The treatment of coronary artery disease aims to slow down the progression of the disease, reduce or eliminate structural and functional stenosis or obstruction of the coronary arteries, and correct the imbalance of myocardial blood and oxygen supply and demand, with the objectives of preventing cardiovascular events, prolonging the patient’s life, reducing or relieving symptoms, restoring or protecting cardiac function, and improving the quality of life.
Current treatments for myocardial ischemia in coronary artery disease are mainly pharmacological, interventional (PCI) and surgical (coronary artery bypass graft surgery, CABG). In addition to anti-myocardial ischemia, the treatment of coronary artery disease should include comprehensive control of the risk factors of atherosclerosis, prevention and treatment of mechanical dysfunction of the heart and serious disturbance of cardiac electrical activity caused by ischemia, and maintenance of good hemodynamic status of the whole body and local coronary circulation. The so-called “three treatments” for coronary artery disease are for the treatment of myocardial ischemia, while other aspects of treatment mainly rely on drug therapy.
I. Drug therapy
Even patients who choose interventional or surgical treatment need to receive drug therapy to control the risk factors of coronary heart disease, improve the prognosis and treat the residual ischemia after incomplete blood flow reconstruction. Drug therapy mainly includes antithrombotic therapy, anti-ischemic therapy, treatment to delay the progression of coronary vascular lesions or reverse them, and treatment to improve cardiac function and prevent other ischemia-related complications.
1.Anti-thrombotic drugs: thromboembolism is an important factor causing the reduction or interruption of blood flow in the coronary arteries of patients with coronary heart disease, and acute thrombotic events are the main cause of acute myocardial infarction and death from coronary heart disease, and anti-thrombotic therapy has become the cornerstone of coronary heart disease treatment.
(1) Platelet inhibitors: mainly include aspirin, ADP receptor antagonists and platelet membrane glycoprotein IIb/IIIa receptor antagonists.
Aspirin irreversibly inhibits platelet cyclooxygenase and prevents the formation of thromboxane A2, thereby inhibiting platelet aggregation and activation. Numerous studies have demonstrated that aspirin is effective and cost-effective for the primary prevention of vascular events and secondary prevention of coronary heart disease in high-risk groups.
ADP receptor antagonists: If allergic to or intolerant to aspirin, the ADP receptor antagonists clopidogrel (Povidone and Tegretol) or ticlopidine may be used instead. The benefit of combining clopidogrel for non-ST-segment elevation ACS is greater than that of aspirin monotherapy. Patients with unstable angina and non-ST-segment elevation myocardial infarction, patients undergoing intervention, and patients with ST-segment elevation myocardial infarction may benefit from combined antiplatelet therapy; therefore, patients with acute coronary syndromes and patients undergoing intervention should be treated with a combination of aspirin and clopidogrel.
Platelet membrane glycoprotein IIb/IIIa receptor antagonists: high-risk interventional patients may further benefit from the combined application of IIb/IIIa receptor antagonists in the acute phase, and currently tirofiban is available in China.
(2) Anticoagulants: including normal heparin, low-molecular heparin, vitamin K antagonists and direct thrombin inhibitors.
In patients with non-ST-segment elevation ACS, early application of UFH can reduce the incidence of AMI and coronary ischemic events; for myocardial infarction with ST-segment elevation, UFH is used as an adjunct to thrombolysis and for the prevention of patients at high risk of embolism; UFH is the most commonly used anticoagulant in PCI. The most important issue in clinical application is dosing and monitoring. The adjustment of heparin dosage is usually guided by the value of aPTT, which is generally maintained at 1.5-2 times the control time (50-75 seconds), but the anticoagulation level to be achieved during PCI exceeds the range of aPTT measurement, so the dose of heparin is determined in the catheterization laboratory by measuring the activated clotting time (ACT).
Low molecular heparin (LMWH) is a depolymerization product of regular heparin and has a higher bioavailability, stronger anti-factor Xa activity, and therefore a stronger antithrombotic effect than regular heparin. Low-molecular heparin is easy to use, and the dose administered is usually calculated based on body weight without laboratory monitoring. Numerous clinical studies have shown that in patients with non-ST-segment elevation ACS and ST-segment elevation myocardial infarction, the effects and safety of low-molecular heparin are at least equivalent to those of regular heparin. Currently, the majority of indications for UFH can be replaced by low molecular heparin. Low-molecular heparin is primarily cleared by the kidneys, and severe renal insufficiency may reduce drug clearance, making monitoring of anti-factor Xa activity necessary.
Vitamin K antagonist-warfarin: Studies have shown that the application of adjusted and fixed doses of warfarin is not superior to aspirin in patients with intermediate-risk and low-risk coronary artery disease with increased bleeding complications. However, certain clinical situations still involve warfarin alone or in combination with aspirin, including the following: patients with high-risk myocardial infarction with large anterior wall myocardial infarction, severe heart failure, echocardiographic findings of cardiac thrombus and a history of thromboembolism; patients with coronary artery disease with persistent atrial fibrillation, left ventricular insufficiency and extensive ventricular wall motion disorders; patients with ischemic stroke with persistent Patients with myocardial infarction with ST-segment elevation in atrial fibrillation; patients with myocardial infarction with ST-segment elevation with risk of cardiogenic embolism such as atrial fibrillation, appendicular thrombus or segmental dyskinesia. For these patients, moderate intensity (INR2.0-3.0) warfarin anticoagulation plus low-dose aspirin (75-100 mg/d) or higher intensity warfarin (INR2.5-3.5) anticoagulation should be used depending on the condition and bleeding risk; patients with intracoronary stents should be treated with moderate intensity warfarin (INR2.0-3.0) anticoagulation plus clobigrel 75 mg. Glivec 75mg. During the application of warfarin, attention should be paid to the regular monitoring of INR and the effect of combined medications on the efficacy of warfarin, avoiding arbitrary changes to the original combined medications as much as possible, and if changes must be made, attention should be paid to monitoring INR values and adjusting warfarin doses.
Direct thrombin inhibitors: mainly include leucovorin, argatroban and bivalirudin. They overcome some of the limitations of heparin-based drugs in that their anticoagulant effects are not dependent on antithrombin, remain effective against thrombin-bound thrombin, inhibit thrombin-mediated platelet activation, have a short plasma half-life, and do not require anticoagulation monitoring. Evidence is accumulating for this class of drugs in the anticoagulant treatment of coronary artery disease. They are not recommended as initial routine anticoagulation in patients with non-ST-segment elevation ACS and are mainly used in patients with heparin-induced thrombocytopenia. Direct thrombin inhibitors have no significant clinical benefit in the adjuvant treatment of thrombolysis in patients with ST-segment elevation myocardial infarction and should be used as an alternative to heparin when thrombocytopenia is present or suspected, e.g., streptokinase thrombolysis can be used in combination with bivalirudin, thus replacing heparin.
2. Thrombolytic drugs: commonly used include urokinase, streptokinase and recombinant tissue-type fibrinogen activator (r-tPA). Urokinase and streptokinase belong to the first generation of thrombolytic drugs, which are non-specific fibrinogen activators; recombinant tissue-type fibrinogen activators belong to the second generation, which are more specific for fibrinogen activation than the first generation, and the third generation of thrombolytic drugs mainly include rPA (rteplase). Thrombolytic drugs are used for AMI patients with ST-segment elevation within the prescribed time window and without contraindications to thrombolytic therapy. For patients with non-ST elevation AMI and other types of coronary artery disease, thrombolytic therapy is not only not beneficial but harmful, so only antithrombotic but not thrombolytic.
3.Anti-ischemic drugs.
(1) Nitrate preparations: can be used to control ischemic attacks or prevent them. Nitroglycerin, a fast-acting drug, is the first-line drug to control ischemic attack, and can be used to control acute myocardial ischemic symptoms and the accompanying treatment of congestive heart failure or hypertension, which can be sublingual or administered intravenously according to the condition. To prevent ischemic attack, medium- and long-acting drugs are mainly used, including cardioplegia, 5-mononitrate isosorbide and 5-mononitrate isosorbide extended-release preparation. Nitrates are prone to drug resistance and can be administered intermittently to provide a drug-free period or “blanking period” of 8-12 hours to avoid the occurrence of drug resistance. It can be combined with drugs that improve prognosis, such as beta-blockers and angiotensin-converting enzyme inhibitors.
(2) β-blockers: block the stimulating effect of sympathomimetic amines on heart rate and cardiac contraction, slow down heart rate and blood pressure, slow down myocardial contraction, reduce oxygen consumption and relieve angina pectoris. β-blockers not only treat myocardial ischemia and control angina pectoris symptoms, but also block neurohumoral activation, prevent malignant ventricular arrhythmias and improve prognosis. Improve prognosis. Beta-blockers should be given to patients with coronary artery disease if there are no contraindications. Contraindications include severe bronchial asthma, decompensated heart failure, bradycardia, severe atrioventricular block, hypotension, and diabetes-related hypoglycemia.
This class of drugs can be combined with nitrates or calcium antagonists for synergistic effects. When discontinuing this class of drugs, the dosage should be gradually reduced and then discontinued, and sudden discontinuation may lead to rebound and serious consequences.
Commonly used drugs include metoprolol (betaxolol), bisoprolol (can), atenolol (aminocardium), etc.
(3) Calcium antagonists: they inhibit the entry of calcium ions into the cells, and also inhibit the role of calcium ions in the excitation-contraction coupling of cardiomyocytes, thus inhibiting myocardial contraction; at the same time, they can dilate peripheral blood vessels, lower arterial pressure, reduce cardiac load, and decrease myocardial oxygen consumption; they can also dilate coronary arteries, release coronary artery spasm, and increase myocardial blood supply. Calcium antagonists are mainly used for the treatment of variant angina pectoris and mixed angina pectoris as well as for patients who do not respond well to or cannot tolerate β-blocker and nitrate therapy. It can be used in combination with nitrates or/and beta-blockers. When discontinuing this drug, it is advisable to gradually reduce the dose and then stop taking it to avoid inducing coronary spasm.
Commonly used calcium antagonists include dihydropyridines (nifedipine, amlodipine, niclodipine, felodipine, etc.) and non-dihydropyridines (verapamil, diltiazem, etc.).
4, statin lipid-regulating drugs: A large number of studies have proved that statins stabilize coronary atherosclerotic plaques through lipid-lowering and other mechanisms, stop the progress of lesions and even reverse them, thus improving clinical prognosis, which is one of the most important elements of coronary heart disease treatment. Even if lipid levels are lower than normal, they should be used consistently.
Commonly used statins include atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, and rasulvastatin.
If hypercholesterolemia is difficult to control or combined with other types of serious disorders of lipid metabolism, other types of lipid-regulating drugs such as fibrates, niacin, bile acid chelators, ezetimibe, etc. can be considered under the guidance of physicians, but these drugs are far from replacing the anti-atherosclerotic effect of statins, and if they are combined with statins, they should start with small doses and Pay close attention to the adverse effects on skeletal muscle and liver.
5, angiotensin-converting enzyme inhibitors: ACEI therapy can improve the prognosis of patients with coronary artery disease. For patients with coronary artery disease, especially AMI with ST-segment elevation, if they can tolerate ACEI, they should be treated with this class of drugs and maintained for a long time.
Commonly used ACEI drugs include captopril, fosinopril, enalapril, lenopril, perindopril, ramipril, etc.
Interventional treatment
Percutaneous coronary intervention (PCI) refers to a group of percutaneous interventional techniques, including intracoronary balloon dilation, intracoronary stent implantation, coronary plaque spinning, plaque grinding, thrombus aspiration, and coronary laser angioplasty, to eliminate or alleviate the stenosis or blockage of autologous coronary arteries or bridge vessels with the support of imaging system and the application of relevant devices and materials. At present, PCI mainly involves intracoronary balloon dilation and intracoronary stent implantation, and other interventional techniques are rarely used. Recently, the application of thrombus aspiration techniques in patients with acute myocardial infarction has received widespread attention and has shown good prospects for application. The application of coronary interventional techniques has been called a revolution in modern medicine. Since its birth in the 1970s, interventional materials have been continuously improved, operation techniques have become increasingly mature, and antiplatelet and antithrombotic therapy have been improved, so that the indications for interventional treatment have been broadened, the risks and complications of the procedure have been gradually reduced, and the success rate and safety of the operation have been improved, and it has become the most important treatment for coronary artery disease because of its small trauma, precise and reliable efficacy. It has become one of the most important tools for the treatment of coronary heart disease because of its low invasion, precise and reliable efficacy. The birth of drug-coated stents and the application of statin lipid-regulating drugs have greatly reduced the incidence of in-stent restenosis, which was a great obstacle to the development of interventional techniques, and have shown encouraging prospects for the treatment of coronary artery disease with blood flow reconstruction.
III. Coronary artery bypass grafting
CABG is a procedure in which a blood vessel is taken from one’s own vessel and bypasses the stenosis of the coronary artery to create a blood flow pathway between the aorta and the distal segment of the coronary artery obstruction.
and Effler were the first to perform a successful aorto-coronary artery bypass surgery using the saphenous vein at Cleveland Hospital in the United States, ushering in a new era of direct coronary revascularization. CABG is one of the most important ways of coronary artery revascularization and has the advantage of more complete revascularization for complex lesions such as severe multi-branch, multi-site and diffuse lesions as well as bifurcation of important vessels, but CABG is a highly invasive procedure with relatively high single-visit medical costs. However, CABG surgery is highly invasive, with relatively high single-visit medical costs and high surgical risks in elderly, frail and high-risk patients with severely impaired vital organ functions, so the indications should be strictly controlled in clinical application. In recent years, the development of small incision and non-stop cardiac bypass surgery has further reduced the surgical trauma and related complications.