Consumer Alert: Use of Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) During First Trimester of Pregnancy Associated With Serious Birth Defects

July 24, 2006

According to a recently published study in the New England Journal of Medicine, ACE inhibitors or ACEIs (short for angiotensin-converting enzyme inhibitors) used to treat high blood pressure can cause serious birth defects if taken during the first trimester of pregnancy.^[¹^] The researchers found that women who took ACE inhibitors during their first trimester of pregnancy were more than twice as likely than women who took other types of blood pressure drugs to give birth to a child with a major birth defect, particularly defects in the cardiovascular system and central nervous system.^[¹^] The FDA has issued an alert in response to these findings, recommending that pregnant women who are taking ACE inhibitors talk to their doctors.^[²^] Some ACEIs are:

Benazepril (Lotensin)
Captopril (Capoten),
Enalapril/Enalaprilat (Vasotec)
Fosinopril (Monopril)
Lisinopril (Zestril and Prinivil)
Moexipril (Univasc)
Perindopril (Aceon)
Quinapril (Accupril)
Ramipril (Altace)
Trandolapril (Mavik)

As explained in more detail below, physicians and researchers have known for some years that ACE inhibitor medications should not be the first choice for treating high blood pressure in almost any situation, and especially not during pregnancy.

More Information About ACEIs and Pregnancy:

The Food and Drug Administration (FDA) issued a warning nearly fifteen years ago that ACEI use during the second and third trimester of pregnancy could cause serious birth defects, such as kidney failure and face or skull deformities.^[³^] At that time the FDA did not warn against using ACE inhibitors during the first trimester of pregnancy, but by 1997 the Centers for Disease Control and Prevention (CDC) had issued a report stating that because of the known risks of ACEI use in the later stages of pregnancy and a lack of data demonstrating safety during the first trimester, "Whenever possible, pregnant women who are using ACEIs should be changed to another antihypertensive medication to maintain normal blood pressure."^[⁴^] A medical article that came out at around the same time similarly concluded that "one should avoid starting ACE inhibitors during pregnancy and discontinue them in current users if at all possible."^[⁵^]

Then, a few years later, came more bad news about ACE inhibitors. At the end of 2002, researchers released the results of the ALLHAT study, a major study comparing an ACE inhibitor (lisinopril), a calcium channel blocker (amlodipine), and a diuretic (chlorthalidone).^[⁶^] According to the American College of Physicians' summary of the study, the researchers found that ACE inhibitors were no more effective than diuretics at controlling blood pressure, but were associated with higher rates of strokes and heart disease: patients taking ACE inhibitors had a 15% higher risk of stroke and a 10% higher risk of cardiovascular disease than patients taking diuretics.^[⁷^] Diuretics are also much less expensive, costing as little as $22 for a year's supply as compared to up to $532 for a year's supply of ACE inhibitor medication, according to the American College of Physicians' report.^[⁷^] The combination of cost considerations and the findings about risks and benefits have led researchers and physicians to conclude that diuretics, not ACE inhibitors, should be the first choice for treating high blood pressure.

Where the manufacturers of ACE inhibitors have been very successful, however, is in marketing their products. According to a survey of 1700 physicians conducted by researchers at the University of Michigan, most physicians overestimated the benefits of ACE inhibitors and underestimated their risks, while underestimating the value of diuretics.^[⁸^] The study found that the physicians who were most likely to rely on ACE inhibitors to treat high blood pressure were also more likely to hand out free drug samples given to them by pharmaceutical companies, leading the researchers to conclude that "the industry influence is pervasive."^[⁹^]

If you were needlessly prescribed an ACE inhibitor during pregnancy and believe that you or your child were harmed as a result, we would be privileged to answer any questions you might have about the issues involved.

Sources:

1. Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA. Major congenital malformations after first-trimester exposure to ACE inhibitors. New England Journal of Medicine, 354(23): 2443-51 (June 8, 2006). [Abstract]
2. Patient Information Sheet: Angiotensin-Converting Enzyme Inhibitor Drugs (ACE Inhibitors), FDA Alert (June 2006).
3. Food and Drug Administration, ACE Inhibitors (March 13, 1992).
4. Centers for Disease Control and Prevention (CDC). Postmarketing surveillance for angiotensin-converting enzyme inhibitor use during the first trimester of pregnancy--United States, Canada, and Israel, 1987-1995. Morbidity & Mortality Weekly Report, 1997 Mar 21;46(11):240-2. [Link]
5. Mastrobattista JM. Angiotensin converting enzyme inhibitors in pregnancy. Seminars in Perinatology, 21(2):124-34 (Apr. 1997). [Abstract]
6. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. [Link]
7. Jason van Steenburgh, American College of Physicians, Diuretics for hypertension get a big boost, but will data change prescribing patterns? ACP Observer (April 2003). [Link]
8. Ubel PA, Jepson C, Asch DA. Misperceptions about beta-blockers and diuretics: a national survey of primary care physicians. Journal of General Internal Medicine, 18(12):977-83 (Dec. 2003). [Abstract]
9. University of Michigan Health System, Press Release: Doctors more likely to prescribe pricey new blood pressure drugs despite standards, U-M study finds (December 19, 2003).

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