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Published on: January 18, 2018
More Than 50 Percent Reduction in LDL Cholesterol in Patients With Target LDL <70 mg/dL After a Stroke
Pierre Amarenco1,2, Philippa C Lavallée1, Jong S Kim3
1APHP, Department of Neurology and Stroke Center, Bichat Hospital, INSERM LVTS-U1148, DHU FIRE, University of Paris, France (P.A., P.C.L., H.C., E.M.).
Insights
Achieving a greater than 50% reduction in low-density lipoprotein (LDL) cholesterol is key for the <70 mg/dL target to effectively reduce cardiovascular events. A reduction below 50% did not show significant benefits.
Area of Science:
- Cardiology
- Neurology
- Clinical Trials
Background:
- Investigating the optimal strategy for lowering low-density lipoprotein (LDL) cholesterol in patients with atherosclerotic disease.
- The effectiveness of targeting LDL cholesterol <70 mg/dL based on the percentage of reduction from baseline was previously unexamined.
Purpose of the Study:
- To determine if a target LDL cholesterol of <70 mg/dL is more effective when LDL is reduced by >50% versus <50% from baseline.
- To analyze the impact of LDL cholesterol reduction magnitude on cardiovascular outcomes in the Treat Stroke to Target (TST) trial.
Main Methods:
- A post hoc analysis of the TST trial involving 2860 patients with ischemic stroke or transient ischemic attack and atherosclerosis.
- Patients were randomized to target LDL cholesterol levels of <70 mg/dL or 100±10 mg/dL, with lipid-lowering therapy adjusted as needed.
- Cox regression was used to analyze the primary outcome (composite of ischemic stroke, myocardial infarction, urgent revascularization, vascular death) considering lipid-lowering therapy as a time-varying variable.
Main Results:
- In the <70 mg/dL target group, patients achieving >50% LDL reduction had significantly lower primary outcome events (HR, 0.61; P=0.007) compared to the higher target group.
- Patients in the <70 mg/dL target group with <50% LDL reduction showed no significant benefit (HR, 0.96; P=0.75).
- Patients with >50% LDL reduction had higher baseline LDL and achieved lower LDL levels (62 mg/dL) compared to those with <50% reduction (74 mg/dL) (P<0.001).
Conclusions:
- Targeting LDL cholesterol <70 mg/dL is beneficial for reducing cardiovascular events, but only when LDL reduction from baseline exceeds 50%.
- The magnitude of LDL cholesterol reduction is as critical as the target level itself in mitigating cardiovascular risk.
- These findings underscore the importance of aggressive lipid-lowering therapy in high-risk patients.
Background:
Whether a strategy to target an LDL (low-density lipoprotein) cholesterol <70 mg/dL is more effective when LDL is reduced >50% from baseline rather than <50% from baseline has not been investigated.
Methods:
The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of <70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2-6] per patient) during 3.9 years (interquartile range, 2.1-6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event.
Results:
Among 2860 patients enrolled, patients in the lower target group who had >50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had <50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, P<0.001 for both). In the <70 mg/dL target group, patients with >50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43-0.88]; P=0.007) and patients with <50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73-1.26]; P=0.75).
Conclusions:
In this post hoc analysis of the TST trial, targeting an LDL cholesterol of <70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve.
Registration:
URL: https://www.
Clinicaltrials:
gov; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.
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