It was mid-2015 and I knew I was in trouble as soon as I walked into my doc’s office – he was grinning from ear to ear and waving a piece of drug company propaganda at me.
“The FDA’s approved a new miracle drug!” he boomed, “And it’s just right for you!”
I rolled my eyes and read the leaflet, and to my surprise there were several ways in which this new drug might actually be a miracle drug. In the first place, it was quite a scientific feat to invent the thing. Unlike statins, which take a blunderbuss approach, mucking around in the liver and reducing cholesterol levels across the board, these new drugs worked very differently.
The so-called PCSK9 inhibitors, herein referred to as “P-inhibitors,” target LDL cholesterol with great precision, mimicking a rare genetic disorder that prevents the body from manufacturing LDL.
The second “miracle drug” aspect of this new compound was that it reduced LDL to preposterous levels – to levels never before observed in normal human populations.
Of course, we might unkindly ask why anyone would want to do such a thing. LDL levels in human (and animal) populations have evolved for tens of thousands of years, as has the relative level of LDL to HDL.
Moreover, we know that LDL plays an important role in human health. LDL is actually a lipoprotein, a carrier protein, and among its jobs is to transport an important chemical to every cell in the body. This chemical is a critical component of cell membranes, is a brain antioxidant, and is the raw material from which we make vitamin D, estrogen, testosterone, progesterone, and cortisol. What is this amazing chemical? That’s right, cholesterol. And here’s a not-so-random factoid for you: 50% of the human brain, by dry weight, consists of cholesterol. I don’t know about you, but I’m rather attached to my few remaining brain cells and am not interested in having them reduced. (There is plenty of evidence that long-term statin use causes malfunctions in the brain.)
I suppose it might be worth the chance of playing God if virtually eliminating LDL also eliminated heart attacks. But that was just the problem.
“Pretty nifty,” I said to my doc, having finished reading the drug company propaganda. “But this doesn’t say anything about preventing heart attacks or reducing deaths.”
My doc waived this away. “Everyone knows,” he said, “that LDL causes heart attacks. Eliminate LDL and we eliminate heart disease! Us cardiologists will be out of work! Of course,” he added soto voce, elbowing me in the ribs, “by that time I’ll be safely retired.” The Heart Cholesterol Hypothesis was obviously alive and well, despite the many drubbings it had taken.
Fortunately, it turned out that I wasn’t the only skeptic. In a sudden attack of common sense, the health insurance industry flat out refused to pay for the P-inhibitors. The entire medical establishment was outraged, but the insurers stuck to their guns. “We’re not in the lowering-LDL business,” said the insurers, “we’re in the saving-lives business.”
This put the drug companies in an awkward position. They’d spent a decade and several hundred million dollars producing the drug, and now not one single patient would ever take it! The companies’ stock prices would collapse, the CEOs and chief medical officers would get sacked, other drug companies would laugh up their sleeves!
Of course, none of this could be allowed to happen, so the drug companies took a deep breath and doubled down. They funded an expensive study designed to demonstrate once and for all what every medical scientist already knew – that if you reduced LDL to trace levels in the human body it would be impossible for a heart attack to occur.
Two years later I innocently returned to my docs’ office and my heart sank. He was grinning again and – knowing of my allergy to drug company propaganda – this time he was waving around a breathless article from the New York Times. “Just as I predicted!” he boomed. “This stuff is a miracle drug!”
I sighed and read through the article. The reporter basically copied the drug company’s press release, quoting a bunch of muckety-muck medical scientists to the effect that P-inhibitors had created “a whole new ballgame,” that “heart troubles will soon be a thing of the past,” blah, blah, blah.
Fortunately, being something of an aficionado of puff pieces masquerading as journalism (I mean, what the hell else is a blog?), I was able to ferret out a couple of clues. The first clue was the sort that hits you over the head like a sledgehammer – if you could only find it. It was buried way down in the middle of paragraph nine, read by me and probably eight other people in the entire world. But it was a doozy: “[The P-inhibitor] did not show a benefit in overall death rates from cardiovascular causes.”
Whaaa?? The drug that was supposed to eliminate heart disease, the one that costs $15,000, the one that you have to take for the rest of your life, didn’t save a single life?
Nope. Here’s the actual data: Number of deaths in the placebo group: 426 Number of deaths among people taking the P-inhibitor: 444
And I ferreted out a second clue as well. The Times reporter pointed out that the reduction in heart “events” (some of them extremely minor) was 15%. But of course that was the relative reduction. The absolute reduction – the one we patients care about – was a bit over 1% for heart attacks and bit under ½ of 1% for strokes.
So let’s say it again – we have to inject ourselves every other week for the rest of our lives, at a cost of $15,000/year, to achieve a 1% reduction in heart “events?” Oh – and no one knows what the long-term consequences of shooting ourselves up with this powerful drug might be. Can these people be serious?
And one final clue. On the day the results of the drug trial were announced, pompous quotes by muckety-mucks notwithstanding, the drug company’s stock price dropped 6%. The New York Times might have been impressed by the results, and the medical establishment was certainly impressed, but the people who had to put their money where their mouths were were distinctly unimpressed.
Given the dismal results of the study, and the extravagant cost of these drugs, I naturally assumed that the health insurers would fall down laughing and that we would never have to hear any more about P-inhibitors.
Not so. Astonishingly, the insurers decided to pay for the drug! How can this possibly be? We’ll find out next week.
Next up: Why We Don’t Take Our Meds (Again), Part 8