Effect of single-pill versus free equivalent combinations on persistence and major adverse cardiovascular events in hypertension: a real-world analysis

OBJECTIVES: Hypertension guidelines recommend the use of single-pill combinations (SPCs) of antihypertensive drugs to improve treatment persistence and blood pressure control. This study aimed to investigate the long-term effects of ramipril/amlodipine (R/A) SPC versus free equivalent dose combinations (FEC) on cardiovascular outcomes and treatment persistence. METHODS: This retrospective, observational study analysed the database of the Hungarian National Health Insurance Fund. The study included patients with hypertension aged at least 18 years who were initiated on R/A SPC or FEC of different dose combinations (R/A 5/5, 5/10, 10/5 and 10/10 mg) between 2012 and 2018, with follow-up for up to 60 months. Imbalances in baseline characteristics were reduced with propensity score-based sub-classification. All analyses were performed with Cox proportional hazard model and propensity score sub-classification to adjust the imbalances in baseline characteristics. Drug persistence and MACEs were the primary and secondary endpoints, respectively. RESULTS: Overall, 104 882 patients with SPC and 68 324 patients with FEC-treated hypertension were included. The R/A 5/5 mg combination represented the largest proportion (62%). The nonpersistence rate was significantly lower with SPC than with FEC from month 1 to month 24 in the R/A 5/5 mg combination ( P < 0.001) and during the entire observation period in the remaining combinations. The MACE rate was significantly reduced with all R/A SPCs versus FECs. No effects on age and sex on both endpoints were noted. CONCLUSION: This study further supports the beneficial effects of the use of SPC on 60-month persistence and MACEs in hypertension.