High-dose atorvastatin is superior to moderate-dose simvastatin in preventing peripheral arterial disease
Open accessAbstract
Objectives: To study whether high-dose versus usual-dose statin treatment reduces the incidence of peripheral artery disease (PAD) and what is the effect of high-dose statin treatment on cardiovascular disease (CVD) outcome in patients with PAD. Methods and results: In the Incremental Decrease in End Points Through Aggressive Lipid Lowering trial, 8888 post-myocardial infarction patients were randomised to high-dose or usual-dose statin therapy (atorvastatin 80 mg/day vs simvastatin 20–40 mg/day). We investigated the effect of high-dose versus usual-dose statins on the pre-specified outcome PAD incidence, and additionally performed a posthoc analysis of the efficacy of high-dose statins in reducing CVD risk among patients with PAD. During a median follow-up of 4.8 years, 94 patients (2.2%) receiving atorvastatin and 135 patients (3.2%) receiving simvastatin developed PAD (HR=0.70, 95% CI 0.53 to 0.91; p=0.007). The risk of major coronary events was almost twofold higher in patients with PAD at baseline, but was no longer significant after adjusting for the adverse cardiovascular risk profile. In PAD patients, major coronary events occurred in fewer patients in the atorvastatin group (14.4%) than in the simvastatin group (20.1%), but the difference did not reach statistical significance. (HR=0.68, 95% CI 0.41 to 1.11; p=0.13). Atorvastatin treatment significantly reduced overall cardiovascular (p=0.046) and coronary events (p=0.004), and coronary revascularisation (p=0.007) in these patients. Conclusions: High-dose statin therapy with atorvastatin significantly reduced the incidence of PAD compared with usual-dose statin therapy with simvastatin. Patients with a history of PAD at baseline were at higher risk of future coronary events and this risk was reduced by high-dose atorvastatin treatment. Trial registration number: NCT00159835 (URL: http://clinicaltrials.gov/show/NCT00159835).
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Patients with peripheral arterial disease who have a coronary artery disease history are at extremely high risk for total mortality and fatal cardiovascular events.
“Patients with PAD who have a CAD history are at extremely high risk for total mortality and fatal cardiovascular events761–767).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [765]
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- Stoekenbroek RM, et al. Heart 2015;101:356-362. doi:10.1136/heartjnl-2014-306906 361 Coronary artery disease Protected by copyright, including for uses related to text and data mining, AI training, and similar technologies. . at Universiteit van Amsterdam on November 10, 2025 http://heart.bmj.com/ Downloaded from 16 January 2015. · DOI
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- Authors
- Stoekenbroek, R. M., Boekholdt, S. M., Fayyad, R., Laskey, R., Tikkanen, M. J., Pedersen, T. R., & Hovingh, G. K.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Pfizer (United States) (US)
- Helsinki University Hospital (FI)
- Oslo University Hospital (NO)
- Corresponding author
- Stoekenbroek, Robert M
- Venue
- Heart
- Publisher
- BMJ
- Published
- 2015-01-16
- Volume
- 101
- Issue
- 5
- Pages
- 356-362
- ISSN
- 1355-6037 (ISSN-L)
- 1468-201X
- OpenAlex
- W2104365808
- Cited by
- 44
- References
- 25
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 5 · 2018: 4 · 2017: 7 · 2016: 8 · 2015: 2
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- Locations
- Heart (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Amgen
- Pfizer
- AstraZeneca
- Sanofi
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91612122)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- atorvastatin, simvastatin, high-intensity statin therapy, peripheral arterial disease, statin dose comparison, post-infarction patients, cardiovascular risk reduction, coronary events, coronary revascularization
- MeSH terms
- Atorvastatin, Aged, Dose-Response Relationship, Drug, Female, Heptanoic Acids, Humans, Cholesterol, LDL, Male, Middle Aged, Myocardial Infarction, Myocardial Revascularization, Netherlands, Prospective Studies, Pyrroles, Scandinavian and Nordic Countries, Incidence, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Peripheral Arterial Disease
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