title: Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial.
abstract: BACKGROUND
  Myocardial fibrosis is dysrhythmogenic and may contribute to the high incidence of cardiac death in stroke survivors, especially if they have long QTc. We tested the hypothesis that procollagen-1-carboxy terminal peptide (P1CP), a biomarker of myocardial fibrosis, might be improved following treatment with spironolactone or amiloride in stroke survivors. We also tested the hypothesis that both drugs would shorten QTc.
  
  
  METHODS
  
  
  
  METHODS
  randomised, double-blinded, placebo-controlled, cross-over trial (spironolactone vs. amiloride vs. placebo). Duration of Study: 3 months (1 month per drug). Primary endpoints: P1CP, QTc
  
  
  RESULTS
  11 stroke survivors (5 female), aged 71 ± 4, BP 139/81 mmHg ± 20/11 mmHg, completed the study. Both spironolactone and amiloride significantly reduced P1CP [Spironolactone-Placebo = -24 ug/L, 95% CI = -40 to -6.9; Amiloride-Placebo = -28 ug/L, 95% CI = -44 to -11]. Spironolactone and amiloride both shortened QTc [Spironolactone vs. Placebo=-18 ms(1/2), 95% CI = -36 to -0.55; Amiloride vs Placebo = -25 ms(1/2), 95% CI = -42 to -7.5].
  
  
  CONCLUSIONS
  Procollagen-1-carboxy terminal peptide was reduced following treatment with spironolactone within a month. Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis. The beneficial effects of both drugs on myocardial fibrosis, coupled with their effects on raising potassium translated to a shortening of QTc. Future studies should test the hypothesis that these drugs might reduce the risk of sudden cardiac death in stroke survivors.
authors.affiliation: Ninewells Hospital and Medical School, University of Dundee, UK; Hull York Medical School, UK. Electronic address: kenneth.wong@hey.nhs.uk.
authors.forename: K Y K
authors.initials: KY
authors.lastname: Wong
authors.forename: S Y S
authors.initials: SY
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: McSwiggan
authors.forename: S A
authors.initials: SA
authors.lastname: Ogston
authors.forename: K Y S
authors.initials: KY
authors.lastname: Sze
authors.forename: R S
authors.initials: RS
authors.lastname: MacWalter
authors.forename: A D
authors.initials: AD
authors.lastname: Struthers
mesh_terms: D000368:Aged; D000584:Amiloride / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D006331:Heart Diseases / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D010919:Placebos; D011188:Potassium / Q000097:blood; D011347:Procollagen / Q000097:blood; D013148:Spironolactone / Q000008:administration & dosage* / Q000009:adverse effects; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D017741:Survivors; D016896:Treatment Outcome
chemical_list: D004232:Diuretics; D010919:Placebos; D011347:Procollagen; D013148:Spironolactone; D000584:Amiloride; D011188:Potassium
keywords: Amiloride; Myocardial fibrosis; QTc; Spironolactone; Stroke