USE OF ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs) IN PREGNANCY

Angiotensin-II receptor blockers (ARBs) (azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan) are used in the treatment of hypertension, heart failure and diabetic nephropathy.

ARB use during the second or third trimester has been associated with a potentially severe fetopathy. Features are secondary to oligo-/anhydramnios and include neonatal renal impairment with or without oligo-/anuria, joint contractures, hypocalvaria/widened skull sutures, and pulmonary hypoplasia. Thrombosis of the vena cava may also be a feature. Iatrogenic preterm delivery (and therefore low infant birth weight) is also common. No controlled cohort studies have quantified rates of these outcomes following ARB exposure in later pregnancy; however, a small prospective case series cited a fetopathy rate of 29% in fetuses exposed from 20 gestational weeks and stated that this was the specific risk period. ARB exposure appears to be associated with a higher risk of fetopathy than exposure to angiotensin-converting enzyme inhibitors (ACE-Is).

There is currently no convincing evidence that first trimester exposure to ARBs is associated with an increased risk of congenital malformation, either overall or for specific anomalies, or other adverse fetal outcomes. However, data specifically relating to first trimester ARB exposure are limited to a collective total of ~420 pregnancies and further information is ideally required.

The National Institute for Health and Care Excellence (NICE) guidelines advise that women taking an ARB who are planning a pregnancy should be offered a medication review. Women who become pregnant while taking an ARB should be offered a different antihypertensive if clinically appropriate. NICE recommends labetalol as first-line antihypertensive for use during pregnancy, with nifedipine or methyldopa being possible alternatives depending on any pre-existing treatment, side effect profiles, risks (including fetal effects) and the woman’s preference.

In rare cases where an ARB is continued beyond the first trimester, either inadvertently or to ensure maternal wellbeing, the woman should be closely monitored by maternal and fetal medicine specialists. This may necessitate transfer to a tertiary referral centre. Serial ultrasound scans to assess fetal growth and wellbeing and amniotic fluid levels are indicated. Discussion with UKTIS is recommended. Women who are pregnant or of childbearing potential who are treated with an ARB should be fully informed of the fetal risks. Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.