Genetic Variant Again Linked With Statin Side Effects

From Heartwire
Michael O’Riordan

October 13, 2009 (Durham, North Carolina) — Carriers of the reduced-function single nucleotide polymorphism (SNP) of the SLCO1B1 gene are at an increased risk of developing mild statin-induced side effects, including myopathy and myalgia, a new study has shown [1].

The risk of adverse events, however, was greatest among those treated with simvastatin and negligible in those assigned to pravastatin.

"We report that carriers of the SLCO1B1*5 allele are at a twofold relative risk of mild statin-induced side effects, the majority of which had normal [creatine kinase] CK levels," according to lead investigator Dr Deepak Voora (Duke University Medical Center, Durham, NC) and colleagues in the October 20, 2009 issue of the Journal of American College of Cardiology. "These results could have potential implications for clinical practice, because the vast majority of patients who are intolerant of statins have mild symptoms without associated CK elevations."

The results confirm a recent genomewide-association study by the SEARCH Collaborative Group, a study reported by heartwire . The SEARCH group identified a strong association between simvastatin-induced myopathy and two tightly linked variants in SLCO1B1, a gene that encodes for a protein involved in the transport of statins and other drugs from the blood into the liver.

In this most recent study, known as the Statin Response Examined by Genetic Haplotype Markers (STRENGTH) trial, 509 patients were randomized to treatment with atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg, with each increased to doses of 80 mg, 80 mg, and 40 mg, respectively. After 16 weeks of follow-up, 99 patients developed an adverse event, a composite end point that included 54 patients who discontinued therapy, 49 who developed myalgias, and nine who had CK elevations greater than three times the upper limit of normal.

The SLCO1B1*5 allele was associated with drug discontinuation, myalgia, and CK elevations. Importantly, statin-induced myalgia side effects also occurred in patients without CK elevations. The study also showed an association between female sex and adverse events among those receiving statin therapy.

In an editorial accompanying the study [2], Drs Joseph Rossi and Howard McLeod (Duke University Medical Center, Durham, NC) are optimistic that "genetic testing may someday become an important adjunct to risk stratification," but in the meantime it is reasonable to pick a statin based on drug interactions, particularly CYP450 interactions, and treatment goals. If a patient develops myalgias or CK elevation with simvastatin, changing agents may provide relief of symptoms, they add.