Atenolol

Clinical question Does the use of prophylactic atenolol in second trimester gravid women with high cardiac output decrease the incidence of preeclampsia?

Background Although the diagnosis of preeclampsia is currently made on the basis of careful third trimester urinalysis and blood pressure screening, physiologic changes associated with preeclampsia, such as high cardiac output, develop during the first and second trimesters. Current management of preeclampsia does not reduce perinatal morbidity and mortality. Early detection of women at risk for preeclampsia and identification of an effective prophylactic agent could lead to improved pregnancy outcomes. However, clinical trials have not demonstrated that aspirin or calcium are effective prophylactic agents. Previous studies of gravid women with new onset hypertension have found that atenolol lowers blood pressure and decreases the development of proteinuria and the need for hospitalization. However, no study has evaluated the effectiveness of prophylactic use of atenolol in preventing preeclampsia and improving perinatal outcomes in preeclamptic women.

Population studied The study population was recruited from a university-based maternal infant care clinic. Subjects were pregnant nulliparous women with no history of significant medical complications or pregnant women with insulin-requiring diabetes but less than 1.0 g of proteinuria per 24 hours.

Study design and validity This was a double-blinded randomized controlled trial. Candidates for the study underwent Doppler cardiac output screening at 22 to 25 weeks' gestation. Those with a cardiac output that placed them at risk for preeclampsia ([is greater than] 7.4 L/min, on the basis of previous studies by this research team) were randomized to 1 of 4 intervention groups: nulliparous women treated with prophylactic atenolol (100 mg/day for the remainder of the pregnancy); nulliparous women given placebo; women with diabetes given atenolol; and women with diabetes given placebo. A control group of nulliparous women with a cardiac output of [is less than] 7.4 liters per minute was also studied. At the conclusion of each pregnancy, blinded investigators performed a chart review and examined the infant to assess the presence or absence of maternal preeclampsia and evaluated infant gestational age, birth weight, and admission to an intensive care unit.

This is a well-done study with no major threats to validity and no major methodologic flaws. The authors correctly point out that the study was not large enough to determine whether the clinical protocol could improve clinical outcomes and that an additional trial including lower doses of atenolol in the treatment arms is needed.

Outcomes measured The primary outcome was the incidence of preeclampsia, and a secondary outcome was the fetal birth weight.

Results The rate of preeclampsia in patients taking atenolol was 3.8%, compared with 18% in the placebo group (number needed to treat [NNT] = 7). Atenolol treatment reduced the incidence of any diagnosis of hypertension from 71% to 29% (NNT = 3). The mean birth weight was 440 g less in infants of the previously nulliparous group treated with atenolol; no difference in mean weight was found between treatment groups of women with diabetes.

Recommendations for clinical practice The results of this well-designed preliminary study justify further studies of prophylactic atenolol for the prevention of pregnancy-induced hypertension and its sequelae. However, larger studies reporting such patient-oriented outcomes as reduction of prematurity and perinatal morbidity are needed before a change in practice is justified. Such studies should include multiple atenolol dosing protocols to explore a possible dose-response effect on birth weight. Studies of the predictive value and cost-effectiveness of targeted Doppler screening for preeclampsia are also needed to develop guidelines for its appropriate use by clinicians.

Easterling T, Brateng D, Schmucker B, Brown Z, Millard SP. Prevention of preeclampsia: a randomized trial of atenolol in hyperdynamic patients before onset of hypertension. Obstet Gynecol 1999; 93:725-33.

COPYRIGHT 1999 Dowden Health Media, Inc.
COPYRIGHT 2004 Gale Group