Combination Anticoagulation Strategy in Pregnancy With Mechanical Valves: The KYBELE Study.

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<0.001), obstructive MVT (16 vs 0%, p=0.04), MVT requiring treatment (28 vs 0%, p=0.003), and cerebral embolism (24 vs 3.4%, p=0.041) 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=0.015) and treatment for MHV thrombus (4.2 vs 28%, p=0.049) 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=0.890 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.