Trends in Kidney Function Outcomes Following RAAS Inhibition in Patients With Heart Failure With Reduced Ejection Fraction

McCallum, Wendy; Tighiouart, Hocine; Ku, Elaine; Salem, Deeb N.; Sarnak, Mark J.

doi:10.1053/j.ajkd.2019.05.010

Cited by 22 publications

(24 citation statements)

References 32 publications

(34 reference statements)

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“…In addition, baseline CKD should not preclude the utilization of ACE‐I/ARBs as their treatment effects are maintained as demonstrated by several renal sub‐analysis of the landmark trials (CONSENSUS, SOLVD, SAVE, ATLAS, Val‐HeFT, CHARM‐Added, CHARM‐Alternative and HEAAL) 63 . However, post‐hoc analysis of the landmark ACE‐I trials in HF show that ACE‐I do not reduce the slope of GFR decline in comparison to patients assigned to placebo, but the short duration of follow‐up and early assessment of eGFR limit the interpretation of slope changes 64,65 . In contrast, in patients with diabetes (with or without HF), ACE‐I and ARBs do reduce the slope of GFR decline over time in trials of similar duration, which probably relates to the fact that diabetes is associated with more intraglomerular hypertension 68 .…”

Section: Renal Effects Of Established Guideline‐recommended Heart Fai...mentioning

confidence: 99%

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Renal effects of guideline‐directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology

Mullens

Martens

Testani

et al. 2022

European J of Heart Fail

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Novel pharmacologic treatment options reduce mortality and morbidity in a cost-effective manner in patients with heart failure (HF). Undisputedly, the effective implementation of these agents is an essential element of good clinical practice, which is endorsed by the European Society of Cardiology (ESC) guidelines on acute and chronic HF. Yet, physicians struggle to implement these therapies as they have to balance the true and/or perceived risks versus their substantial benefits in clinical practice. Any worsening of biomarkers of renal function is often perceived as being disadvantageous and is in clinical practice one of the most common reasons for ineffective drug implementation. However, even in this context, they clearly reduce mortality and morbidity in HF with reduced ejection fraction (HFrEF) patients, even in patients with poor renal function. Furthermore these agents are also beneficial in HF with mildly reduced ejection fraction (HFmrEF) and sodium-glucose cotransporter 2 (SGLT2) inhibitors more recently demonstrated a beneficial effect in HF with preserved ejection fraction (HFpEF). The emerge of several new classes (angiotensin receptor-neprilysin inhibitor [ARNI], SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) and the recommendation by the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic HF of early initiation

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Section: Renal Effects Of Established Guideline‐recommended Heart Fai...mentioning

confidence: 99%

“…63 However, post-hoc analysis of the landmark ACE-I trials in HF show that ACE-I do not reduce the slope of GFR decline in comparison to patients assigned to placebo, but the short duration of follow-up and early assessment of eGFR limit the interpretation of slope changes. 64,65…”

Section: Trial Evidence Of Renal Effects Of Ace-i and Arbmentioning

confidence: 99%

Renal effects of guideline‐directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology

Mullens

Martens

Testani

et al. 2022

European J of Heart Fail

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“…However, there was also no clear beneficial effect in these patients. 21,27,29 Data about ARBs in patients with CKD stage 4 are limited as well; however, although CIs were large, data might suggest a trend toward benefit in reducing cardiovascular death and HF hospitalization. 30 No information on ARB therapy is available in patients with CKD stage 5.…”

Section: Study Characteristics Of Landmark Clinical Trials: Baseline ...mentioning

confidence: 99%

Evidence-Based Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease

et al. 2022

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Chronic kidney disease (CKD) as identified by a reduced estimated glomerular filtration rate (eGFR) is a common comorbidity in patients with heart failure with reduced ejection fraction (HFrEF). The presence of CKD is associated with more severe heart failure, and CKD itself is a strong independent risk factor of poor cardiovascular outcome. Furthermore, the presence of CKD often influences the decision to start, uptitrate, or discontinue possible life-saving HFrEF therapies. Because pivotal HFrEF randomized clinical trials have historically excluded patients with stage 4 and 5 CKD (eGFR <30 mL/min/1.73 m 2 ), information on the efficacy and tolerability of HFrEF therapies in these patients is limited. However, more recent HFrEF trials with novel classes of drugs included patients with more severe CKD. In this review on medical therapy in patients with HFrEF and CKD, we show that for both all-cause mortality and the combined end point of cardiovascular death or heart failure hospitalization, most drug classes are safe and effective up to CKD stage 3B (eGFR minimum 30 mL/min/1.73 m 2 ). For more severe CKD (stage 4), there is evidence of safety and efficacy of sodium glucose cotransporter 2 inhibitors, and to a lesser extent, angiotensin-converting enzyme inhibitors, vericiguat, digoxin and omecamtiv mecarbil, although this evidence is restricted to improvement of cardiovascular death/heart failure hospitalization. Data are lacking on the safety and efficacy for any HFrEF therapies in CKD stage 5 (eGFR < 15 mL/min/1.73 m 2 or dialysis) for either end point. Last, although an initial decline in eGFR is observed on initiation of several HFrEF drug classes (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/mineralocorticoid receptor antagonists/angiotensin receptor blocker neprilysin inhibitors/sodium glucose cotransporter 2 inhibitors), renal function often stabilizes over time, and the drugs maintain their clinical efficacy. A decline in eGFR in the context of a stable or improving clinical condition should therefore not be cause for concern and should not lead to discontinuation of life-saving HFrEF therapies.

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“…[17][18][19] However, acute and sustained declines in eGFR have been observed in post-hoc analyses of trials of RAS inhibitors and MRAs in patients with HFrEF. [5][6][7][8] Moreover, post-hoc analyses of individuals with HFpEF from the CHARM programme 10 and I-PRESERVE studies 11 have reported an accelerated decline in renal function with the use of angiotensin receptor blockers, compared with placebo, suggesting that the pathophysiology of renal dysfunction in heart failure may be different from that observed in patients with CKD and type 2 diabetes mellitus. 20 In addition to providing RAS inhibition, combined angiotensin-neprilysin inhibitors simultaneously augment the endogenous natriuretic peptide system, with early studies of omapatrilat reporting fewer adverse renal impairment events, compared with enalapril, in patients with HFrEF.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin–neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure

Causland

Lefkowitz

Claggett

et al. 2022

European J of Heart Fail

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Trends in Kidney Function Outcomes Following RAAS Inhibition in Patients With Heart Failure With Reduced Ejection Fraction

Abstract: Angiotensin-converting enzyme (ACE) inhibitors are beneficial in heart failure with reduced ejection fraction (HFrEF). We sought to describe longitudinal trends in estimated glomerular filtration rate (eGFR) in HFrEF and how ACE-inhibitor therapy influences these changes.

Cited by 22 publications

References 32 publications

Renal effects of guideline‐directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology

Renal effects of guideline‐directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology

Evidence-Based Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease

Angiotensin–neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure

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