A number of medications had no reported evidence with regards to the population with CKD: loop diuretics; sacubitril-valsartan; and hydralazine- nitrate. The only evidence found on hydralazine-nitrate was the African American Heart Failure Trial327 which was excluded, as the possible CKD subgroup was referred to as having history of chronic renal insufficiency without further definition. Twelve SGAs were considered, 10 of which compared intervention to placebo and 2 that compared different doses of the same drug. There were no intra or inter class comparisons. Most trials considered the intervention on top of existing heart failure drugs (for the era in which the trial took place), except for when Angiotensin II Receptor Blocker (ARB) was considered as an alternative when Angiotensin Converting Enzyme Inhibitors (ACE-I) were not tolerated. Notwithstanding the limitations of the evidence base, the committee agreed that it was important to provide advice for this common subgroup of HFREF patients. Based on the evidence reviewed and the experience of the committee members, consensus was reached on the optimal treatment approach for patients with HFREF and CKD (see discussion below). Trade-off between clinical benefits The committee noted the new HFREF treatment algorithm in this guideline. First-line is double therapy with beta-blocker and ACE-I; or if ACE-I is not Chronic Heart Failure Treating Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 and harms tolerated, an ARB. If still symptomatic, the addition of a Mineralocorticoid Receptor Antagonist (MRA) ( triple therapy ). Beta-blocker, ACE-I/ARB and MRA combined is referred to as triple therapy . Further medication options after seeking specialist advice, might be sacubitril valsartan (in place of ACEi [or ARB]), digoxin, or ivabradine. 