Low-dose aspirin did not prevent pregnancy-induced hypertension in women at moderate risk
ACP J Club. 1993 July-Aug;119:21. doi:10.7326/ACPJC-1993-119-1-021
Italian Study of Aspirin in Pregnancy. Low-dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy-induced hypertension. Lancet. 1993 Feb 13:341:396-400.
To evaluate the effectiveness of low-dose aspirin in preventing pregnancy-induced hypertension among women judged to be at moderate risk.
Randomized controlled trial with follow-up to delivery.
81 obstetrics and nephrology centers in Italy.
1106 women (mean age 31 y) between 16 and 32 weeks of gestation who satisfied the following criteria. For those treated prophylactically, the criteria were 1 or more of age < 18 or > 40 years, mild or moderate chronic hypertension (diastolic blood pressure between 90 and 110 mm Hg), nephropathy with normal renal function and blood pressure, history of pregnancy-induced hypertension with or without proteinuria developing after week 32 of a previous pregnancy, history of intrauterine growth retardation, or current twin pregnancy. For those who received aspirin therapeutically, the criteria were pregnancy-induced hypertension or early signs of intrauterine growth retardation. Exclusion criteria were history of chronic disease, allergy to aspirin, or documented fetal malformations. 186 women (17%) were either lost to follow-up or had missing blood pressure data.
583 women were assigned to treatment with aspirin, 50 mg daily, until delivery. 523 women were assigned to no treatment.
Main outcome measure
Pregnancy-induced hypertension with or without proteinuria. Blood pressure was measured weekly after 20 weeks gestation, and urine was tested for protein every 2 weeks from 28 weeks gestation.
Analysis was by intention to treat. Compliance with treatment was self-reported. Excluding women who had hypertension or proteinuria at randomization, 81 women (19%) developed pregnancy-induced hypertension with or without proteinuria in the aspirin group compared with 51 women (15%) in the no-treatment group (P = 0.15) (Table). Of the 522 aspirin-treated women for whom information was available, 53 (10%) reported 1 interruption of treatment, 12 (2%) reported ≥ 2 interruptions, and 12 (2%) stated that they stopped treatment altogether. Among women allocated to no treatment, no one took aspirin for > 7 days. The groups did not differ for other obstetric outcomes (stillbirths, neonatal deaths, low birth weight, preterm delivery, mode of delivery, or admission to neonatal care unit).
Low-dose aspirin (50 mg daily) did not prevent pregnancy-induced hypertension among women at moderate risk.
Source of funding: Italian National Research Council and Corvenzione CNR-Consorzio Mario Negri Sud.
For article reprint: Dr. F. Parazzini, Istituto di Ricerche Farmacologiche "Mario Negri," via Eritrea 62, 20517 Milano, Italy. FAX 39-2-332-00231.
Table. Aspirin vs no treatment in women at moderate risk for pregnancy-induced hypertension*
|Outcome at delivery||Aspirin||No treatment||RRI (95% CI)||NNH|
|Pregnancy-induced hypertension||19%||15%||26% (-8 to 74)||Not significant|
*Abbreviations defined in Glossary; RRI, NNH, and CI calculated from data in article.
In contrast with an earlier French study of the use of aspirin, 150 mg, with dipyridamole, 300 mg daily (1), and an overview analysis from Oxford cited in the commentary by Keirse (2), this randomized study, which included more patients than did previous trials, failed to show any benefit of aspirin. The patients appeared to be at lower risk than those who participated in other trials; 12.5% of control-group women developed pregnancy-induced hypertension, and only 2.7% exhibited pregnancy-induced hypertension with proteinuria, whereas 16.2% of infants born to mothers in the control prophylaxis group and 27.3% of infants in the control therapeutic group were below the 10th percentile of birth weight.
Aspirin is readily available in many medications and is consumed by a large proportion of women at some time during pregnancy (2). Fortunately, because few women in the no-treatment group reported using aspirin, it is hoped that contamination of the control group with active treatment was avoided. The authors argue convincingly that the major study end point of gestational weight would probably not be influenced by patient or observer bias. The inclusion of an aspirin placebo, however, would have created a higher level of assurance that knowledge of therapy had not influenced other outcomes. The authors indicate that bias caused by knowledge of treatment may have contributed to the somewhat higher cesarean section rate in aspirin-treated women.
Although low-dose aspirin may not prevent pregnancy-induced hypertension or intrauterine growth retardation, this finding is controversial. The matter will probably be resolved when the multinational Collaborative Low-Dose Aspirin Study in Pregnancy concludes this year (2).
In any event, the findings of the Italian Study have been confirmed by the larger CLASP Study (3) which found no benefit of low-dose aspirin for preeclampsia or intrauterine growth retardation, although there was a small reduction in preterm delivery.
S. George Carruthers, MD
Victoria General HospitalHalifax, Nova Scotia, Canada
3. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet 1994;343:619-29.