The 7 things you should know before taking a statin

statins

Should I take a statin? Your cholesterol might be high, you might have already had a heart attack. Your doctor might advise you to take a statin – cholesterol lowering medication. How do you make an informed choice?

Well, here’s the logic and outcomes used in the trials which evaluate if these little pills are indeed worth taking. It’s not my place to prescribe or make a decision for you. That decision always should come down to the individual after considering the possible benefits and possible harms. They will decide if it’s a good idea for them.

In this piece I’m looking at exactly how you can make that decision. If you take medications, or know significant others who do, then this could be an important bit of reading for you.

Here’s the seven bits you need to know before you decide to take a pill. This applies to any pill, not just statins.

1. How drug trials are run and why

The standard for understanding the effectiveness of a drug is the randomised controlled trial (RCT). In an RCT participants in the study (sometimes also called subjects) are randomly assigned to the treatment (getting the drug) or the placebo control group (get a sugar pill which isn’t the drug).

Both groups take their “medication” for some time and then we look at how things differed between the groups. If a lot less “events” (like heart attacks) happen in one group over another, then we might be prepared to judge the treatment as either beneficial or harmful depending on how things happen.

If, say, the treatment group has less heart attacks than the control group, that means the drug is somehow reducing the chance of a heart attack. If more people in the treatment group get, say, cancer then the treatment is harmful.

It is important to realise that you can get benefit and harm at the same time – e.g. reduced heart attack, but increased cancer.

If the drug is beneficial then the researcher, clinician, and you the consumer then have to make a judgement about whether it’s worth taking the drug for the benefit and possible harms. For example, how many people will benefit from taking the drug? How many people suffer adverse events (harm)?

2. What happens in a typical statin trial?

Here’s how it might work. You eventually end up with say 2000 people (with raised LDL-C cholesterol) in the trial. You randomise half to drug treatment (1000) and the other half are placebo control.

After 5 years you follow up the group and discover that 10 people in the treatment group (they got the statin) had a heart attack, 20 people in the control had a heart attack.

So that sounds good right? Yes, of course, half the number of people in the statin (treatment) group had heart attacks. So that would usually be expressed by the change in relative risk of having a heart attack. If we do that we can say that taking the statin drug reduces your chance of a heart attack by 50%. And that’s the way it is generally reported in the scientific literature and explained to you by your doctor.

That’s only one way to think about the beneficial effects. There are several more. Read on.

3, What about expressing the outcome as absolute risk?

Presenting people with the same numbers in a totally different way, called absolute risk, might make you think differently. What these same numbers mean is that if you are in the control group you have a 98% chance of NOT having a heart attack over five years, and if you take the stain you have a 99% chance of not having a heart attack in the next five years. In other words, the drugs gives you a 1% decrease in your chances. Sounds very different – would this affect your decision to take the drug?

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4, Number needed to treat

Another way to express the same data is to think about how many people would have to take the drug for one person to benefit. In this case 1000 people took the drug for 10 less heart attacks. The number needed to treat (NNT) is 1000/10 = 100.

100 people need to take the drug for one person to benefit.

Does that do anything different to your decision making?

5. Adverse events?

So no matter which way you play with presenting the numbers, there are still 10 fewer heart attacks in the treatment group. These are 10 real people having 10 less heart attacks. Heart attacks cost money, aren’t fun and mean you will probably die earlier with more suffering than if you didn’t have one. So if there weren’t any harms through side effects then it’d probably still be a no brainer. We could give them to all sorts of people. We could consider adding it to the water supply (some people have suggested this!).

Some of the common harms assessed in statin trials are cancer, myopathy (muscle pain and poor function), and diabetes.

Using the same hypothetical trial above (we’ll look at actual trials in the table below later), let’s say 10 people in the statin group got cancer over the 5 years and 1 person in the control. 20 got diabetes in the statin group, 10 in the control, and 100 showed myopathy in the statin group and 30 in the control.

So the side effects in the statin group are generally higher for muscle pain, cancer and diabetes. This is a consistent finding in such trials.

Would these numbers change your mind about the benefits versus harms?

Again you could express all of these as relative risk (1000% increase in cancer, 100% increase in diabetes, 333% increase in myopathy). Or you could be more sensible and show a 0.9% increase in the chances of cancer, 1% in diabetes, 7% in myopathy.

In a third way, you could express this as number needed to harm. How many people need to take the statin to be harmed (suffer an adverse event)? The number needed to harm is 100 for cancer, 100 for diabetes, and 14.3 for the muscle pain. One in every 100 people taking the statin will get cancer, one will et diabetes and 1 in 14 will suffer muscle pain caused by the drug.

6. Putting it all together

The website thennt.com gives summary data for statins as well as other drugs for you to consider. It takes recent trials data and meta-analyses to figure this all out. This is a great place to start if you want a summary of what’s going on. I have copied their figures for statin benefit vs harm in both numbers and percentages for people who haven’t had a heart attack (called primary prevention) and second for people who have already had a heart attack (called secondary prevention).

Statin Drugs Given for 5 Years for Heart Disease Prevention (Without Known Heart Disease)

http://www.thennt.com/nnt/statins-for-heart-disease-prevention-without-prior-heart-disease/

Benefits: Expressed as NNT

  • None were helped (life saved)
  • 1 in 104 were helped (preventing heart attack)
  • 1 in 154 were helped (preventing stroke)

Benefits: Expressed as percentages

  • 98% saw no benefit
  • 0% were helped by being saved from death
  • 0.96% were helped by preventing a heart attack
  • 0.65% were helped by preventing a stroke

Harms: Expressed as NNT

  • 1 in 50 were harmed (develop diabetes)
  • 1 in 10 were harmed (muscle damage)

Harms: Expressed as percentages

  • 2% were harmed by developing diabetes
  • 10% were harmed by muscle damage

Statin Drugs Given for 5 Years for Heart Disease Prevention (With Known Heart Disease)

http://www.thennt.com/nnt/statins-for-heart-disease-prevention-with-known-heart-disease/

Benefits: Expressed as NNT

  • 1 in 83 were helped (life saved)
  • 1 in 39 were helped (preventing non-fatal heart attack)
  • 1 in 125 were helped (preventing stroke)

Benefits: Expressed as percentages

  • 96% saw no benefit
  • 1.2% were helped by being saved from death
  • 2.6% were helped by preventing a repeat heart attack
  • 0.8% were helped by preventing a stroke

Harms: Expressed as NNT

  • 1 in 50 were harmed (develop diabetes*)
  • 1 in 10 were harmed (muscle damage)

Harms: Expressed as percentages

  • 2% were harmed by developing diabetes
  • 10% were harmed by muscle damage

7. Other issues: Sneaky reporting and sneaky experimental designs

Now that you know the basics of how these trials are run and how to interpret the results, here are a few things that are common in the way these trials are conducted which are worth considering in making your judgement about the results.

  1. Benefits are also always expressed as changes in relative risk (they sound good – e.g. taking the drug decreases your chance of a heart attack by 50%).
  2. Harms are almost always expressed as absolute risk, or the plain number (10 more developed cancer in the statin arm). This makes it hard to judge the benefit/harm against one another and minimises the discussion of the side effects.
  3. Statin trials often “run in periods” which effectively remove people who suffer adverse events in the first month. That’s correct, they want to take these people out of the equation so you can be excluded in the first month of the trial if you suffer immediate adverse events. The most likely of this is the muscle pain. So if anything, the trials underestimate the amount of adverse events. It is estimated that muscle pain affects about 40% of people who take statins, although there is no easy way to determine this under the “run in” conditions. Most of the large drug company funded trials don’t make their databases available.
  4. Adverse events are often explained away as an “anomaly”. I kid you not. For example “there is no known link between statins and cancer so the fact that the statin group had 10 times more cancer must just be accidental”.
  5. Adverse events are often grouped and analysed in ways which make it hard to tell what is going on. For example, muscle pain might only be considered harmful if it is 9 or more out of the 10 point scale. Groupings might be made so it is harder to detect statistical significance. For example, muscle pain might be put into 5 different “bins” and because numbers aren’t taken as a whole, the results appear “not significant” when in fact they are.
  6. There is evidence of adverse events in the following areas – muscle pain, cancer risk, cognitive functioning, and diabetes. Not all these are always measured, nor is the study necessarily set up to find these differences between groups for various statistical reasons. That doesn’t mean they will happen, but it is possible, and some trials have shown this to greater or lesser extents.

Look, I’m not the one who should prescribe or tell you whether you should take a statin or not. What I can help you do though is decipher what the benefits and risks are and help you ask your doctor the right questions about these.

They should be able to answer these questions and then you should be able to make a decision about the medications you should take.

These are ultimately your decisions, not your doctor’s.

14 comments

  1. Maguerite · · Reply

    Hi Doc okay I have to utter my concern re: WHAT ABOUT US! the legions of ppl with HEFH. What do we do? Not a single doctor in the new low carbing rock world it seems will touch us re KETO (my sister in NZ flies to every conference on LCHF) but she did not inherit the mutation but I and my sons have. My one son at 34 had quintuple bypass surgery – are we not your prime subjects to show the world how well keto works. I WAS on it for 2 years and my numbers plummeted for the first time since birth and I thought I’d been given a life line for longevity (though given the women in our family do not die from this ailment, my mom is 84 and she’s our direct carrier). But now my sons (who are in real danger) are with heart surgeons who tell them differently (based on heart foundation rules) and I, as a mother just think WHY should I stay on a diet for long life when my sons are being given carbohydrates and zero fat lifestyles which I know in my KNOWER is bad for them. BOTH my boys have the mutation and my heart is really sore. BUT, I also acknowledge what this diet can do for uswise, but not a single doctor in the world is prepared to take us on. I do realise that people with a double mutation (HOFH) must be a real conundrum and they go for something akin to dialises, but for us with one mutation – surely here is the chance for the lot of you to prove to the world, your very stellar science. I believe that it will give us good health, but if my sons get 2 opposing opinions they will gravitate to the guys, well certainly the one, who operated on his arteries. I’m afraid that obesity has hijaced this diet for themselves when in fact there is a mass (pardon the pun) of very thin people (such as my family) who have even more to gain but we’re being ignored in the fray (due to fearfulness from both doctors and patient), not to mention the panic attack disorders which are plonked into our psyches by these very same cardiac doctors, honestly – they put the fear of G-d into our lives, though I (seemingly the only one in the universe) believe differently because I DID do the diet and the results DID astound my GP. What now?

  2. trekkiemaiden · · Reply

    Thanks Prof, a really useful insight. Have shared it to my “I Love My Cholesterol” Facebook page. Of course there’s the other point to look at which concludes that lowering cholesterol is completely futile unless you have had your particle size measured, in which case if you have small dense LDL particles and high triglycerides, you only need to adjust your diet accordingly – not go down a medication route at all!!

  3. […] The 7 things you should know before taking a statin. […]

  4. Thank you. It’s good to have a concise low down. So much anecdotal evidence LCHF diets work & that coming off Satins – sorry typo – I mean Statins have more harmful effects than good. My partner came off statins & his memory has improved. He gets no more cramps & also came off Nexium. We then went LCHF.As expected his Triglycerides are down & HDL ratio has improved tremendously. He has (had) Rhuematoid Arthritis in his hands. We have been on the diet since Nov 2013. Two weeks ago his inflammatory markers were so good that he came off the Methotrexate. His hands are fine. He hasn’t had a cold either! Your information is life saving – certainly our quality of life is soaring. Thank you all at SOHP, & all those proponents of LCHF Jennifer

    1. Robbie · · Reply

      I think you meant “coming off Satan’s”

  5. Trudi · · Reply

    How do you get the mainstream medical world acknowledging familial hypercholesterolemia is a metabolic problem, not heart disease? Is anyone researching this? I want to know why our bodies go into cholesterol overdrive. Is it the liver, what we eat? We are 3 generations of this, with total cholesterol levels over 14. All fit active people, that watch what we eat.On statins, down to about 6. My mum is the carrier, no health problems at 74 yrs. my brother at 49 just had a quadruple bypass, been on statins for 25 years, they really worked, aye. My son was tested at birth ,level 6, now at 14 yrs it is 8. Doctors want him on statins, immediately. I am avoiding this. Is anyone in the nutritional studies sector interested in looking at 3 generations of this, and helping us to stay off statins? Doctors are always giving us grief over it.
    I have followed LCHprotein adding coconut oil and such, and got my levels down to 6 unmedicated. Asked by GP how, I Told my GP I was on coconut oil he flipped out.
    Any suggestions on who we can see as clients for nutrional advise would be great. Thank you.

    1. Dr Caryn Zin is our dietician and she can help you

  6. jillm · · Reply

    We don’t hear much about the number needed to harm.

  7. Statins accelerate coronary artery calcification, although they may also stabilise plaque. Basically they slightly reduce heart attacks, but increase congestive heart failure, providing a more profitable living death of patients. Mechanisms: Depletion of CoQ10, Vitamin K2, selenium containing proteins. Low carb high fat diets, and diets containing bacterially fermented foods typically contain more vitamin K2 than other diets, contributing to better heart and bone health. Sources of K2 include natto, cheese, liver. Simplistically vitamin D3 gets calcium from the gut into blood, Vitamin K2 gets calcium out of arteries into bones and teeth.

    Okuyama H et al. Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert Review of Clinical Pharmacology, 2015, 8(2), pp 289-199. PMID 25655639.

    Puri R et al. Impact of Statins on Serial Coronary Calcification during Atheroma progression and regression. 2015, 65(13), p 1275-2283.

    Henein M et al. High dose and long-term statin therapy accelerate coronary artery calcification. Int J Cardiol 2015, 284, p 581-586.

    Geleijnse JM, et al. Dietary Intake of Menaquinone is associated with a reduced risk of coronary heart disease: The Rotterdam Study. J Nutr, 2004, 134, p3100-3105.

  8. Your (unreferenced) comment under 4. “there is no known link between statins and cancer so the fact that the statin group had 10 times more cancer must just be accidental” is very misleading. I realise you are exaggerating to make a point and that there are actually no trials that show that the statin group had 10 times more cancer, but a lay person reading this may take it literally and be scared off taking the drug for spurious reasons. This is bad journalism

    1. The CARE trial was a secondary-preventive trial including 4159 patients (576 women and 3583 men) with MI and aver- age cholesterol levels [1]. Half of the patients were administered 40 mg pravastatin, half of them placebo. After 5 years treat- ment, 24 (1.15%) had died because of CHD in the treatment group and 38 (1.83%) in the placebo group, resulting in an ARR of 0.68 percentage points.

      The most serious adverse event was breast cancer, which occurred in 12 of the women (4.2%) in the pravastatin group but in only one of the women (0.34%) in the placebo group. Although the difference in the incidence between the groups was statistically significant (p = 0.002), the authors dismissed the increased risk by stating: ‘There is no known potential bio- logic basis. . .the totality of evidence suggests that these findings in the CARE trial could be an anomaly and may be best inter- preted in the context of the trial’s very low event rates and sta- tistical testing of many adverse events.’

      Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events trial investigators. N Engl J Med 1996;335:1001-9

      Also see How statistical deception created the appearance that statins are safe and effective in primary and secondary prevention of cardiovascular
      disease

      http://www.ncbi.nlm.nih.gov/pubmed/25672965

  9. […] to look at the same number another way (from Grant Schofield), 98% saw no benefit, 0.96% benefited from preventing a (non-fatal) heart attack, 2% were harmed by […]

  10. Eileen Darwin · · Reply

    Hi Grant. Do you see people for consultations?

    Thanks Eileen

    Eileen Darwin Sent from my iPad

    >

  11. […] to look at the same number another way (from Grant Schofield), 98% saw no benefit, 0.96% benefited from preventing a (non-fatal) heart attack, 2% were harmed by […]

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Richard David Feinman

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