Endocrine Abstracts

Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalising cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolised on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19.

We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidaemic patients (age 61.3±9.9 years) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in five patients (4.95%); clinical hypothyroidism in two and hyperthyroidism in three cases. 11patients had a positive history for hypothyroidism (10.9%). There were no significant differences in the TSH, fT₄ and fT₃ levels between patients with myopathy and patients with other adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other adverse effects (P<0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs 38%, NS), while significantly less patients with myopathy were on fluvastatin treatment (13% vs 33%, P<0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP3A4, 2C9 and 2C19 are common in our patients with statin induced adverse effects. Normalising the thyroid hormone status and optimising of the concomitant medication may reduce the risk of statin induced adverse effects.