β-Blocker pharmacogenetics in heart failure

Abstract

Abstractβ-Blockers (metoprolol, bisoprolol, and carvedilol) are a cornerstone of heart failure (HF) treatment. However, it is well recognized that responses to a β-blocker are variable among patients with HF. Numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to a β-blocker, including left ventricular ejection fraction improvement, survival, and hospitalization due to HF exacerbation. This review summarizes the pharmacogenetic data for β-blockers in patients with HF and discusses the potential implications of β-blocker pharmacogenetics for HF patients.

Pharmacogenetics and Cardiovascular Disease—Implications for Personalized Medicine

“…The pharmacokinetics of these drugs are clearly affected based on CYP2D6 genotype; however, there is less evidence for differences in efficacy or side effects (Fukami et al, 2004;Terra et al, 2005b;Dorn, 2009;Shin and Johnson 2010;Lu 2011;Chan et al, 2012b). This is most likely attributed to the fact that patients on b-blockers typically undergo dose titration to a heart rate ,60 beats/min, thus minimizing the impact of pharmacokinetic differences.…”

Modeling the Effects ofβ1-Adrenergic Receptor Blockers and Polymorphisms on Cardiac Myocyte Ca2+Handling

“…Genetic differences among patients also impact b-blocker efficacy (Shin and Johnson, 2010). Patients with the b 1 -Arg389 variant have a better prognosis after b-blocker administration compared with patients with the b 1 -Gly389 polymorphism.…”

β-Arrestin-Mediated Signaling Improves the Efficacy of Therapeutics

“…Carvedilol is a non-selective β-blocker / α 1 -blocker, and it is widely used for the treatment of mild to moderate congestive heart failure (18). Recent studies on carvedilol indicate that it activates cardioprotective signaling through β-adrenergic receptors, β-arrestin, and ERK1/2 activation.…”