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

Background 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. Purpose 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 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. Results 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 = 0.52, 95% CI: 0.33–0.83, P=0.005) and heart failure admission (hazard ratio = 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: hazard ratio = 1.41, 95% CI: 0.99–2.02, P=0.059; heart failure admission: hazard ratio = 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 less than 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. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Roche