The Prescription Characteristics, Efficacy and Safety of Spironolactone in Real-World Patients With Acute Heart Failure Syndrome: A Prospective Nationwide Cohort Study

Soo Jin Na; Jong-Chan Youn; Hye Sun Lee; Soyoung Jeon; Hae-Young Lee; Hyun-Jai Cho; Jin-Oh Choi; Eun-Seok Jeon; Sang Eun Lee; Min-Seok Kim; Jae-Joong Kim; Kyung-Kuk Hwang; Myeong-Chan Cho; Shung Chull Chae; Seok-Min Kang; Dong-Ju Choi; Byung-Su Yoo; Kye Hoon Kim; Byung-Hee Oh; Sang Hong Baek

doi:10.3389/fcvm.2022.791446

The Prescription Characteristics, Efficacy and Safety of Spironolactone in Real-World Patients With Acute Heart Failure Syndrome: A Prospective Nationwide Cohort Study

Front Cardiovasc Med. 2022 Feb 22:9:791446. doi: 10.3389/fcvm.2022.791446. eCollection 2022.

Authors

Soo Jin Na^{1

2}, Jong-Chan Youn³, Hye Sun Lee⁴, Soyoung Jeon⁴, Hae-Young Lee⁵, Hyun-Jai Cho⁵, Jin-Oh Choi⁶, Eun-Seok Jeon⁶, Sang Eun Lee⁷, Min-Seok Kim⁷, Jae-Joong Kim⁷, Kyung-Kuk Hwang⁸, Myeong-Chan Cho⁸, Shung Chull Chae⁹, Seok-Min Kang¹⁰, Dong-Ju Choi¹¹, Byung-Su Yoo¹², Kye Hoon Kim¹³, Byung-Hee Oh¹⁴, Sang Hong Baek³

Affiliations

¹ Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
² Department of Medicine, Catholic University Graduate School, Seoul, South Korea.
³ Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic Research Institute for Intractable Cardiovascular Disease, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
⁴ Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea.
⁵ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
⁶ Department of Internal Medicine, Sungkyunkwan University College of Medicine, Seoul, South Korea.
⁷ Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁸ Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South Korea.
⁹ Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, South Korea.
¹⁰ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
¹¹ Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
¹² Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea.
¹³ Department of Cardiovascular Medicine, Chonnam National University Medical School, Gwangju, South Korea.
¹⁴ Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, South Korea.

Abstract

Background: Randomized clinical trials of spironolactone showed significant mortality reduction in patients with heart failure with reduced ejection fraction. However, its role in acute heart failure syndrome (AHFS) is largely unknown.

Aim: To investigate the prescription characteristics, efficacy and safety of spironolactone in real-world patients with AHFS.

Methods: 5,136 AHFS patients who survived to hospital discharge using a nationwide prospective registry in Korea were analyzed. The primary efficacy outcome was 3-year all-cause mortality.

Results: Spironolactone was prescribed in 2,402 (46.8%) at discharge: <25 mg in 890 patients (37.1%), ≥25 mg, and <50 mg in 1,154 patients (48.0%), and ≥50 mg in 358 patients (14.9%). Patients treated with spironolactone had a lower proportion of chronic renal failure and renal replacement therapy during hospitalization and had lower serum creatinine level than those who did not. In overall patients, 3-year mortality was not different in both groups (35.9 vs. 34.5%, P = 0.279). The incidence of renal injury and hyperkalemia was 2.2% and 4.3%, respectively, at the first follow-up visit. The treatment effect of spironolactone on mortality was different across subpopulations according to LVEF. The use of spironolactone was associated with a significant reduction in 3-year morality in patients with LVEF ≤ 26% (33.8 vs. 44.3%, P < 0.001; adjusted HR 0.79, 95% CI 0.64-0.97, P = 0.023), but not in patients with LVEF > 26%.

Conclusions: Although spironolactone was frequently used at lower doses in real-world practice, use of spironolactone significantly reduced 3-year mortality in patients with severely reduced LVEF with acceptable safety profile. However, our findings remain prone to various biases and further prospective randomized controlled studies are needed to confirm these findings.

Keywords: acute heart failure syndrome; drug therapy; mineralocorticoid receptor antagonists; outcome; spironolactone.