title: Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure　- Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.
abstract: BACKGROUND
  It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients.
  
  
  RESULTS
  From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P<0001). Furthermore, on IPTW multivariate Cox modeling for multiple treatments, both low-dose (<40 mg/day) and high-dose (≥40 mg/day) loop diuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both P<0.001). Triple blockade with RAS inhibitor(s), mineral corticoid (aldosterone) receptor antagonist(s) (MRA), and β-blocker(s) was significantly associated with better prognosis in those on low-dose but not on high-dose loop diuretics.
  
  
  CONCLUSIONS
  Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Miura
authors.forename: Koichiro
authors.initials: K
authors.lastname: Sugimura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sakata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyata
authors.forename: Soichiro
authors.initials: S
authors.lastname: Tadaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Takeo
authors.initials: T
authors.lastname: Onose
authors.forename: Kanako
authors.initials: K
authors.lastname: Tsuji
authors.forename: Ruri
authors.initials: R
authors.lastname: Abe
authors.forename: Takuya
authors.initials: T
authors.lastname: Oikawa
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kasahara
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nochioka
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D004232:Diuretics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists