Lowering IL-6 or hsCRP-measured systemic inflammation reduces cardiovascular events regardless of the anti-inflammatory agent used

The claim is that lowering systemic inflammation, as measured by IL-6 or hsCRP, reduces cardiovascular events whatever drug does the lowering. Read this way, the biomarker is a valid surrogate across mechanisms. The trial record weighs against that.

Some agents that lower these markers do reduce events. Canakinumab, which blocks IL-1β, cut major adverse cardiovascular events by about 15% in CANTOS, and the benefit was concentrated in patients whose hsCRP or IL-6 fell. Low-dose colchicine reduced events in COLCOT and LoDoCo2. Other evidence breaks the link between the marker and the outcome. Colchicine lowered CRP but did not reduce events after myocardial infarction in CLEAR SYNERGY (OASIS 9). In the phase 3 ZEUS trial, which enrolled more than 6,300 patients with atherosclerotic disease, chronic kidney disease and raised inflammation, the IL-6 ligand inhibitor ziltivekimab did not reduce major adverse cardiovascular events compared with placebo (hazard ratio 0.99, 95% CI 0.88 to 1.11). Several other anti-inflammatory programmes, including darapladib, varespladib and losmapimod, also failed, although they did less to lower these markers, so they test the claim less directly.

Taken together, the benefit looks tied to particular pathways (IL-1β and NLRP3) or particular clinical settings, not to lowering the biomarker as such. A universal "regardless of agent" claim is undercut by a well-powered trial in which the markers fall and events do not, and ZEUS is such a trial. The ongoing ziltivekimab outcome trials (ARTEMIS, HERMES) and the full ZEUS publication would sharpen the judgment.