ANTICOAGULATION FOR PREGNANT WOMEN WITH MECHANICAL HEART VALVES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Purpose: To systematically compare maternal and fetal outcomes arising from the use of methods of anticoagulation – vitamin K antagonists (VKA), heparin and combination treatment - in pregnant women with mechanical heart valves (MHVs).

Method: Three bibliographic databases were searched. Two reviewers independently selected articles, extracted data from included studies and assessed the risk of bias using a modified Newcastle-Ottawa Quality Assessment Scale for cohort studies. Pooled incidence rates [95% confidence interval (CI)] were calculated. Primary outcomes included maternal death, thromboembolic complications (TECs), live births and congenital anomalies. 

Result: Forty-six studies, mainly at high risk (27/46) of bias, were included in the meta-analysis. Incidences of maternal mortality and TECs were [9/1000 (95%CI 4-14/1000) and 21/1000 (95%CI 13-28/1000)] with VKA use throughout pregnancy; 31/1000 (95%CI 7-54/1000) and 93/1000 (95%CI 51-134/1000) with heparin use and 20/1000 (95%CI 8-31/1000) and 58/1000 (95%CI 38-77/1000) with combination treatment respectively. Live-birth rates for the three groups were 715/1000 (95%CI 642-788/1000), 854/1000 (95%CI 760-948/1000) and 799/1000 (95%CI 743-856/1000) respectively. Congenital anomaly rates were 35/1000 (95%CI 21-49/1000), 37/1000 (95%CI 7-67/1000) and 14/1000 (95%CI 3-25/1000). On subgroup analysis, use of low molecular weight heparin throughout pregnancy was associated with the highest live-birth rate [920/1000 (95%CI 861-980/1000)]. Congenital anomaly rates with daily VKA dose of ≤ 5mg were 22/1000 (95%CI 5-39/1000), which was no different from the use of standard VKA doses (26/1000 – 95%CI 5-46/1000).  

Conclusion: VKA are associated with low maternal complication rates but also with low live-birth rates. LMWH may be a suitable alternative in pregnant women with MHVs, both in the first trimester as well as throughout pregnancy. There is insufficient evidence to recommend the use of warfarin in the first trimester even if the daily dose is ≤ 5mg, or the use of UFH throughout pregnancy. Further multi-center studies comparing three strategies and assessing maternal and neonatal outcomes on a large-scale is needed.