PCSK9 inhibitors – past, present and future

Written just as PCSK9 inhibitors were arriving, this short editorial is a snapshot of a drug class at its hopeful, unproven dawn.

The author traces the path from the discovery of the PCSK9 gene to the first approved antibodies, alirocumab and evolocumab, summarizing their striking power: LDL reductions of 40–72%, good tolerability even at very low LDL levels, and clear promise for statin-intolerant and very-high-risk patients. The candid caveat, accurate for 2015, is that the cardiovascular outcome trials hadn’t reported yet, and cost loomed as a barrier.

The practical takeaway, read in hindsight, is a marker of where the field stood before FOURIER and ODYSSEY OUTCOMES confirmed the benefit. The status-quo tension it names — costly injectable biologics challenging cheap oral statins — has played out largely as predicted.

We rate the evidence low: a brief editorial by a credentialed expert (with disclosed Sanofi ties) before the outcome data existed, with no systematic method. Its clinical significance is higher and was subsequently validated — PCSK9 inhibitors did prove to reduce events — so this reads now as an early, correct bet rather than established proof at the time.