Although the benefits of statin therapy are modified to a large extent by CHD risk, data are limited on whether adherence rates differ between primary and secondary prevention populations. The relationship between high adherence levels and improved CHD outcomes is documented in several populations with varying levels of CHD risk.^8–10 However, the published data on statin adherence are largely derived from clinical trials and retrospective studies that enrolled either primary or secondary, but not both, prevention populations.^{1–6,11–13} While recent studies have reported differences in statin adherence rates among elderly patients at varying levels of CHD risk,^14,15 they lack generalizability given their focus on older, publicly insured patients.

Because current evidence suggests that individuals treated for secondary prevention have relatively more to gain from statin therapy than those treated for primary prevention, our primary objective was to compare nonadherence and discontinuation rates in these 2 prevention populations. An additional aim was to identify modifiable factors that may affect those behaviors. In response to the mounting evidence suggesting that out-of-pocket expenditures are a barrier to adherence with prescription drugs,^16–18 we assessed the role of patient copayment on statin nonadherence and discontinuation rates.

In an analysis of statin-naive patients, we detected a significantly higher discontinuation rate among primary prevention patients when compared to those treated for secondary prevention. This finding suggests that some degree of augmented retention occurs in those most likely to benefit from statin therapy, independent of the “day-to-day” adherence to active statin therapy. However, the likelihood of discontinuation observed was unacceptably high in both populations. The 50% discontinuation rate after 3.4 years found among secondary prevention patients in our study—higher than reported previously—should be of great concern to practitioners in lieu of recent findings documenting the risks of statin discontinuation in acute coronary syndrome or stable CHD patients.^23,24 Moreover, the discontinuation rate detected in our primary prevention patients (50% at 3.7 years) was higher than those observed in WOSCOPS,¹ EXCEL,² and AFCAPS/TexCAPS,³ where the discontinuation rates were 26% at 5 years, 16% at 1 year, and 29% at 5.2 years, respectively.

Using methods that define adherence by the percentage of time a patient has drug available (or the percentage of time in which refill gaps are not present), several retrospective studies reported similar rates of statin adherence ranging from 64% to 84%.^12,13,25 A study of elderly Canadian and U.S. populations observed higher adherence rates for individuals with risk factors for future cardiac event.¹² A recently published study involving this same elderly Canadian population confirmed these observations.¹⁴ Similar findings were reported in a different elderly Canadian population with and without acute coronary syndrome.¹⁵ The generalizability of these studies may be limited because only publicly insured patients older than 65 were enrolled. Recent surveys have demonstrated that elderly patients and those enrolled in Medicaid or other prescription assistance programs report difficulty in the procurement of prescription medications beyond that of the general population.^16–18 These poor levels of adherence to statin therapy as reported in the literature, coupled with our population where 38.3% of all patients had a CMG greater than 20%, are alarming given the recent evidence that patients with CMG levels greater than 20% have recurrent myocardial infarction and all-cause mortality outcomes not significantly different than patients who were not taking statin.²⁶

One significant finding from our analysis was that the level of patient copayment was an independent factor for statin discontinuation. Compared to those who had less than a $10 copayment, patients who paid greater than or equal to $20 were more than 4 times more likely to discontinue their statin; patients who paid between $10 and $20 per month per statin prescription were also more likely to cease therapy. Coincidence alone cannot explain the lower rates of discontinuation in clinical trials, where study medication is almost always provided free of charge to study subjects, as compared to statin discontinuation described within our study population where mean monthly prescription copayment had such a profound effect. Previously published studies report that an increase in prescription copayment can lead to a decrease in drug utilization.^27,28 Making matters worse, it is possible that this undesirable effect of copayment on statin adherence may be even greater in the secondary prevention cohort for whom the mean out-of-pocket expense per prescription was significantly higher than those taking statins for primary prevention.

Consumer cost-sharing has been a longstanding component of pharmaceutical cost containment. MCOs implement various cost-sharing arrangements to balance the demands for increased access to pharmaceuticals with pressures to constrain pharmaceutical cost growth. Conceptually, MCOs want to allow consumers to express their preferences for selected products by their willingness to pay, while ensuring that no prescription goes unfilled due to a patient's inability to pay the copay. There is a growing body of evidence demonstrating that effective therapies are not being used due to the requirement of a patient out-of-pocket expenditure. The results presented herein would support the argument that modern cost-containment strategies are failing to constrain drug cost growth while optimizing essential drug utilization.

A copay structure based on potential clinical benefit, rather than drug acquisition cost, would alleviate some financial burden and allow patients to prioritize their out-of-pocket expenditures.²⁹ What distinguishes this “Benefit Based Copay” from existing systems is its determination of patient copays based on medical need and not drug acquisition costs, as best determined from the available medical and economic evidence. If implemented, a benefit-based copayment structure would decrease the economic burden for the secondary prevention population and thereby potentially improve adherence in those high-risk patients.

In our study, several factors in addition to cost-sharing and prevention category were predictive of nonadherence and discontinuation to statin therapy. Being female, younger, and of a minority race corresponded to both non-compliant behavior and discontinuation. These findings support previous research describing medication adherence and procurement in minority groups ³⁰ and female patients.^11,13,31 The number of cardiologist visits and LDL tests performed also were associated with improved statin adherence. The observed influence of these factors may argue that more intensive follow-up can improve patient adherence or, alternatively, these factors may simply serve as a proxy for patient adherence to a broad range of health care utilities. Finally, an increase in the complexity of the statin regimen influenced nonadherent behavior supporting previously published research examining the effects of dosing frequency on adherence.³² Patients who were prescribed their medications more frequently than once daily or experienced multiple brand and/or dosage switches were more likely to refill their medication in a nonadherent fashion. Thus, physicians and pharmacists can potentially enhance patient adherence by prescribing and filling simplified drug regimens that optimize patients’ insurance limits.

Several limitations of our study are worth noting. First, we cannot account for tablet splitting. Such behavior would artificially increase the number of apparent gaps in therapy overall, but should have an equal effect on both prevention cohorts. Second, we lack information regarding the incidence of drug-related adverse events and the exact reason for discontinuation of statin therapy. Statin discontinuation may be clinically appropriate, such as for lack of efficacy or side effects. We completed our analyses under the assumption that patients who had been initiated on statin therapy would require it for life. Operating under this assumption, any stoppage in statin therapy should have been followed by initiation of a non-statin antihyperlipidemic agent. Third, as with any study that utilizes pharmacy claims databases, we could only determine that a prescription was filled and not if the patients actually took the medications at the time of day and at the frequency prescribed by their clinicians. Fourth, our use of medical claims and administrative databases for identification of our population lends to certain inherent weakness as recent claims and services may not reflect previous illness. Our use of a misidentification quality assurance check minimized the effect of inappropriately allotting a truly secondary prevention patient to the primary prevention cohort. Last, because our analysis was performed in a single site and we did not include Medicaid enrollees, the generalizability of our findings may be limited. Nevertheless, our study population is representative of managed care enrollees nationwide, a large population for whom these outcomes have yet to be published.