Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients | Clinical Trial - EXACT-HF


The goal of the trial was to evaluate treatment with the xanthine oxidase inhibitor allopurinol compared with placebo among patients with symptomatic heart failure and elevated serum uric acid levels.

Contribution to the Literature: The EXACT-HF trial failed to show that allopurinol in symptomatic heart failure improved clinical status, exercise capacity, or quality of life.

Study Design

  • Placebo Controlled
  • Blinded
  • Randomized
  • Parallel

Patient Populations:

  • Patients with symptomatic heart failure (New York Heart Association class II-IV)
  • Heart failure symptoms for 3 months despite standard therapy
  • Left ventricular ejection fraction ≤40%
  • Serum uric acid level ≥9.5 mg/dl
  • One additional high-risk characteristic: hospitalization for heart failure in the last year, left ventricular ejection fraction ≤25%, or N-terminal pro-B-type natriuretic peptide >1500 pg/ml

    Number of enrollees: 253
    Duration of follow-up: 24 weeks
    Mean duration of heart failure: 5.1 years
    Median patient age: 63 years
    Percentage female: 14%; diabetics: 57%
    Mean body mass index: 31 kg/m2
    Mean left ventricular ejection fraction: 25%

Exclusion Criteria:

  • Estimated glomerular filtration rate <20 ml/min

Primary Endpoints:

  • Composite clinical endpoint of heart failure functional assessment

Secondary Endpoints:

  • Quality of life
  • Submaximal exercise capacity

Drug/Procedures Used:

Patients with symptomatic heart failure and elevated serum uric acid levels were randomized to allopurinol (n = 128) versus placebo (n = 125). Allopurinol was started at 300 mg daily and up-titrated to 600 mg daily.

Principal Findings:

Allopurinol significantly reduced serum uric acid levels 3.5 mg/dl vs. placebo at 24 weeks (p < 0.001).

The proportion of patients that worsened was 45% vs. 46%, stayed the same was 42% vs. 34%, or improved was 13% vs. 19%, respectively, for allopurinol vs. placebo (p = 0.68).

Quality of life (p = 0.16) and submaximal exercise (p = 0.64) were also similar between groups.

Death or heart failure hospitalization was marginally reduced, favoring allopurinol (p = 0.06).

There were more skin and subcutaneous adverse events in the allopurinol group (15 vs. 6, p < 0.05).


Among symptomatic heart patients, the use of allopurinol compared with placebo was not beneficial at improving functional status, quality of life, or exercise capacity. The indication for allopurinol remains for the treatment of symptomatic gout.


Givertz MM, Anstrom KJ, Redfield MM, et al., on behalf of the NHLBI Heart Failure Clinical Research Network. Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The EXACT-HF Study. Circulation 2015;Apr 14:[Epub ahead of print].

Presented by Dr. Michael M. Givertz at the American College of Cardiology Scientific Session, Washington, DC, March 30, 2014.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Stress

Keywords: Allopurinol, Gout, Follow-Up Studies, Ventricular Function, Left, Oxidative Stress, Uric Acid, Xanthine Oxidase, Body Mass Index, Quality of Life, Heart Failure, Peptide Fragments, Stroke Volume, Diabetes Mellitus, Natriuretic Peptide, Brain, ACC Annual Scientific Session

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