Baxdrostat: A Novel Aldosterone Synthase Inhibitor for Treatment Resistant Hypertension.

Hypertension is a global epidemic, affecting around 30.4% of the population and being the leading preventable risk factor for death. Despite the availability of numerous antihypertensive agents, less than 20% of individuals have their blood pressure controlled. Resistant hypertension poses a challenge, but a new class of medication, aldosterone synthase inhibitors (ASI), shows promise. ASI reduces aldosterone production by inhibiting aldosterone synthase. This review article focuses on Baxdrostat, a highly potent ASI currently in phase 3 trials. It discusses the drug's biochemical pathway, efficacy trials in animals and humans, and its potential in uncontrolled hypertension, chronic kidney disease, and primary aldosteronism.

Safety and efficacy of new potassium binders on hyperkalemia management in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF. METHODS: MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin-aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60-1.93; p = 0.801; I2 = 0%). CONCLUSION: The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.

Aldosterona e os sistemas cardiovascular e renal: do diagnóstico ao tratamento / Aldosterone and the cardiovascular and renal systems: from diagnosis to treatment

O sistema renina-angiotensina-aldosterona vem despertando cada vez mais interesse em relação a seus efeitos no sistema cardiovascular. Atualmente, crescentes avanços nos estudos clínico-experimentais tem proporcionado melhor esclarecimento da fisiopatologia deste sistema , com ênfase no papel da aldosterona como indutora de lesão de órgãos-alvo, por promovar inapropriada expansão da volemia, remodelamento e fibrose do sistema cardiovascular, sobretudo do coração e dos rins. No coração, a aldosterona está relacionada ao desenvolvimento de hipertrofia ventricular, fibrose e falência cardíaca. Níveis elevados de aldosterona plasmática estão associados a pior prognóstico na insuficiência cardíaca congestiva e na fase aguda do infarto agudo do miocárdio. No rim, a aldosterona promove infalmação, injúria, fibrose e alteração da hemodinâmica glomerular, com consequente aumento da proteinúria e piora progressiva da função renal. Produz, também, aletrações no metabolismo da glicose e está relacionada à obesidade e à hipertensão arterial sistêmica. Os efeitos causados pela aldosterona são mais exuberantes em pacientes com hiperaldosteronismo primário, sendo de extrema importância seu reconhecimento precoce. O uso de antagonistas da aldosterona diminui seu efeito deletério no sistema cardiovascular melhorando a sobrevida e o prognóstico dos pacientes com insuficiência cardíaca congestiva, nefropatia e hiperaldosteronismo primário.

Effect of chronic oral administration of a low dose of captopril on sodium appetite of hypothyroid rats. Influence of aldosterone treatment.

Rats rendered hypothyroid by treatment with methimazole develop an exaggerated sodium appetite. We investigated here the capacity of hypothyroid rats (N = 12 for each group) to respond to a low dose of captopril added to the ration, a paradigm which induces an increase in angiotensin II synthesis in cerebral areas that regulate sodium appetite by increasing the availability of circulating angiotensin I. In addition, we determined the influence of aldosterone in hypothyroid rats during the expression of spontaneous sodium appetite and after captopril treatment. Captopril significantly increased (P<0.05) the daily intake of 1.8% NaCl (in ml/100 g body weight) in hypothyroid rats after 36 days of methimazole administration (day 36: 9.2 +/- 0.7 vs day 32: 2.8 +/- 0.6 ml, on the 4th day after captopril treatment). After the discontinuation of captopril treatment, daily 1.8% NaCl intake reached values ranging from 10.0 +/- 0.9 to 13.9 +/- 1.0 ml, 48 to 60 days after treatment with methimazole. Aldosterone treatment significantly reduced (P<0.05) saline intake before (7.3 +/- 1.6 vs day 0, 14.4 +/- 1.3 ml) and after captopril treatment. Our results demonstrate that, although hypothyroid rats develop a deficiency in the production of all components of the renin-angiotensin-aldosterone system, their capacity to synthesize angiotensin II at the cerebral level is preserved. The partial reversal of daily 1.8% NaCl intake during aldosterone treatment suggests that sodium retention reduces both spontaneous and captopril-induced salt appetite.

Effect of chronic oral administration of a low dose of captopril on sodium appetite of hypothyroid rats: Influence of aldosterone treatment

Rats rendered hypothyroid by treatment with methimazole develop an exaggerated sodium appetite. We investigated here the capacity of hypothyroid rats (N = 12 for each group) to respond to a low dose of captopril added to the ration, a paradigm which induces an increase in angiotensin II synthesis in cerebral areas that regulate sodium appetite by increasing the availability of circulating angiotensin I. In addition, we determined the influence of aldosterone in hypothyroid rats during the expression of spontaneous sodium appetite and after captopril treatment. Captopril significantly increased (P<0.05) the daily intake of 1.8 percent NaCl (in ml/100 g body weight) in hypothyroid rats after 36 days of methimazole administration (day 36: 9.2 + or - 0.7 vs day 32: 2.8 + or - 0.6 ml, on the 4th day after captopril treatment). After the discontinuation of captopril treatment, daily 1.8 percent NaCl intake reached values ranging from 10.0 + or - 0.9 to 13.9 ± 1.0 ml, 48 to 60 days after treatment with methimazole. Aldosterone treatment significantly reduced (P<0.05) saline intake before (7.3 + or - 1.6 vs day 0, 14.4 + or - 1.3 ml) and after captopril treatment. Our results demonstrate that, although hypothyroid rats develop a deficiency in the production of all components of the renin-angiotensin-aldosterone system, their capacity to synthesize angiotensin II at the cerebral level is preserved. The partial reversal of daily 1.8 percent NaCl intake during aldosterone treatment suggests that sodium retention reduces both spontaneous and captopril-induced salt appetite