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. 2018 Jun 28:3:e83-e89.
doi: 10.5114/amsad.2018.76826. eCollection 2018.

Personalized rosuvastatin therapy in problem patients with partial statin intolerance

Aleksandr B Shek  1 , Ravshanbek D Kurbanov  1 , Rano B Alieva  1 , Guzal J Abdullaeva  1 , Aleksandr V Nagay  1 , Alisher A Abdullaev  2 , Shavkat U Hoshimov  1 , Ulugbek I Nizamov  1
Affiliations

Personalized rosuvastatin therapy in problem patients with partial statin intolerance

Aleksandr B Shek et al. Arch Med Sci Atheroscler Dis. .

Abstract

Introduction: The aim was to study the pharmacogenetic determinants of switching simvastatin-intolerant ethnic Uzbek patients with coronary artery disease (CAD) to rosuvastatin treatment.

Material and methods: The study included 50 patients with CAD, who demonstrated statin-induced adverse liver symptoms, accompanied by an elevation in transaminase level (3-fold or more in 37 cases) or statin-induced adverse muscle symptoms, accompanied by elevations in serum (CK > 3 times above the upper limit of normal (ULN)) in simvastatin treatment with a dose of 10-20 mg/day. The control group consisted of 50 patients without side effects. Patients were genotyped for polymorphisms in the genes coding for the cytochrome P450 (CYP) metabolic enzymes CYP3A5(6986A>G), CYP2C9(430C>T), CYP2C9(1075A>C), and hepatic influx and efflux transporters SLCO1B1(521T>C) and BCRP(ABCG2, 421C>A) by means of the PCR-RFLP method.

Results: When the 50 patients of the case group were switched to the starting rosuvastatin dose of 5 mg, intolerance symptoms were not observed in 29 (58%) versus 21 with adverse symptoms. In this case-control study, the groups differed significantly only in the prevalence of the *3/*3 genotype CYP3A5 (OR = 5.25; 95% CI: 1.6-17.8; p = 0.014).

Conclusions: In a considerable proportion of ethnic Uzbek patients with CAD and simvastatin intolerance symptoms, serious side effects when switching to a starting dose of rosuvastatin were not observed, and it should be noted that in most cases (72.4%) this phenomenon was observed among the carriers of *3/*3 genotype of the CYP3A5 (6986A> G) gene.

Keywords: genetic determinants; personalized rosuvastatin therapy; statin intolerance.

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Conflict of interest statement

The authors declare no conflict of interest.

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