More intensive low-density lipoprotein cholesterol (LDL-C)-lowering statin-based therapies may be more effective and safer for recurrent stroke risk reduction than less intensive LDL-C-lowering statin-based therapies, especially in patients with atherosclerosis, according to a study in JAMA Neurology.

Previous research has found that among patients with established atherosclerotic cardiovascular disease, more intense LDL-C-lowering statin-based therapies are associated with reduced major cardiovascular events (MACE). However, the effect of LDL-lowering with statins on MACE risk in patients with stroke is inconsistent. The objective of the current study was to evaluate the association of more intensive vs less intensive LDL-C-lowering statin-based therapies with outcomes for patients with ischemic stroke.

The researchers conducted a systematic review and meta-analysis after a literature search on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from January 1, 1970, to July 31, 2021. Eligible studies were randomized clinical trials that included all or an identifiable subset of patients who had a history of stroke or transient ischemic attack and that evaluated more intensive vs less intensive LDL-C-lowering statin-based therapies. Recurrent stroke was the primary outcome.


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A total of 11 randomized clinical trials with 20,163 patients (13,518 men [67.0%]; mean [SD] age, 64.9 [3.7] years) with stroke were included. The mean follow-up was 4 years (range, 1-6.1 years).

More intensive vs less intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of recurrent stroke (absolute risk, 8.1% vs 9.3%; relative risk [RR], 0.88; 95% CI, 0.80-0.96; P =.004; I2 = 0%; number needed to treat in 4 years, 90), according to pooled results from the fixed-effects model.

No statistically different benefit was found among the LDL-C-lowering strategies (statins vs no statins: RR, 0.90; 95% CI, 0.81-1.01; more statins or ezetimibe vs fewer statins or ezetimibe: RR, 0.77; 95% CI, 0.62-0.96; and proprotein convertase subtilisin/kexin type 9 inhibitors plus statins vs placebo plus statins: RR, 0.90; 95% CI, 0.71-1.15; P =.42 for interaction; I2 = 0%).

More intensive compared with less intensive LDL-C-lowering statin-based therapies were associated with a decreased risk of major adverse cardiovascular events (absolute risk, 13.9% vs 16.7%; RR, 0.83; 95% CI, 0.78-0.89; P < .001; I2 = 0%; number needed to treat, 35), according to pooled results from 8 trials. In addition, more intensive vs less intensive LDL-C-lowering statin-based therapies were associated with a lower risk of recurrent ischemic stroke (absolute risk, 6.3% vs 7.7%; RR, 0.82; 95% CI, 0.74-0.91; P <.001; I2 = 0%; number needed to treat, 72).

More intensive vs less intensive LDL-C-lowering statin-based therapies were associated with a decreased risk of recurrent stroke in trials that included all patients having evidence of atherosclerosis (RR, 0.79; 95% CI, 0.69-0.91) but not in trials with most patients not having evidence of atherosclerosis (RR, 0.95; 95% CI, 0.85-1.07; P =.04 for interaction; I2 = 75%).

The researchers noted that the primary purpose of several trials was not to assess more intensive vs less intensive LDL-C-lowering statin-based therapies for patients with ischemic stroke, and so a subgroup of patients with a history of stroke was used in the meta-analysis. In these cases, the characteristics of the index stroke and the duration between the index stroke and the trial initiation were generally vague. Also, the sample sizes varied, and the trials were conducted in mostly high-income countries.

“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 of hemorrhagic stroke associated with intensive LDL-C lowering,” stated the researchers. “Also, further data from randomized clinical trials are warranted to elucidate whether intensive LDL-C-lowering statin-based therapies are beneficial for certain racial and ethnic groups, such as Asian individuals.”

Reference

Lee M, Cheng C-Y, Wu Y-L, Lee J-D, Hsu C-Y, Ovbiagele B. Association between intensity of low-density lipoprotein cholesterol reduction with statin-based therapies and secondary stroke prevention: a meta-analysis of randomized clinical trials. JAMA Neurol. Published online February 21, 2022. doi: 10.1001/jamaneurol.2021.5578