During the pandemic we were treated to a common, but curious site in traffic: A driver gliding by, alone in the car, windows up—wearing a mask. Like Covid was hiding in the glove compartment.

It’s tough to count the things that went wrong to make such a moment possible. For starters, masking during Covid wasn’t to protect the wearer. It was to protect people from the wearer. Masking alone, in a car, protects exactly no one. Also, research suggests that at best, masks probably do very little. To avoid Covid the best thing was (and is) an open air environment.

So maybe crack the windows, pal?

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And yet in some places driving a car alone, without a mask on, was illegal. During Covid even health authorities were selling crazy. But that doesn’t mean masks are always worthless. Any indoor setting with people in close proximity is a reasonable place to try masking. If it’s going to work, it’ll be there. But not alone in a car.

Context is everything.

The same is true for lowering cholesterol. For most people without heart disease lowering cholesterol is demonstrably silly, and more harmful than helpful. For people with heart disease and at ultra-high risk, however, it may be a perfectly reasonable addition, once everything else has been handled (BP control, aspirin, exercise, Mediterranean Diet, quitting smoking). But I’ve podcasted and written lots about the fruitlessness and harms of lowering cholesterol in anyone else, because recent studies have nailed the cholesterol coffin shut.

But last week a paper presented at the AHA’s annual meeting and published in the vaunted New England Journal of Medicine, “Evolocumab in Patients without a Previous Myocardial Infarction [heart attack] or Stroke,” found a ‘25% reduction’ in heart attacks, strokes, or cardiovascular deaths with cholesterol lowering.

So is it true? Did people without a prior heart attack or stroke benefit?

Sort of! Here’s how it worked. The study was run by the makers of evolocumab, a drug that massively lowers cholesterol, on average from 200 mg/dL to about 50 (way more powerful than statins). The trial compared the drug to a placebo in over 12,000 people. The catch? To get in the study participants had to have “coronary artery disease, atherosclerotic cerebrovascular disease, peripheral artery disease, or high-risk diabetes [i.e. with vascular disease].”

In other words, people with known heart and vascular disease. That’s a very high risk group. But even that risk wasn’t high enough to get in. The participants were also “required to have at least one additional criterion that placed them at higher risk.” Plus, they had to have high (or “very elevated”) cholesterol levels.

This is strange: The title is clearly intended to sound like ‘primary prevention’, treatment to prevent a first heart problem. ‘Secondary prevention’ is for second (or third or fourth) heart problems. That’s an easier target (it’s harder to reduce heart problems in people who rarely have them). But secondary prevention in ultra-high risk people is the only thing evolocumab (and its class) has ever worked for. Even then the benefit is tiny and the drug doesn't save lives.

Thus it’s technically correct that the study participants were ‘without a previous MI or stroke’. But it’s a lot like saying crocodile-wranglers are people without a previous crocodile bite. Technically true. But I too have, so far, avoided being bitten by a crocodile. And yet I’m not quite ready to purchase crocodile bite insurance. The wranglers, on the other hand, might want to look in to it.

Predictably, the study participants receiving the drug (painful, twice-monthly shots) didn’t live any longer than those who didn’t. But 1 in every 56 of them, or less than 2%, avoided a (nonfatal) heart attack. Pretty much exactly what earlier studies—all of which openly admitted to being secondary prevention—showed.

So, nothing new here: The drugs had a tiny effect and didn’t save lives for secondary prevention.

Why did the NEJM allow the company to title the study in such a misleading way? Two reasons. First: marketing. The AHA press releases, cardiology news splashes, and Medpage headlines. Good press, and lots of clicks for the Journal. Better yet, the drug company will now buy millions of dollars worth of reprints from the New England Journal of Medicine. Reprints are glossy paper versions of the title-page or full study, handed out by attractive drug company representatives who bring lunch (and pens and chotchkes) to doctors’ offices. The reps brim with confidence that few if any doctors will read past the title or summary.

Reason two: FDA approval. Impossibly, the FDA apparently didn’t read past the title. The drug is now approved for use in primary prevention, based on this trial of clear secondary prevention. The FDA, in a move as dumb as buying croc-bite insurance, or wearing a mask alone in a car, fell hook and sinker for the company’s and the journal’s title.

The drug costs about $7,000 per year and the company will see a windfall. So, too, will the New England Journal of Medicine. The co-dependent ecosystem of journal and drug company wins again.

And we can add Repatha (the drug’s brand name) to our list: Masking in the car, croc-bite insurance, and Repatha for primary prevention.

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