Safety and Efficacy of an Auto-Titrating Diuretic Protocol: A Pilot

Griffin, Matthew; Flemming, Johannes; Pattoli, M.; Stewart, B.; Gomez, Nicole; Barnett, J.; Thomas, A.; Wycallis, E.; Struyk, G.; Shamlian, P.; Mahoney, Devin; Ivey‐Miranda, Juan Betuel; Rao, Veena S.; Testani, Jeffrey M.

doi:10.1016/j.cardfail.2019.07.147

Cited by 2 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…for this reason MRAs were originally introduced as potassium-retaining diuretic agents (12). SGLT2 inhibitors reduce glucose (and sodium) reabsorption in the proximal renal tubule and, therefore, also have a diuretic action, among other actions (1,9,10). Because of these distinct renal effects, the interplay between SGLT2 inhibitors and MRAs is potentially complex.…”

Section: Discussionmentioning

confidence: 99%

“…From a safety perspective, MRAs may result in further volume reduction, immediate decline in kidney function when added to a loop or thiazide diuretic, and increase in serum potassium concentration when added to a renin-angiotensin system blocker (5)(6)(7). Therefore, the safety of adding dapagliflozin to 3 other agents acting on volume, sodium, potassium, and glomerular filtration, was uncertain, given the potentially complex renal interactions between these 2 classes of drug (5)(6)(7)(8)(9)(10). Whereas SGLT2 inhibitors act in the proximal tubule, MRAs act in the distal tubule and collecting ducts and, therefore, MRAs might amplify any diuretic action of SGLT2 inhibition (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

“…Therefore, the safety of adding dapagliflozin to 3 other agents acting on volume, sodium, potassium, and glomerular filtration, was uncertain, given the potentially complex renal interactions between these 2 classes of drug (5)(6)(7)(8)(9)(10). Whereas SGLT2 inhibitors act in the proximal tubule, MRAs act in the distal tubule and collecting ducts and, therefore, MRAs might amplify any diuretic action of SGLT2 inhibition (5)(6)(7)(8)(9)(10). Each of SGLT2 inhibitors and MRAs is also believed to affect the renal microcirculation.…”

mentioning

confidence: 99%

“…Although difficult to prove with certainty in humans, SGLT2 inhibitors are thought to cause afferent glomerular arteriolar constriction by enhancing tubulo-glomerular feedback (5)(6)(7)(8)(9)(10). Conversely, MRAs are believed to inhibit the vasoconstrictive action of aldosterone on the glomerular efferent arteriole (8).…”

mentioning

confidence: 99%

“…If correct, these combined actions could lead to a major reduction in intraglomerular pressure and filtration and loss of the ability to autoregulate glomerular filtration rate (GFR), especially in the face of a decrease in arterial (i.e., renal perfusion) pressure. On the other hand, if MRAs exert some of their benefit by augmenting diuresis, there may be less scope for further benefit from this action with SGLT2 inhibitors, if diuresis contributes to their efficacy in HFrEF (5)(6)(7)(8)(9)(10). In view of this potentially complex interplay between SGLT2 inhibition and MRAs, subgroup analysis of the effect of SGLT2 inhibition according to MRA use at baseline was prespecified in DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists

Shen

Kristensen

Bengtsson

et al. 2021

JACC: Heart Failure

View full text Add to dashboard Cite

BACKGROUND MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination.METHODS A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes. RESULTS A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/ IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m 2 ), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction ¼ 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo. CONCLUSIONS Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124)

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists

Shen

Kristensen

Bengtsson

et al. 2021

JACC: Heart Failure

View full text Add to dashboard Cite

show abstract

Pharmacokinetic characteristics and morphometric effects of sodium-glucose contransporter-2 inhibitors in men and women with type 2 diabetes mellitus (literature review and own results)

Прибила

2021

Mìžnarodnij endokrinologìčnij žurnal

View full text Add to dashboard Cite

Background. According to the latest international clinical guidelines, gliflozins — sodium-glucose cotransporter-2 inhibitors — are indicated as oral antidiabetic drugs of second-third-line therapy in type 2 diabetes mellitus. Due to insulin-independent stimulation of glucosuria, gliflozins have extraglycemic effects such as weight loss, improved adipose tissue distribution, better plasma lipid profile, and decreased uricemia that in generally reduce the risk of cardiovascular complications. The purpose of this study was to evaluate the effectiveness of dapagliflozin in the treatment of men and women with type 2 diabetes mellitus with a metabolically unhealthy phenotype. Materials and methods. The study included 17 individuals with diabetes mellitus type 2 (11 men and 6 women), aged 58.0 ± 1.7 years (95% confidence interval 53–62), whose body composition was evaluated by bioelectric impedance using a Tanita analyzer BC-545N (Japan). Patients received therapy with dapagliflozin, antihypertensive and antihyperlipidemic drugs (statins). Results. A three-month use of dapagliflozin in a dose of 10 mg once daily caused a decrease in body mass index, waist circumference, improvement of body composition, in particular a reduction in total body fat (the significance of changes was determined using a paired t-test). No significant changes in muscle and bone mass, body composition, lipid profile, and uricemia level were observed. The group of women, in contrast to men, had a decreased level of visceral fat, which was accompanied by an improvement in the body’s water supply, and a reduction in the estimated metabolic age. Conclusions. Treatment of type 2 diabetes patients with sodium-glucose cotransporter-2 inhibitors for 3 months has reduced the degree of obesity and improved some indices of body composition. Confirmation of this trend can be obtained in further observations.

show abstract

Safety and Efficacy of an Auto-Titrating Diuretic Protocol: A Pilot

Cited by 2 publications

References 0 publications

Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists

Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists

Pharmacokinetic characteristics and morphometric effects of sodium-glucose contransporter-2 inhibitors in men and women with type 2 diabetes mellitus (literature review and own results)

Contact Info

Product

Resources

About