Cardiovascular effects of irbesartan in haemodialysis patients

INTRODUCTION: Cardiovascular (CV) events are a major cause of morbidity and mortality in haemodialysis (HD) pa­ tients. Hypertension, increased arterial stiffness and left ventricular (LV) hypertrophy are highly prevalent and are often poorly controlled. Volume overload is an important factor and survival could be improved by treatment strat­ egies that preserve residual renal function (RRF), reduce blood pressure, and decrease arterial stiffness and LV hy­ pertrophy. Angiotensin II receptor blocker (ARB) treatment can prevent CV events in patients with hypertension and heart failure. However, few data exist in patients with chronic renal failure and it is not known whether ARB treat­ ment improves clinical outcome in HD patients. MATERIAL AND METHODS: This is a randomized, controlled and double­blinded intervention study. A total of 82 HD pa­ tients from six Danish HD centres will be treated for a year with an ARB (irbesartan) or placebo. The inclusion criteria are urine output > 300 ml/day, dialysis vintage LV ejection fraction > 30%. The primary outcomes are change in RRF, LV hypertrophy, arterial stiffness and intra­ dialytic haemodynamics. CONCLUSION: If ARB­treatment improves RRF and interme­ diate CV endpoints in a group of newly started HD patients, it may improve the survival for this high risk population. FUNDING: The trial is investigator­initiated, investigator­ driven and supported by the Danish Agency for Science, Technology and Innovation and several private foundations. TRIAL REGISTRATION: Clinical Trials ID: NCT00791830. The mortality rate in incident European dialysis patients is 192 per 1,000 person­years compared with 12 in the general population. The most common cause of death is cardiovascular (CV) disease, which accounts for 39% [1]. Dialysis patients often have an elevated blood pres­ sure (BP) due to volume overload. In addition, chronic renal failure causes increased arterial stiffness, which is reported to be a strong independent risk factor for CV mortality [2]. The mechanisms causing increased arterial stiffness are incompletely understood. However, it is generally accepted that complete loss of renal function markedly accelerates this process, thereby potentiating traditional CV risk factors such as diabetes, hypercholes­ terolemia, obesity and smoking. Furthermore, the loss of kidney function leads to reduced removal and increased cytokine generation as well as impaired immune system [3]. Thus, many dialysis patients have chronic low­grade inflammation [4], which is associated with increased risk of atherosclerotic complications [5]. Various treatment strategies to preserve residual renal function (RRF) and counteract inflammation and development of CV disease have been suggested. Among these are agents blocking the renin­angiotensin­ aldosterone system (RAAS). In peritoneal dialysis (PD) patients, two Asian open­ labelled studies have shown that an angiotensin­con­ verting enzyme inhibitor (ACE­I) as well as an angioten­ sin II receptor blocker (ARB) can preserve RRF [6, 7]. Regarding the anti­inflammatory properties and protec­ tion against CV disease in haemodialysis (HD) patients, the results of ACE­I and ARB treatment are conflicting, both in short­term and longer follow­up studies [8, 9]. Data on large artery stiffness are scarce, whereas left Renal and cardiovascular effects of irbesartan in dialysis patients – a randomized controlled trial protocol (saFiR study) Christian Daugaard Peters1, 2, Krista Dybtved Kjaergaard1, 2, Bente Jespersen1, 2, Kent Lodberg Christensen3 & Jens Dam Jensen1, 2 PROTOcOl aRTiclE 1) Department of Renal Medicine, Aarhus University Hospital 2) Institute of Clinical Medicine, Aarhus University 3) Department of Cardiology, Aarhus University Hospital Dan Med J 2013;60(4):A4602