Intracranial Hemorrhage in the TST Trial

Abstract

Background and Purpose: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. Methods: Patients with ischemic stroke in the previous 3 months or transient ischemic attack 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 (low-density lipoprotein) cholesterol of <70 mg/dL or 100±10 mg/dL, using statin or ezetimibe. Results: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31], P =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62], P =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. Conclusions: Targeting an LDL cholesterol of <70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

Remnant cholesterol but not LDL cholesterol is associated with 5-year bleeding following percutaneous coronary intervention

“…Multiple studies have focused on the relationship between LDL-C and ICH, but their results have been inconsistent. Several prospective studies mainly in the field of CHD have demonstrated no significant association between them, 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 which were consistent with our results. Of notice, many of these studies were the prespecified analyses of well-known clinical randomized trials where ICH was evaluated as one of the safety endpoints (e.g., IMPROVE-IT, 27 FOURIER, 26 and SPARCL trials 28 ).…”

Lowering Cholesterol and Intracerebral Hemorrhage: There Won’t Be Blood!

“…In this issue of Stroke, Amarenco et al 3 provide further reassurance that targeting lower levels of LDL following stroke and transient ischemic attack is a safe strategy. In the Treat Stroke to Target trial, patients were enrolled within 3 months of a stroke or transient ischemic attack (<15 days criterion for transient ischemic attack) if there was additional evidence of atherosclerotic disease.…”

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage

“…Although the TST trial (Treat Stroke to Target) investigating a target LDL-C level of <70 mg/ dL (1.8 mmol/L; lower-target group) compared with a target range of 90 mg to 110 mg/dL (2.3-2.8 mmol/L; higher-target group), which excluded patients with a history of ICH and confined eligibility to patients with ischemic stroke/TIA and atherosclerotic disease, led to only a nonstatistically significant increased risk of ICH. 31,32 The TST trial was ended prematurely and may have had limited power to detect a difference in risk of ICH with only 33 events occurring during study follow-up relative to 88 ICH events in SPARCL.…”