What anti-angina medications should be prescribed to a patient with angina?

Anti-Angina Medication Selection Algorithm

Beta-blockers and/or calcium channel blockers should be used as initial treatment for most patients with chronic coronary syndrome (CCS) to control heart rate and symptoms. 1

First-Line Therapy Selection

• Short-acting nitrates are recommended for immediate relief of acute angina symptoms in all patients 1
• Beta-blockers are the preferred first-line therapy for most patients with CCS, particularly those with:
  • Prior myocardial infarction 1, 2
  • Heart failure with reduced ejection fraction 1
  • Hypertension 1
  • Atrial fibrillation 1
• Calcium channel blockers (CCBs) are appropriate first-line therapy for patients with:
  • Contraindications to beta-blockers 1
  • Vasospastic angina (dihydropyridine CCBs preferred) 1, 2
  • Microvascular angina 1
  • Hypertension 1

Combination Therapy

• If symptoms are not adequately controlled with a beta-blocker or CCB alone, the combination of a beta-blocker with a dihydropyridine CCB should be considered 1
• When selecting combination therapy, consider:
  • Avoid combining non-dihydropyridine CCBs (verapamil, diltiazem) with beta-blockers due to risk of excessive bradycardia 1
  • Avoid non-dihydropyridine CCBs in patients with heart failure with reduced ejection fraction 1

Add-On Therapy Options

• Long-acting nitrates or ranolazine should be considered as add-on therapy when symptoms persist despite beta-blockers and/or CCBs 1
• Nicorandil or trimetazidine may be considered as add-on therapy in patients with inadequate symptom control on beta-blockers and/or CCBs 1
• Ivabradine should be considered as add-on therapy specifically in patients with:
  • Left ventricular systolic dysfunction (LVEF <40%) 1
  • Inadequate symptom control on other therapies 1
  • Heart rate >70 bpm despite beta-blocker therapy 1, 2

Special Populations

• For patients with microvascular angina:
  • Ranolazine and trimetazidine are particularly effective 1, 3
• For patients with vasospastic angina:
  • Dihydropyridine CCBs are first-line therapy 1
  • Nicorandil or nitrates can be added for better symptom control 1
• For patients with low heart rate and/or blood pressure:
  • Ranolazine and trimetazidine are reasonable options as they have minimal hemodynamic effects 1, 4

Important Considerations

• Beta-blockers are contraindicated in:
  • Sick sinus syndrome 1
  • Atrioventricular conduction disorders 1
  • Use with caution in peripheral arterial disease and chronic obstructive pulmonary disease 1
• Nitrates are contraindicated in:
  • Hypertrophic cardiomyopathy 1
  • Co-administration with phosphodiesterase inhibitors 1
• Ranolazine is contraindicated with:
  • Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) 4
  • CYP3A inducers (e.g., rifampin, St. John's wort) 4
  • Liver cirrhosis 4
• Ivabradine should not be combined with non-dihydropyridine CCBs 1

Dosing Considerations

• Ranolazine: Start at 500 mg twice daily and increase to 1000 mg twice daily based on clinical response 4
• Beta-blockers: Titrate to achieve resting heart rate of 55-60 bpm for optimal antianginal effect 1
• Long-acting nitrates: Require a daily "nitrate-free" interval of 10-12 hours to prevent tolerance 2

Efficacy Evidence

• Ranolazine has demonstrated significant reduction in angina frequency and nitroglycerin use compared to placebo when added to standard therapy 4
• Recent systematic reviews have questioned the traditional hierarchical classification of antianginal drugs, finding little evidence that one class is superior to another for symptom control 5, 6
• The selection of antianginal therapy should be guided by the patient's hemodynamic profile, comorbidities, and the underlying pathophysiological mechanism of angina 1

Common Pitfalls to Avoid

• Failing to provide adequate "nitrate-free" intervals when prescribing long-acting nitrates, leading to tolerance 2
• Combining non-dihydropyridine CCBs with beta-blockers or ivabradine, which can cause excessive bradycardia 1
• Using three antianginal drugs simultaneously without optimizing the dosing of each drug first, which may provide less symptomatic protection than two well-optimized drugs 1
• Overlooking the underlying pathophysiological mechanism of angina (obstructive, vasospastic, or microvascular) when selecting therapy 1, 3