High-intensity statin treatment to lower low-density lipoprotein cholesterol (LDL-C) target levels after ischemic stroke or transient ischemic attack (TIA) is associated with a reduced risk for subsequent cardiovascular events, according to study results published in The New England Journal of Medicine.
Current clinical guidelines for the treatment of ischemic stroke recommend intense statin therapy but do not provide target LDL-C levels. Often, patients are started on a high-intensity regimen as directed, but are later prescribed a lower statin dose and achieve only moderate reductions in LDL-C levels. The study researchers aimed to determine whether more intense statin therapy to lower target LDL-C levels reduces the frequency of cardiovascular events after ischemic stroke or TIA in the randomized parallel-group event-driven Treat Stroke to Target trial (ClinicalTrials.gov Identifier: NCT01252875).
Conducted in both France and South Korea, the study enrolled a total of 2860 patients who had experienced either an ischemic stroke without significant disability within the past 3 months or a TIA accompanied by a speech disturbance or motor deficit in at least 1 limb within the past 15 days. All patients also had evidence of atherosclerotic disease and an indication for statin treatment. Patients were assigned 1:1 to a lower-target group (target LDL-C level, <70 mg/dL) or a higher-target group (target LDL-C level, 90-110 mg/dL). Physicians were allowed to prescribe any type or dose of statin to reach target levels.
In both groups, the mean baseline LDL-C level was approximately 135 mg/dL. Over the course of the trial, 65.9% of patients in the lower-target group received a statin only, and 33.8% received a statin plus ezetimibe. At follow-up (median, 3.5 years), the mean LDL-C level in the lower-target group was 65 mg/dL, and patients spent 52.8% of the time within the target range. In the higher-target group, 94% of patients received a statin only, with an additional 5.8% who received a statin plus ezetimibe. At follow-up, the mean LDL-C level was 96 mg/dL, with patients spending only 32.2% of time in the assigned target range. An additional 48.5% of patients had levels below the target range (<90 mg/dL). No heterogeneity was observed between the French and South Korean groups.
The primary end point of a major cardiovascular event occurred in 121 patients (8.5%; 2.27 per 100 person-years) in the lower-target group compared with 156 patients (10.9%; 2.98 per 100 person-years) in the higher-target group (adjusted hazard ratio, 0.78; 95% CI, 0.61-0.98; P =.04). Cerebral infarctions and strokes of underdetermined origin accounted for the majority of events in both groups, with 81 (5.7%) observed in the lower-target group and 100 (7.0%) observed in the higher-target group.
The researchers acknowledged that the premature termination of the trial should be considered when interpreting the results, but also noted that the 277 observed events provided sufficient statistical power to detect a 25% lower relative risk in the lower-target group.
“After an ischemic stroke or [transient ischemic attack] with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter,” the researchers concluded.
Disclosure: Funding for the study was provided by Pfizer, AstraZeneca, and Merck. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.
Amarenco P, Kim JS, Labreuche J, et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020;382:9-19.