Five-year follow-up with the incidence of cardiovascular adverse events after prescribing single-pill combination of antihypertensive drugs: retrospective cohort study

BACKGROUND: This study aimed to investigate whether medication adherence was changed by the prescription of a single-pill combination (SPC) of antihypertensive drugs and whether it was associated with the incidence of major adverse cardiovascular events (MACE) at the 5-year follow-up. METHODS: The medical records of 707 patients whose medication adherence could be assessed at least one year before and after the date SPC was first prescribed were retrospectively reviewed. The patients' baseline characteristics included sex, age, medical and medication history within the past year (MACE, antidiabetic drugs, and antihyperlipidemic drugs), and polypharmacy (six or more drugs taken orally). Medication adherence was evaluated as the proportion of days covered, and the patients were divided into poor adherence (n = 28) and good adherence (n = 679) groups. Fisher's exact test and the Mann-Whitney U test were used to examine the differences in variables between the groups. Kaplan-Meier survival analysis was performed to assess time-to-event data, with group differences evaluated using the log-rank test and Cox proportional hazards models adjusted for baseline variables. RESULTS: No significant differences were observed in the patients' baseline characteristics between the good and poor adherence groups. During the first year after the initiation of prescribing the SPC of antihypertensive drugs, the percentage of patients who developed MACE was higher in the poor adherence group than in the good adherence group (21.4% and 11.8%, respectively), but the difference was not statistically significant (p = 0.137). No significant difference in the cumulative incidence of MACE during the 5-year observation period was observed between the poor and good adherence groups (p = 0.199). In the Cox proportional hazards analysis, 75 years of age or older, the occurrence of MACE within the past year, and polypharmacy were associated with increased risk of 5-year MACE compared to the references (adjusted hazard ratios 1.42 [95% Confidence Intervals: 1.10-1.83], p = 0.007; 0.72 [0.55-0.93], p = 0.011; and 1.36 [1.01-1.83], p = 0.044, respectively). CONCLUSIONS: The present findings demonstrated that age 75 or older age, history of MACE, and polypharmacy were significant risk factors for MACE after the prescription of antihypertensive SPC.