Potent Antiplatelet Agents Research Articles

Design and Synthesis of Butylphthalide-Hydroxycinnamic Acid Hybrid Derivatives as Potential Antiplatelet Agents.

Thirty-eight novel butylphthalide-hydroxycinnamic acid hybrid derivatives were designed and synthesized to discover effective antiplatelet agglutination drugs. Among these compounds, 3 o gave the optimal inhibitory activity against AA-induced platelet aggregation in vitro and also exhibited better inhibition than the precursor 3-n-butylphthalide (NBP) against thrombin-induced platelet contraction, carrageenan-induced tail thrombosis, and FeCl3-induced common carotid artery thrombosis. Further investigations on the anti-ischemic stroke activity revealed that compound 3 o exhibited a remarkable protective effect against ischemic/reperfusion brain injury. The PAMPA-BBB permeability and liver microsomal stability tests indicated that compound 3 o could traverse the blood-brain barrier and possessed favorable metabolic stability. This research provides a new candidate compound for treating and preventing cerebrovascular diseases caused by thrombosis.

Ticagrelor or prasugrel versus clopidogrel in patients with coronary heart disease

Abstract Introduction Antiplatelet therapy is pivotal in the management of coronary heart disease (CHD), especially after percutaneous coronary intervention (PCI). Clopidogrel has long been the cornerstone of dual antiplatelet therapy. However, newer agents like prasugrel and ticagrelor boast of faster onset of action and greater platelet inhibition, which may translate to improved outcomes. Purpose Our hypothesis is that prasugrel or ticagrelor are superior to clopidogrel in reducing cardiovascular mortality in chronic CHD patients. Methods We conducted a retrospective cohort study using the TriNetX network database, including patients with chronic CHD on dual antiplatelet therapy. A total of 1,420,165 patients on clopidogrel and 197,783 on prasugrel or ticagrelor were identified. We assessed the primary composite endpoint of cardiovascular mortality over a 5-year follow-up period, using event-free survival as our main outcome measure. Results The 5-year follow-up data revealed a significant difference in event-free survival between the groups. Patients on prasugrel or ticagrelor had a markedly higher event-free survival rate of 83.156% compared to 73.209% for those on clopidogrel. The Log Rank test showed a confidence interval of 1.544 to 1.592 with a highly significant p-value of <0.0001. Discussion The data suggest a clear benefit of prasugrel or ticagrelor over clopidogrel for event-free survival in CHD patients. This could be attributed to the more potent antiplatelet effects of these drugs, leading to reduced thrombotic events. Given the substantial sample size and robustness of the data, the findings advocate for a paradigm shift in the choice of more potent antiplatelet agents in clinical practice. Conclusion Our analysis supports the hypothesis that prasugrel or ticagrelor are associated with significantly lower cardiovascular mortality compared to clopidogrel in patients with chronic coronary heart disease.5-year Kaplan-Meier curves for mortality

Pre-formulation Characteristics of Ticagrelor: A Comprehensive Exploration

Ticagrelor is a potent antiplatelet agent that plays a crucial role in preventing cardiovascular events. Preformulation studies are essential in the drug development process to assess the physicochemical properties of the active pharmaceutical ingredient (API) and its suitability for formulation into a final dosage form. This abstract provides an overview of the preformulation studies conducted on Ticagrelor. The preformulation studies encompassed an extensive analysis of Ticagrelor's physical properties, including solubility, melting point, and crystal structure. Additionally, the drug's stability under various environmental conditions, such as temperature and humidity, was evaluated. Spectroscopic techniques, such as UV-Vis and FTIR, were used to characterize the chemical structure of the compound. The results of these preformulation studies provide valuable insights into the potential challenges and opportunities in formulating Ticagrelor into stable and bioavailable dosage forms. These findings will guide further formulation development and optimization, ensuring the delivery of an efficacious and safe drug product to patients.

Potential antiplatelet agents with grape seed – backbone polyphenols: computational studies

The study focused on grape seed-derived polyphenols for their antiplatelet, anti-inflammatory, and fibrinolytic properties through molecular docking and dynamics simulations. Compounds were evaluated for their effects on P2Y12, PTP1B, thromboxane A2, and other targets. Compounds 1 and 6 showed strong inhibitory potential on P2Y12. Compounds 2 and 7, plus epigallocatechin gallate, demonstrated effective inhibition on NF-KB and COX1. The compounds exhibited drug-like properties and potential for new thrombotic disease therapies. The research sheds light on the interactions between polyphenols and target proteins, paving the way for novel antiplatelet strategies.

Antiplatelet Drugs Use in Pregnancy-Review of the Current Practice and Future Implications.

When clinicians opt for antithrombotic therapy to manage or prevent thrombotic complications during pregnancy, it is imperative to consider the unique physiological state of the pregnant woman's body, which can influence the pharmacokinetics of the drug, its ability to traverse the placental barrier, and its potential teratogenic effects on the fetus. While the efficacy and safety of aspirin during pregnancy have been relatively well-established through numerous clinical studies, understanding the effects of newer, more potent antiplatelet agents has primarily stemmed from individual clinical case reports necessitating immediate administration of potent antiplatelet therapy during pregnancy. This review consolidates the collective experiences of clinicians confronting novel thrombotic complications during pregnancy, often requiring the use of dual antiplatelet therapy. The utilization of potent antiplatelet therapy carries inherent risks of bleeding, posing threats to both the pregnant woman and the fetus, as well as the potential for teratogenic effects on the fetus. In the absence of official guidelines regarding the use of potent antiplatelet drugs in pregnancy, a plethora of cases have demonstrated the feasibility of preventing recurrent thrombotic complications, mitigating bleeding risks, and successfully managing pregnancies, frequently culminating in cesarean deliveries, through meticulous selection and dosing of antiplatelet medications.

Management of high thrombus burden during primary percutaneous coronary intervention

Abstract Managing high thrombus burden during primary percutaneous coronary intervention (PCI) poses significant challenges and is associated with increased procedural complications and adverse clinical outcomes. This abstract reviews current strategies and controversies surrounding the treatment of high thrombus burden in patients undergoing PCI. It discusses pharmacological approaches such as potent antiplatelet agents, glycoprotein IIb/IIIa inhibitors, and novel antithrombotic therapies, alongside mechanical strategies including thrombus aspiration and balloon angioplasty. The importance of individualized treatment based on clinical presentation, thrombus characteristics, and procedural factors is emphasized. Clinical trials and guidelines are reviewed to provide evidence-based recommendations for optimizing outcomes in this complex patient population. Future directions in research and technology aimed at further refining management strategies are also explored.

Impact of antiplatelet therapy on microvascular thrombosis during ST-elevation myocardial infarction.

During an acute coronary syndrome, atherosclerotic plaque rupture triggers platelet activation and thrombus formation, which may completely occlude a coronary artery leading to ST-elevation myocardial infarction (STEMI). Although emergency percutaneous coronary intervention (PCI) is effective in re-opening the main coronary arteries, the downstream microvasculature can become obstructed by embolised plaque material and thrombus. Dual antiplatelet therapy is recommended by guidelines and used routinely for the management of STEMI to reduce the risk of recurrent atherothrombotic events. However it is unclear to what extent antiplatelet therapy reduces microvascular thrombosis, largely because most tools to assess microvascular thrombosis only became available after antiplatelet therapy was already used in the majority of patients. Platelets play a central role in key aspects of microvascular thrombosis, such as atherosclerotic plaque-induced thrombus development, inflammation and microvascular dysfunction, making them a potential target for novel therapeutic interventions. Currently, more potent antiplatelet agents like GPIIb/IIIa inhibitors may be administered during PCI directly into coronary arteries with high thrombus burden but it is not well-established whether this reduces microvascular thrombosis and they significantly increase the risk of bleeding. In this review article we discuss the role of platelets in microvascular thrombosis, describe how microvascular thrombosis and obstruction can be assessed clinically and explore potential new antiplatelet treatments for this. In particular, we highlight novel antiplatelet drugs targeting the platelet receptor GPVI, as well as PAR4, GPIb-IX-V and 5HT2A receptors. We also discuss the potential benefit of P-selectin inhibitors as they have proven to be effective in reducing microvascular thrombosis in sickle-cell disease which could translate into potential benefits in acute coronary syndrome.

Antiplatelet de-escalation switch in patients with acute coronary syndrome and percutaneous revascularisation in real life

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The current indication for the use of potent antiplatelet agents as the first choice after drug-eluting stent implantation in acute coronary syndrome (ACS) is sometimes difficult to achieve due to clinical problems in patients. The switch between higher and lower potency antiplatelet drugs (de-escalation) is particularly relevant and it is usually performed when there are contraindications or adverse effects related to the use of more potent P2Y12 inhibitors (iP2Y12). Purpose Our aim is to analyse the incidence and possible causes of in-hospital de-escalation switching in patients with ACS, as well as to compare the characteristics of these patients with those who continue with the higher potency antiplatelet drug initially indicated. Methods Observational, retrospective, single-centre study of a cohort of 3139 patients admitted to a Coronary Care Unit with ACS, treated with Ticagrelor or Prasugrel as a second antiplatelet agent at admission. Patients were classified according to whether or not they switched to Clopidogrel during their hospitalisation, comparing the characteristics between each group and the clinical events that potentially have caused that switch. Results From 3139 admitted patients, 188 (5.99%) were switched from Ticagrelor or Prasugrel to Clopidogrel. The majority of these occurred among patients receiving Ticagrelor (4.21 vs. 1.78%). Patients with de-escalation switch (mean age 64±11 years, 69% male) were similar to the non-switch group, with no statistical differences in baseline characteristics including the CRUSADE score (25 vs 27), except for the presence of a lower GRACE score (153 vs 146, P=0.02). The diagnosis of ST-elevation ACS as an ischaemic event was more prevalent in the "switch group". Regarding possible causes of de-escalation, a higher frequency of bleeding (9.3 vs 20.7%, P<0.01), new-onset atrial fibrillation (4.14 vs 20.21%, P<0.01) and indication for anticoagulation at discharge (6.64 vs 31.91 %, P<0.01) were observed in the "switch group" compared to the other one. Conclusions Although not very frequent, in-hospital de-escalation switch between iP2Y12 antiplatelet agents is sometimes required because of medical conditions, such as the presence of haemorrhages or the need for anticoagulation due to atrial fibrillation or other reasons; although, other times it happens due to a medical decision, without an objective event. In addition, in our sample, patients who underwent anti-platelet de-escalation switch had a lower ischaemic risk.

Synthesis and Evaluation of Novel Nitric Oxide-Donating Ligustrazine Derivatives as Potent Antiplatelet Aggregation Agents.

Antiplatelet aggregation agents have demonstrated clinical benefits in the treatment of ischemic stroke. In our study, a series of novel nitric oxide (NO)-donating ligustrazine derivatives were designed and synthesized as antiplatelet aggregation agents. They were evaluated for the inhibitory effect on 5'-diphosphate (ADP)-induced and arachidonic acid (AA)-induced platelet aggregation in vitro. The results showed that compound 15d displayed the best activity in both ADP-induced and AA-induced assays, and compound 14a also showed quite better activity than ligustrazine. The preliminary structure-activity relationships of these novel NO-donating ligustrazine derivatives were discussed. Moreover, these compounds were docked with the thromboxane A2 receptor to study the structure-activity relationships. These results suggested that the novel NO-donating ligustrazine derivatives 14a and 15d deserve further study as potent antiplatelet aggregation agents.

Real-world evidence of switching P2Y12 receptor–inhibiting therapies to prasugrel after PCI in patients with ACS: results from EFF-K registry

BackgroundPotent P2Y12 inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS.MethodsThe EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting).ResultsA total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56–2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups.ConclusionsDual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI.Trial registration: KCT0002356, registered June 13, 2017.

Cardiovascular Outcomes Observed with Ticagrelor versus Clopidogrel in Type 2 Diabetes Mellitus Patients with Acute Coronary Syndrome: A Meta-analysis.

Type 2 diabetes mellitus (T2DM) is often associated with macrovascular complications including cardiovascular diseases (CVDs), resulting in acute coronary syndrome (ACS). Newer potent antiplatelet agents have recently been approved for use in clinical practice. In this analysis, we aimed to systematically compare the cardiovascular outcomes observed with ticagrelor versus clopidogrel in T2DM patients with ACS. From August to September 2022, electronic databases were searched for publications that compared cardiovascular outcomes observed with ticagrelor versus clopidogrel in patients with T2DM. The statistical analysis was carried out using RevMan 5.4 software. A random effect statistical model was used to analyze the data. Risk ratios (RR) with 95% confidence intervals (CIs) were used to represent the data post analysis. A total of 5868 participants with T2DM were included in this analysis, of which 1944 participants were assigned to the ticagrelor group and 3924 participants were assigned to the clopidogrel group. Our analysis showed that ticagrelor was associated with a significantly lower risk of major adverse cardiac events (MACEs) (RR: 0.64, 95% CI: 0.49-0.84; P = 0.001), all-cause mortality (RR: 0.65, 95% CI: 0.51-0.83; P = 0.0004), and cardiac death (RR: 0.60, 95% CI: 0.43-0.84; P = 0.003) in comparison to clopidogrel. However, the risks of repeated revascularization (RR: 1.48, 95% CI: 0.44-4.99; P = 0.53), stent thrombosis (RR: 0.70, 95% CI: 0.18-2.71; P = 0.60), reinfarction (RR: 0.85, 95% CI: 0.58-1.23; P = 0.39), and stroke (RR: 0.56, 95% CI: 0.14-2.21; P = 0.41) were similar. Ticagrelor was associated with a significantly higher risk of minor bleeding (RR: 1.53, 95% CI: 1.07-2.19; P = 0.02), whereas the risk for major bleeding (RR: 1.08, 95% CI: 0.55-2.10; P = 0.82) was not significantly different. In these T2DM patients with ACS, a significantly lower risk of major adverse cardiovascular events including all-cause mortality was observed in the ticagrelor group compared with the clopidogrel group. However, T2DM patients who were assigned to ticagrelor showed a significantly higher minor bleeding risk. Larger clinical trials should be able to confirm these hypotheses.

Synthesis of Novel 3-Butylphthalide Derivatives Containing Isopentenylphenol Moiety as Potential Antiplatelet Agents for the Treatment of Ischemic Stroke.

In order to find novel antiplatelet drugs for the treatment of ischemic stroke, a series of 3-butylphthalide derivatives containing isopentenylphenol moiety were designed, synthesized and characterized with spectroscopic analyses. The in vitro antiplatelet activity results indicated that compound 3 better inhibited the arachidonic acid (AA) induced platelet aggregation than aspirin (ASP) and 3-butylphthalide (NBP). Additionally, compared with precursor NBP, compound 3 possessed outstanding antithrombotic activity in the animal experiment model, which could effectively alleviate the formation of tail thrombus and carotid artery thrombus in mice. More importantly, intraperitoneal administration of compound 3 can well protected the rats against ischemia/reperfusion-induced brain injury. Further pharmacokinetic (PK) assay indicated that compound 3 had good absorption characteristics and metabolic stability in vivo. Overall, the present research provides a new candidate compound for the treatment of ischemic stroke caused by platelet aggregation.

Comparison of Clopidogrel, Prasugrel and Ticagrelor Response of Patients by PFA-100-Innovance Test Results.

Devices such as stents and flow diverters require the use of safe and fast antiplatelet therapy. We aimed to compare the responses to clopidogrel, prasugrel, and ticagrelor by assessing the Platelet Function Analysis (PFA-100)-Innovance test results of patients undergoing endovascular stenting to determine their resistance rates. Sixty-one women and 55 men, aged 18-87years, were included in this study. Patients were divided into three groups: clopidogrel treatment, prasugrel treatment, and ticagrelor treatment. The systemic diseases of the patients, especially hypertension and diabetes, were recorded. The test results were evaluated according to the results for the collagen/epinephrine (COL-EPI), collagen/adenosine (COL-ADP), and P2Y results. The PFA-100-Innovance results for COL-EPI and P2Y were significantly higher for patients treated with prasugrel and ticagrelor compared with patients treated with clopidogrel (COL-EPI, p = 0.001; P2Y, p = 0.001). Clopidogrel resistance was identified in 31 patients (26.7%), and prasugrel resistance was identified in 4 patients (3.4%). Ticagrelor resistance was not detected. Therefore, 30.1% of patients were classified as drug-resistant. Perioperative bleeding was not detected in any patient. Hypertension was the most common disease recorded for patients being treated for cerebral aneurysm, and diabetes was the most common disease recorded for patients who underwent peripheral artery stenting (p = 0.002). Potent antiplatelet agents, such as prasugrel and ticagrelor, have a low rate of resistance but are associated with an increased bleeding risk. Thus, the choice of a suitable drug during the treatment window remains a critical factor when determining treatment strategies.

Comparison between ticagrelor and clopidogrel in high bleeding risk patients with acute coronary syndrome

Abstract Background Potent antiplatelet agents such as ticagrelor are associated with a lower risk of ischemic events than clopidogrel in patients with acute coronary syndrome (ACS). However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in individuals who have a high bleeding risk (HBR). This study aimed to assess treatment outcomes following dual antiplatelet therapy (DAPT) using either ticagrelor or clopidogrel in ACS patients with HBR. Methods All HBR patients enrolled in the SWEDEHEART registry who were discharged with DAPT using ticagrelor or clopidogrel following ACS between 2010 and 2017 were included in this study. Bleeding risk was assessed using the 4-item PRECISE-DAPT score, which consists of age, prior bleeding, haemoglobin concentration and creatinine clearance. HBR was defined as a PRECISE-DAPT score ≥25. Inverse-probability of treatment weighting was used to adjust for baseline differences between the treatment groups. The main analysis consisted of a doubly robust estimation of causal effect using Cox proportional hazards models. Data on major bleeding, recurrent myocardial infarction (MI), ischemic stroke and all-cause mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, ischemic stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and major bleeding. Results Of all ACS patients, 36% (n=25,042) had a PRECISE-DAPT score ≥25. Approximately half of the study participants were treated with ticagrelor (n=11,848). Ticagrelor reduced the risk of MI (hazard ratio [HR], 0.82 [95% CI 0.74–0.91]), ischemic stroke (HR, 0.73 [95% CI 0.60–0.88]) and MACE (HR, 0.90 [95% CI 0.84–0.97]), while also increasing the risk of major bleeding compared to clopidogrel (HR, 1.30 [95% CI 1.16–1.47]). We found no significant differences in all-cause mortality (HR 1.02 [95% CI 0.92–1.12]) and NACE (HR 0.98 [95% CI 0.92–1.05]). Conclusions Ticagrelor was associated with a lower risk of recurrent ischemic events, but a higher risk of major bleeding compared to clopidogrel. There were no significant differences in all-cause mortality and NACE between the treatment groups. These results suggest that more potent antiplatelet agents might not be superior to clopidogrel in ACS patients with HBR. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Stockholm county council

Glenzocimab: A GPVI (Glycoprotein VI)-Targeted Potential Antiplatelet Agent for the Treatment of Acute Ischemic Stroke.

It has previously been shown in several animal experiments that platelet GPVI (glycoprotein VI) contributes to thrombosis, particularly in ischemic stroke. Moreover, GPVI levels are upregulated in stroke patients. This review describes the therapeutic roles of anti-GPVI antibody in preclinical models of ischemic stroke and provides the current evidence for potential benefits of glenzocimab, a Fab fragment of humanized anti-GPVI monoclonal antibody, in stroke patients. Anti-GPVI antibody, JAQ1, significantly decreased infarct volume and improved neurological function in mice with transient middle cerebral artery occlusion, a model of ischemic stroke, with no or minor bleeding tendency. Intravenous injection of glenzocimab in nonhuman primates produced rapid inhibition of ex vivo platelet aggregation induced by collagen (a GPVI ligand). Complete platelet inhibition is observed at 30 minutes following administration without increasing the risk of bleeding. In humans, glenzocimab is well tolerated and produces dose-dependent antiplatelet activity. More importantly, glenzocimab (125-1000 mg) was safe when administered as soon as possible (<3 hours) following reperfusion with the r-tPA (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke. Although glenzocimab 1000 mg (a selected dose) did not demonstrate a significant improvement in overall clinical outcomes, it appeared to provide benefits in severe cases and in patients who required thrombectomy. This promising efficacy together with a good safety profile of glenzocimab warrant further investigation in phase III (ACTISAVE [Adaptive Efficacy and Safety Study of Glenzocimab Used as an Add-On Therapy on Top of Standard of Care in the 4.5 Hours Following an Acute Ischemic Stroke]) clinical study.

Current Status and Future Direction of Antithrombotic Therapy for Patients with STEMI Undergoing Primary PCI.

Since the introduction of the first pharmacological therapy for the treatment of patients with acute myocardial infarction in the early 20th century, treatment of myocardial infarction has evolved extensively throughout the years. Mechanical revascularization therapies such as the percutaneous transluminal coronary angioplasty, combined with the ongoing development of pharmacological therapies have successfully improved the survival of patients with acute myocardial infarction. To date, antiplatelet therapy (consisting of aspirin and an oral inhibitor) and anticoagulation therapy represent the main stay of pharmacological treatment in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The routine use of clopidogrel as antiplatelet agent has been largely replaced by the use of the more potent inhibitors ticagrelor and prasugrel. Unfractionated heparin remains the preferred anticoagulant therapy, despite the development of other anticoagulants, including enoxaparin and bivalirudin. To date, limited evidence exists supporting a pre-hospital initiation of antiplatelet and anticoagulant therapy in STEMI patients. The use of potent intravenous antiplatelet agents, including the glycoprotein IIb/IIIa inhibitors and the intravenous inhibitor cangrelor, is currently restricted to specific clinical settings. While several potent antithrombotic agents already exist, the search for novel potent antithrombotic agents continues, with a focus on balancing antithrombotic properties with an improved safety profile to reduce excess bleeding. This review provides an overview of currently available pharmacological therapies for the treatment of STEMI patients undergoing primary PCI, and an outlook for the ongoing development of novel agents in this field.

Ticagrelor versus Clopidogrel in Patients with Severe Renal Insufficiency Undergoing PCI for Acute Coronary Syndrome.

Background Current guidelines recommend the use of potent antiplatelet agents in patients undergoing percutaneous coronary intervention (PCI) following an acute coronary syndrome (ACS). However, data about optimal platelet inhibition in severe renal insufficiency patients are scarce. The purpose of this study is to determine if ticagrelor is more effective than clopidogrel in patients with ACS and severe renal insufficiency treated with PCI. Methods We retrospectively enrolled patients with ACS and severe renal insufficiency (eGFR ≤ 30 ml/min·1.73 m2 or dialysis) who underwent PCI at our hospital between January 2015 and March 2020. We used the adjusted Cox proportional hazards models to analyze the 1-year outcome endpoints, including the primary endpoint (the composite of cardiovascular death, recurrence of MI, or nonfatal ischemic stroke), death from any cause, and bleeding events (Bleeding Academic Research Consortium, BARC criteria). Results A total of 276 patients with ACS and severe renal insufficiency who were treated with PCI with ticagrelor (n = 108) or clopidogrel (n = 168) were included in the study. After adjustment, there was no statistical difference in risk of the primary endpoint (HR, 0.78; 95% CI, 0.46–1.33; P=0.367) and death from any cause (HR, 0.86; 95% CI, 0.38–1.89; P=0.708) in the ticagrelor group against the clopidogrel group. However, the risk of total bleeding was significantly higher in the ticagrelor group (HR, 3.01; 95% CI, 1.81–5.62; P=0.01). Subgroup analysis according to the confounders did not identify any significant subgroup heterogeneity. Conclusion Ticagrelor did not improve the major adverse cardiovascular events and all-cause mortality when compared to clopidogrel, but significantly increased the risk of bleeding in Chinese patients with ACS and severe renal insufficiency undergoing PCI.

Experience with the use of combination antithrombotic therapy in a patient with acute coronary syndrome and underlying severe coronavirus infection

The paper presents the experience of treating a patient with acute coronary syndrome without ST segment elevation and underlying severe novel coronavirus infection (COVID-19) complicated by polysegmental viral pneumonia and significant respiratory events. Emphasis has been placed on the use of antithrombotic therapy after endovascular treatment. A 56-year-old patient underwent respiratory support (non-invasive face mask lung ventilation followed by high-flow oxygenation), urgent diagnostic coronary angiography followed by percutaneous coronary intervention (balloon angioplasty and stenting of the right coronary artery and anterior interventricular artery). In addition to the etiopathogenetic therapy for coronavirus infection, the patient received combination antithrombotic therapy, including acetylsalicylic acid, prasugrel, FRaMon monoclonal antibodies (single exposure, intraoperatively), sodium enoxaparin. The therapy resulted in normalization of hemodynamic parameters, stable normothermia, absence of catarrhal events, improvement of exercise tolerance. A chest ultrasound imaging showed consolidation events, inflammatory markers significantly decreased, circulatory deficiency events were compensated, anginal pains did not recur. On the 20th day of hospitalization, the patient was discharged home with outpatient follow-up. The use of potent antiplatelet agents such as prasugrel or ticagrelor combined with IIb/IIIa receptor inhibitors and prolonged anticoagulant therapy can potentially improve the outcome of the disease in acute coronary syndrome with underlying severe coronavirus infection. In the presented clinical example, the use of aggressive approaches to the antithrombotic therapy did not lead to the development of significant hemorrhagic or other complications.

In-Hospital Bleeding in Elderly Patients With Acute Coronary Syndrome: Are Potent Antiplatelet Agents Safe?

Despite implementation of new interventional techniques and therapeutic advances, elderly patients with acute coronary syndrome (ACS) continue to be susceptible to in-hospital bleeding compared with younger ones. Thus, we investigated the incidence of in-hospital bleeding events and associated risk factors in elderly (≥ 75°years) ACS patients. We also wanted to define the bleeding sites, characteristics, and associated mortality. Bleeding Academic Research Consortium (BARC) classification type 2, 3, or 5 was used to define bleeding events. Overall, 539 patients were included in the study (mean age: 82.5 ± 4.8°years; 282 (52.3%) females). Of these patients, 69 (12.8%) developed in-hospital bleeding. Factors that were independently related with in-hospital bleeding were age (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.011.14, P = .01), acute kidney injury (OR: 3.66; 95% CI: 2.016.69; P < .01), tirofiban (OR: 4.43; 95% CI: 1.7810.99; P < .01), and ticagrelor (OR: 1.93; 95% CI: 1.013.73; P = .04) administration. The urinary tract was the most frequent bleeding site, followed by femoral arteries. In conclusion, ticagrelor and tirofiban should be used with caution in elderly ACS patients.

Abstract TP261: Oenanthe Javanica , A Potential Therapeutic Agent For Dual Antiplatelet Therapy To Overcome Clopidogrel Resistance

Background: Dual antiplatelet therapy with clopidogrel and aspirin prescription is standard for various clinical settings such as Acute Coronary Syndrome. However, the therapy is less effective on a large portion of the Asian population due to clopidogrel resistance. Oenanthe javanica (O. J.) has been used in traditional Chinese medicine for a range of ailments. In this study, we aimed to evaluate Oenanthe javanica extract’s antithrombotic effects and its potential to be used in Dual Antiplatelet Therapy (DAPT) to overcome clopidogrel resistance. Method: Prothrombin time (PT), activated partial thromboplastin time (aPTT), ADP and ASPI were measured using blood samples collected from 2 healthy volunteers. One volunteer took 2 75mg clopidogrel (CPG) tablets 2 hours before the experiment. The blood samples were incubated with O. J. extract for 30min before the measurement. For in vivo experiments, FeCl 3 thrombosis were induced to right common carotid arteries of Sprague Dawley rats (270-300g). The rats were divided into 5 groups (N=5-6): Control group, O. J. group, CPG group, CPG+O. J. group, and CPG+ASA group. O. J. extract was orally administered 200mg/kg per day for 3 days. CPG and ASA were orally administered 10mg/kg 2 hours before the experiment. Thrombosis was induced using filter paper doused with 10μL of 20% FeCl 3 solution. After the induction, blood flow was measured for 55min and thrombus weight was measured. Results: O. J. extract did not have any effect on PT, aPTT, and ASPI. However, O. J. extract did have an effect on ADP value, even though the volunteer had clopidogrel resistance. In FeCl 3 thrombosis model, O. J., CPG, CPG+ASA, and CPG+O. J. group all significantly increased the time-to-occlusion (TTO) compared to the Control group. This was true for thrombus weight as well. Conclusion: Our results indicate that O. J. extracts is a potential antiplatelet agent for dual antiplatelet therapy for patients with clopidogrel resistance.