Point-of-care devices (POCDs) for monitoring long-term oral anticoagulation therapy (OAT) may be a useful alternative to laboratory-based international normalized ratio [INR] testing and clinical management.
To determine clinical outcomes of the use of POCDs for OAT management by performing a meta-analysis. Previous meta-analyses on POCDs have serious limitations.
PubMed, the Cochrane Library, DIALOG, MEDLINE, EMBASE, BIOSIS Previews and PASCAL databases.
Randomized controlled trials of patients on long-term OAT, comparing anticoagulation monitoring by POCD with laboratory INR testing and clinical management.
1) rates of major hemorrhage; 2) rates of major thromboembolic events; 3) percentage of time that the patient is maintained within the therapeutic range; 4) deaths. Outcomes were compared using a random-effects model. Summary measures of rates were determined. The quality of studies was assessed using the Jadad scale.
Seventeen articles (16 studies) were included. Data analysis showed that POCD INR testing reduced the risk of major thromboembolic events (odds ratio [OR] = 0.51; 95% confidence interval [CI] 0.35–0.74), was associated with fewer deaths (OR = 0.58; 95% CI = 0.38–0.89), and resulted in better INR control compared with laboratory INR testing. No significant difference between the two management modalities with respect to odds ratios for major hemorrhage was found.
Quality scores varied from 1 to 3 (out of a maximum of 5). Only 3 studies defined how thromboembolic events would be diagnosed, casting doubt on the accuracy of the reporting of thromboembolic events. The studies suggest that only 24% of patients are good candidates for self-testing and self-management. Compared with patients managed with laboratory-based monitoring, POCD patients underwent INR testing at a much higher frequency and received much more intensive education on OAT management.
The use of POCDs is safe and may be more effective than laboratory-based monitoring. However, most patients are not good candidates for self-testing and self-management. Patient education and frequency of testing may be the most important factors in successful PODC management. Definitive conclusions about the clinical benefits provided by self-testing and self-management require more rigorously designed trials.
Background and objectives
International Normalized Ratio (INR) is a world-wide routinely used factor in the monitoring of oral anticoagulation treatment (OAT). However, it was reported that other factors, e. g. factor II, may even better reflect therapeutic efficacy of OAT and, therefore, may be potentialy useful for OAT monitoring. The primary purpose of this study was to characterize the associations of INR with other vitamin K-dependent plasma proteins in a heterogenous group of individuals, including healthy donors, patients on OAT and patients not receiving OAT. The study aimed also at establishing the influence of co-morbid conditions (incl. accompanying diseases) and co-medications (incl. different intensity of OAT) on INR.
Design and Methods
Two hundred and three subjects were involved in the study. Of these, 35 were normal healthy donors (group I), 73 were patients on medication different than OAT (group II) and 95 were patients on stable oral anticoagulant (acenocoumarol) therapy lasting for at least half a year prior to the study. The values of INR and activated partial thromboplastin time (APTT) ratio, as well as activities of FII, FVII, FX, protein C, and concentration of prothrombin F1+2 fragments and fibrinogen were obtained for all subjects. In statistical evaluation, the uni- and multivariate analyses were employed and the regression equations describing the obtained associations were estimated.
Of the studied parameters, three (factors II, VII and X) appeared as very strong modulators of INR, protein C and prothrombin fragments F1+2 had moderate influence, whereas both APTT ratio and fibrinogen had no significant impact on INR variability. Due to collinearity and low tolerance of independent variables included in the multiple regression models, we routinely employed a ridge multiple regression model which compromises the minimal number of independent variables with the maximal overall determination coefficient. The best-fitted two-component model included FII and FVII activities and explained 90% of INR variability (compared to 93% in the 5-component model including all vitamin K-dependent proteins). Neither the presence of accompanying diseases nor the use of OAT nor any other medication (acetylsalicylic acid, statins, steroids, thyroxin) biased significantly these associations.
Among various vitamin K-dependent plasma proteins, the coagulation factors II, VII and X showed the most significant associations with INR. Of these variables, the two-component model, including factors II and VII, deserves special attention, as it largely explains the overall variability observed in INR estimates. The statistical power of this model is validated on virtue of the estimation that the revealed associations are rather universal and remain essentially unbiased by other compounding variables, including clinical status and medical treatment. Further, much broader population studies are needed to verify clinical usefulness of methods alternate or compounding to INR monitoring of OAT.
International Normalized Ratio (INR) of prothrombin time; clotting factors; protein C; prothrombin fragment F1+2; multivariate analysis
Patient self-monitoring (PSM) of oral anticoagulation therapy (OAT) can improve anticoagulant control, but poor uptake and high dropout rates have prompted suggestions that PSM is suitable for only a minority of patients in the UK.
To determine whether PSM could be a viable alternative to regular hospital anticoagulant clinic attendance, if offered from the start of treatment.
318 consecutive patients referred, for the first time, to an anticoagulation clinic were assessed for eligibility using established criteria. Patients electing for PSM attended training and, following successful assessment, performed a capillary blood INR every two weeks or more frequently if directed to do so by the anticoagulation clinic. Primary outcome measures were uptake of PSM and the percentage time in target therapeutic INR range (TIR) compared to patients electing for routine clinic care.
Of 318 patients referred for OAT, 188 were eligible for PSM. 84 (26%) elected to self-monitor, of whom 72 (23%) remained self-monitoring or had completed their course of treatment at the end of the audit. Self-monitoring patients had significantly better anticoagulant control than those receiving routine hospital anticoagulation clinic care (TIR 71% vs 60%, p = 0.003) and significantly less time outside critical limits, ie, INR <1.5 or >5.0 (0.45% vs 2.04%, p = 0.008).
Patients offered PSM from the start of treatment show increased uptake compared to previous UK studies and a level of oral anticoagulation control comparable to that reported in previous clinical trials.
To identify factors that determine patients’ intentions to use point-of-care medical devices, ie, portable coagulometer devices for self-testing of the international normalized ratio (INR) required for ongoing monitoring of blood-coagulation intensity among patients on long-term oral anticoagulation therapy with vitamin K antagonists, eg, warfarin.
A cross-sectional study that applied the technology-acceptance model through a self-completed questionnaire, which was administered to a convenience sample of 125 outpatients attending outpatient anticoagulation services at a district general hospital in London, UK. Data were analyzed using descriptive statistics, factor analyses, and structural equation modeling.
The participants were mainly male (64%) and aged ≥ 71 years (60%). All these patients were attending the hospital outpatient anticoagulation clinic for INR testing; only two patients were currently using INR self-testing, 84% of patients had no knowledge about INR self-testing using a portable coagulometer device, and 96% of patients were never offered the option of the INR self-testing. A significant structural equation model explaining 79% of the variance in patients’ intentions to use INR self-testing was observed. The significant predictors that directly affected patients’ intention to use INR self-testing were the perception of technology (β = 0.92, P < 0.001), trust in doctor (β = −0.24, P = 0.028), and affordability (β = 0.15, P = 0.016). In addition, the perception of technology was significantly affected by trust in doctor (β = 0.43, P = 0.002), age (β = −0.32, P < 0.001), and affordability (β = 0.23, P = 0.013); thereby, the intention to use INR self-testing was indirectly affected by trust in doctor (β = 0.40), age (β = −0.29), and affordability (β = 0.21) via the perception of technology.
Patients’ intentions to use portable coagulometers for INR self-testing are affected by patients’ perceptions about the INR testing device, the cost of device, trust in doctors/clinicians, and the age of the patient, which need to be considered prior to any intervention involving INR self-testing by patients. Manufacturers should focus on increasing the affordability of INR testing devices for patients’ self-testing and on the potential role of medical practitioners in supporting use of these medical devices as patients move from hospital to home testing.
oral anticoagulation; INR self-testing; technology-acceptance model; trust in doctor; home testing; affordability; structural equation modeling
Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). According to the World Health Organization recommendation, International Normalized Ratio (INR) results obtained from the same patient samples with the major PT methods (Quick and Owren) should be the same when the therapeutic range is the same. In our study blood samples were obtained from 207 OAT patients. We analyzed the samples using two Quick and two Owren PT (combined thromboplastin) reagents for INR and assessed the sensitivity and true coagulation activity using a new-generation PT method. The INR values with the Quick PT and Owren PT methods were very similar around the normal range, while unacceptable differences were seen within the therapeutic range and at higher INR values. The Quick PT results as INR are clearly lower than those given by Owren PT and the difference increases toward higher INR. The new PT method functions well with both Owren PT reagents, and we can calculate the true active INR. The Quick PT methods show no sensitivity to coagulation inhibition measurement. The harmonization of the INR is an important goal for the safety of OAT patients. More accurate INR results reduce morbidity and mortality, and the therapeutic ranges should be similar worldwide. In this study we found unacceptable differences in INR results produced by the two PT methods. The new method showed a lack of sensitivity to Quick PT. For the global harmonization of OAT therapy and for INR accuracy only the more sensitive Owren PT method should be used.
International Normalized Ratio; oral anticoagulant therapy; prothrombin time; warfarin.
There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians. We carried out a randomized controlled trial to evaluate these 2 models of anticoagulant care.
We randomly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practices. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio (INR) of patients receiving warfarin sodium was within the target therapeutic range ± 0.2 INR units (expanded therapeutic range) while they were managed in anticoagulation clinics as opposed to family physicians' care over 3 months. We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups.
Of the 221 patients enrolled, 112 were randomly assigned to anticoagulation clinics and 109 to family physicians. The INR values of patients who were managed by anticoagulation clinics were within the expanded therapeutic range 82% of the time versus 76% of the time for those managed by family physicians (p = 0.034). High-risk INR values (defined as being < 1.5 or > 5.0) were more commonly observed in patients managed by family physicians (40%) than in patients managed by anticoagulation clinics (30%, p = 0.005). More INR measurements were performed by family physicians than by anticoagulation clinics (13 v. 11, p = 0.001). Major bleeding events (2 [2%] v. 1 [1%]), thromboembolic events (1 [1%] v. 2 [2%]) and deaths (5 [4%] v. 6 [6%]) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively. Of the 170 (77%) patients who completed the patient satisfaction questionnaire, more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by their family physicians (p = 0.001).
Anticoagulation clinics provided better oral anticoagulant management than family physicians, but the differences were relatively modest.
Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices.
Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages.
The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT.
Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum particularly for patients with chronic illness.
Patients taking anticoagulants orally over the long term have international normalized ratios (INRs) outside the individual therapeutic range more than one-third of the time. Improved anticoagulation control will reduce hemorrhagic and thromboembolic event rates. To gauge the potential effect of improved anticoagulation control, we undertook to determine the proportion of anticoagulant-associated events that occur when INRs are outside the therapeutic range.
We conducted a meta-analysis of all studies that assigned hemorrhagic and thromboembolic events in patients taking anticoagulants to discrete INR ranges. We identified studies using the MEDLINE (1966–2006) and EMBASE (1980–2006) databases. We included studies reported in English if the majority of patients taking oral anticoagulants had an INR range with a lower limit between 1.8 and 2 and an upper limit between 3 and 3.5, and their INR at the time of the hemorrhagic or thromboembolic event was recorded.
The final analysis included results from 45 studies (23 that reported both hemorrhages and thromboemboli; 14 that reported hemorrhages only; and 8, thromboemboli only) involving a median of 208 patients (limits of interquartile range [25th–75th percentile] 131–523 subjects; total n = 71 065). Of these studies, 64% were conducted at community practices; the remainder, at anticoagulation clinics. About 69% of the studies were classed as having moderate or high quality. Overall, 44% (95% confidence interval [CI] 39%–49%) of hemorrhages occurred when INRs were above the therapeutic range, and 48% (95% CI 41%–55%) of thromboemboli took place when below it. The mean proportion of events that occurred while the patient's INR was outside the therapeutic range was greater for studies with a short mean follow-up (< 1 yr). Between-study heterogeneity was significant (p < 0.001).
Improved anticoagulation control could decrease the likelihood of almost half of all anticoagulant-associated adverse events.
Objective To find out how accurately two point of care test
systems—CoaguChek Mini and TAS PT-NC (RapidPointCoag)—display
international normalised ratios (INRs).
Design Comparison of the INRs from the two systems with a
“true” INR on a conventional manual test from the same sample of
Setting 10 European Concerted Action on Anticoagulation centres.
Participants 600 patients on long term dosage of warfarin.
Main outcome measures Comparable results between the different
Results The mean displayed INR differed by 21.3% between the two
point of care test monitoring systems. The INR on one system was 15.2% higher,
on average, than the true INR, but on the other system the INR was 7.1% lower.
The percentage difference between the mean displayed INR and the true INR at
individual centres varied considerably with both systems.
Conclusions Improved international sensitivity index calibration of
point of care test monitors by their manufacturers is needed, and better
methods of quality control of individual instruments by their users are also
The quality control of oral anticoagulant therapy (OAT) during the initiation and maintenance treatment is generally poor. Physicians' ordering of OAT (especially fluindione and warfarin) can be improved by dose adjustment algorithms, taking into account the results of International Normalized Ratio (INR). Reminders at the point of care, computerized or not, have been demonstrated to be effective in changing physicians prescription behavior.
However, few studies have addressed the benefit of personalized reminders versus non personalized reminders, whereas the personalized reminders require more development to access patient record data and integrate with the computerized physician order entry system.
The Hospital Information System of George Pompidou European Hospital integrates an electronic medical record, lab test and drugs order entry system. This system allows to evaluate such reminders and to consider their implementation for routine use as well as the continuous evaluation of their impact on medical practice quality indicators.
The objective of this study is to evaluate the impact of two types of reminders on overtreatment by oral anticoagulant: a simple reminder of text formatted dose adjustment table and a personalized recommendation for oral anticoagulant dose and next date of INR control, adapted to patient data. Both types of reminders appear to the physician at the moment of drug ordering.
The study is an alternating time series experiment with three 6 months periods, each one including every 2 months according to a Latin square scheme: a control period without any reminder, a period with the simple non personalized reminder, a period with personalized reminder. All patients hospitalized in departments using the computerized physician order entry system and ordered fluindione or warfarin, will be included in the study between November 2004 and May 2006.
Main outcome will be the proportion of overcoagulation, as expressed by the proportion of observation time with INR over 4.5, assuming INR change linearly. Secondary outcome is the incidence of major haemorrhagic events. Data will be collected thanks to Hospital Information Systems databases.
Data will be analyzed taking into account patient and physician clustering effect.
Life-long and meticulous control of anticoagulation is mandatory following mechanical valve replacement to prevent thromboembolism. Two patients who underwent mechanical mitral valve replacement with third generation bi-leaflet valves and in whom therapeutic anticoagulation could not be achieved for many months postoperatively form the basis for this report. In the first patient, the target international normalised ratio (INR) of 2.5–3.5 could not be achieved until 53.5 months postoperatively despite good compliance with oral anticoagulation and INR monitoring. In the second patient, the target INR was achieved after 16.9 months of oral anticoagulation treatment and regular INR monitoring. No thromboembolism occurred in either patient; nor did any valve-related event occur. The two patients are in excellent physical health 8 and 5 years, respectively, after the procedure. This unusual phenomenon is reviewed in light of the few reported cases of patients with mechanical heart valves surviving for prolonged periods without anticoagulation.
Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy. The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within the therapeutic target range compared to traditional oral anticoagulant therapy by physicians.
54 patients were randomized equally into 3 groups. Patients in two groups used CoaguChek® systems to measure international normalized ratio (INR) values and had dosages of anticoagulation treatment calculated in a computer system by an algorithm specific to each group. The third group received traditional anticoagulation treatment by physicians. The obtained INR values were compared regarding the time to reach, and the time spent within, the therapeutic target range, corresponding to INR values from 2 to 3.
Patients randomized to computer-assisted anticoagulation and the CoaguChek® system reached the therapeutic target range after 8 days compared to 14 days by prescriptions from physicians (p = 0.04). Time spent in the therapeutic target range did not differ between groups. The median INR value measured throughout the study from all patients by CoaguChek® at 2.5 (2.42–2.62) was lower than measured by a hospital-based Clinical and Biochemical Laboratory at 2.6 (2.45–2.76), (p = 0.02).
The therapeutic target range was reached faster by the use of computer-assisted anticoagulation treatment than prescribed by physicians, and the total time spent within the therapeutic target range was similar. Thus computer-assisted oral anticoagulant therapy may reduce the cost of anticoagulation therapy without lowering the quality. INR values measured by CoaguChek® were reliable compared to measurements by a clinical and biochemical laboratory.
Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR). The development of reliable near patient testing (NPT) systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care.
The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics.
The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.
Oral anticoagulants (OAC) are effective and safe if the international normalized ratio (INR) is maintained within a narrow therapeutic range. Hospitalization is independently associated with poor anticoagulation control. The objective of this study is to describe how anticoagulation control changes in the peri-hospitalization period. This study is a retrospective cohort study using population-based administrative databases. INR results were retrieved from a population-based laboratory database. INR levels between laboratory measures were estimated using linear interpolation. Auto-regressive, integrated, moving average (ARIMA) time-series modeling was used to determine how anticoagulation control changed in the peri-hospitalization period. The study included 5,380 elderly patients in Eastern Ontario between 1 September 1999 and 1 September 2000 taking OACs. Results showed that 951 (17.7%) were hospitalized during their OAC therapy [thrombotic, n = 52 (1.0%); hemorrhagic, n = 140 (2.6%); other hospitalization types, n = 759 (14.1%)]. All measures of anticoagulation control changed significantly in the peri-hospitalization period. Before hemorrhagic admissions, mean INR and proportion with INR > 5 increased significantly (daily increase 0.024, P = .03 and 0.2%, P = .01). Following other hospitalization types, the proportion of patients with INR < 1.5 was significantly increased (daily increase 0.19%, P = .02). Patients admitted to the hospital for a variety of indications have significantly worse anticoagulation control in the peri-hospitalization period. Anticoagulated patients discharged after medical hospitalizations could be targeted for improved anticoagulation control.
anticoagulation; hospitalization; time-series analysis
Maintaining the international normalized ratio (INR) within the therapeutic range in patients on oral anticoagulant treatment is a challenge for the physician. Excessive anticoagulation poses the risk of bleeding in patients. Management strategies vary among clinicians although standard guidelines exist for the same. We conducted an audit in patients on oral anticoagulant therapy in our hospital with excessive anticoagulation. This retrospective study was carried out among patients on oral anticoagulant therapy for various thrombotic conditions with at least a single INR recording of 5 or more. Other than demographic details, the type of oral anticoagulant used, indication, duration of treatment, dosage and concomitant use of interacting drugs or alcohol were also recorded. Detail of the nature and site of bleed and management for the same was also noted. Data were analyzed using descriptive statistics. Fifty episodes with INR ≥ 5 (5.0–10.75) were noted in 44 patients (M:F = 1:1). Their age ranged from 20 to 88 years (mean 50.3 ± 16.4 years). The duration of anticoagulant therapy varied from 3 days to 180 months. Of the 43 episodes in patients who had no bleeding, the anticoagulant was stopped on 32 occasions for variable periods with dose reduction in the rest of the patients. Spontaneous bleeding was seen in seven patients (6 major and 1 minor). Among the seven patients with bleeding, other than stopping he oral anticoagulant drug, other measures taken were vitamin K therapy, fresh frozen plasma or packed red cell transfusion. Overall management strategy of patients with high INR was in compliance with standard recommendations.
Bleeding; International normalized ratio (INR); Management; Oral anticoagulant
Purpose. Monitoring patients' international normalized ratio (INR) within a family medicine setting can be challenging. Novel methods of doing this effectively and in a timely manner are important for patient care. The purpose of this study was to determine the effectiveness of a pharmacist-led point-of-care (POC) INR clinic. Methods. At a community-based academic Family Health Team in Toronto, Canada, charts of patients with atrial fibrillation managed by a pharmacist with usual care (bloodtesting at lab and pharmacist follow up of INR by phone) from February 2008 to April 2008 were compared with charts of patients attending a weekly POC INR clinic from February 2010 to April 2010. Time in therapeutic range (TTR) was measured for both groups. Results. 119 patient charts were reviewed and 114 had TTR calculated. After excluding patients with planned inconsistent Coumadin use (20), such as initiating Coumadin treatment or stopping for a surgical procedure, the mean TTR increased from 64.41% to 77.09% with the implementation of the POC clinic. This was a statistically significant difference of 12.68% (CI: 1.18, 24.18; P = 0.03). Conclusion. A pharmacist-led POC-INR clinic improves control of anticoagulation therapy in patients receiving warfarin and should be considered for implementation in other family medicine settings.
We conducted a feasibility study to monitor coagulation using a point-of-care device (proTime micro coagulation system) in ventricular assist device (VAD) patients. The aim of the study was to compare International Normalized Ratio (INR) readings using a standard laboratory method and proTime micro coagulation device in order to confirm a correlation between these two methods. The nurse's feedback about anticoagulation monitoring using portable anticoagulant monitoring devices in the hospital was also assessed. Four patients admitted in the cardiac surgery unit at University of Maryland, Baltimore were enrolled between 25 November 2006 and 17 January 2006. These patients had given consent to undergo both venous and finger-stick blood samplings to monitor their anticoagulant levels. Six hospital nurses participated in the study. Forty-one INR readings were compared using both methods. Correlation coefficients determined association between INR readings using two methods. All the patients were males and were hypertensive. Significant positive association was seen in the INR readings using two methods (r=0.96; P<0.0001). Four of the six nurses believed patients would be significantly safer if INR is monitored by VAD patients in their homes. Further research needs to be done to determine the impact of home INR monitoring and long-term health in these patients.
Anticoagulation; Ventricular assist device; Portable device; Point-of-care; Nurses
Background: The increase in numbers of patients receiving warfarin treatment has led to the development of alternative models of service delivery for oral anticoagulant monitoring. Patient self management for oral anticoagulation is a model new to the UK. This randomised trial was the first to compare routine primary care management of oral anticoagulation with patient self management.
Aim: To test whether patient self management is as safe, in terms of clinical effectiveness, as primary care management within the UK, as assessed by therapeutic international normalised ratio (INR) control.
Method: Patients receiving warfarin from six general practices who satisfied study entry criteria were eligible to enter the study. Eligible patients were randomised to either intervention (patient self management) or control (routine primary care management) for six months. The intervention comprised two training sessions of one to two hours duration. Patients were allowed to undertake patient self management on successful completion of training. INR testing was undertaken using a Coaguchek device and regular internal/external quality control tests were performed. Patients were advised to perform INR tests every two weeks, or weekly if a dose adjustment was made. Dosage adjustment was undertaken using a simple dosing algorithm.
Results: Seventy eight of 206 (38%) patients were eligible for inclusion and, of these, 35 (45%) declined involvement or withdrew from the study. Altogether, 23 intervention and 26 control patients entered the study. There were no significant differences in INR control (per cent time in range: intervention, 74%; control, 77%). There were no serious adverse events in the intervention group, with one fatal retroperitoneal haemorrhage in the control group. Costs of patient self management were significantly greater than for routine care (£90 v £425/patient/year).
Conclusion: These are the first UK data to demonstrate that patient self management is as safe as primary care management for a selected population. Further studies are needed to elucidate whether this model of care is suitable for a larger population.
oral anticoagulation; patient self management; primary care
Background and objectives
The number of patients treated with oral anticoagulation (OAC) is increasing and these patients are monitored by International Normalized Ratio (INR). Bleeding complications are common and we speculate if this is related to the limitation of INR only reflecting the initiation steps of the haemostatic process. The objective of the present review was to reassess the evidence for using INR as a tool to guide administration of prothrombin complex concentrates (PCC) to OAC patients. A Medline and Cochrane database search was conducted using the following keywords: prothrombin complex concentrate, reversal of oral anticoagulation and international normalized ratio (INR). Thirty-three articles were contracted and a total of ten studies were eligible after applying inclusion and exclusion criteria encompassing only 339 patients. No consensus regarding optimal target INR value to aim for when reversing OAC was found. In three of the studies it was reported that patients reaching their target INR continued to bleed, whereas three studies reviewed reported good haemostatic response also in patients that did not reach their target INR. The present review found limited evidence for the usefulness of INR as a tool to monitor and guide reversal of OAC induced coagulopathy in patients with PCC, which is expected given that it is a plasma-based assay only reflecting a limited part of the haemostatic process.
INR; PCC; OAC; Anticoagulation reversal; Haemostatic efficacy
The effectiveness of the Birmingham model of primary care oral anticoagulation management has previously been demonstrated within a randomised controlled trial. The aim of this study was to assess the effectiveness of the Birmingham model in routine care. All patients from 12 primary care centres attending either practice-based or hospital-based anticoagulation clinics were retrospectively followed up from October 1996 to March 1998. Outcome measures were therapeutic International Normalised Ratio (INR) control, haemorrhagic and thrombotic episodes, and recall frequency; 452 patients who had two or more INR results during the follow-up period were investigated. There were no significant differences between practice-based and hospital-based populations in terms of the percentage time in range, (69% and 64% respectively). The proportion of tests in range was significantly higher in the practice-based group (61% practice-based, 57% hospital-based; P = 0.015). There was no difference between the two populations in terms of mean follow-up time (36 days in each group). There were no significant differences between groups for the number of clinical outcomes per patient. This study confirmed that, within these practices, oral anticoagulation management is safe and effective using the Birmingham model.
Self management of anticoagulation: a randomised trial (SMART) was the first large scale UK trial to assess clinical and cost effectiveness of patient self management (PSM) of oral anticoagulation therapy compared to routine care. SMART showed that while PSM was as clinically effective as routine care, it was not as cost effective. SMART adds to the growing body of trial data to support PSM; however there are no data on clinical effectiveness and cost of PSM in routine care.
To evaluate clinical effectiveness of PSM compared to routine care outside trial conditions.
A retrospective multicentre matched control study. 63 PSM patients from primary care in the West Midlands were matched by age and international normalised ratio (INR) target with controls. INR results were collected for the period 1 July 2003–30 June 2004. The primary outcome measure was INR control.
38 PSM and 40 control patients were recruited. INR percentage time in range was 70% PSM vs 64% controls. 60% PSM were having a regular clinical review, 45% were performing an internal quality control (IQC) test and 82% were performing external quality assurance (EQA) on a regular basis.
PSM outside trial conditions is as clinically effective as routine UK care.
Oral anticoagulant therapy (OAT) is used to prevent/treat thromboembolism. Major bleeding is common in patients on OAT; eg, warfarin increases intracranial hemorrhage (ICH) risk.
A 71-year-old male on warfarin (to reduce stroke risk) presented at Accident and Emergency Minor Injuries Unit with headache after reportedly sounding ‘drunk’. On triage, the patient appeared lucid and well. However, International Normalized Ratio (INR) was 4.1. Head computed tomography (CT) indicated a large right-sided subdural hematoma. Prothrombin complex concentrate (PCC; Beriplex® P/N, CSL Behring) with vitamin K normalized the INR within minutes of administration. The patient underwent neurosurgery without complications, and was discharged after 5 days, with no residual neurological symptoms.
ICH patients can present with no neurological signs. In OAT patients with headache, INR must be established; if ≥3.0, normalization of INR and head CT are essential. PCC is the best option to rapidly reverse anticoagulation and correct INR pre-surgery.
anticoagulation reversal; Beriplex® P/N; computed tomography; International Normalized Ratio; intracranial hemorrhage; prothrombin complex concentrate
Increasing the predictability and reducing the rate of side effects of oral anticoagulant treatment (OAT) requires further clarification of the cause of about 50% of the interindividual variability of OAT response that is currently unaccounted for. We explore numerically the hypothesis that the effect of the interindividual expression variability of coagulation proteins, which does not usually result in a variability of the coagulation times in untreated subjects, is unmasked by OAT.
We developed a stochastic variant of the Hockin-Mann model of the tissue factor coagulation pathway, using literature data for the variability of coagulation protein levels in the blood of normal subjects. We simulated in vitro coagulation and estimated the Prothrombin Time and the INR across a model population. In a model of untreated subjects a "canalization effect" can be observed in that a coefficient of variation of up to 33% of each protein level results in a simulated INR of 1 with a clinically irrelevant dispersion of 0.12. When the mean and the standard deviation of vitamin-K dependent protein levels were reduced by 80%, corresponding to the usual Warfarin treatment intensity, the simulated INR was 2.98 ± 0.48, a clinically relevant dispersion, corresponding to a reduction of the canalization effect.
Then we combined the Hockin-Mann stochastic model with our previously published model of population response to Warfarin, that takes into account the genetical and the phenotypical variability of Warfarin pharmacokinetics and pharmacodynamics. We used the combined model to evaluate the coagulation protein variability effect on the variability of the Warfarin dose required to reach an INR target of 2.5. The dose variance when removing the coagulation protein variability was 30% lower. The dose was mostly related to the pretreatment levels of factors VII, X, and the tissue factor pathway inhibitor (TFPI).
It may be worth exploring in experimental studies whether the pretreatment levels of coagulation proteins, in particular VII, X and TFPI, are predictors of the individual warfarin dose, even though, maybe due to a canalization-type effect, their effect on the INR variance in untreated subjects appears low.
Interindividual variability; stochastic model; oral anticoagulant treatment; INR; coagulation cascade; canalization
Objectives: To assess the long term efficacy of and risks associated with computer aided oral anticoagulation for non-rheumatic atrial fibrillation (NRAF) in a district hospital setting.
Design: Retrospective, age stratified, event driven clinical database analysis.
Setting: District general hospital.
Participants: 739 patients receiving warfarin for NRAF between 1996 and 2001. Patients were selected from an anticoagulation database through appropriate filter settings.
Main outcome measures: Anticoagulation control (international normalised ratio (INR)) and hospitalisations for bleeding complications, thromboembolic events, and stroke.
Results: Over 1484 patient-years, computer assisted anticoagulation was uncontrolled in 38.3% of patients (INR < 2.0 or > 3.0). No significant differences in INR control were observed with respect to patient age (< 65, 65–75, and > 75 years), although to achieve adequate control of anticoagulation, the frequency of testing increased significantly with age. Annual risks of bleeding complications, thromboembolism, and stroke were 0.76%, 0.35%, and 0.84%, respectively. No significant differences in these events were observed between the three age groups studied. Patients who had thromboembolic events and haemorrhagic complications were significantly more likely to have been under-anticoagulated (INR < 2.0) and over-anticoagulated (INR > 3.0), respectively, at the time of their clinical event.
Conclusions: Computerised long term oral anticoagulation for NRAF in a community setting of elderly and diverse patients is safe and effective. Anticoagulation control, bleeding events, thromboembolic episodes, and stroke rates are directly comparable with those reported in major clinical trials. The authors therefore support the strategy of rate control with long term oral anticoagulation for NRAF in general clinical practice.
atrial fibrillation; warfarin; long term oral anticoagulation
To investigate the effectiveness of patient self-management (PSM) of anticoagulation using warfarin in a typical primary care site in Canada and to determine the feasibility of conducting a future large-scale trial in this setting.
An 8-month pragmatic open-label randomized crossover trial.
A typical Canadian primary care practice in British Columbia.
Patients were randomized to PSM or physician management for 4 months, after which allocation was reversed. The PSM group members were instructed to monitor their serum international normalized ratio (INR) at community laboratories and to adjust their warfarin doses independently using provided nomograms. Education on warfarin dose adjustment was limited to a single 15-minute office visit.
Main outcome measures
The primary outcome was the proportion of INR values in the therapeutic range among participants. Feasibility outcomes included proportion of eligible patients consenting, patients’ preference of management strategy, patients’ satisfaction, and visits or phone communication with physicians regarding dose adjustment. Safety outcomes included bleeding or thromboembolic events.
Eleven patients completed the trial, contributing 99 patient-months of monitoring and providing 122 INR measures. The mean proportion of INR values in therapeutic range among subjects in the PSM and physician-management groups was 82% and 80%, respectively (P = .82). The improvement in patient satisfaction with PSM was not significant. Ten of the 11 patients preferred PSM to physician management and elected to continue with this strategy after study completion (P = .001). No calls or visits were made to the physician regarding dose adjustment during the PSM period. There were no episodes of major bleeding or thromboembolic events.
Patient self-management was not demonstrated to be superior to standard care, but was easily implemented and was the method preferred by patients. Our feasibility outcomes justify a larger trial and suggest that subject recruitment and protocol adherence would not pose barriers for such a study.
Trial registration number