If you already have heart disease, should your cholesterol treatment start with a statin alone, or with a statin plus a second pill called ezetimibe from day one? On November 7, 2026, at the American Heart Association Scientific Sessions in Chicago, South Korean researchers presented a new answer from the Ez-PAVE trial, published the same day in Circulation. The short version: starting with both drugs lowered LDL cholesterol more, but it did not cut heart attacks, strokes or other major events any further over three years.
Here is what that means, what it does not mean, and which blood tests help you and your clinician see where you stand.
What the Ez-PAVE trial tested
Ez-PAVE enrolled 3,048 adults with atherosclerotic cardiovascular disease, meaning plaque build-up in the arteries that had already caused a problem such as a heart attack or a blocked artery. It ran at 17 hospitals in South Korea. The average age was 64, and about one in five participants was a woman. Everyone was randomized twice. The first randomization, reported in March 2026 in the New England Journal of Medicine, set the LDL goal: below 55 mg/dL (1.4 mmol/L) or below 70 mg/dL (1.8 mmol/L). The second, new this week, decided how treatment began: a statin plus ezetimibe together (1,525 people) or a statin alone (1,523 people). Doses were then adjusted by protocol until each person reached their goal.
What the new results show
According to the Circulation report, the combination did what it was designed to do on the lab report. Median LDL during follow-up was 53 mg/dL with the combination versus 62 mg/dL with a statin alone in the group aiming for below 55, and 63 versus 70 mg/dL in the group aiming for below 70.
The clinical picture, however, was a tie. Over three years, the main outcome (cardiovascular death, nonfatal heart attack, nonfatal stroke, any procedure to reopen an artery, or a hospital stay for unstable angina) occurred in 8.5% of people who started with the combination and 7.9% of those who started with a statin alone. That difference is not statistically meaningful (hazard ratio 1.07, 95% confidence interval 0.83 to 1.37). Safety results were similar.
One detail explains much of the result: in the statin-only groups, ezetimibe was added later for 34.3% of people aiming for below 55 and 24.8% of those aiming for below 70, because the statin was not enough to reach the goal. In other words, many people in the "statin first" arm ended up on both drugs anyway.
How it fits with the March result
The earlier Ez-PAVE report found that the lower goal itself mattered. People treated to below 55 mg/dL had fewer events at three years than those treated to below 70 (6.6% versus 9.7%, hazard ratio 0.67). The new analysis suggests that the route to the goal matters less than reaching it: a statin first with ezetimibe added when needed worked about as well as starting with both. Limits to keep in mind: the trial was open-label, it was run in South Korea, and not everyone reached their goal. It is also one trial, so guidelines will not change on it alone.
Which tests can monitor or screen for this?
- A lipid panel with LDL cholesterol, the number the trial used to steer treatment. Our guide to calculated versus measured LDL explains why values can differ between labs.
- Non-HDL cholesterol, which is easy to calculate from the same panel and captures all the cholesterol carried by harmful particles.
- An advanced lipid panel with ApoB, and lipoprotein(a), when your clinician wants a closer look at particle burden (see also LDL particle number).
- CK and liver enzymes if you have muscle pain on a statin (read our article).
Recent advances
A smaller 2026 trial in adults aged 70 and over with heart disease, published in the Journal of the American Heart Association, compared a moderate-dose statin plus ezetimibe with a high-intensity statin alone. LDL targets were reached equally often, but muscle symptoms were less frequent with the combination (0.7% versus 5.4%). For readers who struggle with statin side effects, this is a reason to ask about options, not to change anything alone. Overall, the research is moving from "which drug first?" to "did you reach your number, and can you keep taking the treatment?"
When to see a doctor
Talk to your clinician if you have heart disease and have never had your LDL checked against a goal, if your LDL is above the goal you were given, or if you have muscle pain, weakness or dark urine on a statin. Never stop or switch a cholesterol medicine on your own. Call 911 right away for chest pain, sudden shortness of breath, or signs of a stroke such as a drooping face, arm weakness or trouble speaking.
Glossary
- Ezetimibe: a pill that lowers LDL cholesterol by reducing how much cholesterol the gut absorbs.
- Statin: a medicine that lowers LDL cholesterol by slowing its production in the liver.
- Secondary prevention: treatment to prevent another event in someone who already has cardiovascular disease.
- Hazard ratio: a measure comparing how often an event happens in two groups; 1.0 means no difference.
- Open-label trial: a trial in which participants and doctors know which treatment is given.
Frequently asked questions
Is ezetimibe better than a statin?
No. They work differently and are often used together. Statins have the longest track record for preventing heart attacks and strokes. Ezetimibe is usually added when a statin alone does not bring LDL low enough.
Does the Ez-PAVE trial mean I should start both drugs at once?
Not necessarily. Starting with both lowered LDL more but did not reduce events more than a statin first with ezetimibe added when needed. The right plan depends on your starting LDL and your risk, so ask your clinician.
What is a good LDL level if I have heart disease?
Targets are set by your clinician. The March Ez-PAVE trial found fewer events when LDL was kept below 55 mg/dL than below 70 mg/dL, but guidelines have not changed on one trial alone.
How often should I check my cholesterol?
Usually a few weeks after starting or changing treatment, then about once a year if stable. Your clinician sets the schedule.
Are there side effects with ezetimibe?
It is generally well tolerated. Safety outcomes were similar between the two strategies in Ez-PAVE. Report any new symptoms to your clinician.
Sources
- Lee SH, Byun YS, Kim JW, et al. Statin-ezetimibe combination therapy versus statin monotherapy in atherosclerotic cardiovascular disease: a prespecified secondary analysis of the randomized Ez-PAVE trial. Circulation. 2026. DOI: 10.1161/CIRCULATIONAHA.126.083811
- Lee YJ, Lee SJ, Kim JW, et al. Intensive LDL cholesterol targeting in atherosclerotic cardiovascular disease. N Engl J Med. 2026;394:1365-1375. DOI: 10.1056/NEJMoa2600283
- Cha JJ, Shin Y, Joo HJ, et al. Metabolic and safety outcomes of statin-ezetimibe versus high-intensity statin in older patients. J Am Heart Assoc. 2026. DOI: 10.1161/JAHA.125.048711
- American College of Cardiology. STREAM, eZ-PAVE add new insights into statin therapy treatment. November 2026
- American College of Cardiology. More aggressive cholesterol lowering improves heart outcomes. March 2026
- Medical Xpress. Starting with a statin or statin plus ezetimibe to lower LDL led to similar heart outcomes. November 9, 2026
- ClinicalTrials.gov. Ez-PAVE, NCT04626973
Further reading
- Statins after 70: the STAREE trial
- Statin muscle pain and the CK blood test
- Calculated versus measured LDL cholesterol
- Normal LDL levels: a guide to healthy ranges
- The lipid panel
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