What drug plays no role in reducing mortality in patients with chronic stable angina?

Nitrates Play No Role in Reducing Mortality in Chronic Stable Angina

Nitrates have not been shown to reduce mortality in patients with previous myocardial infarction or in patients with coronary artery disease, and are used solely for symptom relief in chronic stable angina. 1

Evidence on Mortality Benefits in Chronic Stable Angina

The pharmacological management of chronic stable angina includes several classes of medications, each with different effects on symptoms and mortality:

Medications That Reduce Mortality:

1. Aspirin: Reduces cardiovascular death, MI, and stroke in patients with established CAD (Level of evidence: A) 1, 2
2. Beta-blockers: Reduce mortality in patients with previous MI (Level of evidence: A) and are recommended as first-line therapy 1, 2
3. Statins: Low-density lipoprotein cholesterol-lowering therapy with statins decreases the risk of adverse ischemic events in patients with established CAD (Level of evidence: A) 1, 2
4. ACE inhibitors: Reduce cardiovascular death, MI, and stroke in patients at risk for or with vascular disease without heart failure (Level of evidence: A) 1, 2

Medications That Do Not Reduce Mortality:

1. Nitrates: While effective for symptom relief, nitrates have not been shown to reduce mortality in patients with previous MI or in patients with CAD 1, 3
2. Calcium Channel Blockers: Immediate-release or short-acting dihydropyridine calcium antagonists may increase adverse cardiac events, though long-acting formulations may relieve symptoms without increasing mortality 1
3. Dipyridamole: Should not be used to prevent MI or death in patients with chronic stable angina (Level of evidence: B) 1
4. Chelation therapy: Should not be used to prevent MI or death in patients with chronic stable angina (Level of evidence: B) 1

Appropriate Use of Nitrates in Chronic Stable Angina

Despite not reducing mortality, nitrates have an important role in angina management:

• Sublingual nitroglycerin or nitroglycerin spray: Recommended for immediate relief of angina (Level of evidence: B) 1, 2
• Long-acting nitrates: Should be used when beta-blockers are contraindicated or in combination with beta-blockers when beta-blockers alone are unsuccessful (Level of evidence: B) 1, 2

Important Considerations When Using Nitrates:

• Require a daily "nitrate-free" interval of 10-12 hours to prevent tolerance 2, 4
• Long-acting nitrates may reduce the number of angina attacks (by approximately 2.89 episodes weekly for continuous administration) 3
• Improve exercise duration (by approximately 31-53 seconds) 3
• Common side effect: headache (reported in 51.6% of patients) 3

Clinical Algorithm for Chronic Stable Angina Management

1. First-line therapy: Beta-blockers (mortality benefit + symptom relief)
2. Add or substitute if needed:
   • Long-acting calcium channel blockers (when beta-blockers are contraindicated)
   • Long-acting nitrates (for symptom relief only)
3. For all patients:
   • Aspirin (75-150 mg daily)
   • Statin therapy
   • ACE inhibitor (particularly for patients with diabetes, hypertension, or LV dysfunction)

Common Pitfalls in Angina Management

• Relying solely on nitrates for angina management without addressing mortality risk with evidence-based therapies
• Failing to provide a nitrate-free interval, leading to tolerance
• Inappropriate combinations of medications (e.g., beta-blockers with non-dihydropyridine calcium channel blockers)
• Overlooking aspirin therapy, which is essential for all patients with stable coronary disease 2

Special Considerations

• Ivabradine showed no benefit in stable coronary artery disease with or without stable heart failure in the BEAUTIFUL and SIGNIFY trials 5
• For refractory angina despite optimal medical therapy, newer techniques such as enhanced external counterpulsation, spinal cord stimulation, or transmyocardial revascularization may be considered, though their long-term efficacy requires further evaluation 6