Subtherapeutic Anticoagulation Control under Treatment with Vitamin K-Antagonists—Data from a Specialized Coagulation Service

2019 ◽  
Vol 119 (08) ◽  
pp. 1347-1357 ◽  
Author(s):  
Jürgen H. Prochaska ◽  
Christoph Hausner ◽  
Markus Nagler ◽  
Sebastian Göbel ◽  
Lisa Eggebrecht ◽  
...  

AbstractIn contrast to overanticoagulation, evidence on risk factors and outcome of subtherapeutic oral anticoagulation (OAC) with vitamin K-antagonists (VKAs) under optimum care is limited. We investigated the clinical phenotype, anticoagulation control, and clinical outcome of 760 VKA patients who received OAC therapy by a specialized coagulation service in the thrombEVAL study (NCT01809015). During 281,934 treatment days, 278 patients experience ≥ 1 episode of subtherapeutic anticoagulation control and had lower quality of OAC therapy compared to 482 patients without subtherapeutic international normalized ratio: 67.6%, interquartile range (IQR) 54.9%/76.8% versus 81.0%, IQR 68.5%/90.4%; p < 0.001. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, and treatment characteristics, female sex (hazard ratio [HR], 1.4, 95% confidence interval [CI], 1.0/1.9; p = 0.03), diabetes (HR, 1.4, 95% CI, 1.0/2.0; p = 0.03), and living alone (HR, 1.5, 95% CI, 1.1/2.1; p = 0.009) were independent risk factors of subtherapeutic anticoagulation control, whereas atrial fibrillation (HR, 0.6, 95% CI, 0.4/0.9; p = 0.02) and self-management of OAC therapy (HR, 0.2, 95% CI, 0.1/0.6; p = 0.001) were protective. In addition, active smoking (HR, 1.7, 95% CI, 0.9/3.0; p = 0.086) and living in a nursing home (HR, 1.6, 95% CI, 0.8/3.2; p = 0.15) indicated an elevated risk at the borderline of statistical significance. For the prediction of recurrent subtherapeutic anticoagulation, living alone was the only independent risk factor (HR, 1.7, 95% CI, 1.1/2.5; p = 0.013). The present study suggests that women, diabetics, and patients living alone experience an increased risk of low-quality VKA therapy and might potentially benefit from treatment with direct-acting anticoagulants.

Author(s):  
Myrthe M. A. Toorop ◽  
Nienke van Rein ◽  
Suzanne C. Cannegieter ◽  
Felix J. M. van der Meer ◽  
Pieter H. Reitsma ◽  
...  

Abstract Background Major bleeding occurs in 1 to 3% of patients treated with oral anticoagulants per year. Biomarkers may help to identify high-risk patients. A proposed marker for major bleeding while using anticoagulants is soluble thrombomodulin (sTM). Methods Plasma was available from 16,570 patients of the BLEEDS cohort that consisted of patients who started treatment with vitamin K antagonists between 2012 and 2014. A case–cohort study was performed including all patients with a major bleed (n = 326) during follow-up and a random sample of individuals selected at baseline (n = 652). Plasma sTM levels were measured and stratified by percentiles. Patients were also categorized by international normalized ratio (INR). Adjusted hazard ratios (for age, sex, hypertension, and diabetes) with 95% confidence intervals (CIs) were estimated by means of Cox regression. Results Plasma sTM levels were available for 263 patients with a major bleed and 538 control subjects. sTM levels were dose-dependently associated with risk of major bleeding, with a 1.9-fold increased risk (95% CI: 1.1–3.1) for levels above the 85th percentile versus the <25th percentile. A high INR (≥4) in the presence of high (≥70th percentile) sTM levels was associated with a 7.1-fold (95% CI: 4.1–12.3) increased risk of major bleeding, corresponding with a bleeding rate of 14.1 per 100 patient-years. Conclusion High sTM levels at the start of treatment are associated with major bleeding during vitamin K antagonist treatment, particularly in the presence of a high INR.


Author(s):  
Matthias Michal ◽  
Lisa Eggebrecht ◽  
Sebastian Göbel ◽  
Marina Panova-Noeva ◽  
Markus Nagler ◽  
...  

Abstract Aims Although depressive symptoms are highly prevalent in patients receiving oral anticoagulation (OAC), the relevance of depression for the outcome of anticoagulated individuals is unknown. Methods and results We analysed data from the multicentre cohort study thrombEVAL (NCT01809015) investigating the efficacy of OAC with vitamin K antagonists. There was an independent study monitoring, and an independent review panel assessed the endpoints. Out of n = 1558 participants, information about depressive symptoms, as measured by the two-item screener of the patient health questionnaire (PHQ-2), was available in n = 1405 individuals. The mean follow-up period was 28.04 months, with a standard deviation of 11.52 months. In multivariable Cox regression analysis, baseline PHQ-2 sum score was a strong and robust predictor of clinically relevant bleeding [hazard ratio (HR) 1.13, 95% confidence interval 1.03–1.24; P = 0.011] and all-cause mortality (HR 1.18, 1.08–1.28; P = 0.001) independent of age, sex, high school graduation, partnership, clinical profile, intake of serotonin reuptake inhibitors, and quality of OAC therapy. Individuals with clinically significant depressive symptoms (PHQ-2 ≥ 3) had a 57% increased risk for clinically relevant bleeding (fully adjusted HR 1.57, 1.08–2.28) and 54% greater risk for death (fully adjusted HR 1.54, 1.09–2.17). There was no association of depressive symptoms with thromboembolic events. For hospitalization, individuals with depressive symptoms (PHQ-2 ≥ 3) did not experience an elevated risk in the fully adjusted model (HR 1.08, 0.86–1.35; P = 0.52). Conclusion Assessment of depression by the PHQ-2 provided independent long-term prognostic information beyond common biomedical risk factors. These findings highlight the need for targeting depressive symptoms in the management of patients receiving OAC therapy.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A N Bonde ◽  
J Bjerre ◽  
M Proietti ◽  
G Gislason ◽  
G Y H Lip ◽  
...  

Abstract Background Efficacy and safety of vitamin K antagonists (VKAs) depend on quality of anticoagulation control, usually measured as time in therapeutic range (TTR). Factors that predict low TTR on VKAs could be used to identify patients who might benefit from interventions, or who would be better treated with a non-VKA oral anticoagulant (NOAC). Patients living alone may have difficulties in taking their medications, managing their diets, or coming to clinic for monitoring. Purpose To assess influence of cohabitation status on TTR with VKA among men and women. Methods We identified all Danish patients with atrial fibrillation (AF) who initiated VKA between 1997 and 2012, and studied patients who had 6 months of continuous VKA use and international normalized ratio (INR) monitoring. Patients were divided according to sex and whether they lived alone or with others. We calculated TTR using the Rosendaal method, and INR variability using Fihns method. We used a linear regression model to test for associations between TTR and covariates, and adjusted for age, income, medications and comorbidities. Results We identified 4,772 AF patients with 6 months of continuous VKA use and INR monitoring. 713 (15%) were men living alone, 1,073 (23%) were women living alone, 2,164 (45%) were men not living alone and 822 (17%) were women not living alone. INR was measured a median of 11 (interquartile range 8–15) times during the 180 days of VKA use, but men who lived alone had 0.6 (95% confidence interval (CI): 0.2 to 1.2) fewer INR measurements during the period. Median TTR was lowest among men living alone (57.2%), followed by women living alone (58.8%), women not living alone (61.0%) and men not living alone (62.5%). After multivariable adjustment, men who lived alone had a 3.6% (CI −5.6 to −1.6) lower TTR compared with men not living alone, but women who lived alone did not have significantly lower TTR (P=0.80) compared with women not living alone. Living alone had significantly greater effect on TTR among men than among women (interaction P=0.02). Men living alone also had higher adjusted INR variability (0.2, CI 0.0 to 0.4) compared with men not living alone. Conclusion Living alone was significantly related to low quality of anticoagulation control among men, but not among women. Acknowledgement/Funding this study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research


2015 ◽  
Vol 5 (2) ◽  
pp. 286-295 ◽  
Author(s):  
Angeliki Tsapanou ◽  
Yian Gu ◽  
Jennifer Manly ◽  
Nicole Schupf ◽  
Ming-Xin Tang ◽  
...  

Background/Aims: To examine the association between self-reported sleep problems and incidence of dementia in community-dwelling elderly people. Methods: 1,041 nondemented participants over 65 years old were examined longitudinally. Sleep problems were estimated using the RAND Medical Outcomes Study Sleep Scale examining sleep disturbance, snoring, sleep short of breath or with a headache, sleep adequacy, and sleep somnolence. Cox regression analysis was used to examine the association between sleep problems and risk for incident dementia. Age, gender, education, ethnicity, APOE-ε4, stroke, heart disease, hypertension, diabetes, and depression were included as covariates. Results: Over 3 years of follow-up, 966 (92.8%) participants remained nondemented, while 78 (7.2%) developed dementia. In unadjusted models, sleep inadequacy (‘Get the amount of sleep you need') at the initial visit was associated with increased risk of incident dementia (HR = 1.20; 95% CI 1.02-1.42; p = 0.027). Adjusting for all the covariates, increased risk of incident dementia was still associated with sleep inadequacy (HR = 1.20; 95% CI 1.01-1.42; p = 0.040), as well as with increased daytime sleepiness (‘Have trouble staying awake during the day') (HR = 1.24; 95% CI 1.00-1.54; p = 0.047). Conclusion: Our results suggest that sleep inadequacy and increased daytime sleepiness are risk factors for dementia in older adults, independent of demographic and clinical factors.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8038-8038
Author(s):  
Amrita Y. Krishnan ◽  
Matthew Mei ◽  
Canlan Sun ◽  
Jennifer Berano-Teh ◽  
Stephen J. Forman ◽  
...  

8038 Background: Studies from the CALGB and IFM have suggested an increased incidence of SPM post ASCT in patients on lenalidomide maintenance. Patients with MM as well as patients post ASCT are inherently at higher risk of SPM. Therefore, assessment of risk factors associated with SPM would be useful in therapeutic decisions re preASCT therapy and post ASCTmaintenance. Methods: We conducted a retrospective cohort study of 841 consecutive MM patients who underwent at least one ASCT at City of Hope from 1989 to 2009. Sixty cases with 70 SPMs were identified. A nested case-control study was also conducted to understand the role of therapeutic exposures associated with SPMs. Controls were MM patients post ASCT matched by year of HCT (±5 years). Results: The median length of follow up was 3.3 yrs. (range 0.3-19.9). Median age at ASCT was 56 yrs (range 18-77). 62% had received a single autologous HCT, 27% tandem autologous HCT, 11% had received multiple HCTs (72 had a second allogeneic HCT)). The overall cumulative incidence of any SPM was 7.4% at 5 years and 15.9% at 10 years; the cumulative incidence of SPMs for patients >55 years approached 21.9% at 10 years. The cumulative incidence of MDS/AML was 1.8% and of solid tumors was 13.0%. Factors examined included age, race, sex, number and individual therapeutic exposures ( pre-ASCT, conditioning, and post-ASCT), disease status at ASCT. Multivariate Cox regression analysis revealed non-Hispanic whites (RR=2.4, 95% CI, 1.2-4.6, p=0.01) and older age (>55) at diagnosis of MM (RR=2.3, 95% CI, 1.3-4.1, p=0.004) to be associated with an increased risk of developing SPMs. Only cumulative thalidomide exposure (both pre-ASCT and post-ASCT) demonstrated a trend toward a positive association (OR=3.5, 95% CI, 0.6-19.4, p=0.15). Six patients (3 cases and 3 controls) were exposed to lenalidomide prior to development of SPM (OR=1.0, 95% CI, 0.14-7.10). Conclusions: This single institution analysis identified non-hispanic whites and older age to be associated with increased risk of developing SPM in pts post ASCT for MM. The trend towards increased risk with thalidomide exposure may be suggestive of a class effect from IMIDs that is not restricted to lenalidomide alone.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Binding ◽  
J.B Olesen ◽  
C Lee ◽  
C Sindet-Petersen ◽  
C.T Pedersen ◽  
...  

Abstract Background/Introduction Patients with atrial fibrillation (AF), who are considered at risk of stroke, are treated with oral anticoagulants (OACs), and non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists in recent guidelines. Poor NOAC compliance among patients with AF could result in an increased risk of thromboembolism and major bleeding, however, it has yet to be evaluated how cohabitant status and gender affects compliance with NOAC treatment among patients with AF. Purpose The aim of this study was to evaluate the risk of NOAC discontinuation among patients with AF according to cohabitant status and gender. Methods Using the Danish national registries we identified and included patients with AF aged 40–90 years in treatment with NOAC. The study period was from 2013 to 2017, and patients were followed for two years, or until death, outcome or emigration. The main outcome was discontinuation of NOAC-treatment for at least 30 days. Absolute risks were calculated as cumulative incidences using the Aalen Johansen estimator, and multiple covariate adjusted Cox regressions were used to calculate hazard ratios (HR). Results We included 32,380 patients with AF in NOAC treatment, where 16.8% were men living alone (median age 72 years), 25.8% were women living alone (median age 79 years), 37.2% were men living with a partner (median age 70 years), and 20.2% were women living with a partner (median age 79 years). Absolute two-year risk of NOAC discontinuation was highest among men living alone (Cumulative Incidence (CI) 0.19; 95% CI: 0.17 to 0.20), followed by men living with a partner (CI 0.18; 0.17 to 0.19), women living with a partner (CI 0.16; 0.15 to 0.17), and women living alone (CI 0.13; 0.12 to 0.14). After adjustment, living alone was associated with an increased risk of NOAC discontinuation among men (HR 1.15, 95% CI: 1.05 to 1.26), but not among women (HR 1.04, 95% CI: 0.93 to 1.15, interaction p=0.32). In an analysis evaluating gender, we found that being male was associated with a significantly higher risk of NOAC-discontinuation (HR 1.18, CI: 1.10 to 1.25) compared to women. Results were similar when we used 60 days discontinuation instead of 30 days discontinuation as outcome. Conclusion Gender and cohabitant status was significantly associated with risk of NOAC discontinuation. Male gender and living alone was associated with a higher risk of NOAC discontinuation among patients with AF in a nationwide population. Adjusted relative two-year risks Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Proietti ◽  
G F Romiti ◽  
B Olshansky ◽  
G Y H Lip

Abstract Introduction Quality of anticoagulation control is essential to ensure better clinical outcomes in patients with atrial fibrillation (AF). Time in therapeutic range (TTR) is recommended as a measure of the quality of anticoagulation control. The International normalized ratio (INR) variability has been suggested as an alternative index, even though large independent validations for this index are still lacking. Purpose To provide validation of clinical usefulness of INR variability as a measure of the quality of anticoagulation control in a large cohort of AF patients. Methods Data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial were analysed. INR variability was defined as the standard deviation (SD) of mean INR values [INR-SD] recorded throughout the follow-up observation for each patient. All patients with available INR values were included in the analysis. Stroke, major bleeding, cardiovascular (CV) death and all-cause death were study outcomes. Results Among the original 4060 patients, a total of 3185 (78.4%) were available for analysis. Mean (SD) INR-SD was 0.58 (0.25). According to INR-SD patients were categorized into four quartiles. Mean (SD) CHA2DS2-VASc score was increased (p=0.040), with no difference in proportions of CHA2DS2-VASc ≥2 (p=0.582) between the subgroups. A significant inverse correlation was found between INR-SD and TTR (Spearman's Rho: −0.536, p<0.001). Continuous INR-SD, after multiple adjustments, was inversely associated with TTR (standardized beta: −0.451, p<0.001) and directly associated with SAMe-TT2R2score (standardized beta: 0.084, p<0.001). A fully adjusted Cox multivariate regression analysis found that INR-SD was directly associated with increased risk of stroke, major bleeding and all-cause death (Table). An INR-SD ≥0.85 was directly associated with all the study outcomes, on multivariate analysis (Table). Cox Regression Analysis INR-SD INR-SD ≥0.85 HR (95% CI) HR (95%) Stroke 2.52 (1.34–4.67) 1.62 (1.00–2.63) Major Bleeding 2.43 (1.49–3.96) 1.61 (1.10–2.36) CV Death 1.50 (0.87–2.59) 1.54 (1.07–2.24) All-Cause Death 1.79 (1.21–2.66) 1.55 (1.17–2.05) CI = Confidence Interval; CV = Cardiovascular; HR = Hazard Ratio; INR-SD = International Normalized Ratio Standard Deviation. Conclusions INR variability, expressed as INR-SD, was significantly correlated and associated with TTR. Both continuous INR-SD and INR-SD ≥0.85 were significantly associated with a higher risk of all study adverse outcomes. Acknowledgement/Funding None


2012 ◽  
Vol 10 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Robert J. Bollo ◽  
Jay Riva-Cambrin ◽  
Meghan M. Brockmeyer ◽  
Douglas L. Brockmeyer

Object Chiari malformation Type I (CM-I) is a congenital anomaly often treated by decompressive surgery. Patients who fail to respond to standard surgical management often have complex anomalies of the craniovertebral junction and brainstem compression, requiring reduction and occipitocervical fusion. The authors hypothesized that a subgroup of “complex” patients defined by specific radiographic risk factors may have a higher rate of requiring occipitocervical fusion. Methods A retrospective review was conducted of clinical and radiographic data in pediatric patients undergoing surgery for CM-I between 1995 and 2010. The following radiographic criteria were identified: scoliosis, syringomyelia, CM Type 1.5, medullary kinking, basilar invagination, tonsillar descent, craniocervical angulation (clivoaxial angle [CXA] < 125°), and ventral brainstem compression (pB–C2 ≥ 9 mm). A multivariate Cox regression analysis was used to determine the independent association between occipitocervical fusion and each variable. Results Of the 206 patients who underwent CM decompression with or without occipitocervical fusion during the study period, 101 had preoperative imaging available for review and formed the study population. Mean age at surgery was 9.1 years, and mean follow-up was 2.3 years. Eighty-two patients underwent suboccipital decompression alone (mean age 8.7 years). Nineteen patients underwent occipitocervical fusion (mean age 11.1 years), either as part of the initial surgical procedure or in a delayed fashion. Factors demonstrating a significantly increased risk of requiring fusion were basilar invagination (HR 9.8, 95% CI 2.2–44.2), CM 1.5 (HR 14.7, 95% CI 1.8–122.5), and CXA < 125° (HR 3.9, 95% CI 1.2–12.6). Conclusions Patients presenting with basilar invagination, CM 1.5, and CXA < 125° are at increased risk of requiring an occipitocervical fusion procedure either as an adjunct to initial surgical decompression or in a delayed fashion. Patients and their families should be counseled in regard to these findings as part of a preoperative CM evaluation.


2013 ◽  
Vol 4 (1) ◽  
pp. ar.2013.4.0049 ◽  
Author(s):  
Michael B. Soyka ◽  
David Holzmann

Epistaxis is one of the most frequent emergencies in rhinology. Patients using anticoagulative medication are at increased risk for epistaxis. We evaluated the prothrombin time and the international normalized ratio (INR) in anticoagulated epistaxis patients. Patients suffering from epistaxis were prospectively included in a database and results from prothrombin testing were analyzed in the context of anticoagulation. One hundred sixteen of 591 epistaxis cases were identified to be on oral anticoagulation. The INR was found to be above therapeutic levels in 19 (16%) of these cases. We strongly recommend prothrombin time and INR testing in all epistaxis patients taking any sort of vitamin K antagonists.


2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Carlos Estevez-Fraga ◽  
Maria Molina-Sanchez ◽  
Rodrigo Alvarez-Velasco ◽  
Pablo Agüero-Rabes ◽  
Leticia Crespo-Araico ◽  
...  

Introduction. Patients treated with vitamin K antagonists (VKA) are at increased risk of intracranial haemorrhage (ICH). The purpose of our study was to determine the quality of previous anticoagulation control in patients with VKA-associated ICH. Materials and Methods. We prospectively assessed every consecutive patient admitted to our stroke unit with VKA-associated ICH between 2013 and 2016. Demographic, clinical, and radiological variables, as well as consecutive international normalized ratios (INR) during 7 previous months, were extracted. Time in therapeutic range (TTR), time over range (TOR), time below range (TBR), and percentage of INR within range (PINRR) were calculated. Results and Discussion. The study population comprised 53 patients. Mean age was 79 years; 42% were women. Forty-eight patients had atrial fibrillation (AF) and 5 mechanical prosthetic valves. Therapeutic or infratherapeutic INR on arrival was detected in 64.4% of patients (95% CI 2.7 to 3.2). TTR was 67.8% (95% CI: 60.2 to 75.6 %) and PINRR was 75% (95% CI: 49.9-100). TOR was 17.2% (95% CI: 10.4 to 23.9% ) and TBR was 17% (95% CI: 10.6 to 23.9%). Conclusion. VKA-associated ICH happens usually in the context of good chronic anticoagulation control. Newer risk assessment methods are required.


Sign in / Sign up

Export Citation Format

Share Document