Warfarin OK in Expectant Moms with Mechanical Heart Valve

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After mechanical heart valve placement, a low-dose regimen of vitamin K antagonist (VKA) may be safest for both mother and child during the hypercoagulable state of pregnancy, a meta-analysis suggested.

Maternal risk -- a composite endpoint including maternal death, thromboembolism, and valve failure -- was 5% with VKAs like warfarin (Coumadin), lower than with the anticoagulation strategy of low-molecular-weight heparin (maternal risk 15.5%, ratio of averaged risk [RAR] 3.1, 95% CI 1.3-7.5).

On the flip side, unsurprisingly, the risk of fetal spontaneous abortion, death, and congenital defects was lower if the mother took low-molecular-weight heparin (13.9%) rather than warfarin (39.2%, RAR 0.4, 95% CI 0.1-0.8), reported Zachary L. Steinberg, MD, of the University of Washington in Seattle, and colleagues in Journal of the American College of Cardiology.

Tipping the scales back in warfarin's favor was the investigators' finding that pregnant women who took 5 mg daily warfarin or less shared a similar fetal risk (4.8%) with those who took low-molecular-weight heparin (RAR 0.9, 95% CI 0.3-2.1).

"On the basis of this contemporary meta-analysis of 800 pregnancies in women with mechanical heart valves and modern anticoagulation regimens, VKA is the anticoagulation regimen associated with the lowest risk of adverse maternal outcomes," Steinberg's group concluded.

"Our results support the American College of Cardiology and American Heart Association guidelines for the management of patients with valvular heart disease, which recommend the use of low-dose warfarin in women who are able to maintain therapeutic international normalized ratios (Class IIa) over the use of either first trimester low-molecular-weight heparin or heparin use (Class IIb)."

Not so fast, suggested Uri Elkayam, MD, of University of Southern California in Los Angeles, in an accompanying editorial. While birth defects and fetal loss have been associated with taking warfarin during pregnancy, particularly in the 6th to 9th weeks, "these results clearly suggest that the detrimental effect of a VKA on fetal outcome is not limited to the first trimester," Elkayam wrote.

"In addition, the use of a VKA during pregnancy has also been shown in other publications to lead to intracranial bleeding, central nervous system abnormalities, minor neurologic dysfunction, and low intelligent quotients at later age."

"Despite the Class I recommendations by both the American and European guidelines for the use of a VKA during the second and third trimesters, there is a need to clearly inform women about the risk-benefit ratio associated with this approach," the editorialist continued.

Furthermore, Elkayam pointed out a caveat in the elevated maternal risk tied to low-molecular-weight heparin that was found in Steinberg's study: "A critical review of the data clearly shows that most if not all of the thromboembolism events were due to subtherapeutic anticoagulation secondary to inappropriate dosing, poor monitoring, or poor patient compliance."

The meta-analysis included 800 pregnancies (from 1974 to 2014) gathered from 18 studies.

Warfarin use throughout pregnancy bested unfractionated heparin followed by warfarin after the first trimester in terms of maternal safety (maternal risk 15.8%, RAR 3.1, 95% CI 1.5-7.1). The strategy trended towards better maternal safety than the switch from low-molecular-weight heparin to warfarin after the first trimester (maternal risk 15.9%, RAR 3.2, 95% CI 0.9-8.8).

Steinberg's group cautioned against directly comparing between groups because of their retrospective analysis. "Additionally, the data for specific anticoagulation regimens were clustered by region, thus introducing the possibility that differences in access to healthcare could have influenced outcomes. Second, there is a paucity of published data reporting maternal and fetal outcomes in pregnant women with modern mechanical heart valves who are receiving many of the newer anticoagulation regimens, and this scarcity increases the likelihood of a type II error," the authors wrote.