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Nowadays, the most common revascularization procedure to combat coronary artery disease is through Percutaneous Coronary Intervention (PCI) with the use of arterial stents. Two of the most recurrent drawbacks of stenting are restenosis and late stent thrombosis. To render the stent effective, a long-term antiplatelet drug delivery system have to be incorporated into a biodegradable polymer to target directly the malevolent site. A novel drug delivery nanosystem of Poly(D, L-lactic acid) (PLA) nanoparticles (NPs) loaded with Dipyridamole (DPM) was fabricated via electrospraying that forms monodispersed, biodegradable drug loaded NPs, as coating for cardiovascular stents. This study presents a feasible degradable NP delivery system that encapsulates, protects and controls the release of DPM, intended to reduce the possibility of thrombosis inside the stent.

Introduction. Acetylsalicylic acid (ASA) is the antiplatelet drug most used in the perioperative period in patients undergoing coronary artery bypass grafting (CABG). Off-pump coronary artery bypass grafting (OPCAB) is likely to alter platelet (PLT) function to a lesser extent than CABG with the use of cardiopulmonary bypass and may potentially result in high on-aspirin platelet reactivity (HAPR) in the postoperative period. Materials and methods. The aim of this prospective study was to characterise serum thromboxane B2 (TXB 2 ) variability and ASA-dependent platelet reactivity in patients with stable coronary artery disease undergoing OPCAB treated with a single daily dose of 75 mg of ASA. Blood sampling was performed 2 hours and 24 hours after ASA intake on the day before surgery, and on the 2 nd and 7 th days after the operation. Results. A PLT counts reduction and a mean platelet volume increase were observed on the 2 nd day after OPCAB. A PLT counts increase was found on the 7 th postoperative day. A significant increase (p = 0.03) in the percentage of patients with insufficient laboratory ASA efficacy (defined by serum TXB 2 ≥ 7.2 ng/mL) was observed on the 7 th postoperative day compared to preoperative values (52% vs 20% respectively, p = 0.02). A significant increase in median platelet reactivity and in the percentage of patients with HAPR (defined by VerifyNow ® Aspirin test result ≥ 550 ARU) was observed on the 7 th postoperative day in comparison with the values before OPCAB (48% vs 12%, p = 0.007). Conclusions. In the group of patients taking a standard daily dose of 75 mg of ASA, a substantial number of patients failed to attain optimal inhibition of serum TXB 2 or had HAPR before surgery and on the 7 th day after OPCAB. A significant decrease in serum TXB 2 levels on the 2nd day after OPCAB did not correlate with PLT reactivity. The optimal dose of ASA is of interest for further studies of efficacy and clinical outcomes after OPCAB.

Anticoagulant and antiplatelet drugs target a specific portion of the coagulation cascade or the platelet activation and aggregation pathway. The primary toxicity associated with these agents is hemorrhage. Understanding the pharmacology of these drugs allows the treating clinician to choose the correct antidotal therapy. Reversal agents exist for some of these drugs; however, not all have proven patient-centered outcomes. The anticoagulants covered in this review are vitamin K antagonists, heparins, fondaparinux, hirudin derivatives, argatroban, oral factor Xa antagonists, and dabigatran. The antiplatelet agents reviewed are aspirin, adenosine diphosphate antagonists, dipyridamole, and glycoprotein IIb/IIIa antagonists. Additional notable toxicities are also reviewed.

International audience; Background: The decision-making on antiplatelet drug withdrawal or continuation before performing a pleural procedure is based on the balance between the risk of bleeding associated with the antiplatelet therapy and the risk of arterial thrombosis due to its interruption. Knowledge on antiplatelet therapy-associated risk of bleeding after pleural procedures is lacking.Research question: Is the risk of bleeding associated with antiplatelet drugs increased in patients undergoing pleural procedures?Study design and methods: We conducted a French multicenter cohort study in 19 centers. The main outcome was the occurrence of bleeding, defined as hematoma, hemoptysis, or hemothorax, during the 24 h following a pleural procedure. Serious bleeding events were defined as bleeding requiring blood transfusion, respiratory support, endotracheal intubation, embolization, or surgery, or as death.Results: A total of 1,124 patients was included (men, 66%; median age, 62.6 ± 27.7 years), of whom 182 were receiving antiplatelet therapy and 942 were not. Fifteen patients experienced a bleeding event, including eight serious bleeding events. The 24-h incidence of bleeding was 3.23% (95% CI, 1.08%-5.91%) in the antiplatelet group and 0.96% (95% CI, 0.43%-1.60%) in the control group. The occurrence of bleeding events was significantly associated with antiplatelet therapy in univariate analysis (OR, 3.44; 95% CI, 1.14-9.66; P = .021) and multivariate analysis (OR, 4.13; 95% CI, 1.01-17.03; P = .044) after adjusting for demographic data and the main risk factors for bleeding. Likewise, antiplatelet therapy was significantly associated with serious bleeding in univariate analysis (OR, 8.61; 95% CI, 2.09-42.3; P = .003) and multivariate analysis (OR, 7.27; 95% CI, 1.18-56.1; P = .032) after adjusting for the number of risk factors for bleeding.Interpretation: Antiplatelet therapy was associated with an increased risk of post-pleural procedure bleeding and serious bleeding. Future guidelines should take into account these results for patient safety.

Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2–81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.

Peripheral artery disease (PAD) is one of the most frequent manifestations of atherosclerosis with high rates of morbidity and mortality. Platelets and coagulation are involved in the progression of atherosclerosis and thromboembolic complications. PAD patients have increased prothrombotic potential, which includes platelet hyperaggregability and increased pro-coagulant state. Therefore, antithrombotic treatment is of utmost importance for the prevention of cardiovascular events in this group of patients. Aspirin is the basic antiplatelet drug, but with limited efficacy in PAD. In contrast to coronary artery disease, its effect on the prevention of cardiovascular events in PAD has been limited proven. Particularly in asymptomatic PAD, there is no evidence for risk reduction with aspirin. Clopidogrel and ticagrelor are more effective than aspirin. Clopidogrel is thus an effective alternative to aspirin for prevention of cardiovascular events in symptomatic PAD. In patients who are non-responders to clopidogrel, ticagrelor is indicated. Dual antiplatelet treatment (DAPT) with aspirin and ticagrelor in patients with coronary artery disease and concomitant PAD significantly decreased the rate of major adverse cardiovascular events, including adverse limb events. However, in the CHARISMA Trial, aspirin and clopidogrel were not more effective than aspirin alone and increased bleeding complications. Therefore, DAPT seems effective only in PAD accompanied by coronary artery disease. Anticoagulant treatment for symptomatic PAD with vitamin K antagonists alone or in combination with aspirin is not more effective than single antiplatelet treatment but increases the rate of major bleeding. Low dose rivaroxaban combined with aspirin in PAD patients significantly reduces cardiovascular events, including limb-threatening ischemia and limb amputations. Anticoagulation and antiplatelet treatment after percutaneous or surgical revascularization of PAD improve the patency of treated vessels. Aspirin with or without dipyridamole improved patency of infra-inguinal by-pass grafts at one year. The combination of clopidogrel with aspirin was more effective than aspirin alone in the prevention of prosthetic graft occlusions in patients undergoing below-knee by-pass-grafting. Oral vitamin K antagonists were not more effective than aspirin in the prevention of infra-inguinal by-pass occlusion. The combination of low dose rivaroxaban and aspirin was effective in preventing major adverse cardiovascular events and adverse limb events after infrainguinal endovascular or surgical revascularization in patients with intermittent claudication. However, the data on antithrombotic treatment after revascularization for limb-threatening ischemia is scanty and inconclusive. In conclusion: Antithrombotic treatment of PAD is a cornerstone for the management of these patients. Antiplatelet drugs prevent the initiation and progression of atherosclerosis and are effective also in the prevention of thromboembolic events. Simultaneous use of antiplatelet and anticoagulation drugs is accompanied by an increased risk of bleeding. However, combined treatment with aspirin and low-dose rivaroxaban is more effective than single antithrombotic treatment and safer than full-dose combined treatment.

Background: Oral anticoagulants (OACs) are effective in preventing stroke in patients with atrial fibrillation (AF), but are challenging for elderly patients because of the higher risk of bleeding complications. Methods and Results: The ANAFIE Registry is a prospective multicenter observational study of elderly (≥75 years) Japanese AF patients. This subanalysis evaluated the current use of OACs. Of 32,713 patients (mean age 81.5 years), 30,068 (91.9%) were receiving OACs, including 8,354 (25.5%) on warfarin and 21,714 (66.4%) on direct OACs (DOACs); 2,645 (8.1%) were not receiving OACs. The most common prescribed dose was a reduced dose for all DOACs. A substantial proportion of patients receiving the reduced dose did not fulfill dose reduction criteria (underdosing): apixaban, 25.1%; rivaroxaban, 26.3%; and edoxaban, 13.7%. Some patients received a lower off-label dose rather than the reduced dose: apixaban, 5.9%; rivaroxaban, 0.3%; edoxaban, 5.3%; and dabigatran, 13.6%. In multivariate analyses, advanced age, history of hemorrhage, paroxysmal AF, and antiplatelet drug use were significantly associated with no OAC. Advanced age, persistent or permanent AF, chronic kidney disease, and concomitant antiplatelet drugs were associated with warfarin rather than DOAC use. Conclusions: In the ANAFIE Registry, >90% of elderly Japanese AF patients received OAC therapy, mostly DOACs. Inappropriate low doses of DOACs that did not fulfill dose reduction criteria were prescribed in 20–30% of patients.

Background Clopidogrel is an antiplatelet drug used in the treatment of ischemic stroke. Safety and efficacy of clopidogrel has been confirmed in CAPRIE, PRoFESS trials. However, these studies focused on patients aged less than 75 years. CYP2C19 polymorphisms resulted in individual differences in clopidogrel response. Our objective was to determine whether elderly stroke patients aged over 75 years would benefit from CYP2C19-genotype-guided strategy for the secondary prevention of stroke. Methods A retrospective analysis of patients aged 75 years or older with non-cardiogenic stroke who received 75 mg clopidogrel was performed. CYP2C19 genotype-guided group included noncarriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles (LoFA) and compared against the non-genotype-guided group which may carriers CYP2C19 LoFA or not. The primary endpoints were composite of stroke and myocardial infarction at 24 months’ follow-up. Results Two hundred one patients were included: 99 in the genotype-guided group and 102 in the non-genotype-guided group. Kaplan-Meier(KM)analysis showed that CYP2C19 gene polymorphism was associated with the rate of the primary endpoints (P = 0.0031). The primary endpoints occurred in 13 patients (13.1%) in the genotype-guided group and in 30 patients (29.4%) in the non-genotype-guided group (hazard ratio(HR), 0.39; 95% confidence interval(CI), 0.20 to 0.75; p = 0.004). Cox regression analysis showed that CYP2C19 genotype-guided strategy was a protective factor for the primary endpoints (HR, 0.39; 95% CI:0.20 to 0.74, P = 0.004). Conclusion The CYP2C19 genotype-guided strategy could reduce the occurrence of composite of stroke and myocardial infarction compared to a non-genotype-guided strategy for non-cardiogenic stroke patients aged 75 years or older who received clopidogrel.

Background Approximately 18% of patients with atrial fibrillation undergo a percutaneous coronary intervention (PCI) to treat coronary heart disease. Pharmacological anticoagulation in patients with atrial fibrillation and PCI involves a trade-off of potential ischemic and hemorrhagic complications. Methods This review is based on pertinent publications that were retrieved by a selective literature search, including current guidelines and recommendations. Results Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and a P2Y12 inhibitor protects against stent thrombosis, but not against thromboembolic stroke. In contrast, oral anticoagulation does provide effective prevention against stroke during atrial fibrillation. Combining DAPT with oral anticoagulation (triple therapy) over the long term, as has been recommended to date, carries an elevated risk of hemorrhage. In a randomized controlled trial, 44% of patients with atrial fibrillation receiving triple therapy sustained a hemorrhagic event, compared to 19.4% of patients receiving dual therapy. A meta-analysis has shown that clinically relevant hemorrhage is less common under combined treatment with one of the new oral anticoagulants (NOAC) and a single antiplatelet drug than under triple therapy including a vitamin K antagonist (hazard ratio, 0.56; 95% confidence interval 0.39; 0.80]), but no significant difference was found with respect to stent thrombosis, myocardial infarction, or overall mortality. Conclusion After coronary stent implantation, dual therapy with a NOAC and a P2Y12 inhibitor is recommended, subsequent to triple therapy given only during the peri-interventional period.

Stroke is one of the world's leading causes of disability and death. Antiplatelet agents are administered to acute ischemic stroke patients as secondary prevention. Clopidogrel involves biotransformation by cytochrome P450 (CYP) enzymes into an active metabolite, and single nucleotide polymorphisms (SNPs) can influence the efficacy of this biotransformation. Despite the therapeutic advantages of aspirin, there is significant inter-individual heterogeneity in response to this antiplatelet drug. In this clinical review, the recent advances in the biomarkers of antiplatelet agents in acute ischemic stroke are discussed. The studies reviewed herein highlight the clinical relevance of antiplatelet resistance, pharmacotherapy of antiplatelet agents predicting drug response, strategies for identifying aspirin resistance, pharmacogenetic variants of antiplatelet agents, miRNAs, and extracellular vesicles (EVs) as biomarkers toward the personalized approach in the management of acute ischemic stroke. The precise pathways contributing to antiplatelet resistance are not very well known but are presumably multi-factorial. It is essential to understand the clinical relevance of clopidogrel and aspirin-related single nucleotide polymorphism (SNPs) as potential predictive and prognostic biomarkers. Prasugrel is a next-generation antiplatelet agent that prevents ADP-platelet activation by binding irreversibly to P2Y12 receptor. There are sporadic reports of prasugrel resistance and polymorphisms in the Platelet endothelial aggregation receptor-1 (PEAR1) that may contribute to a change in the pharmacodynamics response. Ticagrelor, a direct-acting P2Y12-receptor antagonist, is easily absorbed and partly metabolized to major AR-C124910XX metabolite (ARC). Ticagrelor's primary active metabolite, ARC124910XX (ARC), is formed via the most abundant hepatic cytochrome P450 (CYP) enzyme, CYP3A4, and CYP3A5. The integration of specific biomarkers, genotype as well as phenotype-related data in antiplatelet therapy stratification in patients with acute ischemic stroke will be of great clinical significance and could be used as a guiding tool for more effective, personalized therapy.

In recent years, significant changes in stroke prophylaxis in patients with atrial fibrillation (AF) have been observed. Non-vitamin K antagonist oral anticoagulants (NOACs) are more commonly used in the prevention of thromboembolic complications in patients with AF. The aim of the study was to evaluate recommended stroke prophylaxis in patients with AF and to identify predictors of using NOACs in patients treated with anticoagulant therapy. The present study was a retrospective, observational, single-center study which included consecutively hospitalized patients in the reference cardiology center from January 2014 to December 2018. In the study group of 4027 patients with AF, to prevent thromboembolic complications, OACs were used in 3680 patients (91.4%), an antiplatelet drug(s) was used in 124 patients (3.1%), and 223 patients (5.5%) did not undergo any thromboembolic event prevention. In the group of 3680 patients treated with OACs, 2311 patients (62.8%) received NOACs and 1639 patients (37.2%), VKAs. Independent predictors of the use of NOACs were age (OR, 1.02; 95% CI, 1.01–1.03; P < 0.001 ), a previous thromboembolic event (OR, 1.29; 95% CI, 1.01–1.65; P = 0.04 ), nonpermanent AF (OR, 1.61; 95% CI, 1.34–1.93; P < 0.001 ), and eGFR (OR, 1.22; 95% CI, 1.02–1.46; P = 0.03 ). Between 2014 and 2018, an increase of patients treated with OACs, mainly with NOACs, was observed. Age, past thromboembolic complications, nonpermanent AF, and preserved renal function determined the choice of NOACs.

Pivotal clinical trials conducted in the bare metal stent and first-generation drug-eluting stent (DES) eras established the superiority of dual antiplatelet therapy (DAPT) over aspirin monotherapy in preventing ischemic events. Nonetheless, recent advances in stent technology improved the safety profile of these devices, lowered the risk of stent thrombosis, and reduced the need for prolonged DAPT. Furthermore, several studies have shown that the bleeding associated with prolonged DAPT confers an increase in mortality following percutaneous coronary intervention (PCI). Hence, DAPT strategies that minimize the bleeding risk and conserve the ischemic protection became an utmost need. While several studies have shown that short DAPT durations followed by aspirin monotherapy may be safe and feasible in relatively low-risk patients, extrapolation to higher risk patients remains uncertain. Even though aspirin has been the most widely used antiplatelet drug for many decades, recent evidence suggests potential benefits with the use of P2Y12 inhibitor monotherapy after a shortened DAPT duration in patients undergoing percutaneous coronary intervention with current-generation DESs. This concept is even being taken one step further as P2Y12 inhibitor monotherapy after PCI is currently being investigated in selected patients.

Kazumasa Oura,1 Ryo Itabashi,1 Takashi Omoto,2 Mao Yamaguchi Oura,1 Tetsuro Kiyokawa,1 Eisuke Hirai,1 Tetsuya Maeda1 1Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Iwate, Japan; 2Department of Pharmacy, Iwate Medical University Hospital, Iwate, JapanCorrespondence: Kazumasa OuraDivision of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-Cho, Shiwa-Gun, Iwate, 028-3695, JapanTel +81-19-613-7111Fax +81-19-907-6933Email koura@iwate-med.ac.jpPurpose: The effectiveness of Electronic Medication Packaging devices for monitoring drug adherence has been widely reported. However, conventional devices are expensive for routine use and cannot confirm whether the medication was administered. We aimed to determine, in a pilot and feasibility study, the impact of introducing a new medication support device, the Pletaal Assist System®, to monitor and improve cilostazol adherence for stroke prevention at an outpatient clinic.Patients and Methods: We assessed consecutive patients treated with cilostazol for > 3 months at our stroke outpatient clinic from January 2018 to March 2020. The adherence rate was assessed as follows: (the number of pills prescribed minus the number of remaining pills)/the number of pills prescribed. We compared the adherence rates before, during, and after Pletaal Assist System® usage, respectively.Results: Overall, 25 patients (median age, 68.5 years; range, 51– 86 years; male, 64%) were enrolled. All participants were prescribed cilostazol (100 mg) twice a day. There was no significant difference in the adherence rate among the three periods. However, in 10 patients with adherence rate below 100%, the adherence rate during Pletaal Assist System® usage was higher than before usage (99.5% vs 95%, p=0.04), and the rate after using the Pletaal Assist System® tended to be lower compared to the rate during usage (99.5% vs 96%, p=0.05).Conclusion: Our preliminary evidence suggest that the Pletaal Assist System® could further improve cilostazol adherence in outpatients with poor drug adherence and may reduce the risk of recurrent strokes by improving adherence of patients with a history of stroke.Keywords: medication adherence, antiplatelet drug, stroke, electronic medication packaging

Background Intracerebral hemorrhage (ICH) stroke constitute up to 40% of incident strokes in Africa. While ICH patients are at high risk for atherosclerotic events, the risk-benefit of anti-atherosclerotic therapies in this patient population is uncertain. Purpose To assess whether utility of statins and/or antithrombotic agents after surviving an ICH correlates with atherosclerotic risk of an observational cohort. Methods We analyzed data in a stroke registry prospectively collected on consecutively encountered stroke survivors seen at an out-patient clinic in Ghana between January 2018 and March 2020. We collected baseline demographic and clinical details, including diagnosis of ICH, co-morbidities, and key atherosclerotic risk reduction therapies (statins and anti-platelet drugs). We computed ischemic vascular risk using the Framingham Risk Score (FRS) to classify patients into low, intermediate and high vascular risk. Results Of 1101 stroke survivors seen during the period, 244 (22.2%) had ICH. Vascular risk profiles were low (n = 86; 35.2%), intermediate (n = 71; 29.1%) and high (n = 87; 35.7%). Utility of statin use was 76.7% (low risk), 84.5% (intermediate risk), and 87.4% (high risk), p = 0.16 while antiplatelet use trended with atherosclerotic risk being 9.3% (low risk), 25.4% (intermediate risk), and high risk (34.5%), p = 0.0004. Independent factors associated with statin use were hypertension (OR 8.80; 95% CI: 2.34–33.11) and cigarette smoking (OR 0.29; 95% CI: 0.09–0.89) while antiplatelet drug use was associated with age (OR 1.43; 95% CI: 1.06–1.92) and time from index stroke (OR: 1.02; 95% CI: 1.01–1.02). Conclusion Approximately two-thirds of ICH survivors in this African sample had intermediate to high risk of future atherosclerotic events. Clinical trials on the timing, safety, and efficacy of statins and antiplatelet drugs among ICH survivors could help better guide risk mitigation in this population.

Aim According to recent clinical trials, a combination of direct oral anticoagulants with antiplatelet drugs is often recommended for atrial fibrillation patients who receive drug-eluting stents (DESs). Although the optimal combination comprises direct factor Xa inhibitors and a P2Y12 receptor antagonist (or aspirin), their influence on vascular responses to DESs remains unclear. Methods Pigs were given either aspirin and clopidogrel (dual antiplatelet therapy [DAPT] group), aspirin and rivaroxaban (AR group), or clopidogrel and rivaroxaban (CR group), followed by everolimus-eluting stent (Promus Element) implantation into the coronary artery. Stented coronary arteries were evaluated via intravascular optical coherence tomography (OCT) and histological analysis at 1 and 3 months. Results OCT revealed lower neointimal thickness in the DAPT group and comparable thickness among all groups at 1 and 3 months, respectively. Histological analyses revealed comparable neointimal area among all groups and the smallest neointimal area in the CR group at 1 and 3 months, respectively. In the DAPT and AR groups, the neointima continued to grow from 1 to 3 months. A shortened time course for neointima growth was observed in the CR group, with rapid growth within a month (maintained for 3 months). A higher incidence of in-stent thrombi was observed in the AR group at 1 month; no thrombi were found in either group at 3 months. More smooth muscle cells with contractile features were found in the CR group at both 1 and 3 months. Conclusions Our results proved the noninferiority of the combination of rivaroxaban with an antiplatelet drug, particularly the dual therapy using rivaroxaban and clopidogrel, compared to DAPT after DES implantation.

IntroductionIntracerebral haemorrhage (ICH) can be devastating and is a common cause of death and disability worldwide. Pre-ICH antiplatelet drug use is associated with a 27% relative increase in 1 month case fatality compared with patients not using antithrombotic drugs. We aim to assess the feasibility of conducting a randomised controlled testing the safety and efficacy of desmopressin for patients with antiplatelet-associated ICH.Methods and analysisWe aim to include 50 patients within 24 hours of spontaneous ICH onset, associated with oral antiplatelet drug(s) use in at least the preceding 7 days. Patients will be randomised (1:1) to receive intravenous desmopressin 20 µg in 50 mL sodium chloride 0.9% infused over 20 min or matching placebo. We will mask participants, relatives and outcome assessors to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, number of patients receiving allocated treatment, rate of recruitment and adherence to treatment and follow-up. Secondary outcomes include change in ICH volume at 24 hours; hyponatraemia at 24 hours, length of hospital stay, discharge destination, early death less than 28 days, death or dependency at day 90, death up to day 90, serious adverse events (including thromboembolic events) up to day 90; disability (Barthel index, day 90), quality of life (EuroQol 5D (EQ-5D), day 90), cognition (telephone mini-mental state examination day 90) and health economic assessment (EQ-5D).Ethics and disseminationThe Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH) trial received ethical approval from the East Midlands—Nottingham 2 research ethics committee (18/EM/0184). The DASH trial is funded by National Institute for Health and Care Research RfPB grant: PB-PG-0816-20011. Trial results will be published in a peer reviewed academic journal and disseminated through academic conferences and through patient stroke support groups. Reporting will be in compliance with Consolidated Standards of Reporting Trials recommendations.Trial registration numbersNCT03696121;NCT67038373; EudraCT 2018-001904-12.

The aim of this study was to determine the frequency and the risk factors of acute and chronic nephrotoxicity in patients who received cisplatin due to malignancy. Medical records of all patients who received cisplatin-based chemotherapy regimen between January 2013 and July 2019 were retrospectively evaluated. The data of 203 patients who met the study criteria were examined. The patients were evaluated for acute nephrotoxicity at 48 h and late nephrotoxicity at 3rd month after first course of cisplatin. Early and late nephrotoxicity were defined by NCI CTCAE Version 4.0 criteria. The mean age of the study patients was 56.44 ± 12.69 years, 78.8% were males and 21.2% were females. It is revealed that the incidence of cisplatin-induced acute nephrotoxicity was 9.2% and chronic nephrotoxicity was 37.9%. While the development of acute nephrotoxicity was associated with female gender, history of diabetes mellitus, history of ischemic heart disease and use of antiplatelet drug, the development of chronic nephrotoxicity was associated with older age, female gender and using of diuretics. High serum creatinine, urea and low eGFR value before treatment were found to be associated with both early and late nephrotoxicity (p

Objective This study aimed to examine the relationship between total bilirubin levels and initial ischemic stroke in patients with non-valvular atrial fibrillation. Methods This was a retrospective study. Atrial fibrillation was diagnosed by 24-hour Holter electrocardiography and serum total bilirubin levels were divided into quintiles. Ischemic stroke was diagnosed by symptoms, signs, and a medical image examination. The multivariate Cox proportional hazards model and survival analysis were used to estimate the association of total bilirubin with initial ischemic stroke. Results We studied 316 patients with non-valvular atrial fibrillation. During follow-up, there were 42 (13.29%) first ischemic strokes. After multivariate adjustment, for each 1 µmol/L increase in total bilirubin, the risk of first ischemic stroke increased by 4% (95% confidence interval [CI]: 1.01, 1.07). When using the first quintile as the reference, from the second to fifth quintiles, the risks of first ischemic stroke were 0.52 (95% CI: 0.17, 1.65), 0.23 (95% CI: 0.06, 0.87), 0.92 (95% CI: 0.32, 2.67), and 1.33 (95% CI: 1.09, 4.41), respectively. The optimal cut-off point of total bilirubin for the lowest risk of ischemic stroke was 17.0 µmol/L. Conclusions Total bilirubin levels are nonlinearly associated with initial ischemic stroke in patients with non-valvular atrial fibrillation.

With a growing number of patients on ticagrelor therapy after stent implantation, we observe many cases of side effects of the drug, mostly dyspnoea and bradycardia. In our article we present 2 patients, in which the symptoms were particularly severe. Then we describe possible mechanisms of these complications, explain how to carry out differential diagnosis, discuss when to switch ticagrelor to other antiplatelet drug and finally we present the way to deal with the symptoms.

Background Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence. Methods Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined). Results Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139–16.691, p=0.032) in the LAA group. Age (1.030 [1.004–1.057], p=0.026), systolic blood pressure (1.012 [1.003–1.022], p=0.010), and infarct size (2.550 [1.488–4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138–12.318], p=0.030). Conclusions Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.

Background: Epidemiologic evidence is insufficient to draw conclusions on the impact of low-dose aspirin use on breast cancer risk, and the potential impact of other antiplatelet drugs such as clopidogrel needs to be explored. Methods: We investigated the association between breast cancer risk and low-dose aspirin or clopidogrel use in the E3N cohort, which includes 98,995 women, with information on breast cancer risk factors collected from biennial questionnaires matched with drug reimbursement data available from 2004. Women with at least two reimbursements of the drug of interest in any previous 3-month period were considered “ever” exposed. Exposure was considered as time-varying and multivariable Cox regression models were used to estimate HRs of breast cancer. Results: Among 62,512 postmenopausal women followed during 9 years on average, 2,864 breast cancer cases were identified. Compared with never use, a transient higher breast cancer risk was observed during the third year of low-dose aspirin use [HR2–≤3 years of use = 1.49 (1.08–2.07)], followed by a lower risk [HR4+ years of use = 0.72 (0.52–0.99)]. Clopidogrel ever use was associated with a higher breast cancer risk [HR, 1.30 (1.02–1.68)], restricted to estrogen receptor negative (ER−) tumors [HRER+ = 1.14 (0.83–1.57), HRER− = 3.07 (1.64–5.76), Phomogeneity = 0.01]. Conclusions: Low-dose aspirin was associated with a lower breast cancer risk only after several years of use, while ever use of clopidogrel was associated with a higher ER− breast cancer risk. Impact: Antiplatelet drugs are not good pharmacologic candidates for breast cancer prevention.

Tussilagone is a sesquiterpenoid extracted from Tussilago farfara and is used as an oriental medicine for asthma and bronchitis. Although previous studies have shown that tussilagone has an inhibitory effect on platelet aggregation, no studies have been performed to investigate its precise effect on platelets, and the underlying mechanism remains unclear. In the present study, we showed that tussilagone inhibited platelet aggregation induced by collagen, thrombin and ADP, as well as platelet release induced by collagen and thrombin, in mice. Tussilagone decreased P-selectin expression and αIIbβ3 activation (JON/A binding) in activated platelets, which indicated that tussilagone inhibited platelet activation. Moreover, tussilagone suppressed platelet spreading on fibrinogen and clot retraction. The levels of phosphorylated Syk, PLCγ2, Akt, GSK3β, and MAPK (ERK1/2 and P38) and molecules associated with GPVI downstream signaling were downregulated in the presence of tussilagone. In addition, tussilagone prolonged the occlusion time in a mouse model of FeCl3-induced carotid artery thrombosis and had no effect on mouse tail bleeding time. These results indicate that tussilagone inhibits platelet function in vitro and in vivo and that the underlying mechanism involves the Syk/PLCγ2-PKC/MAPK and PI3K-Akt-GSK3β signaling pathways downstream of GPVI. This research suggests that tussilagone is a potential candidate antiplatelet drug for the prevention of thrombosis.

Background: The risk, correlates, and consequences of incident atrial fibrillation (AF) in patients with chronic coronary artery disease (CAD) are largely unknown. Methods and results: We analyzed incident AF during a 3-year follow-up in 5031 CAD outpatients included in the prospective multicenter CARDIONOR registry and with no history of AF at baseline. Incident AF occurred in 266 patients (3-year cumulative incidence: 4.7% (95% confidence interval (CI): 4.1 to 5.3)). Incident AF was diagnosed during cardiology outpatient visits in 177 (66.5%) patients, 87 of whom were asymptomatic. Of note, 46 (17.3%) patients were diagnosed at time of hospitalization for heart failure, and a few patients (n = 5) at the time of ischemic stroke. Five variables were independently associated with incident AF: older age (p &lt, 0.0001), heart failure (p = 0.003), lower left ventricle ejection fraction (p = 0.008), history of hypertension (p = 0.010), and diabetes mellitus (p = 0.033). Anticoagulant therapy was used in 245 (92%) patients and was associated with an antiplatelet drug in half (n = 122). Incident AF was a powerful predictor of all-cause (adjusted hazard ratio: 2.04, 95% CI: 1.47 to 2.83, p &lt, 0.0001) and cardiovascular mortality (adjusted hazard ratio: 2.88, 95% CI: 1.88 to 4.43, 0.0001). Conclusions: In CAD outpatients, real-life incident AF occurs at a stable rate of 1.6% annually and is frequently diagnosed in asymptomatic patients during cardiology outpatient visits. Anticoagulation is used in most cases, often combined with antiplatelet therapy. Incident AF is associated with increased mortality.

Fentanyl is a potent synthetic opioid used to alleviate severe and chronic pain, as well as an adjunct to general or local anesthesia. Although fentanyl has been used for decades, its full effects are still unknown. Its analgesic and anesthetic activity arises from the stimulation of μ-opioid receptors, resulting in the inhibition of adenyl cyclase and downregulation of cyclic adenosine 3',5'-monophosphate (cAMP), as well as decreased calcium channel activity and increased potassium channel activity. The μ-opioid receptors are abundantly distributed within the central nervous system, where they mediate analgesia, and in the nerve cells of the intestines, where they regulate gastrointestinal tract motility in the secretion or transport of fluids and electrolytes. They are also expressed in blood cells, blood vessel cells, and skin. Given the widespread distribution of μ-opioid receptors, it is likely that fentanyl may also regulate the activity of many other cells, including platelets. Recent findings indicate that it may impair the action of ticagrelor: an oral P2Y12 receptor inhibitor acting as an antiplatelet drug. It could pose a risk of insufficient platelet inhibition and result in thrombotic complications in patients with coronary artery disease. This article tackles the issue of fentanyl interactions with antiplatelet drugs. The mechanism of this phenomenon is not fully understood. Similarly, the biological effects exerted by fentanyl on platelets and the presence of opioid receptors on the platelet surface remain an open question.

Background and Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. Methods: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. Results: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09–1.21]; P =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32–1.34]; P =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia ( P =0.36) or stroke ( P =0.33). Conclusions: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.

Background: COVID-19 pandemic is caused by coronavirus also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The viral infection continues to impact the globe with no vaccine to prevent the infection or highly effective therapeutics to treat the millions of infected people around the world. The disease starts as a respiratory infection, yet it may also be associated with a hypercoagulable state, severe inflammation owing to excessive cytokines production, and a potentially significant oxidative stress. The disease may progress to multiorgan failure and eventually death. Objective: In this article, we summarize the potential of dipyridamole as an adjunct therapy for COVID-19. Methods: We reviewed the literature describing the biological activities of dipyridamole in various settings of testing. Data were retrieved from PubMed, SciFinder-CAS, and Web of Science. The review concisely covered relevant studies starting from 1977. Results: Dipyridamole is an approved antiplatelet drug, that has been used to prevent stroke, among other indications. Besides its antithrombotic activity, the literature indicates that dipyridamole also promotes a host of other biological activities including antiviral, anti-inflammatory, and antioxidant ones. Conclusion: Dipyridamole may substantially help improve the clinical outcomes of COVID-19 treatment. The pharmacokinetics profile of the drug is well established which makes it easier to design an appropriate therapeutic course. The drug is also generally safe, affordable, and available worldwide. Initial clinical trials have shown a substantial promise for dipyridamole in treating critically ill COVID-19 patients, yet larger randomized and controlled trials are needed to confirm this promise.

Background Many adult patients with Fontan circulation are treated with antithrombotic agents, including direct oral anticoagulants (DOACs). However, few studies have investigated the efficacy, feasibility, and safety of DOACs in adult patients with Fontan circulation. Methods and Results In this retrospective cohort study, clinical records of 139 adult patients with Fontan circulation (70 females, 50.4%) from April 2015 to March 2018 were reviewed and classified into five groups according to the therapeutic agents used: DOAC (n = 36), vitamin K antagonist (VKA; n = 41), antiplatelet drug (n = 43), combination of an antiplatelet and anticoagulant (n = 14), and no-antithrombotic prophylaxis (n = 5). In a 1114-patient-year follow-up, 28 major events occurred, including 10 thrombotic and 18 bleeding events; 11 of 18 (61%) female patients had severe menorrhagia. The incidence (% patient-years) of major events was 0.6, 1.42, 3.74, and 5.13 in the DOAC, antiplatelet, VKA, combination, and no-antithrombotic groups, respectively. The Cox proportional hazards analysis revealed that the DOAC group had a lower rate of primary endpoints than the VKA group in males. Conclusions DOAC may be a safe antithrombotic agent for use in adult patients with Fontan circulation, particularly in males. However, these findings should be confirmed in multi-institutional prospective studies.

Platelets are a heterogeneous small anucleate blood cell population with a central role both in physiological haemostasis and in pathological states, spanning from thrombosis to inflammation, and cancer. Recent advances in proteomic studies provided additional important information concerning the platelet biology and the response of platelets to several pathophysiological pathways. Platelets circulate systemically and can be easily isolated from human samples, making proteomic application very interesting for characterizing the complexity of platelet functions in health and disease as well as for identifying and quantifying potential platelet proteins as biomarkers and novel antiplatelet therapeutic targets. To date, the highly dynamic protein content of platelets has been studied in resting and activated platelets, and several subproteomes have been characterized including platelet-derived microparticles, platelet granules, platelet releasates, platelet membrane proteins, and specific platelet post-translational modifications. In this review, a critical overview is provided on principal platelet proteomic studies focused on platelet biology from signaling to granules content, platelet proteome changes in several diseases, and the impact of drugs on platelet functions. Moreover, recent advances in quantitative platelet proteomics are discussed, emphasizing the importance of targeted quantification methods for more precise, robust and accurate quantification of selected proteins, which might be used as biomarkers for disease diagnosis, prognosis and therapy, and their strong clinical impact in the near future.

sHDL is a promising antithrombotic agent delivery system due to its antithrombotic effect itself and improved drug delivery., Antiplatelet agents offer a desirable approach to thrombosis prevention through the reduction of platelet reactivity. However, major bleeding events greatly attenuate the clinical outcomes of most antithrombotic agents. Therefore, the development of safer and more effective strategies to prevent vascular occlusion and avoid bleeding is urgently needed. A reconstituted nanoparticle, synthetic high-density lipoprotein (sHDL), which mimics the native HDL, has been established as clinically safe and is easily manufactured on a large scale. In this study, we propose that the delivery of the antiplatelet drug ML355, a selective inhibitor of 12(S)-lipoxygenase (12-LOX), by sHDL will efficiently inhibit thrombosis by targeting ML355 to the intended site of action, improving the pharmaceutical profile and harnessing the innate antithrombotic efficacy of the sHDL carrier. Our data show that ML355-sHDL exhibits more potent inhibition of thrombus formation in both small arterioles and larger arteries in mice without impairing the normal hemostasis in vivo.

OBJECTIVE The goal of this study was to compare the odds of stroke 24 hours or more after hospital arrival among patients with blunt cerebrovascular injury (BCVI) who were treated with therapeutic anticoagulation versus aspirin. METHODS The authors conducted a retrospective cohort study at a regional level I trauma center including all patients with BCVI who were treated over a span of 10 years. Individuals with stroke on arrival or within the first 24 hours were excluded, as were those receiving alternative antithrombotic drugs or procedural treatment. Exact logistic regression was used to examine the association between treatment and stroke, adjusting for injury grade. To account for the possibility of residual confounding, propensity scores for the likelihood of receiving anticoagulation were determined and used to match patients from each treatment group; the difference in the probability of stroke between the two groups was then calculated. RESULTS A total of 677 patients with BCVI receiving aspirin or anticoagulation were identified. A total of 3.8% (n = 23) of 600 patients treated with aspirin sustained a stroke, compared to 11.7% (n = 9) of 77 receiving anticoagulation. After adjusting for injury grade with exact regression, anticoagulation was associated with higher likelihood of stroke (OR 3.01, 95% CI 1.00–8.21). In the propensity-matched analysis, patients who received anticoagulation had a 15.0% (95% CI 3.7%–26.3%) higher probability of sustaining a stroke compared to those receiving aspirin. CONCLUSIONS Therapeutic anticoagulation may be inferior to aspirin for stroke prevention in BCVI. Prospective research is warranted to definitively compare these treatment strategies.

Antiplatelet drugs are prescribed without considering the diabetic status of the patient. The objective of the current investigation was to determine the impact of clinical factors, CYP4F2 enzyme and 20-hydroxyeicosatetraenoic acid (20-HETE) concentrations on high on-treatment platelet reactivity in patients with diabetes treated with antiplatelet drugs following acute coronary syndromes. A total of 667 patients were included in the study. Dual antiplatelet drug loading dosages with aspirin (300 mg) and ticagrelor (180 mg) or clopidogrel (600 mg) were prescribed to all the studied patients. Testing of platelet aggregation was performed the day after loading antiplatelet drug dosages. Platelet aggregation test was done according to the classical Born method. Multivariate binary regression analysis demonstrated that insulin use and higher 20-HETE concentration increased the odds of high on-treatment platelet reactivity during the initiation of antiplatelet drug therapy (OR: 3.968, 95% CI: 1.478–10.656, p = 0.006 and OR: 1.139, 95% CI: 1.073–1.210, respectively, p p = 0.002). Data from this study revealed that high on-treatment platelet reactivity during dual antiplatelet therapy in patients with diabetes may depend on such factors as insulin prescription and 20-HETE concentration.

Despite the clinical benefits of aspirin, the interindividual variation in response to this antiplatelet drug is considerable. The manifestation of aspirin resistance (AR) is frequently observed, although this complex process remains poorly understood. While AR etiology is likely to be multifactorial, genetic factors appear to be preponderant. According to several genetic association studies, both genome-wide and candidate gene studies, numerous SNPs in cyclooxygenase, thromboxane and platelet receptors-related genes have been identified as capable of negatively affecting aspirin action. Thus, it is essential to understand the clinical relevance of AR-related SNPs as potential predictive and prognostic biomarkers as they may be essential to defining the AR phenotype.

Background: Extensive research has reported that extracellular ADP in the tumour microenvironment can stimulate platelets through interaction with the platelet receptor P2Y12. In turn, activated platelets release biological factors supporting cancer progression. Experimental data suggest that the tumour microenvironment components, of which platelets are integral, can promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Thus, overcoming chemoresistance requires combining multiple inhibitors that simultaneously target intrinsic pathways in cancer cells and extrinsic factors related to the tumour microenvironment. We aimed to determine whether ticagrelor, an inhibitor of the ADP&ndash, P2Y12 axis and a well-known antiplatelet drug, could be a therapeutic option for PDAC. Methods: We investigated a functional P2Y12 receptor and its downstream signalling in a panel of PDAC cell lines and non-cancer pancreatic cells termed hTERT-HPNE. We tested the synergistic effect of ticagrelor, a P2Y12 inhibitor, in combination with chemotherapeutic drugs (gemcitabine, paclitaxel and cisplatin), in vitro and in vivo. Results: Knockdown studies revealed that P2Y12 contributed to epidermal growth factor receptor (EGFR) activation and the expression of SLUG and ZEB1, which are transcriptional factors implicated in metastasis and chemoresistance. Studies using genetic and pharmacological inhibitors showed that the P2Y12&ndash, EGFR crosstalk enhanced cancer cell proliferation. Inhibition of P2Y12 signalling significantly reduced EGF-dependent AKT activation and promoted the anticancer activity of anti-EGFR treatment. Importantly, ticagrelor significantly decreased the proliferative capacity of cancer but not normal pancreatic cells. In vitro, synergism was observed when ticagrelor was combined with several chemodrugs. In vivo, a combination of ticagrelor with gemcitabine significantly reduced tumour growth, whereas gemcitabine or ticagrelor alone had a minimal effect. Conclusions: These findings uncover a novel effect and mechanism of action of the antiplatelet drug ticagrelor in PDAC cells and suggest a multi-functional role for ADP-P2Y12 signalling in the tumour microenvironment.

Background We hypothesized that administration of cilostazol may clarify the occult atrial fibrillation (AF) during hospitalization in mild stroke patients, who has no history of AF. Methods From our prospective non-cardioembolic stroke study, randomized to dual antiplatelet therapy using cilostazol and aspirin or aspirin alone trial (ADS), data on the presence or absence of AF were retrospectively analyzed. In the ADS, during hospitalization, as a routine examination, presence of AF was investigated using electrocardiogram (ECG), ECG monitoring and Holter ECG. Multivariate regression analysis was conducted to evaluate the independent parameters related to the AF. Clinical outcome at 3 months was evaluated using modified Rankin Scale (mRS) score. Results Data on 1194 patients (793 [66%] men; median age [interquartile range] of 69 [61–77] years, National Institutes of Health Stroke Scale score 2 [1–4], onset-to-admission 10.8 [4.7–20.5] hours) were retrospectively analyzed. AF was newly detected in 41 (3%) patients (3 by ECG, 21 by the ECG monitoring and 17 by the Holter ECG) during hospitalization. Patients treated with combined cilostazol and aspirin therapy frequently had the AF than those took aspirin alone (5% vs. 2%, p = .007). Multivariate regression analysis showed that cilostazol administration was one of the independent factors for new-AF (odds ratio 2.672, 95%CI: 1.205–5.927, p = .016). The frequency of mRS 0-1 was 68% in the new-AF group and 67% in the non-AF group (p = 1.000). Conclusion Cilostazol therapy may increase the detectability of AF in acute non-cardioembolic stroke, though the new-AF was not related to clinical outcome at 3 months.

BackgroundDual antiplatelet therapy (DAPT) is frequently discontinued after drug-eluting stent (DES) implantation, which could increase the risk of major adverse cardiovascular events (MACEs). Few studies have attempted to improve DAPT adherence through web-based social media.ObjectiveTo explore the effect of social media on DAPT adherence following DES implantation.Methods/designThe WeChat trial is a multicentre, single-blind, randomised study (1:1). It will recruit 760 patients with DES who require 12 months of DAPT. The control group will only receive usual care and general educational messages on medical knowledge. The intervention group will receive a personalised intervention, including interactive responses and medication and follow-up reminders beyond the general educational messages. The primary endpoint will be the discontinuation rate which is defined as the cessation of any dual antiplatelet drug owing to the participants’ discretion within 1 year of DES implantation. The secondary endpoints will include medication adherence and MACEs. Both groups will receive messages or reminders four times a week with follow-ups over 12 months.Ethics and disseminationEthical approval was granted by Ethics Committee of Guangdong Provincial People’s Hospital (GDREC2018327H). Results will be disseminated via peer-reviewed publications and presentations at international conferences.Trial registration numberNCT03732066

INTRODUCTION Carotid atherosclerosis represents 8 to 15% of ischemic strokes in relation to the concept of "vulnerable" plaque. Contrast enhanced ultrasound (CEUS) can detect moving microbubbles within the plaque corresponding to neovessels that constitute "precursors" of vulnerable plaque and intraplaque hemorrhage. CEUS was not studied specifically in acute ischemic strokes. The aim of this study is to analyse the prevalence of CEUS carotid plaque ipsilateral at the ischemic stroke as well as the main characteristics of contrast-plaques. METHOD A single-centre prospective pilot study involving 33 consecutive patients with a stroke ≤10 days, diagnosed by an MRI with positive diffusion sequence and having a carotid plaque thickness ≥2.5mm with low or heterogeneous echogenicity, located in the ipsilateral carotid territory at the stroke. Plaque echogenicity was done by visual analysis and by measurement of the gray scale median (GSM). A transcranial Doppler monitoring was carried out in search of HITS. The contrast ultrasound was performed after 2.5 cc IV injection of SonoVue®. A video clip was recorded after injection which was used for interpretation by visual analysis in 3 grades, provided by two independent expert readers. RESULTS The population consisted of 10 women and 23 men aged 73 on average. The topography of strokes in the carotid territory was located on the right in 11 (33%) cases and on the left in 22 (67%) cases. Seventeen patients had carotid stenosis between 0 and 49% according to the Nascet method and 16 patients had stenosis of 50 to 99%. The visual characterisation of the plaques had echolucent dominance (Type 1-2) in 18 cases and echogenic dominance (Type 3-4a) in 15 cases. Cardiovascular risk factors were common with no difference by sex. The inter-observer agreement of plaque enhancement was moderate in first reading (k=0.48) and excellent at consensus (k=0.91). Only one disagreement was found. Contrast agent enhancement of carotid plaque was observed in 11/32 patients, representing a prevalence of 34.4% - CI95% [17.9-50.9]. Variables associated with contrast plaque included the absence of antiplatelet drug (63.6% vs. 23.8%, P=0.05) and the presence of a regular edge on the plaque (91% vs. 48%, P=0.04). There was no difference in contrast enhancement for stenosis>or

Background Stent thrombosis (ST) is a rare, but potentially fatal complication. Procedural problems, such as stent under-dimension/under-expansion or dual antiplatelet drug resistance may result into ST. These conditions are more frequent during primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI). Case summary A 60-year-old male patient presented to our hospital with an inferior STEMI. In the emergency department, a dual antiplatelet therapy was administered with ticagrelor 180 mg and aspirin 250 mg IV. During the observation, the patient experienced a ventricular fibrillation. Urgent coronary angiography showed an occlusion of the proximal right coronary artery. Thrombus aspiration was performed followed by implantation of one drug-eluting stent. After 45 min early ST occurred and was treated by immediate thrombus aspiration and post-dilatation. Intravascular ultrasound sonography (IVUS) showed severe strut malapposition due to a partial crush after post-dilatation. Since it was not possible to directly insert the first guidewire in the stent lumen, the IVUS probe was placed between the vessel wall and the crushed stent to guide the manoeuvre. Discussion Crushed stent is a rare complication, being caused by an incorrect passage of the guidewire between the stent’s struts and the vessel wall in case of severe underexpansion. In this case, an IVUS-guided re-entry could be an option to gain the stent true lumen and avoid a second stent implantation.

Introduction: Whether aspirin or other antiplatelet drugs can reduce mortality among patients with coronavirus disease (COVID-19) remains controversial. Methods: We identified randomized controlled trials, prospective cohort studies, and retrospective studies on associations between aspirin or other antiplatelet drug use and all-cause mortality among patients with COVID-19 in the PubMed database between March 2019 and September 2021. Newcastle-Ottawa Scale and Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias. The I 2 statistic was used to assess inconsistency among trial results. The summary risk ratio (RR) and odds ratio (OR) were obtained through the meta-analysis. Results: The 34 included studies comprised three randomized controlled trials, 27 retrospective studies, and 4 prospective cohort studies. The retrospective and prospective cohort studies showed low-to-moderate risks of bias per the Newcastle-Ottawa Scale score, while the randomized controlled trials showed low-to-high risks of bias per the Cochrane Risk of Bias Assessment Tool. The randomized controlled trials showed no significant effect of aspirin use on all-cause mortality in patients with COVID-19 {risk ratio (RR), 0.96 [95% confidence interval (CI) 0.90-1.03]}. In retrospective studies, aspirin reduced all-cause mortality in patients with COVID-19 by 20% [odds ratio (OR), 0.80 (95% CI 0.70-0.93)], while other antiplatelet drugs had no significant effects. In prospective cohort studies, aspirin decreased all-cause mortality in patients with COVID-19 by 15% [OR, 0.85 (95% CI 0.80-0.90)]. Conclusion: The administration of aspirin may reduce all-cause mortality in patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Su, Miao, Guo, Chen, Huang and Ding.)