title: The antianginal efficacy of isosorbide dinitrate therapy is maintained during diuretic treatment.
abstract: OBJECTIVE
  To determine whether the use of a diuretic would maintain the antianginal efficacy of isosorbide dinitrate during 1 week of therapy.
  
  
  METHODS
  During continuous therapy, organic nitrates have a reduction in antianginal effectiveness and cause fluid retention. The study was a randomized, double-blind, placebo-controlled crossover design examining the effect of 1 week of daily treatment with 50 mg hydrochlorothiazide/5 mg amiloride on the antianginal effectiveness of 30 mg isosorbide dinitrate administered every 6 hours. Exercise stress testing was performed before and 3 hours after administration of isosorbide dinitrate at the start and end of the placebo and diuretic treatment phases.
  
  
  RESULTS
  The time to onset of angina (475 +/- 35 versus 490 +/- 29 seconds, difference not significant) and to moderate angina after administration of isosorbide dinitrate (542 +/- 40 versus 566 +/- 37 seconds, difference not significant) were similar at the start and end of the diuretic phase of the study but were reduced at the end of the placebo phase (471 +/- 40 versus 410 +/- 40 seconds, p < 0.05 and 531 +/- 38 versus 466 +/- 39 seconds, p < 0.05, respectively). Total exercise time and time to onset of angina 3 hours after administration of isosorbide dinitrate were longer (p < 0.005) at the end of the diuretic phase compared with the end of the placebo phase. Patients gained weight during the placebo phase and lost weight during the diuretic phase of the study. The change in weight was inversely correlated to the change in total exercise time (r = -0.53, p < 0.05).
  
  
  CONCLUSIONS
  Patients using a diuretic with isosorbide dinitrate maintain an increased anginal threshold and total exercise time compared with placebo. Weight change is inversely related to exercise duration, and this result is consistent with fluid retention restoring cardiac preload during nitrate use. The increased anginal threshold during concurrent isosorbide dinitrate and diuretic use may be attributable to maintenance of the organic nitrate-induced reductions in cardiac preload.
authors.affiliation: Health Science Centre, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: B A
authors.initials: BA
authors.lastname: Sussex
authors.forename: N R
authors.initials: NR
authors.lastname: Campbell
authors.forename: M K
authors.initials: MK
authors.lastname: Raju
authors.forename: D W
authors.initials: DW
authors.lastname: McKay
mesh_terms: D000368:Aged; D000584:Amiloride / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005080:Exercise Test; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D007548:Isosorbide Dinitrate / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
chemical_list: D006852:Hydrochlorothiazide; D000584:Amiloride; D007548:Isosorbide Dinitrate