Coronary artery disease is still the world’s number-one killer.

That’s despite statins, PCSK9 inhibitors, stents, bypasses, and decades of lifestyle messaging.

We’ve gotten better at managing heart attacks, but we haven’t cured heart disease. Or prevented it. Or even figured out exactly what causes it.

As an internist and lipidologist (in recovery), I spent years chasing cholesterol numbers, especially HDL. I gave talks for Abbott. I pushed niacin like it was salvation. Then came the AIM-HIGH and HPS2-THRIVE trials—and the crash of the HDL hypothesis. CETP inhibitors raised HDL spectacularly and did nothing to lower events. Billions were spent, and patients still died.

We pivoted to Lp(a), the latest villain in the lipid storyline. Drugs are already in development. But we’ve skipped an important step: proving that lowering Lp(a) saves lives. Just like we skipped that step with HDL. Again, pharma is leading with marketing instead of medicine.

Meanwhile, compelling evidence linking Chlamydia pneumoniae—a common respiratory pathogen—to atherosclerosis has been largely ignored. Back in the ’90s, researchers like Dr. J. Thomas Grayston and Dr. Allan Shor showed C. pneumoniae inside plaques. Electron microscopy confirmed the organism within macrophages and smooth muscle cells. It was there, at the scene of the crime.

But lipidology had already claimed the narrative. And the idea that heart disease might be infectious didn’t fit the model—or the business plan.

Trials using short-course antibiotics in older patients failed, but they were doomed from the start. No one treats tuberculosis or HIV with monotherapy in late-stage disease and expects success. So why would we expect azithromycin alone to reverse decades of vascular scarring?

We’ve seen this before. TB, leprosy, syphilis—chronic inflammatory diseases once misunderstood, now known to be infectious. Why not atherosclerosis?

I’m proposing a new trial: TACTIC. It would enroll younger patients with early coronary disease (positive CAC or CCTA), and treat them with a three-drug combo to hit C. pneumoniae across all life stages. The outcomes? Measured not by death or MI, but by change in plaque burden via serial CCTA.

It’s not a sexy model. It’s not a billion-dollar molecule. But it might actually work.

The problem? No one wants to fund it. There’s no money in curing heart disease with a few old antibiotics. But there’s a fortune in creating chronic Lp(a)-lowering injectables for millions.

The science is there. The parallels are there. The will? That’s what’s missing.

I’m not saying statins don’t help. I’m saying we’ve built an entire cardiology empire on treating markers, not mechanisms. And if we don’t look seriously at the infectious hypothesis, we may spend another 50 years pretending we don’t know what’s causing heart disease.

Maybe we’ve known all along.

Larry Kaskel is an internal medicine physician and lipidologist.