Improving Cardiovascular Outcomes with Precision Medicine
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.
The frequency of the ADCY9 AA genotype is up to 20% in the total population and is higher than 40% in populations with African descent. These patients might gain protection from future myocardial infarction (MI) with dalcetrapib treatment.