What are the best long-term nitrates for continued management of angina?

Best Long-Term Nitrates for Continued Angina Management

Long-acting isosorbide-5-mononitrate (IS-5-MN) is the preferred long-term nitrate for continued angina management, particularly when administered in an asymmetric twice-daily regimen (morning and 7 hours later) or as a once-daily controlled-release formulation. 1

Nitrate Options and Administration Strategies

Preferred Long-Term Nitrate Options:

1. Isosorbide-5-mononitrate (IS-5-MN)

   • Dosing options:
     • Immediate-release: 20 mg twice daily (morning and 7 hours later)
     • Controlled-release: 120-240 mg once daily in the morning
   • Advantages:
     • Maintains effectiveness during long-term therapy when properly dosed
     • No significant "zero-hour effect" (no rebound angina before next dose)
     • Better tolerance profile compared to other nitrates 1, 2

2. Nitroglycerin (NTG) Patches/Ointment

   • Dosing:
     • Patches: 0.2-0.8 mg/hour (5-20 mg/24h)
     • Ointment: Apply in thin layer to deliver 0.2-0.8 mg/hour
   • Application schedule: Apply for 10-12 hours daily with 10-12 hour nitrate-free interval
   • Caution: May cause rebound angina during nitrate-free interval 3, 4

3. Isosorbide Dinitrate (ISDN)

   • Dosing: 30 mg asymmetric twice daily (7 AM and noon)
   • Note: Less studied for tolerance prevention compared to IS-5-MN 1, 5

Key Administration Principles:

1. Nitrate-Free Interval:

   • Essential to prevent tolerance development
   • Typically 10-12 hours daily 3, 4
   • For patches/ointment: Apply in morning, remove in evening

2. Asymmetric Dosing:

   • For oral nitrates, use asymmetric scheduling rather than evenly spaced doses
   • Example: IS-5-MN 20 mg at 8 AM and 3 PM (7 hours apart) 1

Preventing Nitrate Tolerance

Nitrate tolerance is the primary limitation of long-term nitrate therapy and requires specific strategies:

• Intermittent therapy is the only practical way to avoid tolerance 4
• Avoid continuous 24-hour exposure to nitrates 1, 6
• Combination therapy with beta-blockers is particularly useful as they:
  • Suppress reflex tachycardia induced by nitrates
  • Provide coverage during nitrate-free intervals 3
  • Address potential nighttime angina when nitrates are withdrawn

Special Considerations

• Nocturnal angina: Consider adjusting timing of nitrate-free interval or adding beta-blocker coverage during nitrate-free period 3

• Titration approach: Start with lower doses (e.g., NTG patch 0.2-0.4 mg/hour) and titrate based on symptom control rather than blood pressure response 3

• Monitoring for adverse effects:

  • Headache (most common)
  • Hypotension
  • Reflex tachycardia 3

• Contraindications:

  • Systolic BP <90 mmHg or >30 mmHg below baseline
  • Severe bradycardia or tachycardia
  • Recent use of phosphodiesterase inhibitors
  • Suspected right ventricular infarction
  • Aortic stenosis (use with extreme caution) 3

Comparative Effectiveness

According to the American College of Cardiology/American Heart Association guidelines, long-acting calcium antagonists are often preferable to long-acting nitrates for maintenance therapy due to their sustained 24-hour effects 7. However, nitrates remain an important option when:

• Beta-blockers are contraindicated
• Additional therapy is needed when beta-blockers alone are unsuccessful
• Patient-specific factors favor nitrates 7

Remember that no long-term nitrate regimen provides complete 24-hour anti-anginal coverage, which is why combination therapy is often necessary for optimal management.