Pravastatin in Managing Poor Obstetric Outcomes in APAS

Anti-phospholipid antibody syndrome (APAS) is an autoimmune non-inflammatory condition characterized by vascular thrombosis and pregnancy morbidity in the background of anti-phospholipid (aPL) antibodies. Up to one-third of lupus patients may have concomitant APAS which further complicates management. Evidence suggests that presence of lupus anti-coagulants correlate with risks for developing poor pregnancy outcomes and vascular events and these risks are multiplied by the presence of additional aPLs. While a variety of options are available to treat APAS related vascular events, there are limited options to treat pregnancy morbidity.

Pregnancy morbidity in APAS include:

  • ≥1 unexplained fetal death after 10 weeks AOG
  • ≥1 premature birth due to severe pre-eclampsia or placental insufficiency before 34 weeks AOG
  • ≥3 consecutive spontaneous abortions before 10 weeks AOG (need to exclude anatomic, hormonal and chromosomal abnormalities as reasons for abortion)

Statins have been shown to demonstrate anti-thrombotic activity beyond its ability to lower LDL-cholesterol. Mouse models have shown a potential role for statins in treating APAS.

Lefkou E, et al. explored the efficacy of pravastatin 20mg once daily in treating pre-eclampsia (PE) and intra-uterine growth retardation (IUGR) in pregnant patients who met APAS criteria and developed these problems despite being given LMWH and low dose ASA since confirmation of pregnancy. This was a non-randomized unblinded interventional trial involving 21 pregnant APAS patients who received similar treatments for PE.

Of the 10 in the control group, following diagnosis of PE and/or IUGR, pregnancies continued for a mean of 4 weeks (IQR 2-6 weeks) with 7 pregnancies terminated prematurely (mean of 26.2 weeks AOG and IQR 26-32) via emergency CS for fetal distress or maternal health concerns and 3 ending in stillbirth. The 7 infants were all admitted to the NICU due to prematurity – 2 of which died. Of the 5 that survived, 3 demonstrated neurologic and gastrointestinal developmental problems.

Of the 11 who received pravastatin, it was observed that BP and proteinuria improved significantly (compared to those in the control group) within 10 days of starting treatment and there was also doppler evidence showing improvement in uteroplacental blood flow with some fetuses demonstrating weight gain. Pregnancies continued for a mean of 13 weeks following diagnosis of IUGR and/or PE (IQR 10-15 with p<0.01 compared to controls). All were able to complete pregnancies after 34 weeks AOG (median 36, IQR 35-36) with 8 delivering at 36 weeks AOG. In 2 pregnancies, neonates had to be admitted to the NICU due to severe IUGR but were able to be discharged well from the unit. All neonates in this group were doing well at the end of the study and none demonstrated developmental problems

We do have to note that pravastatin is contraindicated in pregnancy based on the updated FDA pregnancy and lactation classification. Although, updated data show no expected risk for teratogenicity with pravastatin from limited human trials but is possible from conflicting and limited data from other statins. A larger and better designed trial may dispel doubts on its safety and further confirm its effficacy in obstetric APAS.

But with this study, pravastatin is definitely something to watch out for in APAS treatment.

Reference: Lefkou E, et al. Pravastatin improves pregnancy outcomes in obstetric APS refractory to anti-thrombotic therapy. J Clin Invest 2016; 126(8): 2933-40.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s