Small reduction in CV outcome after ischemic stroke with lower LDL target, but also harms; no change in all-cause mortality

Reference

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

Synopsis

Inpatient (any location) with outpatient follow-up Synopsis: This 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/dL if not taking a statin or greater than 70 if already taking a statin. The 2860 patients were then randomized to an LDL target of 70 mg/dL or an LDL target of 90 to 110 mg/dL using any type or dose of statin preferred by their physicians (plus ezetimibe, if needed). The total number of patients recruited was less than the authors stated target of 3786. The included patients were followed up 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/dL with approximately half already taking a statin. Groups were balanced and analysis was by intention to treat. The patients hit their mean LDL targets: 65 mg/dL in the low target group and 96 mg/dL in the higher target group. The authors had a very 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). Looking more closely, approximately 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), although the confidence interval was wide for this outcome. Intracerebral hemorrhage and newly diagnosed diabetes were also more common in the lower target group, although these differences were not statistically significant.