Clinical and economic consequences of statin intolerance in the United States: Results from an integrated health system

Highlights

• Scarcity of data on the clinical and economic impact of statin intolerance

• First retrospective claims analysis to evaluate impacts of statin intolerance

• Patients with statin intolerance are less likely to reach LDL-C treatment goals

• Statin intolerance is associated with higher health care costs

• Patients with statin intolerance are at higher risk for some CV events

Background

Although statins are considered safe and effective, they have been associated with statin intolerance (SI) in clinical and observational studies.

Objective

The objective of this study was to describe the clinical and economic consequences of SI through comparison of an SI cohort of patients with matched controls.

Methods

This study used data extracted from an integrated health system's electronic health records from 2008 to 2014. Adults with SI were matched to controls using a propensity score. Patients were hierarchically classified into 6 mutually exclusive cardiovascular (CV)-risk categories: recent acute coronary syndrome (ACS; ≤12 months preindex), coronary heart disease, ischemic stroke, peripheral artery disease, diabetes, or primary prevention. The study endpoints, low-density lipoprotein cholesterol (LDL-C) goal attainment, medical costs, and time to first CV event were compared using conditional logistic regression, generalized linear, and Cox proportional hazards models, respectively.

Results

Patients with SI (n = 5190) were matched with controls (n = 15,570). Patients with SI incurred higher medical costs and were less likely to reach LDL-C goals than controls. Patients with SI were at higher risk for revascularization procedures in all CV risk categories except ACS, and those in the diabetes risk category were at higher risk for any CV event. There was a lower risk of all-cause death among patients with SI.

Conclusions

Patients with SI were less likely to reach LDL-C goals, incurred higher health care costs, and experienced a higher risk for nonfatal CV events than patients without SI. Alternative management strategies are needed to better treat high CV risk patients.

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.