New Data Support Safety Profiles of PCSK9 Inhibitors

Cholesterol-lowering drugs targeting the gene PCSK9 do not cause heart failure or other adverse cardiac events in humans despite an association found in a recent animal study, according to a report appearing in this week's JAMA Cardiology. PSCK9 encodes a protein that helps regulate cholesterol levels in the blood and has become a promising therapeutic target for hypercholesterolemia. While therapies that block PCSK9 expression have shown favorable safety profiles, a recent study in mice showed that PCSK9 deficiency caused cardiac remodeling and heart failure. To see if this effect translates to humans, researchers from the University of Copenhagen analyzed data from around 35,000 individuals within the UK Biobank, using genotyping and exome-sequencing data, common variants, and loss-of-function variants as proxies of PCSK9 inhibition. By combining the genetic data with cardiac magnetic resonance imaging data, the scientists determined that there are no associations between PCSK9 genetic variants and altered cardiac structure, cardiac function, or heart failure in humans. The results, they write, are "in line with safety data from the shorter-term trials that indicate that a partial to complete reduction of the PCSK9 protein in humans is unlikely to result in the severe phenotypes observed in model organisms.