Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: a meta-analysis

Abstract

The continuation of warfarin throughout pregnancy in patients with a mechanical valve prosthesis is a valid anticoagulation regimen, provided that warfarin dose does not exceed 5 mg/day. Two decades after being introduced, the efficacy and safety of this regimen merit evaluation. We performed a systematic review for cases published between January 1991 and January 2013. We compiled our prospective data on 55 pregnancies and calculated pooled estimates (95% confidence interval) of adverse foetal and maternal outcomes. Events were expressed as proportions of total pregnancies, except embryopathy and maternal death, which were related to the number of live births and number of patients, respectively. There were 494 eligible pregnancies reported in 11 studies. The rate of embryopathy was 0.9% (0.4-2.4%) and most of the 13.4% (8.4-24.7%) foetal losses were due to the 12.8% (7.7-22.7%) rate of spontaneous abortion. No maternal mortality was encountered (0-1.3%) but 0.6% (0.3-2%) prosthetic valve thrombosis, 1.8% (1.1-3.6%) total thromboembolic events and 3.4% (2-5.1%) major maternal bleeding events were recorded. Foetal loss, spontaneous abortions and foetal embryopathy dropped to 8.1% (2.9-13.7%), 7.3% (3.1-11.8%) and 0.6% (0.1-2.1%) among the 344 pregnancies (69.6%) observed in the 6 prospective studies (54.5%). Prosthetic valve thrombosis (0.6%; 01-2%), total thromboembolic (2.3%; 1.2-4.6%) and major bleeding events (2.9%; 1.8-6%) remained comparable with overall results. Foetal embryopathy and prosthetic valve thrombosis were not robust on sensitivity analysis, regardless of the study design. A prospective subgroup of 96 patients (19.4%) received smaller warfarin dose, through targeting a lower international normalized ratio (INR) between 1.5 and 2.5. The associated rate of foetal loss (2.1%; 0.5-6.9%) was significantly lower than that observed in the remaining patients targeting a higher INR between 2.5 and 3.5 (16.1%; 13.1-34.4%). Adverse maternal outcomes were also fewer but rates remained comparable. Limited dose warfarin throughout pregnancy was associated with improved foetal outcomes, without jeopardizing maternal safety. Foetal outcomes were better when patients were followed up prospectively or receiving smaller warfarin doses through targeting a lower INR than recommended (1.5-2.5). Large randomized controlled trials are mandatory to evaluate our findings.

Anticoagulation in pregnancy and puerperium: With a focus on the benefits and risks of the applications of vitamin K antagonists on the prevention of mechanical heart valves thrombosis

“…Unfractionated heparin and low molecular weight heparins do not cross the placenta and therefore do not aff ect the formation and development of the fetus, but carry an increased risk of thrombotic complications in mothers with prosthetic heart valves, even with a properly adjusted dose and careful monitoring [14,21]. Heparin administration during pregnancy virtually eliminates the risk of embryopathy, has no adverse eff ect on development of the fetus, but does not provide protection from thrombotic complications equivalent to that of ensured by VKA administration [14,23].…”

“…Heparin administration during pregnancy virtually eliminates the risk of embryopathy, has no adverse eff ect on development of the fetus, but does not provide protection from thrombotic complications equivalent to that of ensured by VKA administration [14,23].…”

“…A combined approach of treatment with VKA and heparin drugs throughout the period of absolute risk for embriopathy, signifi cantly, almost completely eliminates the risk of embryopathy but increases the risk of thromboembolism and thrombosis of prosthetic valves [14].…”

“…Th erefore, interruption of VKA therapy at 34-36 weeks of gestation is recommended or a cesarean section suggested reducing the possibility of hemorrhage in the child due to birth trauma [9]. Some authors specifi cally point out the development of retroplacental hematoma as a common cause of fetal loss [14]. Th e European guidelines state that VKA administration in the third trimester of pregnancy can cause fetal and neonatal hemorrhage and placental abruption as well as lead in any trimester to abnormalities in the central nervous system, such as optic atrophy, microcephaly, mental retardation, hypotonia and spasticity [9,10,11,15].…”

Bioprosthetic Aortic Valve Replacement in the Young

“…3 Furthermore, a substantial number of young, adult-sized patients facing AVR are female and may wish to avoid VKA during childbearing years, despite recent reports describing favorable outcomes in women with carefully supervised VKA-based anticoagulation during pregnancy. 4 Thus, for young, adult-sized patients (and their parents), the contemplation of which valve is the best, or least worst, choice is based on multiple factors, as shown in the Table, with the final selection based on the combination of risk assessment and lifestyle preferences unique to each young patient. (For the sake of completeness, the Table includes the option of stentless bioprostheses, either allograft or xenograft, although they are rarely used except in unusual forms of endocarditis and extremely small aortic root dimension that would cause severe patient-prosthetic mismatch with conventional AVR.)…”