Intensive LDL C lowering below 70 mg/dl reduces CV events after stroke: NEJM

Statins have been widely prescribed to lower cholesterol levels for preventing cardiovascular events in patients at high risk of cardiovascular disease, including stroke. Intensive lipid-lowering therapy by means of statin medications is recommended after a transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin.

Statins are now the essential component of medical management in patients at risk for cardiovascular disease as most trials of primary and secondary prevention with statins have shown a decrease in the incidence of vascular events. But the target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.

In a new trial, it has been found by investigators that patients with an ischemic stroke or TIA and with evidence of atherosclerotic disease, those who were assigned to a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of a composite endpoint of major cardiovascular events than those who were assigned to a target range of 90 mg to 110 mg per deciliter. The study has been published in the New England Journal of Medicine.

Researchers conducted a randomized, parallel-group, event-driven trial at 61 sites in France and 16 sites in South Korea and assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per litre) (higher-target group).

All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary endpoint of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. All the patients provided written informed consent

A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per litre), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per litre) in the lower-target group and 96 mg per deciliter (2.5 mmol per litre) in the higher-target group.

The researchers found that patients with recent ischemic stroke or TIA and evidence of atherosclerotic disease, those who were assigned to a target LDL cholesterol level of less than 70 mg per deciliter had fewer major cardiovascular events than those assigned to a target range of 90 mg to 110 mg per deciliter. The lowering of the LDL cholesterol level was accomplished by adjustment of the statin dose, with the addition of ezetimibe in 33.8% of the patients. In addition to monitoring LDL cholesterol levels, investigators encouraged the targeted treatment of blood pressure and diabetes, along with smoking cessation, with favourable results. The incidence of intracranial haemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.

The researchers concluded that after an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter.

Journal: New England Journal of Medicine

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DOI: 10.1056/NEJMoa1910355