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Evidence summaries

Statin Treatment for Cardiovascular Events in Patients with Coronary Heart Disease and Abnormal Liver Tests

Statin treatment may reduce cardiovascular morbidity and even improve liver tests in coronary heart disease patients with mild-to-moderately abnormal liver tests at baseline (up to 3 times the upper limit of normal) that are potentially attributable to non-alcoholic fatty liver disease. Level of evidence: "C"

A post-hoc analysis of the GREACE study population 1 examined statin treatment in participants with mild-to-moderately abnormal liver tests (ALT or AST of less than 3 times the upper limit of normal). GREACE was a prospective study that randomly assigned patients with coronary heart disease (aged< 75 years, with serum concentrations of LDLcholesterol > 2.6 mmol/L and triglycerides< 4.5 mmol/L; 78% were men) to receive statin (n=800) and to usual care (n=800), which could include statins. The primary outcome of the post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients with normal liver tests.

Mild-to-moderate increases in serum concentrations were noted in 437 of 1 600 patients assessed at baseline (before statin treatment initiation). 396 (91%) of these patients had metabolic syndrome or diabetes mellitus; the remaining 41 patients were lean and did not have metabolic syndrome or type 2 diabetes mellitus, but had high triglyceride concentrations or blood pressure rates (i.e. two of the components of metabolic syndrome). Overall, 396 (56%) of 712 patients with metabolic syndrome and 222 (71%) of 313 patients with diabetes mellitus had abnormal liver tests and non-alcoholic fatty liver disease (NAFLD). Of the 437 patients with abnormal liver tests at baseline, 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.

Fewer patients with abnormal liver tests who received a statin had cardiovascular events than did patients who did not receive a statin (22/227, 10%, 3.2 events per 100 patient-years vs. 63/210, 30%, 10.0 events per 100 patient-years; 68% relative risk reduction, p<0.0001). This benefit was greater (p=0.0074) than that reported for patients treated with a statin who had normal liver tests compared with untreated patients (90/653, 14%, 4.6 events per 100 patient-years vs. 117/510, 23%, 7.6 events per 100 patient-years; 39% relative risk reduction, p<0.0001).

Ten of 880 participants (1.1%) who received a statin had raised ALT or AST concentrations of more than 3 times the upper limit of normal. In 3 of these 10 participants, liver tests were normalised by dose reduction of atorvastatin from 80 mg per day (in 2 patients) and 40 mg per day (in 1 patient) to 10 mg per day. Thus, seven (<1%) of 880 patients were withdrawn fromthe study because of liver-related adverse effects attributed to statin treatment.

Comment: The quality of evidence is downgraded by study quality (violation of randomization in the post hoc analysis).

    References

    • Athyros VG, Tziomalos K, Gossios TD, Griva T, Anagnostis P, Kargiotis K, Pagourelias ED, Theocharidou E, Karagiannis A, Mikhailidis DP, GREACE Study Collaborative Group. 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. Lancet 2010 Dec 4;376(9756):1916-22. [PubMed]

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