title: Hydralazine and nitrates alone or combined for the management of chronic heart failure: A systematic review.
abstract: BACKGROUND
  Hydralazine (H) and nitrates (Ns), when combined, reduced morbidity and mortality in some trials of chronic heart failure (CHF). It is unclear whether either agent used alone provides similar benefits. We aimed to evaluate the effects of H and/or N in patients with CHF.
  
  
  METHODS
  A systematic review of randomised trials assessing the effects of H and N in CHF. For meta-analysis, only the endpoints of all-cause mortality and cardiovascular mortality were considered.
  
  
  RESULTS
  In seven trials evaluating H&N in 2626 patients, combination therapy reduced all-cause mortality (OR 0.72; 95% CI 0.55-0.95; p=0.02), and cardiovascular mortality (OR 0.75; 95% CI 0.57-0.99; p=0.04) compared to placebo. However, when compared to angiotensin converting enzyme inhibitors (ACEIs), combination therapy was associated with higher all-cause mortality (OR 1.35; 95% CI 1.03-1.76; p=0.03), and cardiovascular mortality (OR 1.37; 95% CI 1.04-1.81; p=0.03). For N alone, ten trials including 375 patients reported all-cause mortality and showed a trend to harm (13 deaths in those assigned to nitrates and 7 to placebo; OR 2.13; 95% CI 0.88-5.13; p=0.09). For H alone, three trials showed no difference in all-cause mortality compared to placebo (OR 0.96; 95% CI 0.37-2.47; p=0.93), and two trials suggested inferiority to ACEI (OR 2.28; 95% CI 1.03-5.04; p=0.04).
  
  
  CONCLUSIONS
  Compared to placebo, H&N reduces mortality in patients with CHF. Whether race or background therapy influences benefit is uncertain, but on direct comparison H&N appears inferior to ACEI. There is little evidence to support the use of either drug alone in CHF.
authors.affiliation: Department of Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull HU16 5JQ, UK. Electronic address: mohamedfarag@nhs.net.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Farag
authors.affiliation: Department of Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull HU16 5JQ, UK.
authors.forename: Thato
authors.initials: T
authors.lastname: Mabote
authors.affiliation: Department of Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull HU16 5JQ, UK.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Shoaib
authors.affiliation: Department of Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull HU16 5JQ, UK.
authors.forename: Jufen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Postgraduate Medical School, Ain Shams University, Cairo, Egypt.
authors.forename: Ashraf F
authors.initials: AF
authors.lastname: Nabhan
authors.affiliation: Department of Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull HU16 5JQ, UK.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Clark
authors.affiliation: National Heart & Lung Institute, Imperial College, London, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Cleland
mesh_terms: D002908:Chronic Disease; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006830:Hydralazine / Q000627:therapeutic use*; D009026:Mortality; D009566:Nitrates / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D009566:Nitrates; D014665:Vasodilator Agents; D006830:Hydralazine
keywords: Chronic heart failure; Hydralazine; Morbidity; Mortality; Nitrate; Systematic review