title: Use of quinine and mortality-risk in patients with heart failure--a Danish nationwide observational study.
abstract: OBJECTIVE
  Leg cramps are common in patients with heart failure. Quinine is frequently prescribed in low doses to these patients, but safety of this practice is unknown. We studied the outcomes associated with use of quinine in a nationwide cohort of patients with heart failure.
  
  
  METHODS
  Through individual-level-linkage of Danish national registries, we identified patients discharged from first-time hospitalization for heart failure in 1997-2010. We estimated the risk of mortality associated with quinine treatment by time-dependent Poisson regression models.
  
  
  RESULTS
  A total of 135 529 patients were included, with 14 510 patients (11%) using quinine at some point. During a median time of follow-up of 989 days (interquartile range 350-2004) 88 878 patients (66%) died. Patients receiving quinine had slightly increased mortality risk, adjusted incidence rate ratio (IRR) 1.04 (95% confidence interval [CI] 1.01 to 1.07). The risks differed according to concomitant β-blocker treatment. For patients treated with both quinine and β-blockers IRR was 1.15 (95% CI 1.09 to 1.21) vs. 0.99 (95% CI 0.96 to 1.03) for patients treated with quinine but not β-blockers. The risks were highest shortly after initiation of therapy: for the first 14 days of treatment IRR was 2.12 (95% CI 1.54 to 2.93) for patients in treatment with β-blockers and 1.17 (95% CI 0.86 to 1.59) for patients not treated with β-blockers.
  
  
  CONCLUSIONS
  Use of quinine was common and associated with increased mortality in heart failure, especially if administered together with β-blockers and shortly after treatment initiation. Mechanisms underlying the findings remain to be established.
authors: Department of Cardiology, Copenhagen University Hospital Gentofte, Copenhagen, Denmark.
authors: Anne
authors: A
authors: Gjesing
authors: Gunnar H
authors: GH
authors: Gislason
authors: Stefan B
authors: SB
authors: Christensen
authors: Mads E
authors: ME
authors: Jørgensen
authors: Charlotte
authors: C
authors: Mérie
authors: Mette Lykke
authors: ML
authors: Norgaard
authors: Henrik Enghusen
authors: HE
authors: Poulsen
authors: Finn
authors: F
authors: Gustafsson
authors: Lars
authors: L
authors: Køber
authors: Christian
authors: C
authors: Torp-Pedersen
authors: Charlotte
authors: C
authors: Andersson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced* / Q000401:mortality*; D006760:Hospitalization / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D009125:Muscle Relaxants, Central / Q000009:adverse effects*; D011803:Quinine / Q000009:adverse effects*; D012042:Registries; D012307:Risk Factors
chemical_list: D009125:Muscle Relaxants, Central; D011803:Quinine
keywords: heart failure; mortality; pharmacoepidemiology; quinine