ARE you taking statins? Should you take them? Some cardiologists, Prof Rory Collins in the UK among them, believe everyone above the age of 50 should, even if they have no signs of heart disease whatsoever. Others, among them British consultant cardiologist Dr Aseem Malhotra and Scottish GP Dr Malcolm Kendrick (author of The Great Cholesterol Con), say that’s just crazy. University of Cape Town emeritus professor Dr Tim Noakes calls statins “the single most ineffective drug ever invented”. Kendrick has lambasted the powerful pharmaceutical industry and ‘unquestioning medical profession’ for perpetuating the ‘madcap concepts’ of ‘good’ and ‘bad’ cholesterol to make millions of people spend billions on statins. Still, the global ‘statin insanity’ goes on. Here’s a peek into what some doctors call ‘statin insanity’ – the overuse and abuse of cholesterol-lowering drugs. I also look at ‘new-generation’ statins that may be no better than their predecessors.
Welcome to “statin insanity” – the extraordinary world of blockbuster cholesterol-lowering drugs that have become the world’s most prescribed pharmaceutical preparation and “the most profitable drug in the history of medicine”.
Statins have always been clever at their job of lowering cholesterol. The only problem is lowering cholesterol isn’t always a smart thing to do. It can even be harmful. The experts say your body needs cholesterol, both “good” and “bad”. So it really makes no sense to talk about cholesterol as good or bad, because without it, you’d be dead.
There is even research to suggest that statins may cause heart disease when they are supposed to prevent it. If that were not bad enough, statins are shown to increase your chances of becoming diabetic and to ramp up your risk of Parkinson’s, kidney failure, liver problems, cataracts and more.
So why do doctors want you to take them?
Cholesterol-lowering drugs were introduced in 1987 for secondary prevention of cardiovascular disease (CVD) – that is, for patients who have had a heart attack or stroke, or with established CVD.
Millions around the world take statins; many doctors says the drugs have been lifesaving. They point to millions of lives saved, and millions of heart attacks and strokes prevented.
However, just as many doctors say these drugs don’t actually work well at all. They don’t agree with the current push for statins to be used for primary prevention of CVD – in other words, in lower-risk, otherwise healthy patients, including children, to prevent a heart attack or stroke.
They say that’s just “statin insanity”.
The push comes in revised US guidelines introduced late 2013 by the American Heart Association (AHA) and American College of Cardiology (ACC) that dropped the 10-year CVD risk threshold to treat from 10% to 7.5%. In the UK in 2014, the National Institute for Clinical Excellence (NICE) issued guidelines dropping the risk to 10%.
In the US alone, at least about 25 million people take statins. Guidelines could mean 10 million more on statins (some say the figure is closer to 30 million) including children. In Britain, around 8 million people are on statins, and if doctors follow NICE guidelines, another 5million will be taking the drugs.
That’s an awful lot of people on statins, and an awful lot of money going into the coffers of drug makers that have already made billions annually from the drugs.
Doctors opposed to statins for primary prevention say:
- It medicalises healthy people;
- Data on benefits are from industry-funded studies;
- Risk data have been suppressed;
- 50% to 75% of people with “normal cholesterol” have a heart attack;
- 80% of CVD is caused by lifestyle;
- Higher cholesterol is associated with longevity in the elderly; and
- Pharmaceutical companies unduly influence doctors.
Collins was asked to elaborate further on statins for this blog, but declined – probably not all that surprising, given the withering critique of him on HealthInsight UK by award-winning health and medical journalist Jerome Burne. Burne wades into Collins for concluding that statins are perfectly safe, despite having “no data other than what the drug companies had published – a suspect source of information”. (Some of Burne’s other comments would be funny were they not so serious in intent.)
Certainly, medical experts remain deeply divided over the “collateral damage” in “statin wars” – the drugs’ side effects. The list of possible side effects is long, and daunting to the lay person. It includes diabetes, muscle aches, kidney and liver problems, cataracts, sexual dysfunction, memory and cognitive decline, and more recently a study showing that statins may increase the risk of Parkinson’s and Alzheimer’s.
If that were not bad enough, Japanese research in the journal, Expert Review of Clinical Pharmacology, suggests that statins may actually cause atherosclerosis (hardening of the arteries) that is the leading cause of heart attacks, stroke, and peripheral vascular disease. That’s precisely the reason your doctor would have perscribed statins for you in the first place.
The researchers give the pharmacological mechanisms behind which statins can do this, and are to my mind relatively restrained in their conclusions. They say that “paradoxically”, the pervasive use of statins may be aggravating the epidemic of atherosclerosis and heart failure worldwide, and propose that current treatment guidelines “be critically reevaluated”.
There appears to be consensus that the diabetes risk is real. However, some experts say the incidence of side effects is grossly overstated – that most are minor, and occur only in one in 1000 people. A major review of the evidence by UK researchers, published in the European Journal of Preventive Cardiology in 2014, supports this, and concludes that few commonly reported side effects were genuinely related to taking the drugs, compared with placebo.
Other experts say side effects are under-reported, and the incidence is at least 20%.
The Parkinson’s link is concerning. It comes in research over 20 years, involving nearly 16,000 people, suggesting that cholesterol plays a vital role in protecting the brain and nervous system.
Study lead author Dr Xeumei Huang, neurology professor at Penn State College of Medicine, says in a university release that her analysis, published in the Journal of Movement Disorders, is based on a “fairly small number of cases”. However, the preliminary data suggest that statins do not protect against Parkinson’s disease as was previously thought to be the case.
Huang is concerned at widespread prescription of statins, and says that while more research is needed, “what’s good for the heart may not be good for the brain”.
The AHA, ACC, and NICE don’t appear to share that concern – not sufficiently to warrant any revisiting of their guidelines at any rate. NICE in particular quickly dismissed Huang’s study as “nonsense”.
Kendrick has said that if Huang’s paper is right – and he sees no reason to suspect it isn’t – the NICE guidelines will “inevitably result in hundreds of thousands of extra people developing Parkinson’s disease, at a cost of billions to the NHS – leaving aside the added suffering and Disability Added Life Years (DALYs) this will bring”.
Statins’ reputation has taken another knock in a class-action lawsuit over the diabetes risk in the US against the makers of Crestor (Rosuvastatin), the only branded statin remaining on the market. Lipitor (astorvastatin) is also the subject of lawsuits.
Still, as US cardiologist and assistant professor at Harvard Medical School Dr Thomas Gaziano says, there’s “no free lunch from any medication”.
“Doctors must recognise the patient’s risk, weigh up benefit versus risk of medication, and thereafter make a sound judgment,” says Gaziano.
He says there’s “no question that statin benefits outweigh risks for secondary prevention”, and there’s “good evidence for primary prevention too”.
By way of example, Gaziano cites the large, randomised JUPITER trial published in the JAMA in 2008. Other evidence – reviews and meta-analyses of RCTs (randomised controlled trials, the gold standard of scientific research) – includes a 2013 analysis by the Cochrane Collaboration, “one of the most respected independent bodies for reviewing the literature”.
That analysis reversed the Cochrane’s own conclusion reached two years earlier It found that evidence from the Cholesterol Treatment Trialists collaboration, led from the Clinical Trials Support Unit at Oxford and co-directed by Collins, now justifies statins in lower-risk patients.
Gaziano agrees there’s an increased diabetes risk, but says the 46% figure in the Finnish observational study overestimates the risk. After controlling for baseline variables (regression analysis) including cholesterol and blood sugar, he says the risk is closer to 28%.
That’s still high, but Gaziano says it could just be from established diabetes risk factors. Data from the meta-analysis of RCTs from the Cholesterol Treatment Trialists group is lower at 9% increased relative risk.
“Cohort participants in the Finnish study taking statins still could have had the 20% to 50% reductions in mortality or having heart attacks from taking statins despite increased diabetes risk,” he says.
“The diabetes risk was mitigated by overwhelming benefits of statins shown in the previous trials.”
Gaziano doesn’t believe the new US and UK guidelines will medicalise healthy people, as cardiologists routinely advise on diet and exercise, not just drugs, and says “healthy is relative here”: “No one is 100% healthy, in terms of zero risk of dying or a heart attack in the next 10 years.”
He says some people are at higher risk than others. The question remains at what risk and with what interventions it makes sense to offer a medication to reduce that risk.
South African-born US cardiologist Dr Dennis Goodman, professor of medicine, and director of integrative medicine at New York University, says doctors “would be a whole lot happier if statins were harmless, but they clearly aren’t” .
Many people can’t tolerate statins. Doctors have to decide how and for which patients we’ll use them appropriately.
Goodman agrees that data on statins for secondary prevention “can’t be refuted”. However, he says primary prevention data are “much softer”.
US family physician and “Denver’s Diet Doctor” Jeffry Gerber agrees, and says: “Statins have been around for nearly 30 years, they’ve had a good run, but they clearly are not a panacea.”
Gerber addresses CV risk regularly with his patients, and says he uses statins in his practice selectively and mostly for secondary prevention. For primary prevention, he finds the new risk calculator “problematic”. He uses additional tools to detect potential high risk patients including cardiovascular imaging, advanced blood lipid testing, cardiac inflammatory markers, blood sugar and other markers for insulin resistance and pre-diabetes.
“One might say that atherosclerosis is a secondary complication of blood sugar,” Gerber says.
He considers proper diet reducing sugars, starch, grains and processed foods to be a “ sensible dietary approach” rather than using medications such as statins for primary prevention.
“Research is still focused on lowering cholesterol instead of addressing atherosclerosis as a complex and inflammatory metabolic process,” Gerber says.
Another problem is what Gerber calls “statistical shenanigans” – statin research that often inflates results using relative risk, which doesn’t actually tell you what’s really important – your individual risk.
“The Finnish study is guilty of the same and serves as an illustration,” Gerber says.
The Finnish finding of a 46% increased (relative) risk of diabetes sounds “pretty powerful”, he says. The real relevance is very different. It involves translating relative risk into absolute risk, and working out the NNT (number needed to treat) – a vital figure in drug research which shows how many patients need to be treated for an effect, in this case diabetes, to occur. It’s a “much better indicator of individual risk”, he says.
The NNT in the Finnish study works out at 1 in 18.
“We’ve now properly adjusted for absolute risk but here’s where the statin plot really thickens,” says Gerber:
When you compare the NNT of 1 in 18 reported here, with the NNT for patients treated with a statin to prevent a heart attack (1 in 150 as reported in the general literature), you get to the really relevant and shocking finding: “Placing patients on a statin would make them 8 times (4 times based on regression analysis) more likely to develop diabetes than preventing a heart attack! ”
Although the Finnish study is observational, and has limitations, it is the first to show such a significant risk, adds to other studies, and builds the case for not using statins for primary prevention, Gerber says.
Other drugs in the pipeline as alternatives to statins include the class of PCSK9 inhibitors hailed as “revolutionary” two years ago – Gerber calls them statin killers. Early trials of an experimental PCSK9 inhibitor presented at the ACC annual conference in San Diego in March are said to be “looking good”.
Gaziano is less sanguine. He says that while PCSK9 inhibitors are “showing promise”, they will be much more expensive than generic statins for years to come. He points out that these drugs currently don’t have “ the many years of follow-up data that statins which show they are generally safe and with risks outweighing benefits except for those at very low overall risk for CVD”.
In his opinion, “Big Pharma doesn’t have interest in most statins now because they are generic and very cheap with limited profit. Now that the poorest of the world may finally have access to them, it would be a shame if those who have much to gain from them are scared away from them.”
South African cardiologist Dr Riaz Motara says patients are still over-treated for cholesterol.
“Look at how many have ‘normal’ cholesterol and still have a heart attack,” Motara says. “Look at populations, such as the Inuit, who have high cholesterol, eat a diet high in saturated fat, and have hardly any heart disease.”
Primary CVD prevention should focus on reducing inflammation, he says. Statins must be supplemented with CoQ10, an anti-inflammatory enzyme in the body depleted with statin use. Patients should also have a liver test after two weeks on statins.
“This seldom happens,” Motara says.
A last word on the subject, from Dr Kailash Chand, GP and deputy chair of the British Medical Association, in a blog for The Guardian last year: “Good medicine should always be evidence based and given to the right patient at the right time.”