Volume 187 - Issue 4
Potential link between HMG-CoA reductase inhibitor (statin) use and interstitial lung disease
Authors: Beatrice A Golomb and Marcella A Evans
Med J Aust 2007; 187 (4): 253-253. || doi: 10.5694/j.1326-5377.2007.tb01223.x
Published online: 20 August 2007
Published online: 20 August 2007
To the Editor: Walker and colleagues recently reported a series of patients with interstitial pneumonitis following use of statin cholesterol-lowering drugs.1 They state that other investigators have previously reported biopsy findings resembling amiodarone-induced pulmonary toxicity in pneumonitis associated with statin therapy. We believe this observation is pivotal to understanding the authors’ findings.
Amiodarone produces mitochondrial toxicity, which is recognised to be a potential initiating event in amiodarone-induced pulmonary toxicity.2 Statins also produce mitochondrial toxicity in vulnerable individuals. Adverse effects of statins on muscle have been linked to mitochondrial abnormalities,3 and other clinical manifestations of statin mitochondrial toxicity have been reported.
Mitochondrial respiratory chain disease is famously protean in its manifestations, but most classically produces a mitochondrial encephalomyopathy — with muscle, brain, or both affected. Consistent with this, muscle and cognitive symptoms are the most widely reported adverse effects in our reporting database of statin adverse effects (comprising 2478 patients to date), and these symptoms frequently occur together, consistent with a common mechanism.
Statin–amiodarone combinations have produced heightened toxicity relative to each agent alone. Interference with cytochrome P450 metabolism has been the presumed mechanism,4 but additive or synergistic mitochondrial toxicity may also be a factor.
The occurrence of amiodarone-like interstitial pulmonary disease in statin users adds to concerns that a range of clinical presentations of mitochondrial toxicity may ultimately be reported with statins in susceptible individuals, with mitochondrial heteroplasmy and threshold effects determining the specific manifestations.5
Competing interests
The work we cite in this letter is funded by a Robert Wood Johnson Generalist Physician Faculty Award to Beatrice Golomb. The funding source had no role in study design, data collection, analysis and interpretation, or writing and publication of this letter.
References
- Walker T, McCaffery J, Steinfort C. Potential link between HMG-CoA reductase inhibitor (statin) use and interstitial lung disease. Med J Aust 2007; 186: 91-94.
- Bolt MW, Card JW, Racz WJ, et al. Disruption of mitochondrial function and cellular ATP levels by amiodarone and N-desethylamiodarone in initiation of amiodarone-induced pulmonary cytotoxicity. J Pharmacol Exp Ther 2001; 298: 1280-1289. 0_i1091822
- Phillips PS, Haas RH, Bannykh S, et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med 2002; 137: 581-585. 0_i1091824
- Alsheikh-Ali AA, Karas RH. Adverse events with concomitant amiodarone and statin therapy. Prev Cardiol 2005; 8: 95-97. 0_i1091826
- Fadic R, Johns DR. Clinical spectrum of mitochondrial diseases. Semin Neurol 1996; 16: 11-20. 0_i1091829