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Statins pros and cons (advantages and disadvantages) of lipid lowering drugs
Drug reviews: use, side effects, effectiveness

Statins PROS and CONS [TOP LIST]

Statins, also known as lipid-lowering drugs, are a popular class of drugs prescribed in the UK. When looking at the most popular drugs in the UK, atorvastatin was the most prescribed drug. Simvastatin also made to the top of most commonly prescribed drugs. Historically, statins have been subject to scrutiny from the press, mostly picking on a negative aspect of stain treatment. In today’s post, I will discuss statins pros and cons (advantages and disadvantages). I will also review other areas of statin treatment, like sid effects, effectiveness and more, to support the most comprehensive list of statins pros and cons.

Table of Contents

  • What are statins?
  • The legal classification of statins
  • Can you get simvastatin over the counter?
  • High dose – statins over the counter
  • Most popular statins in the UK  
  • Who needs to take statins
  • What are side effects associated with statin therapy?
  • Statins – pros and cons
  • Statins – interaction with other drugs
  • Statins pros and cons – conclusion

What are statins?

Statins are a group of drugs which reduce the level of ‘bad’ cholesterol. Low-density lipoprotein (LDL) cholesterol – ‘bad’ cholesterol contributes over time to narrowing and hardening of the blood vessels (the arteries). Narrowing of arteries can cause serious conditions, including:

  • Blockage of the arteries (atherosclerosis)
  • Heart attack (supply of the blood the heart is stopped)
  • Stroke (supply of the blood to the brain is restricted)
  • Angina (chest pains caused by an inadequate supply of blood to the heart)
  • Coronary heart disease (restriction of the blood supply to the heart)

Cardiovascular disease (heart attack, angina, heart failure) is one of the leading causes of death in the UK.

The legal classification of statins

In the UK, most statins are classified as prescription-only medicines (POM). POMs need to be prescribed by a doctor or another qualified prescriber.

Can you get simvastatin over the counter?

In 2004, simvastatin 10mg was reclassified from prescription-only medicine to pharmacy-only medicine; however, the first ‘over the counter’ statin called Zocor Heart-Pro was discontinued a few years later. Currently, pharmacy-only simvastatin is not available for sale in the UK, simply because none of the pharmaceutical manufactures produce this drug.  

Availability of high dose statins over the counter

In 2019, the availability of high dose statins came into a spotlight again, after the announcement by NHS that statins may be available from pharmacies without a prescription (NHS, 2019). The decision on the availability of high dose statins over the counter has not been made.

Most popular statins in the UK  

In the UK five statins are available on prescription:

  • atorvastatin
  • simvastatin
  • pravastatin
  • rosuvastatin
  • fluvastatin

The above statins may come in generic form or as branded medicines.

Statins are divided into three categories (NICE, 2016), based on their effectiveness to reduce low‑density lipoprotein cholesterol (LDL cholesterol):

  • low intensity: expected reduction of LDL is 20% to 30%
  • medium intensity: expected reduction of LDL is 31% to 40%        
  • high intensity: expected reduction of LDL is above 40%.

The table below reflects the popularity of each statin supported with prescribing information for the last 12 months (Openprescribing.net, 2021).

RankNameItems prescribed (mln)
1Atorvastatin49.2
2Simvastatin20
3Rosuvaastatin2.8
4Pravastatin2.5
5Fluvastatin0.1

 Data source: OpenPrescribing.net Period: (Dec ’19—Nov ’20)

Who needs to take statins?

Patients who are considered for statin therapy, need to have a blood sample taken to determine total cholesterol levels, high‑density lipoprotein (HDL) cholesterol, non‑HDL cholesterol, and triglycerides (a type of fat).

Statins can be prescribed for patients as primary or secondary prevention of cardiovascular disease (CVD). Primary prevention describes treatment to prevent a health condition from happening. For example, in terms of CVD, this usually means prevention of heart attack or stroke. Secondary prevention described treatment aiming to prevent further disease progression, for example, reducing future episodes of heart attacks in individuals who have had a heart attack.    

Statins are usually recommended as primary prevention in individuals who (NICE, 2020):  

  • Have estimates risk of developing cardiovascular disease 10% or more in the next 10 years. Risk is based on an assessment called QRISK.
  • Type 1 diabetic patients, aged over 40 who have had diabetes for more than 10 years or have other risk factors for developing cardiovascular disease or have diabetic neuropathy.
  • Have chronic kidney disease or high cholesterol runs in the family

Secondary prevention with statis is considered in patients who (ibid):

  • Patient with cardiovascular disease, for example, patients who have had a heart attack, angina, mini-stroke or peripheral arterial disease.

What are side effects associated with statin therapy?

Side effect profile differs between each statin. Atorvastatin (the most common statin in the UK) can commonly cause the following side effects (BNF, 2021):

  • Epistaxis (nose bleeds)
  • Hyperglycaemia (increased sugar level)
  • Hypersensitivity (allergic reactions)
  • Joint disorders
  • Laryngeal pain (pain in the larynx)
  • Muscle complaints
  • Nasopharyngitis
  • Pain

Additionally, the following common side effects are listed in the licensing information for atorvastatin (eMC, 2019):

  • Headache
  • Constipation, diarrhoea, flatulence, dyspepsia, nausea
  • Abnormal liver function tests
  • Increased blood creatine kinase

Statins – pros and cons

Now let’s talk about statins pros and cons.

Statins – pros

Statins work – reduction of cardiovascular disease and strokes  

Statins are the most effective lipid-lowering drugs. Statins lower LDL cholesterol effectively and thus reduce the risk of developing or progressing cardiovascular disease as part of primary and secondary prevention. Lowering of LDL cholesterol reduces the risk of coronary death, ischaemic stroke, myocardial infarction (heart attack) and revascularisation (CCT, 2012).

Statins produce an anti-inflammatory effect

Cardiovascular diseases, for example, atherosclerosis (build-up of fats and cholesterol in arteries) are characterised by chronic inflammation. Many studies confirmed that statins produce anti-inflammatory effect contributing to more beneficial treatment (Jain & Ridker, 2005).

Statins produce an anti-thrombotic effect

Statins may help to prevent a blood clot formation by different means. Statins were also found to help with the destruction of blood clots (Pinal-Fernandez et al., 2018).

Statins produce a pleiotropic effect

the pleiotropic effect is an umbrella term which describes benefits of statins which go beyond a lipid-lowering effect, for example improving endothelial function (endothelium forms inside lining of the arteries), decreasing oxidative stress and inflammation.

High cholesterol weakens the endothelium, which promotes the process of atherosclerosis, which is characterised by a build-up of fatty materials in arteries, which restrict the blood flow and may result in the clot formation.  

The effect of statin on endothelium is a complex topic. By lowering the cholesterol statins improve the function of the endothelium. It is proposed that statins produce an antioxidant effect and increase nitric oxide production, bringing additional benefits in the process (Liao & Laufs, 2005).

Statins – cons

The second part of stains pros and cons may seem to be more lengthy and more detailed. I reviewed certain risk factors with statin therapy more thoroughly to diminish any misunderstandings associated with statin therapy.

Muscle toxicity (including myopathy and rhabdomyolysis)

All statins can cause muscle toxicity. However, the increased risk is observed in individuals taking a higher dose of stains or in certain patients, for example (BNF, 2021):  

  • a family history of muscle illness
  • previous episodes of muscle toxicity
  • high alcohol consumption
  • reduced performance of kidneys (renal impairment) and
  • hypothyroidism.

Patients at higher risk of muscle toxicity should typically have a blood test to determine creatine kinase levels (CK). CK indicates muscle injuries and muscular disease. Statin therapy should not be initiated if CK is too high (five times more of the upper limit). Some individuals, for example, ‘muscly’ people, may have high CK, due to increased muscle in the body.

Rhabdomyolysis, destruction of muscle cells, is the most severe side effect of statins, which may cause kidney failure and even death. Rhabdomyolysis is not a common side effect. A large study (252,460 patients) investigated number rhabdomyolysis cases in patients taking lipid-lowering drugs (atorvastatin, pravastatin, or simvastatin). An average incidence of rhabdomyolysis was 0.44 per 10,000 person-years, which means 0.44 of person out of 10,000 people experienced rhabdomyolysis during observation for a year (Graham et al., 2004).

A more recent review of clinical trials estimated that only about 2-3 individuals per 100,000 patients who take statins might develop rhabdomyolysis and acuter renal (kidney) failure (ibid).

The frequency of statin-related myopathy (muscle pain, muscle weakness, cramps and tendon pain) was found to be slightly higher. Another large study which took place in the UK set the incidence of myopathy at 1.2 per 10,000 person-years (Gaist et al., 2001). Taking certain drugs alongside statins increases the risk of myopathy (see the next paragraph).     

Statins – interaction with other drugs

Like other drugs, statins can interact with other medicines, when taken at the same time. Taking certain medications with statins at the same time, for example, fibrates increase the risk of rhabdomyolysis (see above).

A common interaction seen in community pharmacy involves statins and some antibiotics, such as erythromycin or clarithromycin. It is usually recommended for simvastatin to avoid the combination of both drugs (BNF, 2021 & Gov.uk, 2014). For atorvastatin, patients are typically asked to suspend taking medicine for the duration of antibiotic treatment.

The list of drugs that interact with statins is much longer. Speak to your GP or pharmacist if you are unsure about the treatment with statins.   

Can statin cause diabetes?

Many studies investigated and reported an increased risk of diabetes development in patients on statins. The exact mechanism is not known; multiple factors are proposed. However, the increased risk of diabetes is narrowed to individuals who are already at risk for developing diabetes (Robinson, 2015). Overall the increased risk of statin-related diabetes is most likely unimportant because reducing cardiovascular risk outweighs any potential negative impact of the treatment with statins (ibid).   

Can statins cause liver disease?

Liver function tests are usually performed before the initiation with statins and occasionally after the treatment is commenced. Several reasons can impact the level of transaminases, for example, a ‘fatty liver’ or alcoholic liver disease. Use of statins is cautioned in patients who drink alcohol a lot or have a history of liver disease.     

Statins can temporarily increase certain chemicals called transaminases without any symptoms present. The frequency of liver damage caused by statins is estimated at 1% (Gillett et al., 2011). However, a liver complication caused by statins varies between studies with some reporting liver complications of very rare frequency. In the US, the Federal Drug Administration (FDA) reported serious, statin-caused liver disease as extremely rare (ibid).

Can statins cause stroke?

Statins may increase the risk of intracerebral haemorrhage (a type of stroke) in patients who previously had a stroke. A large study which investigated the over 500,000 patients over ten years concluded that during the first six months of therapy patients on statins had a similar risk of intracerebral haemorrhage as patients without treatment. However, after the six months of the treatment patients on statins had a lower risk of stroke. Overall this study suggested that statins reduce the risk of intracerebral haemorrhage in patients who had not had this type of stroke before (Ribe et al., 2019).

On the contrary, some reports suggest that statins may increase the risk of haemorrhagic stroke. However, this risk is outweighed by a clear reduction of ischaemic stroke (another type of stroke) together with the decrease of other cardiovascular events and death caused by a blood clot (CTT, 2012).   

Bad reputation

To a certain degree, statins have a ‘bad’ reputation. Over the years, mainstream media picked on various aspects of statin therapy with tabloids very often being the best in dramatisation or rather the worst in delivery of clear, unbiased information.   

Dose timing

Some statins, for example, simvastatin must be taken at night. This is because simvastatin stops cholesterol synthesis, which happens at night. Atorvastatin, the most common statin in the UK can be taken during the day, making this disadvantage less important.   

Statins: pros and cons – conclusion

Statins are an effective class of drugs, which reduce cholesterol and any possible cardiovascular events and stroke. Review of around 57000 patients from various clinical trials, which took place between 1994 and 2008 – concluded that statins reduce ‘all-cause’ mortality (death), significant cardiovascular evens (for example a heart attack) and revascularisations with no ‘excess’ of side effects (Taylor et al., 2013).  

Although treatment with statins can be associated with muscle problems when treated in the community. Muscle side effects have rarely been reported in clinical trials (Ganga at el., 2014).  

References:

BNF (2021). ATORVASTATIN. Available at: https://bnf.nice.org.uk/drug/atorvastatin.html#sideEffects Accessed on 07/02/2021

BNF (2021). Statins. Available at: https://bnf.nice.org.uk/drug-class/statins.html Accessed on 08/02/2021

BNF (2021). Simvastatin: interactions. Available at: https://bnf.nice.org.uk/interaction/simvastatin-2.html Accessed on 09/02/2021

Cholesterol Treatment Trialists’ (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012 Aug 11;380(9841):581-90. doi: 10.1016/S0140-6736(12)60367-5. Epub 2012 May 17. PMID: 22607822; PMCID: PMC3437972. Available at: https://doi.org/10.1016/s0140-6736(12)60367-5 Accessed on 09/02/2021

eMC (2019). Atorvastatin 10 mg Film-coated Tablets. Available at: https://www.medicines.org.uk/emc/product/4339/smpc Accessed on 07/02/2021

Gaist D, Rodríguez LA, Huerta C, Hallas J, Sindrup SH. Lipid-lowering drugs and risk of myopathy: a population-based follow-up study. Epidemiology. 2001 Sep;12(5):565-9. doi: 10.1097/00001648-200109000-00017. PMID: 11505177. Available at: https://doi.org/10.1097/00001648-200109000-00017 Accessed on 08/02/2021

Ganga HV, Slim HB, Thompson PD. (2014) A systematic review of statin-induced muscle problems in clinical trials. Am Heart J. 2014 Jul;168(1):6-15. doi: 10.1016/j.ahj.2014.03.019. Epub 2014 Apr 12. PMID: 24952854. Available at: https://doi.org/10.1016/j.ahj.2014.03.019 Accessed on 09/02/2021 

Gillett RC Jr, Norrell A. Considerations for safe use of statins: liver enzyme abnormalities and muscle toxicity. Am Fam Physician. 2011 Mar 15;83(6):711-6. PMID: 21404982. Available at: https://www.aafp.org/afp/2011/0315/p711.html Accessed on 09/02/2021

Gov.uk (2014). Statins: interactions, and updated advice for atorvastatin. Available at: https://www.gov.uk/drug-safety-update/statins-interactions-and-updated-advice-for-atorvastatin Accessed on 09/02/2021

Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, Gurwitz JH, Chan KA, Goodman MJ, Platt R. Incidence of hospitalised rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004 Dec 1;292(21):2585-90. doi: 10.1001/jama.292.21.2585. Epub 2004 Nov 22. PMID: 15572716. Available at: https://doi.org/10.1001/jama.292.21.2585 Accessed on 08/02/2021

Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov. 2005 Dec;4(12):977-87. doi: 10.1038/nrd1901. PMID: 16341063. Availablet at: https://doi.org/10.1038/nrd1901 Accessed on 06/02/2021         

Liao JK, Laufs U. (2005). Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118. doi:10.1146/annurev.pharmtox.45.120403.095748 Available at: https://dx.doi.org/10.1146%2Fannurev.pharmtox.45.120403.095748 Accessed on 08/02/2021

NHS (2019). NHS to review making statins available direct from pharmacists as part of Long Term Plan to cut heart disease. Available at: https://www.england.nhs.uk/2019/09/nhs-to-review-making-statins-available-direct-from-pharmacists-as-part-of-long-term-plan-to-cut-heart-disease/ Accessed on 04/02/2021

NICE (2016). Cardiovascular disease: risk assessment and reduction, including lipid modification. Available at: https://www.nice.org.uk/guidance/cg181/chapter/Introduction Accessed on 06/02/2021

NICE (2020). Lipid modification – CVD prevention. Available at: https://cks.nice.org.uk/topics/lipid-modification-cvd-prevention/ Accessed on 07/02/2021

Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Statins: pros and cons. Med Clin (Barc). 2018;150(10):398-402. doi:10.1016/j.medcli.2017.11.030 Available at: https://dx.doi.org/10.1016%2Fj.medcli.2017.11.030 Accessed on 07/02/2021

Robinson JG. Statins and diabetes risk: how real is it and what are the mechanisms? Curr Opin Lipidol. 2015 Jun;26(3):228-35. doi: 10.1097/MOL.0000000000000172. PMID: 25887679. Available at: https://doi.org/10.1097/mol.0000000000000172 Accessed on 09/02/2021

Taylor F, Huffman MD, Macedo A, Moore THM, Burke M, Davey Smith G, Ward K, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub5 Available at: https://doi.org/10.1002/14651858.cd004816.pub5 Accessed on 09/02/2021

I am a community pharmacist working in UK. I blog about drugs, health and pharmacy.

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