Donepezil, a potential therapeutic agent for heart failure

Abstract

Donepezil, an inhibitor of cholinesterase, has been used to treat Alzheimer's disease. We read with great interest the study by Li et al. who demonstrated that the addition of donepezil prevented the deterioration of heart dysfunction and improved the long-term survival in rats with chronic heart failure (CHF) beyond that seen with losartan alone.1 This suggested that combination treatment with losartan plus donepezil might be a potential therapeutic strategy for CHF. Earlier studies also conducted by Li's team revealed that donepezil decreased heart rate, improved haemodynamic parameters, prevented cardiac remodelling, and suppressed BNP, catecholamine, and inflammatory factors in rats with CHF.2, 3 A similar result was also obtained by Handa et al. in mice with CHF.4 Chronic administration of donepezil for 2 weeks could not only induce vagal nerve activation, but could also reduce sympathetic nerve activation, as demonstrated by Umegaki and Khookhor in a recent study.5 Cardiac autonomic imbalance is one of the most important features of CHF. Antiadrenergic drugs have been used to treat CHF for decades as an effective strategy. However, an agent that could increase parasympathetic nerve activation has not been tested in patients with CHF. The effect of donepezil on the balance of the autonomic nervous system during CHF demands our attention. Unfortunately, so far no prospective trial has proved the effect of donepezil in CHF patients. Nonetheless, a retrospective investigation indicated smaller hazard ratios for total and cardiovascular mortality among patients treated with donepezil.6 The association between cholinesterase inhibition and a reduced risk of myocardial infarction and death was also verified by Nordstrom et al. in a recent observational study.7 These experimental and clinical studies suggest that donepezil might be a novel agent to treat CHF. Randomized controlled trials are warranted to translate this into clinical use. Conflict of interest: none declared. Ao Chen Department of Cardiology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China Ying-Min Chen Department of Cardiology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Dongfang Road Shanghai China, 200127 Tel: +86 136 81980901 Fax: +86 021 34611387 Email: [email protected]