Oral nifedipine or intravenous labetalol for severe hypertension?

Abstract

The systematic review by Shekhar et al. adds to both the relevant Cochrane review [Duley et al. Cochrane Database Syst Rev 2013;31(7):CD001449] and other recent reviews of oral antihypertensive therapy (Firoz et al. BJOG 2014;121:1210–8; Shi et al. Int J Cardiol 2015;178:162–4), by including two abstracts from conferences in India and three new trials, and clarifying data excluded from the Cochrane review. Shekhar et al. provide evidence that oral nifedipine is more effective than intravenous labetalol based on the results of seven trials and 363 women with severe hypertension, due to pre-existing or gestational hypertension, or pre-eclampsia. Five of the seven trials were assessed as being at low risk of bias. Oral nifedipine (usually tablets) was associated with less persistent (severe) hypertension [6/182, 3.3% (nifedipine) versus 15/181, 8.3% (labetalol); relative risk (RR) 0.42, 95% confidence interval (95% CI) 0.18–0.96; seven trials, 363 women] that was defined in various ways, all clinically relevant: a blood pressure persistently > 150–160/100 mmHg or failure to achieve either a 25% reduction in blood pressure (despite maximal doses of drug) or an absolute blood pressure of ≤ 150/95 mmHg within an hour. Although the authors report that the results were no longer significant (and there was also notable heterogeneity) when risk difference was then used as the summary statistic, the latter is not usually recommended because it is unlikely to give consistent estimates of treatment effect. Alternatively, one could conclude that there is a 5.0% reduction in the incidence of persistent severe hypertension with nifedipine versus intravenous labetalol. Of additional interest is the adverse-effect profile seen in the included trials. Although there are fears that nifedipine is associated with more maternal and, potentially, more perinatal adverse effects compared with other antihypertensive agents used for severe hypertension, this was not borne out in Shekhar et al.'s systematic review. Nifedipine was associated with fewer maternal adverse effects of headache, nausea, vomiting, or palpitations [19/106 (nifedipine) versus 32/101 (labetalol); RR 0.57, 95% CI 0.35–0.94; three trials, 207 women]. The incidence of hypotension was very low, with only one documented occurrence in a woman who received nifedipine [1/176 (nifedipine) versus 0/167 (labetalol)]. Also, nifedipine was not associated with more stillbirths [13/166 (nifedipine) versus 18/157 (labetalol); RR 0.66, 95% CI 0.13–1.27; five trials, 323 women] and was associated with fewer neonatal deaths [3/116 (nifedipine) versus 10/105 (labetalol); RR 0.27, 95% CI 0.09–0.87; four trials, 221 women], although gestational age at delivery was not reported by any of the trials. This review provides further evidence that nifedipine (tablets or capsules swallowed whole) is a reasonable antihypertensive for treatment of severe pregnancy hypertension, regardless of the underlying hypertensive disorder of pregnancy. This is good news for the global obstetric community, as nifedipine is widely available for treatment of preterm birth, in both high- and low-and-middle-income countries. Units providing maternity care are encouraged to reconsider the use of nifedipine as an antihypertensive of choice for pregnant women with severe hypertension. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.