TST-Diabetes_Appendix_SupplementalFile_20210408.pdf (277.17 kB)

Impact of Lower vs Higher LDL Cholesterol Targets on Cardiovascular Events After Ischemic Stroke in Diabetic Patients

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posted on 12.05.2021, 22:10 by Pierre Amarenco, Jong S Kim, Julien Labreuche, Hugo Charles, Maurice Giroud, Byung-Chul Lee, Philippa C Lavallée, Marie-Hélène Mahagne, Elena Meseguer, Norbert Nighoghossian, Philippe Gabriel Steg, Éric Vicaut, Eric Bruckert, Treat Stroke to Target Investigators
After an ischemic stroke with evidence of atherosclerosis, lipid lowering treatment with a target LDL cholesterol of less than 70 mg/dL compared to 100±10 mg/dL, reduced the risk of subsequent cardiovascular events. In this analysis, we explored the effect in the diabetic compared to nondiabetic subgroup and newly diagnosed diabetes.

Patients with ischemic stroke in the previous 3 months or TIA within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL cholesterol of less than 70 mg/dL or 100±10 mg/dL, using statin or ezetimibe. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. We did a pre specified analysis to evaluate the effect in diabetic patients.

Among 2,860 patients enrolled, 643 were diabetic at baseline with a mean age of 66.2 years and baseline LDL cholesterol of 127 mg/dL and were followed for a median of 3 years. The primary composite endpoint occurred in 27/328 (8.2%) patients in the lower target group and in 44/315 (14.0%) patients in the higher target group (adjusted hazard ratio, 0.56 [95% CI, 0.34 to 0.89]; P=0.016), while hazard ratio was 0.87 (95% CI, 0.66 to 1.14; P=0.31) in nondiabetic patients (Pinteraction=0.15). In diabetics, there were 3 intracranial hemorrhages in both randomization groups (0.9% vs. 1.0%, respectively). Newly diagnosed diabetes occurred in 98/1070 (9.2%) and in 80/1085 (7.4%) patients in the lower and higher target group, respectively (HR=1.27 [95% CI, 0.94 to 1.71], P=0.11) and baseline higher HbAIc was the unique multivariable predictor.

In conclusions, after an ischemic stroke with evidence of atherosclerosis, targeting an LDL cholesterol of less than 70 mg/dL compared to 100±10 mg/dL consistently reduced the risk of subsequent stroke and other major vascular events in diabetic and nondiabetic patients, but the higher risk in diabetic patients yielded a higher absolute risk reduction with an NNT of 17 (ClinicalTrials.gov NCT01252875- EUDRACT Identifier number 2009-A01280-57).

Funding

This study was an investigator-driven initiative and received a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique, PHRC 2009 [AOM09002], and from SOS-Attaque Cérébrale Association (a not-for-profit organization), with unrestricted grants obtained from Pfizer, AstraZeneca and Merck for French sites, and from Pfizer for South Korean sites.

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