A global study has shed light on the benefits of achieving very low LDL-C levels, down to below 40 mg/dL, for reducing the risk of recurrent ischaemic stroke.

Professor Anthony Keech. Source University of Sydney

The investigators, including University of Sydney Professor Anthony Keech, said their data suggested ischaemic stroke patients may benefit from achieving lower LDL-C levels than what is endorsed by several current guidelines.

The research was published in Circulation and was presented over the weekend at the American Heart Association’s 2025 Scientific Sessions meeting in New Orleans.

Analysis included 5,291 patients enrolled in the FOURIER trial [link here], a placebo-controlled study of evolocumab in patients with stable atherosclerotic cardiovascular disease, funded by the drug’s maker Amgen.

Findings showed that, compared with patients with LDL-C of >70 mg/dL, those who achieved levels of lower than 40 mg/dL saw lower incidence of the primary MACE endpoint (IRR 0.69), all stroke (IRR 0.73) and ischaemic stroke (0.75).

“There was no apparent relationship between achieved LDL-C and hemorrhagic stroke, in contrast with prior reports of some statin trials,” the authors said.

Data supports escalation of lipid-lowering therapies 

The research team acknowledged further RCTs would be needed to establish optimal LDL-C and other lipid goals for this patient group.

Despite this, “by demonstrating significantly lower rates of MACE and of recurrent stroke alone in patients with prior ischaemic stroke who achieved an LDL-C <40 mg/dL, our study supports escalation of lipid-lowering therapies to achieve lower goals than currently recommended”, they said.

Meanwhile, current guidelines differed in their approach to aggressive lipid-lowering treatment for patients with prior stroke.

“Although guidelines recommend targeting an LDL-C <70 mg/dL with high intensity statins to reduce recurrent MACE in patients with ischaemic stroke with no major sources of embolism, substantial differences are noted regarding further escalation strategies,” they wrote.

The European Stroke Organisation (ESO) guidelines on secondary prevention of stroke highlighted uncertainty over the use of PCSK9, they said.

Meanwhile, American Heart Association guidelines restricted use of PCSK9 inhibitors to patients with history of ischaemic stroke and persistent LDL-C >70 mg/dL.

There were a number of limitations to the study, including that patients were categorised according to two early LDL-C values.

“Since the FOURIER trial excluded patients within 4 weeks of ischaemic stroke, these results may not apply to patients with a more recent ischaemic stroke,” the authors noted.

Despite this, the data suggested that the lower a patient’s achieved LDL, the lower their risk of major cardiovascular events and stroke in future.

“These findings support the concept that more intensive LDL-C lowering in patients with prior ischemic stroke may be warranted,” they said.