Loop diuretics for chronic heart failure: a foe in disguise of a friend?

Abstract

Loop diuretics are recommended for relieving symptoms and signs of congestion in patients with chronic heart failure and are administered to more than 80% of them. However, several of their effects have not systematically been studied. Numerous cohort and four interventional studies have addressed the effect of diuretics on renal function; apart from one prospective study, which showed that diuretics withdrawal is accompanied by increase in some markers of early-detected renal injury, all others converge to the conclusion that diuretics receipt, especially in high doses is associated with increased rates of renal dysfunction. Although a long standing perception has attributed a beneficial effect to diuretics in the setting of chronic heart failure, many cohort studies support that their use, especially in high doses is associated with adverse outcome. Several studies have used propensity scores in order to match diuretic and non-diuretic receiving patients; their results reinforce the notion that diuretics use and high diuretics dose are true risk factors and not disease severity markers, as some have suggested. One small, randomized study has demonstrated that diuretics decrease is feasible and safe and accompanied by a better prognosis. In conclusion, until elegantly designed, randomized trials, powered for clinical endpoints answer the unsettled issues in the field, the use of diuretics in chronic heart failure will remain subject to physicians' preferences and biases and not evidence based.

Sacubitril/valsartan eligibility and outcomes in the ESC‐EORP‐HFA Heart Failure Long‐Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM‐HF trial, ESC guidelines, and real world

“…This lower risk in PARADIGM‐HF could potentially be explained by the stricter selection that inevitably occurs in trials, the higher risk profile (i.e. higher prevalence of end‐stage renal disease and more use of loop diuretics) and the less regular follow‐up in the registry vs. the PARADIGM‐HF and other trial populations . However, this consideration is not supported by the fact that the sub‐populations of HFrEF patients enrolled in the ESC‐EORP‐HFA HF‐LT Registry that were eligible for LCZ696 both by PARADIGM‐HF and ESC guideline criteria had better outcome in terms of survival compared to patients in the enalapril arm of PARADIGM‐HF, although they had similar baseline characteristics.…”

“…higher prevalence of end-stage renal disease and more use of loop diuretics) and the less regular follow-up in the registry vs. the PARADIGM-HF and other trial populations. 30 However, this consideration is not supported by the fact that the sub-populations of HFrEF patients enrolled in the ESC-EORP-HFA HF-LT Registry that were eligible for LCZ696 both by PARADIGM-HF and ESC guideline criteria had better outcome in terms of survival compared to patients in the enalapril arm of PARADIGM-HF, although they had similar baseline characteristics. This could be possibly explained either by the effect of unrecognized confounders or, although it is far-fetched, by the under-reporting of adverse events (such as hospitalizations), which has been recognized as a significant drawback of clinical trials.…”

Congestion and Diuretic Resistance in Acute or Worsening Heart Failure

“…[ 24 ] At the same time, in chronic stable HF, it has been described that patients on high doses versus low doses have higher risk for mortality, sudden death and pump failure death. [ 67 ] This certainly reflects confounding by severity, but loop diuretics reduce intravascular fluid and cause compensatory maladaptive neurohormonal activation and may be a risk factor, in addition to a risk marker, for worse outcomes. [ 10 ] Indeed the beneficial haemodynamic effects of angiotensin receptor neprilysin inhibitors (ARNi) may reduce the need for diuretics.…”

Drug therapy in elderly heart failure patients

“…Therefore, the pharmacotherapy of HFrEF in elderly patients is recommended to be the same as for patients in all other age groups according to the ESC/HFA guidelines, 2 and is based on ACE inhibitors (or angiotensin receptor antagonists [ARB] or angiotensin receptor-neprilysin inhibitors [ARNI]), beta-blockers, mineralocorticoid receptors (MRA), ivabradine to improve clinical outcomes, along with loop diuretics, and sometimes digoxin to further alleviate HF symptoms 16 , 17 …”