9 NOV 2026 — Starting heart patients on a statin plus ezetimibe from day one did not lead to fewer heart attacks, strokes or other cardiac events over three years than starting on a statin alone, provided doctors kept adjusting the drugs to hit a cholesterol goal. The result comes from Ez-PAVE, a trial of 3,048 adults at 17 hospitals in South Korea, and was presented on 7 November at the American Heart Association's Scientific Sessions in Chicago, according to the association's news release. A paper went up in Circulation the same day.
It is the second result from the same trial. The first, published online in March, found that the cholesterol goal itself did change outcomes, and the two make most sense read together.
One trial, two random assignments
Every patient had atherosclerotic cardiovascular disease and was randomised twice. The first draw set the LDL ("bad") cholesterol target below 55 mg/dL (the stricter goal) or below 70 mg/dL (the conventional one). The second draw set how treatment began, with a statin plus ezetimibe, a drug that cuts how much cholesterol the gut absorbs, or with a statin alone.
The 2-by-2 factorial design answers two questions in one group of patients and shows whether one answer depends on the other. Doses could move up or down at follow-up visits under a set protocol in both starting groups, depending on how far each patient sat from target. The trial registration lists rosuvastatin as the statin in the combination arm, and rosuvastatin or atorvastatin for statin-alone patients.
Both comparisons counted the same events over three years: cardiovascular death, non-fatal heart attack or stroke, any procedure to reopen an artery, and hospital admission for unstable angina.
The target mattered, the starting pill did not
The goal comparison came first. The abstract in the New England Journal of Medicine (online 28 March) reports events in 100 patients (an estimated 6.6%) in the under-55 group and 147 patients (9.7%) in the under-70 group, hazard ratio 0.67. By our arithmetic, that is 47 fewer events, a 3.1 percentage point gap, or roughly one event avoided for every 32 patients over three years. Median LDL was 56 mg/dL versus 66 mg/dL.
The starting-regimen comparison was the new one. In the Circulation abstract, 128 patients who began on the combination (8.5%) had an event, compared with 119 who began on a statin alone (7.9%). The hazard ratio was 1.07 (95% confidence interval 0.83 to 1.37), so the data fit anything from a modest benefit to a modest harm. The authors call it no difference.
Combination starters did reach lower cholesterol. Their median LDL was 53 mg/dL against 62 mg/dL under the stricter goal, and 63 against 70 under the conventional one. But the statin-alone group did not stay that way. Ezetimibe was added for 241 of those patients in the stricter-goal arm and 177 in the conventional arm. Taken together, by our count, that is 418 of the 1,523 people who started on a statin alone, or about 27%, who ended up on both drugs anyway.
The benefit of the stricter goal held whichever way treatment began, the paper says, with no significant interaction between the two assignments. Safety outcomes were similar between starting groups.
"We expected that starting with combination therapy would lead to fewer heart attacks, strokes and other heart problems, but this was not the case," Byeong-Keuk Kim, a Yonsei University cardiologist at Severance Hospital in Seoul, said in the release. He attributed the gap with an earlier large ezetimibe trial in the New England Journal of Medicine to design. That study, he said, was not primarily designed to adjust treatment towards an LDL goal, while Ez-PAVE did so in both arms.
Limits the authors set out
The trial was not sized to compare the two starting regimens, so small differences could have been missed, and three years may be too short for later differences to show. Because the trial was open-label, patients and doctors knew the assigned treatment. Everyone enrolled was treated in South Korea and 79.1% were men, which may limit how far the findings travel.
"Starting with a statin and adding ezetimibe as needed appears to be a reasonable strategy" for people with stable disease whose cholesterol is checked regularly, Kim said, while starting both together lowers LDL faster and may suit patients far above their goal. The study was funded by the Yuhan Corporation and the Cardiovascular Research Center in Seoul. An accompanying Circulation editorial by Michelle L. O'Donoghue carries the title "Clear Target, Multiple Paths: Rethinking Intensive LDL-C Lowering".
Nothing here is a reason to change a prescription without a doctor. Patients who have had a lipid panel can see how labs estimate LDL from total cholesterol; RECATOOLS covered the blood-pressure trials from the same meeting on 8 November.
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