Cardiovascular Drugs and Therapy最新文献

Purpose: Hypoxemia is a risk factor for mortality and long-term neuropsychological impairment during severe acute respiratory distress syndrome (ARDS). Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a potential treatment for such cases but may not suffice. We aimed to evaluate the effects of pharmacological interventions for cardiac output (CO) control using ivabradine or beta-blockers for refractory hypoxemia during VV-ECMO.

Methods: The study involved retrospective analysis of consecutive patients with severe ARDS who underwent VV-ECMO at a tertiary university hospital between March 2020 and May 2022. Patients with refractory hypoxemia under VV-ECMO were included. Pharmacological interventions included ivabradine and/or short half-life beta-blockers. The primary endpoint was the change in ECMO flow/CO ratio and secondary endpoints were changes in macrocirculation (mean arterial pressure), oxygenation [arterial saturation (SaO₂) and oxygen transport (DO₂)] and tissue hypoxia (lactate levels).

Results: Out of 70 patients on VV-ECMO, ten had refractory hypoxemia under VV-ECMO and received pharmacological interventions to control CO. The ECMO flow/CO ratio significantly increased with pharmacological intervention overall (from 60% [50-66] to 69% [61-81], p = 0.02), as well as with beta-blockers or ivabradine individually. However, DO₂ decreased, especially with beta-blockers and to some extent with ivabradine. There were no reported immediate adverse events, and lactate levels remained below the anaerobic threshold.

Conclusion: Ivabradine and beta-blockers were clinically well-tolerated and improved the ECMO flow/CO ratio in patients with refractory hypoxemia during VV-ECMO. However, the improvement of arterial oxygenation was associated with decreased DO₂.

Purpose: This meta-analysis aimed to conduct a systematic evaluation of the comparative efficacy and safety of new oral anticoagulants (NOACs) versus warfarin for the treatment of deep venous thrombosis (DVT).

Methods: A systematic computerized search of databases including PubMed, Medline, Web of Science, Embase, Cochrane Library, and www.

Clinicaltrials: gov . was performed to gather research on the efficacy and safety of NOACs versus warfarin in the treatment of DVT, encompassing all records from the inception of each database through September 2024. The discrete data were presented as odds ratios (ORs) with their corresponding 95% confidence intervals (CIs), and the meta-analysis was executed utilizing the Review Manager 5.4.1 and Stata 16 softwares.

Results: A comprehensive analysis of 16 studies encompassing 10,084 patients was conducted, with 6704 individuals in the experimental group receiving NOACs and 3380 in the control group treated with warfarin. The findings are as follows: (1) NOACs demonstrated enhanced treatment efficacy over warfarin, particularly in achieving vascular patency (OR = 1.57, 95% CI (1.09, 2.24), P = 0.01). (2) Regarding the incidence of major bleeding events (OR = 0.65, 95% CI (0.54, 0.78), P < 0.00001), other clinical adverse events-including pulmonary embolism, mortality, stroke, myocardial infarction and recurrent thrombosis (OR = 0.77, 95% CI (0.67, 0.88), P = 0.0002), and post-thrombotic syndrome (PTS) (OR = 0.62, 95% CI (0.47, 0.80), P = 0.0003); NOACs offered improved safety profiles in comparison to warfarin. Furthermore, subgroup analysis revealed that the preventive efficacy of NOACs against PTS improves with longer follow-up periods (P = 0.02).

Conclusion: NOACs have demonstrated superior efficacy and safety profiles in the treatment of DVT compared to traditional warfarin anticoagulant therapy.

Clinical trial registration: This project did not involve any clinical data collection; the data utilized were derived from articles published in PubMed.

Purpose: Inflammatory responses induced by NLRP3 inflammasome contribute to the progression of atherosclerosis. This study seeks to investigate the effect of emodin on the NLRP3 inflammasome in atherogenesis and to probe the underlying mechanism.

Methods: ApoE-knockout (ApoE^-/-) mice were treated with a high-fat diet (HFD) for 12 weeks and intragastrically with emodin for 6 weeks. Human mononuclear cell line THP-1 was pretreated with emodin or signaling pathway inhibitors and induced into macrophages using phorbol 12-myristate 13-acetate (PMA) for 48 h. The NLRP3-mediated inflammatory response was studied both in vivo and in vitro. The level of the inflammation was detected by western blot, real-time PCR analysis, and ELISA.

Results: Emodin attenuated atherosclerotic lesions in HFD-treated ApoE^-/- mice. Emodin dramatically decreased the expression of NLRP3, GSDMD, IL-1β, and IL-18 in HFD-treated ApoE^-/- mice and PMA-induced macrophages. Moreover, emodin significantly hindered the activation of nuclear factor kappa-B (NF-κB) by inhibiting the formation of the TLR4/MyD88 complex in PMA-induced macrophages.

Conclusion: Our data demonstrate that emodin can inhibit the development of atherosclerotic plaques by alleviating NLRP3/GSDMD-induced inflammation through repressing the TLR4/MyD88/NF-κB signaling pathway in macrophages. This finding suggests that emodin can be a potential candidate for the treatment of atherosclerosis.

Purpose: Cardiovascular diseases, exacerbated by cardiac fibrosis, are the leading causes of mortality. We aimed to determine the role of quercetin (QU) in cardiac fibrosis and the underlying mechanism.

Methods: In this study, 8-week-old mice were subjected to either transverse aortic constriction (TAC) or sham surgery, then they were administered QU or saline. Thereafter, cardiac function and cardiac hypertrophy were accessed. In vitro, cardiac fibroblasts (CFs) were treated with angiotensin II (Ang II) with or without QU. Western blot, qPCR, EdU incorporation assay, and immunofluorescence staining analysis were used to investigate the molecular and cellular features.

Results: For the TAC mouse model, cardiac fibrosis was alleviated by QU. The study revealed that the trans-differentiation and proliferation of CFs promoted by Ang II would be reversed by QU in vitro. Mechanistically, QU exerted the anti-fibrotic effect by regulating the SIRT3/TGF-β/Smad3 signaling pathway.

Conclusion: Quercetin protects against cardiac fibrosis by mediating the SIRT3 signaling pathway.

Purpose: The management of heart failure (HF) frequently includes gastroprotection via proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). This systematic review evaluates their impact on HF outcomes, including exacerbation, hospitalization, mortality, and major adverse cardiac events (MACE).

Methods: In accordance with PRISMA guidelines, a complete search across databases such as PubMed/Medline, Scopus, and Web of Science was conducted until December 10, 2023. The inclusion criteria covered research on adult patients with HF that focused on the effects of PPI and H2RA usage. The risk of bias was determined via the Newcastle-Ottawa Scale (NOS), and data were synthesized quantitatively.

Results: Eleven studies encompassing 996,498 participants were analyzed. The data is not consistent across all research; however, some have suggested that PPI use may be linked to an increased risk of cardiovascular illnesses and heart failure aggravation. Conversely, H2RAs appeared to offer potential benefits in certain high-risk groups, potentially reducing all-cause and cardiovascular mortality. However, the limitations of the available studies should be taken into consideration when interpreting these findings.

Conclusion: The review suggests that there may be differences in the impact of PPIs and H2RAs on HF outcomes. While some evidence indicates that PPIs may be linked to increased risks in HF patients, and H2RAs may offer potential benefits, these findings are not definitive and should be interpreted with caution. Further research is necessary to clarify these associations and guide clinical practice.

Registration: PROSPERO CRD42023491752.

Purpose: Proton pump inhibitors (PPIs) are widely prescribed for gastrointestinal disorders. Lansoprazole, a PPI, has been recognized for its potential effects of improving insulin resistance, reduction of oxidative stress, and improvement in atherosclerosis through peroxisome proliferator-activated receptor gamma (PPARγ) induction. This study aims to investigate whether lansoprazole poses a distinct risk of coronary heart disease (CHD) compared to other PPIs.

Methods: A retrospective cohort study utilized data from the National Health Insurance Research Database in Taiwan spanning from 2000 to 2013. The exposed cohort included 1666 patients with lansoprazole use, while the comparison cohort comprised 6664 patients using other PPIs. The primary outcome was incident CHD. Cox regression models were employed to assess the association between lansoprazole use and CHD risk, presenting hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Patients prescribed lansoprazole demonstrated a significantly reduced risk of CHD compared to those undergoing other PPI treatments in individuals without a history of CHD. Lansoprazole users exhibited a 25% lower risk of developing CHD compared to other PPI users (adjusted HR 0.75; 95% CI 0.65-0.87). Intriguingly, this inverse association between lansoprazole use and CHD risk was consistent across genders and various age groups.

Conclusion: This study suggests that lansoprazole is associated with a decreased risk of CHD in comparison to other PPIs in patients without a history of CHD. Further research is warranted to elucidate the clinical implications of these findings.

Several reports suggest that in animal models, as well as in the clinical setting, long-term warfarin use increases coronary artery calcifications. The same has been reported for statins prescribed for patients at risk or with established atherosclerosis. Coronary calcifications are considered a risk marker for further cardiovascular events. However, numerous clinical trials have established that statins reduce the risk for cardiovascular events. Warfarin also has been shown to reduce the risk of cardiovascular events, including re-infarction. It has been suggested that the increase in coronary calcification can be viewed as a marker of stabilization of the coronary plaque in such patients. Warfarin inhibits the activation of Vitamin K epoxide reductase complex 1 (VKORC1), which blocks the regeneration of reduced vitamin K1 and K2. Vitamin K1 is predominantly localized to the liver, serving to carboxylate clotting factors. Vitamin K2 travels through systemic circulation, with significant and wide-ranging effects. Several studies using animal models of atherosclerosis have shown that vitamin K2 supplement can attenuate the progression of atherosclerosis, as well as coronary calcification. Clinical studies supporting this effect in patients are lacking. Yet, there is an increase in the use of over-the-counter vitamin K2 supplements, and several manuscripts recommended its use in patients receiving long-term warfarin to attenuate coronary calcification. However, it is unclear if this occurs in patients with atherosclerosis receiving warfarin or statins and if attenuating coronary calcification has beneficial or detrimental effects on cardiovascular outcomes.