Is romosozumab (Evenity) contraindicated in a patient with carotid stenosis?

Is Evenity (Romosozumab) Contraindicated in Carotid Stenosis?

Romosozumab carries a black box warning against initiation in patients who have had a myocardial infarction or stroke within the preceding year, but carotid stenosis alone—without recent cardiovascular events—is not an absolute contraindication. 1, 2

FDA Black Box Warning and Cardiovascular Contraindications

• Romosozumab should NOT be initiated in patients with myocardial infarction or stroke in the preceding 12 months. 1, 2
• The ARCH trial demonstrated a numerical increase in serious cardiovascular adverse events (MACE) with romosozumab compared to alendronate, though the mechanism remains unclear. 1, 2
• Post-marketing pharmacovigilance data from the FDA Adverse Event Reporting System identified elevated reporting odds ratios for MACE (ROR 4.07,95% CI: 2.39-6.93), particularly in Japanese populations. 3

Risk Stratification for Patients with Carotid Stenosis

The decision to use romosozumab in a patient with carotid stenosis depends on whether the stenosis is symptomatic and the patient's overall cardiovascular risk profile:

Symptomatic Carotid Stenosis (Recent TIA/Stroke)

• Do NOT use romosozumab if the patient has had ipsilateral retinal or hemispheric ischemic symptoms (TIA, stroke, amaurosis fugax) within the past 6 months. 4, 5
• This aligns with the black box warning against use within 12 months of stroke. 1, 2

Asymptomatic Carotid Stenosis

• Romosozumab may be considered cautiously in patients with asymptomatic carotid stenosis if they are at very high fracture risk and have otherwise low cardiovascular risk. 2
• However, additional cardiovascular risk factors (hypertension, coronary artery disease, prior cardiovascular events) should prompt consideration of alternative osteoporosis therapies. 2, 6
• The presence of severe bilateral carotid stenosis (70-99%), contralateral carotid occlusion, or rapidly progressive stenosis represents higher-risk features that warrant extra caution. 7, 8

Clinical Decision Algorithm

For patients with carotid stenosis being considered for romosozumab:

1. Determine symptom status: Has the patient had any stroke, TIA, or amaurosis fugax in the past 12 months? 4

   • If YES → Romosozumab is contraindicated. 1, 2

2. Assess cardiovascular risk profile: Does the patient have additional CV risk factors (prior MI, heart failure, uncontrolled hypertension, diabetes)? 2, 6

   • If high CV risk → Consider alternative therapies (bisphosphonates, denosumab, teriparatide). 2

3. Evaluate stenosis severity and stability: Is the stenosis severe (≥70%), bilateral, or rapidly progressive? 7, 8

   • If severe/unstable → Defer romosozumab until after carotid revascularization or use alternative therapy. 7, 8

4. Assess fracture risk: Is the patient at very high fracture risk (prior fragility fractures, very low BMD, high FRAX score)? 1, 2

   • If fracture risk is moderate → Use safer alternatives first. 2
   • If fracture risk is very high AND CV risk is low → Romosozumab may be considered with informed consent. 2

Important Caveats and Monitoring

• The cardiovascular risk signal with romosozumab remains controversial, with conflicting evidence from randomized trials versus real-world data. 1, 9
• Real-world pharmacovigilance studies suggest the signal may be stronger in certain populations (e.g., Japan), though baseline cardiovascular risk factors were similar across groups in trials. 3
• If romosozumab is used in a patient with asymptomatic carotid stenosis, ensure optimal medical therapy for the carotid disease is in place: antiplatelet therapy (aspirin or clopidogrel), high-intensity statin (atorvastatin 80 mg), and blood pressure control (target <140/90 mmHg). 4, 5
• Patients should be counseled about potential cardiovascular risks and instructed to report chest pain, shortness of breath, or neurological symptoms immediately. 2, 6

Alternative Osteoporosis Therapies in High CV Risk Patients

• For patients with carotid stenosis and high cardiovascular risk, consider:
  • Bisphosphonates (alendronate, zoledronic acid) as first-line therapy 2
  • Denosumab for patients who cannot tolerate bisphosphonates 2
  • Teriparatide for very high fracture risk, though it lacks the potency of romosozumab 1