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The American Journal of Medicine Jan 2024Apparent resistant hypertension, defined as uncontrolled office blood pressure despite ≥ 3 antihypertensive medications including a diuretic or use of ≥ 4... (Review)
Review
Apparent resistant hypertension, defined as uncontrolled office blood pressure despite ≥ 3 antihypertensive medications including a diuretic or use of ≥ 4 medications regardless of blood pressure, occurs in ≤ 15% of treated hypertensives. Apparent refractory hypertension, defined as uncontrolled office pressure despite use of 5 or more medications including a diuretic, occurs in ≤ 10% of resistant cases. Both are associated with increased comorbidity and enhanced cardiovascular risk. To rule out pseudo-resistant or pseudo-refractory hypertension, employ guideline-based methodology for obtaining pressure, maximize the regimen, rule out white-coat effect, and assess adherence. True resistant hypertension is characterized by volume overload and aldosterone excess, refractory by enhanced sympathetic tone. Spironolactone is the preferred agent for resistance, with lower doses. Spironolactone, potassium binders, or both, are preferred if the estimated glomerular filtration rate is below 45. If significant albuminuria, finerenone is indicated. The optimal treatment of refractory hypertension is unclear, but sympathetic inhibition (α-β blockade, centrally acting sympathoinhibitors, or both) seems reasonable. Renal denervation has shown minimal benefit for resistance, but its role in refractory hypertension remains to be defined.
Topics: Humans; Spironolactone; Hypertension; Antihypertensive Agents; Blood Pressure; Diuretics; Blood Pressure Monitoring, Ambulatory
PubMed: 37832756
DOI: 10.1016/j.amjmed.2023.09.015 -
Reviews in Cardiovascular Medicine Dec 2021Hospitalization for congestive heart failure represents a growing burden for health care systems. Heart failure is characterized by extracellular fluid overload and loop... (Review)
Review
Hospitalization for congestive heart failure represents a growing burden for health care systems. Heart failure is characterized by extracellular fluid overload and loop diuretics have been for decades the cornerstone of therapy in these patients. However, extensive use of intra-venous diuretics is characterised by several limitations: risk of worsening renal function and electrolyte imbalance, symptomatic hypotension and development of diuretic resistance. Extracorporealveno-venous ultrafiltration (UF) represents an interesting adjunctive therapy to target congestion in patients with heart failure and fluid overload. UF consists of the mechanical removal of iso-tonic plasma water from the blood through a semipermeable membrane using a pressure gradient generated by a pump. Fluid removal through UF presents several advantages such as removal of higher amount of sodium, predictable effect, limited neuro-hormonal activation, and enhanced spontaneous diuresis and diuretic response. After twenty years of "early" studies, since 2000 some pilot studies and randomized clinical trials with modern devices have been carried out with somehow conflicting results, as discussed in this review. In addition, some practical aspects of UF are addressed.
Topics: Diuretics; Heart Failure; Hospitalization; Humans; Ultrafiltration; Water-Electrolyte Imbalance
PubMed: 34957772
DOI: 10.31083/j.rcm2204137 -
Journal of Cardiac Failure Apr 2021Identifying patients at risk of poor diuretic response in acute heart failure (AHF) is critical to make prompt adjustments in therapy. The objective of this study was to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Identifying patients at risk of poor diuretic response in acute heart failure (AHF) is critical to make prompt adjustments in therapy. The objective of this study was to investigate whether the circulating levels of soluble ST2 predict the cumulative diuretic efficiency (DE) at 24 and 72 hours in patients with AHF and concomitant renal dysfunction.
METHODS AND RESULTS
This is a post hoc analysis of the IMPROVE-HF trial, in which we enrolled 160 patients with AHF and renal dysfunction (estimated glomerular filtrate rate of <60 mL/min/1.73 m). DE was calculated as the net fluid output produced per 40 mg of furosemide equivalents. The association between sST2 and DE was evaluated by using multivariate linear regression analysis. The median cumulative DE at 24 and 72 hour was 747 mL (interquartile range 490-1167 mL) and 1844 mL (interquartile range 1142-2625 mL), respectively. The median sST2 and mean estimated glomerular filtrate rate were 72 ng/mL (interquartile range 47-117 ng/mL), and 34.0 ± 8.5 mL/min/1.73 m, respectively. In a multivariable setting, higher sST2 were significant and nonlinearly related to lower DE both at 24 and 72 hours (P = .002 and P = .019, respectively).
CONCLUSIONS
In patients with AHF and renal dysfunction at presentation, circulating levels of sST2 were independently and negatively associated with a poor diuretic response, both at 24 and 72 hours.
Topics: Acute Disease; Diuretics; Furosemide; Heart Failure; Humans; Kidney Diseases
PubMed: 33038531
DOI: 10.1016/j.cardfail.2020.10.002 -
European Heart Journal Jun 2023Acetazolamide inhibits proximal tubular sodium and bicarbonate re-absorption and improved decongestive response in acute heart failure in the ADVOR trial. It is unknown... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Acetazolamide inhibits proximal tubular sodium and bicarbonate re-absorption and improved decongestive response in acute heart failure in the ADVOR trial. It is unknown whether bicarbonate levels alter the decongestive response to acetazolamide.
METHODS AND RESULTS
This is a sub-analysis of the randomized, double-blind, placebo-controlled ADVOR trial that randomized 519 patients with acute heart failure and volume overload in a 1:1 ratio to intravenous acetazolamide (500 mg/day) or matching placebo on top of standardized intravenous loop diuretics (dose equivalent of twice oral maintenance dose). The primary endpoint was complete decongestion after 3 days of treatment (morning of day 4). Impact of baseline HCO3 levels on the treatment effect of acetazolamide was assessed. : Of the 519 enrolled patients, 516 (99.4%) had a baseline HCO3 measurement. Continuous HCO3 modelling illustrated a higher proportional treatment effect for acetazolamide if baseline HCO3 ≥ 27 mmol/l. A total of 234 (45%) had a baseline HCO3 ≥ 27 mmol/l. Randomization towards acetazolamide improved decongestive response over the entire range of baseline HCO3- levels (P = 0.004); however, patients with elevated baseline HCO3 exhibited a significant higher response to acetazolamide [primary endpoint: no vs. elevated HCO3; OR 1.37 (0.79-2.37) vs. OR 2.39 (1.35-4.22), P-interaction = 0.065), with higher proportional diuretic and natriuretic response (both P-interaction < 0.001), greater reduction in congestion score on consecutive days (treatment × time by HCO3-interaction <0.001) and length of stay (P-interaction = 0.019). The larger proportional treatment effect was mainly explained by the development of diminished decongestive response in the placebo arm (loop diuretics only), both with regard to reaching the primary endpoint of decongestion as well as reduction in congestion score. Development of elevated HCO3 further worsened decongestive response in the placebo arm (P-interaction = 0.041). A loop diuretic only strategy was associated with an increase in the HCO3 during the treatment phase which was prevented by acetazolamide (day 3: placebo 74.8% vs. acetazolamide 41.3%, P < 0.001).
CONCLUSION
Acetazolamide improves decongestive response over the entire range of HCO3- levels; however, the treatment response is magnified in patients with baseline or loop diuretic-induced elevated HCO3 (marker of proximal nephron NaHCO3 retention) by specifically counteracting this component of diuretic resistance.
Topics: Humans; Acetazolamide; Sodium Potassium Chloride Symporter Inhibitors; Bicarbonates; Diuretics; Heart Failure; Treatment Outcome
PubMed: 37138385
DOI: 10.1093/eurheartj/ehad236 -
Revue Medicale Suisse Jan 2021Several studies published in 2020 showed new data supporting the prescription of statins in some old and very old patients. Despite the enthusiasm about SGLT-2... (Review)
Review
Several studies published in 2020 showed new data supporting the prescription of statins in some old and very old patients. Despite the enthusiasm about SGLT-2 inhibitors, caution must remain in frail and dependent older diabetic patients who are not well represented in most studies. Antihypertensive treatment appears more beneficial when taken at night rather than in the morning but beware of the prescribing cascade of a diuretic when a new prescription of a calcium channel blocker. Biomarkers, including plasmatic biomarkers, are becoming increasingly important in the diagnostic strategy of neurocognitive disorders. Finally, fall prevention studies showed heterogeneous results but multimodal interventions remain mainstream.
Topics: Aged; Antihypertensive Agents; Calcium Channel Blockers; Diuretics; Geriatrics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension
PubMed: 33443828
DOI: No ID Found -
American Journal of Cardiovascular... Nov 2021The inpatient treatment of acute heart failure (AHF) is aimed at achieving euvolemia, relieving symptoms, and reducing rehospitalization. Adequate treatment of AHF is... (Review)
Review
The inpatient treatment of acute heart failure (AHF) is aimed at achieving euvolemia, relieving symptoms, and reducing rehospitalization. Adequate treatment of AHF is rooted in understanding the pharmacokinetics and pharmacodynamics of select diuretic agents used to achieve decongestion. While loop diuretics remain the primary treatment of AHF, the dosing strategies of loop diuretics and the use of adjunct diuretic classes to augment clinical response can be complex. This review examines the latest strategies for diuretic management in patients with AHF, including dosing and monitoring strategies, interaction of diuretics with other medication classes, use adjunctive therapies, and assessing endpoints for diuretic. The goal of the review is to guide the reader through commonly encountered clinical scenarios and pitfalls in the diuretic management of patients with AHF.
Topics: Diuretics; Heart Failure; Humans; Inpatients; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 33709346
DOI: 10.1007/s40256-020-00463-5 -
American Journal of Physiology. Renal... Sep 2022Loop diuretics are commonly used diuretics in the treatment of fluid retention but induce hypovolemia-related renal dysfunction. Na-glucose cotransporter 2 (SGLT2)...
Loop diuretics are commonly used diuretics in the treatment of fluid retention but induce hypovolemia-related renal dysfunction. Na-glucose cotransporter 2 (SGLT2) inhibitors induce osmotic diuresis, but body fluid volume is maintained by stimulating vasopressin-induced fluid intake and collecting duct water reabsorption as previously reported in diabetic rats. We aimed to test the hypothesis that unlike SGLT2 inhibitors, loop diuretics lack activation of similar fluid homeostatic mechanisms. Nondiabetic male Sprague-Dawley rats were treated daily by oral gavage with vehicle, the SGLT2 inhibitor ipragliflozin (5 mg/kg), or the loop diuretic furosemide (50 mg/kg) and monitored in metabolic cages for 2 or 7 days. Ipragliflozin and furosemide similarly increased urine volume on . This was associated with increased serum Na concentration, urine vasopressin excretion, fluid intake, and solute-free water reabsorption in response to ipragliflozin but not to furosemide. Ipragliflozin maintained fluid balance (fluid intake - urine volume) on and total body water measured by bioimpedance spectroscopy and serum creatinine on . In comparison, furosemide decreased fluid balance on and decreased total body water and increased serum creatinine on . Furosemide, but not ipragliflozin, increased plasma renin activity, and systolic blood pressure was similar among the groups. In conclusion, the osmotic diuresis of the SGLT2 inhibitor increased serum Na concentration and the vasopressin-related stimulation of fluid intake and renal water retention maintained fluid balance, whereas the loop diuretic did not engage the compensatory vasopressin system. The data suggest differences in vasopressin and fluid homeostatic responses between SGLT2 inhibitors and loop diuretics. In nondiabetic rats, the Na-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin increased vasopressin-related stimulation of fluid intake and free water reabsorption and maintained fluid balance and serum creatinine, whereas the loop diuretic furosemide reduced vasopressin and induced a negative fluid balance followed by a subsequent increase in serum creatinine. This study suggests that differences in vasopressin secretion in response to a SGLT2 inhibitor or loop diuretic may contribute to differences in body fluid status and subsequent renal function.
Topics: Animals; Creatinine; Diabetes Mellitus, Experimental; Diuretics; Furosemide; Glucose; Male; Rats; Rats, Sprague-Dawley; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Vasopressins; Water
PubMed: 35900341
DOI: 10.1152/ajprenal.00070.2022 -
American Journal of Physiology. Renal... Mar 2023Sex differences in renal function and blood pressure have been widely described across many species. Blood pressure dips during sleep and peaks in the early morning....
Sex differences in renal function and blood pressure have been widely described across many species. Blood pressure dips during sleep and peaks in the early morning. Similarly, glomerular filtration rate, filtered electrolyte loads, urine volume, and urinary excretion all exhibit notable diurnal rhythms, which reflect, in part, the regulation of renal transporter proteins by circadian clock genes. That regulation is sexually dimorphic; as such, sex and time of day are not two independent regulators of kidney function and blood pressure. The objective of the present study was to assess the effect of sex and administration time on the natriuretic and diuretic effects of loop, thiazide, and K-sparing diuretics, which are common treatments for hypertension. Loop diuretics inhibit Na-K-2Cl cotransporters on the apical membrane of the thick ascending limb, thiazide diuretics inhibit Na-Cl cotransporters on the distal convoluted tubule, and K-sparing diuretics inhibit epithelial Na channels on the connecting tubule and collecting duct. We simulated Na transporter inhibition using sex- and time-of-day-specific computational models of mouse kidney function. The simulation results highlighted significant sex and time-of-day differences in the drug response. Loop diuretics induced larger natriuretic and diuretic effects during the active phase. The natriuretic and diuretic effects of thiazide diuretics exhibited sex and time-of-day differences, whereas these effects of K-sparing diuretics exhibited a significant time-of-day difference in females only. The kaliuretic effect depended on the type of diuretics and time of administration. The present computational models can be a useful tool in chronotherapy, to tailor drug administration time to match the body's diurnal rhythms to optimize the drug effect. Sex influences cardiovascular disease, and the timing of onset of acute cardiovascular events exhibits circadian rhythms. Kidney function also exhibits sex differences and circadian rhythms. How do the natriuretic and diuretic effects of diuretics, a common treatment for hypertension that targets the kidneys, differ between the sexes? And how do these effects vary during the day? To answer these questions, we conducted computer simulations to assess the effects of loop, thiazide, and K-sparing diuretics.
Topics: Female; Male; Mice; Animals; Diuretics; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Hypertension; Kidney Tubules, Distal; Sodium; Thiazides
PubMed: 36701479
DOI: 10.1152/ajprenal.00296.2022 -
European Heart Journal Jun 2023
Topics: Humans; Diuretics; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Combined Modality Therapy
PubMed: 37082880
DOI: 10.1093/eurheartj/ehad217 -
European Heart Journal Jun 2023
Topics: Humans; Diuretics; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Combined Modality Therapy
PubMed: 37082881
DOI: 10.1093/eurheartj/ehad189