The impact of acute diarrhea on the coagulation status of patients with vitamin K antagonists

AbstractAcute diarrhea is associated with a reduced absorption of both vitamin K antagonists (VKA) and vitamin K itself. To date, the net effect on the coagulation status of subjects with VKA remains elusive. We performed a systematic retrospective single-center analysis using an electronic data extraction approach to identify subjects with plasmatic anticoagulation (either VKA or direct oral anticoagulant (DOAC)) and diarrhea in a German University Hospital over a period of eight years. Acute diarrhea and complete documentation of coagulation status on admission were defined as inclusion criteria, anticoagulation other than VKA/DOAC and obvious inadherence as exclusion criteria. Subjects with VKA/DOAC admitted for hypertension served as control group. Data extraction yielded 356 subjects with gastrointestinal diagnoses and 198 hypertensive subjects, 55 and 83 of whom fulfilled all in- and exclusion criteria. INR values of subjects with VKA were significantly higher in subjects with diarrhea than in hypertensive controls (4.3 ± 3.7 vs. 2.3 ± 0.7, p < 0.001). The distribution of subjects having INR values lower, higher or within the target range differed significantly among groups with a substantially higher prevalence of overanticoagulation in the diarrhea group (46.4% vs. 14.3%, p < 0.001). In a multinomial logistic regression model, acute diarrhea was significantly associated with overanticoagulation (odds ratio 7.2, 95% confidence interval 2.163–23.921; p < 0.001), whereas age, sex, creatinine, and indication of anticoagulation were not (p > 0.05 each). Acute diarrhea is associated with a highly increased risk for overanticoagulation in patients with VKA. Thus, gastroenteritis necessitates a close monitoring of INR in order to identify subjects needing a temporary pause of VKA therapy.

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Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based

Blood ◽

10.1182/blood-2007-11-123711 ◽

2008 ◽

Vol 111 (9) ◽

pp. 4471-4476 ◽

Cited By ~ 64

Author(s):

Marcel Levi ◽

G. Kees Hovingh ◽

Suzanne C. Cannegieter ◽

Marinus Vermeulen ◽

Harry R. Büller ◽

...

Keyword(s):

Clinical Trials ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Careful Consideration ◽

Exclusion Criterion ◽

Exclusion Criteria ◽

Risk Of Bleeding ◽

Increased Risk ◽

Risk Of Hemorrhage ◽

Control Study

Abstract Vitamin K antagonists (VKAs) are effective antithrombotic agents and advocated in guidelines for the management of cardiovascular disease. However, in the trials underlying these guidelines, many patients were excluded. We performed a case-control study in 993 patients receiving VKAs, who required hospitalization for bleeding, and contrasted them to 993 matched control patients on VKAs, who were hospitalized for an infection. We analyzed whether patients and controls would have been eligible for the clinical trials on which their indication for anticoagulation was based, and estimated the risk of hemorrhage associated with exclusion criteria as applied in those trials. Approximately one quarter (23% [95% CI: 21%-26%]) of controls had one or more exclusion criteria for the trials, supporting the use of anticoagulation for their condition. Forty percent of patients presenting with bleeding had one or more exclusion criteria (95% CI: 37%-43%). Having one exclusion criterion resulted in a 2.9-fold increased risk of bleeding (95% CI: 2.2-3.9), and this risk increased sharply when more than one exclusion criterion was present. VKAs are often prescribed to patients who would not have qualified for clinical trials, and in these patients a careful consideration should be made regarding the expected efficacy and the risk of bleeding.

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Permanent discontinuation of different anticoagulants in patients with atrial fibrillation and the impact on clinical outcome: data from the GARFIELD-AF registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0639 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F Cools ◽

D Johnson ◽

K.S Pieper ◽

A.J Camm ◽

J.-P Bassand ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Time Dependent ◽

Funding Source ◽

Increased Risk ◽

History Of ◽

Baseline Factors ◽

The Impact

Abstract Background Non-Vitamin K Antagonists (NOAC) are replacing vitamin K Antagonists (VKA) as first line oral anticoagulant therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF). Discontinuation of OAC might put patients at increased risk. It was anticipated that patients who were on NOAC would discontinue OAC less. Purpose We compare the rates and impact on outcome of the discontinuation of NOAC and VKA using data from the GARFIELD-AF registry. Methods Patients included in GARFIELD-AF, had a new diagnosis of NVAF and at least 1 stroke risk factor. In this analysis 26,299 patients (VKA: 13,012; NOAC: 13,287) that received OAC were included. Permanent discontinuation was defined as stopping OAC for at least 7 consecutive days (whether or not restarted during follow-up). Marginal structural Cox proportional hazards models estimated the effect of discontinuation on death, cardiovascular (CV) death, non-haemorrhagic stroke + systemic embolism (NHS+SE), myocardial infarction (MI), or combined endpoints. Adjustments were made for both baseline factors and time dependent variables. Results Of all patients, 15.6% discontinued OAC (VKA: 15.4%; NOAC: 15.8%) over a median follow-up of 181 days (IQR: 359). Most discontinued early (67.0% of patients on VKA and 47.1% of patients on NOAC ≤4 months). Significantly higher discontinuation risk was seen with worsening kidney function, coronary artery disease, history of bleeding (baseline factors), as well as with all types of bleeding (time dependent factors). Lower discontinuation rates were seen with history of stroke/TIA, hypertension, increasing age, permanent AF (all p<0.01). Mean CHA2DS2-VASc score was 3 in all groups. Patients in both treatment arms who discontinued were at increased risk for death, NHS+SE, MI as well as combined endpoints of death/NHS+SE/MI, death/NHS+SE and a trend towards higher CV death (Figure 1). All interaction tests for the interaction of treatment and discontinuation had a p value >0.4. The association between discontinuation and outcomes did not change when a 30 day discontinuation window was used. Conclusion The rate of discontinuation in this study was 15.8% and comparable for VKA and NOAC over a 2-year follow-up. Discontinuation rates were the highest soon after the initiation of treatment. When VKA or NOAC was stopped for ≥7 consecutive days, the risk of NHS+SE, death, MI or any combined endpoints were significantly worse in both treatment arms. These data suggest that discontinuation of anticoagulant treatment with VKA or NOAC should be discouraged. HR of patients who discontinued OAC Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The GARFIELD-AF registry is funded by an unrestricted research grant from Bayer AG.

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Routine use of immunosuppressants is associated with mortality in hospitalised patients with COVID-19

Therapeutic Advances in Drug Safety ◽

10.1177/2042098620985690 ◽

2021 ◽

Vol 12 ◽

pp. 204209862098569

Author(s):

Phyo K. Myint ◽

Ben Carter ◽

Fenella Barlow-Pay ◽

Roxanna Short ◽

Alice G. Einarsson ◽

...

Keyword(s):

Medical Attention ◽

Close Monitoring ◽

Plain Language ◽

Discharge Data ◽

Specific Patient ◽

Risk Of Death ◽

Hospitalised Patients ◽

Increased Risk ◽

The Uk ◽

The Impact

Background: Whilst there is literature on the impact of SARS viruses in the severely immunosuppressed, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, across the UK and Italy. Data were collected between 27 February and 28 April 2020 by trained data-collectors and included all unselected consecutive admissions with COVID-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. Primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge. Data were analysed with mixed-effects, Cox proportional hazards and logistic regression models using non-users of immunosuppressants as the reference group. Results: In total 1184 patients were eligible for inclusion. The median (IQR) age was 74 (62–83), 676 (57%) were male, and 299 (25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113 (~10%) were on immunosuppressants. Any immunosuppressant use was associated with increased mortality: aHR 1.87, 95% CI: 1.30, 2.69 (time to mortality) and aOR 1.71, 95% CI: 1.01–2.88 (14-day mortality). There also appeared to be a dose–response relationship. Conclusion: Despite possible indication bias, until further evidence emerges we recommend adhering to public health measures, a low threshold to seek medical advice and close monitoring of symptoms in those who take immunosuppressants routinely regardless of their indication. However, it should be noted that the inability to control for the underlying condition requiring immunosuppressants is a major limitation, and hence caution should be exercised in interpretation of the results. Plain Language Summary Regular Use of Immune Suppressing Drugs is Associated with Increased Risk of Death in Hospitalised Patients with COVID-19 Background: We do not have much information on how the COVID-19 virus affects patients who use immunosuppressants, drugs which inhibit or reduce the activity of the immune system. There are various conflicting views on whether immune-suppressing drugs are beneficial or detrimental in patients with the disease. Methods: This study collected data from 10 hospitals in the UK and one in Italy between February and April 2020 in order to identify any association between the regular use of immunosuppressant medicines and survival in patients who were admitted to hospital with COVID-19. Results: 1184 patients were included in the study, and 10% of them were using immunosuppressants. Any immunosuppressant use was associated with increased risk of death, and the risk appeared to increase if the dose of the medicine was higher. Conclusion: We therefore recommend that patients who take immunosuppressant medicines routinely should carefully adhere to social distancing measures, and seek medical attention early during the COVID-19 pandemic.

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Management of Oral Anti-Coagulation in Patients with Heart Failure—Insights from the ThrombEVAL Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1673380 ◽

2018 ◽

Vol 118 (11) ◽

pp. 1930-1939

Author(s):

Sebastian Göbel ◽

Jürgen Prochaska ◽

Lisa Eggebrecht ◽

Ronja Schmitz ◽

Claus Jünger ◽

...

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Vitamin K Antagonists ◽

Plasma Concentrations ◽

Regular Care ◽

Increased Risk ◽

Patients With Heart Failure ◽

Specialized Care ◽

The Impact

AbstractPatients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.

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New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.742428 ◽

2021 ◽

Vol 8 ◽

Author(s):

Eve Cariou ◽

Kevin Sanchis ◽

Khailène Rguez ◽

Virginie Blanchard ◽

Stephanie Cazalbou ◽

...

Keyword(s):

Vitamin K ◽

Cardiac Amyloidosis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Complications ◽

Prognostic Impact ◽

Transthyretin Amyloidosis ◽

Increased Risk ◽

All Cause Mortality ◽

History Of

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA.Methods and Results: 273 patients with CA and history of AA with long term anticoagulation−69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)–were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality.Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.

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Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding

Thrombosis and Haemostasis ◽

10.1160/th16-07-0498 ◽

2017 ◽

Vol 117 (03) ◽

pp. 491-499 ◽

Cited By ~ 17

Author(s):

Niklas Wallvik ◽

Joakim Eriksson ◽

Jonas Höijer ◽

Matteo Bottai ◽

Margareta Holmström ◽

...

Keyword(s):

Vitamin K ◽

Vitamin K Antagonists ◽

Bleeding Event ◽

Optimal Timing ◽

Thromboembolic Events ◽

Gi Bleeding ◽

Upper Gi Bleeding ◽

Upper Gi ◽

Increased Risk ◽

Upper Gastrointestinal

SummaryThe optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the ‘total risk’, based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58 %) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2–3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07–0.55) and death (HR 0.61; 95 % CI, 0.39–0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95 % CI, 1.4–4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3–6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.

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HEMATURIA AND OTHER KINDS OF BLEEDINGS ON NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN UPDATED OVERVIEW ON OCCURRENCE, PATHOMECHANISMS AND MANAGEMENT

Wiadomości Lekarskie ◽

10.36740/wlek202011135 ◽

2020 ◽

Vol 73 (11) ◽

pp. 2528-2534

Author(s):

Dagmara Wojtowicz ◽

Anna Tomaszuk-Kazberuk ◽

Jolanta Małyszko ◽

Marek Koziński

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Anticoagulant Activity ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Bleeding Complications ◽

Reversal Agents ◽

Limited Availability ◽

Increased Risk

Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended for oral anticoagulation in patients with non-valvular atrial fibrillation. In the setting, NOACs effectively prevent from stroke and systemic embolic events. In spite of the favorable safety profile of NOACs when compared with vitamin K antagonists, the use of any kind of anticoagulation is associated with an increased risk of bleeding. However, there is still a lack of direct comparisons of effectiveness and safety among NOACs. The results of indirect comparisons and meta-analyses suggest that the risk of various types of hemorrhagic complications differ among the particular NOACs. Management of bleeding in patients under NOAC therapy can be challenging because of limited availability of antidotes and the lack of routine laboratory test monitoring the NOAC anticoagulant effect. In case of life-threatening or critical site bleeding, reversal of NOAC anticoagulant activity is essential together with immediate implementation of causative treatment. Moreover, some patients on chronic NOAC therapy may require urgent surgery or invasive procedures. Specific reversal agents for NOACs have been developed, i.e. more widely available idarucizumab for the factor IIa inhibitor (dabigatran) and andexanet alfa for the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with limited availability. This review summarizes the occurrence and management of NOAC-related bleeding complications with a particular emphasis on hematuria.

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Comparison of Three Methods to Assess Therapeutic Quality Control of Treatment with Vitamin K Antagonists

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614372 ◽

1999 ◽

Vol 82 (10) ◽

pp. 1260-1263 ◽

Cited By ~ 14

Author(s):

Martin Prins ◽

W. Ken Redekop ◽

Jan Tijssen ◽

Siem Heisterkamp ◽

Harry Büller ◽

...

Keyword(s):

Quality Control ◽

Vitamin K ◽

Hybrid Method ◽

Vitamin K Antagonists ◽

Linear Interpolation ◽

Target Range ◽

Therapeutic Level

SummaryDuring treatment with vitamin K antagonists, International Normalized Ratios (INR) are determined periodically to maintain a therapeutic level of anticoagulation. We evaluated two existing methods for therapeutic quality control (linear interpolation and equidivision), with regard to their validity and reproducibility. In addition, we proposed and evaluated a (hybrid) method that takes into account potential effects of dosage modifications when INRs are far out of the target range. Validity was assessed by deleting intermediary INR results and estimating this INR based on the two surrounding INRs with each of the three methods. The estimated INRs were then compared with the observed INR.Reproducibility of time spent in an INR range was evaluated for each of the three methods by deleting at random increasing proportions of INRs and comparing these estimates with the situation without deletions. We found that estimates of time spent in INR categories obtained with equidivision were most reproducible, but least valid. The hybrid method showed slightly higher validity and reproducibility in comparison with linear interpolation. Since these differences were small, linear interpolation is preferable to the hybrid method, since the calculations involved are easier.

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P1187Pocket-Hematoma after cardiac implantable electronic devices surgery: a single centre study

EP Europace ◽

10.1093/europace/euaa162.302 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

L Spighi ◽

F Notaristefano ◽

R Annunziata ◽

M D"ammando ◽

G Zingarini ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Antithrombotic Therapy ◽

Pulse Generator ◽

Dual Antiplatelet Therapy ◽

Vitamin K Antagonists ◽

Multivariate Regression Analysis ◽

New Device ◽

Increased Risk ◽

The Impact ◽

Pocket Hematoma

Abstract Intro Pocket hematoma is a common complication after pacemaker (PMK) or implantable cardioverter defibrillator (ICD) surgery. In this clinical setting anticoagulant and antiplatelet therapy are associated with an increased risk of hemorrhagic complications, but data are sparse. Purpose We examined the impact of antiplatelet therapy and anticoagulation with vitamin K antagonists (VKA) or heparin on the risk of pocket hematoma. Materials and method: between august 2017 and june 2019, a total of 639 devices were implanted or replaced at our centre. Predictors of hematoma occurrence were determined by multivariate regression analysis. We used a specific definition of pocket hematoma: a) any palpable swelling in the pocket area requiring an unscheduled visit or prolonged hospitalization > 24 h or re-hospitalization for hematoma, b) interruption of antithrombotics, c) reoperation, d) hemoglobin drop > 2 g/dl or blood transfusion. The above criteria were assessed during hospitalization and up to 10 days after discharge. Results: the incidence of pocket hematoma was 7.5%. Among 639 patients (pts) including in the study 33.5% (214 pts) didn’ t take any antithrombotic therapy, 40.2 % (257 pts) were on single antiplatelet therapy (SAPT), 8.8 % (56 pts) were on dual antiplatelet therapy, 11.1 % (71 pts) were on uninterrupted VKA (mean INR 2). Heparin bridging was administered in 6.4% (41 pts). Ejection fraction (43 ±13 %) and hemoglobin value before implantation (12.3 ±2.6 g/dL) in patients who developed hematoma were significantly lower compared with whose without hematoma. Patients with hematoma had a higher prevalence of congestive heart failure, ischemic cardiomyopathy and intake antithrombotic therapy. After adjusting for confounding factors with multivariate logistic regression only the use of dual antiplatelet therapy (OR 5.9 95% CI 1.5-21 p = 0.008) and the bridging with enoxaparin (OR 5.6 95% CI 1.4-22 p = 0.013) increased the risk of pocket hematoma. Single antiplatelet therapy (OR 2.6 95% CI 0.8-8.4 p = ns) and uninterrupted VKA (OR 0.9 95% CI 0.7-11 p = ns) did not increased the risk of pocket hematoma compared to no antithrombotic therapy. Pulse generator change and new device implant/upgrading (OR 1.8 95% CI 0.6-5.2 p = ns) carried the same haemorrhagic risk. Conclusion the use of DAPT or bridging with enoxaparin are highly predictive for the occurrence of perioperative pocket hematoma in patients scheduled for pmk/icd surgery. In contrast, single antiplatelet therapy and uninterrupted VKA did not increase the risk of hematoma.

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Long-term quality of VKA treatment and clinical outcome after extreme overanticoagulation in 14,777 AF and VTE patients

Thrombosis and Haemostasis ◽

10.1160/th14-06-0537 ◽

2015 ◽

Vol 113 (04) ◽

pp. 881-890 ◽

Cited By ~ 9

Author(s):

Nic J. G. M. Veeger ◽

Nakisa Khorsand ◽

Hanneke C. Kluin-Nelemans ◽

Hilde A. M. Kooistra ◽

Karina Meijer ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Clinical Outcome ◽

Vitamin K ◽

Vitamin K Antagonists ◽

P Value ◽

Risk Of Bleeding ◽

Increased Risk

SummaryVitamin K antagonists (VKA) are widely used in atrial fibrillation and venous thromboembolism (VTE). Their efficacy and safety depend on individual time in the therapeutic range (iTTR). Due to the variable dose-response relationship within patients, also patients with initially stable VKA treatment may develop extreme overanticoagulation (EO). EO is associated with an immediate bleeding risk, but it is unknown whether VKA treatment will subsequently restabilise. We evaluated long-term quality of VKA treatment and clinical outcome after EO. EO was defined as international normalized ratio (INR) ≥ 8.0 and/or unscheduled vitamin K supplementation. We included a consecutive cohort of initially stable atrial fibrillation and venous thromboembolism patients. In EO patients, the 90 days pre- and post-period were compared. In addition, patients with EO were compared with patients without EO using a matched 1:2 cohort. Of 14,777 initially stable patients, 800 patients developed EO. The pre-period was characterised by frequent overanticoagulation, and half of EO patients had an inadequate iTTR (< 65 %). After EO, underanticoagulation became more prevalent. Although the mean time between INR-measurements decreased from 18.6 to 13.2 days, after EO inadequate iTTR became more frequent (62 %), p-value < 0.001. A 2.3 times (95 % confidence interval [CI] 2.0–2.5) higher risk for iTTR< 65 % after EO, was accompanied by increased risk of bleeding (hazard ratio [HR] 2.1;CI 1.4–3.2), VKA-related death 17.0 (HR 17.0;CI 2.1–138) and thrombosis (HR 5.7;CI 1.5–22.2), compared to the 1600 controls. In conclusion, patients continuing VKA after EO have long-lasting inferior quality of VKA treatment despite intensified INR-monitoring, and an increased risk of bleeding, thrombosis and VKA-related death.Note: There have been no previous presentations, reports or publications of the complete data that appear in the article. Parts of the data in this article have been presented as a poster at the American Society of Hematology (ASH) congress 2013, New Orleans, United States.

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