Kumar, Akshay

Background: Resistant hypertension represents a significant clinical challenge, often driven by dysregulated aldosterone production. Aldosterone synthase inhibitors (ASIs) are a novel therapeutic class designed to directly suppress aldosterone biosynthesis. This study aimed to synthesize evidence regarding the comparative efficacy, optimal dosing, and dose–response relationships of three ASIs—baxdrostat, lorundrostat, and osilodrostat—for the treatment of resistant hypertension. Methods: A systematic review and network meta-analysis (NMA) were conducted following PRISMA 2020 guidelines. We searched PubMed, Web of Science, and CENTRAL for randomized controlled trials (RCTs) published up to 31 October 2025. The primary outcome was the mean change in systolic blood pressure (SBP) compared to placebo. We utilized a frequentist random-effects model, characterized dose–response relationships via meta-regression, and ranked treatments using the Surface Under the Cumulative Ranking Curve (SUCRA). Results: The analysis included 8 RCTs comprising 3253 participants. Baxdrostat 2 mg once daily demonstrated the greatest antihypertensive efficacy with a mean SBP reduction of −13.8 mmHg (95% CI: −17.5 to −10.1) versus placebo, followed by Lorundrostat 100 mg (−12.5 mmHg) and Baxdrostat 1 mg (−11.5 mmHg). SUCRA analysis identified Baxdrostat as the highest-ranked treatment (83.0%), followed by Lorundrostat (67.8%) and Osilodrostat (55.5%). Dose–response meta-regression revealed strong linear correlations for Baxdrostat (R2 = 0.91), Osilodrostat (R2 = 0.81), and Lorundrostat (R2 = 0.80). Conclusions: ASIs, particularly Baxdrostat and Lorundrostat, offer robust blood pressure reductions in patients with resistant hypertension. The strong linear dose–response relationships suggest these agents have a favorable therapeutic window for titration. While effective, clinical implementation requires careful monitoring for adverse events.

Angiosarcoma is a rare type of soft-tissue sarcoma arising from endothelial cells. It is considered ‘high-grade’ by definition, reflecting its aggressive behavior. We sought to investigate the role of surgery in cardiac angiosarcoma, identify late mortality predictors, and identify interactions with other modalities in its treatment using a national dataset. The 2004–2017 National Cancer Database was reviewed for patients with primary cardiac angiosarcoma. Late mortality predictors were evaluated with Kaplan–Meier curves and Cox regression analysis. Surgery in primary cardiac angiosarcoma was performed in 130 patients (median age 50.5 years; female sex 36.9%). The median follow up was 72.02 months, with a median overall survival (OS) of 14.32 months. In patients treated with surgery in combination with other modalities compared with those treated with surgery alone, median OSs were 17.28 and 2.88 months, respectively (log-rank = 0.018). Older patients (age > 57 years) experienced lower OS compared to those with an age < 57 (log-rank = 0.012). This may be partially explained by the difference in treatment strategies among age groups: those with increasing age, less surgery (p = 0.037), and less chemotherapy (p < 0.001) were chosen. With multivariable Cox regression analysis, age and race other than white or black were identified to be significant independent predictors of late mortality. Cardiac angiosarcoma has poor overall survival, and our findings should further encourage the use of surgery in combination with other therapeutic modalities in treating such an aggressive disease whenever possible.