Clinical Question

Does a lower low-density lipoprotein (LDL) target following ischemic stroke reduce the likelihood of major adverse cardiovascular events?

Bottom Line

A lower LDL target slightly reduced the likelihood of a broad composite outcome (number needed to treat [NNT] = 43 over 3.5 years), largely by reducing nonfatal strokes (NNT = 77; statistical significance not reported). The benefit was seen only in patients whose index event was a stroke; risk may be increased in those with transient ischemic attack (TIA). (Level of Evidence = 1b)

Synopsis

The study identified adults with a recent ischemic stroke or TIA of at least 10 minutes duration in France or South Korea who had a modified Rankin score of 0 to 3 (functionally independent or largely so). All patients underwent imaging and had stenosis of a cerebral artery or known coronary artery disease. They also had an LDL level greater than 100 mg per dL (2.59 mmol per L) if not taking a statin or greater than 70 mg per dL (1.81 mmol per L) if already taking a statin. The 2,860 patients were then randomized to an LDL target of 70 mg per dL or an LDL target of 90 to 110 mg per dL (2.33 to 2.85 mmol per L) using any type or dose of statin preferred by their physicians (plus ezetimibe [Zetia], if needed). The total number of patients recruited was less than the authors' stated target of 3,786. The included patients were followed for a median of 5.3 years in France but only 2.0 years in South Korea. The mean age of participants was 67 years, 67% were men, 64% had hypertension, and their baseline LDL level was 135 mg per dL (3.50 mmol per L) with approximately one-half already taking a statin. Groups were balanced, and analysis was by intention to treat. The patients hit their mean LDL targets: 65 mg per dL (1.68 mmol per L) in the low target group and 96 mg per dL (2.49 mmol per L) in the higher target group. The authors had a broad primary composite outcome of cardiovascular death, nonfatal stroke, acute coronary syndrome, or urgent coronary or carotid revascularization, which was lower in the low LDL target group (8.5% vs. 10.9%; P = .04; NNT = 42 over 3.5 years to prevent one event). Approximately one-half of the events prevented in the composite outcome were nonfatal ischemic strokes. The authors do not report statistical significance testing for any of the individual outcomes, although they say that none of the individual outcome differences were statistically significant. All-cause mortality was similar between groups (6.2% vs. 6.5%). There was a significant increase in the likelihood of the primary composite outcome in patients whose index event was a TIA rather than an ischemic stroke (11.7% vs. 6.0%; P < .05), but the confidence interval was wide for this outcome. Intracerebral hemorrhage and newly diagnosed diabetes mellitus were more common in the lower target group, but these differences were not statistically significant.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Setting: Inpatient (any location) with outpatient follow-up

Reference: Amarenco P, Kim JS, Labreuche J, et al.; Treat Stroke to Target Investigators. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020;382(1):9–19.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.