Abstract
Introduction: Allopurinol used in the treatment of gout has been shown to improve the vascular endothelial dysfunction and reduce the dysfunction of the failing heart. This study was done to evaluate the effect and safety of allopurinol in non-hyperuricemic patients with chronic severe left ventricular (LV) dysfunction. Methods: In this study, 35 consecutive cases of non-hyperuricemic patients with chronic heart failure who had severe LV systolic dysfunction (ejection fraction of less than 35%) and were on optimal guideline directed medical therapies for at least 3 months were included. Allopurinol was administered with the dose of 300 mg po daily for 1 week and then it was up-titrated to a dose of 600 mg po daily for 3 months. Six minute walk test, strain imaging, laboratory testing were done for every patient at baseline and after 3 months treatment with allopurinol. Results: In this study 30 heart failure (HF) patients with a mean age of 49.3 ± 14.4 years old were evaluated. No adverse effects were reported except for one case of skin rash after 4 days treatment which was excluded from the study. Study showed significant improvement of six minute walk test of the patients from 384.5 ± 81.5 meters to 402.8 ± 89.6 meters and the global longitudinal peak strain (P < 0.001). There was also significant decrease in the level of erythrocyte sedimentation rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) after 3 months. Conclusion: Allopurinol could be of benefit in non-hyperuricemic patients with severe LV systolic dysfunction without significant adverse effects. Randomized clinical trials are needed in future to confirm the results.
Highlights
Allopurinol used in the treatment of gout has been shown to improve the vascular endothelial dysfunction and reduce the dysfunction of the failing heart
Exact–heart failure (HF) and OPT-CHF trials,[5,8] the largest prospective, randomized, controlled trials testing the effect of xanthine oxidase (XO) inhibition on mortality and clinical outcomes in patients with HFrEF, failed to show beneficial effects of allopurinol on clinical status and outcomes of these patients, many experimental and clinical studies indicate allopurinol use reduces oxygen free radicals formation as well as oxidative damage and has favorable effects on myocardial energy metabolism, endothelial function, mechanoenergetic coupling, myocardial oxygen consumption, ventricular remodeling and clinical status in the setting of HF.[3, 4,6,7,8,9,10,11,12]
Most of the studies in this regard are small studies which use different doses of allopurinol and it has been shown that the effect of allopurinol on endothelial function and uric acid (UA) lowering in HF is dose dependent and the drug is most useful with high doses or in patients with elevated UA level.[3,4,6,8,12,20]
Summary
Allopurinol used in the treatment of gout has been shown to improve the vascular endothelial dysfunction and reduce the dysfunction of the failing heart. This study was done to evaluate the effect and safety of allopurinol in non-hyperuricemic patients with chronic severe left ventricular (LV) dysfunction. Methods: In this study, 35 consecutive cases of non-hyperuricemic patients with chronic heart failure who had severe LV systolic dysfunction (ejection fraction of less than 35%) and were on optimal guideline directed medical therapies for at least 3 months were included. Conclusion: Allopurinol could be of benefit in non-hyperuricemic patients with severe LV systolic dysfunction without significant adverse effects. Allopurinol which is a XO inhibitor and used in the treatment of gout has been shown to improve the vascular endothelial dysfunction and reduce the dysfunction of the failing heart. Allopurinol use reduces oxygen free radicals formation as well as oxidative damage and has favorable effects on myocardial energy metabolism, endothelial function, mechanoenergetic coupling, myocardial oxygen consumption, ventricular remodeling and clinical status in the setting of HF.[3,4,5,6,7,8,9] allopurinol’s effect is under question in HF patients without hyperuricemia.[2,3,4,5,6,7,8,9,10,11,12,13] In the present study we aimed to assess the effects of allopurinol and its tolerability in terms of presence of side effects in HF patients without hyperuricemia
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