Magnitude of LDL-C Reduction Associated With Improved Outcomes After Stroke

Reducing low-density lipoprotein cholesterol (LDL-C) by more than 50% in patients with ischemic stroke who are assigned a target LDL cholesterol of less than 70 mg/dL reduces risk for major vascular events, according to a study in Stroke.

The post hoc analysis of the Treat Stroke to Target trial (ClinicalTrials.gov Identifier: NCT01252875) assessed the outcomes of lowering LDL-C by more than 50% from baseline levels or less than 50% in patients assigned an LDL-C target level of less than 70 mg/dL, compared with a target level of 100±10 mg/dL.

All patients were enrolled from March 2010 to December 2018. Included patients had a proven ischemic stroke on neuroimaging (modified Rankin Scale score of 0 to 3) that occurred within the previous 3 months or a transient ischemic attack (TIA) within the prior 15 days with at least 1 motor deficit of the arm and leg or a speech disturbance that lasted more than 10 minutes.

The primary outcome was a composite of nonfatal cerebral infarction or stroke of undetermined cause, nonfatal myocardial infarction, hospitalization for unstable angina followed by urgent coronary artery revascularization, TIA with need for urgent carotid revascularization, or cardiovascular death including unexplained sudden death.

Of the 2860 patients who were followed for a median of 3.9 years (IQR, 2.1-6.8), 1430 were assigned an LDL-C target of 100±10 mg/dL (the control group; mean age, 67 years; 67.3% men). The LDL-C target of less than 70 mg/dL with less than 50% LDL-C reduction group included 692 patients (mean age, 66.9 years; 68.8% men), and the LDL-C target of less than 70 mg/dL with 50% or more LDL-C reduction group included 492 patients (mean age, 65 years; 70.3% men).

At enrollment, patients in the lower target group with a more than 50% decrease in LDL-C from baseline had a mean baseline LDL-C of 155±32 mg/dL, and participants with a less than 50% decrease in LDL-C from baseline had a mean baseline LDL-C of 121±34 mg/dL (136±38 mg/dL in the control group).

Participants in the lower target group with a more than 50% LDL-C decrease from baseline had decreased risk for a major cardiovascular event (hazard ratio [HR], 0.61; 95% CI, 0.43-0.88; P =.007), but patients with a less than 50% LDL cholesterol reduction from baseline did not (HR, 0.96; 95% CI, 0.73-1.26; P =.75), compared with patients in the control group.

A study limitation is that only the target LDL-C of less than 70 mg/dL group is randomized and the magnitude of LDL-C reduction from baseline (>50% and <50%) is not randomized. Also, 256 patients in the lower target group were excluded because they did not have sufficient follow-up LDL-C measurements.

“…when clinicians consider targeting an LDL cholesterol of less than 70 mg/dL, they should also be careful to reduce LDL cholesterol by more than 50%,” wrote the investigators.

Disclosure: This study received unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites, and from Pfizer for South Korean sites, and Athera Pharmaceuticals for this post hoc analysis. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.