Coronary heart disease is a kind of heart disease caused by myocardial ischemia and hypoxia (angina pectoris) or myocardial necrosis (myocardial infarction) caused by organic coronary artery stenosis or occlusion, also known as ischemic heart disease. Usually, what we call coronary heart disease is mostly caused by organic stenosis or obstruction of arteries, also known as coronary atherosclerotic heart disease. Its coronary artery stenosis is mostly caused by the accumulation of fatty substances along the inner wall of blood vessels, which is called arteriosclerosis. When arteriosclerosis develops to a certain extent, coronary artery stenosis is gradually aggravated, which limits the blood flow into myocardium. If the heart does not get enough oxygen supply, chest discomfort, that is, angina pectoris, will occur. Different people have different manifestations of angina pectoris. Most people describe it as "chest pressure", "abdominal distension" and "oppressive feeling". Some patients feel released to bilateral shoulders, back, neck and throat, and rest or take nitroglycerin to relieve it. Myocardial infarction is another manifestation of coronary heart disease. The symptoms of chest pain are persistent and severe, and rest or taking nitroglycerin is ineffective. During myocardial infarction, the coronary artery is completely blocked, and this part of myocardial necrosis is because the blood has no oxygen supply. Most of them are caused by thrombosis, rupture of atherosclerotic plaque or vasospasm in stenosis.
Acute coronary syndrome
Acute coronary syndrome (ACS) is a group of clinical syndromes caused by acute myocardial ischemia, including acute myocardial infarction (AMI) and unstable angina pectoris (UA), among which AMI is divided into ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Platelet activation plays an important role in the occurrence of ACS.
Anti-thrombotic therapy strategy for acute coronary syndrome
Acute Coronary Syndrome (ACS) is a group of clinical syndromes based on the rupture or erosion of coronary atherosclerotic plaque, followed by complete or incomplete occlusive thrombosis. It is a series of clinical symptoms including unstable angina pectoris, non-Q wave myocardial infarction and Q wave myocardial infarction. Long-term clinical practice has found that many patients have different clinical symptoms, but their coronary arteries have very similar pathophysiological changes, that is, coronary atherosclerotic plaques change from stable to unstable, and then rupture leads to thrombosis. Therefore, antithrombotic therapy for acute coronary syndrome is very important, especially for ACS with non-ST segment elevation. Antithrombotic therapy can be divided into antiplatelet therapy and antithrombin therapy.
Acute coronary syndrome can be divided into ST-segment elevation type and non-ST-segment elevation type according to ECG manifestations, in which non-ST-segment elevation type is divided into unstable angina pectoris and non-ST-segment elevation type myocardial infarction, while ST-segment elevation type mainly refers to acute myocardial infarction. The physiological difference between them may be that the physiological basis of non-ST-segment elevation disease is that thrombus completely blocks arteries or microemboli, while ST-segment elevation disease is that thrombus completely blocks arteries and blood vessels. Although their physiological processes are similar, their clinical manifestations and treatment strategies are quite different.
I. Non-ST segment elevation acute coronary syndrome
Non-ST segment elevation acute coronary syndrome includes unstable angina pectoris and non-ST segment elevation myocardial infarction. In 2002, ACC/AHA introduced a new treatment guideline for UA/NSTEMI, in which the suggestions on antiplatelet and anticoagulant therapy are as follows:
class A
coronary artery
1, antiplatelet therapy should be started quickly. Aspirin is the first choice (level of evidence: A).
2. Patients who are allergic to aspirin or intolerant of gastrointestinal diseases should use clopidogrel (evidence level: A).
3. For hospitalized patients who are not ready for early interventional therapy, clopidogrel should be used as much as possible except aspirin at the time of admission, and the medication time is 1 (evidence level: a)-9 months (evidence level: B).
4. Clopidogrel should be used for more than 0 months (level of evidence: a) and 9 months (level of evidence: b) if there are no high-risk factors of bleeding in hospitalized patients who are ready for intervention.
5. Patients who are preparing for elective CABG and are using clopidogrel should stop taking drugs for 5-7 days (evidence level: B).
6. In addition to antiplatelet therapy with aspirin or clopidogrel, intravenous heparin or subcutaneous LMWH should also be used for anticoagulant therapy (evidence level: A).
7. For patients who are ready for cardiac catheterization and PCI, besides aspirin and unfractionated heparin, they should also use GPIIb/IIIa receptor antagonist (level of evidence: A) class IIa.
1. For patients with persistent ischemia and elevated troponin, or patients who are not ready for invasive treatment but have other high-risk manifestations, aspirin and low-molecular-weight heparin are used.
2. Compared with unfractionated heparin, enoxaparin is the first choice anticoagulant for UA/NSTEMI patients, unless they are prepared to undergo CABG surgery within 24 hours (evidence level: A).
3. For patients who have already used heparin, aspirin and clopidogrel and are ready for cardiac catheterization and PCI, GPIIb/IIIa receptor antagonists should be used or used before PCI (evidence level: B).
Class IIb
In addition to aspirin and low molecular weight heparin, GP IIb/IIIa receptor antagonists are used for patients without persistent ischemia and other high-risk manifestations or patients who are not ready for invasive treatment (evidence level: A).
The third category
1, patients without acute ST segment elevation, posterior myocardial infarction or new LBBB received intravenous thrombolysis (evidence level: A).
2. Use abciximab (A) for patients who are not prepared to receive PCI.
This guide guides our clinical work for a long time. However, the development of medical science is very rapid. In recent years, with the development of various large-scale clinical research and the continuous emergence of new drugs, many new evidence-based medical evidence has been placed in front of us, and the guidelines should be updated and improved accordingly. In 2004, the American College of Chest Physicians issued the guideline ACCP7 on thrombotic diseases. We will talk about the antithrombotic strategy of acute coronary syndrome according to ACCP7.
Antiplatelet therapy of (1)NSTE-ACS
The commonly used antiplatelet drugs in clinic include aspirin, ticlopidine, dipyridamole and platelet glycoprotein IIb/IIIa receptor antagonist. Combined antiplatelet therapy will improve the clinical prognosis.
1, aspirin
Aspirin is the basis of antiplatelet therapy. Cyclooxygenase-1 (COX- 1) acting on platelets inhibits its activity, thus reducing the degradation of arachidonic acid, reducing the production of TXA2, and inhibiting the activation of GpIIb/IIIa receptors, thus achieving the effect of inhibiting platelet activation. ACCP7 recommends aspirin as follows:
For all NSTE ACS patients who are not allergic to aspirin, it is recommended to take 75 to 325mg aspirin immediately, and then 75 to 162mg aspirin every day (grade 1a).
Walletin et al. confirmed that long-term use of aspirin can significantly reduce the mortality and myocardial infarction rate of ACS patients, and this advantage gradually increases with time. Another meta-analysis shows that ACS after taking aspirin means poor clinical prognosis.
2. Ticlopyridine drugs
Include ticlopidine and clopidogrel. They are platelet ADP receptor antagonists. It acts on ADP receptor and inhibits the activation of platelet GpIIb/IIIa receptor, thus achieving the effect of inhibiting platelet activation. ACCP7' s recommendations for ticlopyridine drugs are as follows:
For all NSTE ACS patients who are not allergic to aspirin, it is recommended to take clopidogrel 300 mg orally immediately and then 75 mg daily (grade 1A).
For NSTE-ACS patients who can't perform diagnostic catheterization or CABG immediately within 5 days after coronary angiography, it is recommended to take clopidogrel 300 mg orally immediately, and then take aspirin (grade 1A) for 75 mg to 9 to 12 months every day.
For NSTE-ACS patients who will receive coronary angiography within 24 hours, it is recommended to start taking clopidogrel (Grade 2A) after the coronary anatomy is confirmed.
For patients who are taking clopidogrel and preparing for CABG surgery, it is recommended to stop clopidogrel for 5 days before operation (grade 2A).
The purpose of the cure test is to study whether it is beneficial to block platelet aggregation caused by ADP pathway on the basis of aspirin treatment. 12562 patients with UA/NSTEMI were randomly divided into placebo group and clopidogrel group within 24 hours (loading dose 300mg, then 75mg for a day), and then followed up for 3 ~ 12 months. All the patients took aspirin. The incidence of composite end point events (cardiovascular death, myocardial infarction or stroke) was 1 1.5% in placebo group and 9.39% in clopidogrel group (RR 0.80, P
3. Pan Shengding
Dipyridamole, dipyridamole, is a phosphodiesterase inhibitor, which inhibits platelet activation by inhibiting the production of cAMP. Compared with aspirin, dipyridamole does not increase the risk of gastrointestinal bleeding, even when combined with warfarin. However, there is no evidence that dipyridamole can replace or be used with aspirin and clopidogrel in the acute treatment of NSTE-ACS patients.
4. Platelet glycoprotein IIb/IIIa receptor antagonists play a very important role in the pathogenesis of atherosclerosis, thrombosis and acute coronary syndrome. Glycoprotein (GP) receptor on platelet membrane is closely related to platelet activity, and the binding of GPIIb/IIIa receptor with fibrinogen is the last pathway in the process of platelet aggregation caused by various platelet agonists. Platelet glycoprotein GPIIb/IIIa receptor antagonist inhibits platelet aggregation by binding with GPIIb/IIIa receptor, which is a new generation of platelet inhibitors. ACCP7 makes the following recommendations for glycoprotein IIb/IIIa inhibitors:
For patients with middle and high risk NSTE-ACS, it is suggested to use etibatide or tirofiban in combination with aspirin and unfractionated heparin (1A grade) at an early stage. For patients with middle and high risk NSTE-ACS taking clopidogrel, it is suggested to use etibatide or tirofiban at the early stage (grade 2A).
For patients with NSTE-ACS, abciximab is not recommended as the initial treatment. Unless the coronary artery anatomy is clear (1A grade), PCI will be performed within 24 hours.
Clinical trials show that the combination of GPIIb/IIIa receptor antagonist and aspirin can reduce the occurrence of ischemic complications, including death, acute myocardial infarction, the need for emergency coronary artery bypass grafting (CABG) or re-interventional therapy; Patients with unstable angina pectoris and AMI without ST-segment elevation can also benefit from the application of GPIIb/IIIa receptor antagonists. Clinical research includes PURSUIT, PRISMPLUS, PRISM and PARAGON. In the follow-up trial, the incidence of 30-day death and MI in patients with unstable angina pectoris in etibatide group (14.2%) was lower than that in placebo group (15.7%) (P=0.04). The incidence of death and MI in 96 hours, 7 days and June also decreased 1.2%- 1.5%. In PRISM-PLUS test, the mortality, MI and intractable angina of AMI patients with unstable angina pectoris and without ST-segment elevation at 7 and 30 days were lower than those of patients with aspirin and heparin alone, which were 65,438 02.9% and 65,438 07.9% respectively (P = 0.04). Within 30 days, it was 18.5% and 22.3% respectively (p = 0.03). In June, the absolute value still dropped by 3.0%-3.2%. PRISM trial compared the efficacy of tirofiban aspirin and heparin aspirin in patients with unstable angina pectoris. The incidence of joint end points (death, myocardial infarction and intractable ischemia) within 48 hours in the former was 3.8%, which was 32% lower than that in the latter (5.6%) (P = 0.01). GPIIb/IIIa receptor inhibitors, as efficient and specific antiplatelet drugs, are the most prominent progress in acute coronary syndrome at present, but large-scale prospective clinical research is still going on to further understand their dosage, efficacy and safety.
(2) Anticoagulant therapy of 2)NSTE-ACS
Commonly used anticoagulants in clinic include: ordinary heparin, low molecular weight heparin, selective indirect anti-Xa factor inhibitor (synthetic pentose), selective direct anti-Xa factor inhibitor (DX-9065a) and thrombin direct inhibitor.
1, ordinary heparin
Heparin combined with antithrombin III increases AT-III activity, thus inactivating coagulation factors such as IIa and Xa. ACCP7' s recommendations for unfractionated heparin are as follows:
For patients with NSTE-ACS, it is suggested that short-term heparin combined with antiplatelet therapy should replace simple antiplatelet therapy (1A grade). It is suggested that the dosage of heparin should be adjusted according to kg body weight, and aPTT should be maintained at 50 ~ 75 seconds (1C level).
A meta-analysis confirmed that antiplatelet combined with short-term unfractionated heparin can reduce the mortality and myocardial infarction rate of NSTE-ACS patients within 2 weeks. Heparin is an important basis for anticoagulant therapy of ACS.
2. Low molecular weight heparin
Low molecular weight heparin (LMWH) is the product of ordinary heparin after enzymolysis or chemical degradation, and its anticoagulant effect is almost the same as that of ordinary heparin. Because of its small molecular weight (average molecular weight is 4500 daltons), the ratio of anti-Xa to anti-IIa activity increases, and it also inhibits the combination of factor Xa with platelets, so its antithrombotic effect is more obvious. LMWH has low nonspecific binding force with plasma protein, high bioavailability and long half-life, and its anticoagulant effect has obvious dose-effect relationship. Subcutaneous injection absorbed well, almost 100%. The following are the recommendations of ACCP7 for low molecular weight heparin:
For patients with NSTE-ACS, it is suggested to replace ordinary heparin with low molecular weight heparin (1B grade).
It is suggested that routine monitoring of anticoagulant effect of low molecular weight heparin (1C grade) is unnecessary.
For patients who have received low molecular weight heparin anticoagulation NSTE-ACS, it is recommended to continue to use low molecular weight heparin anticoagulation (grade 2C) during PCI.
For NSTE-ACS patients treated with GP IIb/IIIa receptor antagonists, it is recommended to use low molecular weight heparin instead of ordinary heparin for anticoagulant therapy (grade 2B).
From the meta-analysis, it can be seen that the current standard antithrombotic drugs are unfractionated heparin (UFH) and aspirin. However, LMWH has more advantages than UFH in practice and clinic, and can be considered as an effective alternative to medical treatment and surgical intervention of ACS. It can obviously reduce the 30-day mortality of acute coronary syndrome and the occurrence of complex cardiac events.
3. Indirect anti-Xa factor inhibitor (synthetic pentose)
A large-scale randomized trial to evaluate the safety and efficacy of fondaparinux sodium in TE-ACS and NSTE-ACS is under way. In 2005, the results of Oasis-5 were published on ESC, which was the first large-scale clinical study of fondaparinux sodium in the treatment of ACS. Oasis-5 study is a multicenter, randomized, double-blind, placebo-controlled clinical trial, involving 20,000 ACS patients from 576 centers in 465,438+0 countries. Objective To evaluate the efficacy and safety of fondaparinux sodium in the treatment of acute coronary syndrome. The results showed that fondaparinux sodium was as effective as enoxaparin in preventing cardiovascular events, death and ischemic attacks within 9 days after ACS, and significantly reduced the complications of severe bleeding. Studies have shown that fondaparinux sodium can significantly reduce the mortality within 1 month after ACS, and it is also effective during the 6-month follow-up period. This discovery indicates that fondaparinux sodium may become a new choice of antithrombotic drugs for ACS patients.
4. Direct thrombin inhibitor
Hirudin and bivalirudin can selectively bind thrombin and inactivate it. Clinically, it is mostly used for anticoagulant therapy of heparin-induced thrombocytopenic purpura. Meta-analysis of comprehensive clinical trials shows that compared with unfractionated heparin, direct thrombin inhibitors can not significantly reduce the probability of death and myocardial infarction in ACS patients, and increase the risk of related bleeding. The following is ACCP7' s recommendation for direct thrombin inhibitors: DTIs is not recommended as the first choice for anticoagulant therapy in patients with NSTE-ACS( 1B grade).
In order to make the guideline more practical, ACC/AHA introduced UA/NSTEMI guideline in 2005, emphasizing the treatment in emergency room. According to the risk stratification of UA/NSTEMI, patients were divided into early conservative group and early intervention group, and their treatment strategies were different.
Early conservative strategy:
1, aspirin (class ia); When aspirin is banned, choose clopidogrel (class IA).
2. Clopidogrel should be taken at least 1 month (category IA) to 9 months (category IB); If early intervention is not feasible, clopidogrel should be used in emergency room as soon as possible.
3. Enoxaparin or unfractionated heparin (Class IA)
4. Etibatide or tirofiban: continuous ischemia (IIaA grade), increased TNI or TnT (IIaA grade) and other high-risk factors (IIAA grade).
5. Unplanned PCI should not be used early in abciximab (Class IIIA).
Early intervention strategies:
1, aspirin (class ia); When aspirin is banned, choose clopidogrel (class IA).
2. Low molecular weight heparin or ordinary heparin (class IA); Compared with unfractionated heparin, enoxaparin is the first choice for patients with UA/NSTEMI, unless they are prepared to undergo CABG surgery (IIaA grade) within 24 hours.
3. If early intervention is prepared, GP IIb/IIIa receptor antagonists (Class Ia) should be used as soon as possible.
4. If early intervention is planned, GP IIb/IIIa receptor antagonists should be used in combination with aspirin, heparin and clopidogrel (class IIaB).
5. If preparing for PCI, you should take clopidogrel for at least 1 month (category IA) to 9 months (category IB).
This change will make the guide more operational and practical. The American Journal of Cardiology recently published an article saying that Japanese scientists found that vascular endoscopy can effectively detect patients with unstable acute coronary syndrome and predict the higher risk of patients with multiple yellow plaques in blood vessels.