A prospective randomized trial of direct oral anticoagulant therapy with a fully magnetically levitated LVAD: the DOT-HM3 study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F24%3A00085006" target="_blank" >RIV/00023001:_____/24:00085006 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.ahajournals.org/doi/epub/10.1161/CIRCULATIONAHA.124.069726" target="_blank" >https://www.ahajournals.org/doi/epub/10.1161/CIRCULATIONAHA.124.069726</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1161/CIRCULATIONAHA.124.069726" target="_blank" >10.1161/CIRCULATIONAHA.124.069726</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A prospective randomized trial of direct oral anticoagulant therapy with a fully magnetically levitated LVAD: the DOT-HM3 study

Popis výsledku v původním jazyce

Purpose: Although the fully magnetically levitated HeartMate 3 (HM3) LVAD has demonstrated superiority in reducing pump thrombosis and stroke outcomes, the need for anti-thrombotic therapy with a Vitamin-K Antagonist (VKA) remains suboptimal and resource intensive . Whether direct oral anticoagulants (DOAC) that inhibit Factor Xa when used instead of Vitamin-K Antagonists (VKA) with the HM3 pump are safe and preserve hemocompatibility-related adverse event outcomes, remains unknown. This is particularly important since legacy devices have shown an increase in thrombotic complications with use of DOACs.Methods: We enrolled patients with the HM3 LVAD at least 3 months post-implant, who were free of a major hemocompatibility-related adverse event and tolerating a VKA targeted to an INR of 2-3. Randomization (2:1) to either apixaban 5mg twice daily or continued therapy with VKA was accomplished, and those allocated to apixaban were further randomized (1:1) to either continued use of 100 mg aspirin once daily or withdrawal (based on the ARIES-HM3 study which showed reduced bleeding rates with elimination of aspirin, while preserving clinical outcomes).Endpoints In this trial, the primary safety endpoint was survival-free of pump thrombosis, disabling stroke, or major bleeding at 3 months post-randomization, and patients were followed for clinical outcomes to at least 6 months. Comprehensive surveillance for pump thrombosis was mandated based on an established clinical algorithm that included measurement of pro-thrombosis biomarkers and pump parameter interrogation.Results: Study enrollment was completed with 45 patients (warfarin plus aspirin n=14, apixaban plus aspirin n=15 and apixaban alone n=16). The enrolled population included 40 males, mean age 62 years (range 24-77), 51% with ischemic etiology, and 54% bridge to transplant goal. All patients reached 6 months of follow-up. No episodes of thromboembolism (pump thrombosis or stroke were noted in either of the 3 study groups at 3 months or at 6 months. In the VKA group, 2 patients developed uterine bleeding (day 21 and 54) and 1 epistaxis (day 2); 1 patient in the apixaban plus aspirin arm experienced a gastrointestinal bleed (day 20) while no patients experienced bleeding in those randomized to apixaban alone. Six heart transplants were performed in apixaban treated patients and 1 among the warfarin group, without adverse outcome or excessive post-operative bleeding. Reversal antidotes to apixaban were not required in any patients receiving apixaban. Four patients were withdrawn for reasons other than a transplant procedure (1 in the VKA arm who transitioned to palliative care on day 85; 3 patients in the apixaban groups for a gastrointestinal bleed, mediastinitis and medical non-adherence).Summary: The DOT-HM3 study has demonstrated a) safety of using a DOAC (with or without aspirin) in the short-term of 6 months, b) No occurrence of thrombosis or bleeding in those treated with a DOAC alone without aspirin, c) safety of bridging to heart transplant without an excess in bleeding complications post procedure.Conclusion: In carefully selected stable patients 3 months after HM3 LVAD implantation, a strategy that switches a VKA to a DOAC appears safe in the short term of 6-months in either bridge to transplantation or destination therapy patients. These findings provide reassurance for testing the use of DOACs in HM3 LVAD implanted patients within large-scale trials with long-term follow up duration.

Název v anglickém jazyce

A prospective randomized trial of direct oral anticoagulant therapy with a fully magnetically levitated LVAD: the DOT-HM3 study

Popis výsledku anglicky

Purpose: Although the fully magnetically levitated HeartMate 3 (HM3) LVAD has demonstrated superiority in reducing pump thrombosis and stroke outcomes, the need for anti-thrombotic therapy with a Vitamin-K Antagonist (VKA) remains suboptimal and resource intensive . Whether direct oral anticoagulants (DOAC) that inhibit Factor Xa when used instead of Vitamin-K Antagonists (VKA) with the HM3 pump are safe and preserve hemocompatibility-related adverse event outcomes, remains unknown. This is particularly important since legacy devices have shown an increase in thrombotic complications with use of DOACs.Methods: We enrolled patients with the HM3 LVAD at least 3 months post-implant, who were free of a major hemocompatibility-related adverse event and tolerating a VKA targeted to an INR of 2-3. Randomization (2:1) to either apixaban 5mg twice daily or continued therapy with VKA was accomplished, and those allocated to apixaban were further randomized (1:1) to either continued use of 100 mg aspirin once daily or withdrawal (based on the ARIES-HM3 study which showed reduced bleeding rates with elimination of aspirin, while preserving clinical outcomes).Endpoints In this trial, the primary safety endpoint was survival-free of pump thrombosis, disabling stroke, or major bleeding at 3 months post-randomization, and patients were followed for clinical outcomes to at least 6 months. Comprehensive surveillance for pump thrombosis was mandated based on an established clinical algorithm that included measurement of pro-thrombosis biomarkers and pump parameter interrogation.Results: Study enrollment was completed with 45 patients (warfarin plus aspirin n=14, apixaban plus aspirin n=15 and apixaban alone n=16). The enrolled population included 40 males, mean age 62 years (range 24-77), 51% with ischemic etiology, and 54% bridge to transplant goal. All patients reached 6 months of follow-up. No episodes of thromboembolism (pump thrombosis or stroke were noted in either of the 3 study groups at 3 months or at 6 months. In the VKA group, 2 patients developed uterine bleeding (day 21 and 54) and 1 epistaxis (day 2); 1 patient in the apixaban plus aspirin arm experienced a gastrointestinal bleed (day 20) while no patients experienced bleeding in those randomized to apixaban alone. Six heart transplants were performed in apixaban treated patients and 1 among the warfarin group, without adverse outcome or excessive post-operative bleeding. Reversal antidotes to apixaban were not required in any patients receiving apixaban. Four patients were withdrawn for reasons other than a transplant procedure (1 in the VKA arm who transitioned to palliative care on day 85; 3 patients in the apixaban groups for a gastrointestinal bleed, mediastinitis and medical non-adherence).Summary: The DOT-HM3 study has demonstrated a) safety of using a DOAC (with or without aspirin) in the short-term of 6 months, b) No occurrence of thrombosis or bleeding in those treated with a DOAC alone without aspirin, c) safety of bridging to heart transplant without an excess in bleeding complications post procedure.Conclusion: In carefully selected stable patients 3 months after HM3 LVAD implantation, a strategy that switches a VKA to a DOAC appears safe in the short term of 6-months in either bridge to transplantation or destination therapy patients. These findings provide reassurance for testing the use of DOACs in HM3 LVAD implanted patients within large-scale trials with long-term follow up duration.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Circulation

ISSN

0009-7322

e-ISSN

1524-4539

Svazek periodika

150

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

3

Strana od-do

509-511

Kód UT WoS článku

001284927200017

EID výsledku v databázi Scopus

2-s2.0-85194357467