A 75-year-old man comes to the clinic due to a 6-month history of periodic substernal chest pressure, which he experiences when walking uphill or climbing 2 flights of stairs. His medical history is significant for hyperlipidemia, for which he takes atorvastatin. The patient smokes a pack of cigarettes daily and occasionally consumes alcohol. Blood pressure is 120/78 mm Hg and pulse is 75/min. Physical examination shows no abnormalities. Resting ECG is normal. A treadmill stress test shows a horizontal ST-segment depression in leads V1-V4 at 73% of predicted maximal heart rate. Echocardiography demonstrates normal resting left ventricular systolic function. The patient prefers medical management. He is prescribed sublingual nitroglycerin to take as needed when anginal pain occurs and he is also prescribed a daily medication to help prevent anginal episodes. The daily medication most likely functions through which of the following mechanisms?
Treatment of chronic stable angina | |
Beta blockers |
|
Nondihydropyridine CCBs |
|
Dihydropyridine CCBs |
|
Nitrates |
|
Ranolazine |
|
CCBs = calcium channel blockers. | |
This patient has coronary artery disease with symptoms and clinical findings consistent with stable angina. Stable angina is defined as chest discomfort that predictably occurs with exertion and is relieved with rest; it results from a mismatch of myocardial oxygen supply and demand. In patients for whom coronary revascularization is not possible or desired, stable angina is treated medically. The 3 main medication classes for the prevention of stable angina symptoms are beta blockers, calcium channel blockers, and long-acting nitrates.
Beta blockers (eg, metoprolol, atenolol) are recommended as first-line therapy for controlling anginal symptoms and improving exercise tolerance in patients with stable angina. These drugs primarily function by reducing myocardial oxygen demand through a decrease in heart rate and myocardial contractility and are highly effective in minimizing or eliminating exertional angina. Nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem) treat angina primarily through the same mechanisms and are an alternative first-line therapy in patients with a beta blocker contraindication.
(Choice A) Ranolazine exerts its antianginal effect by inhibiting the late phase of sodium influx into ischemic cardiac myocytes. This causes reduced calcium influx through the sodium-calcium exchanger, leading to a reduction in ventricular wall stress and myocardial oxygen demand. Ranolazine is often reserved for patients with stable angina that is refractory to other medical therapies.
(Choices B and C) The dihydropyridine calcium channel blockers (eg, amlodipine, felodipine) treat angina in 2 ways: They increase myocardial oxygen supply through coronary artery vasodilation and reduce myocardial oxygen demand through systemic arterial vasodilation and a reduction in cardiac afterload (beta blockers only mildly reduce afterload). The dihydropyridines are typically used in combination with beta blockers because monotherapy can result in reflex tachycardia and worsening anginal symptoms.
(Choice D) Nitrates treat angina primarily through the dilation of venous capacitance vessels and a reduction in cardiac preload. The result is a reduction in left ventricular wall stress and reduced myocardial oxygen demand. Long-acting nitrates (eg, isosorbide mononitrate) are often added to beta blockers in patients with persistent, stable angina. As-needed, short-acting nitrates (eg, sublingual nitroglycerin) can provide brief anginal relief but are not used for long-term anginal prevention.
Educational objective:
Beta blockers are first-line therapy for preventing symptoms and improving exercise tolerance in patients with stable angina. They help prevent angina by decreasing exertional heart rate and myocardial contractility, leading to a reduction in myocardial oxygen demand. Calcium channel blockers and long-acting nitrates are also used.