Diuretics

Oedema can arise from other causes, including dependent oedema due to immobility, impaired venous return, venous stasis, and altered vasomotor tone [362]. Although data on the prevalence of oedema are limited, a recent study suggests that approximately 20% of individuals aged 50 and over experience persistent peripheral oedema [363]. Diuretics are frequently prescribed to older people for managing hypertension or fluid retention associated with conditions including heart failure, liver cirrhosis, or renal failure. Loop diuretics (furosemide, bumetanide) are particularly beneficial for acute symptom relief in people with fluid overload due to heart failure [364].

As mentioned in the 'Digoxin/Sotalol' section, the management of heart failure has advanced over the past decade. The 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America guideline for the management of heart failure recommends guideline-directed medical therapy (GDMT) for people with heart failure and reduced ejection fraction (HFrEF) [283]. The GDMT, also known as the “four pillars”, includes a renin-angiotensin system inhibitor, a heart-failure specific beta-blocker, a mineralocorticoid receptor antagonist and a sodium-glucose cotransporter 2 inhibitor, as the four main recommended drug treatment regimens for HFrEF. This quadruple therapy is recommended as the regimen for HFrEF due to its demonstrated benefits in reducing morbidity and mortality [284].

Long-term diuretic use has been linked to increased mortality in individuals with heart failure [365]. Diuretics are also among the leading drug classes associated with medicine-related hospital admissions in older people [366]. It is crucial to consider the underlying indication for diuretic use to identify people who may benefit from deprescribing.

The use of diuretics in older people requires careful monitoring as they are more susceptible to electrolyte imbalances (hyponatraemia, hypokalaemia and hyperkalaemia) and orthostatic hypotension [177]. The potential for drug-drug interactions should be emphasised, particularly considering the high prevalence of multimorbidity in the older population and that existing treatment guidelines are often disease-specific [367]. One common concern in the context of diuretics is the 'triple whammy,' which refers to the co-administration of ACE inhibitors or ARBs diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs). This combination increases the risk of acute kidney injury [368]. Older people with pre-existing renal impairment are particularly vulnerable to the adverse effects of the 'triple whammy'. The New Zealand Health Quality and Safety Commission reported that 3.2% of people aged 65 and over, or approximately 25,000 individuals, were dispensed with this combination within a 90-day period in 2019 [369]. This indicator may be underrepresented as people who purchased and used NSAIDs over the counter were not included in the data.

Refer to the narrative evidence summary, the GRADE Summary of Findings table in the guidelines, and the Technical Report for a complete presentation of the deprescribing evidence based on the GRADE framework (including other factors considered in developing the recommendations).

The primary goal of diuretic therapy is to achieve euvolaemia [370]. Once euvolaemia is reached, the necessity for long-term diuretic therapy should be reassessed, especially in asymptomatic or minimally symptomatic individuals, and deprescribing should be considered when appropriate. Prolonged use of diuretics can lead to diuretic resistance and rebound oedema upon discontinuation [371, 372].

Unlike GDMT for heart failure, long-term use of furosemide is associated with increased mortality in older people, and its use should be limited to people with evidence of fluid overload [373]. Despite this, loop diuretics are often overprescribed in older people [374, 375]. Deprescribing should be considered when appropriate criteria are met, such as the suitability of alternative GDMT agents or the absence of a clear indication for continued use. Deprescribing should be prioritised in individuals experiencing known adverse drug effects associated with diuretics, such as hyponatraemia with furosemide and thiazide, and gout with loop or thiazide diuretics. In contrast, individuals taking aldosterone antagonists for heart failure, particularly those with reduced ejection fraction (HFrEF), should likely continue therapy due to strong evidence supporting their role in improving mortality and reducing hospitalisations, independent of their diuretic effect [376].

While the benefits of aldosterone antagonists in heart failure with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) are less clear, some evidence suggests that these agents, especially non-steroidal mineralocorticoid receptor antagonist finerenone, may reduce cardiovascular mortality or heart failure-related hospitalisation [377, 378]. Additionally, finerenone has been shown to significantly reduce the progression of chronic kidney disease and cardiovascular events in people with chronic kidney disease and type 2 diabetes [379].

Deprescribing of inappropriate prescribing cascade should be considered. A common example of a prescribing cascade involves lower extremity oedema, which may occur as a side effect of a calcium channel blocker. Rather than discontinuing the causative medicine, a diuretic is often added [230]. If potassium supplements are being used alongside thiazide or loop diuretics, they should also be adjusted in coordination with any changes to the diuretic therapy to avoid the continuation of a 'relic' of prior prescribing.

Deprescribing may also be appropriate when the potential benefits of a medicine are outweighed by the risk of harm. This is particularly relevant when precautions are necessary for continued use or when contraindications are present, as the risk of harm may be inherently higher, especially in older people.

Loop diuretics account for the retention of up to 25% of filtered sodium and are more potent diuretics than thiazide diuretics [380]. In the context of diuretics used for oedema, when a thiazide and loop diuretic are used in combination, it may be appropriate to first attempt deprescribing the thiazide diuretic as it may associated with a comparatively lower risk of symptom recurrence.

We identified seven studies (five RCTs and two before-and-after studies) related to diuretics deprescribing from the systematic review and meta-analysis [381-387].

Overall, the current evidence from available studies is of low and very low certainty. Deprescribing diuretics may lead to peripheral oedema and an increase in blood pressure. In people without a current indication of heart failure or hypertension, the majority were able to stop diuretics without serious adverse events and symptom recurrence. There was also no significant difference in mortality compared to those who continued treatment. However, there is a lack of quality evidence to inform evidence-based recommendations.

It may be appropriate to monitor fluid status (e.g. changes in body weight), serum potassium, renal function (including blood urea nitrogen, serum creatinine, and eGFR), blood pressure, and if applicable, symptoms of heart failure during dose tapering and after discontinuation. When encouraging individuals to self-monitor, it may be helpful to provide concrete examples of symptoms (e.g. swollen ankles) to improve recognition and reporting. Since many symptoms are non-specific, individuals may not realise they could signal the worsening of an underlying condition.

For potassium-sparing diuretics, it may also be necessary to review and adjust other medications and/or lifestyle factors that influence potassium levels, in coordination with any changes to the diuretic regimen.

Various methods were used for deprescribing in the included studies and there was no direct evidence that any particular method was associated with the greatest benefits and harms. However, compared to abrupt cessation, dose tapering is likely more acceptable and helpful in determining the lowest effective dose for some people requiring dose reduction rather than complete cessation. Tapering, if required, may be undertaken by reducing the dose by 50% every one to two weeks depending on the baseline dose.