Combined blockade of renin-angiotensin-aldosterone system reduced all-cause but not cardiovascular mortality in dialysis patients: A mediation analysis and systematic review

Abstract Background and aims Full blockade of renin-angiotensin-aldosterone system (RAAS) is believed to decrease morbidity and mortality of patients with chronic kidney disease. In non-dialysis patients, combined RAAS blockade with two different RAAS blockers causes more adverse events without improving survival, but its role in maintenance dialysis patients is still unclear. We conducted a systematic review and mediation analysis to investigate the efficacy and safety of combined RAAS blockade in dialysis patients. Methods Comprehensive search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library database to June 2017 to identify relevant studies. Studies comparing combined with single RAAS blockade and reporting all-cause death, cardiovascular death, hypotension or hyperkalemia in dialysis patients were included. Effect sizes were calculated with randomized effects model and summarized as odd ratios (OR). Results A total of 9 studies with 13,050 dialysis patients were included. Compared with single blockade, combined blockade significantly reduced all-cause mortality (OR 0.71, 95% confidence interval 0.54–0.93, p  = 0.01), while cardiovascular mortality remained unchanged (0.85, 0.45–1.59, p  = 0.61). Combined blockade tended to increase odd of hypotension but not odd of hyperkalemia (1.54, 1.00–2.38, p  = 0.05; 0.89, 0.76–1.05, p  = 0.17). Further mediation analysis indicated that hypotension might exert a suppression effect on the survival benefit of angiotensin-converting enzyme inhibitor plus angiotensin receptor blocker treatment on cardiovascular mortality. Conclusions Combined RAAS blockade might be a promising treatment in dialysis patients to further reduce mortality if blood pressure was well controlled.