Starting with a statin or statin plus ezetimibe to lower LDL led to similar heart outcomes

Research Highlights:

• In a study of more than 3,000 adults in South Korea with heart or blood vessel disease, starting cholesterol treatment with a statin alone or with a statin plus ezetimibe (a non-statin medication that reduces the absorption of cholesterol from foods and the production of cholesterol by the body) led to similar rates of heart and stroke events. Researchers measured heart-related death, heart attack, stroke, procedures to reopen blocked arteries, and hospitalization for worsening chest pain over three years, and medications were adjusted during follow-up to reach an assigned low-density lipoprotein (LDL) or "bad" cholesterol goal.
• The researchers said that, regardless of the starting treatment, regularly checking LDL cholesterol and adjusting medications to reach the goal is important. They noted that for adults with stable heart or blood vessel disease, starting with a statin and adding ezetimibe if needed appears reasonable, and that starting both medications together may lower LDL cholesterol more quickly when levels are far above the goal.
• Note: This trial is simultaneously published today as a full manuscript in the peer-reviewed scientific journal Circulation.

Embargoed until 3:45 p.m. CT/4:45 p.m. ET, Saturday, Nov. 07, 2026

CHICAGO, Nov. 7, 2026 - Adults with heart or blood vessel disease who started treatment with a statin alone had rates of heart attack, stroke and other heart problems over three years similar to those who started with a statin plus ezetimibe (a non-statin medication to help limit cholesterol absorption in the intestine), when medications were adjusted to reach an assigned goal for low-density lipoprotein (LDL) or "bad" cholesterol, according to new, independent, preliminary late-breaking science presented today at the American Heart Association's Scientific Sessions 2026. The meeting on Nov. 6-9 in Chicago is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.

According to the American Heart Association's 2026 Heart Disease and Stroke Statistics, about 1 in 4 U.S. adults (25.5%) had high LDL cholesterol (130 mg/dL or higher), based on 2017 to 2020 data.

"Lowering high LDL is among the most effective ways to reduce the risk of heart attack and stroke," said study author Byeong-Keuk Kim, M.D., Ph.D., a professor of cardiology at Yonsei University College of Medicine's Severance Hospital in Seoul, South Korea. "Doctors can lower LDL cholesterol with a statin alone or in combination with ezetimibe, which lowers cholesterol more. However, it remains unclear if starting both together reduces heart attacks, strokes and other heart issues compared to starting with a statin alone and adding additional medications like ezetimibe later. This is a crucial question for doctors."

Statins work by reducing cholesterol production in the liver and are often the first medication prescribed to lower LDL. Ezetimibe is a non-statin medication that reduces the amount of cholesterol absorbed in the intestines. It is often the first non-statin medication added when a statin alone does not lower LDL cholesterol levels enough.

Researchers in the Ez-PAVE study enrolled more than 3,000 adults with heart or blood vessel disease across 17 study sites in South Korea. At enrollment, participants were randomly assigned to one of two LDL cholesterol goals: a lower LDL goal (less than 55 mg/dL) or a conventional LDL goal (less than 70 mg/dL). Participants were also randomly assigned to start treatment with either a statin plus ezetimibe or a statin alone, with about half of participants in each group.

In both groups, medication doses were adjusted during follow-up to help reach the target LDL goals. During follow-up visits, lipid-lowering therapy could be modified in either group according to a predefined protocol, based on each participant's LDL cholesterol level relative to the assigned target. Medication changes were permitted in both directions, from monotherapy to combination therapy, and from combination therapy to monotherapy, as long as they were consistent with the protocol. Then, all participants' results were analyzed according to the group to which they were originally assigned.

At three years, after annual follow-up, the analysis reviewed rates of heart-related death, heart attack, stroke, procedures to reopen blocked arteries and hospitalization for worsening chest pain for all participants.

What are the study's main findings?

• The participants receiving combination treatment with a statin plus ezetimibe achieved lower LDL cholesterol levels than those treated with statins alone.
• For the lower cholesterol goal group (<55 mg/dL), average LDL was 53 mg/dL with combination therapy vs. 62 mg/dL for those in the statin-only group.
• For the conventional LDL goal group (<70 mg/dL), average LDL was 63 mg/dL with combination therapy vs. 70 mg/dL for the statin-only group.
• Many participants who started treatment with only a statin eventually had ezetimibe added during follow-up, as directed by the study protocol, to reach their LDL goal: about 1 in 3 people (more than 34%) in the lower-goal LDL group, and about 1 in 4 people (nearly 25%) in the conventional LDL-goal group.
• During the three-year study, the rate of heart disease-related death, heart attack, stroke, procedures to reopen blocked arteries or hospitalization for worsening chest pain was 8.5% among people who started on combination therapy vs. 7.9% among those in the statin-only group. This small difference is not statistically meaningful.
• The benefit of the lower LDL goal, reported previously from this study, was consistent whether people started on combination therapy or a statin alone.
• Side effects and safety concerns were similar whether adults started on combination therapy or statin-only treatment.

"We expected that starting with combination therapy would lead to fewer heart attacks, strokes and other heart problems, but this was not the case," Kim said. "A previous large study published in the New England Journal of Medicine showed that adding ezetimibe to a statin reduced the rate of cardiovascular deaths, nonfatal heart attacks, unstable angina requiring rehospitalization, coronary revascularization or nonfatal stroke. However, that study was not primarily designed to adjust treatment to reach a target LDL cholesterol goal, and medication dose changes were limited. We believe the difference was that in our study, medication doses in both treatment groups were adjusted to reach the target LDL cholesterol goal."

"Starting with a statin and adding ezetimibe as needed appears to be a reasonable strategy for people with long-term, stable heart or blood vessel disease whose cholesterol levels are checked regularly and medication doses are adjusted to reach their goals," said Kim. "Starting with combination therapy can lower cholesterol more quickly and may be a practical option, particularly for people whose LDL cholesterol numbers are much higher than their goal LDL level."

Future research is needed to help identify which patients with high LDL cholesterol would likely benefit the most from starting with combination therapy.

Study details, background, design and limitations:

• A total of 3,048 adults with a diagnosis of atherosclerotic cardiovascular disease (average age of 64.4 years; 79.1% men and 20.9% women) were enrolled in the study. Of these, 1,525 were assigned to statin-ezetimibe combination therapy, and 1,523 were assigned to the statin-only treatment group.
• Participants were enrolled from January 2021 to July 2022 and received care at 17 hospitals in South Korea, with a median follow-up of three years.
• Participants' lipid levels, safety laboratory data and clinical events were collected at scheduled follow-up visits at one, 12, 24 and 36 months during the three-year study period.
• At these visits, participants' LDL cholesterol levels were measured, and lipid-lowering therapy was adjusted as needed to reach each participant's assigned LDL cholesterol target.
• Ez-PAVE was a multicenter, open-label, randomized trial with a 2-by-2 factorial design, meaning participants were randomly assigned twice: once to an LDL cholesterol goal and once to a starting treatment. This design lets researchers answer two questions in the same study and check whether the results of one assignment differ depending on the other. The study compared intensive vs. conventional LDL cholesterol goals, and combination therapy vs. statin-alone treatment. Medication doses were adjusted according to the protocol to achieve the assigned LDL cholesterol target.
• The study then calculated the three-year composite risk of cardiovascular death, nonfatal heart attack, nonfatal stroke, any revascularization or hospitalization for unstable angina.
• Limitations of this research include that the study population may not have been large enough to detect small differences in heart-related conditions in the two treatment groups. Another limitation is that the study's three years of follow-up may not have been long enough to detect differences between the two groups that could emerge over a longer period of time. In addition, the number of participants in this part of the study was not specifically calculated to compare the two starting treatments. The study was also open-label, meaning participants and their doctors knew which treatment was assigned, and all participants were in South Korea and about 4 in 5 were men, so the results may not apply to other populations.

Co-authors and disclosures are listed in the abstract. The Yuhan Corporation and Cardiovascular Research Center (Seoul, South Korea) funded the study.

Statements and conclusions of studies that are presented at the American Heart Association's scientific meetings are solely those of the study authors and do not necessarily reflect the Association's policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association's scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

The Association receives more than 85% of its revenue from sources other than corporations. These sources include contributions from individuals, foundations and estates, as well as investment earnings and revenue from the sale of our educational materials. Corporations (including pharmaceutical, device manufacturers and other companies) also make donations to the Association. The Association has strict policies to prevent any donations from influencing its science content and policy positions. Overall financial information is available here.

Additional Resources:

• Multimedia is available on the right column of the release link
• View the abstract in the American Heart Association Scientific Sessions 2026 Online Program Planner
• American Heart Association news release: ACC/American Heart Association Issue Updated Guideline for Managing Lipids, Cholesterol (March, 2026)
• American Heart Association health information: Cholesterol Tools and Resources
• American Heart Association health information: Life's Essential 8™ Your checklist for lifelong good health
• About Scientific Sessions 2026
• For more news at the American Heart Association's Scientific Sessions 2026, follow us on X @HeartNews, #ScientificSessions26

###

About the American Heart Association

The American Heart Association is a relentless force for a world of longer, healthier lives. Dedicated to ensuring equitable health in all communities, the organization has been a leading source of health information for more than one hundred years. Supported by more than 35 million volunteers globally, we fund groundbreaking research, advocate for the public's health, and provide critical resources to save and improve lives affected by cardiovascular disease and stroke. By driving breakthroughs and implementing proven solutions in science, policy, and care, we work tirelessly to advance health and transform lives every day. Connect with us on heart.org, Facebook, X or by calling 1-800-AHA-USA1.

For Media Inquiries and American Heart Association Expert Perspective:

American Heart Association Communications & Media Relations in Dallas: 214-706-1173; [email protected]

Michelle Kirkwood: [email protected]

For Public Inquiries: 1-800-AHA-USA1 (242-8721)

heart.org and stroke.org