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Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up
Open accessAbstract
Background: Patients with primary elevations of low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are at a higher risk of atherosclerotic cardiovascular disease as a result of long-term exposure to markedly elevated LDL-C levels. Therefore, initiation of statin therapy is recommended for these individuals. However, there is a lack of randomized trial evidence supporting these recommendations in primary prevention. In the present analysis, we provide hitherto unpublished data on the cardiovascular effects of LDL-C lowering among a primary prevention population with LDL-C ≥190 mg/dL. Methods: We aimed to assess the benefits of LDL-C lowering on cardiovascular outcomes among individuals with primary elevations of LDL-C ≥190 mg/dL without preexisting vascular disease at baseline. We performed post hoc analyses from the WOSCOPS (West of Scotland Coronary Prevention Study) randomized, placebo-controlled trial, and observational posttrial long-term follow-up, after excluding individuals with evidence of vascular disease at baseline. WOSCOPS enrolled 6595 men aged 45 to 64 years, who were randomly assigned to pravastatin 40 mg/d or placebo. In the present analyses, 5529 participants without evidence of vascular disease were included, stratified by LDL-C levels into those with LDL-C <190 mg/dL (n=2969; mean LDL-C 178±6 mg/dL) and those with LDL-C ≥190 mg/dL (n=2560; mean LDL-C 206±12 mg/dL). The effect of pravastatin versus placebo on coronary heart disease and major adverse cardiovascular events were assessed over the 4.9-year randomized controlled trial phase and on mortality outcomes over a total of 20 years of follow-up. Results: Among 5529 individuals without vascular disease, pravastatin reduced the risk of coronary heart disease by 27% ( P =0.002) and major adverse cardiovascular events by 25% ( P =0.004) consistently among those with and without LDL-C ≥190 mg/dL ( P -interaction >0.9). Among individuals with LDL-C ≥190 mg/dL, pravastatin reduced the risk of coronary heart disease by 27% ( P =0.033) and major adverse cardiovascular events by 25% ( P =0.037) during the initial trial phase and the risk of coronary heart disease death, cardiovascular death, and all-cause mortality by 28% ( P =0.020), 25% ( P =0.009), and 18% ( P =0.004), respectively, over a total of 20 years of follow-up. Conclusions: The present analyses provide robust novel evidence for the short- and long-term benefits of lowering LDL-C for the primary prevention of cardiovascular disease among individuals with primary elevations of LDL-C ≥190 mg/dL.
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“This graded approach is based on evidence from multiple meta-analyses and individual randomized controlled trials (RCTs), which show a consistent and graded reduction in ASCVD risk in response to reductions in TC and LDL-C levels (see Recommendations for cardiovascular disease risk estimation below) [31-41].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [40]
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Metadata
- Authors
- Vallejo-Vaz, A. J., Robertson, M., Catapano, A. L., Watts, G. F., Kastelein, J. J., Packard, C. J., Ford, I., & Ray, K. K.
- Affiliations
- Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, United Kingdom (A.J.V.-V., K.K.R.).
- University of Glasgow (GB)
- University of Milan (IT)
- The University of Western Australia (AU)
- Amsterdam UMC Location University of Amsterdam (NL)
- Imperial College London (GB)
- ORCID
- Venue
- Circulation
- Published
- 2017-11-14
- Volume
- 136
- Issue
- 20
- Pages
- 1878-1891
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2751778625
- Cited by
- 185
- References
- 33
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 14 · 2023: 19 · 2022: 20 · 2021: 20 · 2020: 23 · 2019: 25 · 2018: 38 · 2017: 6
- FWCI
- 25.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- LDL cholesterol lowering, primary prevention, hypercholesterolemia, pravastatin, statin therapy, coronary artery disease, major adverse cardiovascular events, cardiovascular mortality, atherosclerotic cardiovascular disease, WOSCOPS, men
- MeSH terms
- Anticholesteremic Agents, Cardiovascular Diseases, Coronary Disease, Follow-Up Studies, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Middle Aged, Primary Prevention, Scotland, Pravastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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