Journal of Cardiovascular Pharmacology最新文献

Abstract: Diabetic cardiomyopathy (DCM), a global cardiovascular complication of diabetes, is characterized by concurrent diastolic and systolic ventricular dysfunction that progressively leads to heart failure, arrhythmias, and cardiogenic shock. Despite advancements in modern therapeutics, DCM continues to exhibit high mortality rates, underscoring the critical need for novel preventive and therapeutic strategies. In recent years, traditional Chinese medicine (TCM) has gained prominence in DCM management due to its established safety profile and emerging evidence of clinical efficacy. Current research focuses on elucidating TCM's multitarget mechanisms, particularly its regulatory effects on metabolic homeostasis, oxidative stress, and inflammatory pathways-key pathological processes in DCM progression. This review systematically investigates the latest advancements in TCM for DCM management through 3 principal dimensions: First, it synthesizes the etiological understanding of DCM from both TCM theory and modern medical perspectives, highlighting their complementary mechanisms in disease pathogenesis. Second, it critically evaluates the therapeutic potential of clinically validated Chinese herbal agents, focusing on their bioactive compounds that target myocardial energy metabolism and oxidative stress pathways. Third, it systematically summarizes evidence-based TCM therapeutic strategies. By consolidating existing evidence, this review aims to provide a rigorous assessment of TCM's clinical value in DCM management, while proposing standardized frameworks to facilitate deeper integration of TCM principles with evidence-based cardiology practice.

Injectable PCSK9 inhibitors effectively lower LDL-C levels in patients with hypercholesterolemia; however, their high cost and requirement for parenteral administration limit their widespread use. Oral PCSK9 inhibitors have emerged as a convenient alternative. This review and meta-analysis of the literature evaluate the effectiveness and safety of oral PCSK9 inhibitor treatment for adults with hypercholesterolemia. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through September 2025 for randomized controlled trials comparing oral PCSK9 inhibitors with placebo. The primary outcome was percentage change in LDL-C, with secondary lipid and safety outcomes. We used Cochrane RoB 2.0 tool to assess risk of bias, and pooled estimates were calculated using a random-effects model. Certainty of evidence was evaluated with GRADE. From 1,253 records, three trials were included. Participants were mostly male, aged 61-65 years, with elevated baseline LDL-C. Oral PCSK9 inhibitors significantly reduced LDL-C and ApoB in a dose-dependent manner and achieved modest reductions in triglycerides (MD -6.56 mg/dL; 95% CI: -12.30 to -0.83) and total cholesterol (MD -25.25 mg/dL; 95% CI: -30.67 to -19.83). Effects on lipoprotein(a) were inconsistent. Adverse events (RR 1.06; 95% CI: 0.91-1.23) and serious adverse events (RR 1.32; 95% CI: 0.41-4.26) were comparable to placebo. According to our review, oral PCSK9 inhibitors are a promising therapeutic option for treating hypercholesterolemia due to their potent lipid-lowering effects and an overall favorable safety profile. However, more trials are needed to confirm their impact on cardiovascular outcomes.

Cardiovascular disease remains a leading cause of global illness and death, accounting for approximately 17.9 million deaths annually, according to the World Health Organization. There is a growing need for more precise and individualized therapeutic strategies to reduce this burden. Artificial intelligence (AI) has the potential to enhance cardiovascular outcomes by facilitating personalized risk stratification and informing treatment decisions, particularly through advancements in AI-powered cardiovascular imaging and machine learning models. Traditional approaches rely on population-level risk assessments and generalized treatment guidelines, which often fail to capture the complex and diverse nature of individual patient presentations. This review examines the transformative impact of AI-enhanced cardiovascular imaging modalities, including echocardiography, cardiac magnetic resonance imaging, computed tomography angiography, and nuclear cardiology, on optimizing medical therapy. Machine learning algorithms can rapidly and accurately analyze large volumes of imaging data, improving efficiency, standardizing image acquisition and interpretation, reducing inter-observer variability, and increasing diagnostic confidence. By integrating AI with cardiovascular imaging, clinicians can achieve personalized risk assessments, early disease detection, and tailored treatment plans that range from pharmacotherapy to interventions and lifestyle modifications. These advances hold promise for improving outcomes in patients with cardiovascular disease or at risk for its development. The review also addresses current challenges and future directions, highlighting the potential of AI to usher in a new era of individualized cardiovascular care.

Background: The therapeutic effects of different combination therapies containing cholesteryl ester transfer protein (CETP) inhibitors vary. Evidence from head-to-head comparisons is scarce and inconsistent. This study aims to evaluate the impact of CETP inhibitor-based combination therapy on lipid levels and explore its adverse events (AEs).

Method: Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane Library, and Web of Science up to August 30, 2025. Thirteen RCTs were analyzed via STATA 14.0.

Results: This systematic review and network meta-analysis of 13 studies (9,248 participants) evaluated CETP inhibitor-based combination therapies. For HDL-C elevation, obicetrapib + ezetimibe + statin ranked highest (SUCRA = 95.1%). Evacetrapib + statin achieved reduction in LDL-C (SUCRA = 94.3%). Obicetrapib + ezetimibe + statin excelled in reducing TC (SUCRA = 100.0%) and TG (SUCRA = 99.9%). Obicetrapib + statin was most effective for ApoAI increase (SUCRA = 100.0%), while obicetrapib + ezetimibe + statin best reduced ApoB (SUCRA = 100.0%). Regarding safety, obicetrapib + statin had the optimal profile for all grade AEs (SUCRA = 19.2%) and severe AEs (SUCRA = 22.5%), conversely, evacetrapib + statin had the worst profile (SUCRA = 83.1% and 66.3% respectively).

Conclusion: Our meta-analysis demonstrated that CETP inhibitor combination therapies offer distinct lipid-modulating benefits and safety profiles. The obicetrapib + ezetimibe + statin triple therapy showed superior comprehensive efficacy, while obicetrapib + statin exhibited the optimal safety. Evacetrapib + statin provided potent LDL-C reduction but had the poorest safety. These findings facilitate personalized treatment selection for dyslipidemia management.

The recent emergence of cardiac myosin inhibitors (CMIs) has established an era of targeted medical therapy for obstructive hypertrophic cardiomyopathy (oHCM), with trials showing decreases in obstructive gradients and improvements in symptoms and exercise capacity. However, not all patients achieve satisfactory responses with CMIs, which can include a "non-response" to medication due to persistent obstruction or continued symptoms despite gradient resolution, or medication failure in cases of discontinuation due to side effects or cost. We present a differential framework for evaluation of CMI non-response or failure, including evaluation for contributors to reduced systolic function, non-oHCM sources of obstruction, or other cardiac and non-cardiac causes of dyspnea. Patients without satisfactory improvement with CMI therapy should undergo a thorough workup according to this framework to identify other potentially addressable concerns that may allow for success with CMIs or indicate other appropriate therapies to address symptoms.

Warfarin inhibits vitamin K-dependent proteins that prevent vascular calcification. We hypothesized that direct oral anticoagulants (DOACs), which do not interact with vitamin K, would slow coronary plaque progression compared to warfarin in atrial fibrillation (AF) patients. Following PRISMA guidelines and a prospectively registered protocol (PROSPERO: CRD420251026977), we systematically searched PubMed, Embase, and Cochrane databases through April 2025 for randomized controlled trials comparing DOACs with warfarin in AF patients. Primary outcomes included changes in coronary plaque volumes (PV). Mean differences were calculated using Mantel-Haenszel method, with trial sequential analysis performed for all outcomes. Three RCTs with 272 patients (136 receiving DOACs) were included. Patients receiving DOACs showed significantly slower progression of calcified PV (MD -7.07 mm3; 95% CI: -12.99 to -1.14; p=0.02; I2=0%) and fibrous PV (MD -12.52 mm3; 95% CI: -24.92 to -0.12; p=0.05; I2=0%) compared to warfarin. No significant differences were observed in total PV, non-calcified PV, fibro-fatty PV, or low attenuation PV. Trial sequential analysis indicated that 391 patients would be necessary for definitive conclusions regarding calcified PV. Risk of bias assessment indicated some concerns for all studies, with moderate certainty of evidence for most endpoints. DOACs significantly reduce progression of calcified and fibrous plaque volumes compared to warfarin in AF patients. These findings suggest DOACs may promote more stable plaque composition, potentially reducing cardiovascular event risk. However, larger studies with longer follow-up are needed to confirm these results.

Ivabradine is one of several off-label treatments for patients with postural orthostatic tachycardia syndrome (POTS). We conducted a systematic review of the literature to identify studies which evaluate ivabradine treatment in patients with POTS. The results were narratively synthesized given methodological heterogeneity among the identified studies. There were 11 studies included in the analysis with 305 participants between 2008 to 2020. The only randomized trial of 22 patients showed that ivabradine improved heart rate compared to placebo and there were symptomatic benefits in terms of physical functioning, and social functioning. All studies suggested a reduction in heart rate with ivabradine treatment; the proportion of patients with symptomatic benefit ranged from 67% to 100%. One study using the Malmo POTS score found that ivabradine improved the total score, including key components such as light-headedness with standing, feeling faint, feeling rapid heart rate, and chest pain. While two studies did not report side effects and two studies described no side effects, others reported adverse effects including bradycardia, nausea, worsening syncope, palpitations, flushing, light sensitivity, headache, light-headedness, fatigue, scalded tongue, itching and burning, and visual disturbance. In conclusion, there is low-quality evidence derived from small observational studies and one small randomized trial that ivabradine is effective in reducing heart rate and improving symptoms in patients with POTS. The exact role of ivabradine in treatment of POTS needs to be clarified in further randomized trials and more robust evidence.

Previously, we showed that vasorelaxant effects of trans-4-methoxy-β-nitrostyrene (T4MN) in rat aorta were mediated through stimulation of the soluble guanylate cyclase (sGC) pathway. The present study tested the hypothesis that bonding of the methoxy electron-donor group at the meta-position instead of the para-position into the aromatic moiety might enhance the interaction of the nitroderivative with sGC. For this purpose, vascular effects of the trans-3-methoxy-β-nitrostyrene (T3MN) were studied in rat aorta. In endothelium-intact preparations, T3MN was 100 times more potent as a vasorelaxant than its stereoisomer, T4MN. T3MN-induced vasodilatory effects remained unaffected by indomethacin, MDL-12,330A or glybenclamide but were significantly reduced by endothelium removal, L-NAME, ODQ, LY294002, TEA, 4-AP, and apamin. Under Ca2+-free conditions, T3MN was unresponsive to transient contractions evoked by caffeine, whereas it inhibited contractions induced by (i) the protein kinase C activator phorbol 12-myristate 13-acetate, (ii) the tyrosine phosphatase inhibitor sodium orthovanadate, (iii) exogenous calcium influx via receptor- or voltage-operated Ca2+ channels and (iv), in an ODQ-preventable manner, those evoked by PHE or Ca2+ influx through stores-operated Ca2+ channels activated by thapsigargin-induced Ca2+ store depletion. In conclusion, T3MN induced a potent vasorelaxant effect that seems to be mediated partly by an endothelium-dependent mechanism involving activation of the Akt/eNOS/NO pathway and partly by an endothelium-independent mechanism through activation of the sGC/cGMP/PKG pathway in vascular smooth muscle, leading to inhibition of Ca2+ influx from the extracellular milieu and IP3-sensitive intracellular Ca2+ release as well as activation of potassium channels.