What are the recommended drugs and their doses for the management of chronic angina?

Management of Chronic Angina: Recommended Drugs and Dosing

For chronic angina management, the recommended first-line medications are beta-blockers and/or calcium channel blockers, with short-acting nitrates for immediate symptom relief, followed by long-acting nitrates, ranolazine, nicorandil, or trimetazidine as add-on therapies when symptoms persist. 1

First-Line Therapy

Immediate Symptom Relief

• Short-acting nitrates (Class I, Level B recommendation) 1
  • Sublingual nitroglycerin tablets: 0.3-0.6 mg as needed for acute angina attacks
  • Nitroglycerin spray: 0.4 mg (1-2 sprays) sublingually as needed
  • Advantages of spray formulation: faster onset, effective with dry mouth, lower incidence of headache 2

Initial Maintenance Therapy

• Beta-blockers (Class I, Level B recommendation) 1

  • First choice for most patients with chronic coronary syndrome
  • Examples: metoprolol, bisoprolol, carvedilol at appropriate doses

• Calcium channel blockers (CCBs) (Class I, Level B recommendation) 1

  • Alternative first-line therapy, especially if beta-blockers are contraindicated
  • Dihydropyridines (e.g., amlodipine 5-10 mg daily)
  • Non-dihydropyridines (e.g., diltiazem, verapamil)

Second-Line and Add-On Therapy

When symptoms are inadequately controlled with first-line agents:

1. Combination of beta-blocker and dihydropyridine CCB (Class IIa, Level B) 1

   • Recommended combination for most patients requiring dual therapy

2. Long-acting nitrates (Class IIa, Level B) 1

   • Isosorbide mononitrate: 30-60 mg once daily or 20-40 mg twice daily
   • Isosorbide dinitrate: 20-40 mg twice or three times daily
   • Transdermal nitroglycerin patch: 0.2-0.8 mg/hour applied for 12-16 hours daily with a nitrate-free interval to prevent tolerance 3, 4

3. Ranolazine (Class IIa, Level B) 1, 5

   • Starting dose: 500 mg twice daily
   • Can be increased to 1000 mg twice daily based on clinical response
   • Particularly useful in patients with bradycardia, hypotension, or diabetes 5

4. Nicorandil (Class IIb recommendation) 1

   • 10-20 mg twice daily
   • May be considered as add-on therapy or for patients with coronary artery spasm

5. Trimetazidine (Class IIb recommendation) 1

   • 35 mg twice daily
   • May be considered as add-on therapy or for patients with microvascular angina

Special Considerations

Ivabradine

• Consider as add-on therapy specifically in patients with:
  • Left ventricular systolic dysfunction (LVEF <40%) 1
  • Inadequate control of symptoms
• Not recommended in patients with:
  • LVEF >40% without clinical heart failure
  • In combination with non-DHP CCBs or strong CYP3A4 inhibitors 1

Important Contraindications

• Nitrates: Contraindicated in patients with:

  • Hypertrophic cardiomyopathy
  • Concomitant use of phosphodiesterase inhibitors (e.g., sildenafil) 1

• Ranolazine: Contraindicated in patients with:

  • Hepatic impairment or liver cirrhosis
  • Concomitant use of strong CYP3A inhibitors 5

Treatment Algorithm

1. Start with short-acting nitrates for immediate relief of angina attacks
2. Initiate beta-blocker and/or CCB as first-line maintenance therapy
3. If symptoms persist:
   • Combine beta-blocker with dihydropyridine CCB, or
   • Add long-acting nitrates, ranolazine, nicorandil, or trimetazidine based on patient characteristics
4. For patients with LVEF <40%: Consider adding ivabradine if symptoms persist

Monitoring and Follow-up

• Review patient response to therapy within 2-4 weeks after drug initiation 1
• Assess for side effects, particularly headache with nitrates, constipation with ranolazine, and bradycardia with beta-blockers
• Monitor ECG for QT prolongation in patients on ranolazine 5

This evidence-based approach to chronic angina management emphasizes symptom control while considering individual patient characteristics, comorbidities, and potential drug interactions to optimize outcomes and quality of life.