Objective: To assess the effects of pill burden on adherence, persistence, non-fatal cardiovascular (CV) events and all-cause mortality in adult patients treated with the combination of perindopril (PER), indapamide (IND), amlodipine (AML) and bisoprolol (BIS). Design and method: This was an observational, retrospective, longitudinal cohort study of administrative healthcare databases based on the Italian National Healthcare Service. Eligible patients were at least 18 years old and received PER+IND+AML+BIS with data available at least 1 year before and 1 year after quadruple therapy identification. Primary endpoints were adherence to the four drugs (calculated as proportion of days covered by prescription PDC, assessed as low =80%) and persistence (presence of dispensation of the four drugs in last trimester) at 6, 9 and 12 months, stratified by number of pills. Secondary endpoints included non-fatal CV events and all-cause mortality. Cox's proportional hazards model was applied to estimate hazard ratios (HRs) adjusting for baseline covariates, including demographics, comorbidities and previous treatments. Results: Overall, 8007 patients (mean age 68.9±11.5 years, 52.5% male) received PER+IND+AML+BIS; 2489 (31.1%) had diabetes and 1279 (16.0%) ischaemic heart disease. Most patients received PER+IND+AML+BIS as two pills (Table). Adherence and persistence at all timepoints were significantly higher for patients receiving two pills versus three. Cox's proportional hazards model showed that the risk of non-fatal CV events decreased significantly in patients with moderate (HR=0.75 95% confidence interval (CI) 0.60, 0.95; P=0.017) or high (HR=0.74 95% CI 0.60, 0.92, P=0.006) adherence compared with low adherence. Non-fatal CV event risk also decreased significantly in persistent patients (HR=0.79 95% CI 0.68, 0.92; P=0.003) over non-persistent patients at 12 months. Risk of all-cause mortality decreased significantly in persistent patients (HR=0.79 95% CI 0.68, 0.92; P=0.002), while no significant changes were observed depending on adherence levels.Conclusions: In patients receiving PER+IND+AML+BIS, both adherence and persistence were significantly improved with a lower pill burden. Better adherence and higher persistence were associated with a reduced risk of non-fatal CV events. Further reducing pill burden by means of a quadruple single-pill combination could address important needs in this patient population.
Mancia et al. (Fri,) studied this question.