgroundAtrial fibrillation (AF) affects 0.5% to 2.0% of the general population and is usually associated with cardiac structural diseases, hemodynamic damage, and thromboembolic complications. Oral anticoagulation prevents thromboembolic events and is monitored by the international normalized ratio (INR).ObjectivesTo evaluate INR stability in nonvalvular AF patients treated with warfarin anticoagulation, to evaluate thromboembolic or hemorrhagic complications, and to identify the group at higher risk for thromboembolic or hemorrhagic events.MethodsData from the medical records of 203 patients who received medical care at a tertiary hospital in Brazil were reviewed, and the time in therapeutic range (TTR) was calculated using the Rosendaal method. The possible TTR influencing factors were then analyzed, and the relationship between the TTR and thromboembolic or hemorrhagic events was calculated. The level of significance was 5%.ResultsThe mean TTR was 52.2%. Patients with INR instability in the adaptation phase had a lower mean TTR (46.8%) than those without instability (53.9%). Among the studied patients, 6.9% suffered hemorrhagic events, and 8.4% had a stroke. The higher risk group for stroke and bleeding consisted of patients with INR instability in the adaptation phase.ConclusionsThe quality of anticoagulation in this tertiary hospital in Brazil is similar to that in centers in developing countries. Patients with greater INR instability in the adaptation phase evolved to a lower mean TTR during follow-up, had a 4.94-fold greater chance of stroke, and had a 3.35-fold greater chance of bleeding. Thus, for this patient group, individualizing the choice of anticoagulation therapy would be advised, considering the cost-benefit ratio.     

Accuracy, reproducibility and clinical utility of the CoaguChek S portable international normalized ratio monitor in an outpatient anticoagulation clinic

The accuracy and reproducibility of the CoaguChek S, and its clinical agreement with conventional laboratory international normalized ratio (INR) determination, were evaluated in an outpatient anticoagulation clinic setting. Forty-three patients provided 248 paired INR measurements for analysis. The paired results were highly correlated (r = 0.90). The mean coefficient of variation for the CoaguChek S for a random sample of 21 patients with three repeated tests each, was 4%. Clinical applicability was also measured by discrepant INR values, as defined in the literature by expanded and narrow agreement, and by INR values resulting in a different clinical decision by a blinded haematology registrar. Expanded agreement and narrow agreement between the two INR values occurred 90 and 88% of the time, respectively. The stricter criteria set down by the clinician resulted in 73% of paired results producing the same dosage decision. The CoaguChek S displayed good correlation with laboratory determination of INR and compared relatively well with expanded and narrow clinical agreement criteria.