More intensive cholesterol-lowering statins effective in stroke with atherosclerosis

More intensive LDL cholesterol–lowering statin-based therapies may benefit patients with ischemic stroke with evidence of atherosclerosis, according to a meta-analysis published in JAMA Neurology.

“Statins plus cholesterol absorption inhibitors (eg, ezetimibe) or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab and evolocumab) compared with statins alone were associated with reduced major cardiovascular events and strokes for patients with a history of acute coronary syndrome or atherosclerotic cardiovascular disease in clinical trials,” Meng Lee, MD, of the department of neurology at Chang Gung University College of Medicine in Taiwan, and colleagues wrote. “However, whether those medications (ezetimibe or PCSK9 inhibitors) are beneficial as add-on therapy to statins for patients with prior stroke has not been definitively established, to our knowledge.”

Lee and colleagues conducted a meta-analysis that included randomized clinical trials comparing the link between more intensive vs. less intensive LDL cholesterol (LDL-C)-lowering statin-based therapies and outcomes among patients with ischemic stroke. They searched four databases between Jan. 1, 1970, and July 31, 2021.

Recurrent stroke served as the primary outcome, with major adverse cardiovascular events (MACE) and hemorrhagic stroke as the secondary outcomes. They included 11 randomized clinical trials with 20,163 patients (67% men; mean age, 64.9 years) with stroke, with a mean follow-up of 4 years.

Pooled results revealed an association between more intensive LDL-C-lowering statin-based therapies and a reduced risk for recurrent stroke vs. less intensive LDL-C-lowering statin-based therapies (absolute risk, 8.1% vs. 9.3%; RR = 0.88; 95% CI, 0.8-0.96). The benefit linked to these LDL-C-lowering therapies did not differ among LDL-C-lowering strategies ([statins vs. no statins, RR = 0.9; 95% CI, 0.81-1.01]; [more statins or ezetimibe vs. less statins or ezetimibe, RR = 0.77; 95% CI, 0.62-0.96]; proprotein convertase subtilisin/kexin type 9 inhibitors plus statins vs. placebo plus statins, RR = 0.9; 95% CI, 0.71-1.15).

The researchers noted an association between more intensive LDL-C-lowering statin-based therapies and reduced risk for major cardiovascular events; however, they were linked to increased risk for hemorrhagic stroke vs. less intensive LDL-C-lowering statin-based therapies. Further, researchers noted an association between more intensive LDL-C-lowering statin-based therapies and reduced risk for recurrent stroke in trials in which all patients had evidence of atherosclerosis (RR = 0.79; 95% CI, 0.69-0.91) but not in trials in which most patients did not have evidence of atherosclerosis (RR = 0.95; 95% CI, 0.85-1.07) compared with less intensive LDL-C-lowering statin-based therapies.

“This meta-analysis of accumulated clinical trial data suggests that more intensive compared with less intensive LDL-C–lowering statin-based therapies might be associated with a reduced risk for recurrent stroke among patients with ischemic stroke, but this reduced risk might be confined to patients with evidence of atherosclerosis,” Lee and colleagues wrote.

“Also, more intensive compared with less intensive LDL-C–lowering statin-based therapies might be associated with a reduced risk of MACE, ischemic stroke and myocardial infarction but might also be associated with an increased risk for hemorrhagic stroke and new-onset diabetes,” they added. “For patients without evidence of atherosclerosis, intensive LDL-C–lowering statin-based therapies might not be needed in most situations considering the uncertain benefits of secondary stroke prevention and the increased risk for hemorrhagic stroke associated with intensive LDL-C lowering.”

In a related editorial, Didier Leys, MD, PhD, of the University of Lille in France, and colleagues outlined the clinical relevance of this study.

“The message for clinicians is, therefore, that the level of LDL-C should be lowered below 70 mg/dL by any means after an ischemic stroke in patients with evidence of atherosclerosis,” they wrote. “For those without atherosclerosis, the benefit of lowering the level of LDL-C below 70 mg/dL vs. between 90 and 110 mg/dL is much smaller, and an individualized evaluation of the risk to benefit ratio, bearing in mind a small increase in risks of intracerebral hemorrhage and type 2 diabetes, is needed.”