OBJECTIVES: this real-world analysis aimed to evaluate adherence, outcomes and direct healthcare costs in hypertensive patients treated with 4 antihypertensive drugs belonging to ACE-inhibitor/calcium-antagonist/diuretic/beta-blocker(ACE-I/CCB/DIU/BB) classes or with perindopril/amlodipine/indapamide/bisoprolol(PER/AML/IND/BIS), in Italy.

METHODS: an observational analysis was performed using administrative databases covering approximately 7 million health-assisted subjects. Adult patients prescribed with ACE-I/CCB/DIU/BB or PER/AML/IND/BIS during 2018 were included. Index-date corresponded to first prescription of the four drugs (prescribed within 30 days). Follow-up was 1 year after index-date. Adherence was evaluated as proportion of days-covered, PDC (PDC<40%=non-adherence; PDC=40-79%=partial-adherence; PDC≥80%=adherence). Outcomes [incidence rate/1,000-person/year of death and cardiovascular (CV) events] and mean annual direct healthcare costs were calculated. Among patients treated with the 4 monocomponents, the number of those potentially eligible for fixed-combination was estimated.

RESULTS: 27,423 (48.4% male, mean age 71 years) and 5,677 patients (50.6% male, mean age 70 years) had an ACE-I/CCB/DIU/BB or PER/AML/IND/BIS prescription, respectively. During one-year follow-up, 35% patients were adherent to ACE-I/CCB/DIU/BB, 30% partially-adherent, 35% non-adherent. Among PER/AML/IND/BIS-treated patients, 44% were adherent, 24% partially-adherent, 32% non-adherent. In patients adherent to ACE-I/CCB/DIU/BB, death/CV events incidence rate decreased (65.7/1,000-person/year) versus non-adherent and partially-adherent (84.6 and 72.9/1,000-person/year, respectively, p<0.001). Similarly, in patients adherent to PER/AML/IND/BIS, death/CV events incidence rate decreased (62.7/1,000-person/year) versus non-adherent and partially-adherent (88.1 and 76.8/1,000-person/year, respectively, p<0.001). In ACE-I/CCB/DIU/BB and PER/AML/IND/BIS-treated patients, respectively, mean total annual cost was higher for non-adherent (€2,147 and €2,456) compared to adherent (€1,903 and €2,071) (p<0.001). By considering patients receiving 4 combinations from ACE-I/CCB/DIU/BB classes and by reproportioning data to the Italian population, 306,403 patients during 2018 were potentially eligible for a fixed-combination.

CONCLUSIONS: This real-world analysis provides novel insights into concomitant use of four antihypertensive drugs in Italy. Optimal adherence was observed in less than 50% of patients. In adherent patients, lower incidence of deaths/CV events and lower total healthcare costs were observed.