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Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and
Meng Lee1, Chun-Yu Cheng2, Yi-Ling Wu3
1Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Insights
Intensive statin therapy significantly reduces recurrent stroke risk compared to less intensive approaches. This benefit is particularly pronounced in patients with atherosclerosis, though it may increase hemorrhagic stroke risk.
Area of Science:
- Cardiology
- Neurology
- Clinical Trials
Background:
- The established benefits of statin therapy in reducing cardiovascular events are well-documented.
- However, the optimal intensity of low-density lipoprotein cholesterol (LDL-C)-lowering therapy for preventing recurrent stroke remains unclear.
- Understanding the risk-benefit profile of intensive LDL-C reduction is crucial for patient management.
Purpose of the Study:
- To evaluate the association between more intensive versus less intensive LDL-C-lowering statin-based therapies and patient outcomes, specifically recurrent stroke.
- To compare the efficacy and safety of different LDL-C-lowering strategies in stroke patients.
Main Methods:
- A meta-analysis of randomized clinical trials was conducted, searching major databases from 1970 to 2021.
- Included trials compared intensive versus less intensive LDL-C-lowering statin therapies in patients with stroke.
- Data extraction and quality assessment followed PRISMA guidelines, with relative risk (RR) and 95% confidence intervals (CI) used for analysis.
Main Results:
- The analysis included 11 trials with 20,163 patients, followed for a mean of 4 years.
- More intensive LDL-C-lowering statin therapies were associated with a reduced risk of recurrent stroke (RR, 0.88; 95% CI, 0.80-0.96).
- This intensive therapy also reduced major cardiovascular events but increased the risk of hemorrhagic stroke. The benefit was significant in patients with atherosclerosis (RR, 0.79; 95% CI, 0.69-0.91).
Conclusions:
- More intensive LDL-C-lowering statin-based therapies appear more favorable for recurrent stroke risk reduction compared to less intensive approaches.
- The findings suggest a tailored approach may be beneficial, especially for patients with evidence of atherosclerosis.
- Further research may clarify the balance between benefits and risks, including hemorrhagic stroke risk, with intensive LDL-C lowering.
Importance:
The benefits and risks associated with intensive low-density lipoprotein cholesterol (LDL-C)-lowering statin-based therapies to lessen the risk of recurrent stroke have not been established.
Objective:
To conduct a meta-analysis of randomized clinical trials to evaluate the association of more intensive vs less intensive LDL-C-lowering statin-based therapies with outcomes for patients with ischemic stroke.
Data Sources:
PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1970, to July 31, 2021.
Study Selection:
This meta-analysis included randomized clinical trials that compared more intensive vs less intensive LDL-C-lowering statin-based therapies and recorded the outcome of recurrent stroke among patients with stroke.
Data Extraction And Synthesis:
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Relative risk (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive LDL-C lowering with primary and secondary outcomes.
Main Outcomes And Measures:
The primary outcome was recurrent stroke, and the secondary outcomes were major cardiovascular events and hemorrhagic stroke.
Results:
The final analysis included 11 randomized clinical trials with 20 163 patients (13 518 men [67.0%]; mean [SD] age, 64.9 [3.7] years) with stroke. The mean follow-up was 4 years (range, 1-6.1 years). Pooled results showed that more intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of recurrent stroke compared with less intensive LDL-C-lowering statin-based therapies (absolute risk, 8.1% vs 9.3%; RR, 0.88; 95% CI, 0.80-0.96) and that the benefit associated with these LDL-C-lowering therapies was not different among LDL-C-lowering strategies (statins vs no statins: RR, 0.90; 95% CI, 0.81-1.01; more statins or ezetimibe vs less 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). More intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of major cardiovascular events, but with an increased risk of hemorrhagic stroke, compared with less intensive LDL-C-lowering statin-based therapies. More intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of recurrent stroke in trials with 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), compared with less intensive LDL-C-lowering statin-based therapies.
Conclusions And Relevance:
This study suggests that the benefits and risks of more intensive LDL-C-lowering statin-based therapies for recurrent stroke risk reduction might be more favorable than the benefits and risks of less intensive LDL-C-lowering statin-based therapies, especially for patients with evidence of atherosclerosis.
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