| Excerpt from The WHO Reproductive Health Library | Published by Update Software Ltd. |
This review evaluates the benefits and potential adverse effects of using antihypertensive agents for mild-to-moderate hypertension in pregnancy. Mild-to-moderate hypertension was defined only in some trials. The trials in which this was the case, it was defined as systolic blood pressure of 140–169 mmHg and diastolic blood pressure of 90–109 mmHg.
The review includes 40 trials in which 3797 women had participated. The poor quality of many trials, lack of standardized definitions, lack of standardized recruitment criteria and small sample sizes limited the soundness of the results of the review.
The twenty-four trials, that compared an antihypertensive agent with no antihypertensive therapy, revealed a halving in the risk of developing severe hypertension (relative risk: [RR] 0.52; 95% confidence interval [CI] 0.41 to 0.64). This was independent of the class of drug, the type of hypertensive disorder, gestational age at entry into the trial or use of placebo. Nine to seventeen women need to be treated to prevent one episode of severe hypertension. The overall risk of proteinuria or pre-eclampsia was unchanged. In subgroup analyses, calcium channel blockers (541 women, RR: 1.68; 95% CI: 1.17 to 2.41) increased, while beta-blockers (783 women, RR: 0.76; 95% CI: 0.59 to 0.98) seemed to reduce the risk of pre-eclampsia. The risk of preterm birth was unchanged. An increased risk of having small for gestational age (SGA) babies was seen in only women taking part in the comparison of beta-blockers versus no drug (RR: 1.56 95% CI: 1.1 to 2.22). There were no other meaningful differences in clinical outcomes. Thus, although the incidence of severe hypertension was reduced, the expected clinical impact in terms of a reduction in preterm births and caesarean sections was not evident.
The seventeen trials that compared one antihypertensive agent with another included comparisons of methyldopa with beta-blockers, nifedipine with ketanserin; nifedipine with glyceryl trinitrite; labetolol with monohydralazine and metoprolol with nicardapine. There were no significant differences in risk with respect to development of severe hypertension or the overall risk of proteinuria/pre-eclampsia in these comparisons. Other antihypertensive agents appeared to be better than methyldopa in reducing the risk of the baby dying (1010 women RR: 0.49; 95% CI: 0.24 to 0.99). The reviewers attributed this result to possible random error or bias.
This review concludes that the benefits and harms of the use of antihypertensive agents in mild to moderate hypertension in pregnancy are unclear. In addition, there is little evidence that any particular antihypertensive agent is better than others. The review suggests that women should make the decision regarding the use of an antihypertensive agent in pregnancy in consultation with their obstetricians.
The strategy employed for identifying suitable trials was appropriate. The trials were analysed equally appropriately. However, the number of trials comparing an antihypertensive agent with no drug or a placebo, add up to 25 and not 24 trials, as mentioned in the review (beta-blockers-15, methyldopa-5, calcium channel blockers-4 and prazosin-1). This may be due to the fact that one trial had three arms and hence got included twice.
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