Evidence-based medication adherence among seniors in the first year after heart failure hospitalisation and subsequent long-term outcomes: a restricted cubic spline analysis of adherence-outcome relationships.

Purpose: Non-adherence to heart failure (HF) medications is associated with poor outcomes. We used restricted cubic splines (RCS) to assess the continuous relationship between adherence to renin-angiotensin system inhibitors (RASI) and β-blockers and long-term outcomes in senior HF patients.

Methods: We identified a population-based cohort of 4234 patients, aged 65-84 years, 56% male, who were hospitalised for HF in Western Australia between 2003 and 2008 and survived to 1-year post-discharge (landmark date). Adherence was calculated using the proportion of days covered (PDC) in the first year post-discharge. RCS Cox proportional-hazards models were applied to determine the relationship between adherence and all-cause death and death/HF readmission at 1 and 3 years after the landmark date.

Results: RCS analysis showed a curvilinear adherence-outcome relationship for both RASI and β-blockers which was linear above PDC 60%. For each 10% increase in RASI and β-blocker adherence above this level, the adjusted hazard ratio for 1-year all-cause death fell by an average of 6.6% and 4.8% respectively (trend p < 0.05) and risk of all-cause death/HF readmission fell by 5.4% and 5.8% respectively (trend p < 0.005). Linear reductions in adjusted risk for these outcomes at PDC ≥ 60% were also seen at 3 years after landmark date (all trend p < 0.05).

Conclusion: RCS analysis showed that for RASI and β-blockers, there was no upper adherence level (threshold) above 60% where risk reduction did not continue to occur. Therefore, interventions should maximise adherence to these disease-modifying HF pharmacotherapies to improve long-term outcomes after hospitalised HF.