Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Antihypertensive treatment improved pregnancy outcome in primigravid women with mild hypertension

ACP J Club. 1991 Nov-Dec;115:79. doi:10.7326/ACPJC-1991-115-3-079


Source Citation

Phippard AF, Fischer WE, Horvath JS, et al. Early blood pressure control improves pregnancy outcome in primigravid women with mild hypertension. Med J Aust. 1991 Mar 18;154:378-82.


Abstract

Objective

To evaluate the effect of strict blood pressure (BP) control in primigravid women who develop mild hypertension.

Design

Randomized, double-blind, placebo-controlled trial.

Setting

Hospital in Australia with 1500 primigravid deliveries annually.

Patients

Primigravid women between 28 and 34 weeks gestation with previously normal BP who were hospitalized for detailed assessment because of BP of ≥ 130/75 mm Hg in the antenatal clinic. Those who continued to have BPs "more than 1 SD above the reported mean for gestational age" were eligible for entry into the trial. Women showing abnormalities on baseline clinical, laboratory, or fetal assessment, or whose BP was above 170 /110 mm Hg, were excluded. The pretreatment mean BP was 129/84 mm Hg in the placebo group and 126/82 mm Hg in the treated group.

Intervention

The treated group received clonidine in increasing doses from 200 to 800 mg/d plus hydralazine, 0 to 200 mg/d, according to a 6-level predetermined dose schedule as BP increased (n = 25). All patients remained hospitalized until delivery. The code was broken for patients who reached end points; those in the placebo group were given the same active medication as those in the treatment group. The control group received placebo (n = 27).

Main outcome measures

Delivery before 38 weeks. Additional end points included severe hypertension (systolic BP ≥ 170 mm Hg, diastolic BP ≥ 110 mm Hg on 2 occasions 5 minutes apart; fall in platelet count to < 150 × 109/L); hyper-reflexia or other signs of impending eclampsia; elevated hepatic enzymes; proteinuria > 3 g/d; ultrasound evidence of retarded fetal growth; and fetal distress.

Main results

22 of 25 treated patients reached 38 weeks gestation compared with 17 of 27 controls {88% vs 63%, P < 0.05}.* This absolute risk improvement of 25% means that 4 patients would need to be treated (NNT) with clonidine plus hydralazine (rather than placebo) for 1 additional patient to reach 38 weeks gestation, 95% CI 2 to 63; the relative risk improvement was 40%, CI 2% to 103%}.* 3 of 25 treated patients were withdrawn because of reaching an end point (1 thrombocytopenia, 1 retarded fetal growth, 1 spontaneous labor) compared with 10 of 27 controls (4 severe hypertension, 3 premonitory signs of eclampsia, 1 hepatic dysfunction, 2 retarded fetal growth) {12% vs 37%, P < 0.05; absolute risk reduction 25%; NNT 4, CI 2 to 63; relative risk reduction 68%, CI 57% to 90%}.* 4 babies from the placebo group but none from the treatment group required intensive neonatal care.

Conclusion

Early antihypertensive treatment reduced the risk for third-trimester complications and need for pre-empting labor in women hospitalized for the management of mild or moderate third-trimester hypertension.

Source of funding: In part, Boehringer Ingleheim Pty Ltd.

Address for article reprint: Dr. A.F. Phippard, Department of Renal Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NS W 2050, Australia.


Commentary

Phippard and colleagues make a strong case for early third trimester, antihypertensive therapy for mild BP elevation (beginning at 130/75 mm Hg) in primigravid women without evidence of preexisting hypertension. The main results of this trial with clonidine and hydralazine are largely consistent with the favorable results of similar randomized trials with β-blockers (atenolol [1], labetalol [2]). Birth weight was not affected. Because of associated intrauterine growth retardation, beginning β-blockers for mild essential hypertension in the first trimester is hazardous (3). By design, the present study did not clarify the birth weight effect of first- or second-trimester treatment with clonidine.

Placebo-controlled randomized trials of antihypertensive agents cannot be truly "blinded" because BP reduction is correlated (although not perfectly) with the active treatment. In this study, efforts to strictly define end points reduced potential bias. Study of perinatal mortaity, an unambiguous end point, was not practical because of its rarity and the need for a large number of study patients.

Given the small number of pregnancies in all the studies to date, general acceptance should await completion of much larger trials. Of interest will be the relation between the secondary prevention outlined here and the new and evolving use of low-dose aspirin as primary prevention of pregnancy-induced hypertension (4).

Kirk Shy, MD
University of WashingtonSeattle, Washington, USA


References

1. Rubin PC, Butters L, Clark DM, et al. Placebo-controlled trial of atenolol in treatment of pregnancy-associated hypertension. Lancet. 1983;1:431-4.

2. Pickles CJ, Symonds EM, Pipskin FB. The fetal outcome in a randomised double-blind controlled trial of labetalol versus placebo in pregnancy-induced hypertension. Br J Obstet Gynaecol. 1989;96:38-43.

3. Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. BMJ. 1990;301:587-9.

4. Schiff E, Peleg E, Goldenberg M, et al. The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin. N Engl J Med. 1990;322:204-5.