Statin therapy compliance of 80% or higher during the first 2 years of treatment is associated with reduced healthcare resource utilization in the following year.
To investigate whether compliance during the first 2 years of statin therapy is associated with reduced hospitalization rates and direct medical costs during year 3.
An integrated pharmacy and medical claims database was used to identify adult patients with a new statin prescription between July 1, 2001, and June 30, 2002. The study tracked statin prescription refills during the first 2 years after the initial statin claim and tracked hospitalizations and direct medical costs during the first 3 years.
Patients were stratified according to compliance in the first 2 years using the medication possession ratio, where 80% or higher is compliant and less than 80% is noncompliant. The relationship between compliance rates and direct medical costs was evaluated using a generalized linear model. Adjusting for covariates that may affect cardiovascular risk, the relationship between compliance and the likelihood of hospitalization was assessed using logistic regression models.
The 2-year medication possession ratio was 80% or higher in 3512 patients (compliant) and was less than 80% in 6715 patients (noncompliant). Compared with the noncompliant patients, the compliant patients during year 3 had significantly fewer hospitalizations (16% vs 19%) and lower total direct medical costs (excluding the cost of statin therapy) ($4040 vs $4908 per patient) (P <.01 for both).
Compliance with statin therapy in the first 2 years of use may reduce hospitalization rates and direct medical costs in the subsequent year.
(Am J Manag Care. 2010;16(6):459-466)
Compliance rates of 80% or higher during the first 2 years of statin therapy were associated with significantly reduced hospitalization rates and direct medical costs in the subsequent year among a heterogeneous group of statin users.
An estimated 16 million Americans have coronary heart disease (CHD).1 It is the most common cause of mortality among American adults. Because of the morbidity and mortality burden of CHD, it is not surprising that costs associated with this condition are high. In the United States in 2008, direct medical costs for CHD exceeded $87 billion, while indirect costs (lost productivity of the patient and the caregiver) accounted for an additional $70 billion.1 Therefore, identifying strategies for reducing the incidence of CHD can lead to significant monetary savings.
One proven strategy for prevention of CHD is to reduce low-density lipoprotein cholesterol (LDL-C) levels.2 A considerable body of evidence demonstrates that hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) are effective and well-tolerated agents for decreasing LDL-C levels and for reducing cardiovascular (CV) events.3-5
However, treatment can be expected to provide a clinical benefit only in patients who take their medication continuously on a long-term basis. Several studies have demonstrated that LDL-C level and CV risk reduction with lipid-lowering therapy is greater in patients who are compliant with therapy6,7 and that poor compliance may account for the difference in outcomes between randomized controlled trials and clinical practice.8,9 Data are limited about the effect of compliance on outcomes within the first 1 to 2 years of treatment with statins. Veterans Healthcare Administration data indicate that compliance during the first 1 to 2 years of statin treatment can reduce mortality in the subsequent year among patients with diabetes.10 However, that study was conducted in a high-risk population, and it is unknown whether early compliance with statin therapy can provide tangible benefits in terms of healthcare resource utilization among a more heterogeneous population.
The objective of the present study was to evaluate the effect of statin therapy compliance during the first 2 years of treatment on healthcare resource utilization in year 3 from the payer perspective. We hypothesized that patients with continuous statin treatment compliance will incur lower healthcare costs in the following year than patients with less compliance, even in early stages of treatment.
This was a retrospective analysis of integrated medical and pharmacy claims data between January 1, 2000, and June 30, 2004. Adult patients who met the following criteria were identified and included in the study: (1) received a statin prescription between July 1, 2001, and June 30, 2002, and had no prescription for statins in the 6 months before this prescription (ie, they were presumed to be new to statin therapy); (2) had continuous coverage by the health plan for the 6 months before the initial (index) statin prescription and 3 years after the index statin prescription; (3) filled 2 prescriptions on 2 different dates or 1 prescription with at least 45 days supply in the first year following the index date; (4) were at least 18 years old at the index date; and (5) underwent no pregnancy or fertility procedures during the follow-up period. All patients had to be continuously enrolled in the health plan to be eligible for inclusion; therefore, no study patients died during the follow-up period, and the effect of statin compliance on mortality was not examined.
Medical claims were obtained from a deidentified administrative claims database that is available for research purposes. The database was maintained by a health plan organization for all medical plan types, including health maintenance organizations, preferred provider organizations, traditional fee-for-service plans, and Medicare Advantage. Drug utilization data were obtained from the prescription claims database of Medco Health Solutions, Inc, the pharmacy benefits management company responsible for the prescription benefit plan among this population.
For each patient (using member identification), the following medical claim information was collected: service date, place of service, copayment amount, deductible amount, amount the health plan paid, Current Procedural Terminology (CPT) code, and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code. Similarly, the following pharmacy claim information was collected for each patient’s prescription history: date filled, days supply (number of days), National Drug Code number, drug name, copayment amount, deductible amount, and the amount the health plan paid. All pharmacy claims, including statins, were included in the analysis of drug utilization. Data on age and sex were drawn from an eligibility database maintained by the health plan organization. Medical and pharmacy claims data were integrated at the patient level, with all personal identifying information removed.
Medical and pharmacy claims data were analyzed for the 6 months before the first statin prescription (index date) and for the 3 years after the index prescription. Drug and medical claims were tracked concurrently for the 3-year period after the index date of initial statin prescription. All statin prescriptions for an individual patient were considered during this period; a switch from one statin to another was considered continuous statin therapy. Because statin costs were based on pharmacy claims, patients with lower compliance incurred lower statin costs, and vice versa.
Medication compliance over the first 2 years of statin therapy was assessed using the medication possession ratio (MPR), defined as the proportion of a period in which a patient had medication supply. The MPR numerator was derived by summing the number of days with prescription medication from the date of the index claim until 2 years after this date. This was then divided by 730 (total number of days in 2 years) to derive the MPR. Patients with an MPR of 80% or higher were considered compliant, and patients with an MPR of less than 80% were considered noncompliant. The MPR was chosen for this analysis because it is the most frequently cited measure of compliance in the literature,11 and 80% is the most common threshold for compliance.11,12 In a secondary analysis, patients in the sample were stratified into the following 5 categories according to their MPR: 0% to 19%, 20% to 39%, 40% to 59%, 60% to 79%, and 80% or higher.
Using the medical claims data, outcomes in the third year after the index statin prescription were compared between patients who were considered compliant versus noncompliant in the preceding 2 years. The outcomes evaluated during that year were the number of hospitalizations per 100 patients, the percentage of patients hospitalized, and the total medical costs (with and without statin therapy cost) per patient. Data were derived from primary, secondary, and tertiary diagnoses defined by ICD-9-CM codes in medical claims data and from CPT codes for angina, CV disorders, cerebrovascular disorders, and peripheral vascular disease procedures (eAppendix available at www.ajmc.com). In the secondary analysis, the same variables were evaluated in the groups stratified by 20% increments of MPR. The ICD-9-CM and CPT codes were chosen because clinical trials demonstrated an effect of statin therapy on these outcomes2,4,5,13-15 or on reducing morbidity and mortality after these procedures or events.16-19 All healthcare utilization costs related to each ICD-9-CM or CPT code were calculated from the claims data for each patient during year 3 of statin treatment, including outpatient visits, emergency department (ED) visits, inpatient overnight stays in a hospital, surgery, physical therapy, laboratory, and pharmacy. All statin costs included the cost to the insurer and the patient copayment. An ED visit was defined as a visit to an ED that did not exceed 1 day. If an ED visit progressed to an overnight stay, it was considered a hospitalization.
Baseline demographic characteristics in the compliant and noncompliant groups were compared using χ2 test and t test. A generalized linear model was used for continuous dependent variables (cost), and logistic regression models were used to evaluate the relationship between medication compliance and dichotomous dependent variables (the likelihood of having an event). Statistical significance was assessed using F test for continuous variables (generalized linear models) and Wald χ2 in the logistic regression models, and 95% confidence intervals (CIs) were calculated. The following covariates were used in the logistic regression model: (1) age; (2) sex; (3) chronic disease score; (4) the use of concomitant medications that may increase or decrease the risk of CV events (specifically antiplatelet agents and antiarrhythmics); (5) comorbidities (diabetes, renal disease, congestive heart failure, chronic obstructive pulmonary disease, depression, or hypertension) during the 2 years after the index statin prescription (period of compliance assessment); and (6) CV disorders (based on ICD-9-CM codes) or the need for CV or peripheral vascular procedures (based on procedural claim codes) during the 2 years after the index statin prescription.
Our analysis identified 10,227 patients who met the inclusion criteria. Patients were aged 18 to 93 years (mean age, 58.5 years). Of these, 3512 (34%) had a 2-year MPR of 80% or higher and comprised the compliant group. The other 6715 patients (66%) had a 2-year MPR of less than 80% and comprised the noncompliant group. The mean (SD) MPRs were 92.4% (5.8%) in the compliant group and 40.2% (22.4%) in the noncompliant group.
Patient demographic characteristics at the time of the index statin prescription are given in . The compliant group was significantly younger, included fewer female patients, had a higher mean chronic disease score, and had more comorbidities than the noncompliant group (P <.001 for all). Compared with the noncompliant group, the compliant group also included more patients who underwent a CV procedure in the 2 years following the index statin prescription (P = .03) and who had depression or hypertension (P <.001 for both) but included fewer patients with renal disease (P =.04), congestive heart failure (P = .001), and chronic obstructive pulmonary disease (P = .002). There was no significant difference between the 2 groups in the use of antiarrhythmic or antiplatelet therapy.
In the logistic regression model, the adjusted percentage of patients hospitalized during year 3 of statin use was significantly lower in the compliant group than in the noncompliant group (16% vs 19%, P <.01) (). In addition, patients who were compliant in the preceding 2 years had significantly fewer hospitalizations in year 3 (25 vs 33 per 100 patients, P <.01).
Results of the generalized linear model for per-patient medical costs are shown in . Excluding the cost of statin therapy, the adjusted per-patient total medical costs in the third year of statin therapy were significantly lower in the compliant group than in the noncompliant group ($4040 [95% CI, $3601-$4478] vs $4908 [95% CI, $4594-$5222], P <.01). When the cost of statin therapy was included, the adjusted total medical costs per patient were still significantly lower in the compliant group ($4909 [95% CI, $4470-$5347] vs $5290 [95% CI, $4976-$5604], P <.01).
When the data were evaluated by 20% increments of MPR, a similar pattern emerged. The adjusted percentage of patients hospitalized and number of hospitalizations per 100 patients were lower for the group with an MPR of 80% or higher versus groups with lower MPRs (P <.001 for variation across quintiles) (), as were the total medical costs (including and excluding the cost of statin therapy) (P <.001) (). The most hospitalizations and the highest costs were seen in the group with the poorest compliance (0%-19% MPR). The incremental difference in adjusted healthcare resource utilization and total medical costs between adjacent categories of MPRs was greatest between groups with MPRs of 60% to 79% and MPRs of 80% or higher. The total per-patient medical costs, excluding the cost of statin therapy, were $4691 (95% CI, $4076-$5306) in the group with MPRs of 60% to 79% and $4035 (95% CI, $3597-$4473) in the group with MPRs of 80% or higher.
Our data indicate that sustained compliance with statin therapy (>80% MPR) in the first 2 years after initiation is associated with reductions in healthcare utilization and direct medical costs in the following year. Using MPRs, Zhang et al10 showed that early compliance with statin therapy (in the first 1-2 years of use) among a population with diabetes resulted in reduced risk of mortality. Patients with diabetes represent a high-risk group, and similar reductions in mortality or major CV outcomes from early statin compliance in a lower-risk cohort have not previously been demonstrated to our knowledge. Even in a heterogeneous population of statin users, our data indicate that early compliance is associated with fewer all-cause and CV-related hospitalizations and with lower healthcare utilization costs. Unlike Zhang et al, we did not analyze the effect of statin compliance on mortality because our study included only patients who were alive for 3 years after the index statin prescription.
Compared with our noncompliant patients, the compliant patients had a higher chronic disease score, more comorbidities, and greater likelihood of undergoing a CV procedure in the first 2 years of statin therapy. This is consistent with other data showing that greater CV risk (real or perceived) is associated with better adherence to statins.6,20,21 In a retrospective analysis similar to ours, Goldman et al20 found that patients at high CV risk (based on age, sex, and comorbidities) were more compliant with lipid-lowering therapy than patients at lower risk. Similar to our results, these researchers found significantly lower rates of all hospitalizations and CV-related hospitalizations among patients with MPRs of 80% or higher versus MPRs of less than 80%, and this was most marked in patients at high or medium risk.20
Similarly, patients with established CHD seem to be more compliant with therapy.22 A 2008 study22 of patients on the CHD registry of the Kaiser Permanente Managed Care Organization found that 74% were compliant with statin therapy (using the proportion of days covered to estimate compliance) compared with 34% in our study. The discrepancy in compliance rates probably reflects differences in the patient groups. In their study, patients had established CHD and were not new to statin therapy, whereas our study included patients who were initiating statin therapy. Previous data have indicated that patients who are new to statin therapy are less likely to be compliant than those who are established statin users and that a new statin prescription is a significant risk factor for poor compliance.23 It is also possible that differences result from the methods used to estimate compliance (proportion of days covered vs MPR), although these 2 methods have been shown to produce concordant results in other investigations.24 Nevertheless, when the adherent and nonadherent cohorts in the study by Ho et al22 were compared, the results are consistent with ours, with statin nonadherence associated with significantly increased risks of CV hospitalization (by 35%) and coronary revascularization (by 11%) over a median of 4 follow-up years.
When we examined our data by 20% increments of MPR, hospitalization rates and medical costs were highest in the 2 lowest quintiles (0%-19% and 20%-39% MPR) and were lowest in the highest quintile (>80% MPR). The middle 2 quintiles (40%-59% and 60%-79% MPR) showed similar hospitalization rates for any condition (29 and 30 hospitalizations per 100 patients, respectively) and for CV-related conditions (21 hospitalizations per 100 patients for both). The test for trend across quintiles was statistically significant (P <.001). Results of the cost analysis by MPR quintiles suggest greater cost saving by motivating patients who are 60% to 79% compliant to be 80% compliant or higher than by motivating patients from lower quintiles of compliance to the next level. For example, according to our analysis, the effect on total medical costs (excluding the cost of statin therapy) would be negligible if a patient moved from being 40% to 59% compliant to being 60% to 79% compliant. However, because ours was a retrospective observational study, this finding is hypothesis generating only and should be confirmed in a prospective analysis of compliance and outcomes. Regardless of the effect on costs, the benefits of compliance with respect to lowering CV risk cannot be overemphasized, and patients with any level of suboptimal compliance should be encouraged to take their lipid-lowering medication daily and to reach and maintain compliance levels of at least 80%.
Several strategies have been investigated to improve compliance with lipid-lowering therapy, including simplified drug regimens, patient information and education, intensified patient care, and behavioral interventions such as group sessions, although no particular intervention has proven to be more effective than another.25 A multifaceted approach to improving adherence is required, including medication factors (adverse effects and ease of administration), psychosocial factors (patient and physician), and environmental factors (family, healthcare system, and medication cost).26
Our study found that the total medical costs in year 3 for patients taking statins was significantly lower in patients with MPRs of 80% or higher versus MPRs of less than 80% when the cost of statin therapy was included. A January 2006 Agency for Healthcare Research and Quality27 publication noted that statins carried the highest mean expense among the top 5 therapeutic drug classes prescribed to US adults. However, the cost of statins to patients and insurers is likely to decrease in coming years as more generic statins become available. In several studies,28-30 higher insurance copayment has been identified as a factor in poor compliance, suggesting that compliance may improve as the cost of statins declines.
Some limitations of our data need to be borne in mind. First, because our study population had medical insurance and did not include persons solely reliant on public assistance, it may not be representative of the national sample of statin users. Second, only direct medical costs were included in our analysis; indirect costs (eg, lost productivity of the patient or caregiver) are difficult to assess retrospectively but are likely to significantly increase the total costs in both study groups. According to 2008 American Heart Association1 estimates, 44% of the total cost of CHD can be attributed to indirect costs.
The MPR measures prescription refills and is an indirect measure of compliance (ie, refilling a prescription does not necessarily equate to taking the drug),31 which is a limitation of claims-based analyses. We chose the MPR because it is the most commonly used measure of compliance in the literature,11 and our threshold MPR of 80% or higher is consistent with similar studies.12,20,32-34 Under our definition of compliance (with a denominator of 730 days in our calculation of the MPR), patients whose medication was stopped by the physician because of intolerance or who were switched to a nonstatin lipid-lowering agent would be classified as poorly compliant or as noncompliant. Although it is possible that compliance was underestimated using the MPR if patients refilled a prescription for which no insurance claim was submitted,24 this is unlikely because we selected a population of patients who were consistently enrolled in an insurance plan for the 3½-year duration of assessment. Similarly, compliance may be underestimated in patients who split tablets, as these patients would be classified as poorly compliant using the MPR. Alternatively, if compliance is overestimated (because the MPR does not equate with consumption of a statin), the actual differences in hospitalization rates and total medical costs may be slightly higher. In addition, we acknowledge that compliance is a continuum and that an estimate of the MPR over a 2-year period does not account for intrapatient fluctuations between MPR categories within that time.
In general, refill behavior is assumed to be a good surrogate measure of medication adherence, especially because measuring actual drug-taking behavior is not necessarily practical or feasible. The consistency of these findings with other published data using similar outcome measurements35 suggests that refill behavior may be an adequate surrogate measure. Also, as with most claims-based analyses, we were able to capture only refill behavior, which does not necessarily reflect prescriber intent.
In our analysis, we examined the overall effect of statin use in a heterogeneous population that is likely representative of a general internal medicine or family medicine practice. We did not attempt to quantify differences in compliance patterns between different agents or to examine the effect of statin dosage on overall medical costs, nor did we attempt to link cost savings with magnitude of LDL-C reduction. Because the magnitude of LDL-C reduction is likely affected by choice of agent, dosage, and compliance, this could be considered a limitation of our study. However, our analysis demonstrates that compliance with statin therapy per se contributes to reduced overall healthcare resource utilization regardless of statin used or statin dosage. Without a placebo comparator, it is impossible to determine how much of this can be attributed to the “healthy adherer” effect, whereby compliance with drug therapy is associated with an overall healthier behavioral profile.36
In conclusion, our study shows that patients who are at least 80% compliant with statin therapy during the first 2 years of use have fewer hospitalizations and incur lower total medical costs during the third year compared with patients who are less compliant. These data reinforce the clinical and economic efficacy of these agents for CV risk reduction, with benefits accruing within the early years of use. The data also suggest that improving compliance among new statin users, who are less likely to be compliant,23 may reduce healthcare utilization. The implication from our analysis that the greatest potential benefit in reducing healthcare utilization can be gained by focusing compliance efforts on patients who are 60% to 79% compliant warrants further study. However, it is essential that physicians reinforce the importance of adherence in all patients taking lipid-lowering medication.
We thank Catherine Rees of PHOCUS, Inc, for assistance with development of the manuscript.
Author Affiliations: From Medco Health Solutions, Inc (REA, JY, FX, SBG), Franklin Lakes, NJ.
Funding Source: This study was funded by Medco Health Solutions, Inc.
Author Disclosures: The authors (REA, JY, FX, SBG) are employees of Medco Health Solutions, Inc, the company that funded this study, but report no other relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (REA, JY, FX, SBG); acquisition of data (JY, FX); analysis and interpretation of data (REA, JY, FX, SBG); drafting of the manuscript (REA, SBG); critical revision of the manuscript for important intellectual content (REA, JY, FX, SBG); statistical analysis (REA, JY, FX, SBG); obtaining funding (JY); administrative, technical, or logistic support (REA, FX, SBG); and supervision (REA, SBG).
Address correspondence to: Ronald E. Aubert, PhD, MSPH, Medco Health Solutions, Inc, 100 Parsons Pond Dr, Franklin Lakes, NJ 07417. E-mail: firstname.lastname@example.org.
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