Key result
Achieving LDL-C </dL cuts major cardiovascular events ~31% after ischemic stroke.
Why the study?
Does achieving very low LDL-C levels (<40 mg/dL) reduce major adverse cardiovascular events in patients with previous ischemic stroke?
RCT (n=5,291)
Placebo-controlled, open-label extension
Randomized
Does achieving very low LDL-C levels (<40 mg/dL) reduce major adverse cardiovascular events in patients with previous ischemic stroke?
Answers are grounded in this paper and cite their sources.
Achieving LDL-C levels <40 mg/dL in patients with previous ischemic stroke is associated with a significantly lower risk of major adverse cardiovascular events and recurrent stroke without increasing hemorrhagic stroke risk.
BACKGROUND: Patients with previous ischemic stroke are at high risk for recurrent stroke and other major adverse cardiovascular events. The benefits of achieving very low levels of low-density lipoprotein cholesterol (LDL-C) in such patients is unclear. METHODS: We analyzed patients with previous ischemic stroke enrolled in FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), a randomized placebo-controlled trial studying evolocumab in patients with stable atherosclerotic cardiovascular disease (median follow-up, 2.2 years), and through the open-label extension (FOURIER-OLE) period (additional median follow-up, 5 years), to examine the relationship between achieved LDL-C and the long-term incidence of the primary end point (cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization) and stroke-related end points. RESULTS: The analysis included 5291 patients with previous ischemic stroke (>4 weeks). Of these, 666 (12.6%), 1410 (26.6%), 586 (11.1%), 508 (9.6%), and 2121 (40.1%) patients achieved LDL-C values of <20, 20 to <40, 40 to <55, 55 to <70, and ≥70 mg/dL, respectively. The incidence of the primary end point, all stroke, and ischemic stroke each decreased in a monotonic fashion with lower achieved LDL-C levels on a continuous scale ( P trend <0.001, 0.002, and 0.002, respectively). Compared with patients with LDL-C ≥70 mg/dL, those who achieved levels <40 mg/dL had incidence rate ratios of 0.69 (95% CI, 0.57–0.84), 0.73 (95% CI, 0.53–0.99), and 0.75 (95% CI, 0.54–1.05) for the outcomes of the primary end point, all stroke, and ischemic stroke, respectively. Hemorrhagic strokes were infrequent and unrelated to achieved LDL-C ( P trend =0.85). CONCLUSIONS: In patients with previous ischemic stroke, it appeared that the lower the LDL-C, down to levels <40 mg/dL, the lower the risk of major adverse cardiovascular events, including recurrent stroke, without a clear increase in risk of hemorrhagic stroke. These findings support the concept that more intensive LDL-C lowering in patients with previous ischemic stroke may be warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01764633/NCT01764633.
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Monguillon et al. (2025) conducted an RCT in Previous ischemic stroke (n=5,291). Achieved LDL-C <40 mg/dL vs. Achieved LDL-C ≥70 mg/dL was evaluated on Cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization (IRR 0.69, 95% CI 0.57-0.84, p=<0.001). Achieving LDL-C levels </dL compared with ≥/dL in patients with previous ischemic stroke reduced the risk of the primary composite cardiovascular endpoint.
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