Is the drug industry honest?

You have probably heard or read about the recent trial named FOURIER where the drug company Amgen has tested a new cholesterol-lowering drug named Evolocumab (a so-called PCSK9-inhibitor) on almost 30,000 patients with heart disease. Half of them got the drug injected twice a month; the other half was injected with an innocent liquid (probably saltwater)., and both groups received statin treatment as well. The “bad” LDL-cholesterol was lowered by 59%; from 92 mg/dl (2.4 mmol/l) to 30 mg/dl (0.78 mmol/l). Very few cholesterol-lowering trials have succeeded with that before.

But what about the outcome? If high LDL-cholesterol is the bad guy – haven´t such low values eradicated all types of cardiovascular disease?

According to the trial report published in New England Journal of Medicine Evolocumab was able to lower the number of various types of heart 1.5 %. As the trial went on for 26 months, it means that to prevent one heart attack per year it is necessary to treat 140 patients. As the costs for one year´s treatment is about $14,500 it means that the costs for preventing one heart attack per year is more than two million dollars. And remember that most heart attacks may heal with few sequels or none at all.

The trial was originally planned to go on for 4 years, but as the number of heart events was significantly lower in the treatment group already after 26 months, the authors decided to stop the trial.

But the number of deaths, both from heart disease and from other causes, had increased! Not with statistically significance, but it might have become significant if the trial had continued. A relevant question is therefore: Did they stop the trial because the total number of events had become significantly lower in the treatment group, or because the number of deaths was increasing?

How do they explain that 444 died in the treatment group, but only 426 among the untreated? I mean, if the “bad” high LDL-cholesterol was the cause of atherosclerosis and heart disease, then we should expect that a 59% lowering of this “poisonous” molecule should lower mortality, not increase it.

The reason is of course that a high level of LDL-cholesterol is not poisonous; it is beneficial, as we have documented in a recent paper published in BMJ Open You can read more about our findings in my June 2016 Newsletter. One of the most interesting findings was that elderly people with the highest LDL-cholesterol levels lived longer than elderly people on statin treatment. A reasonable question is therefore: Why should we lower the bad cholesterol if those with the highest values live the longest?

But our findings haven´t made any impression on the directors of the FOURIER trial. Their conclusion is that “patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets”.

There are also reasons for questioning the beneficial results in the FOURIER trial. According to the paper´s disclosure form three of the main authors (Narimon Honarpour, Thomas Liu and Scott Wasserman) are employees at Amgen, the producer of the drug. All of the others have been paid by Amgen and by other drug companies as well; five of them, including the main author, by more than ten different companies. And in a previous paper you can read that Charles H. Hennekens, head of the trial´s “Independent Data Monitoring Committee” has served on the speaker’s bureaus for AstraZeneca concerning lipids and heart failure, and Bristol-Myers Squibb, Reliant, and Pfizer, concerning lipids; that he has received royalties for authorship or editorship of 3 textbooks; and that he has received royalties as co-inventor on patents concerning inflammatory markers and cardiovascular disease.

Our BMJ Open-paper did not make any impression either on other ”authorities”. Here is what Rory Collins, head of the Cholesterol Treatment Trialists’ (CTT) Collaboration in Oxford, and the main author of the paper we criticized said to the science journalist Michael Brooks in the 11 February issue of New Scientist:

”Those who deny a link (between cholesterol and cardiovascular disease) are talking complete nonsense. The few people who have raised the question are a bit like those individuals who think homeopathy works or think Earth is flat.”

And in the same issue Liam Smeeth at the London School of Hygiene and Tropical Medicine agrees: “I’m all for proper debate, providing the people I’m debating with are not denying science.”

But hitherto none of them have presented any study showing the opposite of our findings. Who are denying science?

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