Statin-associated rhabdomyolysis: is there a dose-response relationship?

Abstract

BACKGROUND:

Statins have a well-established role in prevention of vascular events but are associated with muscle-related adverse events. The dose relationship with these adverse events is unclear. We present an original analysis of Canadian and US case reports of statin-associated rhabdomyolysis with a focus on dose response. A typical clinical case is also summarized.

METHODS:

All cases of statin-associated rhabdomyolysis reported to Health Canada's Canadian Vigilance Program and to the US Food and Drug Administration's Adverse Event Reporting System from 2004-2008 were analyzed by severity and dose equivalence. Canadian national statin utilization data from 2002-2007 were used to estimate the dose-related incidence of rhabdomyolysis corrected for levels of utilization.

RESULTS:

The clinical case illustrates well the potential severity of statin-induced rhabdomyolysis. Combined Canadian/US data revealed an average of 812 cases of statin-induced rhabdomyolysis reported annually with a mean patient age of 64.4 years (35.5% female). The worst outcomes reported were renal dysfunction in 17.0%, acute renal failure in 19.8%, dialysis in 5.2%, and death in 7.6%. Using 10 mg atorvastatin per day as the reference dose, the odds ratios of rhabdomyolysis were 3.8 (95% CI 2.3-6.6) for 40 mg/day atorvastatin dose equivalent and 11.3 (95% CI 6.4-20.4) for 80 mg/day atorvastatin dose equivalent.

CONCLUSIONS:

The results of our adverse drug analysis suggest a dose-response relationship. Given the widespread use of statins, the ability to predict which patients will experience serious muscle-related harm is a research priority.

• Authors: Anne Holbrook, Mitchell Wright, Melani Sung, Christine Ribic, Steven Baker
• Journal: The Canadian journal of cardiology (Can J Cardiol) 2011 Mar-Apr Vol. 27 Issue 2 Pg. 146-51 ISSN: 1916-7075 [Electronic] England
• PMID: 21459261 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2011. Published by Elsevier Inc.

Chemical References

• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Pyrroles
• Atorvastatin

Topics

• Atorvastatin
• Dose-Response Relationship, Drug
• Dyslipidemias (drug therapy)
• Follow-Up Studies
• Heptanoic Acids (administration & dosage, adverse effects)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, adverse effects)
• Male
• Middle Aged
• Pyrroles (administration & dosage, adverse effects)
• Retrospective Studies
• Rhabdomyolysis (chemically induced)