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Therapeutics

Nifedipine reduced maternal blood pressure and fetal distress in severe pre-eclampsia more than hydralazine

ACP J Club. 1991 Sept-Oct;115:47. doi:10.7326/ACPJC-1991-115-2-047


Source Citation

Fenakel K, Fenakel G, Appelman Z, et al. Nifedipine in the treatment of severe preeclampsia. Obstet Gynecol. 1991 Mar;77:331-7.


Abstract

Objective

To compare the effectiveness of sublingual and oral nifedipine with that of intravenous hydralazine in the treatment of severe pre-eclampsia.

Design

Quasi-randomized, controlled trial, using week of month as method of allocation.

Setting

Teaching hospital associated with a medical school in Israel, between January 1985 and December 1988.

Patients

All women who developed severe pre-eclampsia between 26 and 36 weeks of gestation. Eligibility criteria were blood pressure (BP) values ≥ 160/110 mm Hg (the phase IV Korotkoff sound was used for diastolic pressure) on at least 2 occasions 3 hours apart, plus one of proteinuria, generalized edema, or hyper-reflexia. All women were normotensive during the first trimester. 54 women were entered in the trial. Of these, 5 were not included in the analysis because of breach of protocol.

Intervention

24 patients received nifedipine, 10 mg sublingually, repeated 20 and 40 minutes later if BP values were still > 160/110; then orally every 6 hours until delivery. Dosage was increased to 20 mg every 4 hours if BP values remained high. 25 patients received hydralazine, 6.25 mg intravenously (IV), then 12.5-mg boluses as required; when BP was stabilized, IV was stopped and oral hydralazine (20 to 30 mg every 6 hours) continued until delivery. Alpha-methyldopa was added if the BP could not be maintained below 160/110 mm Hg.

Main outcome measures

BP response, proteinuria, prolongation of gestation, and perinatal outcome.

Main results

Prolonged control of BP was achieved in 23 patients (96%) on nifedipine and in 17 patients (68%) on hydralazine (P < 0.05). {This absolute risk improvement of 28% means that 4 patients would need to be treated (NNT) with nifedipine (rather than hydralazine) to have 1 additional patient achieve prolonged control of BP, 95% CI 2 to 14; the relative risk improvement was 41%, CI 9% to 99%}.* Proteinuria increased or creatinine clearance decreased in 4 patients (17%) in the nifedipine group, and in 1 patient (4%) in the hydralazine group. {absolute risk difference 13%, CI -5% to 33%, P = 0.1}.* There were no statistically significant differences between the groups in prolongation of gestation, method of delivery, or birth weight. "Signs of acute fetal distress" were noted in 1 fetus (4%) in the nifedipine group compared with 11 (41%) in the hydralazine group (P < 0.003). {This absolute risk reduction (ARR) of 37% means that 3 patients would need to be treated with nifedione (rather than hydralazine) to prevent 1 additional fetus from having fetal distress, CI 2 to 6; the relative risk reduction (RRR) was 91%, CI 50% to 98%}.* Major neonatal complications occurred in 6 of 26 (23%) of the infants of nifedipine patients and in 9 of 27 (33%) of the hydralazine infants. {ARR 10%, CI -14% to 34%, (P < 0.6)}.*

Conclusions

Nifedipine gave more consistent and prolonged control of BP in patients with severe pre-eclampsia than hydralazine and resulted in fewer diagnoses of acute fetal distress as determined by biophysical tests of fetal well-being. These test results were not reflected in substantively improved neonatal outcomes.

Source of funding: Not stated.

Address for article reprint: Dr. K. Fenakel, Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot 76100, Israel.

*Numbers calculated from data in article.


Commentary

The appropriate treatment for severe pre-eclampsia is still controversial because of the small number of controlled therapeutic trials with clearly defined patient groups. Fenakel and colleagues make a case for the use of nifedipine instead of more conventional treatment with hydralazine for severe pre-eclampsia.

The 49 women assigned to the 2 treatment regimens were referred to as having "severe" pre-eclampsia primarily by BP criteria. All but 2 in both groups had proteinuria. The study groups appeared similar in terms of prognostic features, although there were twice as many nulliparas in the nifedipine group (a nonsignificant difference). 31 of 49 patients were classified as having superimposed pre-eclampsia, but the distribution between the two groups was not given.

The study found a clinically important, but not statistically significant, trend for gestation to be prolonged in the nifedipine group (34.6 vs 33.6 weeks). In addition, the average number of days spent in the neonatal intensive care unit was half as many in the nifedipine group, resulting in 31% lower hospitalization charges. The mothers in both groups fared well and, despite the use of magnesium sulfate, there were more precipitous falls of diastolic BP in the hydralazine group than in the nifedipine group.

The improved BP control in the nifedipine group is not necessarily an important outcome itself, because BP control alone does not seem to prevent the adverse sequelae of pre-eclampsia. However, the marked reduction in the nifedipine group of signs of acute fetal distress and the trends toward lengthening gestation and decrease in perinatal morbidity are compelling and justify further study.

Linda A. Barbour, MD
Colorado UniversityDenver, Colorado, USA