STATIN DRUGS

One of the most frequent questions I am asked as a Cardiologist and physician is – do I really need to take Statin drugs?  On one side doctors are suggesting they be incorporated in a polypill which everyone should take, to other more ‘naturally based’ experts saying they do not work and people should not take them (click here)

This article is my assessment from the current medical literature, and the advice I give to my patients.  Because the article is quite long, I will put my conclusion first as well as at the end, but I would recommend that you read the reasons for my conclusions as well.

My Conclusion – sifting through all of the data below, my recommendations are relatively simple:

1. If you have proven cardiovascular disease (heart attack, angina, stroke, angioplasty, high levels of calcium in cardiac CT scan) then you should take a statin drug preferably at a low dose. This would reduce your risk of a heart attack, stroke or death by about 20%.

2. If you get any side-effects – muscle pain, abnormal liver function tests, or you feel that your mental function has deteriorated, stop the drug for a couple of months, and then restart. Possibly consider restarting with a water-soluble statin such as pravastatin. If the symptoms recur then don't take the statins anymore.If you feel fine, then continue the statin. There is little evidence showing that any other cholesterol-lowering agent provides any benefit.

3. If you don't have cardiovascular disease (primary prevention) unless you have a very high cholesterol, diabetes or an extremely strong family history then I would not recommend that you take a statin drug. My advice would be to have a CT scan for calcium**  which will show early coronary artery disease, if this is strongly positive then maybe you should consider taking a statin drug. If it is negative or normal for age, then I would not take a statin.

4. For elderly people the benefits of statins do continue, but if there is any suggestion of impaired mental function, then stop taking the statin.

5. If you are taking a statin, you must be taking the supplement coenzyme Q 10, at least 100 mg daily.

Few drugs have caused so much debate as have the statins. They are without a doubt the most successful and lucrative drugs of all time in their prescribing, hence the enthusiasm of the pharmaceutical industry not only to retain their use in their primary role (preventing cardiovascular disease) but also seeking other possible benefits.
To the medical profession these drugs are considered mandatory therapy for patients with definite cardiovascular disease, while to many complimentary therapy practitioners, they are considered to be almost poisonous. In the role that I've taken with this website, I will do my best to give an unbiased view, and then conclude with my thoughts.

There is no doubt that deaths from cardiovascular disease are falling (see graph) and have been doing so since the 1960s. Looking at the graph there was a sudden rise in the 1920s and 1930s, a flattening in the 1950s and then a fall since 1970. The statin proponents claim that this fall is due to their medication, but does not explain the rise in the 1920s or the fact that the flattening and reduction occurred before the introduction of the statin drugs. At the same time we have had improved diet, encouraging exercise and other lifestyle changes, huge reduction in cigarette smoking, other drugs including beta-blockers and ACE inhibitors, major advances in open-heart surgery and angioplasty. It is hard for anyone of these to claim the credit, when in fact it is almost certainly due to a combination of all of them, and possibly other factors that we don't yet understand.

There have been more trials on the statin drugs than almost any other drug in the history of mankind, unfortunately the majority have been under the financial control of pharmaceutical firms, which does give some concern about the impartiality of the results. For example many of the early studies showed a very low incidence of side-effects, but in many trials patients were given the active drug (statin) before the study, and if patients did not tolerate them they were not included in the trial. This of course hugely reduced the incidence of reported side-effects.

Trials have been divided into primary and secondary studies, primary - those with no evidence of cardiovascular disease and secondary - those who have had evidence of vascular disease such as a heart attack, stroke, peripheral vascular disease, angina, angioplasty or bypass surgery. The latter group having demonstrated artery disease are obviously at a much higher risk (20 times) of having a cardiac event than those in the primary group.

For those who are interested here is a review of the important trials, but skip to the following paragraph for the conclusions from them:

1. Primary prevention – many early trials with non-statin drug showed no benefit in either cardiovascular disease or mortality. Of the statin drug trials – WOSCOPS followed 6,500 men with high cholesterol for 5 years, the statin drug pravastatin reduced total mortality by 22%. This sounds extremely significant, but the reduction of heart attacks and cardiac death went from 9.4 to 6.46 years, a reduction of 3%. The AFCAPs/TEXCAPS study in the United States air force followed 6600 people without cardiovascular disease including almost 1000 women, and at the end of 5.2 years there was a 2% reduction in cardiovascular events. The ASCOTT-LLA trial studied 10,000 patients with high blood pressure, and although the incidence of heart attacks and strokes were reduced, there was no significant reduction in all-cause deaths, or cardiovascular mortality.  The Jupiter  studied 17,000 healthy men and women with low cholesterol, but unfortunately was stopped early (1.9 years) because of apparent benefit. There was a reduction in cardiovascular events (0 .77 versus 1.3) and all-cause deaths (1.25 versus 1.00). The brevity of this study makes it difficult to confirm that these results would persist. HOPE3 trial - followed 12,000 people without disease for 5 1/2 years (there was a 4 week run in period with active drug which eliminated patients of unacceptable adverse events). The incidence of cardiovascular death, heart attacks and non-fatal strokes was reduced from 4.8% to 3.7.

2. Secondary prevention – the 4S Study reduced total mortality from 12% to 8% over 5 years, Care trial reduced heart attack and death's from 13 to 10% in 5 years, and in the HPS study of 20,500 subjects, all-cause mortality was reduced from 15 to 13% over 5.5 years. Interestingly in the HPS study the level of cholesterol at the commencement of the study made no difference in the apparent benefit. Unfortunately the number of women in these trials were relatively low, but it is believed that women receive similar benefit. Patients with diabetes have the same benefit as those with previous cardiovascular disease. Therefore treating patients with known cardiovascular disease or diabetes reduces the risk of further events and death by approximately 16%. (click here )

It is also believed that older people receive much the same benefit at least till the age of 75.

There is debate on what level of cholesterol doctors should be aiming for, or whether high doses of statins (which undoubtedly produce more side-effects) are more beneficial than lower doses. There is almost no evidence that non-statin drugs provide the same benefit as the statins. To the extent that many evidence-based papers do not recommend the use with the addition of non-statin drugs especially in primary prevention.

Conclusions from the trials – statins undoubtedly do reduce the incidence of cardiovascular disease and death, and for those at higher risk the chances of  benefit are obviously greater. There have been numerous meta-analyses (reviewing a number of trials and putting the results together) and these are shown:

1. Primary prevention – from 11 trials on 65,000 participants all-cause mortality was reduced at the most by 1% per year.

2. Secondary prevention – from a number of meta-analyses, all-cause mortality is reduced 23%, in  over 4 years one death per 110 people would be prevented.

Calculators have been provided for patients and their health professionals to calculate the risk of cardiovascular disease or death, but I think the information in the last 2 paragraphs fairly summarises the situation. To calculate your cardiovascular lifetime risk you can use the QRISK calculator (click here),

Side and Toxic Effects
There is no doubt that the statin drugs do reduce cardiovascular disease and strokes and death, but they do come with significant side-effects. The fact that some of the trials had a run-in period on the active drug and patients with side-effects were eliminated has led to an underreporting of side-effects. Also some of the side-effects are rather subtle, and many patients suffer from them long-term without appreciating that they are caused by the drug. The side-effects include:

 1. Muscle disease (myopathy) – this can vary from mild muscle aches, muscle weakness, myositis (inflammation), myonecrosis (death of muscle tissue) and clinical rhabdomyolysis – severe damage to muscle tissue leading to kidney failure and other complications. Severe myopathy is rare, but is reported in about .1% of patients.

The reason for myopathy is unknown, the statin drugs do affect the production of coenzyme Q 10 which is essential for muscle energy production, but other effects on Beta-sitosterol, oxidation, Atrogin-1 and other enzymes might also be the cause.

2. Liver dysfunction – up to 3% of statin patients have an elevation in liver enzymes, especially in the 1st 3 months. Rare episodes of severe liver injury have also been seen.

 3. Kidney dysfunction – statin drugs do appear to cause leakage of protein through the kidneys, there is some debate about whether this is important or not.

4. mental function – there is huge debate on how important and frequent this is, because mental function has not been reviewed in most studies. There have been reports of acute memory loss shortly after starting taking statins (click here), and one spectacular personal report from an Apollo astronaut has become viral (click here). Because this has not been carefully studied, it does appear that statin drugs can impair mental function, and this is further demonstrated by the fact that drugs that do not enter the brain through the cerebral spinal fluid (pravastatin) have a lower incidence of affecting mental function, and in many cases stopping the statin drugs can make an improvement in mental function.(click here)

5 – Cancer – preclinical studies have found that statin therapy did increase the risk of liver tumours in rats, but careful analysis of all the trials have concluded that there is no convincing evidence that statins increase or decrease the risk of cancer.

6. Diabetes – statin therapy has been proven to slightly increase the risk of developing diabetes. This risk is small, with a 1% increase in developing diabetes.  An analysis in 2016 suggested that statin treatment would lead to 5,200 new cases of diabetes in 10,000 treated individuals.

7. Cataracts – in preclinical studies, dogs developed cataracts when given high doses of statins. Large studies have suggested there is a slightly increased incidence of cataract in patients receiving statin drugs.(click here).

8. Neuropathy – there has been a suggestion that statin drugs might cause peripheral neuropathy (tingling in pain in the fingers and toes) but this is not yet been confirmed or denied.

9. Immune disease – there are some observational studies suggesting that the immune response to influenza and other vaccines may be reduced with statin drugs, and also case reports of patients on statins developing lupus – but these have not been proven.

10. Pregnancy – it is recommended that pregnant women should not take statin drugs during pregnancy, or prior to conception. The limited human data does not suggest that statins are major human teratogens. They should also probably not be taken during breastfeeding.

My Conclusion – sifting through all of the above my recommendations are relatively simple:

1. If you have proven cardiovascular disease (heart attack, angina, stroke, angioplasty, high levels of calcium in cardiac CT scan) then you should take a statin drug preferably at a low dose. This would reduce your risk of a heart attack, stroke or death by about 20%.

2. If you get any side-effects – muscle pain, abnormal liver function tests, or you feel that your mental function has deteriorated, stop the drug for a couple of months, and then restart. Possibly consider restarting with a water-soluble statin such as pravastatin. If the symptoms recur then don't take the statins anymore. There is little evidence showing that any other cholesterol-lowering agent provides any benefit.

3. If you don't have cardiovascular disease (primary prevention) unless you have a very high cholesterol, diabetes or an extremely strong family history then I would not recommend that you take a statin drug. My advice would be to have a CT scan for calcium** which will show early coronary artery disease, if this is strongly positive then maybe you should consider taking a statin drug. If it is negative or normal for age, then  I would not take a statin.

4. For elderly people the benefits of statins do continue, but if there is any suggestion of impaired mental function, then stop taking the statin.

5. If you are taking a statin, you must be taking the supplement coenzyme Q 10, at least 100 mg daily.

** Calcium scanning for calcium

It is very valuable to be able to diagnose early coronary artery disease before it starts causing symptoms. The reason for this is that for almost 50% of people who die of a heart attack, their sudden death is the 1st indication of any problem. (Click here). For this reason cardiologist have been seeking diagnostic tests for many years to identify people at risk of having a heart attack, and treating them before it occurs.

Resting ECG has very little value, and even an exercise ECG has not been shown to improve the diagnostic ability or outlook (click here). Coronary arteriograms (taking x-ray pictures of the coronary arteries), or CT coronary arteriogram is are expensive, and not without risk. Perhaps the most valuable test is also one of the more simple, cardiac CT scanning for the presence of calcium.

When cholesterol starts building up in the artery wall it forms what is called a plaque. Initially this is simply made up of cholesterol, but as it gets bigger and weakens the artery wall, fibrous tissue and then calcium become incorporated into the plaque. One of the problems is that 60% of all heart attacks result from small plaques that do not cause major narrowing of the artery. The plaque can rupture, a clot forms and the artery blocks completely, frequently causing sudden death or a heart attack. Therefore the ideal approach is to identify plaques as early as possible.

X-ray machines can detect calcium (it is the calcium they can see when you have bone x-ray) but because the heart is moving they cannot detect the calcium in the coronary arteries.

Fast spinning CT scanners attached to the ECG can take CT x-ray pictures of the heart when it is stopped between beats. This enables the arteries to be seen, and if they have calcium within them, this could be seen on the x-ray (see picture).

Because it takes some years for the calcium to develop, there is no point in doing a calcium scan before the age of 40 to 45, but thereafter it is probably the best predictive test for silent coronary artery disease (click here)  For this reason cardiologist used this test to identify people at risk.