Journal of Cardiovascular Pharmacology最新文献

Given the high prevalence of cardiovascular disease in the United States, there is a critical need for new medications to improve outcomes of these diseases. The U.S. Food and Drug Administration (FDA) has approved numerous medications that are able to effectively do so. While these drugs have significantly beneficial effects, just like any other medication, they can come with a multitude of unwanted side effects. It has been noted that cardiovascular drugs have been associated with a considerable number of dermatologic reactions. This review examines current literature on the various cutaneous manifestations of these adverse reactions. It focuses on these newly FDA-approved cardiovascular medications from 2013 to 2023, detailing both common and rare effects in the past decade. As more medications continue to enter the market, the necessity for awareness of more systemic side effects will continue to grow. This comprehensive review aims to guide clinicians in identifying drug-induced reactions in patients on these therapies.

Adrenergic overstimulation is detrimental to the left ventricle. However, its effects on the right ventricle (RV) are not clear. Since adrenergic overload increases metabolic demand and oxidative stress, boldine could be a therapeutic option in the treatment of cardiovascular disease due to its antioxidant role. This study aimed to investigate the impact of adrenergic overload on RV remodelling and the cardioprotective effect of boldine. Animals were divided into four groups: control (C), boldine (25 mg/kg i. p.) (B), isoproterenol (5 mg/kg subcutaneously) (ISO), and boldine+isoproterenol (B+ISO). Echocardiography, Fulton index, histology, oxidative stress, inflammation, and β-adrenergic receptor (ADR) were analysed. The diastolic parasternal length [C 0.698 (0.623-0.724) vs ISO 0.77 (0.73-0.81)], Fulton index [C 0.268 (0.231-0.275) vs ISO 0.340 (0.280-0.353)], inflammatory infiltration (∼40%), and ADR [C 0.78 (0.71-0.84) vs ISO 1.74 (1.52-2.00)] were increased in the ISO group (P<0.05). Boldine treatment (B+ISO) reduced the Fulton index [0.240 (0.228-0.263)], lipid peroxidation [2.07 (2.01-2.61)], and ADR [0.71(0.62-0.80)]. Boldine increased total SH levels in B+ISO [C 2.4 (1.78-2.71); ISO 4.01 (2.95-4.66) vs B+ISO 6.77(5.15-8.60)] (P<0.05). There was a positive correlation between lipid peroxidation and the Fulton index, and a negative correlation between total SH and the Fulton index (P<0.05). This is the first study to explore the effects of adrenergic overstimulation on RV and the protective effect of boldine. Such data pave the way for further research involving RV remodelling, such as in pulmonary hypertension, as well as a new therapeutic option.

Isorhynchophylline is a Chinese herbal medicine and has multiple effects such as anti-inflammatory and neuroprotective effects. Whether isorhynchophylline has anti-thrombotic property is unknown. This study aims to evaluate its role in platelet function. Human platelets were incubated with isorhynchophylline (0, 10, 20 and 40 μM) at 37°C for 1 hour to detect platelet aggregation and activation, receptors level, spreading and calcium mobilization. Additionally, isorhynchophylline (5 mg/kg) was injected into mice to measure in vivo hemostasis and thrombosis. Isorhynchophylline dose-dependently reduced platelet aggregation, ATP secretion, P-selectin expression and αIIbβ3 activation induced by collagen-related peptide (CRP) or thrombin without affecting surface level of receptors αIIbβ3, GPIbα, and GPVI. Meanwhile, isorhynchophylline-treated platelets showed reduced spreading. Moreover, isorhynchophylline reduced platelet calcium mobilization, phosphatidylserine exposure and the phosphorylation of PLCγ2 and PKCα. Furthermore, administration of isorhynchophylline into mice impaired platelet hemostatic function and arterial/venous thrombosis without affecting coagulation. In conclusion, Isorhynchophylline impairs platelet function and arterial/venous thrombosis, implying its potential to be a novel agent for treating thrombotic or cardiovascular diseases.

Abstract: Patients with atrial fibrillation (AF) taking antithrombotic (AT) therapy are at an increased risk of gastrointestinal bleeding (GIB). The comparative effect of a combination of anticoagulant (AC) and antiplatelet (AP) versus AC monotherapy on clinical outcomes in patients with AF presenting with GIB is not well characterized. This study compares outcomes in AF patients with GIB on AC alone with those on combination AP and AC therapy, as part of a larger prospective study from 2013 to 2023. One hundred and thirty-seven patients diagnosed with AF who presented with overt GIB were evaluated during their hospitalization, at 1 month and 1 year postdischarge and then annually. The median follow-up of patients was 57 months. Patients in the combination AP + AC therapy group had a higher prevalence of coronary artery disease, myocardial infarction, and coronary/vascular stent placement compared with the AC monotherapy group. No statistically significant differences were noted between the 2 groups in terms of end-of-follow-up mortality, in-hospital mortality, major bleeding, rebleeding, and length of hospital stay. Cox regression analysis revealed chronic kidney disease [hazard ratio (HR) 2.05, 95% confidence interval (1.04-4.05) ( P = 0.038)] and warfarin use [HR 4.94, 95% confidence interval (1.11-22.09) ( P = 0.037)] to be independent predictors of mortality at 12 months. Antithrombotic therapy in patients with AF who experience GIB should be mainly directed by their cardiovascular needs. Health care providers may explore non-vitamin K antagonist oral anticoagulants as alternatives to warfarin for AF patients at risk of GIB, and efforts must be maximized to prevent bleeding in patients with chronic kidney disease.

Abstract: In a randomized double-blinded clinical trial of patients with ST segment elevation myocardial infarction (STEMI), goflikicept, an interleukin-1 blocker, significantly reduced systemic inflammation, measured as the area under the curve (AUC) for high-sensitivity C reactive protein at 14 days. We report secondary analyses of biomarkers at 28 days, and cardiac function and clinical end points at 1 year. Patients received a single administration of goflikicept 80 mg (n = 34), goflikicept 160 mg (n = 34), or placebo (n = 34). Both doses of goflikicept significantly reduced the AUC for high-sensitivity C reactive protein at 28 days compared with placebo, without statistically significant differences between the doses. There were no statistically significant differences between groups in the AUC for natriuretic peptides at 28 days. There were no significant differences between placebo, goflikicept 80 mg, and 160 mg groups in deaths (2.9%, 2.9%, and 0%), hospitalization for cardiovascular reasons (9.1%, 5.9%, and 0%), new-onset or progression of heart failure (9.1%, 5.9%, and 5.9%), and new or increased use of loop diuretics (24.2%, 14.7%, and 17.6%), nor in the number of patients with treatment emergent adverse events, with no treatment-related serious adverse events in any group. In conclusion, in patients with STEMI, interleukin-1 blockade with goflikicept 80 mg or 160 mg was well tolerated and associated with significant reduction of systemic inflammation. Further adequately powered studies are warranted to determine whether the reduction in systemic inflammation with goflikicept translates into a clinical benefit in patients with STEMI.

Abstract: Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality used in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most used anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on cofactors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of cofactors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. In addition, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low-flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.

Abstract: Malnutrition is known to worsen the prognosis of chronic heart failure (HF). To gain information that may be helpful in establishing appropriate nutritional interventions for chronic HF, this study was performed to investigate the efficacy of nutritional management with 2 enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat HF model. After being fed a standard rodent feed (MF) containing 8% NaCl (high salt-MF [HS-MF]) from 6 to 11 weeks of age, rats were assigned to freeze-dried EH or ER diets with an NaCl concentration of 8% (HS-ER or HS-EH) until 18 weeks of age. Serum albumin was significantly higher at 14 and 17 weeks of age in rats fed the HS-ER and HS-EH diets compared with those remaining on the HS-MF diet. Body weight was also significantly higher at 14 and 17 weeks of age in animals fed the HS-ER diet, showing that nutritional deterioration was prevented. In addition, heart weight was significantly lower at 18 weeks of age in the HS-ER group than that in the HS-MF group, suggesting that cardiac hypertrophy was prevented. This study demonstrated improved nutritional status in a HF model in Dahl rats presumably owing to differences in nutritional composition in the diets. Future studies are needed to explore optimal nutritional management with enteral formulas in patients with chronic HF.

Studies have shown an association between cardiovascular disease and abnormal copper metabolism. Cuproptosis is caused by the accumulation of copper in vivo, and is a newly identified form of cell death. It regulates cardiovascular diseases by affecting vascular endothelial function and myocardial energy metabolism through pathways such as oxidative stress, mitochondrial function, and gene expression. The treatment of copper accumulation in traditional Chinese medicine primarily involves heat-clearing and detoxification therapy, supplemented with diuretic therapy. In contrast, Western medicine mainly uses copper chelators. Flavonoids are common active ingredients used in the treatment of copper metabolism-related and cardiovascular diseases. In this article, we reviewed the relationship between copper metabolism, cuproptosis, and cardiovascular disease, providing novel strategies for preventing and treating cardiovascular disease; our ultimate aim is to encourage inspiration and contemplation among readers.

Intravenous (IV) digoxin loading dose recommendations for rate control of atrial arrhythmias in critically ill patients are not well studied. When using digoxin in the setting of atrial fibrillation/atrial flutter (AF/AFL), a loading dose (LD) in either a fixed-dose regimen, weight-based dose, or pharmacokinetic-based calculation to target a serum digoxin concentration (SDC) of 0.8-1.5 ng/mL is recommended. The objective of this study was to assess the safety and effectiveness of digoxin LD used in critically ill patients for rate control of AF/AFL and to assess the SDC achieved. This single center retrospective cohort study included patients who received IV digoxin and had a SDC drawn. The primary endpoint was the median SDC achieved after a digoxin LD. Secondary outcomes included the frequency of SDCs ≥1.5 ng/mL and heart rate (HR) control. A total of 92 patients were included. The median total LD of digoxin for the entire cohort was 11mcg/kg (750 mcg). For 61% of the cohort, the LD was distributed over six-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9, 1.7). The incidence of supratherapeutic SDC was 36% for the total cohort. A target HR < 110 beats per minute within 24 hours from digoxin LD was achieved in 60% of the cohort. In conclusion, a median total digoxin LD of 750 mcg in critically ill patients with AF/AFL, targeting a SDC < 1.5ng/mL may be considered for acute rate control, taking into account drug-drug interactions in the cardiac intensive care unit. Future studies are necessary to confirm our findings.