Objective: Data from electronic dosing monitors and published pharmacokinetic parameters were used to derive medication adherence measures for immediate-release metoprolol and examine their association with health care utilization of outpatients aged 50 years or older with heart failure.
Methods: We used a 1-compartment model and published population pharmacokinetic parameters to estimate mean plasma metoprolol concentrations for patients treated for 6 to 12 months. In the absence of directly measured plasma concentrations, we calculated the intended mean plasma concentration (Cp'(ave)) under the assumption of perfect adherence to the prescribed dose and frequency of administration. Projected mean plasma concentrations (Cp(ave)) were estimated by use of data from recorded dosing times. In addition to taking adherence (percentage of dose taken) and scheduling adherence (percentage of doses taken on schedule), we calculated the deviation from the intended exposure (DeltaCp(ave) = Cp'(ave) - Cp(ave)) and the proportion of intended exposure achieved by the patient (Cp(ave) /Cp'(ave)). We assessed the association between the adherence measures and the numbers of emergency department visits and hospital admissions experienced by the patients.
Results: Patients (N = 80) were aged 62 +/- 8 years. Mean DeltaCp(ave) and Cp(ave)/Cp'(ave) were 7.9 ng/mL (SD, 10.7) and 0.6 (SD, 0.3), respectively. Log-linear models adjusted for patient functional status indicated that greater deviation from the intended metoprolol exposure (DeltaCp(ave)) was associated with increased numbers of emergency department visits ( P < .0001) and hospital admissions (P < .0001). A higher proportion of intended exposure (Cp(ave) /Cp'(ave)) corresponded to a reduced number of emergency department visits (P = .0204) and hospital admissions (P = .0093). Taking adherence was univariately associated with both emergency department visits and hospital visits (P < .0001 and P = .0010, respectively). Scheduling adherence was associated with the number of emergency department visits (P = .0181) but not with the number of hospital admissions (P = .1602). Model selection procedures consistently chose the proposed measures over taking adherence and scheduling adherence.
Conclusion: Deviation from the intended exposure and proportion of intended exposure achieved by the patient are valid adherence measures for immediate-release metoprolol and are associated with health care utilization. The potential utility of these measures for other beta-adrenergic antagonists and perhaps other cardiovascular drugs should be investigated.