‘Between a rock and a couple of hard places’

The management of the pregnant patient with a mechanical prosthetic valve remains a challenging clinical problem, even with recent advances in valve technology, diagnostic and therapeutic strategies. The WHO classification for the assessment of pregnancy risk gives it a class III, which is a significant risk to mother and foetus.

The recent ROPAC registry data showed an event-free pregnancy with a resultant live birth in 58% of women with mechanical valves compared to 78% in women with cardiac disease and no valve intervention.¹ The morbidity and mortality rates for both mother and foetus relate largely to complications stemming from the use of anticoagulation and bleeding, and thromboembolic events.

Jenneker et al. (page 322) provides a comprehensive overview of the current literature and some of the recommendations put forward by the two major international guideline bodies, the American Heart Association/American College of Cardiology (AHA/ACC) and the European Society of Cardiology (ESC). They go on to make a recommendation/algorithm for assessment that is used in their local setting, Inkosi Albert Sisulu Central Hospital, in Durban, KwaZulu-Natal.

Rightfully, the importance of pre-conception counselling and planning is highlighted, together with the proposal of shared decision-making, consisting of a robust and honest discussion of risks and benefits of each regimen with the prospective mother. The three most frequently used strategies are (note, all strategies, swop over to a heparin-based regimen at 36/37 weeks of gestation):

• Warfarin throughout all three trimesters: this regimen is only really to be considered if the required dose of warfarin is to remain within the therapeutic international normalised ratio (INR) range of < 5 mg per day. This is the one considered to have the lowest rate of maternal thrombotic complications, but with a higher rate of foetal miscarriage. The foetal complications are dose dependent (AHA /ACC2 class IIa B/ ESC3 class IIa C recommendation).

• Low-molecular-weight heparin (LMWH) or intravenous (IV) unfractionated heparin (UFH) in the first trimester with switching to warfarin in the second and third trimesters (AHA/ACC2 class IIa B/ESC3 class IIa C).

• LMWH or UFH throughout all three trimesters: although this regimen poses the lowest risk to the foetus, the rate of maternal thrombotic complications can be as high as 33% (AHA/ACC2 class IIb B/ESC3 class IIb C). Unless there is a particularly valid reason with a high risk of warfarin complications, this option is not ideal.

  The data supporting these recommendations are from observational studies and meta-analyses, all of which are wrought with problems of heterogeneity, making direct comparisons between different treatment regimens extremely difficult. The recommendations are therefore frequently noted as level of evidence C (expert opinion or consensus based).^2,3

  When deciding on a particular strategy, the following considerations are to be taken into account in determining the risk–benefit ratio to both the mother and foetus. Some of these challenges are particularly amplified in the South African context and include:

• Adequate anticoagulation with vitamin K antagonists (VKA) (warfarin) and time in therapeutic range (TTR). Numerous local observational studies have noted the difficulty in maintaining TTR in South Africa. A recent retrospective, observational study conducted at two large INR clinics in the Western Cape showed that the mean TTR was 47%, with a mere 25.1% of patients achieving good INR control.⁴ Given the increased thrombotic risk in pregnancy, it is imperative to have facilities available for effective testing and more frequent INR testing compared to the non-pregnant state.

• Staffing, bed availability and IV access. The strategy of IV UFH poses a number of challenges. Patient admission and IV access for a number of weeks is required. The risks of infection from drip sites and the added burden of continued intensive clinical care (doctor and nursing care) in resourcepoor environments make this a less attractive option.

• The availability of factor X levels timeously and regularly is a prerequisite to LMWH use. Both the AHA/ACC2 and the ESC3 give the use of LMWH without regular factor Xa monitoring a class III recommendation, which means it could constitute harm. During pregnancy, the faster renal clearance may result in lower levels. There is no true consensus on the frequency of monitoring levels. The ESC recommends weekly levels whereas the ACC/AHA makes no time recommendation. A big concern remains that although the use of LMWH has gained widespread popularity in our clinical environment, with a favourable risk-factor profile, there is a distinct paucity of availability and resources for factor Xa level monitoring.

• What is a definite ‘NO’? It is important to note that there is no place for the use of aspirin on its own. The addition of aspirin to VKA, although acceptable by the AHA/ACC (class IIb), is not recommended by the ESC, who raise the concern of limited data supporting benefit but with an increased risk of bleeding complications. Given the difficulty of access to emergency care in South Africa, this is to be used with extreme caution.

The use of a direct-acting oral anticoagulants for anticoagulation of mechanical prosthetic valves is contra-indicated. A landmark phase 2 study of dabigatran versus warfarin in 252 patients with mechanical prosthetic mitral or aortic valves was stopped early due to excess thromboembolic and bleeding complications in the dabigatran arm. For this reason, novel oral anticoagulants are not recommended as an alternative to warfarin in mechanical prosthetic valves.⁵

The clinical decision-making in the pregnant patient with a mechanical prosthetic valve remains challenging. Each case is to be considered on an individual level, with consultation and buy-in from both the patient and clinician in a suitably resourced environment.