Why Lowering Inflammation Markers May Not Prevent Heart
Quick Facts
Why Can an Inflammation Drug Lower Biomarkers but Not Prevent Heart Attacks?
Atherosclerosis is not simply cholesterol accumulating inside arteries. Immune cells, inflammatory proteins, blood clotting and changes in the vessel wall all contribute to plaque growth and rupture. High-sensitivity C-reactive protein, or hsCRP, can identify increased inflammatory activity, but it is primarily a risk marker rather than proof that a particular drug will prevent cardiovascular events.
Ziltivekimab is a monoclonal antibody designed to inhibit interleukin-6 signaling. In the randomized phase 2 RESCUE trial, it produced substantial reductions in hsCRP and several other inflammatory and clotting-related biomarkers among people with chronic kidney disease and elevated inflammation. However, biomarker improvement must be followed by adequately powered trials measuring outcomes such as myocardial infarction, stroke and cardiovascular death. According to STAT’s report, the newer heart disease study missed its objective; complete peer-reviewed results will be needed to understand why.
What Has Earlier Research Shown About Treating Cardiovascular Inflammation?
The CANTOS trial provided important evidence that inflammation can be therapeutically targeted in atherosclerosis. It enrolled 10,061 people with a previous myocardial infarction and persistently elevated hsCRP. Canakinumab, an antibody targeting interleukin-1 beta, reduced recurrent cardiovascular events at one tested dose without lowering cholesterol, supporting a causal role for inflammation.
CANTOS also identified an increased risk of fatal infection, demonstrating why suppressing inflammation requires careful safety assessment. Trials of low-dose colchicine have provided additional evidence of cardiovascular benefit in selected patients with coronary disease. These findings do not mean that every anti-inflammatory medicine will work: different drugs affect different immune pathways, and excessive immune suppression may outweigh a modest cardiovascular benefit.
How Should Patients Interpret a Negative Cardiovascular Drug Trial?
Clinical trials can fail because a drug does not sufficiently change disease biology, because patients were treated too early or too late, or because adverse effects offset potential benefits. Investigators must also determine whether participants had the specific inflammatory profile most likely to respond and whether background treatments left enough residual risk for an additional therapy to show value.
Patients should not stop statins, blood-pressure medicines, antiplatelet therapy or other prescribed treatments because of this result. Controlling LDL cholesterol, blood pressure, diabetes and tobacco exposure remains central to cardiovascular prevention. Anti-inflammatory treatment is an evolving addition to those measures, not a substitute for therapies with established clinical benefits.
Frequently Asked Questions
Not necessarily. CRP can rise because of infection, injury and many chronic conditions. Cardiovascular decisions require clinical context, and most anti-inflammatory drugs are not routinely prescribed solely because hsCRP is elevated.
No. Nonsteroidal anti-inflammatory drugs such as ibuprofen are not cardiovascular-prevention treatments and can increase cardiovascular, kidney or bleeding risks in some people.
No. CANTOS and colchicine trials support inflammation as a contributor to cardiovascular disease. The reported result instead suggests that success depends on selecting an effective target, an appropriate patient population and a tolerable treatment.
References
- STAT. Novo Nordisk inflammation-targeting drug misses mark in heart disease study. August 2026.
- Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine. 2017;377:1119-1131.
- Ridker PM, Devalaraja M, Baeres FMM, et al. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. The Lancet. 2021;397:2060-2069.
- Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. New England Journal of Medicine. 2020;383:1838-1847.