Brigham and Women’s Hospital’s TIMI Study Group reports that in patients with prior ischemic stroke, very low achieved LDL-cholesterol correlated with fewer major adverse cardiovascular events and fewer recurrent strokes, without an apparent increase in hemorrhagic stroke.
Study background and patient population
Patients with prior ischemic stroke face a high risk for recurrence and other cardiovascular events. Previous randomized trials of PCSK9 inhibitors and ezetimibe showed benefits of intensive LDL-cholesterol reduction in unselected atherosclerotic disease populations. Limited data existed for the specific subgroup with prior ischemic stroke, leaving uncertainty about the benefits and safety of achieving very low LDL-cholesterol levels in this cohort.
In the study, “Efficacy and Safety of Very Low Achieved LDL-Cholesterol in Patients with Prior Ischemic Stroke,” published as an accepted manuscript in Circulation, researchers analyzed data from FOURIER and its open-label extension to examine the relationship between achieved LDL-cholesterol and long-term incidence of a composite cardiovascular endpoint and stroke outcomes.
Analysis included 5,291 patients with prior ischemic stroke more than 4 weeks before enrollment. Median age was 65 years with 34.1% women. Median time from prior stroke to trial entry was 3.3 years.
LDL-cholesterol categories and outcomes
LDL-cholesterol categories included under 20 mg/dL for 666 patients, 20 to 39 mg/dL for 1,410 patients, 40 to 54 mg/dL for 586 patients, 55 to 69 mg/dL for 508 patients, and 70 mg/dL or more for 2,121 patients.
Analyses demonstrated monotonic decreases in the adjusted annualized incidence of the primary composite and key secondary composite with lower achieved LDL-cholesterol levels on a continuous scale, with p-trend <0.001 for each.
Compared with ≥70 mg/dL, LDL-cholesterol <40 mg/dL corresponded to an incidence rate ratio of 0.69 for the primary endpoint and 0.73 for the key secondary endpoint.
Stroke recurrence
Recurrent stroke incidence declined as LDL-cholesterol decreased for all stroke and ischemic stroke.
Comparison of <40 mg/dL with ≥70 mg/dL yielded an incidence rate ratio of 0.73 for all stroke and 0.75 for ischemic stroke. Hemorrhagic stroke events were infrequent and showed no relationship to achieved LDL-cholesterol with a p-trend of 0.85.
Patients with prior ischemic stroke receiving lipid-lowering therapy, lower LDL-cholesterol below 40 mg/dL appeared to be associated with lower incidence of major adverse cardiovascular events and recurrent stroke.
Findings tentatively support consideration of more intensive LDL-cholesterol lowering in this population.
Written for you by our author Justin Jackson, edited by Gaby Clark, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You’ll get an ad-free account as a thank-you.
More information: Victorien Monguillon et al, Efficacy and Safety of Very Low Achieved LDL-Cholesterol in Patients with Prior Ischemic Stroke, Circulation (2025). DOI: 10.1161/circulationaha.125.077549
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