While researchers have evidence from case-control studies and clinical trials reporting an association between genetic variants of the SLCO1B1 gene and statin myopathy, genetic testing for the presence of these variants continue to be deliberated among clinicians and considered by many to be not medically necessary.
State of statin safety challenges and suboptimal adherence
While countries, employers, insurers, and patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD) determine how they will now pay for the emerging class of low-density lipoprotein (LDL)-lowering drugs known as PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors many clinicians continue to wrestle with statin intolerance and researchers continue to analyze the genetic variants of an individual’s metabolic response. Few doubt that statins have been proven effective in reducing cardiovascular morbidity and mortality; however, these treatments do not come without a challenge in terms of nonadherence due to side effects. For some patients, statin treatment remains suboptimal due to muscle aches, spasms, and pain.
Statin-associated muscle symptoms (SAMS)—a key consideration in treatment discontinuation
SAMS are a key contributor to statin intolerance and the most common cause of statin discontinuation. Researchers suggest the frequency of SAMS to be less than 5% (as seen in well-controlled clinical trials), but the frequency of SAMS has been reported as high as 25% of current statin users or 60% of former users. While SAMS may resolve quickly with the discontinuation of the statin, in the Prediction of Muscular Risk in Observational Conditions (PRIMO) study, SAMS were shown to take as long as two months to resolve. In rare cases, statin-induced myopathy can become debilitating.
The science behind the symptoms—SLCO1B1, SNPs, and SAMS
Some researchers have suggested an association between SAMS and variations in the SLCO1B1 gene. Inherited variations in the SLCO1B1 gene known as SNPs (single nucleotide polymorphisms) affect the function of this transporter. The presence of this variant, especially in homozygotes, results in significantly decreased ability to take up statins, less effectiveness of some statins in lowering LDL-C, higher blood levels after dosing, and an increased risk of SAMS. Studies have shown that people who have particular inherited variations on the SLCO1B1 gene are 4-17 times more likely to suffer SAMS as a side effect. Despite this evidence, further research is needed, as in a recent review on the pharmacogenetics of SAMS, researchers have clearly stated that, “a current, critical evaluation of the literature on pharmacokinetic genetic variants and SAMS for potential translation to clinical practice is lacking.”
A call-to-action for clinicians
In a recent interview, an industry leader in diagnostics testing shared that the “test [for genotyping SLCO1B1 polymorphisms] is not diagnostic, not confirmatory, just indicates a higher risk of getting a problem on a statin.” While we cannot clearly label this approach as personalized or precision medicine like recent cardiovascular advances, data continue to emerge on the association between pharmacokinetic genetic variants and SAMS. As suggested by the SEARCH Collaborative Group, the translation of this research to advance the future of clinical practice will “assist in tailoring both the statin dose and safety monitoring (especially when statins are used in combination with certain other drugs and during the first year of treatment, when the absolute risk of myopathy is greatest) in order to obtain the benefits of statin therapy more safely and effectively.” At this time, genotyping provides the clinician and patient with useful information that may affect a patient’s ability to metabolize statins, minimize the occurrence of SAMS, and understand his/her response to LDL-C lowering therapy with statins.