Bacterial pneumonia, once a leading killer of the old and the very young, is caused by (duh) bacteria. If you kill the bacteria, the pneumonia goes away. It doesn’t really matter how you kill the bacteria, either. If a patient is allergic to one drug that kills the bacteria, a doctor can prescribe a different drug that kills the bacteria and – bingo! – the pneumonia goes away. Why?
BECAUSE THE PNEUMONIA IS CAUSED BY THE BACTERIA, FOR PETE’S SAKE!
And how do we know that?
BECAUSE IF WE KILL THE BACTERIA, THE PNEUMONIA GOES AWAY, FOR PETE’S SAKE!
Okay, but let’s suppose we kill the bacteria we believe causes the pneumonia, but the pneumonia remains and the patient dies. And let’s suppose this happens with multiple patients. Then what would we conclude?
IF KILLING THE BACTERIA DOESN’T MAKE THE PNEUMONIA GO AWAY, THEN THE PNEUMONIA ISN’T CAUSED BY THE BACTERIA, FOR PETE’S SAKE! WHAT ARE YOU, AN IDIOT?
No, I’m just pointing out some basic logic here. If we kill the bacteria but the pneumonia remains, we have to conclude that while a bacterial infection may be associated with pneumonia, it isn’t the cause. That’s what we’d expect any honest scientist to say.
But strangely, this basic logic seems to escape researchers when a cholesterol-lowering drug fails to prevent heart attacks. Here are some quotes from a New York Times article:
It is a drug that reduces levels of LDL cholesterol, the dangerous kind, as much as statins do. And it more than doubles levels of HDL cholesterol, the good kind, which is linked to protection from heart disease.
That’s the Lipid Hypothesis in a nutshell: LDL is dangerous. It causes heart disease — just like that nasty bacteria causes bacterial pneumonia. HDL, meanwhile, protects against heart disease.
As a result, heart experts had high hopes for it as an alternative for the many patients who cannot or will not take statins.
Everybody sing: “Oh, we’ve got hiiiigh hopes. Yes, we’ve got hiiiigh hopes …”
But these specialists were stunned by the results of a study of 12,000 patients, announced on Sunday at the American College of Cardiology’s annual meeting: There was no benefit from taking the drug, evacetrapib.
No benefit? But LDL causes heart disease! Did the drug fail to lower the LDL that causes heart disease?
Participants taking the drug saw their LDL levels fall to an average of 55 milligrams per deciliter from 84. Their HDL levels rose to an average of 104 milligram per deciliter from 46.
Well now, that is an amazing improvement in lipids. The American Heart Association would be delighted with those numbers … although strangely, I can’t find recommended LDL levels on the AHA site anymore. Perhaps they hired the former KGB artists who used to make people disappear from official photos once they became an embarrassment to the Kremlin. Anyway …
Yet 256 participants had heart attacks, compared with 255 patients in the group who were taking a placebo.
In other words, no difference. A total fail.
“We had an agent that seemed to do all the right things,” said Dr. Stephen J. Nicholls, the study’s principal investigator and the deputy director of the South Australian Health and Medical Research Institute in Adelaide.
Yup. If high cholesterol – and specifically high LDL – causes heart disease, then you did indeed have an agent that seemed to do all the right things.
“It’s the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?” he said, referring to the 37 percent drop in LDL levels with the drug.
Boy, that’s a real head-scratcher. Let me think for a minute … uh … uh … perhaps the fact that two things are associated doesn’t mean one is causing the other? I seem to recall a good scientist or two saying as much.
“All of us would have put money on it,” said Dr. Peter Libby, a Harvard cardiologist. The drug, he said, “was the great hope.”
And how are those Enron shares working for ya?
Researchers have hypotheses, but no one is certain what went wrong. “It may be that the LDL level is less important than how it gets changed,” said Dr. Paul Thompson, a cardiologist at Hartford Hospital.
Ah, yes, that must be it. LDL causes heart disease, ya see, but lowering LDL only works if you do it exactly the right way. And if you have bacterial pneumonia, it’s not wiping out the bacteria that cures you; it’s how you kill them. Kill them the wrong way, and you’ll still have pneumonia … even though bacteria cause the pneumonia.
Here’s an alternate hypothesis about why the latest study was a big, fat fail:
LDL DOESN’T CAUSE HEART DISEASE, FOR PETE’S SAKE!
That would be the most logical conclusion: we beat people’s LDL levels down, but they didn’t have fewer heart attacks. So LDL doesn’t cause heart disease. But beating cholesterol levels down is a $36 billion per year (and climbing) business. So we’re getting the illogical conclusion instead:
Cardiologists still have high hopes for a new class of cholesterol drugs, known as PCSK-9 inhibitors, that cause LDL to plummet to levels never seen in drug treatments.
Try to wrap your head around that one: in a multi-year study of 12,000 people, dramatically lowering LDL levels didn’t prevent heart disease. But cardiologists have high hopes for a new class of drugs that lower LDL levels EVEN MORE!
Everybody sing: “Oh, we’ve got hiiiigh hopes. Yes, we’ve got hiiiigh hopes …”
And here’s the reason for those high hopes:
The PCSK-9 inhibitors can cost more than $14,000 a year …
Fourteen grand per patient, per year, year in and year out. Yeah, that would generate a lot of hope.
… while statins can cost just pennies a day, so determining what portion of patients are truly statin intolerant has become an important question.
Yeah, about that “statin intolerant” problem: funny how research funded by drug companies is starting to demonstrate a real problem with statins isn’t it? In one of his many great posts, Dr. Malcolm Kendrick predicted this would happen:
For years the experts have informed us that this is utter rubbish, statins are wonder-drugs, and adverse effect free. All of a sudden, now that the pharmaceutical industry is about to launch new cholesterol lowering agents, we are suddenly going to find that, why, after all, statins do cause a whole range of nasty adverse effects.
I watch this stuff with a kind of morbid fascination. The marketing game is on, billions are about to be spent pushing PCSK9-inhibitors. The Key Opinion Leaders who tirelessly promoted the wonders of statins, and who told us that they were virtually side-effect free, are now singing a completely different tune.
Sure enough, a big ol’ study just concluded that lots and lots of people have real problems with statins. The study was led by Dr. Steve Nissen, one of the long-time pimps for — er, promoters of statins. Returning to the New York Times article:
A second study presented at the cardiology meeting on Sunday and published online in JAMA, the Journal of the American Medical Association revealed just how vexing the issue is.
The study, directed by Dr. Nissen and paid for by Amgen, a pharmaceutical company, included more than 500 people with extremely high levels of LDL cholesterol who had tried two or more statins and had reported aching or weak muscles so severe that they said they absolutely could not continue taking the drugs.
[The result] indicated that 57 percent of patients actually could tolerate statins. Researchers then randomly assigned the remaining 43 percent to take either Amgen’s PCSK-9 inhibitor, evolocumab, or another cholesterol-lowering drug, ezetimibe, which is often taken by statin intolerant patients but has never been shown to reduce heart disease risk when taken without an accompanying statin. The patients tolerated both drugs.
My, my, my … statins go off patent (thus reducing the cost to just pennies per day), and through sheer coincidence, we get a major new study showing that nearly half of all people can’t tolerate statins – but they can tolerate the new drug that costs $14,000 per year.
And of course, we know this new and very expensive drug will prevent heart attacks because it lowers LDL. High LDL cholesterol causes heart disease, ya see. We’ll just continue believing that even when a drug that dramatically lowers LDL fails to prevent heart attacks.
Perhaps someday, after yet another LDL-lowering drug fails to prevent heart attacks, researchers will respond by going before the cameras and announcing that it’s time to bury the Lipid Hypothesis once and for all.
But I don’t have high hopes.