Combination anticoagulation strategy in pregnancy with mechanical valves: The KYBELE study

Mehmet Özkan; Ahmet Güner; Sabahattin Gündüz; Gazi Yıldız; Ayşe İnci Yıldırım; Macit Kalçık; Mahmut Yesin; Emrah Bayam; Semih Kalkan; Mustafa Ozan Gürsoy; Alev Kılıçgedik; Zübeyde Bayram; Münevver Sarı; Mehmet Aytürk; Süleyman Karakoyun; Mehmet Ali Astarcıoğlu; Elif Cansu Gündoğdu; Asuman Biçer; Emre Gürcü; Tuncer Koçak; Recep Demirbağ

doi:10.1016/j.ahj.2024.03.015

Combination anticoagulation strategy in pregnancy with mechanical valves: The KYBELE study

Am Heart J. 2024 Apr 1:273:21-34. doi: 10.1016/j.ahj.2024.03.015. Online ahead of print.

Authors

Mehmet Özkan¹, Ahmet Güner², Sabahattin Gündüz³, Gazi Yıldız⁴, Ayşe İnci Yıldırım⁵, Macit Kalçık⁶, Mahmut Yesin³, Emrah Bayam³, Semih Kalkan³, Mustafa Ozan Gürsoy⁷, Alev Kılıçgedik³, Zübeyde Bayram³, Münevver Sarı³, Mehmet Aytürk³, Süleyman Karakoyun³, Mehmet Ali Astarcıoğlu³, Elif Cansu Gündoğdu⁴, Asuman Biçer⁸, Emre Gürcü⁹, Tuncer Koçak⁹, Recep Demirbağ⁸

Affiliations

¹ Koşuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, Istanbul, Turkey; Ardahan University, Faculty of Health Sciences, Ardahan, Turkey.
² Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Department of Cardiology, Istanbul, Turkey. Electronic address: ahmetguner488@gmail.com.
³ Koşuyolu Kartal Heart Training and Research Hospital, Department of Cardiology, Istanbul, Turkey.
⁴ Kartal Dr. Lutfi Kirdar Research and Training Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey.
⁵ Koşuyolu Kartal Heart Training and Research Hospital, Department of Pediatric Cardiology, Istanbul, Turkey.
⁶ Hitit University, Faculty of Medicine, Department of Cardiology, Corum, Turkey.
⁷ İzmir Katip Çelebi University, Atatürk Training and Reseach Hospital, Department of Cardiology, Izmir, Turkey.
⁸ Harran University, Faculty of Medicine, Department of Cardiology, Şanlıurfa, Turkey.
⁹ Koşuyolu Kartal Heart Training and Research Hospital, Department of Anesthesia and Reanimation, Istanbul, Turkey.

PMID: 38570020
DOI: 10.1016/j.ahj.2024.03.015

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.