Abstract
INTRODUCTION: Patient adherence to a medication regimen is usually expressed as an adherence rate, defined as the proportion of prescribed doses actually taken. An adherence rate threshold, above which the therapeutic effect is maintained, is typically assigned an arbitrary value, commonly 0.8. OBJECTIVE: Here, we determined the value of the adherence rate threshold objectively in different drugs of the same class, using statins as an example. METHODS: We used pharmacokinetic/pharmacodynamic (PK/PD) modeling to predict serum levels of low-density lipoprotein cholesterol (LDL-C) in patients taking simvastatin 20 mg or atorvastatin 5 mg once daily for 30 days. LDL-C reduction was modeled for adherence rates of 1.0, 0.8, 0.6, 0.4, and 0.2. The results were expressed as the percentage of time spent at the LDL-C goal (< 70 mg/dL). The adherence rate threshold was defined as the minimum adherence rate that resulted in the same amount of time at goal as perfect adherence (i.e., a rate of 1.0). RESULTS: For simvastatin, an adherence rate of 0.8 resulted in a significant decrease in time at the LDL-C goal compared to perfect adherence (54.8% versus 85.1%; P < 0.001), and rates < 0.8 resulted in progressively less time at goal. For atorvastatin, the rates of 0.8 and 0.6 resulted in essentially the same amount of time at goal as perfect adherence (87.8% and 87.7%, respectively, versus 88.1%; P > 0.05 for both), with less time at goal only occurring at rates ≤ 0.4 (P < 0.001). Thus, the adherence rate thresholds are > 0.8 for simvastatin and between 0.4 and 0.6 for atorvastatin. CONCLUSION: These results indicate that a value of 0.8 cannot be applied universally.