How much longer will you live if you take a statin?

"Looking at the Heart Protection Study (HPS) done in the UK, we used a technique for analysing survival time called RMST (restricted mean survival time). I won’t go into the details. The HPS study lasted for five years, and we calculated that the average increase in survival time was 15.6 days. This was at the end of five years of treatment (with a confidence interval of 5 days either side). For 4S, the figure was 17 days."

"Framing this slightly differently, what this meant was that taking a statin for one year, in the highest risk group possible, would increase your life expectancy by around three days."

"However, more recently the BMJ did decided to publish another paper entitled: ‘The effect of statins on average survival in randomised trials, an analysis of end point postponement.’

Results: 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively."

Conclusions: Statin treatment results in a surprisingly small average gain in overall survival within the trials’ running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered

Overall their findings were far less impressive, even, than ours. They calculated, approximately, a single day of increase in life expectancy for each year of taking a statin. Slightly more in secondary prevention, slightly less in primary (people who have not previously had a heart attack or a stroke).

The main take away message I believe, is the following. Statins do not prevent fatal heart attacks and strokes. They can only delay them. They delay them by about one or two days per year of treatment. For those who have read my books you will know that I have regularly suggested we get rid of the concept of ‘preventative medicine’. We need to replace it with the concept of ‘delayative medicine’.

Read Dr. Kendrick's complete article here.

Beware: new cholesterol lowering drugs coming - Kendrick

Beware: new cholesterol lowering drugs coming

by Dr Malcolm Kendrick

‘…across the gulf of space, minds that are to our minds as ours are to those of the beasts that perish, intellects vast and cool and unsympathetic, regarded this earth with envious eyes, and slowly and surely drew their plans against us.’ War of the Worlds

An era is coming to an end. Statins, the world’s most widely prescribed and profitable drugs, have, with the exception of Crestor (rosuvastatin), all come off patent and their price has plummeted. Good news for NHS accountants: not so good for company profits.

So a supposedly new, improved, much safer and more effective generation of cholesterol lowering drugs will soon be available at a doctor’s surgery near you. At least that will be the general tone of the marketing. With 80% of the population suffering from “high” cholesterol, according to guidelines drawn up by consultants with links to drug companies, there is obviously a huge need. (For an account of how seriously we should take this “need” see Dr John Briffa’s post.)

This is obviously a great opportunity for the companies but it also faces them with a fascinating dilemma. Statins have been relentlessly promoted as the most beneficial l class of drugs ever, protecting not just against cardiovascular disease but also Alzheimer’s and Parkinson’s and being virtually side-effect free into the bargain.

An alarming press release

But if the companies are going to persuade those NHS accountants and cash-strapped GP commissioning bodies to start paying serious prices for the new drugs, they need to persuade them that statins actually had a serious problem all along but it is one that can be avoided by buying the new products.

Recently I received a press release by email that was the first sign that this process is already underway. It was a warning about something called P9 which, had I been a loyal statin believer, I would have found pretty alarming. After explaining how statins worked by targeting an enzyme known as HMG-CoA in the liver, the email went on to tell me this:

“However, statin treatments have been shown to actually stimulate the production of PCSK9, which is counterproductive, possibly damaging to the liver, and ultimately limits the treatment’s ability to lower LDL cholesterol levels.”

Why weren’t we told about this risk before?

What on earth is PCSK9, you and the medical statin believers might well ask. And if it is not only able to damage the liver but also render the whole purpose of taking a statin self-defeating, why haven’t we been told about it before?

Here was a classic marketing ploy; tell you about a problem and immediately offer a solution in the form of a drug that is able to block the production of damaging PCSK9. The full name of these new drugs is proprotein convertase subtilisin/kexin type 9 inhibitors.

And it’s not the only dauntingly high tech-new cholesterol lowering drug that could be coming your way in the not too distant future. For the sake of completeness here is a list of nearly all the new compounds waiting in the wings. Some will undoubtedly founder on the rocks of side effects that are just too dangerous, never to be seen again.

Other new drugs in the race

• Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors)
• Antisense oligonucleotides (ASOs) targeting the production of apolipoprotein B-100 (apoB-100)
• Microsomal triglyceride transfer protein inhibitors
• Squalene synthase inhibitors
• Peroxisome proliferator-activated receptor agonists
• Thyroid hormone receptor agonists

For the moment though my money for the first out of the gate are the PCSK9 inhibitors, which I will call P9 inhibitors. So what exactly are they? Well P9 is an enzyme that is found mainly in the liver. It binds to receptors that remove the “bad” LDL (low density lipoprotein) cholesterol and destroys them after they have taken just one LDL molecule out of circulation, meaning that they can’t be reused to remove more LDL.

But if you block P9, you allow LDL receptors to continue removing LDL merrily from the bloodstream, so LDL levels fall dramatically. In fact P9 inhibitors appear to lower LDL far more effectively than statins which, if you sign up to the belief that the lower your cholesterol goes the more protection you get, this can only be another major benefit.

The new statin combo

What’s clever about this is that it avoids taking on statins directly. Given how familiar doctors are with them, how most believe in them and how cheap they are, a head on attack would be doomed to failure.  The manufacturers know, damn well, that doctors are not just going to stop using statins, so their P9 inhibitors will be positioned to sit alongside statins, allowing them to work, supposedly, even more safely.  At first anyway.

But there is more to this press release and I could pick it apart for hours, marvelling at the ability to say so much – in so few words. But let’s just focus on the phrase…’possibly damaging to the liver’ in relation to statins. Now, I know that statins do damage the liver – to a greater or lesser degree. Liver enzymes in the blood (a sign of liver damage) are often raised to three times normal levels – sometimes more.

But why not focus on the side-effect that is most clearly recognised with statins?  Namely muscle damage and pain. This is the true Achilles heel of statins. Yet the press release talks about liver damage…

Danger to your liver

The most likely reason is that P9 inhibitors have been found to cause liver problems themselves in both animal studies and phase 1 studies on human volunteers. Knowing their mechanism of action, it is more than likely that PCSK9 blocking agents could damage the liver. If you over-ride negative feedback mechanisms, the body doesn’t like it very much, as you will be overloading cells with toxic waste products. Enzymes to break down LDL receptors are there for a reason.

So, we can expect P9 inhibitors are going to cause liver damage. However, by attacking statins for causing liver damage, the pharmaceutical companies will be hoping to mask the most serious adverse effect of the new drug. The words used to defuse concerns about this problem will be something along the lines of. ‘With our P9 inhibitor we have seen mild elevations of liver enzymes in clinical studies. However, they are similar to those caused by statins, are reversible and cause no long-term damage.’ Blah, blah….  ‘Move along, nothing to see here.’

This fear is not just based on a vague unease that if you block a feedback mechanism in the body you are probably heading for disaster. It is also based on the fact that, if the companies developing P9 inhibitors are already blaming statins for causing liver damage, they are doing to hide their own problems behind a smokescreen. You heard it here first.

I also predict that severe liver damage problems will take years to emerge. In most people the liver is pretty resilient – it takes a lot of alcohol and a lot of time to destroy it. I fear that clinical studies will not be long enough to demonstrate this effect –before the drugs are launched and widely prescribed. I can say all this because it is what has happened with damaging block buster drugs in the past, such as the anti-inflammatory Vioxx and and the diabetes drugs Avandia.

My predictions for P9 inhibitors:

• They will be widely promoted as the new statins
• Pfizer, or Merck, will buy out the patent to one of the new products (they may have already done this)
• They will be launched without any long-term studies to show they actually cut your chance of dying from a heart attack. They will be approved purely on the basis that they lower cholesterol/LDL cholesterol.
• They will make billions upon billions in the first two years and be hailed around the word as a new generation in cholesterol lowering. The chief executives of the companies selling these drugs will be paid massive bonuses
• Key Opinion Leaders (‘experts’) will promote them ruthlessly at major conferences and press launches
• Reports of a high level of liver damage/deaths will  start to emerge
• The companies will deny there is a problem and attack anyone who says there is one
• They will start to be withdrawn from the market two to three years after launch
• There will be lawsuits
• The companies will be fined a small fraction of the profits they made from hyping the drugs
• It will emerge that the problems with liver damage were known by the companies many years before the drugs were launched but not many people will be interested by then, as the next generation of lipid lowering agents will be arriving
• No-one will be held accountable

Yes, the great Nostrokendrickos has spoken.
In the meantime remember that ‘Something unpleasant this way comes’.
Disclosure: I do not believe that a raised LDL/cholesterol level causes heart disease.
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Read the complete article here.

Statins do not help you live longer – or do anything much else for that matter - Kendrick

Statins do not help you live longer – or do anything much else for that matter

  

Sometimes you read a thing quickly, and then you have to read it again to make sure you read it right. Yesterday I was sent a copy of a ‘Patient page’ from the Journal of the American Medical Association (JAMA).  The page was from the April 3^rd 2013 edition, pp 1419. It is stamped ‘JAMA – copy for your patients’. JAMA is one of the highest impact medical journals in the world.

This patient page states that:

‘One question involves disagreement about whether the statin side effects are merely uncomfortable or actually pose significant health risks. The other question is whether reducing bad cholesterol will actually help you live longer than you otherwise would. Some of this disagreement involves how physicians interpret the results of studies. However, a 2010 analysis combined the results of 11 studies and found that taking statins did not lower the death rate for people who did not have heart disease. If your physician recommends taking a statin, talk to him or her about the risks and benefits for your individual situation.’

 

For many years I have been ridiculed by colleagues for saying that, if you do not already have established heart disease, statins do not increase your life expectancy. By which I mean that they don’t’ actually work. ‘Don’t be ridiculous.’ Is what they exclaim to me. I usually reply that the evidence is pretty clear, and always has been. But I know that they don’t believe me.

Recently, without warning, one of the most influential medical journals in the world turned round and confirmed it. JAMA has stated in black and white that if you do not have established heart disease e.g. angina, previous heart attack, you will not live any longer if you take a statin.

Frankly, I think JAMA will now come under ever increasing bombardment from the ‘experts’ and will end up retracting this statement. In fact, I am willing to bet that they will – having now seen some of the outraged letters sent in. However from time to time the truth – like a small grass shoot growing through a concrete pavement – will emerge. As it did in April.

(I should add, at this point, that around 95% of people who take statins do not have established heart disease.)

However, wrapped up in this issue, is an inevitable argument. I know this argument well, for I have heard it a thousand times. ‘Ah, but it is not just death we are talking about here…. statins prevent non-fatal heart attacks and non-fatal strokes and suchlike. These are terrible things that damage the quality of your life. Medicine is not only about getting people to live longer, it is also about quality of life. Preventing a non-fatal stroke is extremely important, and statins do this.’ In other words, statins don’t make you live longer, but they do provide other, very significant benefits, by preventing Serious Adverse Events (SEAs).

This is a good argument. At least it would be if it were true. However, we have no idea about whether it is true or not. For the simple reasons that the data on SEAs is almost entirely hidden from view. Data on SEAs are considered so commercially sensitive that, in most jurisdictions, pharmaceutical companies won’t release them (and don’t have to release them), even if you ask nicely*.

Before moving onto that issue, I know that I need to explain I am talking about here in a little more detail, and clear up a bit of confusion with the nomenclature. For in the area of adverse events/effects, we have two terms that sound very similar, but mean very different things.

Firstly, there are drug related adverse effects. These are often called ‘side-effects’. But side effects can be good, or bad. For example Viagra was developed as an angina drug but it was found to create enhanced erections, as a side-effect. [You can decide if this is a beneficial side-effect or not]. Viagra also causes headaches. This is also a side-effect, but it would be more accurate to call it a drug related adverse effect.

Drug related adverse effects = negative/unpleasant ‘side-effects’ of a drug
A Serious Adverse Event (SEA) may sound similar to a drug related adverse effect, but it means something completely different. An SEA is a significantly bad thing that a drug might prevent e.g. non-fatal heart attack. Or, it could be something that the drug causes e.g. rhabodmyolysis (muscle breakdown), followed by kidney failure. Which is something that is known to be caused by statins.
SEAs can therefore be good, or bad. Depending on whether they are caused by, or prevented by, the drug. This means that there is absolutely no point in presenting figures on SEAs prevented by statins, without knowing if they caused an equal number of SEAs at the same time.

Completely unsurprisingly, whilst we are bombarded with statistics about how many SEAs are prevented by statins, we have very little idea about how many SEAs are caused by statins. Because in most countries, these data are not released. Its’ commercially sensitive dontcha know. [Damned right it’s commercially sensitive. If the public saw these data they would stop taking half their meds overnight.]

There have, however, been glimpses of SEAs with statins – when the data escaped from the clutches of the pharmaceutical companies. When the Cochrane collaboration fist looked at primary prevention studies, two of the five major studies did report ‘negative’ SEAs (although they did not say what the SEAs were, and still won’t). In these two trials AFCPAS and PROSPER, the SEAs were:

Statin arm:      44.2%Placebo arm:  43.9%

‘In the 2 trials where serious adverse events are reported, the 1.8% absolute reduction in myocardial infarction and stroke should be reflected by a similar absolute reduction in total serious adverse events; myocardial infarction and stroke are, by definition, serious adverse events. However, this is not the case; serious adverse events are similar in the statin group, 44.2%, and the control group, 43.9% This is consistent with the possibility that unrecognized serious adverse events are increased by statin therapy and that the magnitude of the increase is similar to the magnitude of the reduction in cardiovascular serious adverse events in these populations.’  (read more…)

In short there were slightly more SEAs in those taking statins than in those taking placebo. Slightly more harm than good.

So what do we now know? We know that if you do not have established heart disease, and you take a statin, you will:

• not live any longer
• not avoid major Serious Adverse Events

Which means that there is no possible improvement in either the quality, or the quantity, of life. On the other hand there is a good chance that you will suffer from significant adverse effects e.g. muscle pain, joint pain, impotence, stomach upset, rashes etc. etc. On balance therefore we can state that, if you do not have established heart disease, statins provide no benefits on any important outcome. All they can do is to give you adverse effects. ‘Oh boy, that sounds like a great deal doc. Can’t wait, can’t wait, can I get them now?’

*Please see petition that I just put up on my blog. This petition arrived coincidentally as I was writing this article. At present the European Medicines Agency (EMA), will provide SEA data if requested (with huge persistence). The UK authorities will not release these data, nor will the FDA in the states. A recent move by the pharmaceutical industry is now threatening that the EMA will be forced to hide SEAs. ‘Six months ago two US pharmaceutical companies AbbVie and InterMune took a legal action against EMA that has closed down access to all trial data for all drugs for all doctors and researchers anywhere in the world.’

Closed down all access to all trial data for all drugs for all doctors and researchers anywhere in the world.

That statement is worth repeating. Be afraid, be very afraid indeed. And sign the petition please. Oh, and write to your MEP, as I am now doing.
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Read the complete article here.

So much for scientific debate - Kendrick

   So much for scientific debate

I thank Ted Hutchinson for pointing me at this article in the Irish Independent. It appeared on the 5^th of October, and I reprint it in full, here.

A LEADING vascular surgeon, whose research review concluded cholesterol-lowering medicines may do more harm than good for many otherwise healthy people, has been gagged by the Health Service Executive.

 

Sherif Sultan, a senior medic at University College Hospital, Galway, reviewed a range of studies of statins and found a lack of evidence to show they should be given as a means of prevention to healthy people with high cholesterol but no heart disease.

Mr Sultan and his surgeon colleague Niamh Hynes said lifestyle changes to reduce cholesterol were better because this allowed people to avoid the risk of statins’ side effects.

 

However, in a statement last night, Dr Pat Nash, a cardiologist and the group clinical director in University College Hospital said the recently published views of his colleagues were “not representative” of those in Galway or neighbouring hospitals.

 

“As group clinical director of the West/North West Hospitals Group, and a working cardiologist, I wish to reassure patients that statins are safe,” said Dr Nash.

 

“These are very important, well-validated drugs for the treatment of elevated cholesterol. We have extensive evidence to show their benefit and to show that they improve outcomes for patients with heart disease and stroke and that they have a role in preventing heart disease and stroke.

 

“As always, if patients have any concerns, they should not discontinue their medication without discussing with their GP or consultant.”      

 

Asked to comment, Mr Sultan said: “I have received an official warning from the HSE and have been instructed not to liaise directly with the press in my capacity as a HSE consultant.” However, he said he could continue to comment as a consultant vascular surgeon at the Galway Clinic, where he has a private practice.

 

The HSE declined to comment on the reasons for ordering Mr Sultan not to speak as a public consultant. He said he stood by his analysis of the role of statins in otherwise healthy patients with high cholesterol. He pointed to another recently published review on exercise versus drug therapy in the management of pre-diabetes and cardiovascular disease.

 

“That ‘British Medical Journal’ analysis showed the superiority of exercise over drug therapy extends even to secondary prevention (where patients have developed disease)¹.

 

This story has been rumbling on for a while. A report on the research paper can be found in the Irish Medical Times from a couple of weeks before.

The under-reporting of findings on major adverse effects of statin therapy and the way in which they had been withheld from the public, and even concealed, is a scientific farce, claims new Irish research.

 

Mr Sherif Sultan, Consultant Vascular and Endovascular Surgeon, and Niamh Hynes, Clinical Lecturer In Vascular and Endovascular Surgery, claimed their study, just published in the Journal of Endocrine and Metabolic Diseases (2013, 3, 179-185) highlights the major side-effects and dangers of statins.

 

They said there is a categorical lack of clinical evidence to support the use of statin therapy in primary prevention. They are both based in the Western Vascular Institute at University College Hospital Galway and the Galway Clinic. “Odds are greater than 100-to-1 that if you’re taking a statin, you don’t really need it²..

 

I was sent the original paper by Sherif Sultan a couple of months ago, and it is very scathing about statins….. very scathing indeed. It even suggests, perish the very thought, that pharmaceutical companies may have been trying to present statins in the best light possible. I find such a suggestion almost impossible to believe. Knowing how completely ethical these companies are.
Anyway, I suppose the key phrase in all of this sorry episode is the following:

“The HSE declined to comment on the reasons for ordering Mr Sultan not to speak as a public consultant.”
If the Health Service Executive were to comment, what could they say to justify their actions?
“The hell with scientific debate. He should just damned will shut up and say what we want him to say?”
“How dare anyone criticise the sainted statins which work in mysterious ways their wonders to perform.”
“We expect utter loyalty from those who work in the glorious Irish Health Service. Those who do not support us can expect serious sanctions……”

On balance, declining to comment is probably the best policy for the HSE. Because if you start trying to justify why you are gagging a researcher for trying to tell the truth then, well, you will end up having to justify state censorship of scientific debate. Which never looks that good on the printed page, I find.

I feel I should sign off this blog with a quote from George Orwell, taken from 1984. “Being in a minority, even in a minority of one, did not make you mad. There was truth and there was untruth, and if you clung to the truth even against the whole world, you were not mad.”

1: http://www.independent.ie/irish-news/hse-gags-surgeon-after-cholesterol-drug-claims-29636095.html
2: http://www.imt.ie/news/latest-news/2013/09/study-claims-to-highlight-the-ugly-side-of-statins.html
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Read the complete article here.

811 deaths and counting - Kendrick/Graveline

811 deaths and counting

  

There is a doctor in the USA called Duane Graveline who I know well. He trained as an astronaut, when such things were seen as exciting. He was very much mainstream in his prescribing and thinking about medicine, until he was started on statins. He took them happily, until he suffered an episode of transient global amnesia. A complete loss of memory, re-booting his brain to the age of about eight.

On the first occasion he had no idea what had happened. He thought he could have had a stroke, but after investigations nothing was found. He asked if the statin could have caused this, and was told no – not a chance. So he started on statins again, and suffered another episode, the same as the last.

He then started investigating and found that thousands of others had suffered from episodes of transient global amnesia whilst on statins. A very, very, rare thing to happen to anyone, but increasingly common nowadays. I wonder why? Dr. Graveline then started to develop a neuromuscular disease, similar to amyotrophic lateral sclerosis (ALS) which he attributes to the statin. Statins can certainly cause neuropathy – but I shall say no more on this issue at present.

Dr. Graveline is not so keen on statins now, nor does he believe that cholesterol causes heart disease – having looked at the evidence again with a fresh eye. For those who do not know, he has a website www.spacedoc.com. Here are listed all of the many adverse effects of statins, and the suffering of many thousands of people.

He believes that the authorities are, basically, turning a blind eye to the many and varied problems with statins. So he has laboriously gone through the Food and Drug Administration (FDA) database of Adverse Drug Events (Medwatch), to find out just exactly how many deaths statins have caused.

This is extremely difficult to analyse as the coding system in Medwatch is complex, poorly linked and many things – frankly – do not seem to make sense. Whilst going through this stuff is an absolute nightmare, it can be done – although you have to make some assumptions along the way.

What Dr. Graveline did was to look for case of rhabdomyolysis (catastrophic breakdown of muscle tissue) linked to statins. Rhabdomyolysis is a pretty specific, and well-accepted, adverse effect of al statins. However, it is considered as so vanishingly rare as to be not worth bothering about by most doctors.

Rhabdomyolysis carries a very high mortality rate, because the waste products of dissolving muscles travel to the kidneys, where they block up the nephrons, causing acute kidney failure. In around ten per-cent of cases rhabdomyolysis is fatal. So you can assume, with reasonable accuracy, that for every ten reported cases of rhabomyolysis, you will get one death. You will also get a number of people with destroyed kidneys who end up on dialysis – hey ho.

At this point I should also point out that adverse drug events are widely known to be a massively under-reported. It is difficult to be certain on the exact figures. However, having read many papers on this subject the general feeling is that about 1 – 5% of all events are actually reported by anyone – ever. Which means that any figures in Medwatch can be pretty reliably multiplied by twenty to one hundred? Which is a topic for another day.

Anyway, with this pre-amble out of the way, I have copied Dr. Graveline’s blog on statins (with his full permission). What he has found is that, over a six year period there were 8,111 cases of rhabodmyolysis reported to Medwatch associated with statins. This represents, at least, 811 deaths in this period. [If you were to multiply this figure by twenty, this is 16,200. Multiply by one hundred and you have 81,110.]

A few years ago one of the statins called Baycol was rapidly removed by the FDA after sixty people died from rhabdomyolysis whilst taking statins. Well, all statins can cause rhabdomyolysis. Hundreds have died, probably more, since Baycol was yanked from the market. Yet there is absolute radio silence on this issue.

Below is Dr. Graveline’s blog…

Relative risk of Statin Associated Rhabdomyolysis

 

A recent study comparing the relative risks of muscle problems with the use of the various statin drugs has recently been reported. Generally the risk of muscle adverse effects varies with the strength of the statin used except for the statin fluvastatin (Lescol). Lescol, usually considered to be the weakest of the commonly used statins now shares with rosuvastatin (Crestor), the strongest of the statins, in being consistently linked to higher adverse muscle events relative to the other commonly used statins. Atorvastatin (Lipitor) and simvastatin (Zocor) showed intermediate risks and pravastatin (Pravachol) and lovastatin (Mevacor) had the lowest risk rates. Designating rosuvastatin’s and fluvastatin’s relative risk as 100%, comparative rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5%.

 

     There were a total of 186,796 case reports listed within the Adverse Event database (Medwatch) during the study period 1 Jul 2005 to 31 Mar 2011. Choosing rhabdomyolysis as one of the more discrete and credible of the muscle diagnoses, a total of 8,111 cases of rhabdomyolysis were reported during this study period, averaging 1,350 cases yearly. Sidney Wolfe MD has previously estimated the statin associated rhabdomyolysis death rate to be 10 percent (giving a total of 811 deaths during this 6 year 4 month time period). Of the total number of rhabdomyolysis cases, fluvastatin was involved in 164, rosuvastatin in 1146, simvastatin in 3395, atorvastatin in 1641, pravastatin in 267 and lovastatin in 161.

 

     Returning to the death rate estimate of 811, this strikes me as extraordinarily high and I cannot believe I am just now discovering this. Back in the Baycol crisis of 2004, sixty deaths caused FDA to rise up and Bayer to take its problematic product off the shelves. Six years later, 811 deaths do not even deserve a mention. What has happened? Where is the media uproar that we had back in 2004? I knew the Medwatch figures for Lipitor because I had obtained a copy of the Medwatch data and counted the rhabdomyolysis cases myself. I counted 2731 cases of rhabdomyolysis from the period 1997 to 2011 from Lipitor alone which fits quite well with this recently published work. So I had a heads up. I predicted the total rhabdomyolysis cases would be 6,000 for all the statins never suspecting I would underestimate by several thousand.

 

     Medwatch exists for FDA to monitor these outrageous post marketing events and report back to the medical community. Where is the FDA report? This is incredible!

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Read the complete article here.

Who shall guard the guardians? - Dr. Malcolm Kendrick

Who shall guard the guardians?

  

Mainstream medicine increasingly relies on Guidelines. Well, they are called guidelines, but increasingly they carry the force of law. In many countries if you try to practice outside the wise and infallible guidelines you may lose your license to practice medicine. In the US, you may well be dragged into court, and if you have not been following the guidelines, you will be sued. You can even be gaoled (or jailed, as we say in the UK).

In short, guidelines are very serious and important things indeed, and they now rule medicine with a rod of steel. In the UK up to 50% of general practice time is spend ensuring that all patients are constantly monitored to ensure that various guidelines are rigorously followed. Is the BP low enough, the cholesterol low enough, have you checked blood sugar levels etc.

But where do guidelines come from – exactly? Who gives people the right to sit on guideline committees? What are the entrance requirements? Who shall guard the guideliners?

The answer is, perhaps shockingly, that there are almost no rules to this. If a group, such as the National Institutes for Health in the US, decides to set up a committee to decide on, for example, what is the healthy level for cholesterol lowering, what happens? They ask a number of Key Opinion Leaders to join the committee. In this case the NCEP (National Cholesterol Education Programme – which is a committee, not a programme).

In 2004 this committee decided that cholesterol levels should be lowered far more aggressively than in the past. Based on, as far as I could see, very flimsy evidence.  Could it be that that committee was, in some way, biased in favour of cholesterol lowering companies?  A number of people, including me, demanded to see if any of the eight invited members of this hugely important committee had financial conflicts.

With much reluctance, the conflicts were revealed (I have highlighted, in bold, the companies who marketed cholesterol lowering agents at the time.) See below

ATP III Update 2004:  Financial Disclosure of NCEP members
Dr. Cleeman: (Chairman) has no financial relationships to disclose.
Dr. Grundy: has received honoraria from Merck, Pfizer, Sankyo, Bayer, Merck/Schering-Plough, Kos, Abbott, Bristol-Myers Squibb, and AstraZeneca; he has received research grants from Merck, Abbott, and Glaxo Smith Kline.
Dr. Bairey Merz: has received lecture honoraria from Pfizer, Merck, and Kos; she has served as a consultant for Pfizer, Bayer, and EHC (Merck); she has received unrestricted institutional grants for Continuing Medical Education from Pfizer, Procter & Gamble, Novartis, Wyeth, AstraZeneca, and Bristol-Myers Squibb Medical Imaging; she has received a research grant from Merck; she has stock in Boston Scientific, IVAX, Eli Lilly, Medtronic, Johnson & Johnson, SCIPIE Insurance, ATS Medical, and Biosite.
Dr. Brewer: has received honoraria from AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Esperion, and Novartis; he has served as a consultant for AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Sankyo, and Novartis.
Dr. Clark: has received honoraria for educational presentations from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer; he has received grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer.
Dr. Hunninghake: has received honoraria for consulting and speakers bureau from AstraZeneca, Merck, Merck/Schering-Plough, and Pfizer, and for consulting from Kos; he has received research grants from AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, and Pfizer.
Dr. Pasternak: has served as a speaker for Pfizer, Merck, Merck/Schering-Plough, Takeda, Kos, BMS-Sanofi, and Novartis; he has served as a consultant for Merck, Merck/Schering-Plough, Sanofi, Pfizer Health Solutions, Johnson & Johnson-Merck, and AstraZeneca.
Dr. Smith: has received institutional research support from Merck; he has stock in Medtronic and Johnson & Johnson.
Dr. Stone: has received honoraria for educational lectures from Abbott, AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, Pfizer, Reliant, and Sankyo; he has served as a consultant for Abbott, Merck, Merck/Schering-Plough, Pfizer, and Reliant.

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm

Of course, as people have stated to me, the mere fact that there were seventy two financial conflicts of interest does not mean that the guidelines themselves were biased. But you know what, I don’t believe it. Imagine if eight Supreme Court judges, ruling on any issue, had seventy two direct financial conflicts of interest to do with that issue…..Well, the outcry would never end.

Yet doctors, it seems, are beyond any suspicion – of any sort. There is not the slightest possibility that any doctor would ever do anything wrong….We are, after all, superior beings. ‘But, what’s that you say skippy…. hold on.’

‘Despite a 2-year-old scandal discrediting key evidence, current guidelines relying on this evidence have not been revised. As a result of physicians following these guidelines, some researchers say, it is possible that thousands of patients may have died each year in the UK alone. It is unlikely that a true understanding of the damage will ever be known…..

The guidelines, which were published in 2009, were based on analyses of the available trials. The strongest evidence came from the DECREASE family of trials, which appeared to strongly support perioperative beta-blockade, and one other large trial, POISE, which raised concerns that beta-blockers might lead to an increase in deaths

In 2011, however, faith in the reliability of the DECREASE trials was shattered as a result of a scientific misconduct scandal centering on the principal investigator of the studies, the now disgraced Dutch researcher Don Poldermans. The issue was further complicated because, in addition to his key role in the trials, Poldermans was the chairman of the committee that drafted the guidelines.

’ http://cardiobrief.org/2013/07/31/european-heart-guidelines-based-on-disgraced-research-may-have-caused-thousands-of-deaths/

Oh well, maybe not.

The fact is that, wherever you look, guidelines are being developed by doctors who have widespread conflicts of interest. And if you go a step further back to review the studies that the guidelines are based on, they are run by, and written up by, doctors who have enormous conflicts of interest. Although sometimes, these conflicts are just…well, forgotten about.

For example, a few opinion leader were ‘named and shamed’ by the Journal of the American Medical Association, when someone pointed out that a number of the authors of the original paper they wrote might just have slipped up in declaring their conflicts:

Unreported Financial Disclosures in: ‘Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins: A Meta-analysis.’

 

….the following disclosures should have been reported:

 

 “Dr Mora reports receipt of travel accommodations/meeting expenses from Pfizer; Dr Durrington reports provision of consulting services to Hoffman-La Roche, delivering lectures or serving on the speakers bureau for Pfizer, and receipt of royalties from Hodder Arnold Health Press; Dr Hitman reports receipt of lecture fees and travel expenses from Pfizer, provision of consulting services on advisory panels to GlaxoSmithKline, Merck Sharp & Dohme, Eli Lilly, and Novo Nordisk, receipt of a grant from Eli Lilly, and delivering lectures or serving on the speakers bureau for GlaxoSmithKline, Takeda, and Merck Sharp & Dohme; Dr Welch reports receipt of a grant, consulting fees, travel support, payment for writing or manuscript review, and provision of writing assistance, medicines, equipment, or administrative support from Pfizer, and provision of consultancy services to Edwards, MAP, and NuPathe; Dr Demicco reports having stock/stock options with Pfizer; Dr Clearfield reports provision of consulting services on advisory committees to Merck Sharp & Dohme and AstraZeneca; Dr Tonkin reports provision of consulting services to Pfizer, delivering lectures or serving on the speakers bureau for Novartis and Roche, and having stock/stock options with CSL and Sonic Health Care; and Dr Ridker reports board membership with Merck Sharp & Dohme and receipt of a grant or pending grant to his institution from Amgen.

 

http://jama.ama-assn.org/content/307/16/1694.3.full?etoc

 

Not a bad little list.

As you can see, Dr Ridker had board membership with Merck Sharp and Dohme…… a company that has made billions from selling statins. Now, here is he is authoring a paper on the benefit of statins (which will be used to develop guidelines on cholesterol lowering), and he simply forgot about this conflict of interest. As for the others, well, they’re also busy people; things must have just slipped their minds, such as thirty three separate financial conflicts.

For this terrible crime against the integrity of medical science, none of them can ever again do medical research, or author a medical paper, or sit on guideline committees. Cue, mad cackling laughter. As you may expect, absolutely nothing happened at all, apart from the publication of that statement you in the Journal in the American Medical Journal (JAMA).

I am sorry, but the system of developing guidelines is, frankly, bust. It has been for many years, but it is a very big and dangerous looking nettle to grasp, and no-one, currently has the will to do it.

Someone, somewhere, needs to ensure that guidelines, and the evidence they are based on, and the interpretation of that evidence, is of the highest quality – and free from potential bias, and financial conflicts of interest. We are about as far from this happy state of affairs as I am from being invited onto any guideline committee, ever, anywhere.

And that, my friend, is a very, very long way away indeed. You would need to Hubble telescope to see across distances as vast as that.
 

This entry was posted in Dr Malcolm McKendrick on August 2, 2013 by Dr. Malcolm Kendrick.

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Read the complete article here.

Salt intake What of Nuns? - Kendrick

Salt intake – What of Nuns?

 

Excess salt intake is one of the great issues in preventative medicine. Last year I watched a bus go by, with an advert for reducing salt plastered all over the side. Some restaurants have taken salt cellars off their tables, to protect customers. Many foodstuffs now have their salt content clearly labeled, with high salt content given a red sticker.

Given all of this you would think, would you not, that the case for excess salt consumption causing cardiovascular disease had been made beyond even the slightest possibility of doubt. One of the arguments in support of the dangers of salt consumption (the one that I am looking at in this article), comes from the native peoples living in the Amazon

The Amazon is an extremely low salt environment, and the average salt consumption of those living there is at very low. Several studies have found that the tribes people living in the Amazon have very low blood pressure which does not increase with age. They also have very little in the way heart disease and strokes.

‘Primitive societies who ingest little or no salt have no hypertension¹’

Proof, the anti-salt lobby cry, that it is excess salt intake that causes our blood pressure to rise dangerously.

Or is it? When presented with ‘proof’ like this I tend to look for contradiction, rather than confirmation. Are there, I wondered, other populations that fail to demonstrate a rise in blood pressure with age, that do not have a low salt consumption. My attention was drawn to nuns, living in Italy.

‘The powerful effect of psychosocial and acculturating influences on population blood pressure trends seems to be confirmed, through longitudinal observations, in the nuns in a secluded order. After initial observations had been made on culture, body form, blood pressure, diet, and other variables in 144 nuns and 138 lay women, included as a control group, a 30-year follow-up study was undertaken. Most striking were opposite trends noted between the two groups in blood pressure trend. During the follow-up period, blood pressure remained remarkably stable among the nuns. None showed an increase in diastolic blood pressure over 90 mm Hg.’

So, nuns do not develop high blood pressure as they age. What happened to the control women in this study?

‘By contrast, the control women showed the expected increase in blood pressure with age. This resulted in a gradually greater difference (delta>30/15 mm Hg) in systolic and diastolic blood pressure between the two groups, which was statistically significant.’

No difference in diet or salt consumption, yet one population developed the ‘normal’ Western rate of hypertension whilst the other did not. What did the authors of this thirty yearlong study think was the reason for this finding?

‘In conclusion, it seems reasonable to attribute much of the difference in blood pressure and cardiovascular events, to the different burden in psychosocial factor and to the preserved peaceful lifestyle of the nuns².’

Now I do not know for sure if those living in the Brazilian rain forests have managed to preserve a traditional peaceful lifestyle – but it seems a reasonable assumption to make.

However, the main point I am trying to make here is that you do not need a low salt diet in order to prevent hypertension. You can find populations with a normal salt diet who do not develop hypertension either.

What factor, or factors, appears to link these two populations? The factor appears to be living a preserved peaceful lifestyle. This would suggest that stress is the cause of hypertension and cardiovascular disease, and not salt. Whilst association cannot prove causation, a lack of association disproves it.

1: Freis ED. The role of salt in hypertension. Blood Pressure 1992; 1: 196-200.
2: Timio M, et al: ‘Blood pressure in nuns in a secluded order: A 30-year follow-up.’ Miner Electrolyte Metab. 1999 Jan-Apr;25(1-2):73-9

JAMA on salt HERE.
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Read the complete article here.
Another article here.

Salt guidelines raised ... as Canadian experts cite existing targets as ‘not feasible’

More data in the Salt Wars - Aug 14, 2014; http://www.medpagetoday.com/Cardiology/Hypertension/47203

An article by Marion Nestle - http://www.foodpolitics.com/2014/08/its-salt-arguments-again-new-research-arguments-over-public-health-recommendations-and-issues-of-conflicts-of-interest/

Potassium, your invisible friend - Kendrick

Poatassium, your invisible friend Dr. Malcolm Kendrick

 

I recognise that I spent a lot of time telling people what does not cause heart disease, and what does not protect against heart disease. My sister told me… ‘well, what advice would you give people, then?’ I usually shrug my shoulders and reply ‘there is no shortage of advice around, I don’t think I need to add to the daily bombardment.’

However, I shall break the habit of a lifetime and, with slight trepidation, announce that I strongly believe that Potassium is good for you. If you consume more of it you will, most likely, live both longer and in better health.

How much should you consume? A couple of extra grams a day should do the trick. Having said this, I do recognise that most people will not have the faintest idea how much potassium they consume and, frankly, neither do I. But you are probably not consuming enough, and your kidneys will easily get rid of any excess.

For those who are not keen on bananas, spinach and broccoli, and other foods high in potassium, you could take it as a tablet. Potassium bicarbonate or potassium citrate appears to be the best formulation. Depending on which brand you decide to buy, it should cost about £15 – 20/year.

Why this sudden potassiumophilia? Well, there is a growing body of research which points to the fact that potassium is very good for you. The first time I became aware that it might be good for you was when I first looked at the Scottish Heart Health study. The researchers looked at twenty seven different ‘factors’ they thought might cause, or protect against, heart disease – and overall mortality.

  The authors noted that:
“[There was] an unexpectedly powerful protective relation of dietary potassium to all-cause mortality,” the study concluded.

The paper showed that:

• Men consuming an average of 5400 mg of potassium per day vs 1840 mg were 55% less likely to die during 7.6 year study (the highest one-fifth of men vs the lowest one-fifth of men)

• Men consuming an average of 5400 mg of potassium per day vs 3350 mg were 22% less likely to die during 7.6 year study (the highest one-fifth of men vs the second highest one-fifth of men)

• Women consuming an average of 4500 mg of potassium per day vs 1560 mg were 59% less likely to die during 7.6 year study (the highest one-fifth of women vs the lowest one-fifth of women)

• Women consuming an average of 4500 mg of potassium per day vs 2700 mg were 15% less likely to die during 7.6 year study (the highest one-fifth of women vs the second highest one-fifth of women

The study can most easily be found here http://www.ncbi.nlm.nih.gov/pubmed/9314758
I immediately liked this finding. Mainly because it was almost completely unexpected, and unexpected findings are always far more likely to be correct than expected findings. Also, this was a very large effect indeed. It turned out that increased potassium consumption was very nearly as protective as smoking was damaging.

Of course, this was an observational study, so I filed it under – most interesting – but did nothing much more about it. As the authors said themselves: ‘ Potassium excretion was very significantly related to risk of death from all causes, having a protective role, whereas its role in coronary events was weaker and that of sodium excretion weak and even paradoxical. These results are unifactorial, without correction other than for age and sex. Our findings need corroboration from elsewhere and more detailed analysis with more events from longer follow-up.’

Since then, a large number of other studies have followed up, and appear to have confirmed that potassium has considerable health benefits. Some of these studies were not just observational, they were interventional. Here is summary of the potential beneficial effects. Potassium:

• lowers blood pressure
• lowers the risk of arrhythmias
• lowers the risk of cardiovascular disease
• lowers the risk of stroke
• lowers the risk of heart attacks
• lowers the risk of cancer, and
• lowers the risk of death

These benefits have been confirmed in a number of different studies. However, as this is a blog, I am not going to turn it into a medical paper and provide references for every statement, so I will stick to a couple of referenced studies. (If enough people are interested I can point you at additional papers).
With regard to blood pressure, a study published in 1997 found that adding roughly 2 grams (2000 mg) of potassium per day lowered blood pressure in older people by 15/8 mm Hg. As good, if not better, than any antihypertensive drug¹. And with no side-effects at all.

When it comes to stroke, it has been found that having a low potassium level is a very potent risk factor for both bleeding (haemorrhagic) and clotting (ischaemic strokes). In an American study it was found that in those with low potassium levels the relative risk of ischaemic stroke increased by 206%. The relative risk increased by 329% for haemorrhagic stroke².

Admittedly, these two studies were done in people with high blood pressure to start with, but these effects are also found in healthy people. However, to my mind, the most important thing about potassium is that I cannot find any study, anywhere, which suggests that increasing potassium consumption may be harmful. In short, it seems to be something that does only good.

I do recognise that a lot of doctors will shudder at the thought of adding potassium to the diet, as they have all been taught that a high potassium level is something terribly dangerous. A condition that needs immediate treatment, or else it will cause arrhythmias and death.

It is true that you need to be careful of adding potassium to the diet of patients taking medications that can raise potassium levels. These are mainly drugs used to lower blood pressure. However, even in this group the risk of overdosing on potassium is exceedingly small. For everyone else the risk seems to be zero. This is why I now recommend potassium supplementation as a good way to live a longer, healthier life.

My goodness, I think this is the first time I have ever recommended a dietary supplement. Must go and lie down.


1: ‘Long term potassium supplementation lowers blood pressure in elderly hypertensive subjects’ Fotherby M.D. et al: Int J Clin Practice 1997 41(4): 219 – 222)
2: Smith NL, et al: ‘Serum potassium and stroke risk among treated hypertensive adults.’ Am J Hypertens. 2003 Oct;16(10):806-13

I recognise that I spent a lot of time telling people what does not cause heart disease, and what does not protect against heart disease. My sister told me… ‘well, what advice would you give people, then?’ I usually shrug my shoulders and reply ‘there is no shortage of advice around, I don’t think I need to add to the daily bombardment.’

 

However, I shall break the habit of a lifetime and, with slight trepidation, announce that I strongly believe that Potassium is good for you. If you consume more of it you will, most likely, live both longer and in better health.

 

How much should you consume? A couple of extra grams a day should do the trick. Having said this, I do recognise that most people will not have the faintest idea how much potassium they consume and, frankly, neither do I. But you are probably not consuming enough, and your kidneys will easily get rid of any excess.

 

For those who are not keen on bananas, spinach and broccoli, and other foods high in potassium, you could take it as a tablet. Potassium bicarbonate or potassium citrate appears to be the best formulation. Depending on which brand you decide to buy, it should cost about £15 – 20/year.

 

Why this sudden potassiumophilia? Well, there is a growing body of research which points to the fact that potassium is very good for you. The first time I became aware that it might be good for you was when I first looked at the Scottish Heart Health study. The researchers looked at twenty seven different ‘factors’ they thought might cause, or protect against, heart disease – and overall mortality.

 

 The authors noted that:

“[There was] an unexpectedly powerful protective relation of dietary potassium to all-cause mortality,” the study concluded.

 

The paper showed that:

• Men consuming an average of 5400 mg of potassium per day vs 1840 mg were 55% less likely to die during 7.6 year study (the highest one-fifth of men vs the lowest one-fifth of men)

• Men consuming an average of 5400 mg of potassium per day vs 3350 mg were 22% less likely to die during 7.6 year study (the highest one-fifth of men vs the second highest one-fifth of men)

• Women consuming an average of 4500 mg of potassium per day vs 1560 mg were 59% less likely to die during 7.6 year study (the highest one-fifth of women vs the lowest one-fifth of women)

• Women consuming an average of 4500 mg of potassium per day vs 2700 mg were 15% less likely to die during 7.6 year study (the highest one-fifth of women vs the second highest one-fifth of women

The study can most easily be found here http://www.ncbi.nlm.nih.gov/pubmed/9314758

I immediately liked this finding. Mainly because it was almost completely unexpected, and unexpected findings are always far more likely to be correct than expected findings. Also, this was a very large effect indeed. It turned out that increased potassium consumption was very nearly as protective as smoking was damaging.

 

Of course, this was an observational study, so I filed it under – most interesting – but did nothing much more about it. As the authors said themselves: ‘ Potassium excretion was very significantly related to risk of death from all causes, having a protective role, whereas its role in coronary events was weaker and that of sodium excretion weak and even paradoxical. These results are unifactorial, without correction other than for age and sex. Our findings need corroboration from elsewhere and more detailed analysis with more events from longer follow-up.’

 

Since then, a large number of other studies have followed up, and appear to have confirmed that potassium has considerable health benefits. Some of these studies were not just observational, they were interventional. Here is summary of the potential beneficial effects. Potassium:

• lowers blood pressure
• lowers the risk of arrhythmias
• lowers the risk of cardiovascular disease
• lowers the risk of stroke
• lowers the risk of heart attacks
• lowers the risk of cancer, and
• lowers the risk of death

These benefits have been confirmed in a number of different studies. However, as this is a blog, I am not going to turn it into a medical paper and provide references for every statement, so I will stick to a couple of referenced studies. (If enough people are interested I can point you at additional papers).
With regard to blood pressure, a study published in 1997 found that adding roughly 2 grams (2000 mg) of potassium per day lowered blood pressure in older people by 15/8 mm Hg. As good, if not better, than any antihypertensive drug¹. And with no side-effects at all.

When it comes to stroke, it has been found that having a low potassium level is a very potent risk factor for both bleeding (haemorrhagic) and clotting (ischaemic strokes). In an American study it was found that in those with low potassium levels the relative risk of ischaemic stroke increased by 206%. The relative risk increased by 329% for haemorrhagic stroke².

Admittedly, these two studies were done in people with high blood pressure to start with, but these effects are also found in healthy people. However, to my mind, the most important thing about potassium is that I cannot find any study, anywhere, which suggests that increasing potassium consumption may be harmful. In short, it seems to be something that does only good.

I do recognise that a lot of doctors will shudder at the thought of adding potassium to the diet, as they have all been taught that a high potassium level is something terribly dangerous. A condition that needs immediate treatment, or else it will cause arrhythmias and death.

It is true that you need to be careful of adding potassium to the diet of patients taking medications that can raise potassium levels. These are mainly drugs used to lower blood pressure. However, even in this group the risk of overdosing on potassium is exceedingly small. For everyone else the risk seems to be zero. This is why I now recommend potassium supplementation as a good way to live a longer, healthier life.

My goodness, I think this is the first time I have ever recommended a dietary supplement. Must go and lie down.

1: ‘Long term potassium supplementation lowers blood pressure in elderly hypertensive subjects’ Fotherby M.D. et al: Int J Clin Practice 1997 41(4): 219 – 222)
2: Smith NL, et al: ‘Serum potassium and stroke risk among treated hypertensive adults.’ Am J Hypertens. 2003 Oct;16(10):806-13

Poatassium, your invisible friend

March 4, 2013Dr. Malcolm KendrickLeave a commentGo to comments

I recognise that I spent a lot of time telling people what does not cause heart disease, and what does not protect against heart disease. My sister told me… ‘well, what advice would you give people, then?’ I usually shrug my shoulders and reply ‘there is no shortage of advice around, I don’t think I need to add to the daily bombardment.’

However, I shall break the habit of a lifetime and, with slight trepidation, announce that I strongly believe that Potassium is good for you. If you consume more of it you will, most likely, live both longer and in better health.

How much should you consume? A couple of extra grams a day should do the trick. Having said this, I do recognise that most people will not have the faintest idea how much potassium they consume and, frankly, neither do I. But you are probably not consuming enough, and your kidneys will easily get rid of any excess.

For those who are not keen on bananas, spinach and broccoli, and other foods high in potassium, you could take it as a tablet. Potassium bicarbonate or potassium citrate appears to be the best formulation. Depending on which brand you decide to buy, it should cost about £15 – 20/year.

Why this sudden potassiumophilia? Well, there is a growing body of research which points to the fact that potassium is very good for you. The first time I became aware that it might be good for you was when I first looked at the Scottish Heart Health study. The researchers looked at twenty seven different ‘factors’ they thought might cause, or protect against, heart disease – and overall mortality. The authors noted that:

“[There was] an unexpectedly powerful protective relation of dietary potassium to all-cause mortality,” the study concluded.

The paper showed that:

• Men consuming an average of 5400 mg of potassium per day vs 1840 mg were 55% less likely to die during 7.6 year study (the highest one-fifth of men vs the lowest one-fifth of men)

• Men consuming an average of 5400 mg of potassium per day vs 3350 mg were 22% less likely to die during 7.6 year study (the highest one-fifth of men vs the second highest one-fifth of men)

• Women consuming an average of 4500 mg of potassium per day vs 1560 mg were 59% less likely to die during 7.6 year study (the highest one-fifth of women vs the lowest one-fifth of women)

• Women consuming an average of 4500 mg of potassium per day vs 2700 mg were 15% less likely to die during 7.6 year study (the highest one-fifth of women vs the second highest one-fifth of women

The study can most easily be found here http://www.ncbi.nlm.nih.gov/pubmed/9314758

I immediately liked this finding. Mainly because it was almost completely unexpected, and unexpected findings are always far more likely to be correct than expected findings. Also, this was a very large effect indeed. It turned out that increased potassium consumption was very nearly as protective as smoking was damaging.

Of course, this was an observational study, so I filed it under – most interesting – but did nothing much more about it. As the authors said themselves: ‘ Potassium excretion was very significantly related to risk of death from all causes, having a protective role, whereas its role in coronary events was weaker and that of sodium excretion weak and even paradoxical. These results are unifactorial, without correction other than for age and sex. Our findings need corroboration from elsewhere and more detailed analysis with more events from longer follow-up.’

Since then, a large number of other studies have followed up, and appear to have confirmed that potassium has considerable health benefits. Some of these studies were not just observational, they were interventional. Here is summary of the potential beneficial effects. Potassium:

• lowers blood pressure
• lowers the risk of arrhythmias
• lowers the risk of cardiovascular disease
• lowers the risk of stroke
• lowers the risk of heart attacks
• lowers the risk of cancer, and
• lowers the risk of death

These benefits have been confirmed in a number of different studies. However, as this is a blog, I am not going to turn it into a medical paper and provide references for every statement, so I will stick to a couple of referenced studies. (If enough people are interested I can point you at additional papers).
With regard to blood pressure, a study published in 1997 found that adding roughly 2 grams (2000 mg) of potassium per day lowered blood pressure in older people by 15/8 mm Hg. As good, if not better, than any antihypertensive drug¹. And with no side-effects at all.
When it comes to stroke, it has been found that having a low potassium level is a very potent risk factor for both bleeding (haemorrhagic) and clotting (ischaemic strokes). In an American study it was found that in those with low potassium levels the relative risk of ischaemic stroke increased by 206%. The relative risk increased by 329% for haemorrhagic stroke².
Admittedly, these two studies were done in people with high blood pressure to start with, but these effects are also found in healthy people. However, to my mind, the most important thing about potassium is that I cannot find any study, anywhere, which suggests that increasing potassium consumption may be harmful. In short, it seems to be something that does only good.
I do recognise that a lot of doctors will shudder at the thought of adding potassium to the diet, as they have all been taught that a high potassium level is something terribly dangerous. A condition that needs immediate treatment, or else it will cause arrhythmias and death.
It is true that you need to be careful of adding potassium to the diet of patients taking medications that can raise potassium levels. These are mainly drugs used to lower blood pressure. However, even in this group the risk of overdosing on potassium is exceedingly small. For everyone else the risk seems to be zero. This is why I now recommend potassium supplementation as a good way to live a longer, healthier life.
My goodness, I think this is the first time I have ever recommended a dietary supplement. Must go and lie down.
1: ‘Long term potassium supplementation lowers blood pressure in elderly hypertensive subjects’ Fotherby M.D. et al: Int J Clin Practice 1997 41(4): 219 – 222)
2: Smith NL, et al: ‘Serum potassium and stroke risk among treated hypertensive adults.’ Am J Hypertens. 2003 Oct;16(10):806-13

Real Life vs. Pharma Company Studies - Kendrick

Real Life vs. Pharma Company Studies

December 21, 2012Dr. Malcolm Kendrick

At what point, exactly, does credibility snap? When does the difference between what we are told, and what we observe, reach such a state of dissonance that it is no longer possible to believe both. Sometimes it seems the answer is ….never.

Here is one example. The clinical trials on statins found that they have virtually no adverse effects. Or, to be a little more accurate, that adverse events were virtually identical to placebo. Here, for example, is part of the press release from the Heart Protection Study (HPS). This was the last major placebo controlled statin study done in people with already diagnosed cardiovascular disease.

As the benefits of statins are now thought so wonderful it would be considered unethical to do a placebo controlled study anymore. You would be withholding statins from people who need them. Which means that you are not going to get any more evidence in this area – ever again. The HPS results were published around ten years ago, and the press release contained the following

‘Although muscle pain was reported by the participants, this happened about as commonly among those allocated the active simvastatin as among those allocated the placebo tablets. Despite 20,536 randomised patients having been followed for an average of five years, blood tests among people reporting muscle symptoms found only 11 simvastatin-allocated patients and 6 placebo-allocated patients with a rise in the muscle enzyme creatine kinase (CK) to more than 10 times the upper limit of normal Of these, 14 met the definition for “myopathy” (i.e. muscle symptoms associated with such CK elevations) of whom 10 were in the simvastatin group and 4 in the placebo group.’

http://www.ctsu.ox.ac.uk/~hps/June02QandA.shtml

Teasing these figures out a little more it seems that an extra six people taking simvastatin suffered muscle ‘problems’ than those taking the placebo. This is six people, out of more than ten thousand taking simvastatin. This represents in one thousand seven hundred and eight 1/1708 (over five years).
If this were true, then muscle problems should be exceedingly rare. The average GP with about two hundred of their fifteen hundred patients taking a statin should see a patient with muscle pains/problems about once every twenty five years. At this rate, you would not even know you had a problem.

Yet, wrapped around my copy of the BMJ last week was an advert for rosuvastatin [Crestor]. The strap line shouted out ‘Myalgia on his initial statin?’ [Myalgia is the medical word for muscle pain]. The main message the advert was… ‘If your patient was suffering muscle pains on their initial statin, they should switch to Crestor 5mg.’

Their ‘initial statin’ will almost certainly be Simvastatin 40mg. The drug, and the dose, used in the HPS study. The same drug, and the same dose recommended by the National Institute of Clinical Excellence (NICE).

Now, you do not run an expensive advertising campaign without doing a lot of market research first. What the market research must have told AstraZeneca – who make Crestor – is that a lot of people are suffering muscle pains on 40mg simvastatin.

Which means that simvastatin, which caused no discernible increase in muscle pains in the clinical study…… actually creates such a massive burden of muscle problems that a pharmaceutical campaign is running a major advertising campaign highlighting this, exact, adverse event.

What does this tell us, gentle reader? It tells us many things. Some of which would be considerable slanderous if I said them out loud. The most outstanding thing it tells me is that, although we have all been repeatedly informed that statins have no more side-effects than placebo, I now find that AstraZeneca encouraging doctors to switch statins due to the burden of side-effects.

F Scott Fitzgerald opined that …“The test of a first-rate intelligence is the ability to hold two opposed ideas in the mind at the same time, and still retain the ability to function.’

I would suggest that there comes a point where you have to decide between which idea is right, and which is wrong. With regard to statins, I did this many years ago when I recognised that they cause a gigantic burden of adverse effects, with muscle pain the single most outstanding. I knew that the clinical trials had somehow or another managed to bury this fact.

Yet, when I speak to most doctors they continue to tell me that statins have very few side-effects, as do most opinion leaders. This belief, whilst AstraZeneca starts up an advertising campaign based on side-effects reported by doctors. F Scott Fitzgerland would be impressed by all these first class intellects. I just despair of them.
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Read the complete article here.

Do Low Cholesterol Levels Cause Cancer?

Do Low Cholesterol Levels Cause Cancer?

March 26, 2012 Dr. Malcolm Kendrick

We live in a world where a high cholesterol is now considered to be virtually the most terrible and dangerous thing known to man. Everything possible must be done to bring the level down, or else you are going to die of a stroke or heart attack.

The anti-cholesterol propaganda has been so successful that six million people in the UK now take statins each and every day to reduce their risk of heart disease. Something which, I strongly believe, future generations will look back on in amazement. ‘Did they not know that cholesterol is essential for human health….what on earth did they think they were doing?’

Can it really be true that a chemical compound, so important that the liver synthesises at least five times as much as you consume in food, can be disastrous to our health. All cell membranes need it, our brains need it, almost all of our hormones are made out of it, and it is used to make vitamin D in our skin. It has always seemed to me that having too little cholesterol is just as likely to be damaging as having too much – probably more so.

One area I have particular concerns about is cancer. For many years it has been noticed that people with low cholesterol levels are more likely to die of cancer. This has been a consistent finding, for many years, from studies done all around the world^1-9.

The statin ‘zealots,’ as I shall call them, are well aware of the association between low cholesterol and cancer, and they have gone out of their way to dismiss the possibility that low cholesterol may cause cancer.

The primary argument they have used is known as reverse causality. This ‘reverse-causality’ hypothesis suggests that depressed LDL-cholesterol levels are the result of subclinical cancer (not the other way round). This idea has been put forward with absolutely no evidence to support it. Despite this, it has been accepted without question.

It is true that if you have advanced cancer, your cholesterol levels fall. This happens for a number of interconnected reasons, including the fact that large tumours use a lot of cholesterol to divide and grow.

However, the idea that a cancer so small, that it cannot not yet be detected, is using up so much cholesterol that it lowers the total cholesterol level throughout the body, is stretching the boundaries of possibility. I would say breaking the bounds of possibility.

The second argument put forward, which is not really an argument, is the ‘how can a low cholesterol level cause cancer anyway.’ It should always be remembered that a great deal of medical research consists of bumping into effects, without understanding how it could happen in the first place – see under penicillin. See more recently under aspirin protecting against cancer. A finding as yet, without any clearly defined mechanism of action.

In short, just because you can’t easily see a mechanism of action, does not mean that it doesn’t exist. In fact, several possible ways that cholesterol, or to be more accurate lipoproteins, could protect against cancer have been researched in some detail¹⁰.

Anyway, as I have always known must happen, the ‘reverse causality’ hypothesis has finally been laid to rest. A recent analysis of the longest running heart disease research project in the world (the Framingham Study) has shown that low cholesterol levels predate cancer diagnosis by many, many, years. And, to quote:

“Based on these data, it would suggest that lower cholesterol predated the development of cancer by quite a long time. Now, that doesn’t necessarily speak to [low cholesterol] causing the cancer; it could have been related to something else altogether, but it’s not supportive of the hypothesis that cancer caused the low levels of LDL cholesterol. We don’t know why it predates cancer, but it would be premature to attribute it to the cancer itself.” ¹¹

In short, it must now be accepted that cancer doesn’t cause low cholesterol levels. Which leaves the possibility that low cholesterol levels might cause cancer. This, inevitably, leads to the next question. If low levels of cholesterol precede cancer, can statins cause cancer?

The evidence is not conclusive, and I would not claim that it was. But there have been some significant warning signs from statin studies. Just to mention three. In the CARE trial¹², twelve women in the statin group had breast cancer at follow up, compared on only one in the placebo group. In the PROSPER study¹³ there were forty six more cases of cancer in the statin group than the placebo group.

Possibly the most worrying figures come from a Japanese study which looked at nearly fifty thousand people taking statins over six years. They found that the number of cancer deaths was more than three times higher in patients whose total cholesterol was less than 4.0mmol/l at follow-up, compared with those whose cholesterol was normal or high:

‘The patients with an exceptionally low TC (total cholesterol) concentration, the so-called ‘hyper-responders’ to simvastatin, had a higher relative risk of death from malignancy than in the other patient groups.’

The authors then went on to warn:
‘Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC (cholesterol) and LDL-C (Low Density Lipoprotein ‘bad cholesterol’) concentrations with low-dose statin.’¹⁴

This is not proof of causation, but these are warning signs. Armed with the Framingham data, I believe that the medical profession has to face up to the painful reality that low cholesterol levels could be a cause of cancer, and this needs to be properly researched. We must remember that it took Richard Peto more than thirty years to prove that smoking caused lung cancer, and no statin trial has lasted longer than six.

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10: http://qjmed.oxfordjournals.org/content/early/2011/12/08/qjmed.hcr243.full.pdf?keytype=ref&ijkey=kZGZxqVjYWEOtoc
11: http://www.theheart.org/article/1375049.do?utm_campaign=newsletter&utm_medium=email&utm_source=20120325_ACC_dimanche_2
12: Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD,Cole TG, et al. Effect of pravastatin on cardiovascular eventsin women after myocardial infarction: the cholesterol and recurrent events (CARE) trial. N Engl J Med 1996;335:1001–9
13: Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM,Cobbe SM, et al. Pravastatin in elderly individuals at risk ofvascular disease (PROSPER): a randomised controlled trial.Lancet 2002; 360:1623–30.
14: . Matsuzaki M, Kita T, Mabuchi H, Matsuzawa Y, Nakaya N,Oikawa S, et al. Japan Lipid Intervention Trial. Large scalecohort study of the relationship between serum cholesterol lconcentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia. Circ J 2002; 66:1087–95.
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