ACE inhibitors and angiotensin II receptor antagonists: not for use in pregnancy
- Medicines and Healthcare products Regulatory Agency
- 1 December 2007
- Therapeutic area:
- Cardiovascular disease and lipidology
Use in women who are planning pregnancy should be avoided unless absolutely necessary, in which case the potential risks and benefits should be discussed
Article date: December 2007
Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists are licensed for various indications, including hypertension, and may be particularly suitable for young patients with high blood pressure (but not those of black ethnic origin) and those with some comorbidities such as diabetic nephropathy.
Angiotensin II is essential for normal kidney development, and use of ACE inhibitors and angiotensin II receptor antagonists in late pregnancy has been associated with renal dysfunction, oligohydramnios, neonatal anuria, and other congenital anomalies such as skull ossification defects. However, data have also suggested an increased risk of congenital anomaly after exposure limited to the first trimester of pregnancy.
A US cohort study1 that used Medicaid data from Tennessee noted an increased risk of congenital anomalies with ACE inhibitors, particularly anomalies of the cardiovascular system and CNS. On the basis of 18 cases (all major anomalies) among 209 infants exposed to ACE inhibitors in the first trimester, the table below shows adjusted risk ratios for congenital anomalies compared with infants who had no exposure to antihypertensive medicines in the first trimester:
Adjusted risks for exposure to ACE inhibitor or other antihypertensive versus no antihypertensive in first trimester
|Risk ratio (95% CI)|
|ACE inhibitor exposure|
|Any major congenital malformation||2·71 (1·72–4·27)|
|Cardiovascular malformation||3·72 (1·89–7·30)|
|CNS malformation||4·39 (1·37–14·02)|
|Other antihypertensive exposure*|
|Major congenital malformation||0·66 (0·25–1·75)|
*Angiotensin II receptor antagonists were excluded.
The table also shows that this study identified no increased risk with other classes of antihypertensives; however, angiotensin II receptor antagonists were excluded.
Because maternal diabetes is independently associated with an increased risk of congenital anomaly, the researchers attempted to exclude mothers with known diabetes. Although the study has some limitations, such as a small number of events, it raises substantial concern about possible teratogenicity with ACE inhibitors in the first trimester of pregnancy.
There are fewer data for the risks with angiotensin II receptor antagonists, although there are case reports2 3 of congenital anomaly after exposure to these agents during the second and third trimesters. Furthermore, there are no data to exclude a possible risk similar to that noted for ACE inhibitors in the first trimester.
Advice for healthcare professionals:
Patients who are planning pregnancy:
- Unless continued treatment with an ACE inhibitor or angiotensin II receptor antagonist is considered essential (eg, in some patients with hypertension and diabetic nephropathy), women who are planning pregnancy should be switched to alternative antihypertensive treatments that have an established safety profile for use in pregnancy
- The balance of risks and benefits of continued treatment with an ACE inhibitor or angiotensin II receptor antagonist versus the potential risk of congenital anomaly should be discussed with the patient
Patients who are pregnant:
- On diagnosis of pregnancy, treatment with an ACE inhibitor or angiotensin II receptor antagonist should be stopped as soon as possible, and, if appropriate, alternative treatment should be started
For further information please see Individual Summaries of Product Characteristics
Article citation: Drug Safety Update Dec 2007; Vol 1 Issue 5: 8
Published: 1 December 2007
Therapeutic area: Cardiovascular disease and lipidology