More Preliminary Signs That PCSK9 Inhibitors May Improve Outcomes

By Larry Husten

Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD

PCSK9 inhibitors dramatically lower LDL cholesterol and may confer a mortality benefit, according to a meta-analysis in the Annals of Internal Medicine. The authors note that the findings should be interpreted with caution until longer studies are complete, however.

Researchers combined data from 24 phase 2 and 3 trials that included over 10,000 patients with hypercholesterolemia randomized to treatment with or without a PCSK9 inhibitor. PCSK9 inhibitors conferred a 55% reduction in mortality. However, absolute mortality rates were extremely low (0.31% with PCSK9 inhibitors vs. 0.53% among controls). There was a statistically significant reduction in myocardial infarction.

Overall, those treated with PCSK9 inhibitors had a 47% reduction in LDL cholesterol, relative to all controls. Compared with ezetimibe, PCSK9 inhibitors resulted in a 36% reduction in LDL.

Editorialists warn that the "included trials were of small or moderate size and mostly had short follow-up periods." In addition, "little is known about the long-term adverse effects of sustained PCSK9 inhibition, including neurocognitive outcomes and diabetes."