On April 3, the results of the PACMAN AMI study were announced during the 2022 ACC Annual Meeting.
A total of 300 patients with acute myocardial infarction who received PCI and had low-density lipoprotein cholesterol (LDL-C) ≥1.8 mmol/L were enrolled in this study. Received rosuvastatin 20 mg/day. They were randomly divided into two groups, the experimental group was given a combination of alicilumab (150 mg, injected once every two weeks), and the control group was given a placebo injection every two weeks. They were followed up for 52 weeks. The primary endpoint was the percent change in atheroma volume determined by IVUS. At baseline, the average LDL-C level in the two groups was 3.95 mmol/L, and at the end of follow-up, the LDL-C level in the aliximab treatment group decreased to 0.61 mmol/L /strong> (85% reduction vs. 51% reduction in the control group). The results showed that the reduction in coronary plaque volume was greater in patients treated with alecizumab (-2.1% vs. 0.9%, p=0.001), indicating that intensive reduction of cholesterol levels can be more effective. To effectively achieve atherosclerotic plaque reversal.
Looking at the results of dozens of large randomized clinical trials of statin and non-statin drugs, it can be considered that for the diagnosis of atherosclerosis Patients with cardiovascular disease (coronary heart disease, ischemic stroke, peripheral arterial disease, etc.) should more aggressively intensify cholesterol-lowering therapy, which is the core strategy for secondary prevention of ASCVD.
In the IMPROVE-IT study, combined use of ezetimibe on the basis of statin therapy to reduce LDL-C to 1.4 mmol/L can still lead to the risk of cardiovascular events In the subsequently concluded FOURIER study, the combined use of evolumab on the basis of statin therapy could further reduce the risk of major adverse cardiovascular events when LDL-C was reduced to 0.78 mmol/L. These studies raise an important question: How low should cholesterol be? Will there be a lower limit to lowering cholesterol? Will there be any adverse health effects from going too low? Studies have shown that the LDL-C level of healthy newborns in my country is 0.8-0.9 mmol/L. Since neonates are the most active period for the development and hormone synthesis of various tissues and organs in the body, it is inferred that adults with LDL-C below this level should be safe and will not have adverse effects on the body.
In the CTTC meta-analysis published in 2018, in the subgroup of patients with an average LDL-C of 1.7 mmol/L, for every 1 mmol/L decrease in LDL-C, the major adverse vascular 22% relative risk reduction for events; baseline LDL-C was 1.6-1.8 mmol/L in 3 large randomized clinical studies (50,627 patients) with a combination of statins and non-statins, on top of statin therapy The addition of non-statin drugs further reduced LDL-C by 0.3-1.2 mmol/L. The analysis results showed that for every 1 mmol/L lowering of LDL-C in this part of patients, the main adverse vascular 21% relative risk reduction of events (Original reference: JAMA Cardiol. Published online August1, 2018. doi:10.1001/jamacardio.2018.2258). The study concluded that adding non-statin drugs to statin therapy to reduce LDL-C from 1.6 mmol/L (median) to 0.5 mmol/L (median) can further reduce the major adverse effects risk of adverse cardiovascular events, with the same dose-response relationship as statin therapy, and no increased risk of serious adverse events such as myalgia, myositis, elevated transaminases, new-onset diabetes, hemorrhagic stroke, and cancer. This analysis further confirms the validity of the cholesterol theory and demonstrates thatlowering LDL-C to 0.5 mmol/L is both effective and safe.
Based on the existing research findings, we have reason to believe that for patients with confirmed atherosclerotic cardiovascular disease, reducing LDL-C to <1.4 mmol/L not only It is reasonable and safe, but also effective and necessary. For patients with a higher risk of recurrent coronary events, lowering LDL-C to <1.0 mmol/L can further stabilize atherosclerotic plaques and reduce the risk of coronary events.
The conclusion of the PACMAN AMI study further confirms the feasibility of reversing atherosclerotic plaque and the correctness of the cholesterol theory.
Follow “Guo Yifang’s Frontiers” and receive the latest academic progress in this field as soon as possible.
(Guo Yifang, Hebei Provincial People’s Hospital)