Lower Cholesterol, Lower Risk: New Study Supports More Aggressive Targets

Lowering “bad” cholesterol more aggressively may significantly reduce the risk of serious heart problems in people already living with atherosclerotic cardiovascular disease (ASCVD), according to new research presented at this year’s American College of Cardiology Annual Scientific Session.

ASCVD occurs when plaque builds up in the arteries, increasing the risk of heart attack, stroke and other complications. A key driver of this plaque buildup is low-density lipoprotein cholesterol (LDL-C), often referred to as “bad cholesterol.” Lowering LDL-C has long been a cornerstone of treatment, but until now, there has been limited direct evidence on how low is best.

In this study, called Ez-PAVE, investigators followed more than 3,000 patients with ASCVD over three years at 17 sites in South Korea. Participants were assigned to one of two cholesterol targets: a traditional goal of less than 70 milligrams per deciliter (mg/dL) or a more aggressive goal of less than 55 mg/dL. To reach these targets, doctors used a combination of treatments, including statins and other cholesterol-lowering medications.

The results were striking. Patients aiming for the lower LDL-C target had a 33% lower risk of major cardiovascular events, such as heart attacks, strokes or the need for procedures to open blocked arteries. Overall, 6.6% of patients in the more aggressive group experienced one of these events, compared with 9.7% in the standard group.

“The consistency across the overall population and key subgroups suggests that the benefit of targeting LDL-C lower than 55 mg/dL is broadly applicable across the spectrum of patients with ASCVD and is not limited to specific patient subsets,” said lead investigator Byeong-Keuk Kim, M.D., director of the Cardiac Catheterization and Intervention Department and professor in the Division of Cardiology at Severance Hospital, Yonsei University College of Medicine in Seoul, South Korea.

Importantly, this added benefit did not come with increased safety concerns. Rates of common side effects, such as muscle symptoms, new-onset diabetes or worsening blood sugar, were similar between the two groups. In fact, there were even fewer signs of kidney function decline in the more intensive treatment group, though more research is needed to confirm this finding.

Another important takeaway from this study is how treatment plans are often built step by step. Many patients with ASCVD start with statins, which are the most commonly prescribed cholesterol-lowering medications. If LDL-C levels remain above target, health care providers may add other therapies. This “layered” approach allows care teams to gradually intensify treatment while monitoring how patients respond and tolerating any side effects. The study reflects real-world care, where treatment is adjusted over time rather than relying on a single medication.

These results support newer guidelines recommending lower LDL-C targets (below 55 mg/dL) for high-risk patients. However, it’s important to note that not all patients in the study were able to reach this goal, and access to newer medications was limited. This means even greater benefits might be possible with broader treatment options.

It’s also worth noting that lifestyle habits continue to play a key role alongside medication. While cholesterol-lowering drugs are highly effective, factors such as diet, physical activity, smoking status and weight management all contribute to overall cardiovascular risk. For example, reducing saturated fats, increasing fiber intake, staying active, and managing conditions like diabetes or high blood pressure can all support better heart health. Medications and lifestyle changes work best together, helping patients not only reach their LDL-C targets but also maintain long-term cardiovascular health.