INR comparison between the CoaguChek Pro PT(N) and a standard laboratory method

BACKGROUND: The prothrombin time (PT), also called thromboplastin time ("Quick"), is usually measured using citrated plasma from venous blood. Recently, portable coagulation monitors have been developed, which measure PT using non-anticoagulant capillary whole blood from a finger stick. In the present study, we compared the International Normalized Ratio (INR) of the standard laboratory method (INRven) with the newly developed reagent PT(N) for the CoaguChek Pro portable monitor (INRcap) in various patient groups: healthy individuals, patients with oral anticoagulation and patients with a deficiency of coagulation factor V, factor VII or factor X, respectively. METHODS: One hundred and fifty-five patients were included in this prospective open comparison study. Capillary PT was measured with the portable coagulation monitor CoaguChek Pro using the new disposable cartridge PT(N) (containing rabbit brain thromboplastin). In comparison, PT was measured using citrated venous plasma and the reagent Innovin on the coagulation analyzer STA-R. RESULTS: We found a correlation coefficient of 0.85 between capillary and venous INR values among the 100 patients with oral anticoagulation. The slope of the regression line was 1.4 and the y-intercept is -0.65. Agreement between both methods was found to be 80% (95% CI: 72-88%) and the standard-agreement was 85% (95% CI: 78-92%). Among the 30 healthy subjects, the individual differences between INRven and INRcap were in 4 cases 0, in 21 cases 0.1 and in 5 cases 0.2. CONCLUSION: The new test cartridge PT(N) was found to be a valuable tool for measuring PT among healthy subjects. However, among patients with oral anticoagulation, agreement between INRcap measured with the new cartridge PT(N) and INRven was only moderate. Our results show that improvements are necessary for a more valuable measurement of capillary PT with portable coagulation monitors.     

Precision of INR measured with a patient operated whole blood coagulometer

INTRODUCTION: The objective of the present study was to evaluate the precision of a portable whole blood coagulometer (CoaguChek S) in the hands of self-managing patients on oral anticoagulant therapy (OAT). MATERIALS AND METHODS: Fifteen patients on self-managed OAT performed measurements of INR by two types of portable whole blood coagulometers (CoaguChek and CoaguChek S) at home for 10 weeks. RESULTS: The coefficient of variation (CV) of INRs determined at home by CoaguChek S by patients on self-managed OAT was 5.5% (95% confidence limits: 4.9%, 6.1%). The biological CV of INR within and between patients was 15.0% and 14.7%, respectively. CONCLUSION: The precision of CoaguChek S is satisfactory.     

INR comparison between the CoaguChek S and a standard laboratory method among patients with self-management of oral anticoagulation

INTRODUCTION: Portable coagulation monitors have been developed to measure International Normalised Ratio (INR) in orally anticoagulated patients using capillary whole blood from a finger stick. Because of unsatisfactory precision of some of the monitors in comparison with laboratory methods new devices are being developed. In the present study we compared INR determination with the CoaguChek S device with a standard laboratory method among patients with self-management of oral anticoagulation (OAC). METHODS: Two hundred and forty-two patients performing self-management of OAC were enrolled into this study. Parallel INR measurements were performed within one hour. Capillary INR measurements (INRcap) were done by the patients with the CoaguChek S and venous INR (INRven) by qualified medical staff using a standard laboratory method. RESULTS: We found a correlation coefficient (r(S)) of 0.85 (95% CI: 0.81-0.88) among the 242 patients between INRven and INRcap. In 84.4% of the INR parallel measurements the difference between the two values was below 0.5 INR units. In only 2 of 242 cases the difference was >1 INR unit (1.1 and 1.3). The slope of the Passing Bablok regression line was 0.91 (95% CI: 0.83-1.0) and the y-intercept 0.06 (95% CI: -0.20-0.25). Agreement between both methods was 90.5% (95% CI: 86.8-94.2) and standard-agreement even 97.1% (95% CI: 95-99.2). CONCLUSIONS: INR measurement with CoaguChek S device by trained patients revealed reliable results in comparison to the values obtained with a standard laboratory method.     

Comparison between CoaguChek S- and Owren-type prothrombin time assay for monitoring anticoagulant therapy

INTRODUCTION: Anticoagulation therapy with warfarin is monitored by the prothrombin time (PT) assay. The PT is standardized using international normalized ratios (INRs). By keeping the INR within specific values, it is possible to reduce potential complications from the treatment. To facilitate the PT monitoring, point-of-care devices suitable for capillary whole blood measurements have been developed. The aims of this study were to compare the INR values obtained by such a device, CoaguChek S, with those obtained from the Owren-type PT assay and to evaluate the differences seen. MATERIALS AND METHODS: In 351 consecutive warfarin-treated patients, INR was measured in capillary whole blood samples with CoaguChek S and was compared to venous plasma samples analyzed with the Owren PT method. Sixty-nine of these patients, including those deviating the most between the methods, were further evaluated according to levels of factor II (prothrombin), factor V, factor VII, factor X, fibrinogen, activated partial thromboplastin time (aPTT) and antiphospholipid antibodies. RESULTS: The results from CoaguChek S produced a correlation coefficient of 0.81 to the Owren-type PT assay and a concordance of 85.2%. Factor V and fibrinogen correlated significantly (p<0.05) to the degree of deviation between the methods. The presence of antiphospholipid antibodies did not influence the degree of deviation between the two methods. CONCLUSIONS: INR analysis of whole blood with CoaguChek S is comparable with INR measured in plasma with Owren chemistry. The activities of factor V and fibrinogen contribute to the deviation seen between the methods. Differences in sensitivity to antiphospholipid antibodies could not be demonstrated.     

Home INR monitoring of oral anticoagulant therapy in children using the CoaguChek S point-of-care monitor and a robust education program

INTRODUCTION: Management strategies such as self-monitoring of anticoagulant therapy have been reported with increased frequency. Whilst patient education is frequently mentioned, details regarding the educational interventions employed are scarce. This study aimed to improve the outcomes of home monitoring of warfarin therapy in children through the development and implementation of a robust intervention, based upon the PRECEDE model of education. MATERIALS AND METHODS: Participating parents had to complete an intensive education and training program. After demonstrating practical and theoretical competency, parents commenced home monitoring. Every second scheduled home INR (H-INR) required a paired INR on the same day, obtained by a trained pathology collector (C-INR). Demographic and statistical outcome data was collected. RESULTS: Parental understanding of warfarin therapy improved significantly following the educational intervention (p<0.0001). 65.5% of H-INRs and 64.4% of C-INRs were within the target range (ns). Lin's correlation coefficient between H-INRs and C-INRs was 0.949. There were no warfarin-related adverse events. CONCLUSION: This study demonstrated a significant improvement in parental knowledge following participation in a robust educational intervention. Furthermore, compared to previous reports in children, a greater level of correlation between home and hospital-based INRs was achieved by participating parents. The use of similar educational interventions may serve to improve the outcomes of similar management strategies.     

Use of INR calibrator plasmas in the routine coagulation laboratory: A study of two thrombolastin reagents

INR values may be either calculated with the ISI values supplied by thromboplastin manufacturers or are directly extrapolated from certified INR calibrator plasmas. We tested the principle of local INR calibration using INR calibrator plasmas (PT-Multi Calibrator, Siemens), two thromboplastin reagents (Neoplastin Plus, rabbit brain, Stago, coagulometer-specific ISI 1.31, and Innovin, recombinant human tissue factor, Siemens) and the same coagulometer (STA-R, Stago) in 100 patients on warfarin. Using a ISI value of 0.77 with Tomenson correction for Innovin (correction factor=1.09), INR values of patients were similar with the two reagents, with a bias of 0.03 INR units and no significant regression of the difference over the average INR by method comparison analysis. With the INR calibrator plasmas, INR values with Neoplastin Plus were lower than Innovin values with an average bias of 0.39 INR units and a significant regression of the difference over the average INR (r=-0.91). Significant bias (0.16 INR units, p<0.00001) and regression (r=-0.77) was also observed by comparison of Neoplastin Plus INRs with Innovin calibrated INRs. Based on a therapeutic INR interval of 2.0 to 3.5, discordance in warfarin dosing was approximately 3 times higher with INR calibration (27% vs 11%). Because of non commutability with fresh plasma samples, local INR calibration with lyophilized calibrator plasmas may not be valid for some reagent-instrument combinations.     

Comparison and evaluation of a Point-of-care device (CoaguChek XS) to Owren-type prothrombin time assay for monitoring of oral anticoagulant therapy with warfarin

Background

The standardized test used for evaluating the effect of warfarin is the prothrombin time (PT) which is measured and expressed in international normalized ratio (INR). Regular control of treatment intensity is required since inappropriate dosage increases the risk for complications. Portable point-of-care analytical instruments for measurement of capillary whole blood PT have been available for the last decades. The purpose of this study was to compare and evaluate INR values obtained by the point-of-care device CoaguChek XS, to Owren PT in a hospital setting.

Materials and Methods

In 397 warfarin-treated patients, capillary whole blood was analyzed with the CoaguChek XS and the results were compared to analysis of venous plasma samples with the Owren PT assay. To study reproducibility and rule out preanalytical errors, a subgroup of 152 patients had two capillary blood samples analyzed with the CoaguChek XS.

Results

In 397 patients, with a median age(±2SD) of 69.0(50-88) years, there was a positive correlation between results from the CoaguChek XS and the Owren-type PT assay (r = 0.94;p < 0.001) and concordance of 88.2%. The mean INR difference (S.D) was 0.02 (0.22). Comparison of the 152 double samples analyzed with the CoaguChek XS, produced a positive correlation of 0.99; p < 0.001.

Conclusions

The CoaguChek XS presents reproducible, highly comparable results with Owren PT at therapeutic levels of INR. The CoaguChek XS seems to produce better results than the earlier CoaguChek S, probably due to a new method of PT measurement where levels of fibrinogen and haematocrit do not affect the outcome.     

Biological variation of INR in stable patients on long-term anticoagulation with warfarin

Within-individual biological variation of INR (CV_B) was assessed in 245 selected stable warfarin-treated patients monitored by three thrombosis centers. Selection criteria were: treatment period of six months or longer before the observation period; at least six consecutive INRs within the therapeutic range of 2.0 - 3.0; interval between consecutive INR measurements of two weeks or longer; no change in warfarin dose; no changes in the patient's circumstances which may influence the INR, such as intercurrent diseases, invasive procedures, starting or stopping drugs interacting with warfarin. The minimum, maximum and mean within-individual coefficient of variation CV_B of the INR measurements in the 245 selected patients were 0.4%, 14.5%, and 9.0%, respectively Analytical performance goals for the INR measurement (imprecision) could be derived from the mean CV_B. For a therapeutic range of 2.0 - 3.0 with warfarin, the desirable and optimum imprecision of INR determination is < 4.5% CV and < 2.25% CV, respectively. The biological variation and analytical performance goals have been derived using classic laboratory methods but should be applicable to point-of-care testing as well.     

Level of agreement between laboratory and point-of-care prothrombin time before and after cardiopulmonary bypass in cardiac surgery

Background

Hemostasis monitoring in cardiac surgery could benefit from an easy to use and fast point-of-care coagulation monitor, since routine laboratory tests have a delay of 30–45 minutes. This study investigated the level of agreement between the point-of-care prothrombin time (PT) with central laboratory PT before and after cardiopulmonary bypass.

Methods

Bland Altman and error grid analysis were used to analyze the agreement between the point-of-care Coaguchek XS Pro device (POC-PT) and the central laboratory prothrombin time (LAB-PT) before cardiopulmonary bypass (CPB) and 3 minutes after protamine administration. Prothrombin times were expressed in international normalized ratios (INR).

Results

The average POC-PT and LAB-PT values of 73 patients were 1.06 ± 0.14 and 1.09 ± 0.13 (P = 0.10) before CPB. POC-PT measurements before CPB showed a good agreement with the LAB-PT, with a bias of − 0.02 ± 0.07 INR and 94% of the values being represented in the clinical acceptable zone of error grid analysis. The mean POC-PT 3 minutes after protamine administration was significantly lower than the LAB-PT (1.35 ± 0.12 vs. 1.70 ± 0.18; P < 0.001). The PT at 3 minutes after protamine administration showed a bias of 0.36 ± 0.14, and 82% of the values were located outside of the clinical acceptable zone in the error grid analysis.

Conclusions

Point-of-care prothrombin time testing was in concordance with conventional laboratory PT prior to cardiopulmonary bypass. At 3 minutes following protamine administration, PT values of the point-of-care device were structurally lower than the laboratory PT values, leading to a disagreement between both tests at that time point.     

Effect of magnesium contamination in evacuated blood collection tubes on the prothrombin time test and ISI calibration using recombinant human thromboplastin and different types of coagulometer

The purpose of the present study was to assess the effect of two types of evacuated blood collection tube on the prothrombin time and international sensitivity index (ISI) of Recombiplastin, a recombinant human thromboplastin. Vacutainer tubes were compared with Venoject II tubes. Magnesium contamination was detected in the sodium citrate solutions contained in the Vacutainer tubes with concentrations ranging from 1.1 to 1.5 mmol/l. In contrast, magnesium ions could not be detected in the Venoject II tubes. The prothrombin ratio was decreased by contamination with magnesium ions and, hence, the ISI was increased. The magnitude of the effect of magnesium contamination on the ISI was influenced by the type of coagulometer and increased in the order: ACL Advance (3%), ACL-300 (4%), Electra-1000 (6%). The ISI bias is transmitted to the international normalized ratio (INR). In the case of the Electra-1000, the INR bias would be approximately 6% at INR 3.0 if the two types of blood collection tubes would be used without distinction. In a secondary study, the effect of magnesium contamination on the prothrombin time was assessed with the current World Health Organization international reference preparation for recombinant human thromboplastin (rTF/95). Magnesium chloride added to patients' blood (0.2 mmol/l) induced 2.3% reduction of the INR determined with rTF/95 and the manual technique. CONCLUSION: The magnitude of the influence of blood collection tubes contaminated with magnesium on ISI and INR determined with recombinant human thromboplastin depends on the coagulometer.     

Warfarin treatment in patients with atrial fibrillation: Observing outcomes associated with varying levels of INR control

Introduction

We aimed to determine the level of INR control associated with reduced stroke and mortality.

Material and methods

The study used a retrospective cohort design using linked inpatient, haematology and mortality data from Cardiff and the Vale of Glamorgan, UK.Anonymised patients admitted with a diagnosis of non-valvular atrial fibrillation (NVAF) were defined as warfarin or non-warfarin treated by number of repeated International Normalised Ratio (INR) tests. Warfarin treated patients (> 5 INR tests) categorised as at moderate or high risk of stroke (CHADS₂ score ≥ 2) with varying levels of INR control were compared to those who did not receive warfarin treatment using Cox proportional hazards models controlling for age, sex and CHADS₂ score. Outcome measures were time to stroke and mortality.

Results

6,108 patients with NVAF were identified. 2,235 (36.6%) of these patients had five or more INR readings and of these 486 (21.7%) had CHADS₂ score ≥ 2. There was significant improvement in time to stroke event in those patients with INR control of greater than 70% of time in therapeutic range (2.0 to 3.0) compared with the non-warfarin treatment group. Overall survival was significantly improved for all warfarin treated groups with INR control of greater than 40% of time in range.

Conclusions

Patients with INR control of above 70% of time in range had a significantly reduced risk of stroke. Patient suitability for warfarin treatment should be continuously assessed based on their ability to maintain a consistently therapeutic INR.     

Interpretation and management of INR results: A case history based survey in 13 countries

Introduction

Standardisation of treatment with vitamin K antagonists (VKAs) is still an issue after 60 years of use. The study aimed to explore aspects of VKA monitoring in primary and secondary care.

Methods

Two case histories were distributed to physicians in 13 countries. Case history A focused on a patient with atrial fibrillation on stable anticoagulation (latest INR 2.3). Physicians were asked about frequency of INR measurement, when to change the VKA dose, and the patient's annual risk of ischemic stroke and bleeding. Case history B focused on a patient with an unexpected INR of 4.8, asking for the patient's 48-hour bleeding risk, the immediate dose reduction and time until a repeat INR.

Results

Altogether, 3016 physicians responded (response rate 8 - 38%), of which 82% were from primary care and 18% from secondary care. Answers varied substantially within and between countries regardless of level of care and VKA used. Median number of weeks between INR measurements was 4 - 6 weeks. Median threshold INR for increasing or decreasing the VKA dose was 1.9 and 3.1, respectively. Risk of ischemic stroke and bleeding were overestimated 2 - 3 times. In case history B, the median dose reduction the two first days was 75% for GPs and 55% for specialists, irrespective of estimates of bleeding risk; with one week to a repeat INR.

Conclusion

Variation in VKA monitoring is substantial implying clinical consequences. Guidelines seem either unknown or may be considered impracticable. Further efforts towards standardisation of VKA management are needed.     

Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal

INTRODUCTION: Patients with nonvalvular atrial fibrillation are at increased risk for systemic embolism, predominantly disabling stroke. To study how stroke and mortality rates vary with different degrees of anticoagulation reflected by the international normalised ratio (INR) we critically assess information from different sources. MATERIALS AND METHODS: 1. Computerized search of the medical literature published between 1980 and July 2004 was performed using MEDLINE applied to various combinations of the search terms of atrial fibrillation, warfarin, anticoagulation, anticoagulation intensity, and INR, not restricted by language. 2. We performed a record linkage analysis with death hazard estimated as a continuous function of INR based on 21,967 patients. Similarly the risk of admission to hospital or death due to diseases of the vessels of the brain was estimated. 3. Re-analysis of data earlier published by Hylek et al. from year 2003.RESULTS AND CONCLUSIONS: 1. One randomised study showed a significantly lower risk of stroke for mean INR 2.4 compared to mean INR 1.3 combined with aspirin. Remaining studies found INRs of 2-2.5 to be as efficacious as higher anticoagulation intensities.2. Mortality as well as risk of admission to hospital or death due to diseases of the vessels of the brain followed U-shaped curves with minimum at INR 2.2 and 2.4, respectively. At high INR the risk increased 2.3 times per 1 unit increase of INR for death and 1.7 times for events in the vessels of the brain.3. The re-analysing of data of Hylek et al. indicated that there might be a substantial increase of the risk of intracranial hemorrhage when INR is increased from 2.5 to 4.We conclude that INRs in the interval 2.0--2.5 give the lowest risk of stroke and death in patients with nonvalvular atrial fibrillation.     

青年脑梗死与凝血酶原G20210A突变关系的研究

目的 研究青年脑梗死与凝血酶原G20210A基因突变的关系。方法 采用聚合酶链反应(PCR)及限制性内切酶技术，研究40例青年脑梗死患者及48例对照者凝血酶原G20210A基因突变频率。结果 所有受检者均未发现凝血酶原G20210A基因突变。结论 凝血酶原G20210A基因突变不是本组青年脑梗死的危险因素。     

Single-dose adjustment versus no adjustment of warfarin in stably anticoagulated patients with an occasional international normalized ratio (INR) out of range

Background

Well-controlled patients on warfarin may still have occasional International Normalized Ratios (INRs) outside the therapeutic range. It is unclear whether there is any benefit of a single-dose correction in this situation.

Aim

To evaluate whether patients with very stable INR results should continue with the maintenance dose of warfarin without a single-dose correction, even when the result unexpectedly is moderately below or above the therapeutic range.

Methods

A) We reviewed retrospectively 364 patients with unchanged maintenance dose for at least 6 months and an occasional INR outside the therapeutic range regarding decision on dosing and the effect on the next INR. B) We randomized 160 patients with at least 3 months of unchanged maintenance dose, an occasional INR deviating to a minimum of 1.5 or a maximum of 4.4 and unexplained or temporary, removable cause to a single-dose Change or No change. Follow-up INRs and telephone interviews were obtained after 2 weeks.

Results

A) Retrospectively, the proportion of follow-up INRs outside the therapeutic range was 29.9% after No change, 27.1% after Increased dose and 25.7% after Skipped/reduced dose. However, the decision on No change was mainly taken in case of minimal INR deviations. B) Forty-eight (60%) of the patients randomized to Change were within the therapeutic range at follow-up versus 45 (56%) of those with No change, odds ratio 1.17 (95% confidence interval 0.59-2.30). For baseline INRs deviating down to 1.6 or up to 3.6 (therapeutic range, INR 2.0-3.0) the 2-week INRs did not differ between the groups.

Conclusion

Our results suggest only a small or no difference between the two managements of an occasional INR out of range in terms of the 2-week follow-up INR. In stable patients on warfarin with an occasional INR outside the therapeutic range it seems reasonable to continue with the same dose without a single-dose change and perform a repeat test in about 2 weeks. (ClinicalTrials.gov number, NCT00814177.)     

Prothrombin, thrombin and prothrombin fragments in plasma of normal individuals and of patients with laboratory evidence of disseminated intravascular coagulation

With specific immunoassays for prothrombin, thrombin-anti-thrombin-III complex and for prethrombin-1 antigen, we measured the levels of these proteins in the plasma of normal individuals and patients suspected of having chronic disseminated intravascular coagulation (DIC). The normal level of prothrombin in plasma was found to be 110–212 mg/liter, and of thrombin-anti-thrombin-III complex and prethrombin-1 antigen approximately 1 μg/ml. In patients with suspected DIC, prothrombin levels, as measured by immunoassay and two-stage clotting assay, were decreased in 14 of 19 studied. Levels of thrombin-anti-thrombin-III complex were normal in all the patients and those of prethrombin-1 elevated in only two of 19. The lack of elevation of these products is probably due to the small amount of prothrombin activated in these patients. Decreased synthesis may account for the low levels of prothrombin observed in some. Measurement of the level of these products of prothrombin is therefore not useful in the diagnosis and management of patients with DIC.     

Quality of individual INR control and the risk of stroke and bleeding events in atrial fibrillation patients: a nested case control analysis of the ACTIVE W study

Introduction

Time in therapeutic range (TTR) for international normalized ratio (INR) is an accepted quality measure of anticoagulation control in patient populations, but its usefulness for predicting stroke and bleeding in individuals is not well understood.

Materials and Methods

In a nested case control analysis among ACTIVE W study patients, cases with stroke and cases with bleeding were separately matched with controls. Several anticoagulation quality measures were compared, overall and in a time-dependent manner.

Results

32 cases with ischemic stroke and 234 cases with bleeding in the analysis were matched in a 4:1 ratio to 122 and 865 controls, respectively. Follow-up duration was 257 ± 154 days for the stroke analysis and 222 ± 146 days for the bleeding analysis. Compared with their respective controls, the study mean TTR of both stroke cases (53.9% ± 25.1 vs 63.4% ± 24.8; p = 0.055) and bleeding cases (56.2% ± 25.4 vs 63.4% ± 26.8; p < 0.001) was lower. Time below range for stroke and time above range for bleeding were only greater in the last month leading up to the event, not over the entire study period. Rather, over the entire study period bleeding cases spent more time below range than controls (26.8% ± 25.9 vs 20.8% ± 24.0; p = 0.001).

Conclusions

TTR was lower in individual AF patients with stroke or bleeding compared with matched controls in ACTIVE W. Maintaining a high TTR, with equal importance to avoid low and high INRs, is a relevant goal of individual patient treatment to prevent stroke and bleeding.     

新疆维吾尔族胶质瘤中ATM及PTEN蛋白的表达与临床意义

目的探讨新疆维吾尔族(维族)胶质瘤中ATM及PTEN蛋白的表达与临床意义。方法运用免疫组化法检测50例新疆维族胶质瘤中ATM及PTEN蛋白的表达,同时以20例胶质瘤旁组织作为对照,分析其表达的差异及其表达与胶质瘤临床病理特征、患者生存期之间的关系。结果 (1)新疆维族胶质瘤和胶质瘤旁组织中ATM蛋白表达的阳性率分别为60%(30/50)和10%(2/20);PTEN蛋白表达的阳性率分别为30%(15/50)和75%(15/20);(2)ATM及PTEN蛋白表达在胶质瘤和胶质瘤旁组织中的表达差异有统计学意义(均P<0.001);(3)ATM蛋白及PTEN蛋白在WHO分级、不同生存期各组中表达的差异均有统计学意义(均P<0.05),在临床表现、性别、肿瘤大小、肿瘤部位、是否复发各组之间的差异均无统计学意义(均P>0.05)。结论 (1)ATM及PTEN蛋白在新疆维族胶质瘤中及胶质瘤旁组织中表达有差异,表明ATM及PTEN蛋白在胶质瘤发生发展中可能起到一定作用;(2)新疆维族胶质瘤中ATM及PTEN蛋白均与WHO分级和不同生存期表达相关,提示ATM及PTEN蛋白可作为判定胶质瘤生物学行为和预后判断的参考指标。     

Impact of short periods with worsened or improved INR control on life expectancy and QALYs in patients with atrial fibrillation

Introduction

Warfarin-treated patients with poor international normalized ratio (INR) control, measured with time in therapeutic range (TTR) or the standard deviation of transformed INR (SDT_INR), have an increased risk for clinical events. To what extent only a short period with an altered INR control may influence outcomes remains unknown. This study assessed the impact of transient periods of worsened or improved INR control on life expectancy and quality-adjusted life years (QALYs) among warfarin-treated patients with atrial fibrillation (AF) using both metrics.

Materials and methods

Warfarin-treated patients with AF, registered in the patient record system Journalia during years 1985–2000, were included. Information on all-cause mortality was collected from the Cause of Death Register. Hypothetical scenarios where patients were assumed to have a transiently altered INR control during 30 days were modeled statistically using hazard functions, and the impact on remaining life expectancy and QALYs was assessed.

Results

When using SDT_INR, a 70-year old man within the 20th best INR control percentile was estimated to lose 7.4 days of life or 0.0100 QALYs from a 30-day long worsened INR control to that of an average 70-year old male patient. Correspondingly, 4.0 days of life or 0.0059 QALYs would be gained if a 70-year old man within the 20th worst INR control percentile would have an average INR control during 30 days. The magnitudes were smaller when TTR was used to determine INR control.

Conclusions

Even short periods of an altered INR control is expected to have impact on life expectancy and QALYs among patients with AF.