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Welcome to the European Society of Cardiology. Our mission: to reduce the burden of cardiovascular disease in Europe
 

‘HDL is Probably the Future of Therapy’ 

Topics: Cardiovascular Disease Prevention - Risk Assessment and Management
Date: 02 Sep 2008
The next era of pharmaceutical prevention in cardiovascular disease is likely to be based on the HDL molecule, said Professor Jacques Genest (McGill University, Montreal, Canada) at a press conference yesterday. “HDL, the good cholesterol, is probably the future of therapy,” he proposed.

He said he did not expect to see any further statins; and although another class of drugs, the PCSK9 inhibitors, will come online in the next four or five years, they act in a similar way to statins.

However, before HDL-raising drugs can be made available, important and basic questions need to be answered. Genest said: “Epidemiologically, the higher the HDL, the better, but we still have not shown conclusively that modifying HDL with drugs decreases cardiovascular risk. It moves in the right direction but we still need large clinical trials and, given the burden of cardiovascular disease in every society, we’d better get this right before we start treating patients.”

Genetic studies such as the Copenhagen Heart Study apparently contradict the epidemiology. It found that patients with a genetic defect (ABCA1 mutation) associated with very low HDL levels did not have an increased cardiovascular risk. “The challenge for us now is to harness this knowledge into clinical medicine,” Genest said.

Research into HDL was set back by data presented at the ESC Congress last year. The ILLUMINATE trial found that the CETP inhibitor torcetrapib increased HDL levels and improved lipid profile, but also increased CV events and mortality.

Conclusion Despite this, other CETP inhibitors are currently being tested in clinical trials. A second approach to raising HDL levels is to harness its early formation via the transporter that makes cholesterol (ABCA1), said Genest. A third is to increase transcriptional regulation of its main protein (apo A1). “All of these molecules are in early clinical development and it will be the clinical trial which will have the last say,” Genest concluded.

Authors: Helen Saul