Impact of a high-dose nitrate strategy on cardiac stress in acute heart failure: a pilot study

J Intern Med. 2010 Mar;267(3):322-30. doi: 10.1111/j.1365-2796.2009.02146.x. Epub 2009 Jun 22.

Abstract

Background: Intravenous nitrate therapy has been shown to improve short-term outcome of acute heart failure patients treated in the intensive care unit. The potential of a noninvasive high-dose nitrate strategy in the Emergency Department and the general ward remains unknown.

Methods: A total of 128 consecutive acute heart failure patients were either treated with standard therapy or high-dose sublingual and transdermal nitrates on top of standard of care treatment. Cardiac recovery, quantified by B-type natriuretic peptide (BNP) levels during the first 48 h, was the primary endpoint. Secondary endpoints ascertained the safety of the nitrate therapy.

Results: The high nitrate group received higher doses of nitrates during the first 48 h compared to the standard therapy group [82.4 mg (46.2-120.6) vs. 20 mg (10-30) respectively, P < 0.001]. The amount of diuretics given in both groups was similar. BNP levels decreased in all patients (P < 0.0001). However, the BNP decrease was larger in the high-dose nitrate group (P < 0.0001). The larger decrease in BNP in the high-dose nitrate group was already apparent 12 h after the initiation of treatment. After 48 h BNP values decreased by an average of 29 +/- 4.9% in the high-dose nitrate strategy group compared to 15 +/- 5.4% during standard therapy. There was a strong trend towards fewer ICU admissions in the high-dose nitrate group [high-dose nitrates: 2 cases (4%) vs. standard therapy: 9 cases (13%); P = 0.06]. During the study period, no intergroup changes were observed in blood pressure, RIFLE classes of acute kidney injury or troponin T. In-hospital and 90-day outcome was similar amongst the two groups.

Conclusions: A noninvasive high-dose nitrate strategy on top of standard therapy is safe and notably accelerates cardiac recovery in patients observed on the general ward.

MeSH terms

  • Acute Disease
  • Administration, Cutaneous
  • Administration, Sublingual
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Nitrates / administration & dosage*
  • Pilot Projects
  • Prospective Studies

Substances

  • Biomarkers
  • Nitrates
  • Natriuretic Peptide, Brain