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Rethinking the JUPITER trial and statin safety

Larry Kaskel, MD
Conditions
October 2, 2025
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We have all been told the story: High cholesterol leads to heart disease, and statins are the magic bullet. The JUPITER trial, published in The New England Journal of Medicine in 2008, became one of the most heavily publicized pieces of “proof” supporting that belief. It claimed that rosuvastatin significantly reduced heart attacks, strokes, and cardiovascular events, even in people with normal LDL cholesterol levels.

But what if I told you that more people died of heart attacks in the rosuvastatin group than in the placebo group?

You will not find this fact highlighted in the abstract or the conclusion. But if you dig through Table 3, and do some simple math, here is what you discover:

  • In the rosuvastatin group, there were thirty-one total MIs, of which twenty-two were nonfatal.
  • In the placebo group, there were sixty-eight total MIs, of which sixty-two were nonfatal.

Do the subtraction, and you are left with: nine fatal MIs in the statin group. Six fatal MIs in the placebo group.

That is a fifty percent increase in fatal heart attacks in the group taking a drug designed to prevent them.

Let that sink in.

This was not a fluke hidden deep in the weeds. It was observable, but ignored. Instead, we were given shiny relative risk reductions (“forty-four percent fewer heart attacks!”) and dramatic early termination of the trial to further inflate the effect size. But what actually matters (real, irreversible outcomes like death) told a very different story.

It is easy to manipulate perception when you combine fatal and nonfatal outcomes into one “composite endpoint.” It is even easier when you stop the trial early, before long-term safety signals emerge. And it becomes nearly impossible to detect harm when the medical community unquestioningly accepts the headline and moves on.

Statins may lower LDL. But the assumption that LDL is the root cause of heart disease is an outdated theory built more on correlation than causation. And if a cholesterol-lowering drug leads to more fatal heart attacks (even as it reduces nonfatal ones), what are we really celebrating?

This is not about being anti-statin. It is about being pro-truth.

As physicians, we owe it to our patients to ask hard questions and demand honest data. A fifty percent increase in fatal heart attacks in the treatment group should not be buried in a table or inferred from subtraction. It should be a headline. And it should make us pause before blindly prescribing.

The JUPITER trial did not prove what we think it proved. But it did reveal something else: how easy it is to shape a narrative when no one looks too closely.

Larry Kaskel is an internist and “lipidologist in recovery” who has been practicing medicine for more than thirty-five years. He operates a concierge practice in the Chicago area and serves on the teaching faculty at the Northwestern University Feinberg School of Medicine. In addition, he is affiliated with Northwestern Lake Forest Hospital.

Before podcasts entered mainstream culture, Dr. Kaskel hosted Lipid Luminations on ReachMD, where he produced a library of more than four hundred programs featuring leading voices in cardiology, lipidology, and preventive medicine.

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He is the author of Dr. Kaskel’s Living in Wellness, Volume One: Let Food Be Thy Medicine, works that combine evidence-based medical practice with accessible strategies for improving healthspan. His current projects focus on reevaluating the cholesterol hypothesis and investigating the infectious origins of atherosclerosis. More information is available at larrykaskel.com.

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Rethinking the JUPITER trial and statin safety
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