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).
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