Statin Pharmacogenomics: Opportunities to Improve Patient Outcomes and Healthcare Costs with Genetic Testing

Abstract

HMG-CoA reductase inhibitors, commonly known as statins, are some of the most widely prescribed medications worldwide and have been shown to be effective at lowering cholesterol in numerous long-term prospective trials, yet there are significant limitations to their use. First, patients receiving statin therapy have relatively low levels of medication adherence compared with other drug classes. Next, numerous statin formulations are available, each with its own unique safety and efficacy profile, and it may be unclear to prescribers which treatment is optimal for their patients. Finally, statins have class-wide side effects of myopathy and rhabdomyolysis that have resulted in a product recall and dosage limitations. Recent evidence suggests that two genomic markers, KIF6 and SLCO1B1, may inform the therapy choice of patients initiating statins. Given the prevalence of statin usage, their potential health advantages and their overall cost to the healthcare system, there could be significant clinical benefit from creating personalized treatment regimens. Ultimately, if this approach is effective it may encourage higher adoption of generic statins when appropriate, promote adherence, lower rates of myopathy, and overall achieve higher value cardiovascular care. This paper will review the evidence for personalized prescribing of statins via KIF6 and SLCO1B1 and consider some of the implications for testing these markers as part of routine clinical care.

Prevalence and Factors Associated With Statin Use Among a Nationally Representative Sample of US Adults: National Health and Nutrition Examination Survey, 2011–2012

“…Medication non-adherence has also limited the projected benefits of statin use 9 . Medication cost is a known factor, given improved use with insurance.…”

“…In 2011, statin use was estimated to cost more than $20 billion in the US 9 and this number is likely to increase greatly in future years based on NHANES projections 10 although the exact number can’t be predicted due to the guidelines calling for a risk-benefit discussion between patient and physician before the initiation of statin therapy in lower risk primary prevention individuals. On the other hand, more than a third of the US adult population have artherosclerotic cardivovascular disease (ASCVD), which accounts for 35% of all deaths 11 , with cardiovascular disease and stroke generating $312.6 billion in direct and indirect health care costs in 2009 12 .…”

ABCG2 Gene Polymorphisms as Risk Factors for Atorvastatin Adverse Reactions: A Case–Control Study

“…Statin-related muscular side effects are the most common cause of withdrawal and statin discontinuation could induce increased vascular events [57]. Currently there is no direct clinical evidence that the personalized prescribing of statins using genotyping will improve patients' medication adherence; however, previous analyses suggest that this is a logical conclusion [58]. There is evidence that genomic information could be used as a behavioral health intervention [59] affecting patient's sense of self efficacy while AKROBATS study provides prospective evidence that pharmacogenetic testing has utility in modifying patient adherence [60].…”

“…All patients were of Croatian ancestry. Median (interquartile range) age was 56 (48-66) and 60 (53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70) in the groups of patients with and without ADRs, respectively. The gender distribution was identical, and atorvastatin median prescribed dose was the same in both groups.…”

Correlation between Apolipoprotein E genetic polymorphism and atrial fibrillation

“…Moreover, these results indicate that higher BMIs lead to a larger LAD and lower ejection fraction (EF) and higher incidence of AF. Old age is an independent risk factor for AF [27][28] . People with a high BMI may have a greater amount of body fat, which increases the prevalence of AF.…”