Tag Archives: Steven Nissen

A farewell to statins – part two

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And so it begins:

‘ …..a Pfizer rep confirmed to me that they were now telling all GP’s that statins do have side-effects and shouldn’t be prescribed anymore but to prescribe the new post-statin drugs…………. how two-faced can you get!!!!’

This was in an e-mail from a friend and supporter of mine, who has close contacts with the pharmaceutical industry.

Well, if you are going to challenge the dominant position of statins, the first thing that you have to do is to attack them. What is the best line of attack? Go after their greatest weakness, which is that they cause serious adverse effects, and damage the quality of life of many people. Something I have been saying for a long, long, time.

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.

If you want to see exactly how this is going to be done, watch this discussion on Medscape.  The Medscape site needs a password, however you can get one fairly simply. In this ‘educational’ discussion we see three professors talking about the new cholesterol lowering agents that are soon to arrive. The dreaded PCSK9-inhibitors.

The names of these three professors are Prof Christie Ballantyne, Prof Stephen Nicholls and – yes, you guessed it – Prof Steven Nissen. Is there a new cardiovascular drug in development that he does not get involved with?

The first part of the discussion focusses entirely on the terrible problem of people being statin intolerant; people being unable to take high doses of statins, and the high burden of adverse-effects from statins.

A slide is shown from the PRIMO observational study showing that 15% of people taking atorvastatin have significant adverse effects, and 20% of those taking simvastatin suffer significant adverse effects. These, of course, are the two statins with by far the greatest market share. My, what a coincidence.

The discussion then opens out into the worrying problems with statins causing both diabetes and cognitive dysfunction (something vehemently denied for many, many years). Ballantyne was particularly eloquent on these issues.

The entire tone is one more of sorrow than anger. ‘Statins….great drugs….hate to see them go, but you know, their time is passing.’ Professor wipes a small tear from his eye at the thought.

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.

Here is what one the panellists Prof Christie Ballantyne had to say about statin adverse effects in his book ‘Dyslipidemia & Atherosclerosis Essentials 2009’. This can be found on page 91, under the heading Adverse Effects and Monitoring.

‘Statins are very well tolerated with infrequent and reversible adverse effects. In large placebo controlled studies the frequency of adverse effects was similar to placebo (2-3%).’

Here, however, is what he said in March 2013

“Some people have hereditary disorders and have extremely high LDLs. And so the statin has some efficacy but not enough to get them down as low as they’d like.  Then some people have less response than others, and we don’t understand all of that. Some of that may be genetic. And it turns out there’s an even probably larger group of people that have a hard time taking a high dose of a statin.”

Even though statins are safe for most people, there are those that can’t take them because they experience side effects.

“Many people complain of some muscle pain, soreness, weakness, excessive fatigability.  There’s some slight increase in diabetes also. That can occur with high dose statins, and some people [who] say that they may have problems with their nerves or cognition.”1

Well, that is all nice and consistent. Finally, here he is on Sunday 8th Dec, quoted as part of a discussion on the new AHA/ACC guidelines.

“Clearly, the focus is to get people on statins,” said Dr. Christie Mitchell Ballantyne, the chief of cardiology and cardiovascular research at Baylor College of Medicine, in Houston. “But if someone has seen four doctors and tried six statins and tells me they can’t take them, what am I going to do? Tell them they are a failure?”

Ballantyne said he would give such patients a non-statin drug, despite the guidelines.’2

….Ballantyne said he would give such patients a non-statin drug, despite the guidelines.’ I wonder what he could possibly mean by this. Perhaps George Orwell had it right.

‘Four legs good, two legs bad’……becomes….’Four legs good, two legs better.’

“The creatures outside looked from pig to man, and from man to pig, and from pig to man again; but already it was impossible to say which was which.”

[A farewell to statins – Part three will arrive at some point.]

P.S. Please watch the video clip soon, as I suspect it may not last very long after this blog.

1: http://www.houstonpublicmedia.org/articles/1362665170-Promising-Baylor-Research-Reduces-Bad-Cholesterol.html

2: http://www.staradvertiser.com/news/20131114_New_cholesterol_advice_startles_even_some_doctors.html

A farewell to statins – part one

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In the end I knew that statins would be overthrown. Their time, like the dinosaurs would come to an end.  I also knew it would be nothing to do with me, or any of the other critics. Nor would it have anything to do with the fact that their terrible burden of adverse effects finally came to light.

No, it would be because their patents ran out, which meant that the big pharmaceutical companies could not make eye-watering profits from them anymore. Inevitably, therefore, they would be replaced. Indeed, for years I have watched, with varying degrees of amusement, the unending efforts to unearth the ‘new’ statins. The wonder drugs to be taken by everyone, for the rest of their lives. The ones that will make billions for the pharmaceutical companies, and several millions for the key opinion leaders promoting them.

Steven Nissen had a go with apoA-1 Milano. This is a little story you may want to look up on Wikipedia.  Basically, a small village was found in Italy (near Milan) where people had very low rates of heart disease, and they also had very low levels of HDL ‘good’ cholesterol.

Turning science on its head, it was therefore decreed that their HDL must be especially ‘good’ at preventing heart disease. [Rather than accept that HDL had bugger all to do with heart disease]. So attempts were made to synthesize their form of HDL, then inject it into patients. This was done in small scale clinical studies.

So brilliantly did Nissen sell the results of these studies that a start-up company called Esperion, which funded the trials, was sold to Pfizer for over a billion dollars on the back of the results. If you want to find out more, the HDL synthesized was called ETC-216, not apoA-1 Milano.

This is what Steven Nissen had to say about the trials.

“The fact that you can actually pull major amounts of plaque out of the artery in five or six weeks is an epiphany,” Nissen says. H. Bryan Brewer, chief of the molecular disease branch at the National Heart, Blood & Lung Institute, adds: “Quite to everyone’s surprise, this indicates that we might be able to be much more successful in a shorter period of time than we thought possible.”

By golly it all sounds very exciting, does it not.  Pulling significant amounts of plaque out of artery walls, in six weeks! This is quite amazing, what a brilliant drug. In truth, though, that quote was from 2003. Has anything since happened since to this magical plaque munching HDL? Is it now on the market, saving lives? Well, as you ask, the answer is no.

However, several other HDL raising agents have also been developed in the last few years. Unfortunately, they also raised the risk of heart attacks and strokes – then disappeared. Torcetrapib, dalcetrapib, anacetrapib…. A yes, anacetrapib, not quite gone yet.

‘Anacetrapib has a knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL,” said Chris Cannon in an AHA press release.  He also said “The lipid effects are jaw dropping in both directions,” Yes, indeed, they were.  Although I am not sure that ‘jaw dropping’ and ‘knock your socks-off’ are truly scientific terms.

But then Forbes ran this headline on the 22nd October

‘Merck Heart Drug Runs Into New Worry.’ 1

As an aside, you can find out far more about drugs in development by reading Forbes magazine than you will ever get from the scientific journals.

Anyway, I wouldn’t bet the house on anacetrapib as I suspect it will soon follow the other ‘trapibs’ into an early grave. But never mind, Lilly has yet another HDL raising agent waiting in the pipeline, evacetrapib. What is it with these unpronounceable names, and why don’t these companies just give up? However, perhaps this one has a better shot than most, because as Steven Nissen said of dalcetrapib…

“Dalcetrapib was always a long shot,” said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. “The worry all along was that it wouldn’t have enough effect to produce a benefit,”

Then, as he went on to say of evacetrapib

“We got everything we could hope for from this drug, and maybe more,” remarked study co-author Steven Nissen, adding that “we are going to move evacetrapib forward as rapidly as possible” into a late-stage trial.” Gosh, he is running a study on evacetrapib too.  He was also lead investigator for Torcetrapib2.

That Steven Nissen, what a busy chap he is?  Wasn’t he the one who said about the new cardiovascular prevention guidelines.  “The evidence was never there” for the LDL targets, he said. Past committees “made them up out of thin air,” he added.  Why yes, I think he was.

Anyway. They have tried raising HDL…fail. They have tried a different way of lowering LDL using ezetimibe. It lowered LDL, and has had absolutely no effect on cardiovascular disease…fail. They have tried combing different HDL raising agents with statins….fail.

You know, you might even begin to think that raising HDL wasn’t that good an idea. Billions have been thrown this target, everything has miserably failed. It is also interesting that LDL lowering agents, other than statins, have failed to have any impact on cardiovascular disease. Has this had any effect on the lipid hypothesis? You must be joking.

Given this litany of disastrous drugs trials, why do I now believe that statins are about to be overthrown? What agents could be out there that are going to sweep them into the dustbin of history.

Clearly it cannot be an agent that lowers LDL even more than statins. Can it? Well, Steven Nissen has recently said the following about LDL lowering. This quote is in connection to new drugs being developed3.

 “….it matters how you lower cholesterol, not just by how much.”

It matters how you lower cholesterol, not just by how much….. Interesting.  Well, if cholesterol does cause heart disease, then it doesn’t really matter how you lower it, does it? The only question is, by how much? Or is Steven Nissen trying to say something else?

As a further aside, if you want to know where the really big bucks are being spent in cardiovascular research, and what is in the pipeline, all you need to do is follow Steven Nissen’s pronouncements. He is the weather vane. You don’t need to be a weather man to know which way the wind is blowing.

…… (to be continued)

 

1: http://www.forbes.com/sites/matthewherper/2013/10/22/merck-heart-drug-runs-into-new-worry/

2: http://online.wsj.com/news/articles/SB10001424052702304363104577389353232022644

3: http://www.forbes.com/sites/johnlamattina/2013/09/05/esperions-novel-approach-to-lowering-cholesterol-will-it-be-successful/

They have now, officially, all gone mad?

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The Mad Hatter: ‘Have I gone mad?’

Alice: ‘I’m afraid so, you’re completely bonkers, but let me tell you something, the best people usually are.’

Alice in Wonderland

I find myself quoting Alice in Wonderland more and more these days. I now think it was never a children’s book, it was an accurate scientific analysis of human behaviour.

As many of you are aware the American medical authorities have come up with the latest guidelines to reduce cardiovascular risk. A major part of the guidelines is now to inform us all that we should forget about lowering cholesterol (LDL) levels, and just take a statin…. no matter what¹.

This is how the New York Times put it:

First, the guidelines have moved away from achieving target cholesterol levels.
Americans have long been urged to focus on their laboratory numbers. Many people are obsessive about checking their cholesterol levels and pursuing even better numbers. Doctors have been told to focus on these numbers and, in some cases, the quality of their care was assessed by the percentage of their patients with low cholesterol levels.

Those days are over. The new guidelines recognize that for patients who have exhausted lifestyle efforts and are considering drug therapy, the question is not whether a drug makes your lab tests better, but whether it lowers your risk of heart disease and stroke. Studies over the past several years have shown that improving your lab profile with drugs is not equivalent to lowering your heart risks².

One of the most influential cardiologists in the world, Steven Nissen, had this to say:
“The evidence was never there” for the LDL targets, he said. Past committees “made them up out of thin air,” he added.

Past committees made them up out of thin air….. Let me try that statement again…. Past committees made them up out of thin air. Exactly. Ex-bleedingly-zactly.

So, ladies and gentlemen, you have been conned. Utterly, completely and barefacedly conned, for the last thirty years. Your cholesterol level has absolutely no impact on your risk of cardiovascular disease. You think not? Well, that is precisely what they are saying in these guidelines. If not in quite such plain words.

But, of course, I am not being entirely fair to them. The level of LDL may actually matter after all – according to the same guidelines. For, as the New York Times article goes on to say.
There’s one exception to the numbers rule. People with very high levels of the harmful cholesterol known as LDL still need to worry about targets. The new guidelines set that LDL level at 190 milligrams per deciliter – but the principle is that if people have very high cholesterol levels, then their cardiovascular risk is so high that it is likely that treatment to reduce the levels would offset any risks of the drug treatment.

So, your LDL level doesn’t matter in the slightest, unless it is a very high level. Then the level does matter a great deal. Please explain, oh great cardiologists, does LDL, or does it not, cause cardiovascular disease.

Well, it seems that it both does, and does not, simultaneously. Amazingly, we have achieved a quantum state with LDL. It simultaneously exists as a molecule that can both cause – and not cause – CVD. Which means, of course, that the levels must be both lowered, and not lowered. Yes, well, this makes perfect sense. At least it would to a lunatic.

Perhaps if we open the box with the ‘at risk cat’ in it, we will find that this new version of Schrodinger’s cat died of a heart attack caused by LDL. Alternatively, it did not. Before opening the box, it exists in both possible states. It is an interesting variation on a theme.
The most astonishing thing is not that these people are now talking the most complete gibberish. They have been doing this for years. The most astonishing thing is that the vast majority of the population will still listen to what they have to say – and follow their advice.
Well, good luck with that all you billions of mad people, following the advice of these mad scientists Good luck with that indeed. I salute you. Meanwhile I shall attempt to find the answer to a far more important question than what causes heart disease.

“Why is a raven like a writing desk?”

1: http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437740.48606.d1
2: http://well.blogs.nytimes.com/2013/11/12/3-things-to-know-about-the-new-cholesterol-guidelines/