Diuretics
Type | Recommendation |
---|---|
When to deprescribe | |
CBR |
We suggest deprescribing decisions be made in consultation with the person and their GP and/or specialist providers (e.g. cardiologist or nephrologist) to ensure it aligns with their preferences, goals and overall treatment plans. Following shared decision-making, we suggest deprescribing of diuretics be offered to older people with:
|
Ongoing treatment | |
CBR |
We suggest continuing diuretics in older people taking long-term diuretics for persistently symptomatic fluid overload due to cardiac, renal, or liver failure, despite optimal management being in place. |
CBR |
We suggest continuing aldosterone antagonists in people with heart failure, especially if reduced ejection fraction (HFrEF), given their benefit in reducing mortality and hospitalisation. |
CBR |
We suggest continuing finerenone in chronic kidney disease (with albuminuria) in people with type 2 diabetes. |
CBR |
If deprescribing is unsuccessful despite two attempts, we suggest maintaining the lowest effective dose; however, reassessing the need for long-term therapy periodically. |
How to deprescribe | |
CBR |
We suggest for furosemide:
For other diuretics, we suggest tapering the dose with monitoring of fluid status, with daily weight monitoring for potential weight gain following down titration of dosing. For combination of thiazide and loop diuretic, we suggest first tapering thiazide diuretic. |
CBR |
If potassium supplements are being used alongside thiazide or loop diuretics, we suggest adjusting or discontinuing potassium supplements in coordination with any changes to the diuretic therapy. For potassium-sparing diuretics, we suggest reviewing and adjusting other medicines and/or lifestyle factors that affect potassium levels in coordination with any changes to the diuretic therapy. |
Monitoring | |
CBR |
We suggest closely monitoring for blood pressure, signs of exacerbations (e.g. peripheral oedema, signs of heart failure), and changes in body weight weekly during tapering for at least three months following deprescribing. After this initial period, we suggest monthly monitoring for ongoing risk factors for at least three months, followed by monitoring every six months thereafter. If in-person visits are impractical, we suggest advising people to self-monitor blood pressure and body weight at home by using a blood pressure monitor and weighing scales respectively, as well as reporting any significant changes to their healthcare provider as needed. If potassium supplements are being used alongside thiazide or loop diuretics, we suggest monitoring serum potassium levels at one week and two weeks and at least monthly thereafter if the level was outside the normal range when last checked. |
CBR |
When discontinuing or changing the dose of diuretics, we suggest closely monitoring for changes in serum potassium and renal function (blood urea nitrogen, serum creatinine and eGFR). |
CBR, consensus-based recommendation
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 and thiazide diuretics can lead to electrolyte imbalances, exacerbate gout, and may elevate blood glucose levels [330].
Similarly, potassium-sparing diuretics can raise the risk of hyperkalaemia, particularly in individuals with renal impairment [330].
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.
Key study characteristics and results
A narrative summary of each study is provided below, highlighting key characteristics and main findings.
De Jonge 1994 randomised 63 people who were taking diuretics for ankle oedema in an RCT to diuretic discontinuation (n=34) or continuation (n=29) [382]. Exclusion criteria were oedema caused by cardiac, hepatic or renal failure, AF, hepatomegaly, or if the diuretics were used for hypertension. Diuretics were withdrawn in 26/34 (76%) participants in the intervention group with eight participants restarting treatment due to symptoms suggestive of heart failure (n=3), hypertension (n=1), being unwell and developed urinary incontinence (n=1), and withdrew consent (n=3). Participants in the intervention group were more likely to report ADWEs, although this was not statistically significant (OR 8.70, 95% CI 0.45, 168.87). The primary outcome was volumetrically determined ankle oedema (oedema index). Oedema appeared to worsen following medicine withdrawal (peaking in the third week), after which it trended towards baseline levels.
Van Kraaij 2000 randomised 32 people with current heart failure with preserved ejection function (HFpEF) to furosemide withdrawal (n=21) or continuation (n=11) [385]. Inclusion criteria were a daily dose of 20-80mg furosemide, two or more prior symptoms (dyspnoea on exertion or at rest, orthopnoea, paroxysmal nocturnal dyspnoea, or peripheral oedema) and one or more prior signs (jugular venous distension, rales, or radiographic pulmonary congestion). Exclusion criteria were SBP > 170 mmHg, DBP > 90 mmHg, persistent AF, symptoms of angina pectoris, overt congestion, or the presence of significant valvular disease. At the three months follow-up, 16/21 (76%) participants did not require recommencement of diuretic therapy. Three participants in the withdrawal group restarted furosemide for ankle oedema, one participant restarted due to hypertension (> 180/100 mmHg) and the reason was not reported for the remaining participant.
Walma 1997 randomised 202 people who had been taking diuretics for at least six months to continuation (n=100) or placebo (n=102) with a six-month follow-up [387]. Participants were excluded if they had hypertension (> 180/100 mmHg), overt heart failure, previous acute decompensated heart failure, hypercalciuria, nephrotic syndrome, glaucoma, taking a daily dose of > 80mg furosemide, or taking fixed combinations of diuretics with beta-blockers or ACE inhibitors, or with alpha-blocker and vasodilators for hypertension. Deprescribing led to a mean increase of 13.5 (95% CI 9.2, 17.8) mmHg in SBP and 4.6 (95% CI 1.9, 7.3) mmHg in DBP. Restarting diuretics was required in 50/102 (49%) participants in the withdrawal group due to the occurrence of symptoms of heart failure or an increase in blood pressure.
Myers 1982 randomised 77 residents in long-term care facilities who had been taking diuretics for more than three months to diuretic continuation (n=39) or placebo (n=38) with a 12-month follow-up [383]. This study excluded people with concurrent digoxin therapy, clinical evidence of hypertension and heart failure. At 12 months, two participants (5%) in the placebo group had to restart their diuretic therapy for hypertension. Participants in the placebo group had a significantly higher final DBP than participants in the continuation group (MD 4.10, 95% CI 3.05 to 5.15). However, participants in the placebo group also had a higher baseline DBP. Ankle oedema did not differ significantly between the two groups (MD 0.30, 95% CI -1.01 to 1.61). At month three, mortality also did not differ significantly between the two groups (OR 3.20, 95 CI% 0.78 to 13.14).
Burr 1977 conducted an RCT that included 106 inpatients who had been taking diuretics for more than a month, without a history of heart failure in the three months prior, nephrotic syndrome, glaucoma or hypertension [381]. The participants were randomised to placebo (n=54) or continuing diuretic therapy (n=52). At 12 months, there was a slight increase in ankle oedema and blood pressure in the placebo group. In the placebo group, 41 (75%) participants remained off their diuretic at 12 months whereas eight (15%) participants restarted diuretic therapy and two (4%) participants dropped out of the trial. Re-commencement of therapy was required in the eight participants due to heart failure (n=4), peripheral oedema (n=2) and bronchopneumonia (n=1). There were three deaths (6%) in the placebo group caused by haemorrhage from gastric ulcer, colon cancer, or bronchopneumonia, compared to one death (2%) in the continuation group caused by myocardial infarction (OR 3.00, 95% CI 0.30 to 29.81).
Straand 1993 conducted a before-and-after study that included 33 community-dwelling, older people who were receiving a stable dose of diuretic for at least six months. Participants were included if there were no signs of hypertensive end organ damage, New York Heart Association functional class III or IV heart failure and BP ≤ 220/110 mmHg. Deprescribing was successful in 18/33 participants (55%), with the remaining 15 participants (45%) restarting treatment due to sudden cardiovascular events (n=4), heart failure (n=2), peripheral oedema (n=3), hypertension (n=3), anxiety (n=2), malignancy (n=1) [384].
Walma 1993 conducted a before-and-after study that included 15 participants who had been using diuretics for at least six months with satisfactory control of blood pressure (< 165/95 mmHg), and free from overt signs of heart failure [386]. Diuretics were discontinued in all 15 participants. At month six, 6/15 (40%) participants remained without diuretic therapy whereas nine participants (60%) restarted diuretic due to congestive heart failure (n=1), hypertension (n=3), bronchial asthma (n=1), ankle oedema (n=2), and subjective complaints (n=2).
In these two before-and-after studies by Straand 1993 and Walma 1993 (n=48), it was reported that 24-53% experienced recurrence of the underlying condition, 9-13% experienced peripheral oedema, 9-20% became hypertensive, and 6-7% had symptoms of congestive heart failure [384, 386]. In the study by Walma 1993, participants were reported to have a mean increase in body weight of 1.2 kg [386] and subjective withdrawal symptoms were reported in 2/15 (13%) participants. In Straand 1993, life-threatening cardiovascular events were reported in 4/33 (12%) participants (two acute heart failure, one myocardial infarction/stroke, one cerebrovascular stroke), of which three out of four cases occurred four months or later after diuretic withdrawal [384].
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.
In the RCT by Walma 1997, participants with a baseline furosemide dose of 40 mg daily had their dose halved for one week before complete withdrawal; if 80 mg daily, the dose was halved for two weeks (n=202, low certainty) [387]. One RCT (n=32) reported diuretic dose was halved for one week, and then substituted by a placebo; however, the study did not report important or critical outcomes associated with deprescribing [385]. The method of deprescribing was not described in three other RCTs [381-383] and one before-and-after study [384]. In the before-and-after study by Walma 1993, thiazide diuretic and furosemide in daily dosages of < 40 mg were stopped abruptly; furosemide daily dosages of 40 mg were halved for one week before stopping completely (n=15, very low certainty) [386].