Very low LDL-cholesterol correlates to fewer heart problems after stroke

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.