Abstract

Abstract Background The current guidelines recommend different medical treatment strategies for heart failure (HF) patients according to category of left ventricular ejection fraction (LVEF). Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE-I/ARB) is an established medical treatment for heart failure with reduced ejection fraction (HFrEF), whereas its usefulness remains to be elucidated for non-HFrEF, especially for heart failure with mid-range ejection fraction (HFmrEF). Purpose This study aimed to assess the difference in association between ACE-I/ARB and clinical outcomes depending on LVEF category. Methods The Kyoto Congestive Heart Failure (KCHF) Registry is a multicentre registry without any exclusion criteria which included consecutive patients hospitalized for congestive HF in Japan. In each LVEF group (HFrEF, HFmrEF and heart failure with preserved ejection fraction [HFpEF]), we compared those who were prescribed ACE-I/ARB as discharge medication and those not, and assessed their 1-year clinical outcomes. We defined the primary outcome measure as a composite of all-cause death and HF hospitalization. We constructed a multivariable Cox regression model incorporating 24 clinically relevant factors. We assessed adjusted hazard ratios (HRs) of those with ACE-I/ARB relative to those not, and also interaction between ACE-I/ARB prescription at discharge and LVEF category. Results A total of 3717 patients were included in this study, where the number of patients in each LVEF group were as follows; 1383 patients with HFrEF, 703 with HFmrEF and 1631 with HFpEF, respectively (Figure). As shown in the table, the HRs for the primary outcome measure were significant in the HFrEF and HFmrEF groups, whereas the HR in the HFpEF group was insignificant. The interaction between ACE-I/ARB prescription and LVEF category for the primary outcome measure was statistically significant. Hazard ratios by LVEF category Outcome measures HFrEF HFmrEF HFpEF P interaction HR (95% CI) P value HR (95% CI) P value HR (95% CI) P value All-cause death + HF hospitalization 0.66 (0.54–0.79) <0.001 0.61 (0.45–0.82) 0.001 0.95 (0.80–1.14) 0.61 0.01 All-cause death 0.62 (0.48–0.81) <0.001 0.52 (0.35–0.77) 0.001 0.73 (0.58–0.93) 0.01 0.10 HF hospitalization 0.73 (0.57–0.92) 0.009 0.59 (0.40–0.87) 0.007 1.14 (0.90–1.44) 0.28 0.07 Hazard ratios of ACE-I/ARB relative to non-ACE-I/ARB for primary outcome measures in each LVEF category. Study flowchart Conclusions The risk ratios of those who were prescribed ACE-I/ARB relative to those not were significantly low in HFmrEF as well as HFrEF, whereas the risk ratios were insignificant in HFpEF. ACE-I/ARB could be a potential choice of treatment for HFmrEF patients.

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