Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis
Abstract
Background Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population.Methods GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged <75 years, with serum concentrations of LDL cholesterol >2·6 mmol/L and triglycerides <4·5 mmol/L) at the Hippokration University Hospital, Thessaloniki, Greece to receive statin or usual care, which could include statins. The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests (defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal) compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients treated (or not) with statin and normal liver tests.Findings Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p<0·0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10%) of 227 patients with abnormal liver tests who received statin (3·2 events per 100 patient-years) and 63 (30%) of 210 patients with abnormal liver tests who did not receive statin (10·0 events per 100 patient-years; 68% relative risk reduction, p<0·0001). This cardiovascular disease benefit was greater (p=0·0074) than it was in patients with normal liver tests (90 [14%] events in 653 patients receiving a statin [4·6 per 100 patient-years] vs 117 [23%] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39% relative risk reduction, p<0·0001). Seven (<1%) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal).Interpretation Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease.Funding None.
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The safety of statins has been well established in individuals with MASLD with no increased risk of hepatotoxicity.
“The safety of statins has been well established in individuals with MASLD 389,390 with no increased risk of hepatotoxicity”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [389]
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- Authors
- Athyros, V. G., Tziomalos, K., Gossios, T. D., Griva, T., Anagnostis, P., Kargiotis, K., Pagourelias, E. D., Theocharidou, E., Karagiannis, A., & Mikhailidis, D. P.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Ippokrateio General Hospital of Thessaloniki (GR)
- The Royal Free Hospital (GB)
- Corresponding author
- Mikhailidis, Dimitri P
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 376
- Issue
- 9756
- Pages
- 1916-1922
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2128460332
- Cited by
- 685
- References
- 31
- Citations by year
- 2026: 21 · 2025: 26 · 2024: 34 · 2023: 40 · 2022: 34 · 2021: 44 · 2020: 34 · 2019: 36 · 2018: 40 · 2017: 27 · 2016: 47 · 2015: 50 · 2014: 78 · 2013: 72 · 2012: 53
- FWCI
- 58.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- statin therapy, atorvastatin, coronary artery disease, elevated alanine aminotransferase, aspartate aminotransferase, non-alcoholic fatty liver disease, cardiovascular events, recurrent cardiovascular events, statin safety, elderly patients, LDL cholesterol, triglycerides, liver enzymes, cardiovascular risk reduction
- MeSH terms
- Aged, Cardiovascular Diseases, Coronary Disease, Fatty Liver, Female, Greece, Humans, Liver Function Tests, Male, Middle Aged, Prospective Studies, Recurrence, Time Factors, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Risk Reduction Behavior, Non-alcoholic Fatty Liver Disease
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