A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke

BACKGROUND: The use of intensive lipid-lowering therapy, primarily through statin medications, is recommended following a transient ischemic attack (TIA) or an ischemic stroke of atherosclerotic origin. However, the optimal target level for low-density lipoprotein (LDL) cholesterol to effectively reduce subsequent cardiovascular events after a stroke has not been thoroughly investigated.

METHODS: In this parallel-group trial, conducted in both France and South Korea, patients who had experienced an ischemic stroke within the preceding 3 months or a TIA within the preceding 15 days were randomly assigned to one of two target LDL cholesterol levels: less than 70 mg per deciliter (1.8 mmol per liter) for the intensive-treatment group, or a range of 90 to 110 mg per deciliter (2.3 to 2.8 mmol per liter) for the standard-treatment group. The primary outcome was a composite of major cardiovascular events, specifically ischemic stroke, myocardial infarction, or urgent revascularization required for ischemic reasons. Secondary outcomes included the individual components of the primary outcome and death from any cause. The median duration of follow-up for participants was 3.5 years.

RESULTS: A total of 2860 patients were included in the final analysis. Throughout the follow-up period, the median LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the intensive-treatment group and 96 mg per deciliter (2.5 mmol per liter) in the standard-treatment group. A primary outcome event occurred in 121 patients (5.5 events per 100 person-years) in the intensive-treatment group, compared to 163 patients (7.3 events per 100 person-years) in the standard-treatment group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). The rates of the individual components of the primary outcome consistently showed a reduction in the intensive-treatment group compared to the standard-treatment group. The incidence of hemorrhagic stroke was similar in both groups, at 0.9% in the intensive-treatment group and 0.8% in the standard-treatment group. The overall incidence of new-onset diabetes mellitus was also comparable, at 2.5% in the intensive-treatment group and 2.3% in the standard-treatment group. The overall rates of adverse events were similar between the two treatment groups.

CONCLUSIONS: Among patients who had experienced an ischemic stroke or TIA of atherosclerotic origin, aiming for an LDL cholesterol level of less than 70 mg per deciliter was associated with a significantly lower risk of subsequent cardiovascular events than targeting a range of 90 to 110 mg per deciliter.

BACKGROUND: The use of intensive lipid-lowering therapy, primarily through statin medications, is recommended following a transient ischemic attack (TIA) or an ischemic stroke of atherosclerotic origin. However, the optimal target level for low-density lipoprotein (LDL) cholesterol to effectively reduce subsequent cardiovascular events after a stroke has not been thoroughly investigated.

METHODS: In this parallel-group trial, conducted in both France and South Korea, patients who had experienced an ischemic stroke within the preceding 3 months or a TIA within the preceding 15 days were randomly assigned to one of two target LDL cholesterol levels: less than 70 mg per deciliter (1.8 mmol per liter) for the intensive-treatment group, or a range of 90 to 110 mg per deciliter (2.3 to 2.8 mmol per liter) for the standard-treatment group. The primary outcome was a composite of major cardiovascular events, specifically ischemic stroke, myocardial infarction, or urgent revascularization required for ischemic reasons. Secondary outcomes included the individual components of the primary outcome and death from any cause. The median duration of follow-up for participants was 3.5 years.

RESULTS: A total of 2860 patients were included in the final analysis. Throughout the follow-up period, the median LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the intensive-treatment group and 96 mg per deciliter (2.5 mmol per liter) in the standard-treatment group. A primary outcome event occurred in 121 patients (5.5 events per 100 person-years) in the intensive-treatment group, compared to 163 patients (7.3 events per 100 person-years) in the standard-treatment group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). The rates of the individual components of the primary outcome consistently showed a reduction in the intensive-treatment group compared to the standard-treatment group. The incidence of hemorrhagic stroke was similar in both groups, at 0.9% in the intensive-treatment group and 0.8% in the standard-treatment group. The overall incidence of new-onset diabetes mellitus was also comparable, at 2.5% in the intensive-treatment group and 2.3% in the standard-treatment group. The overall rates of adverse events were similar between the two treatment groups.

CONCLUSIONS: Among patients who had experienced an ischemic stroke or TIA of atherosclerotic origin, aiming for an LDL cholesterol level of less than 70 mg per deciliter was associated with a significantly lower risk of subsequent cardiovascular events than targeting a range of 90 to 110 mg per deciliter.