Every day a billion things pop into my inbox, and I find my thought dragged this way and that. Mainly, what should I blog on next, and can I be bothered…..so much wine to be drunk.
However, I thought I should give everyone a quick head up on VARESPLADIB. This is the first and last time you are going to hear of this drug, so listen up. The first thing I would like to draw your attention to is the list of authors
Stephen J. Nicholls, MBBS, PhD; John J. P. Kastelein, MD, PhD; Gregory G. Schwartz, MD, PhD; Dianna Bash, RN; Robert S. Rosenson, MD; Matthew A. Cavender,MD, MPH; Danielle M. Brennan, MS; Wolfgang Koenig, MD; J.Wouter Jukema, MD, PhD; Vijay Nambi, MD, PhD; R. Scott Wright, MD; Venu Menon, MD; A. Michael Lincoff, MD; Steven E. Nissen, MD; for the VISTA-16 Investigators 1
Notice anything. Ah yes, Steven Nissen appears once again on a major study. He certainly gets about does our Steven. Another name that means much to me, but nothing to you, is John P Kastelein….he gets about too. Hardly a day passes without these guys running a major clinical trial, and then writing about it. I think they must have been cloned in the past to get through so much work.
Anyhoo, enough of them. What is, or was, VARESPLADIB, and why should you care. Here from the study itself.
‘Varespladib methyl is a nonspecific pan-sPLA2 inhibitor with favorable effects on atherosclerotic lesions in animal studies. Initial studies demonstrated that varespladib reduced levels of sPLA2-IIA by morethan 90%,in addition to lowering low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) in patients with stable coronary disease and ACS.’
So now you know. Or maybe not.
Stripped to its basics, varespladib (which I shall PLAD) is an anti-inflammatory drug specifically designed to reduce the inflammatory cascade that is thought to be a major cause/risk factor for heart disease. Not only that, but it reduces LDL ‘bad/naughty cholesterol’ and C reactive protein too – a sign of inflammation in the arteries. Possibly CRP may even be a cause of CHD… in truth you might think it is a cause, if you are idiot.
Some years ago I wrote that we should await the C-reactive protein lowering agents. On the basis that a high CRP levels had been identified as ‘risk factor’ for heart disease. I wasn’t sure if it would happen, but I suspected it would. I predicted that lowering CRP would be a complete and utter waste of time.
Inflammation cannot, I have always said, be the cause of anything. Inflammation is the way that the body heals itself. If you cut yourself you will develop a red and inflamed area around the cut, otherwise known as inflammation. The inflammation did not cause the cut, the cut caused the inflammation.
However, such is the idiotic thinking in heart disease research that various people, led by Paul Ridker, decreed that inflammation causes heart disease (and not the other way around). They then decreed that if you could lower the inflammation that the risk of heart disease would fall. The noise in the background is the mad stampede of pharmaceutical companies rushing off to find drugs to block the inflammatory pathway, lower CRP, and cure heart disease.
Enter PLAD. Here we have a drug that lowers inflammation, lowers CRP, and as an extra added bonus lowers LDL ‘bad/naughty’ cholesterol, so it should provide a triple benefit. And guess what we find:
‘At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm.’
‘In patients with recent ACS (acute coronary syndrome – a heart attack to you and me), varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.’
I am sure that there are a whole new bunch of anti-inflammatory agents out there, being trialled as I write this. I am also sure that they will fail. Hey guys, you could save billions if you read my stuff.
Now, repeat after me. Blocking inflammation blocks healing. Block healing and you die. End of. Time for a glass of wine.
1: Varespladib and Cardiovascular Events in Patients With an Acute Coronary Syndrome The VISTA-16 Randomized Clinical Trial. JAMA. doi:10.1001/jama.2013.282836
> This is the first and last time you are going to heart of this drug, so listen up.
Interesting typo! 😉
Too much wine, obviously
Now changed, thanks for the spot. Rule 1: Don’t write blogs when you have drunk alcohol.
I would drink a little wine too with the huge responsibility you have. Your book, The Great Cholesterol Con,was one of the few books a layperson like myself can get through because although scholarly, your ability to capture the attention and imagination of readers through humor is a gift. It is as though you HAVE to laugh to keep from crying!! I can’t wait to read the next one, Dr. Kendrick. I have a lot of reading to do. I have read quite a bit in the last several months for I did not come to the decision to stop statins lightly and I am not easily swayed. I see a much different mentality in the U.S with regard to statins. Many are so willing to listen and many I know, just from knowing me and hearing my story, have stopped them and WILL NOT GET BACK ON THEM. They have witnessed my demise and know that something really bad was happening to their friend and family member. I even brow beat a doctor into taking my aunt off a statin. He finally agreed with me. He said I was right…there was no reason for the former doctor to have put my aunt on 80mg statin (no heart disease or signs of heart disease). They know Dr. Kendrick. Look at what the brave Senator did for Dr. Graham when he blew the whistle on unscrupulous activities he witnessed while working for the FDA. Whether more lawmakers have the guts to do something is yet another question. I happen to believe, there are many more brave souls on capitol hill. In one of your blogs (varispladib), you said that if these researchers had read your stuff, they could have saved a lot of money. How do you know they haven’t read your blogs? How do you know they have not read your book (brilliant compilation of proof that statins don’t work and do harm) or seen Statin Nation. The fact is…they have. I would bet money on it. And, they are running scared. I bet that makes you feel so proud of your role here. What you are doing is making a difference!!! It just happens much more slowly than any of us would like. I recall this with my own father as he worked tirelessly both on capitol hill and locally to see change. Some of the changes that came about would blow your Scottish mind!!! Steady, hold your course and, keep your eye on the prize!!!
Thank you. I am but a needle against a hedgehog.
May I just observe that the 2005 McWilliams Mt Pleasant Elizabeth Semillon at Tesco is a lovely drop. Mature Hunter Valley Semillon is probably good for the heart too. And at only 8 years old it will probably improve further.
My God, you couldn’t make this stuff up could you.
What was it called again? I think I’d prefer “Statin”, – rolls of the tongue so much easier.
Don’t worry about curing/preventing the disease lads, just concentrate on treating the symptoms. That’s where the money is.
What I find encouraging is “the independent data and monitoring board recommended termination of the trial for futility and possible harm”. Not “let’s see if we can distort the figures chaps”. Is this a positive change for the better, or just a blip?
Malcolm, You forgot to mention Jukema. I got a file on him. The guy is a public menace. And I always thought that the psycho/sociopaths were in charge of big corporations. They apparently have their underlings elsewhere too.
I couldn’t possible comment as to whether or not someone was a sociopath or not.
My God people, do these “scientists” think we are all uninformed? Many are, but you meaning all of those who believe that statins damage, must, cut them off at the pass (as the cowboys would say) and make some noise!!! If you have to shout it from the rooftops, then so be it. The democratic system in the U.S. works. But, it can’t work, if you don’t use it. It is high time we not only told our horrid stories, but told them to people in a position to stop the charlatans from ruining our lives (or what we have left of them). I don’t care what big Pharma does or thinks. This latest study proves they know we are on to them. I see advertisements on Television where huge trial lawyer firms are announcing that people who took Lipitor and developed diabetes might be eligible for monetary compensation. So, if the FDA and Big Pharma gets caught enough times, money surely does talk, especially if they have to part with it. More lawsuits are on the way…at least here in the USA, mark my word. It is coming as sure as God made little green apples.
I also looked for a certain name somewhat like a certain Japanese car manufacturer and lo and behold, there it was. Quel surprise!
T he context and your comments on wine reminded me of this – and since I’ve learned you like you both wine and quotations ( a man after my own heart! ) here’s a couple for you:
“And much as Wine has play’d the Infidel,
And robb’d me of my Robe of Honor–
Well, I wonder often what the Vintners buy
One half so precious as the stuff they sell. ”
You know, my Friends, how long since in my House
For a new Marriage I did make Carouse:
Divorced old barren Reason from my Bed,
And took the Daughter of the Vine to Spouse.”
Where CVD is concerned currently, the second part most definitely applies. A very wise man, the author. Recommended.
“We at Merck Automotive have noted a significant correlation between car-accidents and the deployment of airbags.
As such, it is clear that therapies for your car which constrain the ability of airbags to deploy will significantly reduce the number of injurious crashes that occur.
To that end, we introduce Debagectomil, a novel treatment which inhibits the chemical pathway which provokes inflation. We begin clinical trials soon, and anticipate substantially fewer accidents in those cars treated with this patented inflation-inhibition therapy”
I like it
Inflammation seems the buzz word at the moment. As it seems to be blamed for causing every disease. I believe it is only the body’s form of protection and trying to prevent it is crazy. The more important research to carry out would be what is causing the inflamation but I think this would not be profitable.
True, true. Because eating properly, eating only enough, exercising every day, keeping stress low, and engaging in regular activities that produce laughter and feelings of comraderie can’t be patented.
So, if heart disease causes inflammation. What causes heart disease?
Inflammation is the body’s reaction to damage (sometimes this reaction can cause further damage e.g. rheumatoid arthritis, asthma, and suchlike). Mostly, inflammation is a healthy repair process
Is it stress doc?
Stress plays a part
Here’s a guess: the problem is infection, by agent or agents unknown. If stress plays a part, it’s buy suppressing the effectiveness of the immune system.
This is incredible!!!! The following is from the BHF. Talk about gobbledygook… RJW
Stress and heart disease
British Heart Foundation:
Stress is not a direct risk factor for cardiovascular disease, but it’s possible that it may contribute to your risk level. It all depends on your coping mechanisms.
Some people cope with stress with risky behaviour – such as smoking, drinking too much alcohol and overeating.
All of these increase your risk of cardiovascular disease.
How does stress affect the heart?
There is no evidence to suggest that stress causes coronary heart disease or heart attacks.
YOU HAVE TO BE KIDDING ME! RJW
But if you have coronary heart disease and experience feelings of anxiety or are under lots of stress, it may bring on symptoms like angina.
THIS IS NOT CARDIOVASCULAR DISEASE????? RJW
What you can do:
Changing your lifestyle in a positive way can help you feel better able to cope with some of the demands put on you. A balanced diet and regular physical activity will help you cope with stress.
WHY BOTHER? STRESS DOESN’T CAUSE CARDIOVASCULAR DISEASE! RJW
If you often feel stressed or anxious, it’s important to learn how to relax.
AGAIN; WHY??? RJW
Some people find that physical activity, yoga or other relaxation techniques can help. You could make a list of things that help you to relax and schedule one every day.
You may need to identify situations that make you feel stressed at home or at work and try to avoid them if you can.
NO! YOU DON’T. THEY DON’T CAUSE CARDIOVASCULAR DISEASE, DO THEY? RJW
You could also learn techniques for managing stress. If you think you are stressed or very anxious, talk to your GP who will be able to help you decide on the best way to deal with it.
WOULDN’T THAT BE COUNTERPRODUCTIVE– AND NOT RELEVANT?
I need to fit the following on a T-shirt:
On the front:
‘I can cope with stress but strain is hard to bear.’
On the back:
‘Don’t push me past my elastic limit.’
Although that second line might be better printed on the waist-band of an undergarment.
It’s geeky but I can tell you that these bogus researchers do stretch my credibility beyond the breaking point.
Thank you for another interesting look into the “dark world”.
This confirms again my present view of medicine as an art of religious beliefs far from science.
Medicine is at best a remedy to me but the only heart medicine, and which I really enjoy – a remedy, is moderate amounts of alcohol regularly. This very moment I am enjoying a good scotch malt whisky while reading the last pages of “An Essay concerning Human Understanding” by John Locke.
Goran, sounds perfect. I am now enjoying a little Glenmorangie whilst trying not to despair of human stupidity. As Einstein once said ‘Only two things are infinite, the universe and human stupidity, and I’m not sure about the former.’ But, hey, someone managed to invent whisky, the internet and chocolate eclairs, so there is some real intelligence out there too.
I am so sad to think of the immensity of “stupidity” (shorthand for lack of ability to employ critical thinking). I would think anyone of the “authors” of the study would be embarrassed to have his/her name appended to such a display of upside down “thinking”.
On another note, how much wine is “too much” and, of course, the answer depends on the company one keeps. no?
Too much is a bit more than me
Read this: http://butterflyenzyme.com/serrapeptaseemphysema-radio-interview/ (Copy and paste if necessary).
In 1990 I underwent an emergency quadruple by-pass but was not informed about this natural product. For five years following the operation I was exceedingly ill and each day felt that I was not about to last the day that was until I read about what medicine I was prescribed. On stopping the prescription medication and taking Serrapeptase (as described in Hans Napier’s book, The Silent Man) and CO-Q10 at 100 mg daily I rapidly recovered and I am not on any medication today, eighteen years later. I do however take occasionally Hawthorn extract. Hopefully, this anecdotal information may add to the discussion.
“including 212 primary end point events”: comedy gold!
All of the above sounds like the scenario of a very bad slapstick, black-and-white, mute comedy from the late 1800’s. A bunch of prop lab coats ‘researching’ something obviously beyond stupid with a straight face.
What year is this, again?
Medical researchers could save (probably, not spending money is not very desirable) a lot of money if they studied first the theory of complex systems, according to which, a complex system (a body, ecosystems, economy) should be self regulated, if micromanaged, it will get into a chaotic state. I grew-up in a socialistic country, and had a lot of opportunity to observe how chaotic everything can get when market forces were replaced by human “planning”, the disintegration of Soviet Union stopped that experiment, but now I have an opportunity to observe how medical professionals try to micro-manage the work of a human body on a massive scale by treating different numbers like the total cholesterol and fighting symptoms of an unaddressed diseases.
Gosh, a great idea. Unfortunately our elected leaders do not have a clue about complex systems. If they did, we would be in a resource based economy and not one based on lots of favours and a broken money system.
The money system drives almost all behaviour. We must consume more products/food/drugs because that’s where the jobs are. What we then do is provide cures for the diseases which all the products/foods/drugs have caused.
These cures are needed as a natural consequence of our behaviour caused by a rotten/poor/lousy system.
A virtuous circle if ever I saw one.
There’s a lot more of course but… Sorry, got to dash and get my fix of sugar, then a trip down to the pharmacy for my magic diet pill:-)
I believe, it is a good idea to remember that in some instances we are dealing with complex systems, then no one would be surprised , for example, that Obamacare had such a messy start, however mess exceeded all expectation when government even failed to produce a functioning web-site which should be absolutely micro-managed into perfection during appointed time.
I don’t think there is a conspiracy to keep people sick, first of all because I don’t think that it is possible perfectly micro-manage processes in a complex system,even IF some group of people conscientiously works in a such direction. Global forces are at work here when the scale is so big. Indeed, the money drive everything in a civilized human society. I suspect there is another reason for the order of things which causes such effect. We all want to be healthy, but it looks like it is not what is needed for the better development of our civilization. So far I see the trend in a human history that societies which consists of sicker and weaker people do better as a group. Most probably it will end as a crisis some day in several centuries, as it is normal, but before that the trend will continue – as the civilization will grow stronger, people in general mass will be getting sicker.
December 4, 2013 at 11:38 AM
I recently pushed my CRP to 414 by running round with a perforated appendix. So I understand very well how it is an important marker of what is going on inside. Artificially reducing it would have hidden my true situation to a dangerous extent.
A very famous Russian actor recently did from a lung cancer. The first symptom of the cancer was a back pain which the actor attributed to multiple injuries while doing all movie tricks like falling from horses and jumping from cars by himself. He went to a famous acupuncturist in China and was very successfully treated for his back pain. Unfortunately, in a while his pains re-started, and it was found he had a cancer.
” the most biased and damaging TV show … medically … in years” – http://www.news.com.au/lifestyle/health/abc-catalyst-tv-show-causes-at-risk-patients-to-stop-their-medicine/story-fneuzlbd-1226773658412
I knew the attacks would be bad. They were pretty much as expected.
I guess internet is damaging for the pharm industry as well
One certainly hopes so
Saying that inflammation cannot be the cause of anything is an oversimplification at best and quite misleading in my opinion. Of course, in most cases, inflammation is a part of a healing process or a result of a normal reaction of the immune system.
We know that inflammation is involved in atherosclerosis. Of course such an inflammation may be a part of a healing process. However, if that inflammatory process leads to an acute occlusion (blockage) of a coronary artery it will lead to a myocardial infarction (heart attack). In this case, although inflammation is a “normal” response, it may be responsible for a serious event and possibly death.
Well, you may be right. But up to now (apart from aspirin, which has significant anti-coagulant effects) all anti-inflammatory agents have greatly increased the death rate from CVD. Steroids being the worst of all. So the experimental evidence is very strong, and it says that trying to reduce inflammation increases death. Or, perhaps you have evidence to the contrary?
Some drugs currently used in cardivascular medicine have anti-inflammatory effects which may contribute to their efficacy, examples are statins (I know you believe they don’t work), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers, Antiinflammatory drugs such as canakinumab and methotrexate are currently being tested in clinical trials.
Interestingly, many lifestyle measures may reduce chronic low grade inflammation. Physical exercise is among those. Many dietary factors have been reported to confer anti-inflammatory effects (benefits?), examples are omega-3, magnesium and many other compounds. A lot of evidence suggest that a Mediterranean type diet may reduce inflammation, which could possibly (although not proven) contribute to its positive effects on cardiovascular risk. Obesity is associated with increased low grade inflammation and losing weight generally reduces the inflammatory response.
Of course you could always say that inflammation is secondary, and thereby suggest that reducing it is not helpful. Acording to this, the cause of inflammtaion should be adressed, not the inflammation itself. Hopefully future resaerch will tell us whether chronic low grade inflammation in itself is harmful or not. I will not claim to know the answer. But, at this stage, I don´t believe we can say that blocking or reducing inflammation is always bad because inflammation is always a healing prcess. Current evidence suggests this is an oversimplification, but it might certainly be put forward as a hypothesis.
Well, it is of course, an oversimplification (deliberate, I may add). By the way, I do not believe that statins do not work (they work a bit). I just don’t believe that they work by lowering LDL, or lowering inflammation. They work, as do ACE-inhibitors, by increasing NO synthesis and thus having powerful anticoagulant effects. Also, of course, exercise lowers inflammation. However, it does a bazillion other things too. Is the lowered inflammation just a ‘marker’ of the benefits of exercise. In my view, yes. In my other view, if you reduce inflammation, you are probably doing good. However, if you are doing this by targeting the inflammatory response itself – you are almost certainly doing bad. You need to target the thing that is causing the inflammation in the first place be it obesity, lack of exercise, on-going arterial damage etc.
This is interesting!
I like the idea of cause – belongs to science!
When one is talking about strengthening our immune system, by for instance by avoiding to much of omega-6 PUFA, that would, with the same logic, be equivalent to a stronger inflammatory response. High doses of corn oil, mostly consisting of PUFA, was evidently originally used to prevent the ejection of transplanted kidneys but this practice had to be abandoned due to the high cancer rate.
Does this make sense?
Hi, No one seems to have a confident answer to what causes inflamation. My belief therefore is that the best cause of action is to study and mimic those populations that have little or no heart disease. As I mentioned elsewhere I am currently reading about the Okinawas. Dr Kendrick believes we cannot become Okinawas. I disagree in the sense that I only want to obtain their health benefits and in terms of diet and lifestyle I can certainly take in many of their ingredients. Yes I cannot absorb all of their lifestyle components but hopefully I dont have to. I will be moving to southern Portugal for most of the winter months in order to enjoy better weather and catch more sun hence Vit D, which has been cited as one of the possible reasons for the hemishpere divide on heart disease. On an unrelated note, I have wanted to take CoQ10 and Ginko Biloba but alas find both cause upset stomach. Anyone have any suggestions ?
Good for the 14 percent of Australian doctors who said they would decrease their prescribing of statins to low risk patients. And good for the patients who rebelled against the system. It’s a start…
An excellent anti-inflammatory agent which is not so widely known is kitchen flour but only as it relates to burns or scaldings. When applied immediately after a burning accident there is no inflammation and the wound heals rapidly if not almost immediately. Serrapeptase too is excellent at reducing inflammation (although needs to be taken on an empty stomach to work its magic) and it reduces and clears bruising and helps to rapidly heal. From experience it would seem that reducing inflammation aids healing (supporting research; what’s that)?
Yup. If you put ice on sprains it reduces inflammation too. However, it hampers healing. There are some instances where the inflammatory response becomes the problem itself e.g. rheumatoid arthritis, asthma. But, in general, over billions of years, nature worked out the best way to heal injuries.
I can think of steroid joint injections that they give, for example, for tennis elbow. They actually cause harm by reducing the inflammatory process, thereby the damaged tendon doesn’t ‘heal’. The injection simply covers up the pain. Much better to do specific strengthening exercises and a lot of time. I know, I’ve had both the injection and then refused a second one when the first wore off after a few months….it actually caused my tennis elbow to get worse and it took at least 18 months of great care and specific exercises to recover which I should have done in the first place.
Sage tablets probably would have helped with the pain Anne and while I know they are beneficial I do not know why. I find them (and interestingly beetroot too) to help at alleviating nocturnal cramp.
If CVD is caused by infectious agents, the huge decline in incidence of CVD since the sixties might be caused, at least in part, by “overmedication” with antibiotics. So perhaps the GPs have been saving many of us from heart attacks unknowingly. If antibiotic-resistant bacteria really do pose the threat that worries people, all bets are off.
@ docsopinion. My uncle had RA and took methotrexate for years under the advice of a rheumatologist. He then developed non Hodgkin’s lymphoma and had to undergo chemo. His oncologist spoke about the risk of methotrexate which no one talks about. So please docsopinion have a look at the links and research about methotrexate which has been shown to cause non Hodgkins lymphoma in 1.8% of patients. If that is an acceptable risk to a member of you family then go ahead and prescribe it.
Dr Malcolm is the only one with the courage to take this on and that CVD is partly caused by stress as I understand, and we have to work on decreasing the stress and get people to reduce the inflammatory processes in the body. Methotrexate is not an answer.
Never say never, but I shall likely fall off my chair if methotrexate does more good than harm.
Don’t blame me. I was only informing you that there is an ongoing double blind placebo controlled study on the effects of methotrexate in patients with coronary artery disease. I wasn’t advocating methotrexate. Never prescribe it by the way.
By the way Dirk, I have actually written a piece on the relationship between stress and heart disease.
Go look at the work by Dr Knut Sroka( German GP for over 30 years)- which is heavily referenced. The cause of Heart seizure (angina) and Heart attack ( spasm) is a completely different story and bears a relationship to what Dr Malcolm Kendrick wrote in his book The Great Cholesterol Con( The cause is stress). Dr Knut Sroka has written some books ( in German). Only about 16% of cases have a connection to arteriosclerosis. Thus coronary artery disease is a slight red-herring at this moment in time.
I would agree that there is far more to a myocardial infarction than atherosclerosis. However, I would disagree with his figure of 16%. Equally, almost all strokes are related to atherosclerosis in the carotid arteries in the neck. There is the Takotsuba (MI) caused by stress. There is MINOCA, Myocardial infarction with no obstructive coronary atherosclerosis. However, this does no mean that the blood clot was never there. It is more complicated than that. I shall do a blog on the ‘heart attack’ at some point.
I suggest that you look at the work by pathologist Baroldi. There is a strong suggestion from histological work that a clot forms AFTER the MI and NOT before.
I have just found some papers, originally researched by Russians about foam cells in the artery walls that are thickened and thus have developed a Vasa Vasorum-I understand this is supplied by Sympathetic ns-F,F,F, system. I also found some papers by a German Surgeon that from his observations, the disease starts from the outside/inwards. This observation may correlate somewhat with the work of the Russians-this paper is on Science Direct.
Dr Knut Sroka does emphasize and educate on the parasym. ns far more than I ever knew or was taught in Physiology.
PS My interest has been for 17 years. I then had 2 heart attacks recently and a Triple bypass surgery 1 month back. This whole subject is so complex, and what is directing it? My first attack of Angina occurred after a severe period of stress dealing with a public health issue. I was not the only one to become unwell. But all settled and my angina disappeared into the background for years without drugs, until my recent events about 2 months ago.