Dyslipidemia is closely related to atherosclerotic cardiovascular disease. Over the past decade or so since the introduction of statins, a number of large-scale international clinical trials on the use of statins for the prevention and treatment of coronary heart disease have achieved world-renowned success. The results of recent basic and clinical studies on betablockers also suggest a beneficial effect of betablockers in the prevention and treatment of cardiovascular events. The inspiration from evidence-based medicine will help us deepen our understanding of dyslipidemia and promote the progress of dyslipidemia treatment, which will help strengthen the primary and secondary prevention of coronary heart disease for the benefit of human beings.
I. Lipid-regulating treatment of acute coronary syndrome
Acute coronary syndrome (ACS), including acute myocardial infarction and unstable angina, is a serious cardiovascular event that causes death and disability, especially in the early stage when the incidence of various serious complications is high. Previous large-scale clinical trials on the prevention and treatment of coronary heart disease randomly selected patients 3-6 months after acute myocardial infarction and lacked reliable evidence to support lipid modifying therapy in the early stage of ACS. 2 clinical studies published in 2001 established the status of lipid modifying therapy in the early comprehensive treatment of ACS.
The Myocardial Ischemia Reduction with AggressiveCholesterol-lowering (MIRACL) was the first large international multicenter clinical trial of intensive lipid-lowering therapy in the early phase of ACS, with 3086 patients with ACS. received atorvastatin 80 mg/d or placebo for 16 weeks starting within 24 to 96 hours after onset of disease. The results showed a 16% reduction in the combined endpoint risk of death, nonfatal myocardial infarction, cardiac arrest, or hospitalization for worsening angina, and a 26% and 50% reduction in the relative risk of angina and stroke, respectively, in the atorvastatin group compared to the placebo group. The results of this trial filled a gap in the secondary prevention of coronary heart disease with lipid-modifying drugs applied early in the course of ACS.
In a prospective team study conducted in 58 hospitals in Sweden from 1995 to 1998, 19,599 patients survived their first acute myocardial infarction and were randomized to the statin group (5528) and the non-statin group (14,071). One-year mortality was 25% lower in the statin group compared with the non-statin group, with a beneficial effect shown within 3 months of dosing and in all age, sex, different clinical baseline characteristics, and past history subgroups. This suggests that early initiation of statin therapy in patients with acute myocardial infarction can significantly alter the prognosis, emphasizing the importance of early drug administration.
Therefore, in patients hospitalized for ACS, lipid measurements should be performed immediately after admission or within 24 hours and used as a reference value for treatment. Early initiation of lipid-modifying therapy in ACS not only reduces acute mortality and improves myocardial ischemia, but also improves patient compliance with lipid-modifying therapy.
Ongoing large clinical trials of early statin use in ACS, such as the ongoing PACT study in Australia, enroll 10,000 patients with acute myocardial infarction or unstable angina who are randomized to receive pravastatin within 24 hours of symptom onset and are being followed for adverse events, among other study endpoints. Another international study (the A-to-Z trial) started long-term treatment with simvastatin early in enrolled AC patients to observe the effect on the primary endpoints of cardiovascular death, recurrent infarction, recurrent ACS, and stroke. These large studies will provide further evidence to support the early use of statins in patients with ACS.
II. Coronary revascularization and lipid-modifying therapy
Revascularization, including percutaneouscoronary intervention (PCI) and coronary artery bypassgraft (CABG), is an important treatment for severe stenosis and occlusion of the coronary arteries, but the cardiovascular event rate after revascularization incidence is still high. Numerous completed randomized clinical trials of coronary prevention have consistently shown that statins significantly reduce the need for PCI and CABG due to worsening myocardial ischemia, as well as adverse cardiovascular events after CABG and PCI, in addition to significantly reducing overall mortality, cardiovascular mortality, lethal and fatal infarction rates.
The Lescol Intervention PreventionStudy (LIPS) used fluvastatin 80 mg/d for an average of 2.7 days after the first PCI in patients with coronary artery disease and followed up for 3 to 4 years to observe the effect of fluvastatin on the occurrence of major adverse cardiac events after PCI. The results found that compared with the placebo group, fluvastatin reduced the incidence of major adverse cardiac events by 22%, more significantly in patients with diabetes or multivessel disease, and independently of baseline TC levels.
One study prospectively looked at the effect of statins on early and long-term prognosis after PCI. A total of 5052 patients underwent PCI, of whom 1337 (26.5%) were taking statins before PCI. The results showed a 47% reduction in 30-day mortality and a 33% reduction at 6 months in those who had taken statins before PCI, suggesting that those who took statins before PCI had a reduced risk of early and long-term death.
The Post-Coronary Artery Bypass Graft Trial (Post-CABG) is a large trial comparing the effect of two lipid-lowering regimens on the progression of atherosclerosis in patients with saphenous vein bridges after coronary artery bypass grafting. In the aggressive lipid-lowering treatment group (LDL-C levels reduced to 93-97 mg/dl) compared with the moderate lipid-lowering treatment group (LDL-C 132-136 mg/dL), progression or complete occlusion of grafted saphenous vein and natural left main lesions was delayed, revascularization rates were reduced by 30%, and composite endpoint events (death, CABG, or PCI) were reduced by 24%.
Whether pharmacologic or revascularization therapy is more effective in patients with stable coronary artery disease has been debated. The aim of the Atorvastatin versus Revascularizationtreatment (AVERT) study was to compare the efficacy of aggressive lipid-lowering therapy with PTCA for stable coronary artery disease. 314 patients with stable angina and a clear indication for PTCA were randomized to atorvastatin The patients with stable angina and clear indication for PTCA were randomized into the atorvastatin treatment group (80 mg/d) and the PTCA+conventional treatment group with a follow-up of 18 months. The atorvastatin-treated group had 36% fewer ischemic events than the PTCA group and a significantly longer time to first ischemic event than the PTCA group. The findings show for the first time that intensive lipid lowering may provide better control of myocardial ischemia than PTCA in at least some patients with stable coronary artery disease.
Therefore, active lipid regulation in patients with stable coronary artery disease may reduce the need for revascularization, and in patients who have already received revascularization therapy, emphasis needs to be placed on combined intensive lipid lowering after revascularization to improve overall cardiovascular prognosis, and the combined application of the two may be superior to their single application.
Third, focus on the role of elevated HDL
Epidemiological studies have well established that low HDL-C is an important risk factor for coronary artery disease, and there is a continuous inverse relationship between HDL-C levels and the risk of coronary heart disease, independent of LDL-C and VLDL-C levels, as well as non-lipid factors of coronary heart disease. Thus, the role of HDL-C in the development of coronary heart disease has been reproduced.
Most patients with coronary artery disease do not have significantly elevated blood TC or LDL-C levels, and low levels of HDL-C are often the primary lipid abnormality, thus confusing the development of primary targets for lipid-modifying therapy. a VeteransAffairs HDL-C intervention trial (VeteransAffairs High- Density Lipoprotein Cholesterol InterventionTrial (VA-HIT), in which patients with coronary artery disease who had low HDL-C levels and normal LDL-C were treated with gemfibezil. after 1 year, the treatment group showed a 2.8% reduction in TC levels, no change in LDL-C, a 24.5% reduction in TG, and a 7.5% increase in HDL-C. 7.5%. The combined endpoint of coronary heart disease death and non-fatal acute myocardial infarction was reduced by 22% in the treatment group. The trial demonstrated that increasing HDL-C in patients with coronary artery disease had a significant clinical benefit in the absence of LDL-C reduction.
Low HDL-C is often accompanied by hypertriglyceridemia and small dense LDL, called atherogenic lipoproteinprofile (ALP), which is often associated with metabolic syndrome including abnormal glucose metabolism, postprandial lipemia, hypertension, central obesity, inflammatory response and thrombotic tendency. Because of the concentration of risk factors, ALP is a marker of accelerated progression of coronary lesions and is often seen in high-risk groups. therefore, in the secondary prevention of coronary heart disease, a comprehensive improvement of ALP should be achieved while focusing on LDL-C reduction.
The clinical trials have shown that these drugs can delay the progression of coronary artery lesions and reduce the risk of coronary heart disease events. Clinical studies related to the reduction of coronary heart disease mortality and total mortality by fibrates are underway and will provide evidence-based evidence to establish the role of elevated HDL-C levels in the prevention and treatment of coronary heart disease.
IV. Target values for lipid-regulating therapy for dyslipidemia
Since 1988, the U.S. National Cholesterol Education Program Adult Treatment Group has developed guidelines for the treatment of dyslipidemia three times, especially since the 1990s when the results of five landmark large-scale international clinical trials were available, which laid the foundation for the development and improvement of guidelines for the treatment of dyslipidemia. 1997 saw the development of recommendations for the prevention and treatment of dyslipidemia in China. Both international and domestic guidelines or recommendations emphasize stratified treatment based on the presence or absence of coronary heart disease and the number of risk factors for coronary heart disease.
1.National Cholesterol Education Program (NCEP): The target value (ATP II) set by the National Cholesterol Education Program Adult Treatment Panel (ATP) for the second time in 1993 recommended that the target value of lipid regulating treatment for those without coronary heart disease but with less than 2 risk factors for coronary heart disease is LDL-C<160mg/dL, and for non-coronary heart disease patients with 2 or more risk factors LDL -C<130mg/dL; the drug lipid regimen for patients with coronary artery disease should make TC<180mg/dL and LDL-C<100mg/dL, this standard has been adopted by many countries. 40 mg/dL.
In ATP III, in addition to specifying again the LDL-C target values for lipid-regulating therapy in patients with coronary heart disease, intensive lipid-lowering therapy is also proposed for critical conditions such as coronary heart disease, including: (i) atherosclerosis by other clinical manifestations, including peripheral artery disease, abdominal aortic aneurysm and symptomatic carotid artery disease; (ii) diabetes mellitus; and (iii) the presence of multiple risk factors and an expected 10-year risk of coronary heart disease > 20%.
2. Recommendations for the prevention and treatment of dyslipidemia in China: Cardiovascular experts in China have developed guidelines for the prevention and treatment of dyslipidemia in China based on the ATP II in the United States and programs in other Asian countries and regions. Patients with coronary artery disease receiving lipid-regulating therapy should have the same target values of blood TC and LDL-C as ATP III.
3. The lipid intervention recommendation in the guidelines for the prevention and treatment of coronary heart disease developed by the European Society of Cardiology: for patients who already have coronary heart disease or other atherosclerotic diseases, blood TC should be reduced to less than 190 mg/dL and LDL-C to less than 115 mg/dL. However, this intervention recommendation does not set out target values for treatment regarding HDL-C and TG.
The ATP III published in 2001 and the 1997 recommendations for the prevention and treatment of dyslipidemia in China set the adjustment of TG level <150mg/dL as the ideal target value. Theoretically higher HDL-C target values are better, but there is also insufficient evidence, and ATP III recommends at least >40 mg/dL.
Although most guidelines use LDL-C <100mg/dL as a target value in patients with coronary artery disease, there are still international studies exploring the optimal level for adjusting LDL-C. The Post-CABG and AVERT studies concluded that LDL-C below 100mg/dL, such as up to 77mg/dL, is associated with a greater reduction in coronary events. Two large ongoing international trials, such as the Treatment to New Target Levels (TNT) trial and the PROVE
IT trial looking at the effect of statin therapy to reduce LDL-C levels below 100 mg/dL on major cardiovascular events, the results of which will help to suggest the optimal level for adjusting LDL-C therapy in patients with coronary artery disease.