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New Data on ACE Inhibitors in Renal Failure and in Pregnancy

ACE inhibitors slow the progression of even advanced renal disease ... but ACE inhibitors should be avoided in women who may become pregnant.

Two studies with important implications for the prescription of angiotensin-converting–enzyme (ACE) inhibitors in primary care were published this year.

ACE inhibitors slow the progression of mild to moderate renal insufficiency (creatinine <3.0 mg/dL). However, less is known of their effect in patients with advanced renal disease, and many clinicians are reluctant to use ACE inhibitors in this setting. In a randomized, double-blind study from China (Journal Watch Jan 17 2006), nondiabetic patients with advanced renal insufficiency (creatinine, 3.1–5.0 mg/dL) were treated with benazepril (20 mg/day) or placebo. Patients were excluded if they had a cough, hyperkalemia, or a >30% rise in serum creatinine during a run-in period. The incidence of the primary composite endpoint (doubling of serum creatinine, need for dialysis or renal transplantation, or death) among 224 participants was significantly lower with benazepril than with placebo (41% vs. 60%). Rates of adverse events were similar in the two groups.

This study strongly suggests that ACE inhibitors slow the progression of even advanced renal insufficiency. However, as discussed in an accompanying editorial (Journal Watch Jan 17 2006), caution must be exercised: ACE inhibitors should be started at a low dose, and patients should be monitored closely for hyperkalemia.

In pregnancies, ACE inhibitors increase the risk for congenital anomalies when used in the second and third trimesters and are therefore contraindicated; similar risk had not been shown for first-trimester exposures. To assess the risk for major congenital anomalies among fetuses exposed to an ACE inhibitor during the first trimester, researchers used the Tennessee Medicaid database to identify infants born between 1985 and 2000 (Journal Watch Jun 27 2006). In all, 209 infants were exposed to an ACE inhibitor in the first trimester alone, 202 were exposed to other antihypertensive agents, and more than 29,000 had no exposure to antihypertensive agents. Infants exposed to ACE inhibitors in the first trimester had a higher rate of congenital anomalies (7.1%) than infants exposed to other antihypertensives (1.7%) or those not exposed to any antihypertensives (2.6%).

The design of this study limits our ability to draw definitive conclusions. Nevertheless, the findings suggest that ACE inhibitors should be avoided during the first trimester of pregnancy — and possibly in women who might become pregnant — given that alternative agents exist.

— Jamaluddin Moloo, MD, MPH

Published in Journal Watch General Medicine December 28, 2006