Similar outcomes between vitamin K and non-vitamin K antagonist oral anticoagulants associated intracerebral hemorrhage

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA2DS2VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39–1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55–2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants- and vitamin K antagonists-associated intracranial hemorrhage, despite unavailability of non-vitamin K antagonist oral anticoagulants-specific reversal agents.

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Vitamin K Antagonist–associated Intracerebral Hemorrhage: Lessons from a Devastating Disease in the Dawn of the New Oral Anticoagulants

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2013.06.034 ◽

2014 ◽

Vol 23 (4) ◽

pp. 732-742 ◽

Cited By ~ 9

Author(s):

Marta Suárez-Pinilla ◽

Ángeles Fernández-Rodríguez ◽

Lorena Benavente-Fernández ◽

Sergio Calleja-Puerta

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

New Oral Anticoagulants

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Coagulation Testing in Intracerebral Hemorrhage Related to Non-vitamin K Antagonist Oral Anticoagulants

Neurocritical Care ◽

10.1007/s12028-017-0403-x ◽

2017 ◽

Vol 27 (2) ◽

pp. 208-213 ◽

Cited By ~ 6

Author(s):

Jan C. Purrucker ◽

◽

Timolaos Rizos ◽

Kirsten Haas ◽

Marcel Wolf ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Coagulation Testing

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Intracerebral hemorrhage associated with warfarin versus non-vitamin K antagonist oral anticoagulants in Asian patients

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2018.10.102 ◽

2019 ◽

Vol 61 ◽

pp. 160-165 ◽

Cited By ~ 3

Author(s):

Ho Geol Woo ◽

Inyoung Chung ◽

Dong Seok Gwak ◽

Baik Kyun Kim ◽

Ji Hoon Kang ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Asian Patients

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Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

Stroke ◽

10.1161/strokeaha.120.031827 ◽

2021 ◽

Vol 52 (4) ◽

pp. 1450-1454

Author(s):

Maurizio Paciaroni ◽

Giancarlo Agnelli ◽

Michela Giustozzi ◽

Valeria Caso ◽

Elisabetta Toso ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Intracerebral Hemorrhage ◽

Vitamin K ◽

Stroke Prevention ◽

Oral Anticoagulants ◽

Antiplatelet Agents ◽

Vitamin K Antagonist ◽

Logistic Regression Models ◽

Artery Disease

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

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Non–Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients With Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.118.023797 ◽

2019 ◽

Vol 50 (4) ◽

pp. 939-946 ◽

Cited By ~ 7

Author(s):

Peter Brønnum Nielsen ◽

Flemming Skjøth ◽

Mette Søgaard ◽

Jette Nordstrøm Kjældgaard ◽

Gregory Y.H. Lip ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Risk Reduction ◽

Vitamin K ◽

Risk Ratio ◽

Absolute Risk ◽

Oral Anticoagulants ◽

Absolute Risk Reduction ◽

Vitamin K Antagonist

Background and Purpose— Recurrent bleeding associated with oral anticoagulants (OACs) causes a dilemma in patients with atrial fibrillation (AF) sustaining an intracerebral hemorrhage. Treatment recommendations guiding clinical practice on optimal OAC agent selection in this population are lacking. This study aimed to investigate the comparative effectiveness and safety of non–vitamin K antagonist OAC (NOAC) versus warfarin in patients with AF sustaining an intracerebral hemorrhage. Methods— We conducted a nationwide observational cohort study including patients with AF sustaining an intracerebral hemorrhage and who subsequently claimed an OAC prescription. Contrasts of 1-year risks for ischemic stroke and intracerebral hemorrhage risks were obtained and evaluated by inverse probability treatment weighted absolute risk reduction and risk ratios. Results— Among 622 AF patients with intracerebral hemorrhage, 274 claimed a warfarin prescription and 348 a NOAC prescription. Mean age was 76 years (39% females); 72% had an index nonsevere event and 28% moderate to severe index event according to the Scandinavian Stroke Severity scale. The 1-year ischemic stroke risk was 7.85% for warfarin and 4.01% for NOACs, with a weighted absolute risk reduction of 3.78% (95% CI, −0.15% to 7.71%); the weighted risk ratio was 0.52 (0.27–1.00). For recurrent intracerebral hemorrhage, the risk was 7.00% for warfarin and 5.07% for NOACs. The absolute risk reduction was 1.93% (−2.02% to 5.87%), with an a weighted risk ratio of 0.72 (0.38–1.38). Conclusions— NOACs were associated with a nonsignificant lower risk of ischemic stroke and recurrent intracerebral hemorrhage compared with warfarin. The results add to current recommendations of selecting a NOAC agent for stroke prophylaxis treatment in patients with AF, including those with sustaining an intracerebral hemorrhage.

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Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality

JAMA ◽

10.1001/jama.2017.21917 ◽

2018 ◽

Vol 319 (5) ◽

pp. 463 ◽

Cited By ~ 93

Author(s):

Taku Inohara ◽

Ying Xian ◽

Li Liang ◽

Roland A. Matsouaka ◽

Jeffrey L. Saver ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Hospital Mortality ◽

Vitamin K ◽

Oral Anticoagulants ◽

Vitamin K Antagonist

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Non-vitamin K antagonist oral anticoagulants and sport

Minerva Cardioangiologica ◽

10.23736/s0026-4725.20.05177-4 ◽

2020 ◽

Vol 68 (2) ◽

Author(s):

Silvio Romano ◽

Elisa Salustri ◽

Antonio G. Robles ◽

Leonardo Calò ◽

Maria Penco ◽

...

Keyword(s):

Vitamin K ◽

Oral Anticoagulants ◽

Vitamin K Antagonist

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Non-Vitamin K Antagonist Oral Anticoagulants in Pulmonary Embolism: An Overview of Systematic Reviews

Current Pharmaceutical Design ◽

10.2174/1381612826666200506114450 ◽

2020 ◽

Vol 26 (23) ◽

pp. 2686-2691 ◽

Cited By ~ 1

Author(s):

Ioannis Doundoulakis ◽

Christina Antza ◽

Haralambos Karvounis ◽

George Giannakoulas

Keyword(s):

Pulmonary Embolism ◽

Vitamin K ◽

Systematic Reviews ◽

Methodological Quality ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Language Restriction ◽

Overview Of Systematic Reviews

Background: Anticoagulation in patients with pulmonary embolism. Objective: To identify how non-vitamin K antagonist oral anticoagulants are associated with multiple outcomes in patients with pulmonary embolism. Methods: We performed a systematic search of systematic reviews via multiple electronic databases from inception to August 19th, 2019, without language restriction. Two authors independently extracted data and assessed the methodological quality of the included systematic reviews using the ROBIS tool. Results: We found twelve systematic reviews. Eleven SRs collected their data from randomized clinical trials and one from observational studies. All the included studies were published between 2014 and 2019 in English. The methodological quality of the 12 systematic reviews was low to high. None of the systematic reviews, which are included in our overview of systematic reviews, has evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. Conclusion: This is the first effort to summarize evidence about non-vitamin K antagonist oral anticoagulants in an overview of systematic reviews focusing exclusively on patients with pulmonary embolism. The evidence suggests that the non-vitamin K antagonist oral anticoagulants seem to be more effective and safer than a dualdrug approach with LMWH- VKA.

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