LDL-C Levels Below 55 mg/dl and Risk of Hemorrhagic Stroke: A Meta-Analysis

• Published in: Journal of stroke and cerebrovascular diseases Vol. 30; no. 4; p. 105655
• Main Authors: Masson, Walter, Lobo, Martín, Siniawski, Daniel, Masson, Gerardo, Lavalle-Cobo, Augusto, Molinero, Graciela
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2021
• Subjects: Biomarkers - blood; Cholesterol, LDL - blood; Down-Regulation; Dyslipidemias - blood; Dyslipidemias - drug therapy; Dyslipidemias - epidemiology; Hemorrhagic stroke; Hemorrhagic Stroke - epidemiology; Humans; Hypolipidemic Agents - adverse effects; Hypolipidemic Agents - therapeutic use; Incidence; Lipid-lowering therapy;LDL-C goals; Meta-analysis; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Hemorrhagic stroke; Lipid-lowering therapy;LDL-C goals; Meta-analysis
• ISSN: 1052-3057; 1532-8511; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2021.105655

•There may be an increased risk of hemorrhagic stroke when reaching low LDL-C levels.•The currently suggested LDL-C goal for very high-risk patients is < 55 mg/dL.•We performed a meta-analysis of randomized trials with lipid-lowering therapies.•This meta-analysis included only trials that achieved LDL-C levels under 55 mg/dl.•We did not find a greater risk of hemorrhagic stroke when reaching LDL-C <55 mg/dl. To evaluate the effect of very low levels of LDL-C (< 55 mg/dl) achieved with lipid-lowering therapy on hemorrhagic stroke incidence. We performed a meta-analysis including randomized trials that achieved LDL-C levels under 55 mg/dl in more intensive lipid-lowering arms, regardless of the lipid-lowering drug used. A fixed-effects model was used. This meta-analysis was performed according to PRISMA guidelines. Eight eligible trials including 122.802 patients, were identified and considered eligible for the analyses. A total of 62.526 subjects were allocated to receive more intensive lipid-lowering therapy while 60.276 subjects were allocated to the respective control arms. There were no differences in the incidence of hemorrhagic stroke between the group that received a more intensive lipid-lowering therapy (achieved LDL-C level <55 mg/dl), and the group that received a less intense scheme (OR, 1.05; 95%CI, 0.85–1.31). The statistical heterogeneity was low (I2 = 2%). The sensitivity analysis showed that the results were robust. The use of more intensive lipid-lowering therapy that achieved an LDL-C level lower than 55 mg/dl in patients with high cardiovascular risk, is not associated with an increased risk of hemorrhagic stroke. Considering the cardiovascular benefit and safety observed with the achievement of very low LDL-C values, the challenging lipid goals recommended by the new guidelines seem consistent.