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Combination anticoagulation strategy in pregnancy with mechanical valves: The KYBELE study - 07/06/24

Doi : 10.1016/j.ahj.2024.03.015 
Mehmet Özkan, MD a, b, Ahmet Güner, MD c, , Sabahattin Gündüz, MD a, Gazi Yıldız, MD d, Ayşe İnci Yıldırım, MD e, Macit Kalçık, MD f, Mahmut Yesin, MD a, Emrah Bayam, MD a, Semih Kalkan, MD a, Mustafa Ozan Gürsoy, MD g, Alev Kılıçgedik, MD a, Zübeyde Bayram, MD a, Münevver Sarı, MD a, Mehmet Aytürk, MD a, Süleyman Karakoyun, MD a, Mehmet Ali Astarcıoğlu, MD a, Elif Cansu Gündoğdu, MD d, Asuman Biçer, MD h, Emre Gürcü, MD i, Tuncer Koçak, MD i, Recep Demirbağ, MD h
a Koşuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, Istanbul, Turkey 
b Ardahan University, Faculty of Health Sciences, Ardahan, Turkey 
c Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Department of Cardiology, Istanbul, Turkey 
d Kartal Dr. Lutfi Kirdar Research and Training Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey 
e Koşuyolu Kartal Heart Training and Research Hospital, Department of Pediatric Cardiology, Istanbul, Turkey 
f Hitit University, Faculty of Medicine, Department of Cardiology, Corum, Turkey 
g İzmir Katip Çelebi University, Atatürk Training and Reseach Hospital, Department of Cardiology, Izmir, Turkey 
h Harran University, Faculty of Medicine, Department of Cardiology, Şanlıurfa, Turkey 
i Koşuyolu Kartal Heart Training and Research Hospital, Department of Anesthesia and Reanimation, Istanbul, Turkey 

Reprint requests: Ahmet Guner, M., Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Department of Cardiology, Turgut Özal Bulvari No:11, 34303, Istanbul, TurkeyIstanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research HospitalDepartment of CardiologyTurgut Özal Bulvari No:11Istanbul34303Turkey

ABSTRACT

Background

Optimal first-trimester anticoagulation is still challenging in pregnant women with mechanical heart valves (MHVs) requiring high-dose warfarin. This multicenter prospective study aims to determine the optimal anticoagulation regimens for pregnant patients with MHVs.

Methods

All women were allocated to one of three treatment options during first trimester including lone low-molecular-weight heparin (LMWH), combination of LMWH + 2.5 mg warfarin, and LMWH+4 mg warfarin. Primary maternal outcome included a combination of death, thromboembolism, severe bleeding, and need for treatment of mechanical valve thrombosis (MVT). Any fetal loss was determined as primary fetal outcome.

Results

The study included 78 pregnancies in 65 women with MHVs. Primary maternal outcome rate was 44%, 12.5%, 3.5%, respectively. The rates of primary maternal outcome (44 vs 3.5%, P < .001), obstructive MVT (16 vs 0%, P = .04), MVT requiring treatment (28 vs 0%, P = .003), and cerebral embolism (24 vs 3.4%, P = .041) were found to be significantly higher in lone LMWH group compared to LMWH + 4 mg warfarin group. Moreover, the rates of primary maternal outcome (12.5 vs 44%, P = .015) and treatment for MHV thrombus (4.2 vs 28%, P = .049) were significantly lower in LMWH + 2.5 mg warfarin group compared to lone LMWH group. The incidences of fetal loss were 8 (32%) in the lone LMWH group, 8 (33.3%) in LMWH + 2.5 mg warfarin group, and 11 (37.9%) in LMWH + 4 mg warfarin group (P = .890 for 3-group).Warfarin related-embryopathy was not observed in any case.

Conclusions

The combined anticoagulation strategy of LMWH plus low-dose warfarin during the first trimester of pregnancy may result in less maternal complications with comparable fetal outcomes in patients with MHVs.

Condensed abstract

Low-molecular-weight heparin (LMWH) is thought to be safer for the fetus, however it is suspected to be less protective for the mother. To solve this dilemma, the authors suggested a novel anticoagulation strategy in pregnant women with prosthetic valves. Seventy-eight pregnancies of 65 women (median age 32 [27-35] years) were included in the study. A combination of LMWH and a reduced dose warfarin were associated with low rates of thrombus-related complications in pregnant patients with mechanical heart valves.

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Graphical abstract




Image, graphical abstract

Il testo completo di questo articolo è disponibile in PDF.

Mappa


 Drs. Jerome Jeffrey Federspiel, MD, PhD and Sarah Goldstein, MD served as Guest Editors for this manuscript.


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