Dealing with statin intolerance and resistance
Patients with hypercholesterolaemia with unchanging LDL-cholesterol levels after 6 weeks of statin treatment should be actively assessed for either statin intolerance or resistance, says an expert at the 7th Malaysian Endocrine and Metabolic Society (MEMS) Annual Congress.
Statin intolerance refers to a partial or complete inability to use statins due to side effects or detected abnormalities in markers of liver or muscle function, such as alanine aminotransferase (ALT) or creatine kinase (CK). Statin resistance refers to an incorrect response or failure to reach target LDL levels despite best available therapy of the highly tolerated dose.
Speaking at the 7th Malaysian Endocrine and Metabolic Society Annual Congress, Dr. Foo Yoke Leong, clinical cardiologist at Hospital Serdang, highlighted the double issues of patients discontinuing statins due to known side effects, and of undetected genetic disorders that could negate the effects of statins. He presented data from the 2012 Pan-Asian CEPHEUS study—assessing LDL-C goal attainment among 8,064 Southeast Asian adults aged 18 and above—which indicated only 45.1 percent of Malaysians on lipid-lowering drug therapies actually reached their target cholesterol levels. In addition, the study found that 35.9 percent of patients were repeatedly prescribed the same medication on follow-up, despite lack of improving LDL levels.
“Most of us do not take much effort to look into it—we just see the patient and continue their statins, but we know that this is wrong,” said Foo. “We need to assess their risk factors, whether they are taking their medicine, and whether they are under the intolerant or resistant group.”
In a 2012 study of 10,409 French patients on statins, 10 percent reported statin intolerance in the form of muscular symptoms (eg, muscular pain, cramps, joint pain, weakness, tendinitis, fatigue and/or sarcopenia). In addition, 30 percent admitted treatment discontinuation due to side effects. [Nutr Metab Cardiovasc Dis 2012;doi:10.1016/j.numedcd.2012.04.012]
“Muscular side effects are the number one cause of discontinuation,” said Foo. “Most patients have mild aches and pains. If you talk further with them, you find they have stopped their statins… A lot of patients are also afraid of what they read online about them.”
In general, common side effects of statin use include myalgia, persistently high CK levels, fatigue, liver derangement and increased risk of type 2 diabetes mellitus. Some patients also may experience rhabdomyolysis or mild cognitive impairment.
Foo advised doctors to take patient comments of any side effects seriously and consider changing the statins prescribed. He added that patients should also be assured that the cardiovascular (CV) benefits by far outweigh the risk as statins are eight times more likely to prevent CV events than cause one case of diabetes. [Evidence-Based Med. 2010;15(3):84–85]
Some patients may also be resistant to statins due to deleterious mutations in genes such as PCSK9, which can reduce the number of functioning LDL-cholesterol receptors in the liver, leading to familial hypercholesterolemia (FH), a condition more common among Southeast Asians than any other part of the world. Additionally, non-genetic factors that can cause statin resistance include diabetes, nephrotic syndrome, hypothyroidism and drug-induced hypertension.
In addition to better patient communication, Foo stressed the importance of obtaining CK and LDL-cholesterol blood test results of patients prior to commencement of statins in order to observe for resistance or intolerance.
Non-statin cholesterol lowering agents such as ezetimibe, bile acid sequestrants, niacin and PCSK9 inhibitors are recommended only after reversible causes of statin intolerance or resistance, such as hypothyroidism and drug-drug interactions, have first been addressed and the patient re-challenged with similar or smaller doses of statins. Foo recommended the American College of Cardiology’s Statin Intolerance Tool (available as mobile app or online) as a useful means of evaluating individual patients and guiding their follow-up according to recommended ACC guidelines for statin therapy.