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Domenic A. Sica - One of the best experts on this subject based on the ideXlab platform.
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Diuretics for the Treatment of Hypertension
Pathophysiology and Pharmacotherapy of Cardiovascular Disease, 2015Co-Authors: Domenic A. SicaAbstract:Diuretics are agents commonly used in diseases characterized by excess extracellular fluid, including chronic kidney disease, nephrotic syndrome, cirrhosis, and heart failure. Diuretics are also commonly used either as monotherapy or in combination with other antihypertensive agents in the management of hypertension. Multiple diuretic classes, including thiazide-type Diuretics, loop Diuretics, and potassium-sparing Diuretics, are used to treat patients with these diseases. An understanding of what determines a patient’s response to a diuretic is a prerequisite to the correct use of these drugs. The response of patients with these diseases to Diuretics, which is related to the dose, is best described by a sigmoid curve whose contour can become distorted by any of the several sodium-retaining states that are directly or indirectly associated with renal disease. The pharmacodynamic effect of Diuretics as used in the treatment of hypertension involves both a volume removal element and more long-term vasodilation. Diuretic actions are of considerable importance to patients who have renal disease, as their effective use assists in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia. Diuretic-related adverse events that involve the uric acid, sodium, and potassium axes are not uncommon; therefore, the clinician must be vigilant in looking for biochemical disturbances. As a result of diuretic-related adverse events, clinicians must be resourceful in the dose amount and frequency of dosing.
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Diuretic use in renal disease
Nature Reviews Nephrology, 2012Co-Authors: Domenic A. SicaAbstract:Diuretics are agents commonly used in diseases characterized by excess extracellular fluid, including chronic kidney disease, the nephrotic syndrome, cirrhosis and heart failure. Multiple diuretic classes, including thiazide-type Diuretics, loop Diuretics and K^+-sparing Diuretics, are used to treat patients with these diseases, either individually or as combination therapies. An understanding of what determines a patient's response to a diuretic is a prerequisite to the correct use of these drugs. The response of patients with these diseases to Diuretics, which is related to the dose, is best described by a sigmoid curve whose contour can become distorted by any of the several sodium-retaining states that are directly or indirectly associated with renal disease. Diuretic actions are of considerable importance to patients who have renal disease, as their effective use assists in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia. Diuretic-related adverse events that involve the uric acid, Na^+ and K^+ axes are not uncommon; therefore the clinician must be vigilant in looking for biochemical disturbances. As a result of diuretic-related adverse events, clinicians must be resourceful in the dose amount and frequency of dosing. Diuretics are commonly used in the treatment of patients with chronic kidney disease. However, many questions remain regarding this practice, such as how best to combine Diuretics and whether loop Diuretics can be used in patients on hemodialysis. In this Review, Dominic Sica addresses these and other important questions surrounding the use of Diuretics in patients with renal disease. Diuretic therapy is mainly used in renal disease to facilitate extracellular fluid volume control, lessen the tendency to develop hyperkalemia and lower blood pressure The response to a loop diuretic is optimized by a clinically relevant time course of urinary drug delivery; a number of aspects of renal failure alter this relationship Although thiazide-type Diuretics can elicit a response in patients with a glomerular filtration rate
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Diuretic use in renal disease
Nature Reviews Nephrology, 2012Co-Authors: Domenic A. SicaAbstract:Diuretics are agents commonly used in diseases characterized by excess extracellular fluid, including chronic kidney disease, the nephrotic syndrome, cirrhosis and heart failure. Multiple diuretic classes, including thiazide-type Diuretics, loop Diuretics and K^+-sparing Diuretics, are used to treat patients with these diseases, either individually or as combination therapies. An understanding of what determines a patient's response to a diuretic is a prerequisite to the correct use of these drugs. The response of patients with these diseases to Diuretics, which is related to the dose, is best described by a sigmoid curve whose contour can become distorted by any of the several sodium-retaining states that are directly or indirectly associated with renal disease. Diuretic actions are of considerable importance to patients who have renal disease, as their effective use assists in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia. Diuretic-related adverse events that involve the uric acid, Na^+ and K^+ axes are not uncommon; therefore the clinician must be vigilant in looking for biochemical disturbances. As a result of diuretic-related adverse events, clinicians must be resourceful in the dose amount and frequency of dosing. Diuretic therapy is mainly used in renal disease to facilitate extracellular fluid volume control, lessen the tendency to develop hyperkalemia and lower blood pressure The response to a loop diuretic is optimized by a clinically relevant time course of urinary drug delivery; a number of aspects of renal failure alter this relationship Although thiazide-type Diuretics can elicit a response in patients with a glomerular filtration rate
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Diuretic use in renal disease
Nature reviews. Nephrology, 2011Co-Authors: Domenic A. SicaAbstract:Diuretics are agents commonly used in diseases characterized by excess extracellular fluid, including chronic kidney disease, the nephrotic syndrome, cirrhosis and heart failure. Multiple diuretic classes, including thiazide-type Diuretics, loop Diuretics and K(+)-sparing Diuretics, are used to treat patients with these diseases, either individually or as combination therapies. An understanding of what determines a patient's response to a diuretic is a prerequisite to the correct use of these drugs. The response of patients with these diseases to Diuretics, which is related to the dose, is best described by a sigmoid curve whose contour can become distorted by any of the several sodium-retaining states that are directly or indirectly associated with renal disease. Diuretic actions are of considerable importance to patients who have renal disease, as their effective use assists in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia. Diuretic-related adverse events that involve the uric acid, Na(+) and K(+) axes are not uncommon; therefore the clinician must be vigilant in looking for biochemical disturbances. As a result of diuretic-related adverse events, clinicians must be resourceful in the dose amount and frequency of dosing.
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chlorthalidone has it always been the best thiazide type diuretic
Hypertension, 2006Co-Authors: Domenic A. SicaAbstract:Modern diuretic therapy evolved from 2 seemingly unrelated events in the 1930s: the development of sulfanilamide, the first truly effective antibacterial agent, and the description of the enzyme carbonic anhydrase. Sulfanilamide was observed to increase sodium (Na+)/potassium and water excretion by inhibition of carbonic anhydrase activity. Recognition of this action proved the impetus for synthesis of compounds, such as acetazolamide, that could more specifically inhibit carbonic anhydrase; however, acetazolamide was a short-acting compound, and Diuretics with greater potency and/or duration of action were quickly sought. Chlorothiazide was the first of these new-generation Diuretics, and its introduction in 1957 set the modern era of diuretic therapy in motion. Shortly thereafter several loop Diuretics and a host of thiazide-type Diuretics found their way to the marketplace as the result of active development programs. As Diuretics began to proliferate in numbers, loop Diuretics were promptly distinguished from thiazide-type Diuretics on the basis of potency and were quickly slotted as the more important diuretic class for volume overload states. Thiazide-type Diuretics were early on seen as agents with greater effectiveness in reducing blood pressure (BP), but with a lesser ability to impact volume overload states. In the early days of thiazide-type diuretic use there was little effort expended to seriously distinguish one from the other in their BP-lowering effect even if there were major intraclass pharmacokinetic differences. Inexorably, the term “class effect” crept in to describe the actions of thiazide-type Diuretics, applied both to BP reduction and ultimately outcomes. Much of the recent debate on diuretic class effect has centered on the similarities and differences between chlorthalidone …
Arno W. Hoes - One of the best experts on this subject based on the ideXlab platform.
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Non-potassium-sparing Diuretics and risk of sudden cardiac death.
Journal of Hypertension, 1995Co-Authors: Diederick E. Grobbee, Arno W. HoesAbstract:Objective : To review current evidence for a possible association between the use of non-potassium-sparing Diuretics and the risk of sudden cardiac death in hypertension. Methods : Examination of published randomized trials and recent case-control studies. Results : Numerous studies have shown that the administration of non-potassium-sparing Diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between Diuretics and sudden death. Published randomized trials on the efficacy of non-potassium-sparing diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including potassium-sparing diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-potassium-sparing Diuretics had approximately double the risk of sudden cardiac death compared with users of potassium-sparing diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. Conclusions : Current evidence supports the hypothesis that diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide Diuretics at a low dose only. Adding a potassium-sparing diuretic drug may further reduce the mortality risk.
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Non-potassium-sparing Diuretics and risk of sudden cardiac death.
Journal of hypertension, 1995Co-Authors: Diederick E. Grobbee, Arno W. HoesAbstract:To review current evidence for a possible association between the use of non-potassium-sparing Diuretics and the risk of sudden cardiac death in hypertension. Examination of published randomized trials and recent case-control studies. Numerous studies have shown that the administration of non-potassium-sparing Diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between Diuretics and sudden death. Published randomized trials on the efficacy of non-potassium-sparing diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including potassium-sparing diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-potassium-sparing Diuretics had approximately double the risk of sudden cardiac death compared with users of potassium-sparing diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. Current evidence supports the hypothesis that diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide Diuretics at a low dose only. Adding a potassium-sparing diuretic drug may further reduce the mortality risk.
Kevin Damman - One of the best experts on this subject based on the ideXlab platform.
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Reduced Diuretic Dose in Patients Treated With Eplerenone: Data From the EPHESUS Trial
Circulation. Heart failure, 2020Co-Authors: Joao Pedro Ferreira, Kevin Damman, Romain Eschalier, Kévin Duarte, Finn Gustafsson, Morten Schou, Nicolas Girerd, Renaud Fay, Stéphane Tala, Bertram PittAbstract:Background: Loop-Diuretics are used for congestion relief and dose-adaptations are usually a consequence of the clinicians` clinical judgement about the congestive status of the patient. In EPHESUS (Eplerenone in Patients with Systolic Dysfunction after Myocardial Infarction) many of the patients had heart failure (HF) requiring Diuretics for congestion relief. We thus hypothesized that blinded allocation to eplerenone would lead clinicians to reduce loop Diuretics, as consequence of the improvement in patients` status. Aims: To study the effect of eplerenone on the diuretic doses during the follow-up, and its prognostic implications. Methods: Cox and mixed effect models were used over a median follow-up of 1.3 years in 6632 patients. Results: A total of 6632 patients were included; at baseline 3352 (50.5%) did not have Diuretics, 2195 (33.1%) had diuretic doses between 1 and 40 mg/day, and 1085 (16.4%) had diuretic doses above 40 mg/day. Patients with higher furosemide equivalent doses had a worse clinical status. Both baseline and follow-up incremental loop diuretic doses were associated with worse prognosis. Eplerenone treatment was associated with lower prescribed loop diuretic doses throughout the follow-up; lower doses were observed at 90 days, and decreased further at 180 days and beyond. Eplerenone treatment led to a mean furosemide equivalent dose reduction of -2.2 mg/day (-2.9 to -1.6) throughout the follow-up. Eplerenone was effective in reducing morbidity and mortality regardless of the baseline loop diuretic dose used: HR (95%CI) for the outcome of cardiovascular death or HF hospitalization =0.83 (0.75-0.92); p for interaction =0.54. Conclusion: Eplerenone treatment led to a loop diuretic dose reduction during follow-up without evidence of treatment effect modification by loop Diuretics. These findings suggest that eplerenone reduces congestive signs and symptoms, which enables clinicians to reduce loop diuretic doses.
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higher doses of loop Diuretics limit uptitration of angiotensin converting enzyme inhibitors in patients with heart failure and reduced ejection fraction
Clinical Research in Cardiology, 2020Co-Authors: Jozine Ter Maaten, Kevin Damman, Pieter Martens, Kenneth Dickstein, Piotr Ponikowski, Stefan D Anker, Chim C Lang, Nilesh J SamaniAbstract:Loop Diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin–angiotensin system. Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score. Baseline median loop diuretic dose was 40 [40–100] mg of furosemide or equivalent. Higher doses of loop Diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA use, and lower doses of ACEi reached at 3 and 9 months (all P < 0.01). After propensity adjustment, higher doses of loop Diuretics remained significantly associated with poorer uptitration of ACEi (Beta per log doubling of loop diuretic dose: − 1.66, P = 0.021), but not with uptitration of MRAs (P = 0.758). Higher doses of loop Diuretics were independently associated with an increased risk of all-cause mortality or HF hospitalization [HR per doubling of loop diuretic dose: 1.06 (1.01–1.12), P = 0.021]. Higher doses of loop Diuretics limited uptitration of ACEi in patients with HFrEF and were associated with a higher risk of death and/or HF hospitalization, independent of their lower likelihood of uptitration and higher baseline risk. This figure was created with images adapted from Servier Medical Art licensed under a Creative Commons Attribution 3.0
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Higher doses of loop Diuretics limit uptitration of angiotensin-converting enzyme inhibitors in patients with heart failure and reduced ejection fraction
Clinical Research in Cardiology, 2020Co-Authors: Jozine Ter Maaten, Kevin Damman, Pieter Martens, Kenneth Dickstein, Piotr Ponikowski, Chim Lang, Stefan D Anker, Nilesh J Samani, Gerasimos Filippatos, John ClelandAbstract:Background: Loop Diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin-angiotensin system. Methods: Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score. Results: Baseline median loop diuretic dose was 40 [40-100] mg of furosemide or equivalent. Higher doses of loop Diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA use, and lower doses of ACEi reached at 3 and 9 months (all P < 0.01). After propensity adjustment, higher doses of loop Diuretics remained significantly associated with poorer uptitration of ACEi (Beta per log doubling of loop diuretic dose: - 1.66, P = 0.021), but not with uptitration of MRAs (P = 0.758). Higher doses of loop Diuretics were independently associated with an increased risk of all-cause mortality or HF hospitalization [HR per doubling of loop diuretic dose: 1.06 (1.01-1.12), P = 0.021]. Conclusions: Higher doses of loop Diuretics limited uptitration of ACEi in patients with HFrEF and were associated with a higher risk of death and/or HF hospitalization, independent of their lower likelihood of uptitration and higher baseline risk.
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the use of Diuretics in heart failure with congestion a position statement from the heart failure association of the european society of cardiology
Почки - Počki, 2019Co-Authors: Wilfried Mullens, Kevin Damman, Pieter Martens, W Wilson H Tang, Velipekka Harjola, Alexandre Mebazaa, Hanspeter Brunnerla Rocca, Jeffrey M Testani, Francesco Orso, Patrick RossignolAbstract:The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of Diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of Diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion.
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Diuretic response in acute heart failure—pathophysiology, evaluation, and therapy
Nature Reviews Cardiology, 2015Co-Authors: Jozine M. Ter Maaten, Mattia A.e. Valente, Kevin Damman, Hans L. Hillege, Gerjan Navis, Adriaan A. VoorsAbstract:The administration of loop Diuretics to achieve decongestion is the cornerstone of therapy for acute heart failure. Unfortunately, impaired response to Diuretics is common in these patients and associated with adverse outcomes. Diuretic resistance is thought to result from a complex interplay between cardiac and renal dysfunction, and specific renal adaptation and escape mechanisms, such as neurohormonal activation and the braking phenomenon. However, our understanding of diuretic response in patients with acute heart failure is still limited and a uniform definition is lacking. Three objective methods to evaluate diuretic response have been introduced, which all suggest that diuretic response should be determined based on the effect of diuretic dose administered. Several strategies have been proposed to overcome diuretic resistance, including combination therapy and ultrafiltration, but prospective studies in patients who are truly unresponsive to Diuretics are lacking. An enhanced understanding of diuretic response should ultimately lead to an improved, individualized approach to treating patients with acute heart failure. Resistance to diuretic therapy to achieve decongestion is common in patients with acute heart failure. In this Review, ter Maaten and colleagues describe the pathophysiology and mechanisms of diuretic resistance, how to evaluate diuretic response, and propose a treatment strategy for patients with acute heart failure who are diuretic resistant. The administration of loop Diuretics to achieve decongestion is the cornerstone of therapy for acute heart failure Impaired diuretic response is a common complication in patients with acute heart failure and is associated with increased rehospitalization and mortality compared with patients who have normal diuretic response Impaired absorption, decreased renal blood flow, azotaemia, hypoalbuminaemia, and proteinuria result in reduced levels of active Diuretics in the tubular lumen, and diminish diuretic effectiveness Several treatment strategies, including increased dose of intravenous loop Diuretics, combination therapy, and ultrafiltration, aim to improve biological availability of the drugs and counteract maladaptive responses in diuretic-resistant patients Quantitative measures of diuretic response have been proposed, but need to be validated in larger populations of patients with acute heart failure An enhanced understanding of diuretic response should ultimately lead to improved individualized approaches to treating patients with acute heart failure
John J V Mcmurray - One of the best experts on this subject based on the ideXlab platform.
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reduced loop diuretic use in patients taking sacubitril valsartan compared with enalapril the paradigm hf trial
European Journal of Heart Failure, 2019Co-Authors: Orly Vardeny, Jessica Kachadourian, Brian Claggett, Akshay S. Desai, Milton Packer, Martin P Lefkowitz, Karl Swedberg, Michael R Zile, John J V McmurrayAbstract:Aims: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM‐HF) trial. Methods and results: Overall, 8399 patients with New York Heart Association class II–IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any Diuretics (n = 6290 for loop Diuretics, n = 496 for other Diuretics); of those, recorded dosage data for loop Diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post‐randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on‐treatment analysis. Conclusion: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop Diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.
Orly Vardeny - One of the best experts on this subject based on the ideXlab platform.
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reduced loop diuretic use in patients taking sacubitril valsartan compared with enalapril the paradigm hf trial
European Journal of Heart Failure, 2019Co-Authors: Orly Vardeny, Jessica Kachadourian, Brian Claggett, Akshay S. Desai, Milton Packer, Martin P Lefkowitz, Karl Swedberg, Michael R Zile, John J V McmurrayAbstract:Aims: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM‐HF) trial. Methods and results: Overall, 8399 patients with New York Heart Association class II–IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any Diuretics (n = 6290 for loop Diuretics, n = 496 for other Diuretics); of those, recorded dosage data for loop Diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post‐randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on‐treatment analysis. Conclusion: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop Diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.
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Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.
'Wiley', 2019Co-Authors: Orly Vardeny, Claggett Brian, Kachadourian Jessica, Desai, Akshay S., Packer Milton, Rouleau Jean, Zile, Michael R., Swedberg Karl, Lefkowitz Martin, Shi VictorAbstract:Aims: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM‐HF) trial. Methods and results: Overall, 8399 patients with New York Heart Association class II–IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any Diuretics (n = 6290 for loop Diuretics, n = 496 for other Diuretics); of those, recorded dosage data for loop Diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post‐randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on‐treatment analysis. Conclusion: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop Diuretics relative to enalapril in patients with heart failure with reduced ejection fraction