From the Guidelines
Initial treatment for angina should include sublingual nitroglycerin 0.4 mg as needed for acute episodes, along with a long-acting nitrate such as isosorbide mononitrate 30-60 mg daily for prevention, as recommended by the American College of Physicians 1.
Key Recommendations
- Beta-blockers like metoprolol succinate 25-200 mg daily are first-line therapy for chronic stable angina, reducing heart rate and contractility to decrease myocardial oxygen demand.
- For patients with contraindications to beta-blockers, calcium channel blockers such as amlodipine 5-10 mg daily can be used as they reduce afterload and myocardial oxygen consumption.
- Long-term management should include dual antiplatelet therapy with aspirin 81 mg daily and often a P2Y12 inhibitor like clopidogrel 75 mg daily.
- For refractory angina, ranolazine 500-1000 mg twice daily can be added as it reduces calcium overload in cardiac cells without affecting heart rate or blood pressure.
Lifestyle Modifications
- Smoking cessation
- Regular exercise
- Weight management
- Control of hypertension and diabetes
Patient Education
- Patients should be educated to take nitroglycerin before activities that typically trigger angina and to seek emergency care if pain persists after three doses taken 5 minutes apart.
- Regular follow-up is necessary to assess medication effectiveness and adjust therapy as needed to minimize symptoms and improve quality of life, as supported by the guidelines from the American College of Physicians 1.
From the FDA Drug Label
In CARISA, the improvement in Exercise Tolerance Test (ETT) in females was about 33% of that in males at the 1000 mg twice-daily dose level. The effects of Ranolazine Extended-Release Tablets on angina frequency and nitroglycerin use are shown in Table 2. Statistically significant decreases in angina attack frequency (p=0.028) and nitroglycerin use (p=0.014) were observed with Ranolazine Extended-Release Tablets compared to placebo. The effectiveness of 5 to 10 mg/day of amlodipine in exercise-induced angina has been evaluated in 8 placebo-controlled, double-blind clinical trials of up to 6 weeks duration involving 1038 patients (684 amlodipine, 354 placebo) with chronic stable angina In 5 of the 8 studies, significant increases in exercise time (bicycle or treadmill) were seen with the 10 mg dose.
The initial and long-term treatment recommendations for patients with angina include antianginal medications such as:
- Ranolazine: shown to be effective in reducing angina frequency and nitroglycerin use, with a significant decrease in angina attack frequency (p=0.028) and nitroglycerin use (p=0.014) compared to placebo 2
- Amlodipine: effective in exercise-induced angina, with significant increases in exercise time (bicycle or treadmill) seen with the 10 mg dose 3
- Nitroglycerin: used as needed to treat angina episodes
- Beta-blockers (e.g. metoprolol succinate): used to reduce heart rate and blood pressure
- Calcium channel blockers (e.g. amlodipine): used to reduce blood pressure and increase exercise tolerance
Key points to consider:
- Ranolazine has been shown to be effective in patients with chronic angina who remained symptomatic despite treatment with the maximum dose of an antianginal agent
- Amlodipine has been shown to be effective in reducing hospitalizations for angina and revascularization procedures in patients with CAD
- Nitroglycerin should be used as needed to treat angina episodes
- Beta-blockers and calcium channel blockers should be used as part of a comprehensive treatment plan to reduce heart rate, blood pressure, and increase exercise tolerance.
From the Research
Initial Treatment Recommendations
- The initial drug therapy for prevention of angina pectoris is β-blockers, such as metoprolol succinate, with a class I B indication 4.
- Long-acting nitrates or calcium channel blockers, such as amlodipine, should be prescribed for prevention of angina when β-blockers are contraindicated or not tolerated secondary to side effects, also with a class I B indication 4.
Long-term Treatment Recommendations
- Long-acting nitrates or calcium channel blockers in combination with β-blockers should be prescribed for angina prevention when initial treatment with β-blockers is unsuccessful, with a class I B indication 4.
- Ranolazine can be used for prevention of angina when initial treatment with β-blockers is not successful, with a class IIa A indication 4.
- If angina persists despite treatment with β-blockers, long-acting nitrates and calcium channel blockers, the addition of ranolazine is recommended for prevention of stable angina pectoris 4.
Antianginal Medications
- Nitroglycerin is used for immediate relief of angina pectoris, with a class I B indication 4.
- Long-acting nitrates are effective antianginal drugs during initial treatment, but their therapeutic value is compromised by the rapid development of tolerance during sustained therapy 5.
- Calcium channel blockers, such as verapamil and amlodipine, are second-line alternatives for the symptomatic treatment of stable angina 6.
- Ranolazine has a limited benefit in preventing angina attacks and is associated with a risk of severe adverse effects, including QT interval prolongation and gastrointestinal disorders 7.
Considerations for Specific Medications
- Ivabradine is not recommended for the treatment of stable angina due to its limited efficacy and increased risk of serious coronary events and severe arrhythmias 6.
- Ranolazine is not worth the risk due to its limited efficacy and potential for severe adverse effects, including QT interval prolongation and pharmacokinetic interactions 7.
- Transdermal nitroglycerin systems can be effective in reducing the frequency of angina and nitroglycerin consumption, but may cause common adverse reactions such as headache and skin rash 8.