Angiotensin-II receptor blockers (ARBs) (azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan) are typically used in the treatment of hypertension, heart failure and diabetic nephropathy.
ARB use during the second or third trimesters of pregnancy 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) are 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 ACE-inhibitors.
There is currently no convincing evidence that first trimester exposure to ARBs is associated with an increased risk of congenital malformation, neither overall nor for specific anomalies, or other adverse fetal outcomes. However, data relating to first trimester ARB exposure are limited to a collective total of ~420 pregnancies and further information is required.
The National Institute for Health and Care Excellence (NICE) guidelines advise that women taking ARBs who are planning a pregnancy should seek specialist advice regarding alternative therapy. Women who become pregnant while taking an ARB should be advised to switch antihypertensive therapy. NICE guidelines identify 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.
Where ARB use beyond the first trimester is considered to be unavoidable or has occurred accidentally, strict supervision is required from experts in both maternal and fetal medicine. This may require transfer of the patient to a tertiary referral centre. All pregnant women and those of childbearing potential who are treated with an ARB should be fully informed of the fetal risks. Discussion with UKTIS is recommended. 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.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.