Statin, to use or not to use, That’s the question!

Dr. Goh Eng Leong

Consultant Cardiologist & Physician

B.Sc. (Med.), M.D. (UKM), M. Med. (S’pore), MRCP (UK), FNHAM, AM

Since 1950s, high cholesterol (LDL – C : Low – Density Lipoprotein Cholesterol) has been identified as a major risk factor for the development of atherosclerotic diseases (ischemic heart disease, stroke and peripheral vessel disease).

Many epidemiological and interventional studies have provided robust evidence to the association between high cholesterol and atherosclerotic disease, which is the number one killer worldwide.

To combat this deadly disease, the quest for drugs that could reduce cholesterol has begun since 1960s. Of all the investigational drugs developed, Statin emerged to be the first established lipid lowering medication that is able to reduce cholesterol effectively.

In 1976, the Japanese biochemist Akira Endo isolated a factor from the fungus Penicillium citrinum which he developed into the first Statin. He named it Compactin or Mevastatin.

In 1978, Alfred Alberts at Merck Research Laboratories discovered a potent inhibitor of HMG – CoA reductase in a fermentation broth of Aspergillus terreus, which was named Lovastatin, Mevinolin or Monacolin K.

Since Lovastatin had been commercialized, six other statins – two semi – synthetic statins (simvastatin and pravastatin) and four synthetic statins (Fluvastatin, Rosuvastatin and Pitavastatin and Atorvastatin) – have been introduced to the market over the years.

As a practicing cardiologist, I think Statin is the most controversial medication in the history of medicine. While many mega – clinical trials have proven the benefits of Statins in term of reduction of cardiovascular mortality and morbidity, a lot of negative publicity on Statins have demonised these medications. Social medias are the major channel where the fallacies of Statins spread virally. The minor side effects of Statins are exaggerated and the therapeutic effect of Statins are covered. These type of negative and bias reports on Statins have caused confusion not only to general public but also to physicians.

I hope I can put the facts of Statins in its correct perspective by presenting the scientific evidence to dispel the confusion and misunderstanding. As Socrates’s famous saying : there is only one good – KNOWLEDGE ; and one evil – IGNORANCE.

LDL and Statin : The irrefutable truth – proven in many mega clinical trials

  • High LDL cholesterol causes cardiovascular disease. There is a strong and graded positive association between LDL cholesterol and the risk of cardiovascular disease. This association applies to men and women, and to those with or without established cardiovascular disease. A 1% increase in LDL cholesterol is associated with a > 2% increase in coronary artery disease over 6 years.
  • Reduction of LDL will reduce mortality and morbidity, the lower LDL better the clinical outcome. Meta – analysis of many Statin trials has showed a dose dependent relative reduction in cardiovascular disease with LDL reduction. Every 1 mol / L reduction in LDL cholesterol is translated into a 20 – 25% reduction in cardiovascular disease mortality.
  • Statin is the mainstay of treatment to reduce LDL and cardiovascular mortality and morbidity.
  • Statin causes atherosclerotic plaque regression.
  • Bad publicity on Statin has caused a reduction in the usage of Statin by patients and prescription of Statin by physicians. The decline in the use of Statin translated into increase in CV morbidity and even death. The benefit of cardiovascular protection of Statins really outweighs the small risk of side effects. Let us have a closer look on the side effects of Statins.

Side effects of Statin

  • Muscle pain :
    • Myalgia : 5%, reversible. The problem of muscle pain can be reduced by monitoring of certain risk factors (old age, kidney impairment and concomitant administration of some medications which may cause drug – drug interaction)
    • Rhabdomyolysis – severe form of muscle breakdown with acute kidney injury is very rare : 1 in 100,000
  • Hepatotoxicity : Side effects on liver
    • Asymptomatic raise in liver enzyme ALT occurs in 3% of patients.
    • Severe acute liver failure is also very rare – 1 in 100,000
  • Cancer : no increase in risk. In fact Statin may confer protection from cancer mortality
  • Dementia and cognition function loss : no increase in risk. In fact Statin may reduce dementia risk.
  • Hemorrhagic stroke : small risk. But Statin reduces overall stroke risk.
  • Diabetes :
    • 5 – 10% risk
    • But the cardiovascular protection is much more than this small diabetic risk.
    • Even if patients develop diabetes they still live longer and healthier compared with those who have high LDL not taking Statin and no Stain induced diabetes.
    • High risk factors of Statin induced diabetes are high baseline blood sugar and metabolic syndrome.
    • Patients who are talking Statins are encouraged to live a healthy lifestyle to reduce the risk of diabetes

Understand these facts of Statins will help us to dispel Statin – phobia. Statins should definitely not be prescribed for all. But the high risk patients should take Statin to reduce the cardiovascular risk. The benefit of Statins should not be denied in these group of high risk patients just because of fear of side effects.

I encourage readers to discuss any issues on Statin use with respective physicians if there is any further doubt.

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