The incidence of coronary heart disease is increasing in our country. The treatment of patients suffering from myocardial infarction is a subject of common interest. One of the greatest advances in medical science in this century, large multicenter randomized clinical trials, have convincingly answered the effectiveness and safety of some treatment options.
In the last 20 years, hundreds of large clinical trials have been conducted internationally, changing the traditional view of the application of antiarrhythmic drugs after myocardial infarction. The previously controversial challenges in the treatment of myocardial infarction drugs have been solved, and world-recognized results have been achieved, improving clinical research and medical care. Based on these results, post-myocardial infarction drug therapy is categorized as ABC.
A is for aspirin (Aspirin).
Aspirin is a nonsteroidal anti-inflammatory drug originally used to reduce fever and relieve pain. In recent decades, the drug has been found to inhibit platelet cyclooxygenase, which hexylates its active site and prevents the conversion of arachidonic acid into thromboxane, thereby inhibiting platelet accumulation and thrombosis. The inhibition of platelets by aspirin is irreversible and lasts for the entire platelet survival period.
After platelets are inhibited, they cannot synthesize new cyclooxygenase, and only new platelets can synthesize cyclooxygenase and restore platelet function. Aspirin has a weak and short-lasting effect on the inhibition of cyclooxygenase in vascular endothelial cells, so it has less effect on the production of prostacyclin.
In the early eighties, the efficacy of aspirin in myocardial infarction was still controversial. Accordingly, clinicians at 417 medical centers in 17 countries, including the United Kingdom, the United States, France, Germany, and other countries, conducted the ISIS-2 trial, observing 16,000 myocardial infarctions treated with 160 mg of oral aspirin daily, which confirmed that aspirin significantly reduced the first-month mortality rate by 23% and reduced nonfatal reinfarction by 44%.
The International Antiplatelet Trials Collaborative Group reported that aspirin saves 20 – 30 lives per 1000 myocardial infarction cases. Large randomized clinical trials such as PARIS and AMIS have also confirmed the benefit of aspirin for secondary prevention in post-myocardial infarction patients.
The effective dose range of aspirin for platelet set inhibition is 100-1500 mg daily. The effects of small daily oral doses are similar to those of high-dose aspirin in myocardial infarction. However, the side effects of aspirin are dose dependent, with higher doses associated with more side effects. Therefore, small doses of aspirin are advocated for the treatment of myocardial infarction.
B is for b-blockers
Over the past 30 years, a large number of studies have been conducted to evaluate the benefit of b-blockers in the treatment of myocardial infarction, which can be broadly divided into 3 phases.
A small study completed by Snow in 1965 confirmed the encouraging results of b-blocker application after myocardial infarction. The application of b-blockers reduced the mortality rate at 1 month of myocardial infarction by more than 50%. This study was a landmark and represents the first phase.
The second phase was from the 1970s to the early 1980s. It was confirmed that b-blockers have the effect of limiting and reducing the scope of myocardial infarction.
Many well-designed clinical trials with large numbers of patients were conducted worldwide after the 1980s, which is the main hallmark of the third phase. These large clinical trials have produced convincing conclusions about the value of b-blockers in myocardial infarction and have explored the mechanisms that produce the beneficial effects.
The most convincing long-term data come from the Norwegian Thimerosal Trial (NMS) and the b-blocker Heart Attack Trial (BHAT) hosted by the American Heart, Lung, and Blood Institute. In the former, 1,884 patients were treated orally with timolocin 100 mg twice daily for up to 33 months, with a mean of 17 months. The BHAT trial demonstrated a 26% reduction in cardiovascular mortality, a 28% reduction in sudden cardiac death, and a 16% reduction in non-fatal recurrent heart attacks with oral administration of 60 or 80 mg three times daily for a mean of 25 months and a maximum of 39 months.
Both the GMT study and the MIAMI study confirmed the benefit of b-blockers in preventing ventricular fibrillation, the leading cause of sudden cardiac death. In the Stockholm Trial (SMT), which was observed for 3 years, those on b-blockers had fewer cerebrovascular events and more normal working days than controls.
There are many types of b-blockers, and trials suggest that all of them have a mortality-reducing effect. However, a comprehensive analysis of the trials showed that there were three main b-blockers with significant reductions in mortality and reinfarction, namely metoprolol, propranolol, and timolol. None of these 3 drugs had endogenous sympathomimetic activity.
The dose of b-blockers is clinically meaningful, but it is difficult to assess and determine the dose. Large variability exists between patients and in the same patient in different states. According to studies, blood concentrations of the same b-blocker applied at the same dose in different patients can vary up to 4-20 times. This is mainly due to individual differences in the tissue distribution and hepatic first-pass effect of the drug.
C is for angiotensin-converting enzyme inhibitors (ACEI)
Angiotensin-converting enzyme inhibitors have been widely used in the treatment of hypertension and heart failure with satisfactory results. In recent years, many scholars have studied the effect of ACEI on the heart, and a lot of research work has been done especially on the effect of myocardial infarction. Many experiments have confirmed that ACEI can prevent or reverse left ventricular hypertrophy, prevent or treat post-infarction left ventricular remodeling, prevent the occurrence of arrhythmias, improve left heart function or treat heart failure.
ACEI has anti-atherosclerotic effects: firstly, ACEI can reduce calcium inward flow. Intracellular calcium overload is a factor that promotes atherosclerosis. Secondly, it has an inhibitory effect on atherogenesis in hereditary hyperlipidemia. Third, ACEI has a mild blood cholesterol-lowering effect.
ACEI has anti-angiotensin II and adrenaline effect: ACEI can inhibit the production of angiotensin II and indirectly inhibit the production of adrenaline. Many experiments suggest that angiotensin II adrenaline can cause vasoconstriction, ventricular enlargement, coronary artery spasm, and arrhythmias due to myocardial ischemia. dr. Sharpe et al. reported that ACEI can improve left ventricular function and prevent left ventricular dilatation in patients with myocardial infarction. dr. Ertl et al. reported that ACEI can reduce the extent of infarction.
ACEI has anti-arrhythmic effect: Dr. Muller et al. found that ACEI can maintain the threshold of ventricular fibrillation after infarction and reduce the occurrence of ventricular fibrillation.
ACEI has improved insulin resistance: insulin resistance is related to hypertension and atherosclerosis. ACEI has improved insulin resistance, which helps to treat hypertension and protect target organs, and also helps to reduce atherosclerosis.
In addition, ACEI inhibits the degradation of bradykinin and prostacyclin, which increases the level of bradykinin and prostacyclin and can cause vasodilation. It also has a stimulating effect on vagal tone and has a slight slowing effect on heart rate.
In recent years, large randomized clinical trials, such as ISIS-4, GISSI-3, SAVE, AIRE, and the famous “Chinese Heart Study-1” (CCS-1) in China, showed that the rate of death in the treatment group was significantly lower than that in the control group; the incidence of heart failure was also significantly lower than that in the control group.
The current criteria for evaluating a treatment regimen are.
1) Impact on patient survival, prolonging patient life and reducing morbidity and mortality.
2) A real effect on the patient’s symptoms or signs.
3)It can improve the patient’s quality of life, increase mobility, improve mental status, etc.
4)The side effects are small and easily tolerated by patients.
5)Easy to use and high compliance.
6)Cheap and easy to be accepted by most patients. The A B C of post-infarction drug therapy basically meets the above six criteria, which has practical significance and value for guiding clinical treatment and improving medical care.