Discontinuing statin therapy in older adults with at least two chronic conditions but no known cardiovascular disease was noninferior to continuation with respect to major cardiovascular events or death from any cause at two years, according to findings from the STREAM trial presented at AHA 2026 and simultaneously published in NEJM.

The international trial involved more than 1,880 participants over the age of 70, nearly half of whom were women, who were taking statins for primary prevention and had at least two chronic conditions. Researchers randomly assigned individuals to either discontinue or continue statin therapy and assessed noninferiority on the basis of the between-group difference in restricted mean event-free survival time at two years.

At two years, results showed the between-group difference in the restricted mean event-free survival time was −2.0 weeks. Over a median follow-up of 103 weeks, 119 participants (12.7%) in the discontinuation group and 87 (9.2%) in the continuation group had a primary-outcome event. At least one serious adverse event occurred in 43% of the those assigned to discontinuation compared with 39.8% of those assigned to continuation.

In presenting the findings, Nicolas Rodondi, MD, reinforced the need for shared decision-making around statin therapy given the increase in numbers of cardiovascular events following discontinuation. He noted that the data and safety monitoring board had also recommended advising participants assigned to the discontinuation group to discuss restarting statin therapy with their care team.

In the eZ-PAVE trial out of South Korea, also presented at AHA 2026 and simultaneously published in Circulation, researchers compared outcomes in more than 3,000 patients with heart or blood vessel disease assigned to cholesterol lowering therapy with a statin alone or with a statin plus ezetimibe.

Results showed that participants receiving combination treatment with a statin plus ezetimibe achieved lower LDL cholesterol levels than those treated with statins alone over three years; however, rates of heart attack, stroke and other cardiovascular events were similar across the two groups.

In other findings, participants assigned to combination therapy, plus a lower cholesterol goal of 55 mg/dL, achieved an average LDL of 53 mg/dL compared with 62 mg/dL among those receiving only statins. In patients assigned to combination therapy and a conventional LDL goal of >70 mg/dL, the average LDL was 63 mg/dL vs. 70 mg/dL.

In presenting the findings, Byeong-Keuk Kim, MD, PhD, noted that many participants in both the low and high LDL goal groups who started treatment with only a statin eventually had ezetimibe added during follow-up in order to reach their LDL goal.

“We expected that starting with combination therapy would lead to fewer heart attacks, strokes and other heart problems, but this was not the case,” said Kim. “A previous large study published … 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.”

Based on the findings, he suggested that “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.”

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins

Keywords: AHA Annual Scientific Sessions, AHA26, Cholesterol, LDL, Primary Prevention, Angina, Unstable, Myocardial Infarction, Stroke