Canadian researchers find that dalcetrapib could be used as personalised therapy for cardiovascular disease

Researchers at the Montreal Heart Institute in Canada have discovered that patients with cardiovascular disease and the appropriate genetic background benefit greatly from a new medication called dalcetrapib, which has shown a reduction of 39% in combined clinical outcomes including heart attacks, strokes, unstable angina, coronary revascularisations and cardiovascular deaths.

These patients also benefited from a reduction in the amount of atherosclerosis (thickened walls) in their vessels.

The results are published in the journal Circulation Cardiovascular Genetics.

The researchers says this discovery may pave the way for a new era in cardiovascular medicine, with personalised or precision drugs.

The team led by Jean-Claude Tardif and Marie-Pierre Dube analysed 5,749 patients who received dalcetrapib or placebo and provided DNA in a clinical study.

A strong association was discovered between the effects of dalcetrapib and a specific gene called ADCY9 (adenylate cyclase 9) on chromosome 16, particularly for a specific genetic variant (rs1967309). In patients with the genetic profile AA at rs1967309, there was a 39% reduction in the composite cardiovascular endpoint with dalcetrapib compared with placebo.

These results will lead to a genetics-guided clinical study in patients with the appropriate genetic background to allow review by health regulatory agencies and to provide personalised therapy with dalcetrapib

Supporting evidence was also obtained from a second study, which showed that patients with the favourable genetic profile also benefited from a reduction in the thickness of their carotid artery walls with dalcetrapib.

'These results will lead to a genetics-guided clinical study in patients with the appropriate genetic background to allow review by health regulatory agencies and to provide personalised therapy with dalcetrapib,' said lead investigator Jean-Claude Tardif, Director of the Research Center at the Montreal Heart Institute and Professor of Medicine at the University of Montreal.

'It also offers great hope for precision treatments for patients with cardiovascular diseases and for curbing atherosclerosis, the first cause of mortality in the world.'

The researchers tested multiple genetic markers across the entire genome in a genome-wide association study.

'We used state-of-the-art genetic and statistical techniques to demonstrate that the effect of the patient's genetic profile was only observed in those treated with dalcetrapib and not placebo,' said Marie-Pierre Dube, Director of the Beaulieu-Saucier Pharmacogenomics Center at the Montreal Heart Institute and Professor of Medicine at the University of Montreal.

'We want to provide patients with additional personalised cardiovascular therapies in the years to come, for more efficacious and safer medicines.'