The Pharmacogenetics of Cardiovascular Drugs / FARMAKOGENETIKA KARDIOVASKULARNIH LEKOVA

Summary This article will primarily summarize the current knowledge of the pharmacogenetics of commonly used drugs for the cardiovascular system: oral anticoagulants, antiplatelet therapy and statins. Coumarin anticoagulants are widely used to treat and prevent thromboembolisms. Variations in the CYP2C9 and VKORC1 genes influence the pharmacodynamic response to coumarins. Genetic variation makes an important contribution to the variation in the response to clopidogrel, the most commonly prescribed antiplatelet treatment. Genetic polymorphisms in the CYP2C19 gene as in the paraoxonase 1 gene are associated with clopidogrel effectiveness and have shown an association with excess of ischemic events such as myocardial infarction and stent thrombosis, but also with serious threat of bleeding. Statin pharmacogenetics has the potential to improve the safety and effectiveness of lipid-lowering therapy by statins. Genetic variations in apolipoprotein E, cholesterol ester transfer protein, kinesin-like protein 6, statin transporter OATP1B1 etc. could partly explain the interindividual variation in statins therapeutic response and adverse reactions. Finally, we comment on the pharmacogenetics of other cardiovascular drugs that have been extensively studied, but for which data are conflicting or that have not yet seen clinical implementation. Based on the available data, it could be expected that in the future genome-tailored drug prescription and use of defined algorithms will contribute to the successful drug action, lowering the frequency of adverse events, and will have greater clinical relevance. Kratak sadržaj Ovaj rad će prvenstveno sumirati sa dašnja saznanja o farmakogenetici najčešće korišćenih kardiovaskularnih lekova i to oralne antikoagulantne i antiagregacione terapije i terapije statinima. Kumarini su antikoagulansi sa širokom primenom u lečenju i prevenciji tromboembolizma. Varijacije u CYP2C9 genu i genu za VKORC1 utiču na farmakodinamski odgovor na kumarine. Genetska varijabilnost značajno doprinosi varijabilnosti u odgovoru na klopidogrel, najčešće propisivanu antiagregacionu terapiju. Genetski polimorfizmi u genu za CIP2C19 i paraoksonazu 1 povezani su sa efektivnošću terapije, kao i sa pojavom ishemijskih događaja kao što su infarkt miokarda i tromboza stenta, ali i sa ozbiljnim rizikom od krvarenja. Farmakogenetika statina mogla bi značajno da doprinese poboljšanju efektivnosti terapije statinima, kao i smanjenju neželjenih efekata. Genska varijabilnost u apolipoproteinu E, proteinu koji transportuje holesterol estre, kinezinu sličnom proteinu 6, transporteru za statine OATP1B1 itd. može donekle da objasni interindividualne varijacije u odgovoru na terapiju statinima i pojavu ne že ljenih efekata. Na kraju, komentarisaćemo farmakogene tiku drugih kardiovaskularnih lekova koji su intenzivno proučavani, ali za koje su dobijeni kontradiktorni podaci ili za koje se još ne vidi jasno klinička primena. Na osnovu raspoloživih podataka, može se očekivati da će u budućnosti propisivanje lekova na osnovu genetike i korišćenje definisanih algoritama doprineti boljem delovanju leka, smanjenju učestalosti neželjenih reakcija na lek, kao i da će imati veći klinički značaj.