Navigating heart failure medications in obstetric practice

Table 1 Precautions for medication use in heart failure during pregnancy

Drug class	Specific agents	Former Food and Drug Administration Category	Safety	Key considerations	Ref.
Absolute contraindications
Renin-angiotensin system inhibitors	Angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, angiotensin receptor-neprilysin inhibitors	D	Contraindicated	Contraindicated throughout pregnancy: Risks of fetal renal dysplasia, oligohydramnios, craniofacial malformations, intra-uterine growth retardation. Discontinue preconception	Bullo et al[33], Nadeem et al[34], van der Zande et al[35]
Mineralocorticoid receptor antagonists	Spironolactone, eplerenone	D (spironolactone), not applicable (eplerenone)	Contraindicated	Spironolactone: Anti-androgenic effects (male fetal feminization). Eplerenone: Critically lacking human safety data	Struthers et al[36], Pandey et al[37], Dey et al[38], Deng et al[39]
Sodium-glucose cotransporter 2 inhibitors	Sodium-glucose cotransporter 2 inhibitors	Not applicable	Contraindicated	Critical lack of human safety data; adverse pregnancy outcomes in animal studies	DeFilippis et al[32]
Agents requiring cautious use
Beta-blockers	Metoprolol, bisoprolol	C	Preferred	No significant harmful effects in pregnant women with structural heart disease (registry of pregnancy and cardiac disease registry)	Ruys et al[31], Halpern et al[40]
	Labetalol	C	Permitted	Pharmacokinetics change: Shorter half-life (upregulation of phase II glucuronidation). Dosage: Oral 200-1200 mg/day (2 and 3 divided doses); intravenous 20-40 mg every 10-30 minutes (maximum 220 mg)	Rogers et al[27], Brown and Garovic[41]
	Carvedilol	C	Vigilant use	Monitor for neonatal hypoglycemia	Kubota et al[42]
	Atenolol	C/D	Contraindicated	Increased risk of fetal growth restriction and low birth weight	Duan et al[43]
Diuretics	Furosemide, bumetanide	C	Safe	No increased risk of congenital anomalies or small for gestational age infants; monitor maternal hypovolemia, uterine underperfusion, decreased lactation	DeFilippis et al[44], van der Zande et al[45], Bandyopadhyay et al[50]
	Torasemide, metolazone	C	Limited evidence	Comparatively limited pregnancy-specific evidence	DeFilippis et al[44]
	Hydrochlorothiazide	B	Restricted use	Recommended dose for gestational hypertension: 12.5-25 mg/day; monitor maternal hypovolemia	Brown and Garovic[41]
Positive inotropes	Dobutamine	Not applicable	Generally safe	Safe when clinically indicated	Stapel et al[47]
	Milrinone	Not applicable	High caution	Potent vasodilatory effects increase hypotension risk (reduced systemic vascular resistance); stringent hemodynamic monitoring is imperative	Bozkurt et al[48]
	Digoxin	C	Relatively safe	PK adjustment: Increased volume of distribution and renal clearance necessitate higher doses. Monitoring: Therapeutic drug monitoring essential for efficacy/toxicity (safe for fetal tachyarrhythmias)	Hebert et al[29], Purkayastha et al[46]
Special agents
Bromocriptine	Bromocriptine	Not applicable	Investigational	Add-on to standard therapy in acute peripartum cardiomyopathy improved left ventricular ejection fraction and mortality (proof-of-concept pilot study)	Anthony and Sliwa[49]