Adherence to Statins and LDL-Cholesterol Goal Attainment

Published Online: April 17, 2014
Margaret D. Chi, MPH; Southida S. Vansomphone, PharmD; In-Lu Amy Liu, MS; T. Craig Cheetham, PharmD, MS; Kelley R. Green, PhD; Ronald D. Scott, MD; and Kristi Reynolds, PhD, MPH
Objectives: To examine the relationship between low-density lipoprotein cholesterol (LDL-C) goal attainment and adherence to statin medications in patients with coronary artery disease (CAD).

Study Design: Cross-sectional study of CAD patients 18 years of age or older in an integrated healthcare system.

Methods: Patients dispensed 2 or more statin prescriptions between May 2009 and May 2010, were identified. Medication possession ratio (MPR) was calculated to estimate adherence. The LDL-C value closest to May 27, 2010, was used to determine goal. Adherence and LDL-C goal were defined as 80% or greater MPR and less than 100 mg/dL or less than 70 mg/dL, respectively. Electronic medical records were used to identify patient demographics and clinical information. Logistic regression was used to estimate the effect of these factors on goal attainment.

Results: A total of 67,100 CAD patients were identified. Overall, 85.8% had LDL-C less than 100 mg/dL, 32.4% had LDL less than 70 mg/dL, and 79.8% were adherent to their statin medication. Over 65% of patients not at LDL-C goal less than 100 mg/dL were adherent. Among patients with LDL-C less than 100 mg/dL, 17.9% were not adherent. Increasing medication adherence was associated with improved LDL-C levels. Adherence to statins, male sex, Asian and Hispanic race/ethnicity, a higher number of concurrent prescriptions, higher Charlson Comorbidity Index, and hypertension were associated with LDL-C goal attainment.

Conclusions: Incorporating LDL-C levels and medication adherence at the point of care allows providers to focus interventions to address either adherence challenges or the need for medication titration in an effort to improve LDL-C goal attainment and ultimately reduce morbidity and mortality.

Am J Manag Care. 2014;20(4):e105-e112
Cardiovascular disease is the leading cause of death in the United States with 1 out of 5 deaths attributable specifically to coronary artery disease (CAD). Each year, approximately 635,000 people in the United States will have a new coronary attack and 280,000 will have a recurrence.1 Patients living with CAD have an increased risk of a recurrent coronary event,2-4 which can lead to disability or death. In addition, in 2008, CAD had an estimated total national economic burden of $190.3 billion.1

To reduce the risk of recurrent events, the National Cholesterol Education Program (NCEP) recommends a low-density lipoprotein cholesterol (LDL-C) goal level of less than 100 mg/dL for patients with CAD through the use of lipid-lowering drugs such as hydroxymethylglutaryl-CoA reductase inhibitors (statins),5 and studies have shown that those who have reached this goal have lower rates of recurrence and mortality.6-9 Despite their efficacy, the use of these drugs in CAD patients has been shown to be suboptimal.10-12

Although studies have focused separately on LDL-C levels as well as adherence to statins among CAD patients, little is known about how adherence directly affects lipid levels in this population. We examined the association between LDL-C goal attainment and adherence to statins among CAD patients. By understanding the association of adherence and LDL-C goal attainment status, it will be possible to target the appropriate populations to ultimately improve patient treatment and outcomes.


Study Setting and Population

This study was conducted at Kaiser Permanente Southern California (KPSC), an integrated healthcare system that provides care to approximately 3.5 million members across 10 counties in Southern California. The Institutional Review Board at KPSC approved this study.

The source population was identified from the KPSC CAD Registry, which identifies patients with CADrelated International Statistical Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes from hospitalization and outpatient and inpatient CAD-related ICD-9-CM procedure codes (available upon request). The registry includes “risk equivalent” atherosclerotic cardiovascular diseases including ischemic stroke, peripheral arterial disease, and abdominal aortic aneurysm. Deceased members and those living in skilled nursing facilities are excluded from the registry.

Patients eligible for this study included all adult members 18 years or older in the registry as of May 27, 2010, with 12 months of continuous prior enrollment. Patients were included if they had filled at least 2 statin prescriptions (simvastatin or a combination of simvastatin and ezetimibe) and had at least 1 LDL-C result in this time period. Patients with rhabdomyolysis, creatinine kinase greater than 10,000 IU/L, allergy or intolerance to statins, and those without continuous membership or drug benefits between May 2009 and May 2010, were excluded. A total of 67,100 members were eligible and included in this analysis (Figure 1).

Data Collection and Measures

Information on patient demographics including age, gender, race/ethnicity, and clinical information including laboratory tests, prescription medications, healthcare utilization and comorbidities were extracted from health plan electronic databases. When multiple LDL-C measurements were present, the most recent measurement in the study period was extracted. LDL-C goal attainment was defined according to guidelines by the NCEP5 as less than 100 mg/dL and the optional goal of less than 70 mg/dL for these high-risk patients.

Information on healthcare utilization during the study period included the number of unique prescription medications (based on the generic product identified subclass), the numbers of clinic and emergency department (ED) visits and number of hospital admissions. The Deyo adaptation of the Charlson Comorbidity Index (CCI) was determined using ICD-9-CM diagnosis codes from inpatient and outpatient encounters as an overall measure of disease burden.13

Pharmacy fill data were extracted for each eligible individual and a medication possession ratio (MPR) was calculated looking back 400 days from May 27, 2010, as the sum of the days of supply divided by the total number of days between the first dispense date and May 27, 2010, when the most recent prescription was overdue. If the most recent prescription was not overdue, then MPR was calculated as the sum of the days of supply, excluding the last refill, divided by the total number of days between the first dispense date and last dispense date. The most recent refill was disregarded when the prescription was not overdue to avoid inflating the MPR. Adherence was defined as MPR 80% or greater, as suggested by previous studies.4,14

Statistical Analysis

Descriptive statistics (means and proportions) were used to present patient characteristics categorized by LDLC goal attainment (<100 mg/dL; optional <70 mg/dL). Mean LDL-C levels were calculated according to various levels of adherence. Logistic regression was used to estimate the effect of adherence on LDL-C goal attainment controlling for multiple patient characteristics including adherence to statin medication, age, gender, race/ethnicity, concomitant medication use, utilization of healthcare services, CCI, and hypertension. All statistical analysis was performed using SAS version 9.2 (SAS Institute, Cary, North Carolina).


PDF is available on the last page.

Issue: April 2014
More on AJMC.COM