Original ArticleClinical and economic consequences of statin intolerance in the United States: Results from an integrated health system
Introduction
Given the evidence in support of statins for reducing low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease events,1, 2, 3, 4 statins are the lipid-modifying therapy (LMT) that is most widely recommended by cholesterol management guidelines.5, 6, 7, 8, 9 Despite these recommendations, data suggest that statins are underutilized even among patients with established atherosclerotic cardiovascular disease.10, 11, 12, 13 One cause for underutilization, suboptimal dosing, adherence, and discontinuation is statin intolerance (SI) resulting mainly from muscle-related symptoms.7, 14, 15 The real-world prevalence of SI due to muscle-related symptoms has been reported to be as high as 25%.7, 16, 17, 18, 19, 20, 21, 22
Currently, there is no gold-standard definition of SI, although guidelines and major organizations have attempted to clarify the definition.7, 15, 23, 24 The National Lipid Association (NLA) SI Panel (a component of the Statin Safety Assessment Task Force) defines SI as a decision to decrease or stop the use of an otherwise beneficial statin because of adverse effects, which can most often be attributed to muscle-related symptoms impacting quality of life.15, 25 Specifically, the NLA characterizes SI as a clinical syndrome defined by the inability to tolerate ≥2 statins as a result of unwanted symptoms (real or perceived) or abnormal laboratory values: one statin at the lowest starting daily dose and another at any daily dose. Other known causes of these symptoms should be excluded, and symptoms should be temporally related to statin treatment, reversible on discontinuation, and reproducible by reexposure. The NLA definition is consistent with definitions and guidance from other groups, including the European Atherosclerosis Society Consensus Panel and the Canadian Consensus Working Group.7, 26 Many guidelines and recommendations advocate maintaining therapy even in patients with SI because of the clinical benefits associated with statins.7, 8, 27, 28
Despite the reported prevalence of SI,7, 16, 17, 18, 19, 20, 21, 22 the clinical and economic impacts of SI are largely unknown. Therefore, the objectives of this study were to summarize the clinical characteristics of patients with SI and to quantify differences in LDL-C goal attainment, health care costs, and CV events among patients with SI compared with a matched cohort of statin users who do not have SI.
Section snippets
Study design and environment
This retrospective observational study extracted data from the Geisinger Health System (GHS) electronic health record (EHR) from January 1, 2008, through September 30, 2014. This study was approved by the Geisinger Institutional Review Board.
Patient population and subgroups
Patients ≥18 years and who had ≥12 months of health system encounters during the study period were included. Patients with a history of SI were identified by either a GHS custom diagnosis code (EP914) or International Classification of Diseases, Ninth
Patient disposition and baseline characteristics
Initially, 11,207 patients with SI and 206,561 control patients were identified in the EHR (Fig. 1). The rate of SI diagnosis among all patients treated with statins during the study period was 5%. Of those patients with an SI diagnosis, 89% were classified based on a statin allergy documented either by ICD-9-CM code or notation on the patient's allergy list, 5% were classified using a GHS custom SI diagnosis code, and the remaining were documented with both (6%). Forty-six patients had both a
Discussion
On average, patients with SI, both in the primary prevention and the high CV-risk categories, were less likely to achieve their LDL-C goals, experienced higher health care resource use, and had a higher risk for revascularization procedures. Additionally, SI patients in the diabetes risk category had a higher risk for any CV event except death. These results suggest that patients with SI have relevant clinical and economic consequences that highlight the need for alternative treatment
Conclusions
In summary, most of the patients diagnosed with SI in this study were able to tolerate at least a nondaily dose of statin. However, most patients diagnosed with SI were not on high-intensity statin regimens. Patients with SI were less likely to reach LDL-C goals, incur higher health care costs and have a higher risk of some CV events compared with patients without SI. Therefore, alternative lipid-modifying treatment options are needed for patients with SI.
Acknowledgment
The authors wish to thank Steven R. Steinhubl, MD, Geisinger Center for Health Research, Danville, PA, USA, and Scripps Translational Science Institute, La Jolla, CA, USA, for his contributions to this research and for review of the manuscript. Writing and editorial support was provided by MicroMass Communications, Inc, with funding from Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA, and Sanofi US, Bridgewater, NJ, USA.
Submission declaration: The work described has not been published
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This study was funded by Regeneron Pharmaceuticals, Tarrytown, NY, USA, and Sanofi US, Bridgewater, NJ, USA. The sponsors were involved in the study design and in the collection, analysis, and interpretation of data. The sponsors were also involved in the writing of the report and the decision to submit the article for publication.