Can patients with coronary artery disease (CAD) safely use Calcitonin Gene-Related Peptide (CGRP) inhibitors, such as erenumab (erenumab), galcanezumab (galcanezumab), or fremanezumab (fremanezumab), for migraine treatment?

CGRP Inhibitors in Patients with Coronary Artery Disease

Patients with coronary artery disease (CAD) should use CGRP inhibitors with caution due to potential cardiovascular risks, particularly with erenumab which has been associated with hypertension in post-marketing studies. 1

Safety Considerations for CGRP Inhibitors in CAD

Cardiovascular Effects of CGRP Inhibition

• CGRP is a potent vasodilator that may serve as a protective mechanism during cardiac ischemia 2
• Blocking CGRP could theoretically compromise this protective vasodilatory response during ischemic events 2
• Erenumab has been specifically associated with development or worsening of hypertension in post-marketing studies 1
• Blood pressure monitoring studies have shown:
  • Mean systolic BP increases of up to 5.2 mmHg and diastolic increases of 3.5 mmHg with CGRP inhibitors 3
  • Some patients (3.7%) with normal baseline BP required antihypertensive treatment after starting erenumab 3

Differences Between CGRP Inhibitors

• Erenumab (targets CGRP receptor) has the strongest evidence for BP effects and hypertension risk 1, 3
• Fremanezumab, galcanezumab (target CGRP ligand) may have less pronounced effects on blood pressure 3
• Gepants (oral CGRP antagonists like atogepant, rimegepant) have less data regarding cardiovascular effects in CAD patients

Clinical Decision Algorithm for CAD Patients Needing Migraine Prevention

1. First-line options for CAD patients:

   • Beta-blockers (metoprolol, propranolol) - particularly beneficial as they are indicated for both CAD and migraine prevention 1
   • Venlafaxine or amitriptyline - if beta-blockers are contraindicated 1

2. Second-line options if first-line fails:

   • Consider gepants (atogepant, rimegepant) before monoclonal antibodies due to:
     • Shorter half-life allowing discontinuation if cardiovascular concerns arise
     • Oral administration preferred by patients over injections 1, 4

3. Third-line options with careful monitoring:

   • If considering CGRP monoclonal antibodies:
     • Fremanezumab or galcanezumab may be preferred over erenumab in CAD patients 1, 3
     • Implement regular blood pressure monitoring (baseline and at least quarterly) 3
     • Consider cardiology consultation before initiating therapy

4. Contraindications and special precautions:

   • Use extreme caution with erenumab in:
     • Patients with uncontrolled hypertension
     • Recent myocardial infarction
     • Unstable angina
   • Consider avoiding all CGRP inhibitors in patients with small vessel disease 5

Monitoring Recommendations

• Baseline cardiovascular risk assessment before initiating CGRP inhibitors
• Regular blood pressure monitoring:
  • Before treatment initiation
  • 1 month after starting treatment
  • Every 3 months thereafter
• Educate patients about potential cardiovascular symptoms requiring immediate attention
• Consider discontinuation if significant hypertension develops or cardiovascular symptoms worsen

Key Takeaways

• Beta-blockers should be first-line for migraine prevention in CAD patients when not contraindicated
• CGRP inhibitors are not absolutely contraindicated in CAD but require careful consideration
• Erenumab carries the highest risk for hypertension among CGRP inhibitors
• Regular cardiovascular monitoring is essential when using CGRP inhibitors in CAD patients
• The long-term cardiovascular safety profile of CGRP inhibitors in CAD patients remains incompletely characterized 5