Effect of renin-angiotensin system inhibition on cardiac structure and function and exercise capacity in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials


Targeting the renin-angiotensin system (RAS) pathways has been considered a logical intervention for patients with heart failure with preserved ejection fraction (HFpEF), due to its hypothesized link to left ventricular (LV) remodeling. Although the effects of RAS inhibitors including angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and direct renin inhibitors (DRIs) on LV structure and function and exercise capacity in HFpEF patients have been examined in multiple randomized controlled trials (RCTs), results are inconsistent due partly to limited power. We conducted a meta-analysis of RCTs on the effects of RAS inhibitors on LV structure and function as well as exercise capacity in HFpEF patients. The search of electronic databases identified 7 trials including 569 patients; 4 trials were on ACE-Is; 2 on ARBs; and 1 on DRIs. Follow-up duration ranged across trials from 12 to 52 weeks. The pooled analysis showed that RAS inhibitors significantly increased EF compared with control (weighted mean difference [95% CI] = 2.182 [0.462, 3.901] %). In contrast, RAS inhibitors did not significantly change the ratio of peak early to late diastolic mitral inflow velocities (weighted mean difference [95% CI] = 0.046 [− 0.012, 0.105]), early diastolic mitral annular velocity (0.327 [− 0.07, 0.725] cm/s), the ratio of early diastolic mitral inflow to annular velocities (0.291 [− 0.937, 1.518]), LV mass (− 6.254 [− 15.165, 2.656] g), or 6-min walk distance (1.972 [− 14.22, 18.163] m) compared with control. The present meta-analysis suggests that RAS inhibitors may increase LVEF in HFpEF patients.

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Correspondence to Hidekatsu Fukuta.

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Dr. Ohte has received lecture fees from Daiichi Sankyo Co. and grant support from Takeda Pharmaceutical Co. Ltd., Daiichi Sankyo Co., Ltd., and Otsuka Pharmaceutical Co., Ltd. Dr. Kamiya has received lecture fees from Astellas Pharma Inc. and Mochida Pharmaceutical Co., Ltd.

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Fukuta, H., Goto, T., Wakami, K. et al. Effect of renin-angiotensin system inhibition on cardiac structure and function and exercise capacity in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials. Heart Fail Rev (2020). https://doi.org/10.1007/s10741-020-09969-1

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  • Heart failure
  • Meta-analysis
  • Randomized controlled trial
  • Pharmacotherapy
  • Renin angiotensin system