What is the first-line treatment for Prinzmetal's (variant) angina?

First-Line Treatment for Prinzmetal's (Variant) Angina

Calcium channel blockers are the first-line therapy for Prinzmetal's variant angina, along with long-acting nitrates. 1

Pathophysiology and Diagnosis

• Prinzmetal's variant angina is characterized by episodes of transient ST-segment elevation during chest pain (typically at rest, often in early morning hours) that resolves when pain abates 1
• The underlying mechanism involves focal coronary artery spasm due to dysfunctional endothelium that exposes medial smooth muscle to vasoconstrictors 1
• Diagnosis is confirmed by documenting ST-segment elevation during chest pain episodes, with prompt relief by nitroglycerin 1
• Coronary angiography is usually part of the workup to assess for underlying coronary disease, as spasm can occur in normal or atherosclerotic vessels 1

First-Line Treatment Options

Calcium Channel Blockers

• Calcium channel blockers are highly effective first-line agents for Prinzmetal's angina 1
• Usually started at moderate to high doses:
  • Verapamil 240 to 480 mg per day 1
  • Diltiazem 180 to 360 mg per day 1
  • Nifedipine 60 to 120 mg per day 1
• Dihydropyridine CCBs (like amlodipine) block coronary spasm by inhibiting calcium influx into vascular smooth muscle cells 2
• Amlodipine has been specifically FDA-approved for vasospastic (Prinzmetal's) angina and can be used as monotherapy or in combination with other antianginal agents 2
• Clinical trials have shown that amlodipine decreases vasospastic angina attacks by approximately 4/week compared to placebo 2

Nitrates

• Nitrates are also considered first-line therapy alongside calcium channel blockers 1
• Nitroglycerin is exquisitely effective for acute relief of spasm 1
• Long-acting nitrates are used for prevention of attacks 1
• For acute coronary spasm during angiography, 0.3 mg of nitroglycerin should be infused directly into the involved coronary artery 1

Treatment Algorithm

1. Initial therapy: Start with a calcium channel blocker at moderate to high dose 1
2. If inadequate response: Add long-acting nitrates 1
3. For very active disease: Consider combination of nitrates and two calcium channel blockers of different classes (e.g., a dihydropyridine with verapamil or diltiazem) 1
4. For refractory cases: Alpha-receptor blockers may be beneficial, especially in patients not responding completely to calcium channel blockers and nitrates 1

Important Considerations and Cautions

• Beta-blockers have theoretical adverse potential in vasospastic angina and their clinical effect is controversial; they are generally not recommended 1, 3
• Smoking cessation is essential as it can trigger coronary spasm 1
• Patients with normal or near-normal coronary arteries generally have an excellent prognosis with appropriate medical therapy (89-97% 5-year survival) 1
• Patients with coronary spasm superimposed on fixed obstructive coronary artery disease have a worse prognosis 1
• Occasional patients may require a pacemaker to prevent transient AV block or a defibrillator to prevent sudden death associated with ischemia-induced ventricular fibrillation 1

Monitoring and Follow-up

• Monitor for symptom relief and frequency of anginal attacks 1
• Ambulatory ECG monitoring may be used to assess the results of medical therapy in controlling vasospastic events 1
• Patients with coronary artery vasospasm superimposed on fixed obstructive coronary artery disease require closer monitoring due to worse prognosis 1