What is the optimal LDL cholesterol target to aim for during treatment for established atherosclerotic disease?

Background:
In patients with atherosclerosis-related cardiovascular disease (CVD), strategies to lower LDL cholesterol (the “bad” cholesterol) have become increasingly stringent in line with both European and American guidelines.
Therapeutic targets have recently been lowered, shifting from a threshold below 0.70 g/L to a stricter target of <0.55 g/L for patients considered to be at high or very high risk of cardiovascular events, respectively.
This shift is based on a series of studies demonstrating that a greater reduction in LDL cholesterol, achieved through high-intensity statins or in combination with other therapies, is associated with a significant reduction in cardiovascular (CV) risk. These results are the basis for the so-called “lower is better” theory: “The lower, the better.”
However, these studies primarily compared different treatment strategies without directly evaluating the impact of specific LDL cholesterol targets, thereby fueling a controversy that can be summarized as follows: Is it worthwhile to achieve lower numbers with potentially more side effects and perhaps little or no cardiovascular benefit?
Patients for whom statin therapy is essential are reluctant to take this treatment for fear of side effects, even though they have been told that the benefits are limited.
To achieve these new goals, we face the classic criticism that higher doses and/or more medications will be required.
However, in the absence of formal proof, the question remains open. For example, vascular neurologists treat stroke with an LDL cholesterol target of <0.7 g/L because a French study formally proved this: SPARCL in 2006 by Prof. Pierre AMARENCO, whereas after a myocardial infarction, the current consensus is a target of <0.55 g/L. A new study is currently underway by the same team to determine whether the target of 0.55 g/L might be preferable. It should be noted that in the first study, patients received 80 mg of atorvastatin, whereas in the second, they received 80 mg of atorvastatin plus 10 mg of ezetimibe—thus a more intensive treatment regimen.
The EZ-PAVE Study:
The objective of this study is to evaluate whether an intensive LDL-cholesterol reduction strategy, targeting a level < 0.55 g/L, is superior to a conventional strategy targeting LDL-cholesterol < 0.70 g/L for preventing CV events in patients with established atherosclerosis.
Method: This is a randomized study conducted at 17 centers in South Korea between January 2021 and July 2022. It included patients aged 19 to 80 years with a documented CV event: a history of myocardial infarction, stable angina, arterial revascularization, stroke, or transient ischemic attack, or peripheral artery disease. The 3,048 patients were divided between an “intensive” strategy targeting an LDL cholesterol level < 0.55 g/L and a more conventional strategy with a target of < 0.70 g/L. In each group, patients received either a statin alone (rosuvastatin or atorvastatin) or a combination of a statin and ezetimibe to achieve the lipid target.
The resultscover 1,526 patients in the intensive strategy group and 1,522 patients in the conventional group, with a 3-year follow-up in this high-CV-risk population. The LDL cholesterol level achieved was 0.56 g/L in the intensive group versus 0.66 g/L in the conventional group, reflecting a moderate but significant difference in treatment intensity. The composite endpoint combining CV death, non-fatal myocardial infarction, non-fatal stroke, revascularization, or hospitalization for unstable angina occurred in 6.6% of patients in the intensive group versus 9.7% in the conventional group, representing a 33% reduction in risk. This benefit is primarily due to a reduction in non-fatal myocardial infarctions and revascularizations. Consistent with this, the composite endpoint of CV death, myocardial infarction, and stroke was also reduced: 2.3% vs. 3.6%, confirming the consistency of the results regarding major ischemic events. In terms of tolerability, it was comparable between the two groups, with no increase in muscle-related adverse effects, new cases of diabetes, or glycemic imbalance.
Key findings of the study:
- The EZ-PAVE study is one of the first to directly compare two LDL cholesterol targets (<0.55 g/L vs. <0.7 g/L) in patients with established atherosclerotic disease.
- An LDL cholesterol target of < 0.55 g/L significantly reduces CV events.
- A difference of approximately 0.1 g/L in LDL cholesterol is sufficient to produce a significant clinical benefit. The reduction in events is primarily linked to a decrease in myocardial infarctions and revascularizations.
- The intensive strategy has a safety profile (side effects) comparable to that of the conventional strategy.
Conclusion:
In patients with established cardiovascular disease, does aiming for a lower LDL cholesterol level actually yield better results?
The EZ-PAVE study provides a clear answer: a target of 0.55 g/L slows the progression of atherosclerosis more effectively than a target of 0.7 g/L, thereby confirming, as indicated in the guidelines, the benefits of more intensive lipid-lowering therapy.
Reference
Based on the presentation: Yeong-Keuk Kim et al. “Intensive LDL cholesterol targeting in atherosclerotic cardiovascular disease: The EZ-PAVE randomized clinical trial”
American College of Cardiology 2026, New Orleans, March 28–30, 2026.