The impact of pharmacogenetics testing on the efficacy and safety of rosuvastatin and atorvastatin lipid-lowering therapy in patients with high and very high cardiovascular risk

BACKGROUND. Atherosclerosis is the most common cause of cardiovascular diseases, leading to early disability and high mortality among the population of developed countries. Lipidemia control is the cornerstone of prevention and treatment of atherosclerosis complications. Meanwhile, adherence to statin treatment is critically low. One of the reasons of the low compliance is the fear of side effects. The safety and possibly the effectiveness of treatment with various statin drugs depend on the genetic characteristics of their metabolism.

THE AIM: to determine the benefits of pharmacogenetic research in the appointment of therapy with atorvastatin and rosuvastatin in patients with high and very high cardiovascular risk.

PATIENTS AND METHODS. A prospective study involving 2 groups of similar age, gender, and cardiovascular risk. The study group consisted of 43 patients each (47.9±10 years old, 67 % men), for whom pharmacogenetic study data were taken into account when prescribing or correcting statin therapy. The control group consisted of 43 patients (46.9± 11 years old, 70 % men) who were prescribed statins in accordance with the clinical recommendations, but did not take into account the genetic characteristics of metabolism. Both groups were followed for 12 months with an interval of 3 months. At each point, the following items were assessed: adverse cardiovascular events; the fact that LDL-C targets were reached, the presence of statin-associated adverse symptoms, and treatment adherence.

RESULTS. Normal function of SLCO1B1, ABCG2, and CYP2C9 was detected in 25 patients (58.1 %), delayed function in 15 subjects (34.8 %), and slow metabolism of rosuvastatin and atorvastatin in 3 patients (7.0 %). The frequency of achievement of LDL-C targets did not differ between the study and control groups (p>0.05), the proportion of cardiovascular events was higher in patients in the control group (the frequency of reaching the composite endpoint: 7 % and 20.9 %, respectively). However, the initial proportion of these events in the control was also higher, which does not allow us to draw unambiguous conclusions. Statin-associated muscle symptoms (SAMS) were significantly less common in study group patients than in the control (1 case (7 %) versus 9 cases (20.9 %), p=0.015), which corresponded to an 89 % reduction in relative risk. Compliance with statin therapy was low and amounted to 30 % in the study group and 25.6 % in the control group (p>0.05).

CONCLUSIONS. Pharmacogenetic testing of patients before prescribing statins can significantly reduce the risk of developing ACS.

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