Aletho News

In the midst of the Covid-19 pandemic, almost every other medical condition has been shoved onto the sidelines. However, in the UK last year, heart attacks and strokes (CVD) killed well over 100,000 people – which is at least twice as many as have died from Covid-19.

CVD will kill just as many this year, which makes it significantly more important than Covid-19, even if no one is paying much attention to it right now. So, it is good to see that research goes on, and papers are still being published.

One of the most significant, and of great interest to me personally, was a critical examination of the benefits of lowering cholesterol. This was published on August 4. The paper was called ‘Hit or miss: the new cholesterol targets,’ and it came out in Evidence Based Medicine, one of the key titles that sits under the umbrella of British Medical Journal publishing.

It was carefully worded, as all clinical papers are, but a key section of the press release was as follows: “Setting targets for ‘bad’ (LDL) cholesterol levels to ward off heart disease and death in those at risk might seem intuitive, but decades of research have failed to show any consistent benefit for this approach, reveals an analysis of the available data, published online in BMJ Evidence Based Medicine.”

What is being said here is the following. Everyone thinks that lowering LDL, aka ‘bad cholesterol,’ is considered the single most important way to reduce the risk of heart disease and strokes. However, “decades of research have failed to show any consistent benefit for this approach.”

Surely this flies in the face of almost all the advice we have been bombarded with for the last 50 years or so. Cholesterol – by which we really mean low density lipoprotein (LDL) – is a killer and must be lowered. This is the whole point of statins, the single most widely prescribed type of drug in the history of medicine. Drugs that have racked up sales of nearly $1 trillion since their launch.

Now, newer and far more expensive LDL-lowering medications are available, riding on the success of statins. They are injectable, rather than tablets, and the cost is far higher. In the US, you are looking at around $5,000 per year. In the UK, one of these drugs, Repatha, costs the NHS just over £4,000 ($5,200) per year. These drugs are known as PCSK9-inhibitors.

These are eye-watering costs. It is estimated that around seven million people in the UK take statins currently. If everyone converted to a PCSK9-inhibitor, this would cost the NHS £28 billion ($36.4 billion) a year – not far off the entire defense budget.

But do these drugs work, does lowering LDL work? Surely it does, surely it must. The answer is, not necessarily. Yes, statins have been found to reduce the risk of cardiovascular disease, not by a massive amount, but the effect exists. At least in some studies, if not all.

However, many other drugs also reduce the risk of cardiovascular disease without having any effect on LDL levels, e.g. aspirin. A number of researchers have long argued that the benefits of statins are mainly due to “off-target” effects, by which they mean that, yes, statins lower LDL, but they also have effects on many other things and it is the “other things” that provide the benefit.

For example, statins have been found to have quite strong anti-coagulant (anti-blood-clotting) effects. Same as aspirin, as highlighted in the 2013 paper, ‘Anticoagulant effects of statins and their clinical implications.’ It states: “There is evidence indicating that statins… may produce several cholesterol-independent antithrombotic [anti-coagulant] effects.”

So, it has always remained possible that the main benefit of statins was not due to their impact on lowering LDL. It is because of something else that they do.

In this recent study, the authors decided to examine this possibility. So they gathered together all the LDL lowering trials – at least those big enough, and long enough to count – and try to establish whether the amount that the LDL was lowered matched the reduction, if any, in cardiovascular disease. The technical term for this is “dose-response.”

Or, to put this another way, if the LDL hypothesis is correct, the greater the LDL lowering, the greater the benefit on CVD should be. What did they find? Here are the key findings – from the press release:

“Their analysis showed that over three quarters of all the trials reported no positive impact on the risk of death and nearly half reported no positive impact on risk of future cardiovascular disease.

“And the amount of LDL cholesterol reduction achieved didn’t correspond to the size of the resulting benefits, with even very small changes in LDL cholesterol sometimes associated with larger reductions in risk of death or cardiovascular ‘events,’ and vice versa.

“Thirteen of the clinical trials met the LDL cholesterol reduction target, but only one reported a positive impact on risk of death…

“Considering that dozens of [randomized controlled trials] of LDL-cholesterol reduction have failed to demonstrate a consistent benefit, we should question the validity of this theory.”

And they conclude:

“In most fields of science the existence of contradictory evidence usually leads to a paradigm shift or modification of the theory in question, but in this case the contradictory evidence has been largely ignored, simply because it doesn’t fit the prevailing paradigm.”

In short, what they found was that there was absolutely no correlation between the amount that LDL was lowered and the resulting benefit on CVD. In fact, the benefit was inverse i.e. the less the LDL was lowered, the greater the benefit.

This is a hugely important finding that really ought to be shouted from the rooftops. I admit I have a horse in the race, having long argued that LDL has nothing to do with heart disease (and being roundly condemned for doing so). So, it is nice to have my thoughts so powerfully supported in a peer-reviewed, high-impact journal.

For the average person on the street, what this research means is that you should stop worrying about your LDL levels, and obsessively trying to get them down with drugs or diet. Tucked away in the paper was this significant finding:

“Moreover, consider that the Minnesota Coronary Experiment, a four-year long RCT [randomized controlled trial] of a low-fat diet involving 9,423 subjects, actually reported an increase in mortality and cardiovascular events despite a 13 percent reduction in total cholesterol.”

Cholesterol (LDL) went down, CVD went up. We really are wasting a colossal amount of money.

Malcolm Kendrick is a doctor and author who works as a GP in the National Health Service in England. His blog can be read here and his book, ‘Doctoring Data – How to Sort Out Medical Advice from Medical Nonsense,’ is available here.