Cardiovascular Pharmacogenetics
This chapter will apply the principles and concepts introduced in the "Pharmacogenetics and Pharmacogenomics" chapter in volume 2, namely, discussion of four classes of genetic variants that underlie drug response to cardiovascular agents: (1) pharmacokinetic, (2) pharmacodynamics, (3) underlying disease process, and (4) off-target effects. Where appropriate, we will also discuss the application of pharmacogenetics to cardiovascular medicine. We will review major findings for the main medications used in cardiovascular medicine: antiplatelets, anticoagulants, and statins. The first description of genetic variation underlying the response to warfarin in 1964 where O'Reilly identified members of a family who required remarkably high warfarin doses of 145. mg/day, 20 times the average dose, for therapeutic anticoagulation. Since this inaugural study, cardiovascular pharmacogenetics has become a mainstay research discipline.