Safety and effect of high dose allopurinol in patients with severe left ventricular systolic dysfunction

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.

Effect of Uric Acid-Lowering Agents on Cardiovascular Outcome in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Clinical Studies

“…The net signal from these studies was unclear, some studies claiming that UA-lowering agents improved morbidity, mortality, cardiovascular (CV) events, and hospitalizations, 10 –13 while others found that UA-lowering agents do not cause any significant change in survival of patients with HF or performed even worse than placebo. 14 –20…”

Dioxygen and Metabolism; Dangerous Liaisons in Cardiac Function and Disease

“…Interestingly, in a clinical study led on HF patients, allopurinol was able to restore M-CK activity, hence to sustain the transfer of energy from mitochondria to sarcomere (Hirsch et al, 2012 ). More recent study revealed an improvement of walk effort resistance in patients suffering from left ventricular dysfunction, even with higher administrated dose (300 mg daily for 1 week then 600 mg daily for 3 months) (Ansari-Ramandi et al, 2017 ). However, in patients undergoing percutaneous intervention, allopurinol pretreatment revealed as not effective enough to modify cardiac biomarkers, and especially the level of creatine kinase or troponin-T (Alemzadeh-Ansari et al, 2017 ; Ansari-Ramandi et al, 2017 ).…”

“…More recent study revealed an improvement of walk effort resistance in patients suffering from left ventricular dysfunction, even with higher administrated dose (300 mg daily for 1 week then 600 mg daily for 3 months) (Ansari-Ramandi et al, 2017 ). However, in patients undergoing percutaneous intervention, allopurinol pretreatment revealed as not effective enough to modify cardiac biomarkers, and especially the level of creatine kinase or troponin-T (Alemzadeh-Ansari et al, 2017 ; Ansari-Ramandi et al, 2017 ). This last work may lead to suggest the idea that relevance of such a treatment may depend on numerous parameters.…”

Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP

“…In animals, at least 11 papers reported that heart failure and ischemic heart disease were improved by the administration of allopurinol or febuxostat (DeWall et al, 1971; Arnold et al, 1980; Hopson et al, 1995; Pérez et al, 1998; Ekelund et al, 1999; Khatib et al, 2001; Ukai et al, 2001; Stull et al, 2004; Hou et al, 2006; Xu et al, 2008; Zhao et al, 2008; Yao and Seko, 2017; El-Bassossy et al, 2018). In humans, at least 20 papers, including randomized controlled trials (RCTs) and meta-analyses, reported that heart failure and ischemic heart disease were improved by the administration of allopurinol or febuxostat (Saugstad, 1996; Cappola et al, 2001; Gavin and Struthers, 2005; Pacher et al, 2006; Noman et al, 2010; Rentoukas et al, 2010; Thanassoulis et al, 2010; Kelkar et al, 2011; Gotsman et al, 2012; Hirsch et al, 2012; Agarwal and Messerli, 2013; Agarwal et al, 2013; Larsen et al, 2016; MacIsaac et al, 2016; Singh and Yu, 2016, 2017; Ansari-Ramandi et al, 2017; Foody et al, 2017; Singh et al, 2017; Bredemeier et al, 2018). Because of febuxostat’s more recent approval, most reports analyzed only allopurinol.…”