Association between prognosis and the use of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers in frail patients with heart failure with preserved ejection fraction

Aims The effectiveness of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) has not been demonstrated in patients with heart failure with preserved ejection fraction (HFpEF). We recently reported significant interaction between the use of ACE-I and/or ARB (ACE-I/ARB) and frailty on prognosis in patients with HFpEF. In the present study, we examined the association between ACE-I/ARB and prognosis in patients with HFpEF stratified by the presence or absence of frailty. Methods and results We examined the association between the use of ACE-I/ARB and prognosis according to the presence [Clinical Frailty Scale (CFS) >= 5] or absence (CFS <= 4) of frailty in patients with HFpEF in a post hoc analysis of registry data. Primary endpoint was the composite of all-cause mortality and heart failure admission. Secondary endpoints were all-cause mortality and heart failure admission. Of 1059 patients, median age was 83 years and 45% were male. Kaplan-Meier analysis showed that the risk of composite endpoint (log-rank P = 0.001) and all-cause death (log-rank P = 0.005) in patients with ACE-I/ARB was lower in those with CFS >= 5, but similar between patients with and without ACE-I/ARB in patients with CFS <= 4 (composite endpoint: log-rank P = 0.830; all-cause death: log-rank P = 0.192). In a multivariable Cox proportional hazards model, use of ACE-I/ARB was significantly associated with lower risk of the composite endpoint [hazard ratio (HR) = 0.52, 95% confidence interval (CI) = 0.33-0.83, P = 0.005] and heart failure admission (HR = 0.45, 95% CI = 0.25-0.83, P = 0.010) in patients with CFS >= 5, but not in patients with CFS <= 4 (composite endpoint: HR = 1.41, 95% CI = 0.99-2.02, P = 0.059; heart failure admission: HR = 1.43, 95% CI = 0.94-2.18, P = 0.091). The association between ACE-I or ARB and prognosis did not significantly differ by CFS (CFS <= 4: log-rank P = 0.562; CFS >= 5: log-rank P = 0.100, for with ACE-I vs. ARB, respectively). Adjusted HRs for CFS 1-4 were higher than 1.0 but were <1.0 at CFS 5. Conclusions In patients with HFpEF, use of ACE-I/ARB was associated with better prognosis in patients with frailty as assessed with the CFS, but not in those without frailty.