Is dapagliflozin, sacubitril/valsartan, and eplerenone safe for patients with thyroid-induced cardiomyopathy?

Safety of Dapagliflozin, Sacubitril/Valsartan, and Eplerenone in Thyroid-Induced Cardiomyopathy

Yes, dapagliflozin, sacubitril/valsartan, and eplerenone are safe and recommended for thyroid-induced cardiomyopathy once the patient is hemodynamically stable, following the same guideline-directed medical therapy (GDMT) principles as other forms of heart failure with reduced ejection fraction (HFrEF). 1

Critical First Step: Thyroid Control

Before optimizing heart failure medications, you must address the underlying thyrotoxicosis with thionamides (methimazole, carbimazole, or propylthiouracil), as these have relatively long latency of action 2. In cases of cardiogenic shock, beta-blockers should only be administered after restoring satisfactory blood pressure levels with cautious use of synthetic catecholamines if necessary 2.

Evidence-Based Treatment Algorithm

Initial Stabilization Phase

• Start beta-blockers intravenously in small doses only after hemodynamic stability is achieved 2
• Initiate thionamide therapy immediately for thyroid control 2
• Use standard heart failure therapies including diuretics as needed for volume management 1

GDMT Optimization After Stabilization

Once thyrotoxicosis is controlled and the patient is hemodynamically stable, apply standard HFrEF guidelines:

SGLT2 Inhibitors (Dapagliflozin)

• Start dapagliflozin 10 mg once daily (no titration needed) 1
• This is a Class 2a recommendation for HFrEF to reduce heart failure hospitalization and death 1
• Dapagliflozin demonstrated significant reduction in cardiovascular death or worsening heart failure in the DAPA-HF trial 1
• Safe when combined with sacubitril/valsartan, with similar efficacy and safety profiles regardless of background ARNI therapy 3

Sacubitril/Valsartan (ARNI)

• Start at 24/26 mg to 49/51 mg twice daily, target 97/103 mg twice daily 1
• This is a Class 2b recommendation for HFrEF 1
• Can be initiated de novo in hemodynamically stable patients 1
• Monitor blood pressure before each dose escalation 4
• The combination of sacubitril/valsartan with dapagliflozin further reduces cardiac mortality compared to ARNI monotherapy 5

Eplerenone (Mineralocorticoid Receptor Antagonist)

• Start at 25 mg once daily, target 50 mg once daily 1
• This is a Class 1 recommendation for HFrEF to reduce cardiovascular mortality and heart failure hospitalizations 1
• Monitor potassium and renal function closely, especially if renal dysfunction from chronic congestion is present 4

Monitoring Protocol

Essential monitoring parameters:

• Blood pressure before each medication uptitration 4
• Renal function (creatinine, eGFR) at baseline and after dose changes 4
• Electrolytes (particularly potassium with eplerenone) at baseline and after dose changes 4
• Thyroid function tests to ensure adequate control of hyperthyroidism 2
• N-terminal pro B-type natriuretic peptide levels to assess treatment response 6

Titration Strategy

Uptitrate GDMT as frequently as every 1-2 weeks depending on symptoms, vital signs, and laboratory findings 1. Target the doses proven efficacious in randomized controlled trials, even if symptoms improve at lower doses 1. The goal is to achieve:

• Sacubitril/valsartan 97/103 mg twice daily 1
• Dapagliflozin 10 mg once daily 1
• Eplerenone 50 mg once daily 1

Key Clinical Pitfalls to Avoid

Do not withhold standard HFrEF therapies simply because the etiology is thyroid-related 1. Thyrotoxic dilated cardiomyopathy, while rare (occurring in <1% of hyperthyroid patients with severe LV dysfunction), should be treated with evidence-based heart failure pharmacologic measures supplemented by thyroid-specific therapies 2.

Do not start beta-blockers in cardiogenic shock before hemodynamic stabilization 2. This is a critical safety consideration unique to the acute presentation of thyrotoxic cardiomyopathy.

Do not assume these medications are contraindicated due to the thyroid etiology—there is no pathophysiologic reason to avoid GDMT once thyrotoxicosis is controlled and hemodynamics are stable 1, 2.

Expected Outcomes

With appropriate thyroid control and GDMT optimization, expect:

• Progressive recovery of ejection fraction 6, 7
• Reduction in cardiac volumes 7
• Normalization of natriuretic peptide levels 6
• Reduced rehospitalization rates 5
• Improved functional status and quality of life 1