Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis

Bellos, Ioannis; Pergialiotis, Vasilios; Papapanagiotou, Angeliki; Loutradis, Dimitrios; Daskalakis, Georgios

doi:10.1016/j.ajog.2020.03.016

Cited by 57 publications

(38 citation statements)

References 60 publications

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“…There is indirect evidence (one SR: Abalos 2018 50 ) that use of any calcium channel blocker was not associated with maternal (Low SoE) or fetal/child adverse effects (Low to Moderate SoE). There is also indirect evidence (one SR: Bellos 2020a 52 ) that nifedipine was not associated with fetal/child adverse effects (Low to Moderate SoE).…”

Section: Resultsmentioning

confidence: 99%

“…NSAIDs, [38][39][40][41][42][43][44][45] two antiepileptics, [46][47][48] two β-blockers, [49][50][51] two calcium channel blockers, 50,52 two antiemetics (5-HT3 receptor antagonists), 53,54 two antipsychotics, 55,56 two antihistamines, 57,58 and one each assessed serotonin and norepinephrine reuptake inhibitors (SNRIs), 59,60 tricyclic antidepressants, 59,60 benzodiazepines, 61,62 corticosteroids, 63 oral magnesium, 64 triptans (5-HT1B/1D receptor agonists), 65 analgesics/antipyretics, 66 and intravenous magnesium. 67 Twelve SRs reported maternal adverse effects and 23 reported fetal/child adverse effects.…”

Section: All 26 Srs Assessed Pharmacologic Interventions: Eight Assessedmentioning

confidence: 99%

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Management of primary headaches during pregnancy, postpartum, and breastfeeding: A systematic review

et al. 2021

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Background: Primary headaches (migraine, tension headache, cluster headache, and other trigeminal autonomic cephalgias) are common in pregnancy and postpartum. It is unclear how to best and most safely manage them. Objective: We conducted a systematic review (SR) of interventions to prevent or treat primary headaches in women who are pregnant, attempting to become pregnant, postpartum, or breastfeeding. Methods: We searched Medline, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials. gov, Cochrane Database of SRs, and Epistemonikos for primary studies of pregnant women with primary headache and existing SRs of harms in pregnant women regardless of indication. No date or language restrictions were applied. We assessed strength of evidence (SoE) using standard methods. Results: We screened 8549 citations for studies and 2788 citations for SRs. Sixteen studies (mostly high risk of bias) comprising 14,185 patients (total) and 26 SRs met the criteria. For prevention, we found no evidence addressing effectiveness. Antiepileptics, venlafaxine, tricyclic antidepressants, benzodiazepines, β-blockers, prednisolone, and oral magnesium may be associated with fetal/child adverse effects, but calcium channel blockers and antihistamines may not be (1 single-group study and 11 SRs; lowto-moderate SoE). For treatment, combination metoclopramide and diphenhydramine may be more effective than codeine for migraine or tension headache (1 randomized controlled trial; low SoE). Triptans may not be associated with fetal/child adverse effects (8 nonrandomized comparative studies; low SoE). Acetaminophen, prednisolone, indomethacin, ondansetron, antipsychotics, and intravenous magnesium may be associated with fetal/child adverse effects, but low-dose aspirin may not be (indirect evidence; low-to-moderate SoE). We found insufficient evidence regarding non-pharmacologic treatments.

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Section: Resultsmentioning

confidence: 99%

Section: All 26 Srs Assessed Pharmacologic Interventions: Eight Assessedmentioning

confidence: 99%

Management of primary headaches during pregnancy, postpartum, and breastfeeding: A systematic review

et al. 2021

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“…Currently all three medications are classified as TGA category C—much like labetalol, a beta-blocker frequently used to treat hypertension in pregnancy. Promisingly however, carvedilol and metoprolol are considered safe in pregnancy based on their use in pregnant women with other cardiovascular diseases including heart failure [ 52 ], and the only beta-blocker which is actively contraindicated in pregnancy is atenolol [ 52 ]; it has been associated with small-for-gestational-age infants [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

“…While currently labetalol is the only beta-blocker used in the treatment of preeclampsia as an anti-hypertensive agent [ 51 ], in general many beta-blockers are considered safe in pregnancy based on their use in pregnant patients with cardiovascular disease [ 52 ]. The exception to this is atenolol, which is contraindicated given its association with small-for-gestational-age infants [ 52 , 53 ].…”

Section: Introductionmentioning

confidence: 99%

Pre-Clinical Investigation of Cardioprotective Beta-Blockers as a Therapeutic Strategy for Preeclampsia

Binder

MacDonald

Beard

et al. 2021

JCM

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Despite significant maternal and fetal morbidity, a treatment for preeclampsia currently remains an unmet need in clinical care. As too does the lifelong cardiovascular risks imparted on preeclampsia sufferers. Endothelial dysfunction and end-organ injury are synonymous with both preeclampsia and cardiovascular disease, including heart failure. We propose that beta-blockers, known to improve endothelial dysfunction in the treatment of cardiovascular disease, and specifically known to reduce mortality in the treatment of heart failure, may be beneficial in the treatment of preeclampsia. Here, we assessed whether the beta-blockers carvedilol, bisoprolol, and metoprolol could quench the release of anti-angiogenic factors, promote production of pro-angiogenic factors, reduce markers of inflammation, and reduce endothelial dysfunction using our in vitro pre-clinical preeclampsia models encompassing primary placental tissue and endothelial cells. Here, we show beta-blockers effected a modest reduction in secretion of anti-angiogenic soluble fms-like tyrosine kinase-1 and soluble endoglin and increased expression of pro-angiogenic placental growth factor, vascular endothelial growth factor and adrenomedullin in endothelial cells. Beta-blocker treatment mitigated inflammatory changes occurring after endothelial dysfunction and promoted cytoprotective antioxidant heme oxygenase-1. The positive effects of the beta-blockers were predominantly seen in endothelial cells, with a less consistent response seen in placental cells/tissue. In conclusion, beta-blockers show potential as a novel therapeutic approach in the treatment of preeclampsia and warrant further investigation.

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“…Cardiovascular diseases affect 1% to 2% of pregnancies and represent the most common causes of indirect maternal mortality during pregnancy 1,2 . A recent meta‐analysis of the efficacy and safety of furosemide in pregnant women showed that the incidence of severe hypertension in patients receiving furosemide was similar to that in pregnant women receiving placebo 3 . However, furosemide is relatively safe if used sparingly and can be administered effectively during pregnancy for symptoms of volume overload or volume control in heart failure 3,4 …”

mentioning

confidence: 99%

A Pilot Study of the Maternal‐Fetal Pharmacokinetics of Furosemide in Plasma, Urine, and Amniotic Fluid of Hypertensive Parturient Women Under Cesarean Section

Gonçalves

Moreira

Benzi

et al. 2020

The Journal of Clinical Pharma

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The third trimester of pregnancy is related to physiological changes that can modify the process of absorption, distribution, metabolism, and excretion and, consequently, the efficacy and toxicity of drugs. However, little is known about furosemide pharmacokinetics and placental transfer in pregnancy. This study evaluated the maternal-fetal pharmacokinetics and distribution to amniotic fluid of furosemide in hypertensive parturient women under cesarean section. Twelve hypertensive parturient women under methyldopa (250 mg/8 h) and/or pindolol (10 mg/12 h) treatment received a 40-mg single oral dose of furosemide 1 to 10 hours before delivery by cesarean section. Blood and urine samples were collected for 12 hours after furosemide administration. At delivery, samples were obtained from maternal and umbilical cord blood (n = 8) to assess the transplacental transfer. Amniotic fluid (n = 4) was collected at the time of delivery. The following furosemide pharmacokinetic parameters were obtained as median (interquartile range): C max , 403 ng/mL (229 to 715 ng/mL

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Comparative efficacy and safety of oral antihypertensive agents in pregnant women with chronic hypertension: a network metaanalysis

Cited by 57 publications

References 60 publications

Management of primary headaches during pregnancy, postpartum, and breastfeeding: A systematic review

Management of primary headaches during pregnancy, postpartum, and breastfeeding: A systematic review

Pre-Clinical Investigation of Cardioprotective Beta-Blockers as a Therapeutic Strategy for Preeclampsia

A Pilot Study of the Maternal‐Fetal Pharmacokinetics of Furosemide in Plasma, Urine, and Amniotic Fluid of Hypertensive Parturient Women Under Cesarean Section

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