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How to lower cholesterol when statins are not tolerated

Heart, Stroke | July 9, 2015 | Author: The Super Pharmacist

heart, Stroke

How to lower cholesterol when statins are not tolerated

Statins (HMG-CoA reductase inhibitors) are a class of drug prescribed by doctors to lower cholesterol levels in blood and help reduce the risk of heart attack and stroke. Whilst they can significantly reduce the risk of stroke and heart attack, not all patients who take statins tolerate them very well, and different strategies must be considered to help reduce excessive levels of cholesterol (also known as ‘hypercholestrolemia’ or ‘dyslipidemia’).

How do patients know if they are responsive to statins?

Before taking statins, each patient should have a blood test prior to treatment that checks their routine levels of cholesterol and the functionality of their liver. Further tests are then undertaken between 1-3 months, and again at 12 months, to ascertain how well the liver is responding to the medication. An additional blood test will provide an indicator of cholesterol level to see how efficacious the statin is. All individuals using statins are also generally advised to undertake a range of non-medical interventions, including eating a healthy diet, reducing or stopping smoking, maintaining a healthy weight, and reducing high blood pressure.

What happens when statins are not tolerated?

The most common side effect is a general pain experienced as soreness, weakness and tiredness. Statins can also cause myositis (an inflammation of the muscles) and the risk of muscular injury or muscular inflammation greatly increases if statins are taken in conjunction with other cholesterol reducing drugs known as fibrates (1).

In very rare cases, statins can also be the catalyst for a life-threatening condition known as rhabdomyolysis in which damaged skeletal tissue breaks down rapidly and can cause severe muscle pain, kidney failure, and liver damage. Some statins have been evidenced to result in higher than average cases of rhabdomyolysis, and some statins such as cerivastatin have been removed from the market as a result on the grounds of safety (2).

Statin intolerance is increasingly common in patient groups around with the world, with the evidence suggesting that patients will usually switch between 1-3 medications over the course of usage (3). Historically, it had been thought that testing creatine kinase (CK) levels was a definitive diagnostic test for statin-induced myalgias, but subsequent research has revealed that myositis and other statin-related harms can take place in the absence of biochemical evidence. As such, most statin intolerance tends to be documented through physician or pharmacist interaction with a patient.

Small scale studies have suggested a link between statin intolerance and new onset diabetes, with a meta-analysis of 17 different studies, covering 100,000 patients, showing a small effect and indications of glucose intolerance (4).

Why are some patients intolerant to particular statins?

The different kinetics and metabolism of individual statins can create intolerance in certain individuals (5), so there is often a pharmacological basis for trying a patient who is intolerant of a particular statin on an alternative drug within the same class. Intolerance to statins is estimated to affect between 5-10% of the total population, although some estimates place it higher due to a lack of ‘real world’ evidence regarding statin use (6). There is a very limited evidence base on the management and characteristics of patients who display intolerance to certain statins. There is some speculation that underling medical conditions have an effect on the tolerance of some statins, with a 2003 British study observing that patient comorbidities seemed to play a significant role in statin tolerance among patients who had switched medication.

As the number of patients taking statins will increase significantly in the future as a result of changing lifestyles and a continued rise in non communicable diseases, there is a clear need for further research that understands and formulates treatment strategies for future patients who take statins.

Are there the alternative treatments, other than switching statins, for patients who display intolerance?

Many patients will switch statins on a ‘trial and error’ basis, or have their dose adjusted if they experience negative symptoms. A full pharmaceutical review may also take place to see if there are any possible interactions with other medication, as there is some evidence that statins combined with medications such as amlodipine and diltiazem can result in severe muscle cramps, particularly when taking in conjunction with other medicines such as ciclosporin, danazol, and gemfibrozil (7).

A number of other pharmaceutical options are occasionally used as a statin substitute:

Bile acid sequestrants operate by binding to bile acids that are passed from the liver and the gall bladder into the gut, stopping bile from being absorbed into the bloodstream and lowering cholesterol as a result. The most commonly prescribed options in this family of drugs include colesevelam and colestipol, yet there remains very limited data to underpin their use. A comprehensive systematic review of their efficacy in reducing cholesterol levels, undertaken in 2014 by the National Institute of Health and Social Care Excellence in the UK, found that bile acid sequestrants resulted in no benefits or harms when compared with a number of placebo options (8).

Nicotinic acid has occasionally been used in response to statin intolerance, although due to its very severe side effects including flushing, nausea, vomiting and migraines, and questions regarding its efficacy in lowering cholesterol (9), healthcare professionals and patients alike are often reluctant to consider it as a viable long-term treatment option.

Fish oil. Some patients have experimented with fish oil and other complementary medicines as an alternative to statins, although the evidence for their use is inconclusive. The measurable benefits of taking supplements are not known.

Ezetimibe is often added to statin therapy to improve their efficacy and is occasionally prescribed in isolation. This medication has modest reductions of cholesterol over a significant period of time, particularly in comparison to statin therapy.

The most common response to statin intolerance remains a switch to another statin, or alternate day dosing, which has a limited evidence base for reducing LDL levels over a 12 month period (10). There remains a clear need for further research, and guidelines, for patients who are statin-resistant and need to maintain lower levels of cholesterol through other means.  Australia’s best online discount chemist


1. Desai CS, Martin SS, Blumenthal RS (2014) Non-cardiovascular effects associated with statins BMJ 17;349:g3743

2. Armitage J (2007) The safety of clinical statins in practice Lancet 370(9601): 1781-90

3. Nair RK, Karadi RL, Kilpatrick ES (2008) Managing patience with statin intolerance: a retrospective study Br J Cardiol 15:158-160

4. Navarese EP, Buffon A, Andreotti F, et al (2013) Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am J Cardiol 111:1123-1130

5. Moghadasian MH (2002) A safety look at currently available statins. Expert Opin Drug Saf 1:269–74

6. Simons LA, Levis G, Simons J (1996) Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med J Aust 164:208–11

7. Derosa G, Maffioli P (2011) Drug safety evaluation of amlodipine Expert Opin Drug Saf 10(5):795-804

8. National Clinical Guideline Centre (UK). Lipid Modification: Cardiovascular Risk Assessment and the Modification of Blood Lipids for the Primary and Secondary Prevention of Cardiovascular Disease. London: National Institute for Health and Care Excellence (UK); 2014 Jul. (NICE Clinical Guidelines, No. 181.) 14, Bile acid sequestrants (anion exchange resins) for the prevention of CVD

9. Ip CK, Jin DM, Gao JJ et al. (2015) Effects of add-on lipid-modifying therapy on top of background statin treatment on major cardiovascular events: A meta-analysis of randomized controlled trials Int J Cardiol 191:138-48

10. Juszczyk MA, Seip RL, Thompson PD (2005) Decreasing LDL cholesterol and medication cost with every-other-day statin therapy Prev Cardiol 8(4):197–199

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