Dalcetrapib for ischaemic heart disease?

Clement Loh Chee Hoou, Faculty of Medicine, University of New South Wales, Sydney, Australia

High density lipoprotein (HDL), or ‘good cholesterol’, is an apoprotein containing-lipid particle that plays a vital role in reverse cholesterol transport by removing cholesterol deposits from both intravascular and extravascular tissues and transporting it back to the liver for excretion or re-utilization(1, 2). In conventional medical wisdom, elevated levels of high-density lipoproteins (HDL) translate into lower risk of atherosclerosis and ischaemic heart disease. However, it remains unknown if raising serum levels of HDL has a direct therapeutic effect on reducing the future risk of a coronary event.

In a recent study published by Schwartz et al., it was hypothesized that using dalcetrabip, which is a cholesteryl ester transfer protein (CETP) inhibitor that raises the serum levels of HDL, may have a direct effect on improving cardiovascular outcomes.15781 patients with recent acute coronary syndrome were recruited and randomised to receive either a single dose of 600mg dalcetrabip daily or placebo. The primary endpoint was a composite of: death from a coronary event, nonfatal myocardial infarction, ischaemic stroke, unstable angina, or cardiac arrest with resuscitation(3).

At 31 months of follow-up, HDL levels increased by 31-40% in the dalceitrabip group and by 4-11% in the placebo group. For the 1135 primary endpoint events that occurred, an interim analysis found that dalcetrabip did not significantly alter the risk of suffering from a future coronary event as compared to placebo (cumulative event rate of 8.3% and 8.0% respectively). The administration of dalcetrabip had minimal effects on the serum levels of LDL cholesterol, C-reactive protein levels and mean systolic blood pressure levels(3).

Therefore, the use of dalcetrabip in patients with recent acute coronary syndrome was efficacious in elevating serum levels of HDL, but did not result in a significant reduction of the risk of a recurrent coronary event.

References: 

1. Hall JE. Guyton's Medical Physiology. 12th ed. New York: Saunder Elsevier; 2011.
2. Miller NE. HDL metabolism and its role in lipid transport. Eur Heart J. 1990;11 Suppl H:1-3. doi: 10.1093/eurheartj/11.suppl_H.1
3. Schwartz, G.G., Olsson, A.G., Abt, M., Ballantyne, C.M., Barter, P.J., Brumm, J., Chaitman, B.R., Holme, I.M., Kallend, D., Leiter, L.A., Leitersdorf, E., McMurray, J.J.V., Mundl, H., Nicholls, S.J., Shah, P.K., Tardif, J.-C., Wright, R.S. Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome. N. Engl. J. Med 2012. doi: 10.1056/NEJMoa1206797

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