What does this research mean for the field?

More intensive LDL-C-lowering statin-based therapies reduce the risk of recurrent stroke by 12% compared with less intensive therapies in patients with a history of stroke, particularly among those with atherosclerosis. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the association of more intensive versus less intensive low-density lipoprotein cholesterol (LDL-C)-lowering statin-based therapies with clinical outcomes in patients with ischemic stroke.

February 21, 2022JAMA NeurologyOpen Access

Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Ischemic stroke (n=20163). Intervention: More intensive LDL-C-lowering statin-based therapies vs. Less intensive LDL-C-lowering statin-based therapies. Primary outcome: Recurrent stroke (RR 0.88, 95% CI 0.80-0.96, p=0.004).

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Key result

More intensive LDL-C-lowering statin therapy cuts recurrent stroke ~12% in patients with prior stroke.

RR 0.88
95% CI 0.80-0.96
P=0.004
NNT 90
n=20,163

Why the study?

The benefits and risks associated with intensive LDL-C-lowering statin-based therapies to lessen the risk of recurrent stroke have not been established.

Does more intensive LDL-C-lowering statin-based therapy reduce recurrent stroke in patients with a history of stroke?

Population

20 163 patients with stroke across 11 randomized clinical trials

Comparison

More intensive vs less intensive LDL-C-lowering statin-based therapies

Design

Meta-analysis of randomized clinical trials

Follow-up

Mean 4 years (range, 1-6.1 years)

Authors

MLMeng LeeInje University CCChun-Yu ChengNational Chung Cheng University YWYi‐Ling WuNorth China University of Science and Technology

Discussion

Member takes

Implication

Supports intensifying statin-based LDL-C lowering for secondary stroke prevention; confirms benefit and extends it to atherosclerotic subgroups.

Key Points

To evaluate the association of more intensive versus less intensive low-density lipoprotein cholesterol (LDL-C)-lowering statin-based therapies with clinical outcomes in patients with ischemic stroke.
Conducted a systematic review and meta-analysis of 11 randomized clinical trials (N = 20 163; 13 518 men [67.0%]; mean age, 64.9 years; mean follow-up, 4 years [range, 1-6.1 years]) identified through PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through July 31, 2021.
Evaluated comparisons across three strategies: statins vs no statins, more statins or ezetimibe vs less statins or ezetimibe, and PCSK9 inhibitors plus statins vs placebo plus statins, assessing relative risk (RR) with 95% CI on an intention-to-treat basis.
More intensive LDL-C-lowering statin-based therapies were associated with a reduced risk of recurrent stroke compared with less intensive therapies (absolute risk, 8.1% vs 9.3%; RR, 0.88; 95% CI, 0.80-0.96), with no significant difference across drug strategies (P = .42 for interaction).
More intensive therapy reduced recurrent stroke in trials where all patients had evidence of atherosclerosis (RR, 0.79; 95% CI, 0.69-0.91), but not in trials where most patients lacked evidence of atherosclerosis (RR, 0.95; 95% CI, 0.85-1.07; P = .04 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 therapies.

Study Design

Type

Meta-Analysis (n=20,163)

Structured PICO

Does more intensive LDL-C-lowering statin-based therapy reduce recurrent stroke in patients with a history of stroke?

Population

20,163 patients with a history of stroke from 11 randomized clinical trials, followed for a mean of 4 years.

Intervention

More intensive LDL-C-lowering statin-based therapies (including statins vs no statins, more statins or ezetimibe vs less statins or ezetimibe, and PCSK9 inhibitors plus statins vs placebo plus statins)

Comparator

Less intensive LDL-C-lowering statin-based therapies (including no statins, less statins/ezetimibe, or placebo plus statins)

Outcome

Recurrent strokehard clinical

Main Result

Relative Risk: 0.88 (95% CI 0.8–0.96)

Absolute Event Rate: 8.1% vs 9.3%

Absolute Risk Reduction: 1.2%

Number Needed to Treat: 90

p-value: p=0.004

More intensive LDL-C-lowering statin-based therapies reduce the risk of recurrent stroke and MACE in patients with a history of stroke, particularly those with evidence of atherosclerosis, though they may increase the risk of hemorrhagic stroke.

Limitations

The purpose of several included trials was not primarily to evaluate more intensive vs less intensive LDL-C-lowering therapies for patients with ischemic stroke.
Sample sizes varied significantly among the included trials, with some having fewer than 200 patients.
The included trials mostly represented high-income countries, and it is unknown whether the benefits generalize to Asian populations where some trials showed no reduction in recurrent stroke risk.
Purpose of several included trials was not primarily to evaluate intensive vs less intensive therapies for stroke patients (used subgroups)
Sample sizes varied widely among trials
Trials mostly represented high-income countries, and benefits in Asian populations are uncertain

Cite This Study

Lee et al. (2022) conducted a meta-analysis in Ischemic stroke (n=20,163). More intensive LDL-C-lowering statin-based therapies vs. Less intensive LDL-C-lowering statin-based therapies was evaluated on Recurrent stroke (RR 0.88, 95% CI 0.80-0.96, p=0.004). More intensive LDL-C-lowering statin-based therapies reduced the risk of recurrent stroke by 12% (RR 0.88) compared with less intensive therapies in patients with a history of stroke.

synapsesocial.com/papers/6a1c7cc866d062ff2dc3de6f https://doi.org/10.1001/jamaneurol.2021.5578

Topics

Statin therapy Cardiovascular prevention

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Implication

Supports intensifying statin-based LDL-C lowering for secondary stroke prevention; confirms benefit and extends it to atherosclerotic subgroups.

Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Topics

Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Topics

Also Consider