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PB2452, a neutralizing monoclonal antibody fragment that binds the antiplatelet drug ticagrelor with high affinity, is being developed as a ticagrelor reversal agent. To identify a clinically useful intravenous (i.v.) reversal regimen, a semimechanistic exposure‐response model was developed during the PB2452 first‐in‐human phase I study. From a randomized, double‐blind, placebo‐controlled, single‐dose trial to evaluate the safety, efficacy, and pharmacokinetics (PKs) of PB2452 in 61 healthy volunteers pretreated with ticagrelor, sequential dose cohort data were used to build and refine an exposure‐response model that combined population PK models for ticagrelor (TICA), ticagrelor active metabolite (TAM), and PB2452, and related their binding relationships to the PK of uncomplexed TICA and TAM which is predictive of platelet inhibition. Platelet function was assessed by multiple assays. The model was developed using Bayesian methods in NONMEM. Human PK and pharmacodynamic data from sequential dose cohorts were used to initially define and then refine model parameters. Model simulations indicated that an initial i.v. bolus of PB2452, followed by a high‐rate infusion, and then a slower‐rate infusion would provide immediate and sustained reversal of the antiplatelet effects of ticagrelor. Based on model predictions, a 6 g i.v. bolus followed by 6 g infused over 4 h and then 6 g over 12 h was identified and tested in study subjects and shown to provide complete reversal within 5 min of infusion onset that was sustained for 20–24 h. The model is predictive of the reversal profile of PB2452 and will inform future trials of PB2452.

Patients undergoing coronary artery bypass graft (CABG) surgery or carotid endarterectomy (CEA) continue antiplatelet therapy perioperatively, which may increase bleeding risk. We aimed to investigate whether Rotational thromboelastometry (ROTEM®) platelet, a newly marketed platelet function analysis, would detect antiplatelet therapy in CABG and CEA patients; whether detection of reduced platelet function was associated with increased bleeding; and whether ex vivo desmopressin increased platelet function. We included 20 CABG patients continuing aspirin and 20 CEA patients continuing clopidogrel (n = 1) or clopidogrel and aspirin (n = 19). Platelet function was analyzed with ROTEM® platelet and light transmission aggregometry (LTA). According to the lower reference limit, ROTEM® platelet managed to detect aspirin, but clopidogrel detection was inadequate compared to LTA. Using a previously published cut-off for bleeding risk, 6 (30%) patients receiving aspirin and 4 (21%) patients receiving both clopidogrel and aspirin demonstrated platelet function below this cut-off. One of the four CEA patients below the cut-off died from intracerebral hemorrhage postoperatively. CABG patients below (n = 6) and above (n = 14) the cut-off did not differ in chest tube output (median [range]: 373 ml [250-900] vs. 368 ml [195-820]). Ex vivo addition of desmopressin did not increase platelet function. In conclusion, ROTEM® platelet does reveal aspirin treatment whereas clopidogrel treatment is most often overlooked. Due to low bleeding in the study population, it was not possible to conclude on the association with bleeding risk.

Tetramethylpyrazine (TMP) is commonly used as an antiplatelet drug in clinic. However, the short half-life and low bioavailability limited its applications. 3, 5, 6-Trimethylpyrazine-2-carboxAylic acid (TMP-COOH) and 2-hydroxy-3, 5, 6-trimethylpyrazine (TMP-OH) are the two major active metabolites of TMP in vivo. Both displayed antiplatelet aggregation activity but have obvious disadvantage of rapid metabolism. In this study, conjugates of TMP-COOH/TMP-OH with amino acids were designed to address this issue. We demonstrated that 13 out of 20 conjugates displayed higher antiplatelet aggregation activity than TMP. The optimized compound 4a was further proved to reduce clot retraction, prolong the bleeding time, thrombin time, prothrombin time, activated partial thromboplatin time and reduce fibrinogen content. Taken together, we demonstrated the conjugation strategy could be exploited to develop TMP derivatives for antiplatelet agents.

Background Persons with atrial fibrillation (AF) are at risk for stroke. Atrial fibrillation-related strokes most often result for emboli arising from the left atrial appendage (LAA). Stroke prevention includes the use of anticoagulants and/or antiplatelets. These medications can result in bleeding complications. An alternative to anticoagulants is the WATCHMAN device, which is delivered in the left atria resulting in closure of LAA. Objective The aim of this study was to describe patient, procedural, and follow-up characteristics in patients who have undergone WATCHMAN implantation. Methods This study used a retrospective design to review data previously collected and entered into the National Cardiovascular Data Registry database. Results During a 2-year period, 41 patients underwent the WATCHMAN procedure at our facility. The most common indication for the procedure in this population of patients with nonvalvular AF on oral anticoagulants was bleeding in the gastrointestinal or genitourinary systems. (Gastrointestinal/genitourinary bleed does not limit candidacy for surgical closure of the LAA.) There was only 1 postprocedure adverse event that included a groin hematoma. A transesophageal echocardiogram at 45 days indicated that the LAA seal showed no leak or flow around the device or a leak less than 5 mm. At 1 year, 95% (n = 36) of patients were only taking a single antiplatelet drug with aspirin. Eight patients were on a single antiplatelet medication at the time of follow-up 2 years after the procedure. Discussion A skilled team including a designated AF clinical nurse specialist contributed to program success measured by efficient placement of the WATCHMAN device and discontinuation of anticoagulation.

Supplemental Digital Content is available in the text., Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258–0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206–2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

Introduction: No clear guidelines for treating adult patients with ischemic moyamoya disease (MMD) without cerebral hemodynamic compromise such as misery perfusion have been established. Our previous prospective cohort study of adult patients with MMD without misery perfusion who were treated with medical management alone, including an antiplatelet drug, showed a recurrent ischemic event rate of 3% per 2 years. The present prospective study aimed to elucidate the 5-year clinical, cerebral perfusion, and cognitive outcomes of medical management alone for Japanese adult patients with ischemic MMD without cerebral misery perfusion by following the same patients for another 3 years. Methods: In total, 68 patients without recurrent events at a 2-year follow-up were prospectively followed up for another 3 years. Cerebral blood flow (CBF) in the symptomatic cerebral hemisphere was measured using brain perfusion single-photon emission computed tomography at inclusion and at the end of the subsequent 3-year follow-up. Neuropsychological testing was performed at inclusion and at the end of the initial 2- and subsequent 3-year follow-ups. Results: During the subsequent 3-year follow-up, 2 patients (3%) developed further ischemic events. In patients without further ischemic events, CBF was significantly greater at the end of the subsequent 3-year follow-up than at inclusion (p = 0.0037), and all neuropsychological test scores improved or remained unchanged at the end of initial 2- and subsequent 3-year follow-ups compared with that at inclusion. Conclusion: In adult patients receiving medical management alone for ischemic MMD without cerebral misery perfusion, the incidence of further ischemic events was 6% per 5 years and did not change between the initial 2 years after the last is­chemic event and the subsequent 3 years. In patients without further ischemic events, CBF and cognitive function had not deteriorated at 5 years after the last ischemic event.

Prasugrel Hydrochloride (PHCl) is an antiplatelet drug. It is a class II drug with variable bioavailability. The objective of this work was to enhance the solubility and hence the bioavailability a...

Spontaneous coronary intramural hematoma (SCIH) was one type of spontaneous coronary artery dissection without obvious intimal tear, which is easy to misdiagnose. We aimed to study the characteristics, management, and prognosis of SCIH in our center. All the SCIH patients (n = 30) diagnosed by coronary angiography from January 1, 2012 to December 31, 2018 were enrolled. The demographic characteristics, history, therapy, and follow-up were collected. The mean age of the patients was 51.8 ± 9.5 years. Most of the patients were females (66.7%) with hypertension. Patients with diffuse lesion, focal lesion, and multiple vessels were 70%, 13.3%, and 16.7%, respectively. Conservative treatment was the first choice (76.7%). The mean follow-up time was 29.3 ± 13.5 months. None of the patients had unplanned readmission due to worsening symptoms. Nine patients underwent coronary artery computed tomography reexamination after 10.3 ± 7.5 months, which showed complete recovery of SCIH. Eight patients were hospitalized for coronary angiography 6.4 ± 4.7 months later, which did not show any sign of SCIH. Spontaneous coronary intramural hematoma was most common in post-menopausal women with hypertension. Possibly, antiplatelet drugs should be avoided in SCIH. Waiting for the hematoma to heal was preferable and had a good prognosis.

Introduction Platelets are increasingly appreciated as key effectors during sepsis, raising the question of the usefulness of antiplatelet drugs to treat patients with sepsis. Objective Evaluate the potential contribution of the platelet P2Y12 receptor in the pathogenesis of polymicrobial-induced sepsis and septic shock in mice. Methods The effects of P2Y12 inhibition using clopidogrel treatment and of platelet-specific deletion of the P2Y12 receptor in mice were examined in two severity grades of cecal ligation and puncture (CLP) leading to mild sepsis or septic shock. Results Twenty hours after induction of the high grade CLP, clopidogrel- and vehicle-treated mice displayed a similar 30% decrease in mean arterial blood pressure (MAP) characteristic of shock. Septic shock-induced thrombocytopenia was not modified by clopidogrel treatment. Plasma concentrations of inflammatory cytokines and myeloperoxidase (MPO) were similarly increased in clopidogrel- and vehicle-treated mice, indicating comparable increase in systemic inflammation. Thrombin-antithrombin (TAT) complexes and the extent of organ damage were also similar. In mild-grade CLP, clopidogrel- and vehicle-treated mice did not display a significant decrease in MAP, while thrombocytopenia and plasma concentrations of TNFα, IL6, IL10, MPO, TAT and organ damage reached similar levels in both groups, although lower than those reached in the high grade CLP. Similarly, mice with platelet-specific deletion of the P2Y12 receptor were not protected from CLP-induced sepsis or septic shock. Conclusion The platelet P2Y12 receptor does not contribute to the pathogenesis of sepsis or septic shock in mice, suggesting that P2Y12 receptor antagonists may not be beneficial in patients with sepsis or septic shock.

The necessity of a simple measurement of platelet activation has been increasing in clinical medicine to regulate the proper dose of the antiplatelet drugs for patients having clinical outcomes in acute situations such as angina pectoris, stroke, or peripheral vascular disease or procedures involving angioplasty or coronary thrombolysis. We developed a self-signaling polydiacetylene (PDA) liposome microarray to detect activated platelets from whole blood samples in a single step. A specific antibody, 9F9 antibody, to platelet-bound fibrinogen was selected and conjugated to the PDA liposome microarray to quantify the fibrinogen-bound platelets. The developed PDA liposome-9F9 microarray generated an intense fluorescence signal when activated platelets in whole blood were introduced and also successfully distinguished the reduced platelet activation in the presence of Tirofiban, a model antiplatelet drug. The results of this single-step benchtop assay incorporates simple, sensitive, and rapid attributes that can detect the extent of platelet activation prior to needed clinical procedures.

Ticagrelor is an oral antiplatelet drug that can reversibly bind to the platelet P2Y12 receptor. Ticagrelor is metabolized mainly by CYP3A4 and produces a rapid blood concentration-dependent platelet inhibitory effect. Unlike other P2Y12 receptor antagonists, many clinical features of ticagrelor are not related to P2Y12 receptor antagonism. This review aims to gather existing literature on the clinical effects of ticagrelor after inhibiting adenosine uptake. The current study reviewed literature related to the effects of ticagrelor on adenosine metabolism. The review also examined the drug's biological effects and clinical characteristics to see how it could be used in a clinical setting. Many studies have shown that ticagrelor can inhibit equilibrative nucleoside transporter 1 (ENT1). This inhibition leads to intracellular adenosine uptake, increased adenosine half-life and plasma concentration levels and an enhanced adenosine-mediated biological effect. Based on the studies reviewed, it was found that ticagrelor essentially inhibits adenosine absorption of adenosine into cells through ENT1, which increases the concentration in the blood and subsequently increases the protection of the heart muscle by adenosine. It also prevents platelet aggregation, and extends the biological effects of coronary arteries. Moreover, it leads to a lower mortality rate in acute coronary syndrome (ACS) patients.

The aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to be incorporated into clinical practice. In the absence of specific indications for chronic oral anticoagulation due to concomitant cardiovascular disease, a single antiplatelet agent is the basis for long-term antithrombotic treatment in patients with aortic or peripheral arterial diseases. Its association with another antiplatelet agent or low-dose anticoagulants will be discussed, based on patient’s ischaemic and bleeding risk as well therapeutic paths (e.g. endovascular therapy). This consensus document aims to provide a guidance for antithrombotic therapy according to arterial disease localizations and clinical presentation. However, it cannot substitute multidisciplinary team discussions, which are particularly important in patients with uncertain ischaemic/bleeding balance. Importantly, since this balance evolves over time in an individual patient, a regular reassessment of the antithrombotic therapy is of paramount importance.

Background: The benefit of optimal medical therapy (OMT) on 5-year outcomes in patients with 3-vessel disease and/or left main disease after percutaneous coronary intervention or coronary artery bypass grafting (CABG) was demonstrated in the randomized SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. Objectives: The objective of this analysis is to assess the impact of the status of OMT at 5 years on 10-year mortality after percutaneous coronary intervention or CABG. Methods: This is a subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which evaluated for up to 10 years the vital status of patients who were originally enrolled in the SYNTAX trial. OMT was defined as the combination of 4 types of medications: at least 1 antiplatelet drug, statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. After stratifying participants by the number of individual OMT agents at 5 years and randomized treatment, a landmark analysis was conducted to assess the association between treatment response and 10-year mortality. Results: In 1,472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; 95% CI: 0.292-0.757; P = 0.002) but had a mortality similar to those on 3 types of medications. Furthermore, patients undergoing CABG with the individual OMT agents, antiplatelet drug and statin, at 5 years had lower 10-year mortality than those without. Conclusions: In patients with 3-vessel and/or left main disease undergoing percutaneous coronary intervention or CABG, medication status at 5 years had a significant impact on 10-year mortality. Patients on OMT with guideline-recommended pharmacologic therapy at 5 years had a survival benefit. (Synergy Between PCI With Taxus and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Background and purpose In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. Methods The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1–4, 3) MBs 5–9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. Results Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1–4, 48 (4%) had MBs 5–9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1–4, 94% in the MBs 5–9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1–4, MBs 5–9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). Conclusions MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.

Background: Antiplatelet agents reduce the occurrence of the cardiovascular issue in people with established cardiovascular disease. Objective: To understand the pattern of Antiplatelet drug utilization among cardiovascular disease patients. To evaluate the prevalence of polypharmacy and responsible factors like age, gender, co-morbid condition, and patient-related drug use problems. Methodology: A cross-sectional observational study. Patients with cardiovascular disease above 18 years of age were prescribed antiplatelet agents from the department of cardiology and ICCU were enrolled in the study. Result: A total of 150 patients were enrolled of which male 79% (N=119) and female 21% (N=31). Most patients belong to 51-60 years of age groups. The patients diagnosed with IWMI (inferior wall myocardial infarction) 43.3% (N=65) have highly prescribed antiplatelet agents. Smoking 54.7% (N=82) followed by Alcohol 26.7% (N=40) found to be the most dominant risk factors.60.7% (N=91) patients had no comorbidity followed by 31.3% (N=47) had a comorbid cardiac condition. Most prescribed antiplatelet agents were monotherapy of Aspirin 28.8% (N=43), Clopidogrel 16.7% (N=25), and combination therapy of both 51.2% (N=82). Conclusion: The study concluded that increases in the number of co-morbidities can significantly increase the Utilization of drugs which can further lead to drug use problems. The clinical pharmacist can help to alleviate the problems of polypharmacy and its consequence.

Aspirin, an antiplatelet drug, is commonly used at low doses for numerous indications, including prophylaxis of cardiovascular, neurovascular, and venous thromboembolic events. Due to review articles suggesting that aspirin resistance may result in poorer outcomes, interest in assessing platelet function is increasing. Despite this, platelet function tests are rarely used as part of routine clinical practice and therefore, a basic understanding of these tests may be lacking. Although aspirin resistance can be categorized as clinical or laboratory resistance, determining laboratory resistance is the only way to determine resistance before treatment failure occurs. Therefore, knowledge of platelet assays to determine aspirin resistance is of importance. The following review aims to provide a framework for clinicians to understand the main principles of platelet function tests. This includes comparison of the most frequently used platelet assays to diagnose aspirin resistance, including the basic mechanism, methodology, reference ranges, inter-assay comparison, and their respective clinical considerations when using.

After an ischaemic stroke or transient ischaemic attack, patients have a high risk of having another stroke. Secondary stroke prevention includes antiplatelet therapy, statins and antihypertensives Aspirin, clopidogrel, or a combination of aspirin with dipyridamole are first-line options for secondary stroke prevention in the absence of atrial fibrillation Dual antiplatelet therapy has a benefit in the first three weeks after stroke, but patients should change to a single antiplatelet drug after this time Anticoagulants are indicated if the patient has atrial fibrillation. Avoid combinations of anticoagulants and antiplatelet drugs Patients should be started on statins after an ischaemic stroke. High doses are recommended even if cholesterol concentrations are normal Antihypertensive drugs are recommended for all patients with systolic blood pressures greater than 140/90 mmHg. ACE inhibitors, calcium channel blockers and diuretics are first-line options.

Background: A significant percentage of people who see a dentist are on antiplatelet treatment, and the rest of them have stopped taking these medications for 3 to 7 days prior to dental surgical surgery to avoid unnecessary bleeding and the possibility of adverse thrombotic cases. This study was conducted to compare postoperative bleeding with and without stopping antiplatelet drugs in tooth extraction. Materials and Methods: Patients were divided into two groups, Group A consists of extraction of tooth without discontinuation of antiplatelet and Group B consists of extraction of tooth with discontinuation of antiplatelet with the consent from treating physician/cardiologist. All patients underwent for extraction under local anesthesia. Postoperatively, the amount of blood lost during the operation was calculated, any oozing or bleeding was looked at the operated spot and occurrence or nonappearance of oozing, as well as active bleeding was measured. Results: Mean age of group A patients was 55.08 years and mean age of group B was 52.92 years. After 1 hour assessment of bleeding status, active bleeding was 12% in group A and 6% was in group B, findings were non-significant (p=0.271). After 24 hours assessment of bleeding status, there was no bleeding in 42% patients of group A and 58% patients of group B, oozing was in 34% patients of group A and 26% patients of group B, while active bleeding was 24% in group A and 16% was in group B, findings were non-significant (p=0.271). Mean of bleeding (in grams) was higher in Group A as compared to Group B (p=0.041). Conclusion: There was no significant effect on bleeding during tooth extraction with continuation of anticoagulant therapy

BACKGROUND: The protocol for optimal antiplatelet therapy to prevent thromboembolic and hemorrhagic complications in patients with cerebral aneurysms using an endovascular approach is not clear. PURPOSE: Our study analyzed the safety and efficacy of prophylactic tirofiban administration compared with oral antiplatelet drug therapy. DATA SOURCES: We used the PubMed, EMBASE, MEDLINE, and Cochrane library data bases. STUDY SELECTION: Our study consisted of all case series with >5 patients that reported treatment-related outcomes of patients undergoing endovascular procedures pretreated with tirofiban or oral antiplatelet drug therapy. DATA ANALYSIS: Random effects or fixed effects meta-analysis was used to pool the cumulative rate of complications, perioperative mortality, and good clinical outcomes. DATA SYNTHESIS: Fifteen studies with 1981 patients were registered. Thromboembolic complications were significantly lower in the tirofiban group (3.6%; 95% CI, 1.9%–5.8%) compared with the dual-antiplatelet therapy group (8.5%, 95% CI, 4.5%–13%; P = .04). Pretreatment with tirofiban did not remarkably increase the rate of hemorrhagic complications (3.5%; 95% CI, 1.8%–5.6%) compared with dual-antiplatelet therapy (5.1%; 95% CI, 2.6%–8.5%; P = .371). There was a trend toward lower perioperative mortality with tirofiban (0.8%; 95% CI, 0.2%–1.6%) compared with dual-antiplatelet therapy (1.2%; 95% CI, 0.7%–2.0%; P = .412). There was no significant difference in the safety and efficacy between the tirofiban bolus plus drip and drip alone. LIMITATIONS: The limitations are selection and publication biases. CONCLUSIONS: Prophylactic therapy with tirofiban resulted in significantly lower rates of thromboembolic complications with no increase in hemorrhagic events or mortality than the prophylactic use of dual-antiplatelet therapy.

Background/Aims Coronary endothelial and microvascular function play important roles in cardiovascular disease. We aimed to evaluate the effect of ticagrelor on coronary artery function and tested the antiplatelet effect of low dose ticagrelor in East-Asian patients. Methods Sixty-one consecutive patients with non-significant coronary disease were included in the study. Initially, patients were randomized in 1:1:1 ratio to receive drugs: ticagrelor 90 mg twice a day (bid; n = 22), ticagrelor 45 mg bid (n = 19) or clopidogrel 75 mg once a day (qd; n = 20) and then divided into two groups (ticagrelor vs clopidogrel) for evaluation of coronary artery function, and three groups for evaluation of antiplatelet function. Endothelial dysfunction was measured by coronary flow reserve (CFR), and changes in the levels of asymmetric dimethylarginine (ADMA), cluster of differentiation (CD) 40 ligand, and P-selectin. Microvascular function was evaluated as index of microvascular resistance (IMR). Platelet reactivity was assessed by VerifyNow P2Y12 assay. Results The levels of CFR, ADMA, and CD 40 ligand were not different between the two groups. However, P-selectin was lower in the ticagrelor group compared with clopidogrel group. IMR was significantly lower in the ticagrelor group compared with clopidogrel group (median, 15.0 [interquartile range, 12.0 to 21.0] vs. 47.5 [23.0 to 67.5], p = 0.014). There was significant difference in platelet inhibition among the three groups (ticagrelor 90 mg bid vs. ticagrelor 45 mg bid vs. clopidogrel 75 mg qd; 85.57 ± 47.63 vs. 120.33 ± 51.09 vs. 256.42 ± 55.10, p < 0.001) Conclusions It is hypothesized that ticagrelor might ameliorate the coronary microvascular function. When compared with clopidogrel, low dose ticagrelor exhibited satisfactory antiplatelet effect in the present study.

The authors hypothesized that the cytokine storm described in COVID-19 patients may lead to consistent cell-based tissue factor (TF)-mediated activation of coagulation, procoagulant microvesicles (MVs) release, and massive platelet activation. COVID-19 patients have higher levels of TF+ platelets, TF+ granulocytes, and TF+ MVs than healthy subjects and coronary artery disease patients. Plasma MV-associated thrombin generation is present in prophylactic anticoagulated patients. A sustained platelet activation in terms of P-selectin expression and platelet–leukocyte aggregate formation, and altered nitric oxide/prostacyclin synthesis are also observed. COVID-19 plasma, added to the blood of healthy subjects, induces platelet activation similar to that observed in vivo. This effect was blunted by pre-incubation with tocilizumab, aspirin, or a P2Y12 inhibitor.

Hypoglycemia should be avoided when treating patients with diabetes. Repaglinide is an insulin secretagogue with a low hypoglycemic risk because of its rapid- and short-acting effects. However, its blood concentration has been reported to increase in combination with clopidogrel, an antiplatelet drug, and in patients with severe renal insufficiency. We herein report an elderly patient with type 2 diabetes mellitus and severe renal insufficiency who received repaglinide and hypoglycemia three days after starting clopidogrel. The concomitant use of repaglinide and clopidogrel can lead to hypoglycemia, especially in patients with severe renal insufficiency.

Nonalcoholic fatty liver disease (NAFLD) is a complex disease caused by a number of different pathogenic processes as a result of the systemic interaction between the liver and several other organs. Grape seeds proanthocyanidins extract (GSPE) potency in the liver is associated with improvement of the hepatic enzyme activities as their powerful antioxidant property results from its ability to directly scavenge free radicals and/or chelate metals. 32 male albino rats were assigned into 4 equal groups of 8 rats: 1. Normal control group (G1) of rats provided with standard normal diet for 12 weeks, 2. NAFL group (G2) of rats received high fat diet (HFD)-feeding for 6 weeks for induction of NAFL, followed by normal feeding for other 6 weeks, 3. GSPE treated group (G3) of the HFD-induced NAFL, followed by administration of GSPE for 6 weeks else, 4. GSPE and antiplatletes drug (Clopidogrel) co-treated group (G4), of the NAFL rats, followed by administration of GSPE and clopidogrel co-treatment for another 6 weeks. The results revealed that GSPE alone or with clopidogrel treatment significantly decreased serum AST, ALT and γGGT (G3, 4) that were significantly increased in HFD-NAFL rats (G2), and showed significant upregulation of IL1β, PPARα, TGFβ1 and TIMP1 in livers of NAFL rats (G2), that was significantly downregulated following administration of GSPE alone (G3), or with clopidogrel (G4). Subsequantly, treatment with GSPE alone or with antiplatelet drug can improve the metabolic disruptions associated with the induction of NAFL by improving the liver biomarkers and inflammatory mediator's expressions.

Clopidogrel is an antiplatelet drug that displays significant interindividual variability in treatment response. Its bioavailability depends on the function of P-glycoprotein (P-gp), which is coded by a highly polymorphic ABCB1 gene. Thus, the aim of this study was to investigate the effect of ABCB1 genetic polymorphism on clopidogrel efficacy and safety and to determine the frequency distribution of its most common single nucleotide polymorphisms (SNPs) in 106 Montenegrin cardiology patients. Clopidogrel efficacy and safety were followed up during 1 year after hospitalization, with the lack of efficacy and adverse drug reactions observed in 11 (10.4%) and 8 patients (7.5%), respectively. Genotyping for ABCB1 SNPs rs1128503 (1236C > T), rs2032582 (2677G > A/T), and rs1045642 (3435C > T) was performed by the real-time PCR method, and the variant alleles were detected with the frequencies of 42.9, 44.8, and 52.8%, respectively. No significant association was observed between any of the examined genotypes and clopidogrel efficacy (p = 0.253) or safety (p = 0.424). Due to small sample size, co-treatment with other drugs, and other genetic factors not taken into account, we believe the absence of correlation between ABCB1 genotypes and indicators of clopidogrel efficacy and safety in this study should be apprehended conditionally, and that larger and better-controlled studies are warranted.

Although a reliable procedure in morbid obesity treatment, bariatric surgery may be associated with serious complications such as leakage or bleeding. We aimed to analyze the preoperative factors involved in patients with early postoperative hemorrhage after any type of bariatric surgery who required conservative treatment or reoperation for this complication. Retrospective case-controlled study (1:3) of 2 patient cohorts (postoperative bleeding/controls) matched by type of surgical intervention. Hypertension (Odds Ratio 5.029; 95% Confidence Interval 1.78–14.13) and history of antiplatelet medication (OR 13.263; 95% CI 1.39–125.9) were independent risk factors in the bivariate analyses, confirmed in the logistic regression model on multivariate analysis. With no between-group differences in Body Mass Index (BMI) and type 2 Diabetes (T2D), early hemorrhagic complications were found to be more frequent in patients with hypertension or antiplatelet drug treatment.

Objective: This study aims to discover whether insulin resistance is an independent predictor for antiplatelet drug resistance in patients with ischemic cerebrovascular disease.Methods: This study ...

Introduction Currently, invasive cardiology techniques are the preferred method of treatment for patients with ST-elevation myocardial infarction (STEMI). Improving the care of patients with STEMI is possible by minimizing the time that elapses from the onset of pain to the start of treatment. As studies indicate, early pharmacotherapy, especially with antiplatelet and anticoagulant medications, allows for their early effectiveness. Aim To assess the influence of early administration of antiplatelet (clopidogrel) and anticoagulant medications in the pre-hospital period in patients with ST-elevated myocardial infarction on the frequency of in-hospital deaths and on the left ventricular ejection fraction evaluated at hospital discharge. Material and methods In this study, a retrospective analysis of 573 patients hospitalized due to ST-segment elevation myocardial infarction in one of Krakow's hospitals from January 2011 to December 2015 (excluding the whole of 2013) was used as a research method. Results As many as 97% of patients received pre-hospital pharmacotherapy, but only 46.0% of respondents received unfractionated heparin, and 19.2% received clopidogrel. The in-hospital mortality rate was 6.7%, but among patients prehospitally treated with clopidogrel and unfractionated heparin, the in-hospital mortality rate was 1.1%. Prehospital administration of clopidogrel significantly decreased the possibility of reduced left ventricular ejection fraction (OR = 0.27; 95% CI: 0.09-0.90). Conclusions Among pre-hospital procedures, only administration of a second antiplatelet drug (clopidogrel) significantly decreased the risk of reduced left ventricular ejection fraction, and administration of clopidogrel or heparin, or a combination of both, significantly decreased the risk of in-hospital death in patients with STEMI.

Objective: The innovative approach in this investigation is making an enteric-coated acetylsalicylic acid (ASA) for antiplatelet activity using a novel excipient. Methods: A novel methodology used in making ASA tablets for tackling the stomach irritation of ASA, by including Plantago ovata seed mucilage as a tablet binder. ASA compatibility with P. ovata seed mucilage was judged by differential scanning calorimetry (DSC) and Fourier Transform Infrared (FTIR) studies. All tablets were prosecuted for flow properties, physicochemical constraints, and release. Results: The enteric-coated tablets established no interface by FTIR and DSC lessons. All the tablets possessed physicochemical constraints. The ASA showed its opposition to discharge in the stomach (2 h) and errand in a basic buffer (within 45 min). Conclusions: The work revealed that with the help of P. ovata as a tablet binder will resolve the disputes connected to gastric irritation.

Background: The comparative efficacy and safety of ticagrelor versus clopidogrel in older patients with myocardial infarction (MI) has received limited study. Methods: We performed an observational analysis of all patients ≥80 years (n=14 005) who were discharged alive with aspirin combined with either clopidogrel (60.2%) or ticagrelor (39.8%) after a MI between 2010 and 2017 registered in the national registry SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies). Inverse probability treatment weighting was used in Cox regression models to adjust for differences in demographics, in-hospital therapies, and medications. The primary ischemic outcome (death, MI, or stroke), and bleeding were obtained from national registries at 1 year. A sensitivity analysis in Results: In patients ≥80 years, the incidence of the primary ischemic outcome (hazard ratio [HR], 0.97 [95% CI, 0.88–1.06]) was similar for ticagrelor- and clopidogrel-treated patients. Ticagrelor was associated with a 17% and 48% higher risk of death (HR, 1.17 [95% CI, 1.03–1.32]) and bleeding (HR, 1.48 [95% CI, 1.25–1.76]), but a lower risk of MI (HR, 0.80 [95% CI, 0.70–0.92]) and stroke (HR, 0.72 [95% CI, 0.56–0.93]). In Conclusions: Ticagrelor use among elderly patients with MI was associated with higher risk of bleeding and death compared with clopidogrel. A randomized study of ticagrelor versus clopidogrel in the elderly is needed.