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| |  Allopurinol Improves Diastolic Function and Lowers NT-proBNP Levels in Heart Failure Patients: Presented at HF2008 By Chris Berrie MILAN, Italy -- June 19, 2008 -- The xanthine oxidase inhibitor allopurinol significantly improves left ventricular diastolic function and reduces amino-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels in patients with chronic heart failure (CHF), according to a double-blind, placebo-controlled study. "We know that serum uric acid concentrations are quite elevated in patients with diastolic dysfunction," and these are generally thought to reflect impaired oxidative metabolism, with excess xanthine oxidase activity, said principal investigator Corinna Bergamini, MD, Cardiology Department, University of Verona, Verona, Italy. These uric acid changes correlate strongly with echocardiographic parameters of diastolic function, and allopurinol has been shown to have benefits on endothelial function in hyperuricaemic patients, Dr. Bergamini said in a poster presentation here on June 16 at the Heart Failure 2008 (HF2008) Congress. Therefore, her research team investigated the effects of allopurinol on diastolic function in patients with CHF. Among 53 outpatients with stable CHF, the researchers randomised 27 patients to placebo (mean age, 67.1 years) and 26 to allopurinol 300 mg/day (mean age, 65.0 years). Treatment was continued for 3 months. Clinical and metabolic assessments were carried out at baseline and at end of treatment, along with complete Doppler ultrasound examinations. At baseline, there were no significant differences between clinical characteristics across the placebo and allopurinol treatment groups. Their echocardiographic characteristics were not significantly different at baseline, such as ejection fraction (35.8%, 34.6%, respectively), shortening fraction (0.7%, 0.6%), peak early diastolic flow velocity (E; 0.7, 0.6 m/s), and ratio of E to peak early diastolic mitral annular velocity (E/Ea; 15.5, 9.8). At the end of 3 months, there were no changes in NT-proBNP levels in control patients (1,157 vs 1,111 pg/mL) but allopurinol treatment promoted a significant decrease in NT-proBNP (1,864 vs 1,376 pg/mL; P = .01). Similarly, there were significant improvements for E and E/Ea in patients treated with allopurinol (0.70 vs 0.58 m/s, P = .01; 15.9 vs 10.6, P = .03; respectively). Dr. Bergamini also noted the significant correlation in the allopurinol treatment group between changes in E/Ea and NT-proBNP concentrations (P = .002; r = .54), and a similar, but borderline, relationship between change in uric acid levels and changes in NT-proBNP (P = .053; r = .3). In this first clinical study to examine the effects of allopurinol on diastolic function in patients with CHF, there was an improvement in left-ventricular diastolic function and NT-proBNP levels in patients with stable CHF. Further studies should evaluate the long-term effects of this treatment, Dr. Bergamini said.
[Presentation title: Allopurinol Improves Diastolic Function and Lowers NT-proBNP Plasma Levels in HF Patients: a Double-Blind, Placebo-Controlled Study. Abstract P741]
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