Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: A retrospective cohort study in The Health Improvement Network

Christopher G. Rowan, Steven M. Brunelli, Jeffrey Munson, James Flory, Peter P. Reese, Sean Hennessy, James Lewis, Daniel Mines, Jeffrey S. Barrett, Warren Bilker, Brian L. Strom

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Objective: To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme. Background: Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism. Methods: Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score. Results: The median follow-up time per cohort was 1.5years. There were 7889 muscle toxicity events among 362809 patients and 792665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90-1.66). There were 1449 renal dysfunction events among 272,099 patients and 574584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58-1.44). There were 1434 hepatic dysfunction events among 367612 patients and 815945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45-1.31). Conclusions: Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy.

Original languageEnglish (US)
Pages (from-to)494-506
Number of pages13
JournalPharmacoepidemiology and drug safety
Volume21
Issue number5
DOIs
StatePublished - May 2012

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Pharmacology (medical)

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