Lowering LDL cholesterol beyond current goals cuts heart attack, stroke risk
- There are two main types of cholesterol in the body — HDL or “good” cholesterol, and LDL or “bad” cholesterol.
- Having higher levels of LDL cholesterol can potentially lead to atherosclerosis and atherosclerotic cardiovascular disease (ASCVD).
- High levels of LDL cholesterol are normally treated in a variety of ways, including medications.
- A recently presented study suggests that using cholesterol-lowering drugs more aggressively to lower LDL cholesterol levels may help decrease risk for major cardiovascular events.
There are two main types of cholesterol in the body — high-density lipoprotein (HDL), which is known as “good” cholesterol, and low-density lipoprotein (LDL), called the “bad” cholesterol.
HDL acts as a protector of your blood vessels as it carries excess cholesterol away to the liver where it’s either recycled or excreted from the body.
Conversely, while LDL cholesterol also helps carry cholesterol through the bloodstream, when there’s too much it deposits cholesterol onto the inner walls of the arteries, creating a build-up of plaque that narrows the arteries and makes it harder for the heart to pump blood through the body. This plaque build up is medically known as atherosclerosis.
People with atherosclerosis are at a higher risk of developing atherosclerotic cardiovascular disease (ASCVD), such as coronary artery disease, peripheral artery disease, carotid artery disease, and renal artery stenosis. People with ASCVD are also at an increased risk for heart attack and stroke.
High levels of LDL cholesterol are normally treated in a variety of ways, including lifestyle changes such as eating a heart-healthy diet and getting enough exercise, and taking certain medications.
Now, a new study presented at the American College of Cardiology’s Annual Scientific Session (ACC.26) reports that using cholesterol-lowering drugs more aggressively to lower LDL cholesterol levels further than traditional guidelines suggest may help decrease risk for major cardiovascular events.
The findings of the study were published in The New England Journal of Medicine.
For this study, called Ez-PAVE, researchers recruited more than 3,000 participants in South Korea with an average age of 64 and who all had ASCVD.
Half of the participant population was randomly assigned to reach an LDL cholesterol target of less than 55 mg/dL, while the other half targeted less than 70 mg/dL.
“For the longest time, when a patient has had a heart attack, stroke, or leg artery blockage, doctors have aimed to lower the bad cholesterol, otherwise known as LDL cholesterol, to a goal of 70 mg/dL,” Yu-Ming Ni, MD, a cardiologist and lipidologist at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA, who was not involved in this study, explained to Medical News Today.
“This is based on studies done 20 years ago that showed a significantly lower risk for a repeat event when LDL cholesterol was lowered to 70 mg/dL or less,” he said.
“However, the choice of 70 mg/dL as opposed to any other cholesterol level was largely coincidental, and it has long been believed that the lower the cholesterol level, the lower the risk for future heart disease. Later studies of additional cholesterol lowering medicines showed that certain very high risk people might benefit from an even lower LDL cholesterol level of 55 mg/dL. Unfortunately, as rates of diabetes, obesity, and chronic kidney disease remain high, many patients remain at very high risk for a future cardiac event, even on the standard medications.”
— Yu-Ming Ni, MD
“So the question on everyone’s mind that led to this study was: would it be best to aggressively treat LDL cholesterol to the very high risk goal of 55 mg/dL in every patient with existing heart disease?,” he questioned. “And philosophically, does it really matter if someone is high risk or very high risk for a future event?”
At the study’s conclusion, researchers found that after a three-year follow-up, their composite endpoint — consisting of cardiovascular death, nonfatal heart attack, nonfatal stroke, or any revascularization or hospitalization for unstable angina — occurred in 6.6% of participants with an LDL cholesterol target of less than 55 mg/dL, compared to 9.7% in those targeting less than 70 mg/dL.
According to the researchers, this finding was a 33% risk reduction in favor of a more aggressive LDL cholesterol target, and was primarily driven by a lowering in nonfatal heart attacks and revascularization.
“The Ez-PAVE trial adds practical and clinically meaningful evidence by demonstrating that, in patients with ASCVD, targeting an LDL-C level of less than 55 mg/dL leads to a significantly lower three-year risk of major cardiovascular events compared with the conventional target of 70 mg/dL, without compromising safety,” Byeong-Keuk Kim, MD, director of the Cardiac Catheterization and Intervention Department and professor in the Division of Cardiology at Severance Hospital at Yonsei University College of Medicine in South Korea, and lead author of this study, said in a press release.
The case for further lowering LDL cholesterol
Ni commented that this is a very important study that will definitely influence how cardiologists treat heart and vascular disease.
“The results showed that even though the two groups were only separated by 10 points of LDL cholesterol, that this was enough to prevent a heart event by 33%,” he explained.
“This finding suggests that treating LDL cholesterol more aggressively is worth the additional effort to prevent a future heart event. Given that heart disease remains the number one killer in this country, it is vitally important that we continue to find ways to effectively prevent heart disease. Please note that this study only applies to patients who have existing heart disease.”
— Yu-Ming Ni, MD
MNT also spoke with Robert Fishberg, MD, FACC, FNLA, a cardiologist at Atlantic Health, who said he was very excited about the results of this study.
Fishberg said that the 2026 ACC/AHA Dyslipidemia Guidelines were just released, which emphasize lowering LDL cholesterol to new limits with less than 70 mg/dl for all patients with ASCVD, with an optional goal of less than 55 mg/dl.
“However, the Ez-PACE trial, by prospectively comparing treatment goals of less than 70 mg/dl and less than 55 mg/dl for all patients with ASCVD, showed that a treatment goal of less than 55 mg/dl reduced cardiovascular events by one-third,” he detailed. “The Ez-PACE study, along the new Dyslipidemia Guidelines, have helped ‘to move the needle’ for the treatment of patients with ASCVD.”
“However, there is a real gap between what the guidelines have recommended and the reality of treatment in the US,” Fishberg continued. “According to the Gould Registry published in 2021 looking at 5,006 patients with ASCVD, only one in three patients had LDL cholesterol even less than 70mg/dl. This has been confirmed by multiple studies.