In clinical trials, compared with statins alone, statins plus cholesterol-absorption inhibitors (ezetimibe) or PCSK9 inhibitors (alirocumab or evolocumab) lowered the number of major cardiovascular events and strokes for patients with a history of acute coronary syndrome or atherosclerotic cardiovascular disease.
However, it's unclear whether ezetimibe or PCSK9 inhibitors are beneficial when added to statins in patients with prior stroke.
To investigate, Dr. Meng Lee with Chang Gung University College of Medicine in Taiwan and colleagues did a meta-analysis of 11 randomized clinical trials that compared more-intensive versus less-intensive LDL cholesterol-lowering statin-based therapies and outcomes in a total of more than 20,000 patients with prior ischemic stroke.
After a mean follow-up of four years, there was a statistically significantly lower risk of recurrent stroke with more-intensive LDL-C lowering versus less-intensive LDL-C lowering (8.1% vs. 9.3%; relative risk: 0.88; 95% CI, 0.80 to 0.96), the team reports in JAMA Neurology.
More-intensive LDL-C-lowering statin-based therapies were associated with a 17% reduced risk of major cardiovascular events, but with a 46% increased risk of hemorrhagic stroke, compared with less-intensive LDL-C-lowering statin-based therapies, they say.
"In more practical terms, the number needed to treat to prevent a stroke in four years was 90, and the number needed to prevent a MACE was 35, whereas the number needed to harm was 242 for a hemorrhagic stroke," they note.
"Also, more intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of recurrent ischemic stroke and myocardial infarction, but were associated with a higher risk for new-onset diabetes, compared with less intensive LDL-C-lowering statin-based therapies," they add.
They caution that the pooled data suggest that the benefits associated with more-intensive LDL-C-lowering might only hold for patients with ischemic stroke with evidence of atherosclerosis.
More-intensive LDL-C lowering was associated with a reduced risk of recurrent stroke in trials with all patients having evidence of atherosclerosis, but not in trials with most patients not having evidence of atherosclerosis.
The authors of a linked editorial say this analysis adds to previous knowledge in showing that "the lower the LDL-C level, especially in patients with atherosclerosis, the lower the risks of recurrent stroke and major cardiovascular events."
"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 write.
"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," they add.
SOURCE: https://bit.ly/350B5Ib and https://bit.ly/33HwWZ9 JAMA Neurology, online February 21, 2022.
By Reuters Staff
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