Table 58: PICO characteristics of review question Population Adults with heart failure and chronic kidney disease (at least stage 3A / eGFR <60 mL/min), who are not on dialysis. Interventions / Comparisons Angiotensin Converting Enzyme (ACE) inhibitor Angiotensin Receptor Antagonist / Blocker (ARB) Beta-Adrenergic Antagonia / Blocker (Beta-blocker) Mineralocorticoid Receptor Antagonist (MRA) Digoxin Diuretics loop and loop-related Ivabradine and Sacubitril-Valsartan Hydralazine-Nitrate Compared against each other (class versus class and within class comparisons), against the same drug at a different dose, or against placebo. Outcomes CRITICAL All-cause mortality Quality of life Unplanned hospitalization IMPORTANT Chronic Heart Failure Treating Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Renal function Adverse events - Bradycardia Adverse events - Arrhythmic events Adverse events - Progression to stage five kidney disease / unplanned dialysis Adverse events - Hypotension Adverse events - Hyperkalaemia Study design Systematic Review RCT 6.2.6.3 Clinical evidence A search was conducted for randomised trials comparing the effectiveness of medications for long- term treatment of heart failure (HF) in patients with both HF and chronic kidney disease of stage 3 or all of which were sub-group analyses of randomised controlled trials of HF medication in the wider HF population. Trials of medication versus placebo were identified in the following drug . In addition, there was a dose comparison for ACE inhibitors289 . No evidence was found regarding the use of loop diuretics, sacubitril-valsartan or hydralazine/nitrate in people with HF and CKD. The critical outcomes of mortality and hospitalisation were frequently reported, but no studies reporting quality of life or change in NYHA class were identified. The included studies are summarised in Table 59 below. Evidence from these studies is summarised in the clinical evidence summary below(Table 60 to 65). 