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Revue Medicale Suisse Oct 2023Acute heart failure is a leading cause of hospitalisations with an increasing economic and public health burden. Management of acute heart failure involves the use of... (Randomized Controlled Trial)
Randomized Controlled Trial
Acute heart failure is a leading cause of hospitalisations with an increasing economic and public health burden. Management of acute heart failure involves the use of diuretics to treat congestion and improve morbimortality. Despite current guidelines, numerous patients maintain congestion and often leave the hospital setting with incomplete volume depletion, leading to an increased risk of rehospitalisation. A recent multicentric randomised controlled trial studied the administration of acetazolamide in addition to standard care with loop diuretics in the acute setting. There was a significantly faster decongestion, based on a pragmatic clinical score, with very few side effects.
Topics: Humans; Acetazolamide; Diuretics; Heart Failure; Drug-Related Side Effects and Adverse Reactions; Hospitalization
PubMed: 37878100
DOI: 10.53738/REVMED.2023.19.847.2002 -
Journal of the American Heart... Apr 2024Aldosterone is a steroid hormone that primarily acts through activation of the mineralocorticoid receptor (MR), a nuclear receptor responsible for downstream genomic... (Review)
Review
Aldosterone is a steroid hormone that primarily acts through activation of the mineralocorticoid receptor (MR), a nuclear receptor responsible for downstream genomic regulation. Classically, activation of the MR in the renal tubular epithelium is responsible for sodium retention and volume expansion, raising systemic blood pressure. However, activation of the MR across a wide distribution of tissue types has been implicated in multiple adverse consequences for cardiovascular, cerebrovascular, renal, and metabolic disease, independent of blood pressure alone. Primary aldosteronism, heart failure, and chronic kidney disease are states of excessive aldosterone production and MR activity where targeting MR activation has had clinical benefits out of proportion to blood pressure lowering. The growing list of established and emerging therapies that target aldosterone and MR activation may provide new opportunities to improve clinical outcomes and enhance cardiovascular and renal health.
Topics: Humans; Aldosterone; Blood Pressure; Hyperaldosteronism; Receptors, Mineralocorticoid; Heart; Kidney; Mineralocorticoid Receptor Antagonists; Drug-Related Side Effects and Adverse Reactions; Hypertension
PubMed: 38497438
DOI: 10.1161/JAHA.123.030142 -
Medicina Clinica Jan 2024
Topics: Humans; Diuretics; Heart Failure; Drug Resistance; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 37919121
DOI: 10.1016/j.medcli.2023.10.001 -
Diabetologia Feb 2024The overactivation of the mineralocorticoid receptor (MR) promotes pathophysiological processes related to multiple physiological systems, including the heart,... (Review)
Review
The overactivation of the mineralocorticoid receptor (MR) promotes pathophysiological processes related to multiple physiological systems, including the heart, vasculature, adipose tissue and kidneys. The inhibition of the MR with classical MR antagonists (MRA) has successfully improved outcomes most evidently in heart failure. However, real and perceived risk of side effects and limited tolerability associated with classical MRA have represented barriers to implementing MRA in settings where they have been already proven efficacious (heart failure with reduced ejection fraction) and studying their potential role in settings where they might be beneficial but where risk of safety events is perceived to be higher (renal disease). Novel non-steroidal MRA have distinct properties that might translate into favourable clinical effects and better safety profiles as compared with MRA currently used in clinical practice. Randomised trials have shown benefits of non-steroidal MRA in a range of clinical contexts, including diabetic kidney disease, hypertension and heart failure. This review provides an overview of the literature on the systemic impact of MR overactivation across organ systems. Moreover, we summarise the evidence from preclinical studies and clinical trials that have set the stage for a potential new paradigm of MR antagonism.
Topics: Humans; Diabetic Nephropathies; Heart Failure; Mineralocorticoid Receptor Antagonists; Mineralocorticoids; Naphthyridines; Receptors, Mineralocorticoid
PubMed: 38127122
DOI: 10.1007/s00125-023-06031-1 -
Hypertension (Dallas, Tex. : 1979) Nov 2023Hypertension and osteoporosis are common comorbidities among elderly individuals. Drug therapy has been widely used in clinical practice as the preferred... (Review)
Review
Hypertension and osteoporosis are common comorbidities among elderly individuals. Drug therapy has been widely used in clinical practice as the preferred antihypertensive treatment. Therefore, antihypertensive drugs have become some of the most commonly prescribed drugs in healthcare settings. However, antihypertensive drugs have different effects on bone metabolism. The results of animal and clinical studies on the effects of antihypertensive drugs on osteoporosis or fracture risk are controversial and have aroused widespread concern among clinicians. Recent studies found that angiotensin receptor blockers, selective β-adrenergic receptor blockers, and thiazide diuretics might improve bone trabecular number and bone mineral density by stimulating osteoblast differentiation, reducing osteoclast generation, and other mechanism. Furthermore, nonselective β-adrenergic receptor blockers and dihydropyridine calcium channel blockers were found to have no significant relationship with bone mineral density or bone strength, and α-adrenergic receptor blockers and loop diuretics might increase fracture risk by decreasing bone mineral density. This article aimed to review previous animal experiments, clinical studies, and meta-analyses focusing on the effects of different antihypertensive drugs on bone metabolism, and to provide a new approach for the prevention and treatment of osteoporosis.
Topics: Humans; Aged; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Hypertension; Adrenergic beta-Antagonists; Adrenergic alpha-Antagonists; Fractures, Bone; Osteoporosis; Receptors, Adrenergic, beta; Diuretics
PubMed: 37675564
DOI: 10.1161/HYPERTENSIONAHA.123.21648 -
Journal of the American College of... Apr 2024
Topics: Humans; Diuretics; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38599716
DOI: 10.1016/j.jacc.2024.02.028 -
Current Cardiology Reports Dec 2023Novel non-steroidal mineralocorticoid receptor (MR) antagonists (MRAs) are a new class of drugs blocking adverse MR-mediated effects with an improved benefit-risk... (Review)
Review
PURPOSE OF REVIEW
Novel non-steroidal mineralocorticoid receptor (MR) antagonists (MRAs) are a new class of drugs blocking adverse MR-mediated effects with an improved benefit-risk profile compared to steroidal MRAs. This review will provide information on the preclinical and clinical pharmacology of this new drug class and will discuss their future clinical applications in patients with cardiorenal disease.
RECENT FINDINGS
Non-steroidal MRAs such as esaxerenone, AZD9977, apararenone, ocedurenone (KBP-5074), and finerenone are newly approved or in clinical development for patients with cardiorenal disease including type 2 diabetes (T2D) and chronic kidney disease (CKD), hypertension -/+ CKD or heart failure. Unlike steroidal MRAs, non-steroidal MRAs do not induce sex hormone-related side effects and appear to mediate a lower risk of hyperkalemia while maintaining compelling clinical efficacy. Recently, new data from several clinical trials with non-steroidal MRAs have been published (e.g., FIDELIO-DKD, FIGARO-DKD, ESAX-DN, and BLOCK-CKD), and additional studies are currently underway (e.g., FINEARTS-HF and CLARION-CKD). These data and the clinical scientific basis for the ongoing studies will be discussed. Non-steroidal MRAs have been extensively explored in diabetic kidney disease. Selected candidates of this drug class reduced UACR in patients with varying degrees of CKD and T2D and have shown convincing cardiorenal protection, in particular finerenone. Furthermore, finerenone is currently tested in patients with heart failure with preserved ejection fraction.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Diabetes Mellitus, Type 2; Heart Failure; Diabetic Nephropathies; Renal Insufficiency, Chronic
PubMed: 37991625
DOI: 10.1007/s11886-023-01998-0 -
Aging Clinical and Experimental Research Nov 2023Previous studies have suggested that antihypertensive drugs may play a role in the treatment of osteoarthritis, but these studies may be limited by confounding factors... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies have suggested that antihypertensive drugs may play a role in the treatment of osteoarthritis, but these studies may be limited by confounding factors and lead to biased results. Therefore, we conducted a Mendelian randomization study to investigate the effects of blood pressure and antihypertensive drugs on osteoarthritis.
METHODS
We used published large-scale genome-wide association data and applied univariate and multivariate Mendelian randomization methods. The main analysis model was inverse variance weighting, and the reliability of the results was tested using MR-Egger intercept analysis, Cochran's Q test, and leave-one-out analysis. We comprehensively evaluated the relationship between systolic blood pressure, diastolic blood pressure, 12 antihypertensive drugs, and osteoarthritis. We also conducted verification in the independent queue of UK Biobank and built a simple linear regression model to obtain an independent comparison.
RESULTS
We found no evidence that systolic and diastolic blood pressure significantly affected osteoarthritis. However, among antihypertensive drugs, we observed a significant positive correlation between potassium-preserving diuretics and aldosterone antagonists and all osteoarthritis (OR: 0.560, 95% CI 0.406-0.772, P = 0.0004). Sensitivity analysis showed no horizontal pleiotropy or heterogeneity, and the leave-one-out analysis demonstrated the reliability of the results. This result was replicated with nominally statistical significance in the validation cohort and exhibited significant correlation in the linear regression analysis.
CONCLUSIONS
Our study suggested that controlling the protein targets of potassium-sparing diuretics and aldosterone antagonists may have beneficial results for osteoarthritis. These findings provide valuable medication strategies for the control of hypertension in patients with osteoarthritis.
Topics: Humans; Blood Pressure; Antihypertensive Agents; Genome-Wide Association Study; Mineralocorticoid Receptor Antagonists; Reproducibility of Results; Diuretics; Osteoarthritis; Potassium
PubMed: 37603265
DOI: 10.1007/s40520-023-02530-8 -
Frontiers in Endocrinology 2023SGLT2 inhibitors (SGLT2i) are now the mainstay therapy for both diabetes and heart failure. publications, meta-analysis, and conference presentations of the eight... (Review)
Review
SGLT2 inhibitors (SGLT2i) are now the mainstay therapy for both diabetes and heart failure. publications, meta-analysis, and conference presentations of the eight SGLT2i Cardiovascular Outcomes trials (CVOTS) done in diabetic patients constantly echo that this class of drug decreases mortality, reduces cardiovascular events, and prevents heart failure and kidney disease. This review of medical agencies' SGLT2i analysis (FDA and EMA) helps to understand the reality of SGLT2i results in those trials, avoiding to consider observational and statistically undemonstrated endpoints as validated. They also confirmed the unique diuretic mode of action of SGLT2i, promoting osmotic diuresis, and its potential adverse events secondary to hypovolemia and hematocrit increase. They also support the understanding that the beliefs in SGLT2i morbi-mortality benefits are largely overstated mostly based on undemonstrated endpoints. Finally, it is clear that SGLT2i's antidiabetic action, secondary to its renal mode of action, plateaued after a few months and decreased strongly over time, questioning its long-term goal of maintaining diabetic patients' HbA1c below 7%. Also, this effect in patients with renal impairment is quasi null. We think that this review would be very helpful to every physician treating diabetic patients to better balance belief and reality of SGLT2i prescription effects.
Topics: Humans; Canagliflozin; Diabetes Mellitus, Type 2; Diuretics; Glucosides; Heart Failure; Observational Studies as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37547306
DOI: 10.3389/fendo.2023.1174692 -
International Journal of Molecular... Jul 2023Despite recent advances in heart failure (HF) therapy, the risk of cardiovascular (CV) mortality, morbidity, and HF hospitalization (HFH) are major challenges in HF... (Review)
Review
Despite recent advances in heart failure (HF) therapy, the risk of cardiovascular (CV) mortality, morbidity, and HF hospitalization (HFH) are major challenges in HF treatment. We aimed to review the potential of vericiguat as a treatment option for HF. A systematic literature review was performed using the PubMed database and ClinicalTrials.gov. Four randomized controlled trials were identified, which study the safety and efficacy of vericiguat in HF patients. Vericiguat activates soluble guanylate cyclase (sGC) by binding to the beta-subunit, bypassing the requirement for NO-induced activation. The nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway plays an essential role in cardiovascular (CV) regulation and the protection of healthy cardiac function but is impaired in HF. Vericiguat reduced the risk of CV death and HFH in HF patients with reduced ejection fraction (HFrEF) but showed no therapeutic effect on HF with preserved ejection fraction (HFpEF). The trials demonstrated a favorable safety profile with most common adverse events such as hypotension, syncope, and anemia. Therefore, vericiguat is recommended for patients with HFrEF and a minimum systolic blood pressure of 100 mmHg. Treatment with vericiguat is considered when the individual patient experiences decompensation despite being on guideline-recommended medication, e.g., angiotensin-converting inhibitor/AT1 receptor antagonist, beta-adrenoceptor antagonist, spironolactone, and sodium-glucose transporter 2 inhibitors. Furthermore, larger studies are required to investigate any potential effect of vericiguat in HFpEF patients. Despite the limitations, vericiguat can be recommended for patients with HFrEF, where standard-of-care is insufficient, and the disease worsens.
Topics: Humans; Heart Failure; Treatment Outcome; Stroke Volume; Soluble Guanylyl Cyclase; Cardiotonic Agents; Diuretics
PubMed: 37511587
DOI: 10.3390/ijms241411826