What’s the deal with Statins?

What’s the deal with Statins?

This blog post will cover the controversies related to the use of Statins to lower cholesterol and thereby lower heart disease risk. It will contain arguments from the camps supporting Statin therapy and the camp that expresses serious reservations about the benefits of Statins and concerns around their side effects.

I am going to include some clinical trial data to illustrate the point. Furthermore, I will explain some terminology that is key to making any personal decisions around Statin usage.

What are Statins?

They are a class of drugs that reduce Total Cholesterol and so called Bad Cholesterol (also called Low Density Lipoprotein – LDL). (More on cholesterol in an earlier post here.)

What are Statins used for?

They are used to prevent the occurrence of heart disease and death due to heart disease. It is generally assumed that this benefit is achieved through their cholesterol lowering effect (more about this later).

How many people use Statins?

It is difficult to say but in the US approx. 25 to 30 million take statins and in the UK approx. 5 to 7million take statins (approx. 8 to 10% of total UK population). If this is extrapolated to the wider population of the world (with usage numbers less for the developing world), then it is likely that approx. 250 to 400 million people take Statins daily.

What are the typical Statin drugs?

There are currently six statins on the US market: lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, and rosuvastatin. The brand names are Lipitor, Zocor etc.

How much benefit do Statins provide?

Let’s get into terminology here – RRR (Relative Risk Reduction), ARR (Absolute Risk Reduction) and NNT (Number Needed to Treat). Let’s use an example to explain this.

Supposing we start a clinical trial with 200 people. Let’s randomise them into 2 groups of 100 each (the randomisation process to take away any biases). Let’s call them Groups A and B.

Let’s give Group A (100 people) a Statin and let’s give Group B (100 people) a placebo (a pill with no active ingredient – a sugar pill basically). Let’s also ensure the pills look exactly the same so that patients in Groups A and B can’t figure out who has been given the drug and who has been given the sugar pill.

At the end of 5 years, the trial ends and we look at the results – In Group B (placebo) 4 people got heart attacks whereas in Group A (statin) only 2 people got heart disease. Therefore,

Absolute Risk Reduction is 4 -2 / 100 = 2 %

ARR tells you how many lives actually get saved on a percentage basis.

Relative Risk Reduction is 4-2/4 = 2 / 4 = 50%

RRR is generally used by pharma companies to glorify the benefits of drugs (like most marketing messages do – pharma or no pharma) because 50% sounds much better than 2%.

Number Needed to Treat is 50

This is defined as the number of people that needed to be treated to save 1 life. Since treating 100 people has saved 2 lives (supposedly), then we can say the NNT is 50. If only one life was saved then NNT will be 100. So in essence, in this example 50 people need to take the drug for 5 years to save 1 life.

Statin Clinical Trials

To get a more balanced (or contrarian) picture, let us look at the results of some Statin Trials (reusing work published in some papers)

JUPITER

The first one is the JUPITER trial, in which Rosuvastatin (Crestor) or a placebo was administered to 17,802 healthy people. It was investigating incidences of cardiovascular disease (such as non-fatal and fatal heart attacks, stroke or angina). The trial ended after 1.9 years.

The benefit of Statins was calculated to be between 0.5% and 1%. Slightly fewer people had heart attacks ( < 1%) with the drug but more people died in the group given the drug when they actually had a heart attack. Anywhere between 83 to 244 people need to take the drug for 5 years continuously to reduce their heart attack risk by between 0.5 to 1% over 5 years.

What Else Happened in the Trial?

In the Rosuvastatin group there were 270 new cases of diabetes, but only 216 in the control group (3% vs 2.4%). There was an absolute Risk of 0.6% and a relative risk of 20%.

The following description has been given by a contrarian for the above Trial:

Your chance to avoid a nonfatal heart attack during the next 2 years is about 97% without treatment, but you can increase it to about 98% by taking a Crestor every day. However, you will not prolong your life and there is a risk you may develop diabetes, not to mention other serious adverse effects.

Let’s look at one more Trial before we move on.

PROSPER

PROSPER was a large trial involving 5804 men and women aged 70–82 years with a history of, or risk factors for, vascular disease (diseases of the blood vessels). Half of them were given pravastatin, the other half a placebo. After 3.2 years later, they wrote in the abstract that mortality from heart disease had fallen by 24%. However, according to one of the tables, 4.2% had died from a heart attack in the control group and 3.3% in the treatment group, thus with an ARR of only 0.9 percentage points.

The small cardiovascular benefit was neutralised by a substantial number of patients who had died from cancer. There were 28 fewer deaths from heart disease in the pravastatin group, but 24 more deaths from cancer. If we include nonfatal cancer in the calculation, the cancer difference was statistically significant – 199 in the control group and 245 in the pravastatin group.

Conclusion  – On the whole, a 0.9% ARR was achieved with the taking of Statins, however this came with a raised risk of cancer.

Do Statins have any other Benefits?

There is some evidence to suggest that the small absolute benefit is not because of cholesterol lowering at all but due to something else.

How do we know this – The current Statin drugs can be called v2.0 of cholesterol lowering drugs. The v1.0 drugs lowered cholesterol but had such considerable side effects that some of them had to be withdrawn from the market (more deaths and unintended side effects).

There is a theory that heart disease and other chronic diseases are caused by Inflammation (a topic for future discussion) and that Statins reduce the inflammation slightly (this is a different effect of Statins unrelated to Cholesterol lowering) and thereby provide some benefit – some of the markers for Inflammation like CRP (C Reactive Protein) or hs-CRP (high sensitive C Reactive Protein) are lowered slightly by Statins.

What about Stroke?

Stroke is when poor blood flow to the brain results in cell death (wiki). (For the layman, heart attack is related to the heart and stroke is related to the head). Similar arguments are extended for use of Statins to reduce the risk of Stroke.

Some studies have shown a small absolute benefit but this could be due to non-cholesterol lowering effects of Statins such as a reduction in inflammation. Furthermore, high cholesterol has a weak association with incidences of stroke, which confirms the suspicion that Statins effects could be due to other aspects.

An area to watch, though we also know that there could be an impact on brain functioning.

Interim Summary – What do we know so far?

It appears that Statins reduce the risk of heart attacks by an absolute 1% if you take them for 5 years but with a raised risk of diabetes and cancer. If you do get a heart attack while on the drug you are more likely to die than not taking the drug (from the trial).

What are the side effects of Statins?

The following are the most documented side effects of Statins (in descending order of risk)

  1. Muscle and Joint aches and pains – Anywhere between 10% to 50% of the people report this problem. Officially it is supposedly far less but in practice it seems to occur more. Some people avoid this by switching to a different Statin. Also most people report that the pains go away when they stopped taking Statins.

This side effect has a bigger impact on people if they stop exercising due to this as we all know that proper life style (good diet and plenty of exercise) can make you more healthy and reduce the risk of so many diseases

  1. Diabetes Risk – It appears that there is a higher risk (ARR) of 3 to 4% of diabetes for people on Statin Drugs
  2. Temporal Memory Loss and Mood disorders – Some people have reported episodes of memory loss for short periods of time. Several studies have shown that low cholesterol is associated with lower cognition and Alzheimer’s disease and that high cholesterol is protective. In a study of 143 patients with memory loss or other cognitive problems associated with statin therapy, they reported that 90% of them improved, sometimes within days, after statin discontinuation.
  3. Liver Function – For some people, their liver function seems to have been affected after they start taking Statins

What other Downsides do Statins have?

Everyone (people who promote Statins and people who suggest that Statins are being taken by many people unnecessarily and that their benefits are exaggerated) agree that a proper life Style (a good diet, regular exercise that covers aerobic, strength and weigh training, stress reduction, good sleep, not smoking and limiting alcohol intake) provides good health.

I personally believe that Statins take away some of the incentive for someone with an elevated heart disease risk to make the necessary life style changes. Popping a Statin is an easy way out for people to continue their existing (and perhaps improper lifestyle).

People can benefit from a good life style in many different ways other than just reducing heart disease risk. You’ll get an overall improved health, feel much better, you can be sharper and more focused, can move around lot more, enjoy things more, brains function better etc.

Conclusions

Benefits of Statin

They seem to have a marginal absolute risk reduction of heart Disease (approx. 1% when taken over 5 years) but with a slightly higher overall risk of death  from other causes (Personally it makes no difference whether  I die of Cancer or Heart Disease – whether I die or not is what matters)

Should I take a Statin?

Warning: Do not stop taking any drugs without consulting your doctor. He or She may not agree with below views and it is ultimately a personal decision for you.

The devil is in the detail but based on reading a large number of papers, the general conclusions are as follows:

If you are a woman :

  1. If you already had a heart attack, then it is worth a discussion with your physician (this is called secondary prevention) though there is not much evidence to suggest it is of any net benefit
  2. With no previous heart attack disease, it is very unlikely that Statin is of any NET benefit to you given all the downsides
  3. If you are a woman above the age of 65 or 70, it is very unlikely that Statin is of any NET benefit to you no matter whether you had a heart attack or not

If you are a man

  1. If you already had a heart attack, then you should perhaps consider a Statin (this is called secondary prevention)
  2. With no previous heart attack disease, it is very unlikely that Statin is of any net benefit to you given all the downsides
  3. Above the age of 65 or 70, it is very unlikely that Statin is of any net benefit to you no matter whether you had a heart attack or not

An After-thought

We talked a lot about Heart Disease Risk. How can we quantify the risk? There are a number of Calculators out there but they are very generic and also not as applicable to Asians compared to others.

One of the better ones is the Mayo Clinic calculator. (Your physicians may have their own version)

http://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/heart-disease-risk/itt-20084942

Give it a go!

If you also have blood test results in hand, then check the following out

Assuming your vitamins and minerals are at the right levels, the following Cholesterol levels indicate excellent health according to some experts

HDL (level) >1.2 mmol/L > 60 md/dL
Triglycerides (TG) / HDL Ratio < 1 < 1

 

If you eat a lot of processed carbs, sweets etc. then your Triglycerides are likely to be higher and you’ll struggle to hit the above ratio.

Also check to make sure your Liver Function is solid and that your blood sugar levels are relatively low (HbA1C < 5.5)

Please post any comments on the Blog. Would appreciate it.

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