AHA 2026 Series | ZEUS is a reality check for anti-inflammatory drugs in heart disease

Inflammation plays an important role in cardiovascular disease. But can lowering inflammation actually prevent heart attacks and strokes?

The ZEUS trial tested ziltivekimab, a drug that blocks IL-6, an important driver of inflammation.

The results were striking:

• Inflammation marker hsCRP dropped 64%.

• Free IL-6 dropped 76%.

• Lp(a), a cholesterol-related risk factor, dropped 29%.

But here is the surprising part.

Despite these impressive changes, the drug did NOT reduce heart attacks, strokes, or cardiovascular deaths.

Among 6,376 patients with existing cardiovascular disease, kidney disease, and high inflammation:

• Major cardiovascular events: 17.6% vs 17.7%

• No meaningful reduction in cardiovascular death or overall mortality.

There were also more serious infections in patients receiving the drug (20.4% vs 17.9%).

What can we learn?

Lowering inflammation markers does not necessarily mean fewer heart attacks.

Improving a laboratory result is not the same as improving a patient's health.

Timing may matter. These patients already had advanced cardiovascular and kidney disease.

Even Lp(a) fell by 29%, but cardiovascular events did not decrease.

Does this mean inflammation does not matter? No.

CANTOS, COLCOT, and LoDoCo2 have already shown that some anti-inflammatory treatments can reduce cardiovascular events.

At the end of the day, we need fewer heart attacks and strokes, not just better laboratory numbers.