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Evidence summaries

Drugs for Rapid Treatment of Very High Blood Pressure during Pregnancy

Calcium channel blockers, labetalol, nifedipine, and hydralazineappear to be similarly effective for very high hypertension in pregnancy. Level of evidence: "B"

A Cochrane review [Abstract] 1 included 35 trials with a total of 3573 subjects and 15 different comparisons. Women allocated calcium channel blockers rather than hydralazine were less likely to have persistent high blood pressure (8% versus 22%; relative risk (RR) 0.37, 95% confidence interval (CI) 0.21 to 0.66; 6 trials, n=313). There was no difference between labetalol and nifedipine in persistent high blood pressure, eclampsia, hypotension or adverse effects in two trials. Ketanserin was associated with more persistent high blood pressure than hydralazine (27% versus 6%; RR 4.79, 95% CI 1.95 to 11.73; 3 trials, n=180), but fewer side-effects. Labetalol was associated with a lower risk of hypotension (one trial 90 women; RR 0.06, 95% CI 0.00 to 0.99) and caesarean section (RR 0.43, 95% CI 0.18 to 1.02) than diazoxide. The risk of persistent high blood pressure was lower for nimodipine compared to magnesium sulphate (two trials 1683 women; 47% versus 65%; RR 0.84, 95% CI 0.76 to 0.93), although nimodipine was associated with a higher risk of eclampsia (RR 2.24, 95% CI 1.06 to 4.73). Nimodipine was asociated with a lower risk of respiratory difficulties (RR 0.28, 95% CI 0.08 to 0.99), fewer side-effects (RR 0.68, 95% CI 0.54 to 0.86) and less postpartum haemorrhage (RR 0.41, 95% CI 0.18 to 0.92) than magnesium sulphate. There is no evidence that any one of the other antihypertensive agents is better than another for women with severe hypertension during pregnancy. The authors conclude that magnesium sulphate (although this may be indicated for prevention of eclampsia), high-dose diazoxide, ketanserin, nimodipine and chlorpromazine are best avoided.

A network meta-analysis 2 included 46 trials. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Compared to hydralazine, diazoxide (-15 [-20.6 to 9.4]), nicardipine (-11.8 [-22.3 to -1.2]), nifedipine/celastrol (-19.3 [-27.4, to 11.1])] nifedipine/vitamin D (-17.1 [-25.7, -9.7]), nifedipine/resveratrol (-13.9 [-22.6 to -5.2]) and glyceryl trinitrate (-33.8 [-36.7 to -31]) were observed to achieve the target BP (in minutes) more rapidly. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol.

A meta-analysis 4 included 7 trials (n=363). Oral nifedipine was associated with less risk of persistent hypertension (RR 0.42, 95% CI 0.18 to 0.96) and reported maternal side effects (RR 0.57, 95% CI 0.35 to 0.94) compared to intravenous labatalol. However, on sensitivity analysis the outcome 'persistent hypertension' was no longer significant. Other outcomes did not reach statistical significance.

A systematic review 3 assessed the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension. 15 RCTs (n=915) in pregnancy and one postpartum trial were included. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8-10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; RR 1.07, 95% CI 0.98 to 1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95 to 1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved around 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54-1.33).

Comment: The quality of evidence is downgraded by study limitations (inadequate allocation concealment).

    References

    • Duley L, Henderson-Smart DJ, Meher S. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev 2006;(3):CD001449. [PubMed]
    • Sridharan K, Sequeira RP. Drugs for treating severe hypertension in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials. Br J Clin Pharmacol 2018;84(9):1906-1916. [PubMed]
    • Firoz T, Magee LA, MacDonell K et al. Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review. BJOG 2014;121(10):1210-8; discussion 1220. [PubMed]
    • Shekhar S, Gupta N, Kirubakaran R et al. Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis. BJOG 2016;123(1):40-7. [PubMed]

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