After ACS, hsCRP predicted events independently of IL-6; IL-6 did not

Design

Post hoc biomarker analysis of a randomised trial (ODYSSEY OUTCOMES)

Population

11,817 patients after recent ACS on optimised statin therapy

Primary outcome

Major adverse cardiovascular events and all-cause death

Effect

hsCRP independent predictor of MACE (P<0.0001), IL-6 not (P=0.21); both predicted death

This post hoc analysis of ODYSSEY OUTCOMES (alirocumab versus placebo after recent acute coronary syndrome, on optimised statins) measured both high-sensitivity CRP and interleukin-6 at baseline in 11,817 patients. During follow-up 1,306 had a major adverse cardiovascular event and 458 died.

The two markers correlated only moderately (r = 0.52). With each adjusted for the other and for LDL, diabetes and other factors, hsCRP independently predicted major events (P < 0.0001) while IL-6 did not (P = 0.21). Both independently predicted death. Splitting at 2 mg/L and 5 pg/mL, risk rose clearly only when both were raised. Alirocumab did not change these relationships.

IL-6 is the target of several anti-inflammatory drugs now in cardiovascular trials, so the question of which marker to measure is becoming practical. For now, hsCRP is cheap, standardised and widely available, and this analysis suggests it carries the inflammatory risk information that matters for events.

• Consider measuring hsCRP after ACS, once the acute phase has passed, as a marker of residual inflammatory risk.
• A raised hsCRP above 2 mg/L on a statin flags risk not explained by LDL alone.
• IL-6 testing adds prognostic information on death but not on cardiovascular events beyond hsCRP.
• Risk was clearly higher only when both markers were raised, not when one alone was.
• Use these markers for risk conversations, not yet to select an anti-inflammatory drug.

Why it matters

As IL-6-targeting drugs approach cardiology, this suggests the cheaper test already carries most of the signal.

Don't overread it

This is a post hoc prognostic analysis; it does not show that lowering either marker improves outcomes.

The statistics, in plain English

A P value of 0.21 for IL-6 means that once hsCRP was in the model, IL-6 added no reliable information about events. The correlation of 0.52 means the two markers overlap but are not interchangeable.

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