What is the recommended use of Nikorandil for angina pectoris?

Nicorandil for Angina Pectoris Management

Nicorandil is recommended at a dose of 20 mg twice daily for the prevention of angina pectoris, with an initial starting dose of 5-10 mg twice daily to minimize side effects. 1, 2

Mechanism of Action and Pharmacology

Nicorandil has a dual mechanism of action:

• Potassium channel activator
• Nitrate-like vasodilator properties

This unique combination provides:

• Balanced vasodilation of both arterial and venous vessels
• Reduction in both preload and afterload
• Coronary vasodilation without impairing myocardial contractility
• Strong spasmolytic activity against coronary vasospasm 1, 2

Dosing Recommendations

• Initial dose: 5-10 mg twice daily (to minimize side effects, particularly headache)
• Target dose: 20 mg twice daily for optimal antianginal effects
• Administration: Oral, twice-daily dosing 1, 2

Place in Therapy

For Stable Angina:

1. First-line therapy: Beta-blockers are recommended as first-line treatment

2. Alternative first-line options (if beta-blockers cannot be tolerated):

   • Ivabradine (Class IIa, Level A)
   • Nitrates (Class IIa, Level A)
   • Amlodipine (Class IIa, Level A)
   • Nicorandil (Class IIb, Level C) 1

3. Second-line therapy: Nicorandil may be considered when angina persists despite treatment with a beta-blocker (or alternative) 1

Efficacy

• Comparable efficacy to other antianginal agents including isosorbide dinitrate, beta-blockers (propranolol, atenolol), and calcium channel blockers (nifedipine, diltiazem) 3
• Increases exercise tolerance and time to onset of ST-segment depression during exercise testing 4
• May be effective in patients with variant angina who are refractory to conventional antianginal therapy 3

Advantages Over Traditional Nitrates

• Less development of tolerance with chronic dosing
• No cross-tolerance with nitrates
• Potential cardioprotective properties 1

Side Effects and Precautions

• Common side effects: Headache (most common, occurring in approximately one-third of patients), dizziness 3, 4
• Headache is typically mild to moderate in intensity and tends to decrease with continued treatment
• Approximately 5% of patients may withdraw due to headache, but this rate may be reduced by using a lower starting dose (5 mg twice daily) 3
• Monitor blood pressure, as nicorandil can cause significant reduction in blood pressure 5

Combination Therapy Considerations

Recommended combinations:

• Can be combined with beta-blockers
• Can be combined with calcium channel blockers

NOT recommended combinations:

• Combination with nitrates (lack of additional efficacy)
• Combination with ivabradine or ranolazine (unknown safety) 1

Clinical Pearls

1. Unlike traditional nitrates, nicorandil does not require a "nitrate-free interval" to prevent tolerance
2. May have particular benefit in patients with vasospastic angina
3. Not currently available in the United States, but widely used in Europe, Asia, and other regions 2, 6
4. Consider lower starting doses (5 mg twice daily) in patients at risk for headache or hypotension

Monitoring

• Blood pressure should be monitored, especially when initiating therapy
• Assess for symptomatic improvement in angina frequency and severity
• Evaluate exercise tolerance to gauge effectiveness

Nicorandil represents a valuable alternative or addition to conventional antianginal therapy due to its unique mechanism of action and favorable side effect profile compared to other antianginal medications.