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Carotid Atherosclerosis Evolution When Targeting LDL <70 mg/dl After Stroke
Quick Takes
- The Treat Stroke to Target trial (published in February 2020) showed that in patients with recent stroke/TIA and with atherosclerotic cardiovascular disease, treatment to a target LDL <70 mg/dl compared to 90-110 mg/dl was associated with a lower risk of major adverse cardiac events.
- Treating to a target LDL of <70 mg/dl has become common practice for stroke patients with an atherosclerotic stroke etiology.
- While targeting an LDL <70 mg/dl is associated with a lower risk of recurrent stroke, the mechanisms driving this lower risk are not fully flushed out.
Study Questions:
How does targeting a low-density lipoprotein (LDL) <70 mg/dl compared to an LDL of 90-110 mg/dl in ischemic stroke and transient ischemic attack (TIA) patients with atherosclerotic vessel disease impact the evolution of carotid atherosclerosis?
Methods:
The present randomized controlled trial was nested within the larger Treat Stroke to Target trial. Eligible patients were adults who had had an ischemic stroke within the prior 3 months or a TIA within the prior 15 days, had an indication for a statin, and who had intracranial or extracranial cerebral artery stenosis or aortic arch plaque ≥4 mm in thickness or a known history of coronary artery disease. The lower-target (treatment) group was treated with statins and ezetimibe to a target LDL of <70 mg/dl. The higher-target (control) group was treated to a target LDL of 100 ± 10 mg/dl. Carotid ultrasounds were obtained at baseline and at 2, 3, and 5 years. The primary outcome was newly diagnosed carotid plaque. The secondary outcome was progression of common carotid artery intima media thickness.
Results:
The lower-target (treatment) group consisted of 202 subjects and the higher-target (control) group consisted of 212 subjects. The median follow-up was 3.1 years. The mean LDL was 64 mg/dl in the lower-target group and 106 mg/dl in the higher-target group. The 5-year rate of new carotid plaque in the lower-target group was 26.1% and in the higher-target group was 29.7% (adjusted hazard ratio, 1.01; 95% confidence interval, 0.66-1.53). After adjustment for potential confounders, a more significant decrease in common carotid artery intimal media thickness was observed in the lower-target group than the higher-target group (a difference of -8.37 μm; 95% CI, -13.74 to -2.99).
Conclusions:
No difference was observed in the development of new carotid plaques between the lower-target LDL and higher-target LDL groups. The lower-target group showed more regression of common carotid intima medial thickness than the higher-target group.
Perspective:
The results of this study are interesting and hypothesis-generating but will not change clinical management. Providers should continue to treat patients with atherosclerotic cardiovascular disease and ischemic stroke/TIA to a goal LDL of <70 mg/dl. Future studies may wish to differentiate symptomatic atherosclerotic disease (e.g., carotid stenosis ipsilateral to a hemispheric infarct) from asymptomatic atherosclerotic disease (e.g., aortic plaque in a patient with stroke caused by dissection).
Clinical Topics: Dyslipidemia, Noninvasive Imaging, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins, Echocardiography/Ultrasound
Keywords: Atherosclerosis, Brain Ischemia, Carotid Intima-Media Thickness, Carotid Stenosis, Cholesterol, LDL, Constriction, Pathologic, Coronary Artery Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Ischemic Attack, Transient, Plaque, Atherosclerotic, Secondary Prevention, Stroke, Vascular Diseases
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