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

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4471-4476 ◽  
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.

scholarly journals Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients with Atrial Fibrillation After Acute Coronary Syndrome or PCI: Insights from The AUGUSTUS Trial

Circulation ◽  
2021 ◽  
Author(s):  
Ziad Hijazi ◽  
John H. Alexander ◽  
Zhuokai Li ◽  
Daniel M. Wojdyla ◽  
Roxana Mehran ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Acute Coronary Syndrome ◽  
Kidney Function ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Exclusion Criterion ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Risk Of Bleeding ◽  
Ischemic Events

Background: In the AUGUSTUS trial, apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists (VKA), and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y 12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. Methods: In 4456 patients, the CKD-EPI formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban vs. VKA and aspirin vs. placebo was assessed across kidney function categories using Cox models. The primary outcome was ISTH major or clinically relevant non-major bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance below 30 mL/min was an exclusion criterion in the AUGUSTUS trial. Results: Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30-50 mL/min/1.73m 2 , respectively. During 6-months follow-up a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with VKA, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30-50 mL/min/1.73m 2 for bleeding events with rates of 13.1% vs. 21.3%; HR (95% CI) 0.59 (0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL/min/1.73m 2 : 16.6% vs. 5.6%; HR 3.22 (2.19-4.74); p for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable with aspirin and placebo across eGFR categories with HR ranging from 0.97 (0.76-1.23) to 1.28 (1.02-1.59) and from 0.75 (0.48-1.17) to 1.34 (0.81-2.22), respectively. Conclusions: The safety and efficacy of apixaban was consistent irrespective of kidney function, as compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT02415400

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

2015 ◽  
Vol 113 (04) ◽  
pp. 881-890 ◽  
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.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Johannes Schweinfurth ◽  
Alexander Bauer ◽  
Frederic Bauer ◽  
Felix Sebastian Seibert ◽  
Benjamin Rohn ◽  
...  
Keyword(s):  
Vitamin K ◽  
Acute Diarrhea ◽  
Data Extraction ◽  
Vitamin K Antagonists ◽  
Target Range ◽  
Close Monitoring ◽  
Exclusion Criteria ◽  
Increased Risk ◽  
Coagulation Status ◽  
The Impact

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.

Influence of Concomitant Treatments under Anticoagulants and Statins in Detecting Signals of Adverse Drug Reactions

2019 ◽  
Vol 45 (08) ◽  
pp. 837-845
Author(s):  
Maria-Isabel Jimenez-Serrania ◽  
Carlos Treceño-Lobato
Keyword(s):  
Adverse Drug Reactions ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Cross Sectional Study ◽  
Drug Reactions ◽  
Cross Sectional ◽  
Risk Of Bleeding ◽  
Reductase Inhibitors ◽  
Increased Risk

AbstractThe aim of the present study was to evaluate the risk of adverse drug reactions (ADRs) of concomitant treatments in patients treated with anticoagulants and statins. The authors performed an observational cross-sectional study in two cohorts of surveyed patients treated with vitamin K antagonists (VKAs) or non–vitamin K antagonist oral anticoagulants (NOACs). Different groups were analyzed based on the drug that each patient was taking, that is, VKAs or NOACs, as well as on the use of HMG CoA reductase inhibitors (statins) versus nonuse of these drugs; they also took into account the potential exposure to other common medications. Descriptive, clinical, and ADR data were reported and analyzed through an adaptation of Bayesian methodology (false discovery rate < 0.05) to detect new signals. Eleven different ADRs in patients on VKAs and statins and 12 in patients on VKAs without statins were found. In evaluating the concomitant therapies, the authors found that analgesics and nonsteroidal anti-inflammatory drugs were the most common therapeutic options, followed by proton pump inhibitors (PPIs). Seven ADRs were observed in patients concomitantly treated with NOACs and statins, whereas NOACs without concomitant statins were associated with a significantly lower risk of bleeding. The risk of observing an ADR among the patients who are concomitantly treated with VKAs and statins is lower than with analgesics or PPI, while the concomitant use of NOACs and statins is associated with both an increment in the number of observed ADRs and increased risk of bleeding.

Is a Prolonged Bleeding Time Associated with an Increased Risk of Hemorrhage after Liver Biopsy?

1999 ◽  
Vol 81 (03) ◽  
pp. 378-381 ◽  
Author(s):  
Frank Brosstad ◽  
Thore Egeland ◽  
Tor Egge ◽  
Erik Schrumpf ◽  
Kirsten Boberg
Keyword(s):  
Liver Biopsy ◽  
Bleeding Time ◽  
Hemoglobin Concentration ◽  
Additional Information ◽  
Risk Of Bleeding ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Increased Risk ◽  
Patient Groups ◽  
Risk Of Hemorrhage

SummaryBleeding time determination is not advised as a general preoperative hemostasis screening test, but it might be useful in some patient groups. Patients referred for liver biopsy frequently have coagulation disturbances and are at risk of hemorrhage. In this prospective study 219 liver biopsies were carried out regardless of a prolonged bleeding time, but with minimum requirements for hemoglobin concentration, platelet count, and tests of the internal and external coagulation pathways. The bleeding time was prolonged in the case of 48 (22%) of the biopsies. Significant bleeding as defined by a hemoglobin decrease of ≥2.0 g/dl occurred in nine patients. Three of these patients were bone marrow transplanted. Patients with a prolonged bleeding time carried a five times higher risk of bleeding (odds ratio = 5.0; confidence interval = 1.1-21.8; p = 0.019). We conclude that the bleeding time may give additional information on the risk of bleeding in some patient groups undergoing liver biopsy.

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

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 &lt; 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.

Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding

2017 ◽  
Vol 117 (03) ◽  
pp. 491-499 ◽  
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.

Use of vitamin K antagonists and risk of prostate cancer: Meta–analysis and nationwide case–control study

2018 ◽  
Vol 144 (7) ◽  
pp. 1522-1529 ◽  
Author(s):  
Kasper Bruun Kristensen ◽  
Patricia Hjorslev Jensen ◽  
Charlotte Skriver ◽  
Søren Friis ◽  
Anton Pottegård
Keyword(s):  
Prostate Cancer ◽  
Vitamin K ◽  
Case Control Study ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Case Control ◽  
Control Study

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

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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