Search Results (309)

Background/Objectives: In the last decade, several studies revealed individual response variability to different antiplatelet agents, and patients who have no response to these drugs are considered poor responders. Some studies explored platelet function during antiplatelet treatment to identify those patients with “high on-treatment platelet reactivity” (HPR), which exposes them to increased risk of major adverse cardiovascular events (MACE). Methods: We conducted a study with patients with ST-elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, including long-term follow-up after 5 years. We used thromboelastography, the total thrombus formation analysis system, and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) to analyze HPR with different methods; selected laboratory parameters were measured during hospitalization to check significant correlations. Results: We identified STEMI patients treated with DAPT with HPR as a risk group for MACE in a 5-year follow-up. Additionally, we have shown that HPR is associated with atherosclerosis by analyzing lipid profile parameters. Conclusions: High on-treatment platelet reactivity (HPR) increases the risk of major adverse cardiovascular events in the long term, especially with elevated C-reactive protein or an atherogenic lipid profile. Standardizing HPR assessment is crucial for optimizing individualized antiplatelet therapy and improving patient outcomes post-STEMI. Full article

Background: Antithrombotic therapy plays an important role in acute coronary syndrome (ACS). The combination of anticoagulant and antiplatelet therapy resulted in fewer complications and stronger potency compared to traditional monotherapy. Our net meta-analysis aimed to compare and rank the safety of different treatments used in patients with ACS. Method: We conducted a search for trials in three prominent databases. The main objective of our investigation was to assess hemorrhage. Additional outcomes included mortality, myocardial infarction, stroke, and embolism. We used a frequentist network meta-analysis with a random-effects model to, directly and indirectly, compare safety across different antithrombotic strategies. Result: A total of 30 randomized clinical trials were included in this net meta-analysis with 135,471 ACS patients. In these eight different antithrombotic therapies, SAPT (single-agent platelet inhibitor therapy) showed the lowest risk of bleeding (SUCRA = 0.5%). The highest risk of bleeding was observed in VKA (vitamin K antagonists) + DAPT (dual antiplatelet therapy) (SUCRA = 99.8%). Bleeding among NOAC (non-vitamin K antagonist oral anticoagulants) + DAPT was found to be higher than DAPT (OR = 1.94, 95% CI = 1.42–2.65). NOAC + SAPT significantly reduced the embolism (OR = 1.50, 95% CI = 1.16–1.94) and myocardial infarction (OR = 1.22, 95% CI = 1.08–1.37) events compared with SAPT. In addition, VKA significantly reduced the rate of stroke compared with SAPT (OR = 3.45, 95% CI = 1.17–10.18). However, no significant difference was observed in death events among these eight antithrombotic therapies. Conclusions: We advise against the use of SAPT in ACS due to its elevated risk of embolism, myocardial infarction, and stroke. It is important to mention that the combination of NOAC and SAPT has a lower incidence of myocardial infarction, bleeding and embolism problems. Therefore, the combination of NOAC and SAPT may be the optimal approach to achieve a balance between the risks of bleeding and embolism. This meta-analysis was registered in PROSPERO with the registration number CRD42024542826. Full article

Drug-coated balloons (DCBs) have transformed percutaneous coronary intervention (PCI) by delivering antiproliferative drugs directly to the arterial wall, offering a stent-less approach that mitigates the risks associated with permanent metallic implants. Initially developed for in-stent restenosis (ISR), DCBs have demonstrated robust efficacy in reducing neointimal hyperplasia and target lesion revascularization (TLR) rates across diverse coronary lesions, including small vessel disease (SVD), de novo lesions, and complex anatomies such as bifurcation lesions. Paclitaxel-coated balloons have long been the cornerstone of DCB therapy due to their established clinical outcomes, but sirolimus-coated balloons are emerging as a promising alternative with potentially superior safety profiles and sustained drug release. The pharmacological mechanism of DCBs relies on rapid drug transfer during brief balloon inflation, achieving high local concentrations without residual foreign material. Landmark trials, such as BASKET-SMALL 2, RESTORE SVD, and AGENT IDE, have demonstrated comparable or non-inferior outcomes of DCBs versus drug-eluting stents (DESs) in specific settings, with lower rates of stent thrombosis and shorter dual antiplatelet therapy (DAPT) requirements. Despite these advances, challenges persist, including optimizing drug formulations, ensuring uniform delivery, and addressing calcified lesions. Ongoing research into novel coatings, dual–drug systems, and artificial intelligence (AI)-guided interventions is poised to redefine PCI strategies. This review provides a comprehensive analysis of drug-coated balloon (DCB) angioplasty, not limited to specific clinical scenarios such as in-stent restenosis, small vessel disease, or bifurcation lesions, highlighting their transformative role in coronary artery disease (CAD) management. Instead, it addresses the full spectrum of pharmacological principles, mechanisms of action, clinical indications, comparative efficacy across various coronary artery disease contexts, and future directions of DCBs. Full article

A wide range of water-soluble quaternary ammonium acylhydrazones based on catecholaldehyde were synthesized and characterized using NMR, IR spectroscopy, and elemental analysis. The total antioxidant capacity of the acylhydrazones discussed herein was estimated via coulometric titration with electrogenerated bromine. Pyridinium derivatives 11a–e exhibited the highest antioxidant capacity. Quaternary ammonium acylhydrazones demonstrated high antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus strains. Furthermore, low hemo- and cytotoxicity and the absence of a negative effect on the hemostatic system were confirmed for the studied compounds. According to the results of a CV test, the antimicrobial effect of the most active acylhydrazones, namely, 9a, 10b, 10c, and 11a, is associated with the destruction of the bacterial cell wall. High or moderate activity against phytopathogens of bacterial origin was observed for all the acylhydrazones evaluated. Anti-aggregation activity was observed for compound 10b; the extent was 1.6-fold greater than that exhibited by acetylsalicylic acid. On the contrary, compound 9d exhibited a pro-aggregant effect (with a 6.3% increase in platelet aggregation and a >15% decrease in the latent period compared to the control). Thus, the data obtained can be considered the basis for further pharmaceutical development of these effective drugs with antithrombotic and hemostatic potential. Full article

Cardiovascular disease (CVD) is the leading cause of death worldwide, with pathophysiological mechanisms often involving platelet activation and chronic inflammation. While antiplatelet agents targeting adenosine diphosphate (ADP)-mediated pathways are well established in CVD management, less is known about drug interactions with the platelet-activating factor (PAF) pathway, a key mediator of inflammation. This study aimed to evaluate the effects of several commonly used cardiovascular and anti-inflammatory drug classes—including clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin II receptor blockers (ARBs), β-blockers, and analgesics—on platelet function via both the ADP and PAF pathways. Using human platelet-rich plasma (hPRP) from healthy donors, we assessed platelet aggregation in response to these two agonists in the absence and presence of graded concentrations of each of these drugs or of their usually prescribed combinations. The study identified differential drug effects on platelet aggregation, with some agents showing pathway-specific activity. Clopidogrel and NSAIDs demonstrated expected antiplatelet effects, while some (not all) antihypertensives exhibited additional anti-inflammatory potential. These findings highlight the relevance of evaluating pharmacological activity beyond traditional targets, particularly in relation to PAF-mediated inflammation and thrombosis. This dual-pathway analysis may contribute to a broader understanding of drug mechanisms and inform the development of more comprehensive therapeutic strategies for the prevention and treatment of cardiovascular, hypertension, and inflammation-driven diseases. Full article

S-nitrosoglutathione (GSNO), a promising S-nitrosothiol, has been recognized for its ability to modulate vascular tone through its vasodilatory, antiplatelet, and antiproliferative effects. However, data on its vasodilatory effects in human vessels remain limited, and its mechanisms of action have yet to be fully elucidated. In this study, we aimed to investigate the vasorelaxant effect of GSNO and its underlying mechanisms, with particular focus on the soluble guanylate cyclase (sGC)/nitric oxide (NO) pathway and potassium channels in isolated human saphenous veins (SVs) obtained from patients undergoing coronary artery bypass grafting (CABG). GSNO (10⁻⁸–10⁻⁴ M) produced concentration-dependent relaxations in SV rings precontracted with phenylephrine. These relaxations were unaffected by NO synthase inhibition with L-NAME (10⁻⁴ M, 30 min) or NO scavenging with PTIO (10⁻⁴ M, 30 min), but were significantly reduced by the sGC inhibitor, ODQ (10⁻⁵ M, 30 min). Inhibition of ATP-sensitive (glibenclamid; 10⁻⁵ M, 30 min.), high-conductance Ca²⁺-activated (charybdotoxin; 10⁻⁷ M, 30 min), small-conductance Ca²⁺-activated (apamin; 10⁻⁶ M, 30 min), or voltage-dependent (4-aminopyridine; 10⁻³ M, 30 min) potassium channels did not alter the maximum relaxant responses to GSNO. Furthermore, pretreatment with GSNO (10⁻⁴ M, 30 min) significantly attenuated both the contractile response and sensitivity to phenylephrine. Collectively, these findings demonstrate that GSNO exerts acute vasorelaxant and modulatory effects in human SV primarily via cGMP-dependent mechanisms, highlighting its potential as a local therapeutic agent for preventing graft spasm in CABG. Full article

Coronary no-reflow (CNR) is the failure of blood to reperfuse ischemic myocardial tissue after restoration of the vasculature. CNR poses a significant clinical challenge in the treatment of patients with ST-segment elevation myocardial infarction (STEMI), as it increases mortality and the risk of major adverse cardiac events (MACEs). Myocardial ischemia with subsequent reperfusion results in severe damage to the cardiac microcirculation. The pathophysiological causes of CNR include cardiomyocyte vulnerability, capillary and endothelial damage, leukocyte activation, reactive oxygen species (ROS) production, and changes in microRNA profiles and related gene expression. The impact of percutaneous coronary intervention (PCI) on the occurrence of CNR cannot be overlooked, as it can provoke distal atherothrombotic embolization. Current standards of pharmacological therapy for CNR are confined to intracoronary vasodilators and antiplatelet agents. As our understanding of the pathogenesis of the CNR phenomenon improves, opportunities emerge for developing novel therapeutic strategies. The following literature review provides an overview of the pathophysiology of the no-reflow phenomenon (based on animal and preclinical studies), contemporary treatment trends, and current therapeutic approaches. Full article

Background/Objectives: Cangrelor, an intravenous P2Y12 inhibitor, is increasingly used during percutaneous coronary intervention (PCI) for rapid and reversible platelet inhibition in patients unable to take oral antiplatelet agents, particularly in emergencies such as ST-elevation myocardial infarction (STEMI), cardiac arrest, or cardiogenic shock. This single-centre study evaluates cangrelor and outcomes in a non-surgical centre. Methods: Between June 2017 and December 2021, all the patients for whom cangrelor was used at a district general hospital (DGH) in the UK were included in this study. Data collection included baseline characteristics, admission, procedural details, and patient outcomes. The primary outcome was a composite of all-cause mortality, bleeding, and cardiovascular events, including myocardial infarction, stent thrombosis, and stroke, within 48 h. Secondary outcomes included predictors of the composite outcome at 48 h. Results: During the study period, cangrelor was administered peri-procedurally to 93 patients. Males comprised 85% of the patients; the mean age was 65.5 ± 10.6 years. A total of 1 patient (1.1%) had a cardiovascular event within 48 h of cangrelor administration, whereas all-cause mortality occurred in 17 patients (18%) within 48 h. No major bleeding events were noted at 48 h following cangrelor administration. Regression analysis did not find predictors of composite outcomes at 48 h. Conclusions: Cangrelor offers a potential alternative to oral P2Y12 inhibitors in specific high-risk scenarios. Further research is needed to validate its role in broader populations. Full article

Background: Brain metastases are a common and devastating complication of non-small cell lung cancer (NSCLC), severely affecting prognosis and quality of life. Despite increasing interest in the role of platelets in tumor progression and dissemination, the potential impact of antiplatelet therapy on brain metastasis in NSCLC remains underexplored. Methods: In this retrospective observational study, we analyzed data from 650 patients diagnosed with NSCLC over a four-year period to evaluate whether prior or subsequent exposure to antiplatelet agents correlates with a reduced incidence of brain metastases. Results: Patients exposed to antiplatelet therapy, predominantly aspirin, presented with more comorbidities and were generally older. Despite these differences, they showed a significantly lower risk of developing brain metastases during the disease course (6.9% vs. 20.0%, p < 0.001), particularly among those with advanced-stage disease at diagnosis. A longer time to metastasis development was also observed in antiplatelet users (77.5 vs. 62.6 months, p < 0.001), along with improved progression-free survival. Additionally, patients on antiplatelets before diagnosis had a lower probability of presenting brain metastases at the time of diagnosis (3.9% vs. 12.1%, p = 0.014), and no cases of brain metastases occurred in patients who started antiplatelet therapy shortly after diagnosis. These findings highlight the potential of antiplatelet agents to interfere with key mechanisms of metastatic spread, including immune evasion and premetastatic niche formation. Conclusions: Importantly, this study provides one of the first real-world analyses suggesting a consistent and stage-dependent association between antiplatelet use and reduced brain metastatic burden in NSCLC. By bridging the gap between preclinical insights and clinical outcomes, our work offers a novel and clinically relevant perspective that supports further research into the integration of antiplatelet therapy in NSCLC management. Full article

Endometriosis, traditionally viewed as a gynecological disorder, is increasingly recognized as a systemic disease with significant cardiovascular implications. Recent studies suggest that women with endometriosis are at higher risk for developing atherosclerosis and other cardiovascular diseases (CVDs), due to chronic systemic inflammation, endothelial dysfunction, oxidative stress, and metabolic disturbances. This review aimed to summarize current evidence on the vascular implications of endometriosis. A literature search was conducted in PubMed and Google Scholar, focusing on studies exploring the relationship between endometriosis and cardiovascular risk. In rare cases, endometriosis can affect extrapelvic locations such as the diaphragm or pericardium, presenting with cyclical chest pain or dyspnea and mimicking cardiopulmonary conditions. These atypical manifestations often delay diagnosis and highlight the need for heightened clinical awareness. Advances in imaging and minimally invasive techniques, including robotic surgery, have improved the detection and management of such presentations. Shared molecular pathways between endometriosis and CVDs, including pro-inflammatory cytokines and metabolic dysregulation, provide a rationale for exploring novel therapeutic approaches. Emerging pharmacologic options such as statins, metformin, or antiplatelet agents may offer dual benefits for both reproductive and cardiovascular health. Given the multifactorial nature of endometriosis, a multidisciplinary approach involving gynecologists, cardiologists, and primary care providers is essential. These findings highlight the need for early cardiovascular risk assessment and tailored preventive strategies in this population. Full article

Background-Objectives: Chronic diseases linked to inflammation, such as cardiovascular disease (CVD) and cancer, continue to pose major public health challenges due to their high mortality rates. There is growing interest in natural bioactive compounds, particularly those derived from plants, as potential therapeutic or preventive agents due to their low toxicity profiles. This study aimed to explore two freshwater plants—Nelumbo nucifera (Indian lotus) and Lemna sp.—as potential sources of bioactive compounds with antioxidant, anti-inflammatory, and antithrombotic properties. While N. nucifera has established but incompletely characterized biofunctional properties, Lemna sp. remains largely unexplored in this context. Methods: Amphiphilic extracts from both plant species were analyzed for phenolic and lipid constituents, including unsaturated fatty acids, polar lipids, and carotenoids. Antioxidant capacity was evaluated using DPPH, ABTS, and FRAP assays. Anti-inflammatory and antithrombotic activities were assessed via platelet aggregation assays using PAF and ADP agonists. Structural characterization was performed using Fourier transform infrared spectroscopy (FT-IR) and liquid chromatography–mass spectroscopy (LC-MS) to support structure–activity relationship (SAR) analysis. Results: Extracts, particularly from Lemna sp., showed potent antiplatelet activity against PAF and ADP. LC-MS revealed the presence of polar lipids rich in monounsaturated and omega-3 polyunsaturated fatty acids, with a favorable omega-6/omega-3 ratio, especially in Lemna sp., correlating with strong anti-inflammatory potential. High levels of total phenolics and carotenoids were observed, aligning with substantial antioxidant capacity in both species. Conclusions: These findings suggest that N. nucifera and Lemna sp. are promising sources of bioactive compounds with potential applications in functional foods, cosmetics, and pharmaceuticals targeting inflammation- and thrombosis-related chronic diseases. Further studies are warranted to confirm their safety and efficacy. Full article

The optimal long-term antithrombotic treatment of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains controversial. Current guidelines recommend a short initial period of triple antithrombotic therapy (e.g., 1 week), followed by dual therapy consisting of an oral anticoagulation agent and a single antiplatelet agent for 6 months in patients undergoing elective PCI and 12 months in patients with acute coronary syndromes. After this course of combination therapy, anticoagulation monotherapy is recommended. In daily practice, however, the optimal strategy for long-term antithrombotic therapy remains debated. A growing body of evidence supports the safety and efficacy of oral anticoagulation monotherapy, but its use in clinical practice remains inconsistent. This review aims to evaluate the available evidence on chronic antithrombotic regimens in patients with AF undergoing PCI, with a focus on key clinical considerations, such as the selection of optimal long-term therapy that balances ischemic and bleeding risks. It also highlights that, despite robust supporting evidence, significant gaps persist in real-world implementation. Full article

Effective local hemostasis is essential in oral surgery to prevent complications such as delayed healing, infection, and the need for re-intervention. Postoperative bleeding occurs in 4–6% of cases, increasing to 9–12% in patients receiving anticoagulant or antiplatelet therapy. This review evaluates the efficacy, safety, and clinical utility of local hemostatic agents based on 51 studies published between 1990 and 2023. Traditional agents, such as oxidized cellulose and gelatin sponges, control bleeding in over 85% of standard cases but offer limited regenerative benefits. Autologous platelet concentrates (APCs), including platelet-rich plasma (PRP) and leukocyte- and platelet-rich fibrin (L-PRF), reduce bleeding time by 30–50% and enhance soft tissue healing. Studies show the PRP may reduce postoperative bleeding in dental surgery by 30–50%, and in orthopedic and cardiac surgery by 10–30%, particularly in patients on anticoagulants. Tranexamic Acid mouthwash can reduce postoperative bleeding by up to 50–60%. Fibrin sealants achieve a 70–90% reduction in bleeding among high-risk patients, while topical tranexamic acid decreases hemorrhagic events by up to 80% in anticoagulated individuals without increasing thromboembolic risk. However, comparative studies remain limited, particularly in medically compromised populations. Additional gaps persist regarding long-term outcomes, cost-effectiveness, and the standardized use of emerging agents such as nanomaterials. Future research should prioritize high-quality trials across diverse patient groups and develop clinical guidelines that integrate both safety and regenerative outcomes. Full article

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, frequently arising from platelet hyperactivation and subsequent thrombus formation. Although conventional antiplatelet therapies are available, challenges, such as drug resistance and bleeding complications, require the development of novel agents. In this study, dihydrogeodin (DHG) was isolated from Fennellia flavipes and evaluated using platelets derived from Sprague–Dawley rats. Platelet aggregation induced by collagen, adenosine diphosphate, or thrombin was assessed by light transmission aggregometry; DHG significantly reduced aggregation in a dose-dependent manner. Further assays demonstrated that DHG suppressed intracellular calcium mobilization, adenosine triphosphate release, and integrin αIIbβ₃-dependent fibrinogen binding, thereby impairing clot retraction. Western blot analysis revealed that DHG reduced the phosphorylation of mitogen-activated protein kinases (ERK, JNK, p38) and PI3K/Akt, indicating inhibition across multiple platelet-signaling pathways. Additionally, SwissADME-assisted pharmacokinetics predicted favorable properties without violations of the Lipinski (Pfizer) filter, Muegge (Bayer) filter, Ghose filter, Veber filter, and Egan filter, and network pharmacology revealed inhibition of calcium and MAPK pathways. These results highlight the potential of DHG as a novel antiplatelet agent with broad-spectrum activity and promising drug-like characteristics. Further studies are warranted to assess its therapeutic window, safety profile, and potential for synergistic use with existing antiplatelet drugs. Full article

Bleeding complications are a significant concern in the management of acute coronary syndromes (ACS). The evidence from clinical trials demonstrates the need for balancing efficacy in reducing ischemic events with safety concerns, as bleeding events adversely affect prognosis and mortality. Pharmacological agents like aspirin, P2Y12 inhibitors (e.g., prasugrel, ticagrelor), glycoprotein IIb/IIIa inhibitors, and heparins are fundamental to ACS treatment but carry varying bleeding risks depending on individual patient profile. Recent advancements in risk stratification tools have enabled tailored approaches to dual antiplatelet therapy (DAPT), optimizing its duration based on bleeding and thrombotic risks. Further Emerging therapies, including shortened DAPT protocols and P2Y12 inhibitor monotherapy, have shown promise in minimizing bleeding while maintaining clinical efficacy. The findings underscore the importance of personalized antithrombotic regimens in ACS management, emphasizing precise risk assessment to enhance outcomes and mitigate adverse events. This review examines the mechanisms, risk factors, and strategies to mitigate bleeding associated with anticoagulant and antiplatelet therapies in ACS. Full article