What is the treatment for intermittent exertional angina (stable angina)?

From the Guidelines

Treatment for intermittent exertional angina should prioritize a combination of sublingual nitroglycerin, beta-blockers, and long-acting nitrates to relieve symptoms and improve blood flow to the heart, as recommended by the most recent and highest quality study 1. The goal of treatment is to balance the heart's oxygen supply and demand during exertion.

• First-line therapy includes sublingual nitroglycerin (0.3-0.6 mg) taken as needed when angina occurs or 5-10 minutes before activities that might trigger symptoms, as supported by the American College of Physicians guideline 1.
• For long-term management, daily medications typically include a beta-blocker (such as metoprolol 25-100 mg twice daily) to reduce heart rate and blood pressure, and a long-acting nitrate (like isosorbide mononitrate 30-60 mg once daily) to prevent angina episodes, as suggested by the expert consensus document 1.
• Calcium channel blockers (such as amlodipine 5-10 mg daily) may be added if beta-blockers are contraindicated or insufficient, as recommended by the American College of Physicians guideline 1.
• All patients should take daily aspirin (81-325 mg) to prevent clotting, as supported by the American College of Physicians guideline 1.
• Lifestyle modifications are essential and include regular moderate exercise, smoking cessation, weight management, and stress reduction, as emphasized by the expert consensus document 1. These medications work by either decreasing myocardial oxygen demand (beta-blockers, calcium channel blockers) or increasing oxygen supply (nitrates) to balance the heart's needs during exertion.
• If symptoms persist despite optimal medical therapy, further evaluation for possible coronary revascularization procedures like angioplasty or bypass surgery may be necessary, as suggested by the expert consensus document 1.

From the FDA Drug Label

The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload) Nitroglycerin also produces arteriolar relaxation, thereby reducing peripheral vascular resistance and arterial pressure (afterload), and dilates large epicardial coronary arteries; however, the extent to which this latter effect contributes to the relief of exertional angina is unclear.

Intermittent Exertions Angina Treatment:

• Nitroglycerin is used for the treatment of angina, it works by relaxing vascular smooth muscle and producing dilation of both arterial and venous beds.
• The mechanism of action of nitroglycerin is through the formation of free radical nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues.
• Pharmacodynamics indicate that the onset of the vasodilatory effect of nitroglycerin occurs approximately 1 to 3 minutes after sublingual administration and reaches a maximum by 5 minutes postdose.
• Ranolazine has been shown to be effective in the treatment of chronic angina, with statistically significant increases in modified Bruce treadmill exercise duration and time to angina, and decreases in angina frequency and nitroglycerin use 2, 2.

From the Research

Intermittent Exertions Angina Treatment

• Intermittent exertions angina can be treated with nitrates, which are effective antianginal drugs 3, 4, 5, 6.
• Long-acting nitrates are effective during initial treatment, but their therapeutic value is compromised by the rapid development of tolerance during sustained therapy 3, 5.
• Sublingual nitroglycerin (NTG) is suitable for the immediate relief of angina and maintains its full anti-ischemic effect after initial oral ingestion and after intermittent long-term oral administration 3.
• A nitrate-free interval is required to avoid the development of tolerance, and nitrates vary in their potential to induce tolerance 3, 5, 6.
• Pentaerythritol tetranitrate (PETN) has no tendency to form reactive oxygen species (ROS) and therefore does not induce tolerance or cross-tolerance 3.

Treatment Options

• Nitroglycerin and long-acting nitrates are effective antianginal agents that have been used in clinical medicine for over 100 years 4.
• Beta-blockers, calcium channel blockers, and ranolazine are also used in the treatment of angina 7.
• Revascularization is indicated in certain high-risk individuals and can improve angina, but a substantial percentage of patients return with recurrent or continued angina 7.
• Treatment for refractory angina includes enhanced external counterpulsation, transmyocardial revascularization, and stem cell therapy 7.

Dosage Regimens

• Carefully designed dosing regimens and/or appropriate use of nitrate formulations can decrease or eliminate the problem of nitrate tolerance 4, 5, 6.
• A daily low-nitrate interval is required to prevent tolerance development, and a 12-h patch-free interval should prevent tolerance in most patients 5.
• High single daily doses of isosorbide dinitrate or isosorbide-5-mononitrate can prevent tolerance development and improve patient compliance 5.