Related Experiment Video
Updated: Jun 17, 2025
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Course of the effects of LDL-cholesterol reduction on cardiovascular risk over time: A meta-analysis of 60 randomized
Pascal M Burger1, Jannick A N Dorresteijn1, Stefan Koudstaal2
1Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands.
Insights
The long-term cardiovascular benefits of lowering low-density lipoprotein cholesterol (LDL-C) are stable in secondary prevention but may decrease with age in primary prevention. This finding is crucial for managing cardiovascular disease risk over time.
Area of Science:
- Cardiology
- Preventive Medicine
- Pharmacology
Background:
- Cardiovascular disease (CVD) management often involves long-term low-density lipoprotein cholesterol (LDL-C) lowering therapies.
- Uncertainty exists regarding the sustained efficacy of LDL-C reduction over extended treatment periods.
Purpose of the Study:
- To investigate the long-term course and stability of LDL-C reduction effects on cardiovascular risk.
- To analyze how follow-up duration and patient age influence the effectiveness of LDL-C lowering treatments.
Main Methods:
- Systematic review and meta-analysis of 60 randomized controlled trials (RCTs) involving LDL-C lowering therapies (statins, ezetimibe, PCSK9 inhibitors).
- Meta-regression analyses were used to assess the association between follow-up duration, age, and hazard ratios (HR) for major vascular events per 1 mmol/L LDL-C reduction.
- Individual participant data meta-analysis of atorvastatin trials was conducted to evaluate treatment-by-time interactions.
Main Results:
- A pooled analysis of 408,959 participants showed a significant reduction in major vascular events (HR 0.78 per 1 mmol/L LDL-C reduction).
- No significant association was found between follow-up duration and the HR for major vascular events (p=0.66).
- The HR for major vascular events attenuated with increasing age in primary prevention (p=0.003) but not in secondary prevention (p=0.63).
Conclusions:
- The relative treatment effects of LDL-C reduction are stable over time in secondary prevention based on available RCT data.
- In primary prevention, the efficacy of LDL-C reduction may diminish with increasing age.
- Further research with longer follow-up durations is warranted to fully elucidate long-term treatment effects.
Background And Aims:
Individuals with or at high risk of cardiovascular disease (CVD) often receive long-term treatment with low-density lipoprotein cholesterol (LDL-C) lowering therapies, but whether the effects of LDL-C reduction remain stable over time is uncertain. This study aimed to establish the course of the effects of LDL-C reduction on cardiovascular risk over time.
Methods:
Randomized controlled trials (RCTs) of LDL-C lowering therapies were identified through a search in MEDLINE and EMBASE (1966-January 2023). The primary analyses were restricted to statins, ezetimibe, and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, with other therapies included in sensitivity analyses. Random-effects meta-analyses were performed to establish the hazard ratio (HR) for major vascular events (cardiovascular death, myocardial infarction, unstable angina, coronary revascularization, or stroke) per 1 mmol/L LDL-C reduction. Course of the effects over time was assessed using random-effects meta-regression analyses for the association between follow-up duration, age, and the HR for major vascular events per 1 mmol/L LDL-C reduction. Additionally, treatment-by-time interactions were evaluated in an individual participant data meta-analysis of six atorvastatin trials.
Results:
A total of 60 RCTs were identified (408,959 participants, 51,425 major vascular events). The HR for major vascular events per 1 mmol/L LDL-C reduction was 0.78 (95 % confidence interval [CI] 0.75-0.81). Follow-up duration was not associated with a change in the HR for major vascular events (HR for change per year 0.994; 95 % CI 0.970-1.020; p = 0.66). The HR attenuated with increasing age in primary prevention (HR for change per 5 years 1.097; 95 % CI 1.031-1.168; p = 0.003), but not secondary prevention (HR for change per 5 years 0.987; 95 % CI 0.936-1.040; p = 0.63). Consistent results were found for statin trials only, and all trials combined. In the individual participant data meta-analysis (31,310 participants, 6734 major vascular events), the HR for major vascular events did not significantly change over follow-up time (HR for change per year 0.983; 95 % CI 0.943-1.025; p = 0.42), or age (HR for change per 5 years 1.022; 95 % CI 0.990-1.055; p = 0.18).
Conclusions:
Based on available RCT data with limited follow-up duration, the relative treatment effects of LDL-C reduction are stable over time in secondary prevention, but may attenuate with higher age in primary prevention.
More Related Videos
07:29Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
08:45LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
Published on: November 17, 2018
Related Concept Videos
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:18Lipids: Dietary Sources and Requirements
01:23Assessment of the Cardiovascular System I: Subjective Data
Initial Enquiry
Ask the patient about their primary concern and thoroughly explore all reported symptoms.
Medical History
Investigate past illnesses affecting the cardiovascular system, such as angina, anemia, rheumatic fever, congenital heart disease, stroke, thrombophlebitis, dysrhythmias, varicosities
Inquire about symptoms...
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...