Mechanisms
Review proposes probucol as an alternative stroke-prevention therapy for patients at high haemorrhage risk (Brain Circ 2023)
Original title: Probucol will become a new model for treating cerebral infarction with a high risk of hemorrhage: A narrative review
This narrative review discusses probucol, an antioxidative lipid-lowering drug used for atherosclerotic cardiovascular disease and xanthomas, as a candidate treatment for patients at high risk of both cerebral infarction and haemorrhage. Probucol penetrates LDL cholesterol particles, enhances the activity of plasma CETP and strengthens hepatic scavenger receptor type I to lower LDL cholesterol, while its enhancement of paraoxonase 1 activity upregulates HDL's antioxidant function even as it lowers HDL cholesterol levels, a combination that led to its withdrawal from Western markets alongside rare QT-interval prolongation. The review cites recent clinical evidence that probucol reduces cardiovascular events and mortality irrespective of its HDL-C-lowering effect, proposing it as a valuable alternative to statins in patients at high risk of recurrent cerebral ischaemia and haemorrhage.
Original abstract
Lipid-lowering agents are relevant in stroke prevention. Probucol (PU) is an antioxidative and lipid-lowering drug that has been used to treat atherosclerotic cardiovascular diseases and xanthomas. The drug penetrates the core of low-density lipoprotein cholesterol (LDL-C) particles, enhancing the activity of plasma cholesterol l ester transfer protein (CETP) and strengthening the liver scavenger receptor type I, resulting in reducing LDL-C; by increasing the activity of paraoxonase 1, upregulating the antioxidant function of high-density lipoprotein (HDL), and it decreases the serum HDL-cholesterol (HDL-C) level. This drug has been retired from the Western markets for lowering HDL-C levels and Q-interval prolongation. The latter side effect has been rarely reported and may be transient. Recent clinical evidence supports the effectiveness of PU in preventing cardiovascular events and in reducing mortality, irrespective of the reduction of HDL-C. Based on basic research and clinical studies, it appears that PU might be a valuable alternative when statins are ineffective or contraindicated, in patients at high risk of recurrence of cerebral ischemia and hemorrhage.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.