Improving Cardiovascular Outcomes with Precision Medicine

Dalcetrapib is an investigational therapy that would potentially  be the first pharmacogenomic precision medicine in cardiovascular disease to reduce cardiovascular risk.

Dalcetrapib, while under development by Roche, was evaluated in a Phase 3, double-blind clinical trial, dal-OUTCOMES. The dal-OUTCOMES trial randomized over 15,000 patients with recent acute coronary syndrome (ACS) to investigate the efficacy of dalcetrapib in the prevention of future cardiovascular events. Dalcetrapib was well tolerated but demonstrated no efficacy in the overall patient population.

In 2012, investigators at the Montreal Heart Institute led by Prof. Jean-Claude Tardif and Marie-Pierre Dubé found a significant association between the effects of dalcetrapib in altering cardiovascular events and the allelic polymorphism at the rs1967309 location in the adenylate cyclase type 9 (ADCY9) gene.

The retrospective analysis of 5,749 patients found those with an AA polymorphism had a 39% decline in cardiovascular events (dalcetrapib compared to placebo), while GG had a 27% increase, and GA had a neutral effect, in the cohort of dal-OUTCOMES patients.

Approximately 20% of all patients presenting with CVD have the ADCY9 rs1967309 AA genotype and might gain protection from cardiovascular events with the treatment of dalcetrapib.