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Background and Purpose: Although the amphiphilic nature of the widely used antithrombotic drug Ticagrelor is well known, it was never considered as a membranotropic agent capable of interacting with the lipid bilayer in a receptor‐independent way. In this study, we investigated the influence of Ticagrelor on plasma membrane lipid order in platelets and if this modulates the potency of Ticagrelor at the P2Y12 receptor. Experimental Approach: We combined fluorescent in situ, in vitro and in silico approaches to probe the interactions between the plasma membrane of platelets and Ticagrelor. The influence of Ticagrelor on the lipid order of the platelet plasma membrane and large unilamellar vesicles was studied using the advanced fluorescent probe NR12S. Furthermore, the properties of model lipid bilayers in the presence of Ticagrelor were characterized by molecular dynamics simulations. Finally, the influence of an increased lipid order on the dose‐response of platelets to Ticagrelor was studied. Key Results: Ticagrelor incorporates spontaneously into lipid bilayers and affects the lipid order of the membranes of model vesicles and isolated platelets, in a nontrivial composition and concentration‐dependent manner. We showed that higher plasma membrane lipid order in platelets leads to a lower IC50 value for Ticagrelor. It is shown that membrane incorporation of Ticagrelor increases its potency at the P2Y12 receptor, by increasing the order of the platelet plasma membrane. Conclusion and Implications: A novel dual mechanism of Ticagrelor action is suggested that combines direct binding to P2Y12 receptor with simultaneous modulation of receptor‐lipid microenvironment. [ABSTRACT FROM AUTHOR]

When Berger et al. first reported IgA nephropathy in 1968, the prognosis was generally thought to be benign. However, as more case data were accumulated, it became evident that not all patients with IgA nephropathy necessarily had a good prognosis. IgA nephropathy has a significant morbidity, culminating in end‐stage kidney disease (ESKD) in about 40% of patients without treatment within 20 years of the diagnosis. Although almost 20% of patients remain stable in their renal function, 30%–40% of patients develop ESKD from its onset. The important factors of renal outcome in patients with IgA nephropathy is the severity of histopathological findings, heavy proteinuria, long duration of proteinuria, haematuria and hypertension. [ABSTRACT FROM AUTHOR]

AbstractPlatelet aggregation is a complicated process mediated by different signaling pathways. As the process is highly complex and apparently redundant, the relationships between these pathways are not yet fully known. The aim of this project was to study the interconnections among seven different aggregation pathways in a group of 53 generally healthy volunteers aged 20 to 66 years. Platelet aggregation was induced with thrombin receptor activating peptide 6 (TRAP), arachidonic acid (AA), platelet activating factor 16 (PAF), ADP, collagen, thromboxane A2 analogue U46619 or ristocetin (platelet agglutination) ex vivo in fasting blood samples according to standardized timetable protocol. Additionally, some samples were pre-treated with known clinically used antiplatelet drugs (vorapaxar, ticagrelor or acetylsalicylic acid (ASA)). Significant correlations among all used inducers were detected (Pearson correlation coefficients (rP): 0.3 to 0.85). Of all the triggers, AA showed to be the best predictor of the response to other inducers with rP ranging from 0.66 to 0.85. Interestingly, the antiplatelet response to ticagrelor strongly predicted the response to unrelated drug vorapaxar (rP = 0.71). Our results indicate that a response to one inducer can predict the response for other triggers or even to an antiplatelet drug. These data are useful for future testing but should be also confirmed in patients.

Background: Antiplatelet therapy is used to decrease the risk of graft failure post coronary artery bypass graft surgery. We aimed to compare dual antiplatelet therapy (DAPT) with monotherapy along with a comparison of Aspirin, Ticagrelor, Aspirin+Ticagrelor (A+T) and Aspirin+Clopidogrel (A+C) to determine the major and minor bleeding risk, risk of postoperative myocardial infarction (MI), stroke, and all-cause mortality (ACM). Methods: Randomized Controlled Trials comparing the four groups were included. Odds ratio (OR) and Absolute Risk (AR) were employed to assess the mean and standard deviation (SD) with 95% confidence intervals (CI). The Bayesian random-effects model was used for statistical analysis. Risk difference and Cochran Q tests were used to calculate rank probability (RP) and heterogeneity, respectively. Results: We included 10 trials, consisting of 21 arms and 3926 patients. For the risk of major and minor bleed, A + T and Ticagrelor showed the lowest mean value of 0.040 (0.043) and 0.067 (0.073), respectively, and the highest RP of being the safest group. While a direct comparison between DAPT and monotherapy resulted in an OR of 0.57 [0.34, 0.95] for the risk of minor bleed. A + T was found to have the highest RP and the lowest mean value in terms of ACM, MI, and stroke. Conclusion: No significant difference was found between monotherapy or dual-antiplatelet therapy for the major bleeding risk safety outcome, however DAPT was found to have a significantly higher rate of minor bleeding complications post-CABG. DAPT should be considered as the antiplatelet modality of choice post-CABG. [ABSTRACT FROM AUTHOR]

Purpose: Prasugrel is not approved for patients treated with flow diverters, which have a high metal coverage ratio. However, robust antiplatelet therapy with prasugrel may prevent thromboembolic complications. We administered prasugrel and aspirin to all patients treated with flow diverters and reported the safety of the antiplatelet therapy regimen. Methods: This retrospective, single-center study evaluated the angiographic and clinical data of consecutive patients treated with flow diverters for cerebral unruptured aneurysms between June 2020 and May 2022. All patients received dual antiplatelet therapy, including prasugrel and aspirin. The administration of prasugrel ended 3 or 6 months after the procedure, whereas aspirin use continued for at least 12 months. Periprocedural complications (< 30 days post-procedure) and delayed complications (> 30 days post-procedure) were recorded. Results: During the study period, 120 unruptured aneurysms were treated with flow diverters in 110 patients. All patients, except one, survived longer than 12 months after the procedure. The rate of thromboembolic complications was 6.4%, and more than half of the patients had transient symptoms; one (0.9%) had a major ischemic stroke. One patient (0.9%) each had an asymptomatic, small subarachnoid hemorrhage and significant hemorrhagic complications with melena. The rate of permanent neurological deficits was 1.8%, and the mortality rate was 0.9%. Conclusions: Dual antiplatelet therapy comprising routine use of prasugrel and aspirin for flow diverter-implanted patients possibly contributed to a low rate of thromboembolic complications and low risk of hemorrhagic complications. [ABSTRACT FROM AUTHOR]

Platelet aggregation is a complicated process mediated by different signaling pathways. As the process is highly complex and apparently redundant, the relationships between these pathways are not yet fully known. The aim of this project was to study the interconnections among seven different aggregation pathways in a group of 53 generally healthy volunteers aged 20 to 66 years. Platelet aggregation was induced with thrombin receptor activating peptide 6 (TRAP), arachidonic acid (AA), platelet activating factor 16 (PAF), ADP, collagen, thromboxane A2 analogue U46619 or ristocetin (platelet agglutination) ex vivo in fasting blood samples according to standardized timetable protocol. Additionally, some samples were pre-treated with known clinically used antiplatelet drugs (vorapaxar, ticagrelor or acetylsalicylic acid (ASA)). Significant correlations among all used inducers were detected (Pearson correlation coefficients (rP): 0.3 to 0.85). Of all the triggers, AA showed to be the best predictor of the response to other inducers with rP ranging from 0.66 to 0.85. Interestingly, the antiplatelet response to ticagrelor strongly predicted the response to unrelated drug vorapaxar (rP = 0.71). Our results indicate that a response to one inducer can predict the response for other triggers or even to an antiplatelet drug. These data are useful for future testing but should be also confirmed in patients. [ABSTRACT FROM AUTHOR]

• 29% of mild stroke patients, registered in ADS had the aortic arch atheroma. • Aortic arch atheroma was associated with previous ischemic stroke and multiple infarcts at admission. • New DWI lesion within 14 days was frequently observed in patients with aortic arch plaque. • Combined cilostazol and aspirin therapy did not prevent new DWI comparing aspirin therapy in this cohort. Aortic arch atheroma is one of the embolic sources in patients with ischemic stroke. Although transesophageal echocardiogram (TEE) is the golden standard to evaluate the aortic arch atheroma, it is invasive and may be limited to patients with suspected embolism. Present post-hoc analysis evaluated the acute dual study data on mild stroke patients who had aortic arch atheroma proven by TEE and evaluate whether combined cilostazol and aspirin therapy might reduce the rate of stroke recurrence comparing aspirin therapy. Aortic arch atheroma was defined as aortic arch plaque with a maximal intima-medial thickness of ≥4.0 mm. Stroke recurrence included new diffusion-weighted image (DWI) lesions within 14 days. Among 316 (227 [72%] men; median, 66 [interquartile, 60–76] years old) patients, TEE found that 93 patients (29%) had the aortic arch atheroma, and 223 (71%) did not had it. The aortic arch atheroma group was older (P = 0.001) and accompanied with diabetes mellitus (P = 0.003), dyslipidemia (P = 0.046), smoking (P = 0.034), and had previous ischemic stroke history (P = 0.042) and multiple infarcts (P = 0.024) on admission. During hospitalization, new DWI lesion was frequently observed in the aortic arch atheroma group compared to the group without it (14.1% vs. 6.8%, P = 0.049). The rates of new DWI lesion were not different between dual antiplatelet therapy group and aspirin group (14.9% vs. 13.3%, P = 1.000). Aortic arch atheroma was the representative of systematic arteriosclerosis associated with new DWI lesion in short-term. Combined antiplatelet therapy using cilostazol did not prevent new DWI appearance comparing aspirin therapy in this cohort. [ABSTRACT FROM AUTHOR]

Background: As there is no consensus on the impact of antithrombotic drugs on post-gastrectomy outcomes in gastric cancer patients, this study aimed to investigate the impact of antithrombotic drugs on postoperative outcomes in these patients after gastrectomy. Methods: Patients with Stage I–III primary gastric cancer who underwent radical gastrectomy between April 2005 and May 2022 were included. We performed propensity score matching to adjust for patient background and compared bleeding complications. Multivariate analysis with logistic regression analysis was performed to identify risk factors associated with bleeding complications. Results: Of the 6798 patients, 310 (4.6%) were in the antithrombotic group and 6488 (95.4%) were in the non-antithrombotic group. Twenty-six patients (0.38%) experienced bleeding complications. After matching, the number of patients in each group was 300, with insignificant differences in any factor. A comparison of postoperative outcomes showed no difference in bleeding complications (P = 0.249). In the antithrombotic group, 39 (12.6%) continued drugs, and 271 (87.4%) discontinued them before surgery. After matching, there were 30 and 60 patients, respectively, with no differences in patient background. A comparison of postoperative outcomes showed no differences in bleeding complications (P = 0.551). In multivariate analysis, antithrombotic drug use and continuation of antiplatelet agents were not risk factors for bleeding complications. Conclusion: Antithrombotic drugs and its continuation may not worsen bleeding complications in patients with gastric cancer after radical gastrectomy. Bleeding complications were rare, and further studies are needed on risk factors for bleeding complications in larger databases. [ABSTRACT FROM AUTHOR]

The process of platelet aggregation is often influenced by several factors including sex and age. A literature review confirmed the existence of sex-related differences in platelet aggregation. Although 68 out of 78 papers found such differences, there are still some controversies regarding these differences, which can be due to multiple factors (age, trigger, concomitant disease, sample handling, etc.). These outcomes are discussed in line with novel results obtained from a local study, in which blood samples from a total of 53 overall healthy women and men with ages ranging from 20 to 66 years were collected. Aggregation was induced with seven different triggers (ristocetin, thrombin receptor activating peptide 6 [TRAP-6], arachidonic acid [AA], platelet-activating factor 16 [PAF-16], ADP, collagen, or thromboxane A 2 analog U-46619) ex vivo. In addition, three FDA-approved antiplatelet drugs (vorapaxar, ticagrelor, or acetylsalicylic acid [ASA]) were also tested. In general, women had higher aggregation responses to some agonists (ADP, TRAP), as well as lower benefit from inhibitors (ASA, vorapaxar). The aggregatory responses to AA and TRAP decreased with age in both sexes, while responses to ADP, U-46619, and PAF were affected by age only in women. In conclusion, more studies are needed to decipher the biological importance of sex-related differences in platelet aggregation in part to enable personalized antiplatelet treatment. [ABSTRACT FROM AUTHOR]

Therapeutic peptides are oligomers or short polymers of amino acids used for various medical purposes. Peptide-based treatments have evolved considerably due to new technologies, stimulating new research interests. They have been shown to be beneficial in a variety of therapeutic applications, notably in the treatment of cardiovascular disorders such as acute coronary syndrome (ACS). ACS is characterized by coronary artery wall damage and consequent formation of an intraluminal thrombus obstructing one or more coronary arteries, leading to unstable angina, non-ST elevated myocardial infarction, and ST-elevated myocardial infarction. One of the promising peptide drugs in the treatment of these pathologies is eptifibatide, a synthetic heptapeptide derived from rattlesnake venom. Eptifibatide is a glycoprotein IIb/IIIa inhibitor that blocks different pathways in platelet activation and aggregation. In this narrative review, we summarized the current evidence on the mechanism of action, clinical pharmacology, and applications of eptifibatide in cardiology. Additionally, we illustrated its possible broader usage with new indications, including ischemic stroke, carotid stenting, intracranial aneurysm stenting, and septic shock. Further research is, however, required to fully evaluate the role of eptifibatide in these pathologies, independently and in comparison to other medications. [ABSTRACT FROM AUTHOR]

Ticagrelor is a BCS class IV drug that inhibits platelet action by reversibly binding to the P2Y12 receptor. One of the major challenges faced by the class IV (low solubility, low permeability) drug is the lower dissolution rate leading to low bioavailability. The bioavailability of the marketed formulation of ticagrelor is approximately 36%. Researchers have come up with various techniques to improve the BCS class II and IV drug formulations as an integral part of the development of the pharmaceutical sciences. An increase in solubility can be achieved by various methods such as Salt formation, Complexation, Micronization, Solid Dispersion, altering the pH, Co-solvency, co-crystals, polymeric micelles, etc. A highly efficacious technique is converting a crystalline drug to its amorphous form. An extensive literature search was conducted using various databases like science direct, Taylor and Francis, Springer to extract relevant articles. Keywords like "Ticagrelor", "low permeability", "P2Y12 receptor inhibitor" were used for the literature search. Relevant articles were screened and referred for further study. This article discusses the techniques employed to increase the solubility of ticagrelor, thus highlighting the research conducted and reported. The increase in bioavailability of ticagrelor could be seen when formulated as nanoparticles, co-crystals, ticagrelor loaded self-micro emulsifying and nano emulsifying drug delivery system, solid dispersion, etc. the conversion of the crystalline drug into amorphous drug is a highly recommended approach to increase the solubility of ticagrelor which can be seen in cases of co-crystals and solid dispersion formulation. [ABSTRACT FROM AUTHOR]

De novo cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging (MRI) develop over time in adult moyamoya disease (MMD) and are generally associated with a decline in global cognitive function. The present supplementary analysis of a 5-year prospective cohort aimed to elucidate the incidence of an interval increase in CMBs in adult patients receiving medical management alone for ischemic MMD and its impact on cognitive function. Sixty-four patients without misery perfusion in the symptomatic cerebral hemispheres at inclusion who did not experience any further ischemic symptoms or new hemorrhagic events during a 5-year follow-up period underwent T2*-weighted MRI and five kinds of neuropsychologic tests at inclusion and the end of the 5-year follow-up. When T2*-weighted MRI was compared between inclusion and the end of the 5-year follow-up, 10 patients (15%) had an interval increase in CMBs in the symptomatic cerebral hemisphere at inclusion. The scores from two kinds of neuropsychologic tests significantly deteriorated at the end of the 5-year follow-up compared with those at inclusion in patients with an interval increase in CMBs, whereas the scores of four kinds of neuropsychologic tests significantly improved at the end of the 5-year follow-up compared with those at inclusion in patients without interval increases in CMBs, asymptomatic ischemic lesions, or angiographic disease progression. The incidence of an interval increase in CMBs was 15% per 5 years in adult patients receiving medical management alone for ischemic MMD, and this increase was associated with a decline in cognitive decline. [ABSTRACT FROM AUTHOR]

Abstract Purpose Considering a high prevalence of congenital and especially acquired bleeding disorders, their heterogeneity and the multitude of possible treatments strategies, a review of the scientific data on this topic is needed to implement a treatment guide for healthcare professionals. Methods A selective literature review was performed via PubMed for articles describing oral surgery / dental implant procedures in patients with congenital and acquired bleeding disorders. Out of the existing literature, potential treatment algorithms were extrapolated. Results In order to assess the susceptibility to bleeding, risk stratification can be used for both congenital and acquired coagulation disorders. This risk stratification, together with an appropriate therapeutic pathway, allows for an adequate and individualized therapy for each patient. A central point is the close interdisciplinary cooperation with specialists. In addition to the discontinuation or replacement of existing treatment modalities, local hemostyptic measures are of primary importance. If local measures are not sufficient, systemically administered substances such as desmopressin and blood products have to be used. Conclusions Despite the limited evidence, a treatment guide could be developed by means of this narrative review to improve safety for patients and practitioners. Prospective randomized controlled trials are needed to allow the implementation of official evidence-based guidelines.

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 I2 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. [ABSTRACT FROM AUTHOR]

Background: Ticagrelor or prasugrel are recommended to reduce ischemic events in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). However, in clinical practice, patients are often switched from a potent P2Y12 inhibitor to clopidogrel prior to or at discharge ('de-escalation'). We sought to assess the incidence and predictors of de-escalation.Methods: Consecutive patients who received either a ticagrelor or prasugrel loading dose for AMI PCI at two tertiary centers between Jan 2015-Mar 2019 who survived to discharge were included. Data were obtained from the electronic health record and institutional NCDR CathPCI data. Patients who were de-escalated to clopidogrel were compared with those who remained on potent P2Y12 inhibitors through the time of discharge.Results: Of the1818 patients in the cohort, 1146 (63%) were de-escalated. Patients in the de-escalation group were older, more often Black, had lower prevalence of co-morbidities, less often had private insurance, and had less complex PCI. After adjustment, older age remained positively associated (OR 1.2, CI 1.08-1.34, p = .001) and Caucasian race (OR 0.5, CI 0.33-0.77, p = .002), prior MI (OR 0.7, CI 0.5-0.97, p = .032), bifurcation lesion (OR 0.71, CI 0.53-0.95, p = .019), and greater number of stents (OR 0.82, CI 0.75-0.91, p = .0001) were negatively associated with de-escalation. In de-escalated patients, the rationale was not documented in 75.9% of cases.Conclusions: De-escalation occurred frequently in patients with AMI and was associated with both non-clinical and clinical factors. Medical decision making was poorly documented and represent an area for improvement. [ABSTRACT FROM AUTHOR]

Background and Purpose: Although the amphiphilic nature of the widely used antithrombotic drug Ticagrelor is well known, it was never considered as a membranotropic agent capable of interacting with the lipid bilayer in a receptor-independent way. In this study, we investigated the influence of Ticagrelor on plasma membrane lipid order in platelets and if this modulates the potency of Ticagrelor at the P2Y 12 receptor., Experimental Approach: We combined fluorescent in situ, in vitro and in silico approaches to probe the interactions between the plasma membrane of platelets and Ticagrelor. The influence of Ticagrelor on the lipid order of the platelet plasma membrane and large unilamellar vesicles was studied using the advanced fluorescent probe NR12S. Furthermore, the properties of model lipid bilayers in the presence of Ticagrelor were characterized by molecular dynamics simulations. Finally, the influence of an increased lipid order on the dose-response of platelets to Ticagrelor was studied., Key Results: Ticagrelor incorporates spontaneously into lipid bilayers and affects the lipid order of the membranes of model vesicles and isolated platelets, in a nontrivial composition and concentration-dependent manner. We showed that higher plasma membrane lipid order in platelets leads to a lower IC 50 value for Ticagrelor. It is shown that membrane incorporation of Ticagrelor increases its potency at the P2Y 12 receptor, by increasing the order of the platelet plasma membrane., Conclusion and Implications: A novel dual mechanism of Ticagrelor action is suggested that combines direct binding to P2Y 12 receptor with simultaneous modulation of receptor-lipid microenvironment., (© 2024 British Pharmacological Society.)

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

Purpose: Considering a high prevalence of congenital and especially acquired bleeding disorders, their heterogeneity and the multitude of possible treatments strategies, a review of the scientific data on this topic is needed to implement a treatment guide for healthcare professionals. Methods: A selective literature review was performed via PubMed for articles describing oral surgery / dental implant procedures in patients with congenital and acquired bleeding disorders. Out of the existing literature, potential treatment algorithms were extrapolated. Results: In order to assess the susceptibility to bleeding, risk stratification can be used for both congenital and acquired coagulation disorders. This risk stratification, together with an appropriate therapeutic pathway, allows for an adequate and individualized therapy for each patient. A central point is the close interdisciplinary cooperation with specialists. In addition to the discontinuation or replacement of existing treatment modalities, local hemostyptic measures are of primary importance. If local measures are not sufficient, systemically administered substances such as desmopressin and blood products have to be used. Conclusions: Despite the limited evidence, a treatment guide could be developed by means of this narrative review to improve safety for patients and practitioners. Prospective randomized controlled trials are needed to allow the implementation of official evidence-based guidelines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (ROTEMVR) 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 ROTEMVR platelet and light transmission aggregometry (LTA). According to the lower reference limit, ROTEMVR 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, ROTEMVR 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. [ABSTRACT FROM AUTHOR]

Aims: Patients using antithrombotic drugs after percutaneous coronary intervention (PCI) are at risk for bleeding and recurrent ischemia. We aimed to explore routine and tissue plasminogen activated (tPA) ROTEM results in a post-PCI population on dual antithrombotic treatment.Methods and Results: In this prospective cohort, 440 patients treated with double antithrombotic therapy after recent PCI and with ≥3 risk factors for either ischemic or bleeding complications were included and compared with a control group (n = 95) consisting of perioperative patients not using antithrombotic medication. Laboratory assessment, including (tPA) ROTEM, was performed one month post-PCI and bleeding/ischemic complications were collected over a five-month follow-up. Patients were stratified by antithrombotic regimen consisting of a P2Y12 inhibitor with either aspirin (dual antiplatelet therapy; DAPT, n = 323), a vitamin K antagonist (VKA, n = 69) or a direct oral anticoagulant (DOAC, n = 48). All post-PCI patients had elevated ROTEM clot stiffness values, but only the DAPT group additionally presented with a decreased fibrinolytic potential as measured with tPA ROTEM. Patients receiving anticoagulants had prolonged clotting times (CT) when compared to the control and DAPT group; EXTEM and FIBTEM CT could best discriminate between patients (not) using anticoagulants (AUC > 0.97). Furthermore, EXTEM CT was significantly prolonged in DAPT patients with bleeding complications during follow-up (68 [62–70] vs. 62 [57–68], p = 0.030).Conclusion: ROTEM CT has high potential for identifying anticoagulants and tPA ROTEM could detect a diminished fibrinolytic potential in patients using DAPT. Furthermore, the ability of EXTEM CT to identify patients at risk for bleeding may be promising and warrants further research.

Introduction: Aspirin and anti-P2Y12 are widely prescribed in cardiovascular patients, often in combination with proton pump inhibitors (PPIs) to limit the risk of upper gastrointestinal bleedings. The potential interaction between PPIs and antiplatelet agents has been widely discussed, but doubts remain as to whether PPIs may reduce the cardiovascular protection provided by aspirin, prasugrel, ticagrelor, and clopidogrel., Areas Covered: Many pharmacokinetic (PK) and pharmacodynamic (PD) studies have confirmed the interaction, especially between PPIs and clopidogrel, but with uncertain consequences on clinical outcomes. Therefore, we aimed to summarize the evidence for the widespread combined use of oral antiplatelet drugs and PPIs, to outline the current evidence supporting or opposing drug-drug interaction, and to discuss the clinical implications of such interactions., Expert Opinion: A large body of evidence describes the PK/PD interaction of antiplatelet drugs with PPIs and its potential role in increasing clinical cardiovascular adverse events, but no solid clinical data have confirmed these effects. In the light of the published studies, there seems to be no restriction on the choice of PPI with aspirin, prasugrel, and/or ticagrelor. The choice of a PPI with no (or minimal) interference with the hepatic cytochrome P450 2C19 is preferred in patients receiving clopidogrel.

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. [ABSTRACT FROM AUTHOR]

Background Among patients with atrial fibrillation and stable coronary artery disease, those with histories of atherothrombotic disease are at high‐risk for future ischemic events. This study investigated the efficacy and safety of rivaroxaban monotherapy in patients with atrial fibrillation, coronary artery disease, and histories of atherothrombotic disease. Methods and Results This was a post hoc subanalysis of the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial. Patients with non‐valvular atrial fibrillation and coronary artery disease were recruited and randomized to receive the rivaroxaban monotherapy or combination therapy with rivaroxaban plus antiplatelet drug. For the purpose of this sub‐study, participants were divided into 2 subgroups, including the atherothrombosis group (those with histories of myocardial infarction, stroke, and/or peripheral artery disease; n=1052, 47.5%) and non‐atherothrombosis group (n=1163, 52.5%). The efficacy end point included cardiovascular events or all‐cause death, while the safety end point was major bleeding. Net adverse events consisted of all‐cause death, myocardial infarction, stroke, or major bleeding. In the atherothrombosis group, rivaroxaban monotherapy was significantly associated with a lower risk of net adverse events when compared with combination therapy (hazard ratio [HR], 0.50; 95% CI, 0.34–0.74; P

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.

• This post-hoc research extracted the data from previous dual antiplatelet trial registry. • The association of MBs with clinical outcome was evaluated. • Whether patient characteristics depended on the number of MBs was also analyzed. • MBs did not alter the rate of neurological deterioration and clinical outcome. • Diastolic blood pressure and a history of ICH were universally related to the MBs. In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Background: Actinic keratosis (AK) is a form of premalignant keratinocyte dysplasia. Recently, the role of photosensitizing drugs in the development of AK has been postulated. Objective: This study evaluated a possible association between the use of photosensitizing drugs and the development of AK. A secondary aim was to identify a possible association between any medication other than those primarily examined and AK. Methods: A single-center, case-control study assessed the cumulative drug exposure of 90 patients with AK and 90 controls visiting a dermatology service for other skin ailments. Before the visit, patients were interviewed to collect data on daily therapy and the lag-time of discontinued drugs within the last 2 years, and to record the drug’s active ingredient, dosage, and duration of therapy. In addition, sociodemographic characteristics including age, sex, educational level, skin phototype, and cumulative sun exposure habits were gathered. Results: By logistic regression, exposures to angiotensin II receptor blockers (ARBs) and antiplatelet agents were identified as independent risk factors for the development of AK. ARB intake was associated with AK only at high exposure (OR = 13.6; 95% CI, 2.0-93.8). The use of antiplatelet drugs was borderline, yet not significant, at low exposure (OR = 3.31; 95% CI, 0.86-12.7), but increased in a dose-dependent manner. The strongest correlation was found at the highest cumulative dose (>1100 dose unit-years (OR = 4.38; 95% CI, 1.16-16.6). Conclusions: High exposure to ARBs and antiplatelet agents may promote AK carcinogenesis in at-risk patients.

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. [ABSTRACT FROM AUTHOR]

Study Objectives: By modifying the apneic threshold, the antiplatelet agent ticagrelor could promote central sleep apnea hypopnea syndrome (CSAHS). We aimed to assess the association between CSAHS and ticagrelor administration.Methods: Patients were prospectively included within 1 year after acute coronary syndrome (ACS), if they had no heart failure (and left ventricular ejection fraction ≥ 45%) and no history of sleep apnea. After an overnight sleep study, patients were classified as "normal" with apnea hypopnea index (AHI) < 15, "CSAHS patients" with AHI ≥ 15 mostly with central sleep apneas, and "obstructive sleep apnea hypopnea syndrome (OSAHS) patients" with AHI ≥ 15 mostly with obstructive sleep apneas.Results: We included 121 consecutive patients (mean age 56.8 ± 10.8, 88% men, mean body mass index 28.3 ± 4.4 kg/m2, left ventricular ejection fraction 56 ± 5%, at a mean of 67 ± 60 days (median 40 days, interquartile range: 30-80 days) after ACS. In total, 49 (45.3%) patients had AHI ≥ 15 (27 [22.3%] CSAHS %, 22 [18.2%] OSAHS). For 80 patients receiving ticagrelor, 24 (30%) had CSAHS with AHI ≥ 15, and for 41 patients not taking ticagrelor, only 3 (7.3%) had CSAHS with AHI ≥ 15 (chi-square = 8, p = 0.004). On multivariable analysis only age and ticagrelor administration were associated with the occurrence of CSAHS, (p = 0.0007 and p = 0.0006).Conclusion: CSA prevalence after ACS is high and seems promoted by ticagrelor administration. Results from monocentric study suggest a preliminary signal of safety. CLINICAL TRIALS.Gov Id: NCT03540459. [ABSTRACT FROM AUTHOR]

Objective: Cerebral vasospasm and delayed cerebral ischemia (DCI) are considered complications after aneurysmal subarachnoid hemorrhage (aSAH). Several hypotheses involving platelet activation have been asserted in the pathophysiology of cerebral vasospasm and DCI. This study aimed to investigate the effect of dual antiplatelet treatment (DAPT) on symptomatic vasospasm and DCI in patients with aSAH. Methods: A retrospective study was conducted on patients with aSAH from 2009 to 2018. The patients are divided into 2 groups according to the treatment method such as simple or balloon-assisted coil embolization group (SB coiling), and stentassisted coil embolization group. Patients treated by SB coiling without DAPT were classified as the control group. Patients who required dual antiplatelet treatment due to stent-assisted coil embolization were classified as DAPT group. The incidence of symptomatic vasospasm and DCI was compared between the two groups. Results: Of 743 patients with aSAH, 563 patients were treated with clipping, 115 patients treated with SB coiling, and 65 patients receive stent-assisted coiling. Among 115 patients underwent SB coiling, 14 patients were excluded by the exclusion criteria. Total number of control group (SB coiling) was 101, DAPT group (stentassisted coiling) was 65. Depending on whether or not taking DAPT, the incidence of symptomatic vasospasm was lower in the DAPT group (p=0.010). DCI incidence was also lower in the DAPT group, which was statistically significant (p=0.029). Conclusions: DAPT reduces the frequency of symptomatic vasospasm and DCI in patients with aSAH in our single-center study. To warranting this topic, further, larger prospective and randomized studies should be needed. [ABSTRACT FROM AUTHOR]

Recurrent spontaneous abortion (RSA) is defined as the loss of at least two consecutive pregnancies before the 28th week of gestation. RSA is a complicated pathological condition causedmultiple factors including genetic abnormalities, anatomical factors, endocrine disorders, immune abnormalities, prethrombotic state (PTS) and infection factors. Studies have suggested that anticoagulation and antiplatelet therapy could significantly improve the pregnancy outcomes of RSA patients with PTS and autoimmune abnormalities. Frequently used anticoagulants and antiplatelet drugs are heparin, heparinoid, warfarin, aspirin and clopidogrel. However, the maternal and fetal safety after the of these drugs during pregnancy has long been concerned. Safety of anticoagulants and antiplatelet drugs in patients with recurrent spontaneous abortion during pregnancy is reviewed. [ABSTRACT FROM AUTHOR]

BACKGROUND: One of the concerns in patients with acute ischemic stroke with former history of taking antiplatelet drugs is the risk of intracerebral hemorrhage following venous thrombolysis. The purpose of this study was to evaluate the effect of previous administration of antiplatelet drugs on adverse outcomes of recombinant tissue plasminogen activator (tPA) in patients with acute ischemic stroke. METHODS: In this study, 46 patients with the diagnosis of acute ischemic stroke were recruited. Patients were assessed in a period of three hours after stroke and received the standard dose of tPA (0.9 mg/kg). History of antiplatelet drugs, risk factors, demographic information and stroke severity were collected. The severity of the stroke was determined by the National Institutes of Health Stroke Scale (NIHSS). The outcome was assessed using the Modified Rankin Scale (MRS) and Barthel Index (BI) in the days one, 14 and 90. RESULTS: Patients with history of antiplatelet drugs had an increased rate of intracranial hemorrhage [odds ratio (95% CI) = 7.3 (1.3–40.5)]. Stroke severity scores were higher in patients receiving antiplatelet drugs than the other group at discharge day and day 90. In both groups, the severity of the disease decreased with time. Mortality rate was 42.1% in patients received antiplatelet drugs and 18.5% in the other group (P > 0.05). CONCLUSION: Based on the results of this study, patients with acute ischemic stroke and history of taking antiplatelet drugs have poor outcome following administration of standard dose of tPA. [ABSTRACT FROM AUTHOR]

Our previous acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of neurological deterioration in non-cardioembolic stroke patients. In this post-hoc analysis, we investigated whether the impact of dual antiplatelet therapy (DAPT) may depend on neurological severity, as represented by large artery disease. Neurological deterioration was defined as neurological progression with an increment of the National Institutes of Health Stroke Scale (NIHSS) score of ≥2. NIHSS score subgroups were divided into that of 0–1, 2–4, 5–10, and >10. Among 1014 patients, 203 (20%) had the large artery disease, and 811 (80%) did not. In the total cohort, the rate of neurological deterioration was 10.8% in the DAPT group and 8.3% in the aspirin group (P = 0.197). When we focused on the large artery disease group, DAPT group had a higher rate of neurological deterioration as 18.3% compared to 8.2% in the aspirin group (P = 0.036). Among patients with NIHSS score of 0–1 and 2–4, the rates of neurological deterioration were not different between the two group (both, P = 1.000). However, when NIHSS score elevated to 5–10, 45% in the DAPT group and 9.1% in the aspirin group deteriorated (P = 0.013). Among the patients with NIHSS score of >10, 60% in the DAPT group and none (0%) in the aspirin group had the neurological deterioration (P = 0.045). DAPT with aspirin and cilostazol was associated with higher rate of neurological deterioration when patients have large artery disease and not mild neurological deficits. • Whether the impact of dual antiplatelet therapy (DAPT) using cilostazol may depend on the neurological severity was studied. • Neurological deterioration was defined as neurological progression with an increment of the NIHSS score of ≥2. • In patients with large artery disease, DAPT group had a higher rate of progression compared to the aspirin group. • In patients with NIHSS score of 5–10, 45% in the DAPT group and 9.1% in the aspirin group deteriorated. • DAPT using cilostazol was associated with progression when patients have large artery disease and not mild neurological deficits. [ABSTRACT FROM AUTHOR]

The maintenance dose of prasugrel (PRAS) for neuroendovascular treatment requires much research. We report the antiplatelet effect of PRAS measured by VerifyNow P2Y12 reaction units (PRUs) in patients during the perioperative period of neuroendovascular treatment.Between January 2017 and January 2023, 230 patients who underwent endovascular treatment for unruptured intracranial aneurysms or carotid artery stenosis at our institution were retrospectively identified. Patients received dual antiplatelet therapy with 100 mg aspirin (ASA) and 75 mg clopidogrel (CLP)/day (CLP group, n = 186) or 100 mg ASA and 3.75 mg PRAS/day (PRAS group, n = 44) 2 weeks before the procedures. The PRU value was compared between the CLP and PRAS groups. In the study, we defined 95≦PRU < 208 as the optimal range. Perioperative complications within seven days of surgery were also analyzed.The mean value of PRU was significantly low in the PRAS group (179.13 ± 66.03 in CLP vs. 154.75 ± 54.01 in PRAS, p = 0.024). The proportion of the patients who exhibited 95≦PRU < 208 was significantly higher in the PRAS group (55.4% vs. 72.7%, p = 0.036). Ischemic and hemorrhagic complication rates were not significantly different between the CLP and PRAS groups (7.6% vs. 0%, p = 0.076; 4.7% vs. 0%, p = 0.361). The ischemic complication rate was higher in patients with a PRU > 208 than in those with PRU < 208 (12.5% vs. 3.8%, p = 0.044). The hemorrhagic complication rate was not significantly different between the PRU < 95 and 95≦PRU groups (8.4% vs. 3.2%, p = 0.224).Maintenance dose PRAS further decreased the PRU value and reached the optimal range in more cases than CLP during the perioperative period of neuroendovascular treatment. Ischemic complications significantly increased in the 208 < PRU group. [ABSTRACT FROM AUTHOR]

Background: Coronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease. Methods: This study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation. Results: The mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42 ± 3.32%, respectively (t= −1.278, P= 0.213). The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87 ± 5.10% and 61.94 ± 5.90%, respectively (t = 1.425, P= 0.167). There was no significant difference in the inhibition rates of platelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel. Conclusion: Dialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.

Background: Although antithrombotic agents are widely used for cardiac and cerebrovascular disease prevention, they increase the risk of gastrointestinal (GI) bleeding. Objective: To examine GI bleeding risk in association with an esophagogastroduodenoscopy (EGD) biopsy performed in patients without cessation of antithrombotic therapy. Methods: This study was prospectively conducted at 14 centers. EGD biopsies were performed in patients receiving antithrombotic agents without cessation, as well as age- and sex-matched controls not receiving antithrombotic therapy. Patients treated with warfarin before the biopsy had a prothrombin time-international normalized ratio level

Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non‐Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator‐initiated, prospective, multicenter (34 hospitals in Japan), randomized, open‐label, and aspirin‐controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61–77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1–4) in both groups (P=0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group (P=0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group (P=0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short‐term neurological worsening. Clinical Trial Registration URL: umin.ac.jp/ctr/index/htm. Unique identifier: UMIN000004950.

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates (ADIRs) and average daily bleeding rates (ADBRs) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low‐dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient‐days of follow‐up and assessed within different clinical phases: acute (0–3 days), subacute (4–30 days), and late (31–365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4–2.9) higher than ADBRs. ADIRs were significantly higher in the clopidogrel arm than in the low‐dose prasugrel arm in the subacute phase (Padj

This study aimed to evaluate the safety and necessity of antithrombotic drugs for acute type B aortic dissection (TBAD) treated with thoracic endovascular aortic repair (TEVAR).The patients of acute TBAD treated with TEVAR were retrospectively enrolled from January 2007 to October 2022 in General Hospital of Northern Theater Command. The primary outcomes such as mortality and aortic adverse events [stroke, paraplegia, limb ischemia, organ failure (renal and intestinal tract), endoleak, redissection, aortic rupture, reintervention, and mortality] were recorded and evaluated at 1 month (early term) and 18 months (late term).The 697 patients of TBAD treated with TEVAR were divided into the antithrombotic (AT) group (n = 208) and nonantithrombotic (NAT) group (n = 489). The incidence of early mortality, early aortic adverse events, and the 18 months of cumulative freedom from all-cause mortality and aortic adverse events were not significantly different between the AT and NAT groups (2.4% versus 1.4%, 2.9% versus 4.5%, 94.7% versus 96.5% and 88.4% versus 89.9%, respectively). Log-rank tests also indicated that there were no significant differences. In multivariate Cox regression models, only pleural effusion, partially thrombosed of false lumen, maximum diameter of false lumen, and branch involvement were independent predictors of mortality, whereas the systolic blood pressure (SBP), pleural effusion, partially thrombosed of false lumen, true lumen compression, maximum diameter of false lumen, branch involvement were independent predictors of adverse aortic events.The antithrombotic drug for acute TBAD treated with TEVAR does not influence the mortality and aortic events in the early and late terms.

Background: Immune checkpoint inhibitors (ICIs) are indicated for various cancers and are the mainstay of cancer immunotherapy. They are often associated with ICI-related pneumonitis (CIP), however, hindering a favorable clinical course. Recently, non-oncology concomitant drugs have been reported to affect the efficacy and toxicity of ICIs; however, the association between these drugs and the risk for CIP is uncertain. The aim of this study was to assess the impact of baseline concomitant drugs on CIP incidence in ICI-treated advanced cancer patients., Patients and Methods: This was a single-center retrospective study that included a cohort of 511 patients with advanced cancer (melanoma and non-small-cell lung, head and neck, genitourinary, and other types of cancer) treated with ICIs. Univariable analysis was conducted to identify baseline co-medications associated with CIP incidence. A propensity score matching analysis was used to adjust for potential CIP risk factors, and multivariable analysis was carried out to assess the impact of the identified co-medications on CIP risk., Results: Forty-seven (9.2%) patients developed CIP. In these patients, the organizing pneumonia pattern was the dominant radiological phenotype, and 42.6% had grade ≥3 CIP, including one patient with grade 5. Of the investigated baseline co-medications, the proportion of antiplatelet drugs (n = 50, 9.8%) was higher in patients with CIP (23.4% versus 8.4%). After propensity score matching, the CIP incidence was higher in patients with baseline antiplatelet drugs (22% versus 6%). Finally, baseline antiplatelet drug use was demonstrated to increase the risk for CIP incidence regardless of cancer type (hazard ratio, 3.46; 95% confidence interval 1.21-9.86)., Conclusions: An association between concomitant antiplatelet drug use at baseline and an increased risk for CIP was seen in our database. This implies the importance of assessing concomitant medications for CIP risk management., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

• Cilostazol is used in practice for the management of peripheral arterial disease. • A generic formulation of cilostazol was compared (C max , AUC, T max) with the brand-name product. • No statistically significant differences were found in either the bioavailability or safety profiles of the two products. • The generic version could increase Thai patients' access to cilostazol. Cilostazol is a vasodilator with anticoagulant effect for treatment of peripheral vascular disease. Cilostazol 100-mg tablet was shown to increase walking distance in this patient population. The aim of this study was to investigate and compare the pharmacokinetic profiles and safety of Bestazol 100-mg tablet (Berlin Pharmaceutical Industry Co Ltd, Bangkok, Thailand), which is a generic formulation of cilostazol, with the original brand Pletaal 100-mg tablet (Korea Otsuka Pharmaceutical Co Ltd, Seoul, South Korea) in healthy Thai adult volunteers. The pharmacokinetic profiles of Bestazol (test) and Pletaal (reference) 100-mg tablets were compared in a single-dose, open-label, 2-treatment, 2-period, 2-sequence, randomized crossover study in healthy Thai adult volunteers. This study was conducted at the Siriraj Clinical Research Center, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Each volunteer was initially treated according to either the test–reference or the reference–test sequence, after which each volunteer was switched to the other study sequence after a 2-week washout period. Pharmacokinetic analysis was performed using log-transformed ratios for C max , AUC 0–last , AUC 0–∞, T max , t 1/2 , and λ Z for both cilostazol and 3,4-dehydro-cilostazol (its active metabolite) with 90% CI. Physical examination, clinical laboratory data, vital signs, and adverse events were assessed in all participants. A total of 28 volunteers were included in the final analysis. The ratios of the geometric mean and the 90% CI compared test to reference of cilostazol formulations and were 101.86% (90% CI, 91.88%–112.92%), 107.78% (90% CI, 99.67%–116.56%), and 110.46% (90% CI, 102.68%–118.82%) for C max , AUC 0–last , and AUC 0–∞ , respectively. The ratios of the geometric mean and the 90% CI compared test to reference of 3,4-dehydro-cilostazol and were 106.72% (95% CI, 95.31%–119.50%), 110.54% (95% CI, 101.92%–119.89%), and 107.37% (95% CI, 96.74%–119.16%) for C max , AUC 0–last , and AUC 0–∞ , respectively. No significant difference was observed between formulations for T max. The most common adverse event was headache (51.85%), with no significant difference in incidence between the test and reference groups. No serious adverse events related to the studied drugs were reported. The findings of this study indicate these 2 cilostazol tablet formulations to be bioequivalent. Bestazol 100-mg tablet was bioequivalent to Pletaal 100-mg tablet. Thus, the formulations can be used interchangeably in clinical practice. [ABSTRACT FROM AUTHOR]

One-third to one-half of ischemic strokes occurred in patients taking antiplatelet drugs. The optimal therapeutic strategy for antithrombotic drugs remains uncertain and guidelines provide scarse recommendation. Therefore, aims of our study were to: (i) estimate the prevalence of patients who develop an ischemic stroke while on antiplatelet drugs, (ii) investigate potential factors associated with this phenomenon, (iii) describe management strategies in daily clinical practice. Consecutive adult patients admitted for acute ischemic stroke at the academic hospital of Varese, Italy, from January 2010 till December 2011 were included. Patients were retrospectively identified by searching the administrative database of the hospital. Odds ratios (ORs) and their 95% confidence intervals (CI) for identifying factors associated with dependent variable were estimated using univariate logistic regression. Any variable with a p value < 0.2 at univariate analysis was included in a multivariate model. A total of 419 patients were included. Patients with ischemic stroke while on antiplatelet drugs were 49.6%. The following baseline characteristics were associated with the occurrence of ischemic stroke in patients taking antiplatelet drugs: diabetes mellitus (DM), history of ischemic heart disease (IHD), age > 65 years and previous stroke or transient ischemic stroke (TIA). The following variables were significantly associated with a change of antithrombotic therapy at discharge: DM, history of IHD and previous stroke or TIA. Our study confirms that the occurrence of ischemic stroke during antiplatelet treatment is common and management of antithrombotic therapy is heterogeneous. Factors that may explain therapeutic failure include undetected cardioembolic sources, drug resistance, poor compliance, or the presence of diabetes, atherothrombotic disease, and advanced age. Randomized controlled trials are warranted to assess the optimal antithrombotic strategy for ischemic stroke occurred in patients taking antiplatelet drugs. [ABSTRACT FROM AUTHOR]

Objective: Adult patients with ischemic moyamoya disease (MMD) who receive treatment with antiplatelet drugs reportedly show improvements in neuropsychological test scores after around 2 years. The purpose of the present study subanalyzing the same patient cohort used in a previous study was to determine which antiplatelet drug, clopidogrel or cilostazol, results in better improvement of cognitive function among non-surgical adult patients showing ischemic MMD without severe hemodynamic compromise. Methods: Sixty-six patients without cerebral misery perfusion on 15O gas positron emission tomography were treated with pharmacotherapy alone. Patients ≥50 years old and <50 years old initially received clopidogrel and cilostazol, respectively. Any patient suffering side effects of the antiplatelet drug switched to the other antiplatelet drug. Neuropsychological tests were performed at study entry and at the end of the 2-year follow-up, and differences in each neuropsychological test score between the two time points (second test score - first test score) were calculated and defined as Δ scores. Results: Among the five neuropsychological tests, Δ scores for two tests were significantly greater in patients treated with cilostazol (n = 36) than in those treated with clopidogrel (n = 30), and Δ scores of the remaining three tests did not differ between patient groups. Based on Δ scores, 15 patients (23%) were defined as showing interval cognitive improvement. On multivariate analysis, cilostazol administration (95% confidence interval, 1.19-193.98; P = 0.0361) represented an independent predictor of interval cognitive improvement. Conclusions: Cilostazol may improve cognition better than clopidogrel in non-surgical adult patients with ischemic MMD. [ABSTRACT FROM AUTHOR]