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Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis.
Am J Obstet Gynecol. 2020 10; 223(4):525-537.AJ

Abstract

OBJECTIVE DATA

Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension.

STUDY

Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension.

STUDY APPRAISAL AND SYNTHESIS METHODS

The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence.

RESULTS

Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery.

CONCLUSION

Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy.

Authors+Show Affiliations

Laboratory of Experimental Surgery and Surgical Research N.S. Christeas, Athens University Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: bellosg@windowslive.com.Laboratory of Experimental Surgery and Surgical Research N.S. Christeas, Athens University Medical School, National and Kapodistrian University of Athens, Athens, Greece.Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Pub Type(s)

Comparative Study
Journal Article
Meta-Analysis
Review

Language

eng

PubMed ID

32199925

Citation

Bellos, Ioannis, et al. "Comparative Efficacy and Safety of Oral Antihypertensive Agents in Pregnant Women With Chronic Hypertension: a Network Metaanalysis." American Journal of Obstetrics and Gynecology, vol. 223, no. 4, 2020, pp. 525-537.
Bellos I, Pergialiotis V, Papapanagiotou A, et al. Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis. Am J Obstet Gynecol. 2020;223(4):525-537.
Bellos, I., Pergialiotis, V., Papapanagiotou, A., Loutradis, D., & Daskalakis, G. (2020). Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis. American Journal of Obstetrics and Gynecology, 223(4), 525-537. https://doi.org/10.1016/j.ajog.2020.03.016
Bellos I, et al. Comparative Efficacy and Safety of Oral Antihypertensive Agents in Pregnant Women With Chronic Hypertension: a Network Metaanalysis. Am J Obstet Gynecol. 2020;223(4):525-537. PubMed PMID: 32199925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis. AU - Bellos,Ioannis, AU - Pergialiotis,Vasilios, AU - Papapanagiotou,Angeliki, AU - Loutradis,Dimitrios, AU - Daskalakis,Georgios, Y1 - 2020/03/19/ PY - 2020/01/17/received PY - 2020/03/11/revised PY - 2020/03/12/accepted PY - 2020/3/23/pubmed PY - 2020/11/24/medline PY - 2020/3/23/entrez KW - antihypertensive KW - chronic hypertension KW - metaanalysis KW - preeclampsia KW - pregnancy SP - 525 EP - 537 JF - American journal of obstetrics and gynecology JO - Am J Obstet Gynecol VL - 223 IS - 4 N2 - OBJECTIVE DATA: Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension. STUDY: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence. RESULTS: Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery. CONCLUSION: Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy. SN - 1097-6868 UR - https://www.unboundmedicine.com/medline/citation/32199925/Comparative_efficacy_and_safety_of_oral_antihypertensive_agents_in_pregnant_women_with_chronic_hypertension:_a_network_metaanalysis_ DB - PRIME DP - Unbound Medicine ER -