Improving Cardiovascular Outcomes with Precision Medicine

Dalcetrapib is a unique cholesterol ester transfer protein (CETP) inhibitor, a class of drugs that has been investigated as therapeutics to reduce the risk of cardiovascular events in more than 100,000 patients in over 100 clinical trials.

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 CV events and the allelic polymorphism at the rs1967309 location in the adenylate cyclase type 9 (ADCY9) gene.

Patients with an AA polymorphism had a 39% decline in CV events (dalcetrapib compared to placebo), while GG had a 27% increase, and GA had a neutral effect, in the cohort of dal-Outcomes patients. This retrospective analysis was conducted in 5,749 patients.

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