PS-C36-6: REAL-WORLD ANALYSIS OF ADHERENCE, OUTCOMES AND HEALTHCARE COSTS OF THE QUADRUPLE COMBINATION PERINDOPRIL, INDAPAMIDE, AMLODIPINE AND BISOPROLOL IN ITALY
Authors: Mancia Giuseppe , Brouwers Sofie , Desideri Giovambattista , Esposti Luca Degli , Perrone Valentina , Narkiewicz Krzysztof 
Published: January 2023

Objective:
this real-world analysis aimed to evaluate drug utilization, outcomes and direct healthcare costs in hypertensive patients treated with the combination of perindopril, indapamide, amlodipine and bisoprolol (PER/IND/AML/BIS) in Italy.

Design and method:
a retrospective analysis was performed using administrative databases covering approximately 7 million health-assisted Italian subjects. Adults prescribed with PER/IND/AML/BIS in free combination during 2018 were included. Index date corresponded to first prescription date of the four drugs (prescribed within 30 days). Follow-up was 1 year after index date; patients who died during this period were excluded. Drug utilization was evaluated as adherence (proportion of days covered (PDC): PDC < 40% non-adherence; PDC = 40–79% partial adherence; PDC> = 80% adherence); persistence/interruption (presence/absence of PER/IND/AML/BIS in last trimester of follow-up); add-on (new antihypertensive agent added to PER/IND/AML/BIS), switch (change of at least 1 among PER/IND/AML/BIS). Outcomes [i.e. incidence rate per 1,000-person/year of death and cardiovascular (CV) events] and mean annual direct healthcare costs (related to all-cause drugs, hospitalizations and outpatient services) covered by National Health Service, were evaluated.

Results:
A total of 5,677 patients (50.6% male, mean age 70 years) had a prescription of the antihypertensive drugs PER/IND/AML/BIS. 98.5% had a history of cardiovascular diseases and 35.2% had diabetes. During first year of follow-up, 44% of patients were adherent to PER/IND/AML/BIS, 24% partially adherent, 32% non-adherent. A higher proportion of adherent patients was found among those receiving PER/IND/AML/BIS in 2 pills compared to 3 pills (45.4% and 30.2%, p < 0.001). Among all patients, 682 (12%) received additional antihypertensive treatment to PER/IND/AML/BIS, while 761 (13%) had at least one switch. Switch of therapy was around 5-times more frequent among non-adherent patients (25.3% vs 5.1%, p < 0.001). 53% of patients were persistent to PER/IND/AML/BIS while 47% had an interruption. In adherent patients, a significant reduction of the incidence rate of death and CV events was found (62.7/1,000-person/year) compared to non-adherent and partially-adherent (88.1 and 76.8/1,000-person/year, respectively, p < 0.001). Mean total individual annual direct cost was higher for non-adherent (euro 2,456) compared to adherent (euro 2,071), with hospitalization costs almost 2-fold higher in non-adherent patients (euro 918 vs euro 456, p < 0.001).

Conclusions:
This analysis provides real-world evidence on sub-optimal adherence and persistence in patients treated concomitantly with four antihypertensive drugs in Italy. In non-adherent patients, higher incidence of CV events and higher healthcare costs were reported. Better adherence was observed when fewer pills were taken. Further strategies to improve treatment adherence, especially in poly-medicated patients, are needed.