Fixed Versus Variable Dosing of Prothrombin Complex Concentrate for Bleeding Complications of Vitamin K Antagonists—The PROPER3 Randomized Clinical Trial

Abstract Background Falls from standing are common in the elderly and are associated with a significant risk of bleeding. We have compared the proportional incidence of bleeding complications in patients on either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA). Methods Our retrospective cohort study compared elderly patients (≥65 years) on DOAC or VKA oral anticoagulation who presented at the study site – a Swiss university emergency department (ED) – between 01.06.2012 and 01.07.2017 after a fall. The outcomes were the proportional incidence of any bleeding complication and its components (e.g. intracranial haemorrhage), as well as procedural and clinical parameters (length of hospital stay, admission to intensive care unit, in-hospital-mortality). Uni- and multivariable analyses were used to compare the studied outcomes. Results In total, 1447 anticoagulated patients were included – on either VKA (n = 1021) or DOAC (n = 426). There were relatively more bleeding complications in the VKA group (n = 237, 23.2%) than in the DOAC group (n = 69, 16.2%, p = 0.003). The difference persisted in multivariable analysis with 0.7-fold (95% CI: 0.5–0.9, p = 0.014) lower odds for patients under DOAC than under VKA for presenting with any bleeding complications, and 0.6-fold (95% 0.4–0.9, p = 0.013) lower odds for presenting with intracranial haemorrhage. There were no significant differences in the other studied outcomes. Conclusions Among elderly, anticoagulated patients who had fallen from standing, those under DOACs had a lower proportional incidence of bleeding complications in general and an even lower incidence of intracranial haemorrhage than in patients under VKAs.

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Optimal Anticoagulation Strategy for Cardioversion in Atrial Fibrillation

Arrhythmia & Electrophysiology Review ◽

10.15420/aer.2015.4.1.44 ◽

2015 ◽

Vol 4 (1) ◽

pp. 44 ◽

Cited By ~ 2

Author(s):

Philipp Bushoven ◽

Sven Linzbach ◽

Mate Vamos ◽

Stefan H Hohnloser ◽

◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Stroke Prevention ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Prospective Trial ◽

Bleeding Complications ◽

Order Of Magnitude ◽

Pharmacological Cardioversion

For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion.

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Low-dose Vitamin K can Improve Warfarin Control in Patients on LVAD Support

The VAD Journal ◽

10.14434/vad.v1i0.27860 ◽

2015 ◽

Author(s):

Daizo Tanaka ◽

Venessa L. Kotch ◽

Cheryl Abbas ◽

Gordon R. Reeves ◽

John WC Entwistle III

Keyword(s):

Vitamin K ◽

Low Dose ◽

Statistical Significance ◽

Vitamin K Antagonists ◽

Warfarin Dose ◽

Left Ventricular ◽

Bleeding Complications ◽

Thromboembolic Complications ◽

Before And After ◽

Lvad Support

Background Anticoagulation with oral vitamin K antagonists (VKA) is very important in patients supported on a left ventricular assist device (LVAD) to prevent thromboembolic complications. Some patients tolerate VKAs poorly and have an unstable INR as a result. It is reported that low-dose vitamin K can improve INR control in patients with an unstable INR in other clinical settings. We evaluated its safety and effectiveness in patients on LVAD support. Methods The records of all patients supported on an implantable LVAD between January, 2013 and March, 2014 were reviewed retrospectively to identify those who had received low-dose vitamin K while on warfarin. INR values and warfarin doses before and after initiation of vitamin K supplementation were compared to evaluate its effectiveness. Results There were six LVAD patients who were on low-dose vitamin K due to an unstable INR out of a total of 59 VAD patients followed as an outpatient. The standard deviation (SD) of INR decreased significantly after starting vitamin K (p=0.04) while the SD of warfarin dose did not (p=0.22). Comparing divergence from target INR, INR became significantly closer to target INR after starting vitamin K. The number of bleeding complications tended to be fewer on vitamin K, but this did not reach statistical significance (p=0.09). Conclusions Daily low-dose vitamin K supplementation can improve INR control in LVAD patients with unstable INR without increasing thromboembolic complications.

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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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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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Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-020-02304-3 ◽

2020 ◽

Cited By ~ 2

Author(s):

Marco Valerio Mariani ◽

Michele Magnocavallo ◽

Martina Straito ◽

Agostino Piro ◽

Paolo Severino ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Major Bleeding ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Significant Risk ◽

Bleeding Complications ◽

Efficacy And Safety

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

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A low fixed dose of prothrombin complex concentrate is cost effective in emergency reversal of vitamin K antagonists

Haematologica ◽

10.3324/haematol.2013.085043 ◽

2013 ◽

Vol 98 (6) ◽

pp. e65-e67 ◽

Cited By ~ 6

Author(s):

N. Khorsand ◽

L. Giepmans ◽

K. Meijer ◽

R. M. van Hest ◽

N. J. G. M. Veeger

Keyword(s):

Vitamin K ◽

Prothrombin Complex Concentrate ◽

Vitamin K Antagonists ◽

Cost Effective ◽

Fixed Dose

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Antithrombotische Therapie bei akutem Koronarsyndrom und Vorhofflimmern

DMW - Deutsche Medizinische Wochenschrift ◽

10.1055/a-0955-3257 ◽

2020 ◽

Vol 145 (14) ◽

pp. 978-986

Author(s):

Harald Darius

Keyword(s):

Triple Therapy ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Antiplatelet Agent ◽

Current Status ◽

Bleeding Complications ◽

Coronary Syndrome ◽

Coronary Stent Implantation ◽

Number Of Patients

AbstractThe number of patients with atrial fibrillation (AF) is increasing due to the aging of the population. In addition, the number of patients with AF and an indication for oral anticoagulation (OAC) for the prevention of strokes increases, who are in need for a dual antiplatelet therapy (DAPT) with acetyl salicylic acid (ASA) plus a P2Y12-Inhibitor because of an acute coronary syndrome and/or coronary stent implantation. These patients did receive a triple therapy (TT) for 3–12 months in the past. Triple therapy never has been studied for efficacy or safety, however, the rate of bleeding complications in comparison to OAC or DAPT is significantly higher.Registries and smaller trials showed that dual therapy with an OAC plus a single platelet inhibitor may be sufficient to prevent strokes and stent thromboses/myocardial infarctions. Four prospective randomized trials involving all four NOACs (Non-Vitamin K oral anticoagulants) approved for stroke prevention in AF have been undertaken. The NOACs plus one antiplatelet agent were tested versus vitamin K-antagonists plus DAPT. In the meantime, the trials involving rivaroxaban (PIONEER AF-PCI), dabigatran (RE-DUAL PCI), apixaban (AUGUSTUS), and edoxaban (ENTRUST-AF-PCI) have been published. The current status is that a NOAC plus a single antiplatelet agent, mostly clopidogrel, is superior to TT with respect to the bleeding complications, without any obvious and statistically significant disadvantage for stroke rates or cardiac ischemic events. The international guidelines already recommend to treat with a NOAC and one antiplatelet agent instead of TT in case the patients bleeding risk is prevailing. Thus, TT seems not to be indicated anymore for most patients with AF and ACS or PCI.

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