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

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.