Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure Sanae Hamaguchi, MD, PhD, b Shintaro Kinugawa, MD, PhD, b Miyuki Tsuchihashi-Makaya, RN, PhD, b Kazutomo Goto, MD, PhD, b Daisuke Goto, MD, PhD, b Takashi Yokota, MD, PhD, b Satoshi Yamada, MD, PhD, b Hisashi Yokoshiki, MD, PhD, a,b Akira Takeshita, MD, PhD, b and Hiroyuki Tsutsui, MD, PhD b Sapporo, Japan Background The RALES trial demonstrated that spironolactone improved the prognosis of patients with heart failure (HF). However, it is unknown whether the discharge use of spironolactone is associated with better long-term outcomes among hospitalized systolic HF patients in routine clinical practice. We examined the effects of spironolactone use at discharge on mortality and rehospitalization by comparing with outcomes in patients who did not receive spironolactone. Methods The JCARE-CARD studied prospectively the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed with an average of 2.2 years of follow-up. Results A total of 946 patients had HF with reduced left ventricular ejection fraction (LVEF) (b40%), among whom spironolactone was prescribed at discharge in 435 patients (46%), but not in 511 patients (54%). The mean age was 66.3 years and 72.2% were male. Etiology was ischemic in 39.7% and mean LVEF was 27.1%. After adjustment for covariates, discharge use of spironolactone was associated with a significant reduction in all-cause death (adjusted hazard ratio 0.612, P = .020) and cardiac death (adjusted hazard ratio 0.524, P = .013). Conclusions Among patients with HF hospitalized for systolic dysfunction, spironolactone use at the time of discharge was associated with long-term survival benefit. These findings provide further support for the idea that spironolactone may be useful in patients hospitalized with HF and reduced LVEF. (Am Heart J 2010;160:1156-62.) Aldosterone plays an important role in the development and progression of chronic heart failure (HF). It induces vascular damage, 1,2 cardiac hypertrophy, 3-5 and fibrosis. 6-9 Higher level of serum aldosterone has been shown to be an independent predictor of increased mortality risk in patients with HF. 10 The RALES demonstrated that spironolactone reduces the risk of mortality and morbidity in patients with HF and systolic dysfunction. 11 Current guidelines from American College of Cardiology/ American Heart Association/AHA and European Society of Cardiology recommend the use of spironolactone in HF patients with reduced left ventricular ejection fraction (LVEF) who were symptomatic under the use of angiotensin-converting enzyme (ACE) inhibitors or an- giotensin receptor blockers (ARBs) and diuretics. 12,13 However, RALES was performed among carefully select- ed severe HF patients with current or recent HF of New York Heart Association (NYHA) functional class IV. In addition, it excluded the patients with a serum creatinine concentration of N2.5 mg/dL. Moreover, the use of β- blockers was as low as 10% among the patients enrolled in RALES. Therefore, the patients in the RALES were clearly different from those in the “real world” under current standard practice for HF who are more elderly and have more comorbidities including hypertension, diabetes, and renal dysfunction. However, many patients who received new prescriptions for spironolactone after the publication of RALES have been reported not to have severe HF and about one third had renal dysfunction. 14 These findings indicated that the effect of spironolactone on outcomes needed to be assessed in an unselected population of patients with HF. The JCARE-CARD studied prospectively the character- istics and treatments in a broad sample of patients hospitalized with HF in Japan from January 2004 to June 2005, and the outcomes including death and From the Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. a Dr Akira Takeshita died on March 15, 2009. b For the JCARE-CARD Investigators. Submitted April 7, 2010; accepted August 21, 2010. Reprint requests: Hiroyuki Tsutsui, MD, PhD, Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. E-mail: htsutsui@med.hokudai.ac.jp 0002-8703/$ - see front matter © 2010, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2010.08.036