Cardiovascular Drugs and Therapy最新文献

The 2025 ESC/EAS Dyslipidaemia Focused Update provides a targeted revision of the 2019 guidelines, integrating newly available evidence with the potential to influence clinical decision-making before the next full update. While LDL-C treatment targets remain unchanged, the document reshapes how they should be achieved, emphasizing faster therapeutic intensification, broader use of combination therapy and improved risk stratification with SCORE2/SCORE2-OP, lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) scoring. New evidence supporting bempedoic acid, inclisiran and evinacumab expands the therapeutic armamentarium, particularly for patients at high, very high and extreme cardiovascular risk or those with statin intolerance. In the acute coronary syndrome (ACS) setting, the update reinforces a more proactive, early-intensification approach. Overall, the Focused Update refines the operational framework of LDL-C management, promoting earlier, more personalized and more sustained lipid lowering to reduce cumulative atherosclerotic exposure.

Purpose: Kawasaki disease (KD) is classified as a "WenBing" syndrome in traditional Chinese medicine (TCM), characterized by systemic inflammation and vasculitis. Jiawei Baihu Tang (JWBHT) is an optimized herbal formulation derived from the classical Baihu Tang (BHT), a renowned ancient TCM prescription traditionally used to treat WenBing syndromes by clearing heat, reducing fever, and promoting body fluid production. However, the precise pharmacological mechanisms underlying JWBHT's intervention effects remain largely unexplored. We aimed to assess the protective effects of JWBHT on coronary artery inflammation in mice with KD and explore the underlying mechanisms, with a focus on the lipocalin-2/matrix metalloproteinase 9 (LCN2/MMP9) axis in vascular remodeling.

Methods: Histopathological analysis, multiplex immunofluorescence, data-independent acquisition (DIA) proteomics, and non-targeted metabolomics were employed to comprehensively measure the effects of JWBHT on coronary artery injury. The experiments were conducted using a Candida albicans water-soluble fraction (CAWS)-induced murine model of KD vasculitis. Multi-omics integration also revealed the role of JWBHT in regulating extracellular matrix (ECM)-receptor interaction and enhancing α-linolenic acid metabolism.

Results: JWBHT significantly alleviated coronary arteritis by reducing inflammatory cell infiltration, preserving ECM integrity, and alleviating fibrosis. Multi-omics analysis indicated that JWBHT regulated ECM-receptor interaction and restored lipid metabolism, particularly α-linolenic acid metabolism, which was closely linked to ECM stabilization. Mechanistically, JWBHT suppressed the LCN2/MMP9 axis, a critical mediator of vascular remodeling. Validation based on the clinical dataset revealed elevated levels of LCN2/MMP9 in patients with acute KD, which were normalized after treatment.

Conclusion: For the first time, this study unveiled the multi-target mode of action of JWBHT in KD through the crosstalk between ECM and lipid metabolism, and LCN2 was identified as a potential novel intervention target. Our findings suggest that JWBHT is a promising traditional Chinese medicine for preventing the cardiovascular complications of KD.

Purpose: Current research on potentially clinically significant drug-drug interactions (DDIs) in individuals with atrial fibrillation (AF) has predominantly focused on DDIs involving direct oral anticoagulants (DOACs), with limited evidence regarding other medications. Our study aimed to: (i) assess the overall prevalence of DDIs; (ii) investigate potential demographic correlates of DDIs; and (iii) examine the association of DDIs with adverse clinical outcomes in a nationwide cohort of older adults with AF and multimorbidity.

Methodology: Data from the Swedish national registers were linked to establish a cohort with a 2-year follow-up of adults ≥ 65 years who, on 1 January 2017, had a diagnosis of AF, ≥ 1 comorbidity and were prescribed ≥ 2 medications (n = 192,716). This study describes the prevalence of 72 potentially clinically significant DDIs from an adapted explicit international consensus list and a review focused specifically on DDIs involving DOACs. Correlates of DDIs were assessed through logistic regressions. Cox regression analyses were conducted to examine the association between DDIs and adverse clinical outcomes: overall and cardiovascular (CV) mortality, overall and CV hospitalisation, stroke, bleeding, and falls.

Results: In the overall population, 37.5% presented with ≥ 1 potential DDI, with CV (33.8%) and central nervous system (CNS) drugs (12.4%) most frequently involved. Sex, age, and civil status were most consistently associated with DDIs. Individuals with ≥ 1 DDI had a higher hazard of CV death (hazard ratio 1.28 95% confidence interval (CI) [1.24-1.32]), CV hospitalisation (1.12 [1.10-1.15]) and falls (1.06 [1.02-1.09]). DDIs with DOACs were associated with gastrointestinal bleeding (2.80 [1.35-5.81]). DDIs with CNS drugs were associated with stroke (1.19 [1.09-1.29]) and falls (1.32 [1.27-1.39]).

Conclusion: Potentially clinically significant DDIs were prevalent in older adults with AF and multimorbidity, with adverse clinical implications. Identifying these high-risk groups is essential for preventive strategies and effective clinical management.

Purpose: Atrial fibrillation (AF) recurrence after radiofrequency ablation is closely associated with patient prognosis, while the potential impact of heart failure with preserved ejection fraction (HFpEF) remains unclear. This study aimed to explore the effect of HFpEF on recurrence within 1 year after catheter ablation.

Methods: We enrolled 455 patients who underwent atrial fibrillation ablation, with 241 in the HFpEF group and 213 in the non-heart failure (non-HF) group. Baseline characteristics, 12-month AF recurrence rates, and predictors were compared between groups. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to assess the recurrence risk, and propensity score matching (PSM) was performed for verification.

Results: The HFpEF group exhibited significantly higher recurrence than the non-HF group (25.0% vs. 9.8%, P < 0.001), and Kaplan-Meier analysis confirmed significant differences in 1-year recurrence-free survival (Log-rank P < 0.001). Multivariable Cox regression identified HFpEF as an independent risk factor for 1-year recurrence (HR = 1.92, 95% CI:1.06-3.47), whereas paroxysmal AF was a protective factor(HR = 0.55, 95% CI:0.31-0.98). Subgroup analysis further revealed that compared with the paroxysmal AF without heart failure (NoHF-pAF) group, HFpEF with persistent AF (HFpEF-PerAF) had significantly elevated recurrence risk (adjusted HR = 4.12, 95% CI:2.20-7.75; P < 0.001), and HFpEF with paroxysmal AF (HFpEF-pAF) also showed increased risk (HR = 2.58, 95% CI:1.14-5.84, P = 0.023). After PSM, the HFpEF group maintained significantly higher recurrence (23.0% vs. 10.0%, P = 0.016), with HFpEF remaining the sole independent predictor (HR = 2.42, 95% CI:1.17-5.00, P = 0.017).

Conclusion: HFpEF is an independent risk factor for 1-year recurrence after AF ablation, with highest risk in persistent AF patients. Implementing comprehensive individualized treatment strategies is essential to improve prognosis.

Purpose: Dual antiplatelet therapy (DAPT) is the cornerstone for patients with coronary atherosclerotic heart disease (CHD) undergoing percutaneous coronary intervention (PCI) while increasing the risk of bleeding, particularly when combined with gastrointestinal disease (GID). Rivaroxaban 10 mg once daily is widely used in Asia. This study compared the effects of low-dose rivaroxaban (10 mg daily) plus clopidogrel vs. DAPT in CHD patients with GID undergoing PCI.

Methods: In this prospective, single-center, randomized controlled trial, eligible CHD patients with GID undergoing PCI were randomized (1:1) to either the dual pathway inhibition (DPI) group (rivaroxaban 10 mg plus clopidogrel 75 mg daily) or the DAPT group (aspirin 100 mg plus clopidogrel 75 mg daily). The primary outcome was Bleeding Academic Research Consortium (BARC) type 2-5 bleeding. The secondary outcome was major adverse cardiovascular or cerebrovascular events (MACCE), which included cardiac death, nonfatal myocardial infarction, ischemia-driven target vessel revascularization, all-cause death, stent thrombosis, and stroke during the 6-month follow-up.

Results: A total of 1042 patients were enrolled and analyzed (DPI, 522; DAPT, 520). Low-dose rivaroxaban (10 mg daily) plus clopidogrel was non-inferior to DAPT in BARC type 2-5 bleeding [8 (1.5%) vs. 6 (1.2%), absolute risk difference 0.38%, 95% confidence interval (CI) (- 1.02-1.78), p < 0.0001 for non-inferiority]. Abdominal pain was significantly lower in the DPI group (p = 0.009). Other abdominal discomforts, gastrointestinal bleeding, or MACCE were similar.

Conclusions: In CHD patients with GID undergoing PCI, low-dose rivaroxaban (10 mg daily) plus clopidogrel was non-inferior to DAPT.

Trial registration: Chinese Clinical Trial Registry ChiCTR2100044319. Registered on March 16, 2021.

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: The purpose of this study was to investigate the protective effects of biochanin A (BCA) on cardiac hypertrophy and to elucidate the underlying molecular mechanisms. The research question was whether BCA can reverse heart dysfunction and attenuate cardiomyocyte hypertrophy induced by pressure overload and AngII, respectively, and how it interacts with the NLRP3 pyroptosis pathway to achieve these effects.

Methods: We employed an animal model of pressure overload-induced cardiac hypertrophy and an in vitro model of AngII-induced cardiomyocyte hypertrophy to assess the effects of BCA. The expression of NLRP3 and its related signaling molecules was analyzed by western blotting, and the activity of the NLRP3 pathway was measured using pyroptosis assays. The role of Cbl-b, an E3 ubiquitin ligase, in BCA-mediated NLRP3 inhibition was also investigated.

Results: BCA was found to reverse heart dysfunction and attenuate cardiomyocyte hypertrophy induced by pressure overload and AngII. Mechanistically, BCA mitigated cardiac hypertrophy by targeting the NLRP3 pyroptosis pathway. The reduction in NLRP3 expression by BCA was predominantly mediated through the upregulation of Cbl-b, which enhanced the ubiquitination and subsequent degradation of NLRP3. Additionally, BCA facilitated the upregulation of Cbl-b expression by interacting with NF-κB, preventing NF-κB binding to the promoter region of Cbl-b and reversing its suppressive action on Cbl-b expression.

Conclusion: This study provides initial evidence that BCA can protect against cardiac hypertrophy. Its mechanism of action involves interacting with NF-κB to promote the expression of Cbl-b, which facilitates the ubiquitination and degradation of NLRP3, ultimately inhibiting pyroptosis. This finding suggests that BCA may be a potential therapeutic agent for the treatment of cardiac hypertrophy.

Purpose: Transcatheter aortic valve replacement (TAVR) has emerged as a critical innovation for managing severe aortic stenosis, prompting the development of numerous clinical practice guidelines worldwide. This study systematically evaluates the guideline development methodologies of major international TAVR guidelines using the AGREE II and AGREE-REX instruments, aiming to enhance understanding of current development processes.

Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, and specialized guideline repositories. Twenty-four TAVR-specific guidelines were independently evaluated by four reviewers using the AGREE II and AGREE-REX instruments. The guidelines were categorized as evidence- or consensus-based, and statistical analysis was performed using SPSS to standardize scores and assess inter-rater reliability.

Results: Systematic assessment revealed significant methodological variations across guidelines. The AGREE II evaluation showed the highest performance in scope and purpose (83.9 ± 10.0%) but lower scores in rigor of development (43.5 ± 29.0%) and applicability (42.4 ± 26.8%). The AGREE-REX analysis demonstrated stronger performance in implementability (78.6 ± 14.5%) while identifying gaps in the integration of values and preferences (35.7 ± 17.2%). Evidence-based guidelines consistently outperformed consensus-based ones across multiple domains, particularly in terms of methodological rigor and implementation planning.

Discussion: This evaluation highlights key areas for improving guideline development methodology, including standardized evidence evaluation processes, systematic stakeholder engagement, and structured implementation planning. The considerable variability in methodological quality underscores the need for more standardized approaches.

Conclusion: Current TAVR guidelines exhibit significant heterogeneity in methodological quality, with evidence-based guidelines demonstrating superior performance in development rigor and implementation planning. Systematic approaches to evidence synthesis and stakeholder engagement are crucial for high-quality guideline development.