Assessment of adverse events of the novel cardiovascular drug vericiguat: a real-world pharmacovigilance study based on FAERS.

BACKGROUND: This study aims to analyze the adverse event reports (AERs) to vericiguat using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) and provide evidence for the clinical use. METHODS: AERs due to vericiguat from 2021Q1 to 2024Q1 identified as the primary suspect were screened, with duplicate reports subsequently eliminated. Various quantitative signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, were then employed for data mining and analysis. Signal strength is represented by the 95% confidence interval, information component (IC), and empirical Bayesian geometric mean (EBGM). RESULTS: A total of 617 vericiguat-related AERs were identified. Strong signals were observed in 21 system organ classes. Furthermore, the most frequently reported preferred terms (PT) was hypotension (n = 86, ROR 25.92, PRR 24.11, IC 4.59, EBGM 24.07), followed by dizziness (n = 52, ROR 6.44, PRR 6.20, IC 2.63, EBGM 6.20), malaise (n = 25, ROR 3.59, PRR 3.54, IC 1.82, EBGM 3.54), blood pressure decreased (n = 23, ROR 20.00, PRR 19.64, IC 4.29, EBGM 19.61), and anemia (n = 21, ROR 6.67, PRR 6.57, IC 2.72, EBGM 6.57). CONCLUSIONS: This study extended the adverse reactions documented in the FDA instruction and provided supplementary evidence regarding the clinical safety of vericiguat.

Phenotyping cardiogenic shock that showed different clinical outcomes and responses to vasopressor use: a latent profile analysis from MIMIC-IV database.

Background: Cardiogenic shock (CS) is increasingly recognized as heterogeneous in its severity and response to therapies. This study aimed to identify CS phenotypes and their responses to the use of vasopressors. Method: The current study included patients with CS complicating acute myocardial infarction (AMI) at the time of admission from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Laboratory and clinical variables were collected and used to conduct latent profile (LPA) analysis. Furthermore, we used a multivariable logistic regression (LR) model to explore the independent association between the use of vasopressors and endpoints. Result: A total of 630 eligible patients with CS after AMI were enrolled in the study. The LPA identified three profiles of CS: profile 1 (n = 259, 37.5%) was considered as the baseline group; profile 2 (n = 261, 37.8%) was characterized by advanced age, more comorbidities, and worse renal function; and profile 3 (n = 170, 24.6%) was characterized by systemic inflammatory response syndrome (SIRS)-related indexes and acid-base balance disturbance. Profile 3 showed the highest all-cause in-hospital mortality rate (45.9%), followed by profile 2 (43.3%), and profile 1 (16.6%). The LR analyses showed that the phenotype of CS was an independent prognostic factor for outcomes, and profiles 2 and 3 were significantly associated with a higher risk of in-hospital mortality (profile 2: odds ratio [OR] 3.95, 95% confidence interval [CI] 2.61-5.97, p < 0.001; profile 3: OR 3.90, 95%CI 2.48-6.13, p < 0.001) compared with profile 1. Vasopressor use was associated with an improved risk of in-hospital mortality for profile 2 (OR: 2.03, 95% CI: 1.15-3.60, p = 0.015) and profile 3 (OR: 2.91, 95% CI: 1.02-8.32, p = 0.047), respectively. The results of vasopressor use showed no significance for profile 1. Conclusion: Three phenotypes of CS were identified, which showed different outcomes and responses to vasopressor use.

UPLC-QTOF/MS-Based Metabolomics Reveals the Protective Mechanism of Hydrogen on Mice with Ischemic Stroke.

As a reductive gas, hydrogen plays an antioxidant role by selectively scavenging oxygen free radicals. It has been reported that hydrogen has protective effects against nerve damage caused by ischemia-reperfusion in stroke, but the specific mechanism is still unclear. Therefore, this study aims to investigate the protective effects of hydrogen on stroke-induced ischemia-reperfusion injury and its detailed mechanism. Two weeks after the inhalation of high concentrations (66.7%) of hydrogen, middle cerebral artery occlusion (MCAO) was induced in mice using the thread occlusion technique to establish an animal model of the focal cerebral ischemia-reperfusion. Then, a metabolomics analysis of mouse cerebral cortex tissues was first performed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to study the metabolic changes and protective mechanisms of hydrogen on stroke ischemia-reperfusion injury. According to the metabolomic profiling of cortex tissues, 29 different endogenous metabolites were screened, including palmitoyl-L-carnitine, citric acid, glutathione, taurine, acetyl-L-carnitine, N-acetylaspartylglutamic acid (NAAG), L-aspartic acid, lysophosphatidylcholine (LysoPC) and lysophosphatidylethanolamine (LysoPE). Through pathway analysis, the metabolic pathways were concentrate on the glutathione pathway and the taurine pathway, mitochondrial energy metabolism and phospholipid metabolism that related to the oxidative stress process. This result reveals that hydrogen may protect against ischemic stroke by reducing oxidative stress during ischemia-reperfusion, thereby protecting nerve cells from reactive oxygen species(ROS).