Coronary artery disease relief strategies and special type identification: From nitrate drug use to the prevention and treatment of cardiac syndrome X

Beta-blockers. Patients with chronic stable angina, congestive heart failure, and post-myocardial infarction should receive long-term secondary prevention treatment with beta-blockers, which can reduce cardiovascular events, readmission rates, and mortality.

The national guidelines recommend Class I (consistent recommendation) drug treatment to improve prognosis: (1) Patients with stable angina pectoris due to coronary heart disease should take 75-150 mg of aspirin orally daily if there are no contraindications to aspirin (such as active gastrointestinal bleeding, aspirin allergy, or a history of aspirin intolerance). (2) All patients with stable angina pectoris due to coronary heart disease should receive statin therapy, with a target LDL-C value of <2.60 mmol/L. (3) All patients with hypertension, diabetes, chronic kidney disease, heart failure, left ventricular systolic dysfunction, or post-myocardial infarction left ventricular dysfunction should use ACEIs. (4) Patients with stable angina pectoris or heart failure after myocardial infarction should use β-blockers. (Level A of evidence)

Medications that relieve symptoms and combat ischemia. These medications improve symptoms and signs of myocardial ischemia by reducing myocardial oxygen consumption and/or increasing blood flow to ischemic areas of the myocardium. Commonly used antianginal drugs fall into three classes: beta-blockers, calcium channel blockers, and nitrates.

(1) Nitrates. ● Short-acting nitrates. Nitrates are endothelial-dependent vasodilators that reduce myocardial oxygen demand and improve myocardial perfusion, thereby improving angina symptoms. Nitrates reflexively increase sympathetic tone, leading to a faster heart rate. Therefore, they are often combined with negative rate-regulating drugs such as beta-blockers or non-dihydropyridine calcium channel blockers to treat chronic stable angina. The antianginal effect of combination therapy is superior to that of monotherapy. Nitroglycerin 0.25-0.5 mg, taken sublingually as needed; isosorbide dinitrate 5-10 mg 2-3 times/day, also taken sublingually as needed. Sublingual nitroglycerin has a rapid onset of action and can last for 20-45 minutes, relieving symptoms by reducing cardiac preload and afterload and dilating coronary arteries. It is important to check for nitroglycerin expiration; it should be stored away from light and replaced every 3-6 months. Delayed onset or ineffectiveness suggests severe coronary artery disease or possible myocardial infarction. Repeated use over a long period of time in a short period of time may lead to tolerance and reduced efficacy; effectiveness can be restored after a period of discontinuation.

●Long-acting nitrates. Long-acting nitrates can be used when β-blockers are not tolerated or are ineffective. Care should be taken to avoid drug tolerance; sufficient drug-free intervals should be provided daily to reduce the occurrence of tolerance. For example, patients with exertional angina should take the medication during the day and stop at night; skin patches should be applied during the day and removed at night. Long-acting nitrates can be used as a treatment alternative for patients who do not respond to CCB therapy or CCB combined with β-blockers. Adverse reactions to nitrates include headache, facial flushing, reflex tachycardia, and hypotension; these adverse reactions are more pronounced with short-acting nitroglycerin. Orthostatic hypotension may occur during the first use of sublingual nitroglycerin. Patients using sildenafil (an erectile dysfunction medication) should not use nitroglycerin or other nitrate preparations within 24 hours to avoid hypotension, which could be life-threatening. Nitrates are not recommended for angina caused by severe aortic stenosis or hypertrophic obstructive cardiomyopathy. Nitrates reduce cardiac preload and left ventricular volume, which can further increase the degree of left ventricular outflow tract obstruction. In patients with severe aortic stenosis, the use of nitrates can also reduce cardiac output due to the reduction in preload, which may cause syncope.

(2) β-blockers. These reduce myocardial oxygen consumption by lowering heart rate, myocardial contractility, and blood pressure, effectively improving angina attacks and increasing exercise tolerance. After administration, the resting heart rate should be reduced to 55-60 beats/min; in severe angina patients without bradycardia, this can be reduced to 50 beats/min. However, β-blockers can worsen symptoms in angina caused by vasospasm (variant angina). Unless contraindicated, β-blockers should be used as initial treatment for stable angina. β-blockers can reduce the risk of death and re-infarction in patients with stable angina after myocardial infarction. Many β-blockers are currently available for treating angina, and when administered at adequate doses, they can effectively prevent angina attacks. Currently, selective β₁ blockers, such as metoprolol, atenolol, and bisoprolol, are preferred. The main side effects of beta-blockers are sinus bradycardia, worsening of symptoms of bronchial asthma or chronic obstructive pulmonary disease, adverse effects on glucose and lipid metabolism at high doses, and the potential adverse effects on cardiovascular and cerebrovascular diseases from long-term high-dose use are also a concern. Respiratory side effects are rare with beta₁-blockers.

(3) Calcium channel blockers (CCBs). Calcium channel blockers relieve angina by improving coronary blood flow and reducing myocardial oxygen consumption. They are first-line drugs for variant angina or angina primarily caused by coronary artery spasm. Non-dihydropyridine calcium channel blockers, such as verapamil and diltiazem, have strong negative inotropic effects and can significantly reduce heart rate and worsen atrioventricular block. They are often used for angina patients with atrial fibrillation or atrial flutter. These two drugs should not be used in patients with severe bradycardia, high-degree atrioventricular block, or sick sinus syndrome, and should be avoided in combination. The combination of long-acting calcium channel blockers and beta-blockers is more effective than using either drug alone. In addition, when the two drugs are used in combination, beta-blockers can also reduce the adverse reaction of reflex tachycardia caused by dihydropyridine calcium channel blockers. Non-dihydropyridine calcium channel blockers such as diltiazem or verapamil can be used as alternative treatments for patients who have contraindications to beta-blockers. The main side effects of calcium channel blockers include headache, dizziness, facial flushing, ankle edema, and hypotension caused by arterial vasodilation, as well as fatigue and constipation.

(4) Novel antianginal drugs. Metabolic drugs (trimetazidine and ranoprazine) treat myocardial ischemia by promoting fatty acid-related glucose metabolism, without acting by lowering heart rate and blood pressure, and therefore can be used in combination with drugs with hemodynamic effects. Metabolic drugs can be used in combination with conventional antianginal drugs, or alone for patients who cannot tolerate conventional treatment.

The national guidelines recommend the following Class I (consistent recommendation) drug treatments for relieving symptoms and improving ischemia: (1) Use short-acting nitroglycerin to relieve and prevent acute attacks of angina (Level B evidence). (2) Use β-blockers and gradually increase to the maximum tolerated dose, choosing appropriate dosage forms and dosing frequencies, with the goal of providing 24-hour anti-myocardial ischemia. (3) When β-blockers are not tolerated or the effect of β-blockers as initial treatment is unsatisfactory, calcium channel blockers can be used (Level A evidence), or long-acting nitrates can be tried. (4) When the effect of β-blockers as initial treatment is unsatisfactory, long-acting dihydropyridine calcium channel blockers or long-acting nitrates can be used in combination (Level B evidence). (5) Long-acting calcium channel blockers can be used as initial treatment for patients with coronary heart disease and hypertension (Level B evidence).

Special types of coronary artery disease. Asymptomatic coronary artery disease. The diagnosis of asymptomatic coronary artery disease is based on a history of myocardial infarction, a history of revascularization and/or evidence of ischemia on electrocardiogram, abnormal coronary angiography, or abnormal stress test without corresponding symptoms. Examination, diagnosis, and risk stratification are the same as for chronic stable angina. Patients with confirmed asymptomatic coronary artery disease should be treated with medication to prevent myocardial infarction or death, and related risk factors should be treated. Treatment recommendations are the same as for chronic stable angina.

Cardiac Syndrome X. Cardiac Syndrome X, also known as microvascular angina, is a specific type of stable angina. Patients present with exertional angina, evidence of myocardial ischemia, or a positive exercise test. Nitroglycerin can relieve symptoms, but coronary angiography is normal, and coronary artery spasm can be ruled out. Nitrates are effective in about half of the patients, and long-acting nitrates can be used as initial treatment. If symptoms persist, long-acting calcium channel blockers or beta-blockers can be used in combination. ACE inhibitors and statins help improve underlying endothelial dysfunction and should be considered.

The Chinese Guidelines for the Diagnosis and Treatment of Chronic Stable Angina recommend the following pharmacological treatments for improving symptoms of Cardiac Syndrome X: Class I (Consensus Recommendation): ● Monotherapy or combination therapy with nitrates, beta-blockers, and calcium channel blockers (Level B Evidence). ● Statins for patients with hyperlipidemia (Level B Evidence). ● ACE inhibitors for patients with hypertension or diabetes (Level B Evidence). Class II (Opinions or evidence are not entirely consistent, but tend to be effective): Other antianginal drugs, including nicorandil and the metabolite trimetazidine (Level C Evidence).