Acetylsalicylic Acid Therapy Research Articles

A study of the comparative effectiveness of dual antiplatelet therapy and a combination of acetylsalicylic acid with colchicine in patients in the acute period of “minor” ischemic atherothrombotic stroke during hospitalization. Interim analysis of data from the «COLCHIDA» study

Influence on inflammation is currently becoming a priority target for the prevention of recurrent atherothrombotic events, including stroke. In 2022, we planned the KOLCHIDA study, a two-center, prospective, randomized, open-label, controlled clinical trial with endpoint assessment (ClinicalTrials.gov identifier: NCT06102720). The purpose of this study is to conduct a comparative assessment of the clinical effectiveness of dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel and the combination of ASA with colchicine in patients in the acute period of “minor” ischemic atherothrombotic stroke. The purpose of this publication is to present the basic concept of the protocol, its design and the first intermediate results. Material and methods. The intervention consisted of colchicine 0.5 mg/day in addition to ASA versus dual antiplatelet therapy (DAPT) in patients with non-severe ischemic stroke. 31 patients were included in the colchicine and ASA group, and 34 patients were included in the DAPT group. Results. In the comparison group, 7 (20.6%) recurrent non-fatal strokes were recorded, in contrast to the colchicine group, where acute vascular events were recorded in only two patients (6.5%) [RRR 2.2, NNT = 7, χ2 = 2, 9, p = 0.09]. There were no clinically significant bleeding or other adverse events in both groups. Conclusion. Interim results of the study indicate possible confirmation of the hypothesis that anti-inflammatory therapy with low doses of colchicine in combination with standard therapy is not inferior to the combination of ASA and clopidogrel, and perhaps more effectively reduces the number of early neurological deteriorations and recurrent ischemic strokes in patients in the acute period of mild atherothrombotic stroke with equal security profile.

Acetylsalicylic acid and dihydroartemisinin combined therapy on experimental malaria-associated acute lung injury: analysis of lung function and the inflammatory process

BackgroundSevere malaria can cause respiratory symptoms, which may lead to malaria-acute lung injury (MA-ALI) due to inflammation and damage to the blood-gas barrier. Patients with severe malaria also often present thrombocytopenia, and the use of acetylsalicylic acid (ASA), a commonly used non-steroidal anti-inflammatory drug with immunomodulatory and antiplatelet effects, may pose a risk in regions where malaria is endemic. Thus, this study aimed to investigate the systemic impact of ASA and dihydroartemisinin (DHA) on ALI induced in mice by Plasmodium berghei NK65 (PbNK65).MethodsC57BL/6 mice were randomly divided into control (C) and PbNK65 infected groups and were inoculated with uninfected or 104 infected erythrocytes, respectively. Then, the animals were treated with DHA (3 mg/kg) or vehicle (DMSO) at the 8-day post-infection (dpi) for 7 days and with ASA (100 mg/kg, single dose), and analyses were performed at 9 or 15 dpi. Lung mechanics were performed, and lungs were collected for oedema evaluation and histological analyses.ResultsPbNK65 infection led to lung oedema, as well as increased lung static elastance (Est, L), resistive (ΔP1, L) and viscoelastic (ΔP2, L) pressures, percentage of mononuclear cells, inflammatory infiltrate, hemorrhage, alveolar oedema, and alveolar thickening septum at 9 dpi. Mice that received DHA or DHA + ASA had an increase in Est, L, and CD36 expression on inflammatory monocytes and higher protein content on bronchoalveolar fluid (BALF). However, only the DHA-treated group presented a percentage of inflammatory monocytes similar to the control group and a decrease in ΔP1, L and ΔP2, L compared to Pb + DMSO. Also, combined treatment with DHA + ASA led to an impairment in diffuse alveolar damage score and lung function at 9 dpi.ConclusionsTherapy with ASA maintained lung morpho-functional impairment triggered by PbNK65 infection, leading to a large influx of inflammatory monocytes to the lung tissue. Based on its deleterious effects in experimental MA-ALI, ASA administration or its treatment maintenance might be carefully reconsidered and further investigated in human malaria cases.

Selective binding of cationic fibrinogen-mimicking chitosan nanoparticles to activated platelets and efficient drug release for antithrombotic therapy

Thrombosis is the main cause of catastrophic events including ischemic stroke, myocardial infarction and pulmonary embolism. Acetylsalicylic acid (ASA) therapy offers a desirable approach to antithrombosis through a reduction of platelet reactivity. However, major bleeding complications, severe off-target side effects, and resistance or nonresponse to ASA greatly attenuate its clinical outcomes. Herein, we report a cationic fibrinogen-mimicking nanoparticle, denoted as ASA-RGD-CS@TPP, to achieve activated-platelet-targeted delivery and efficient release of ASA for safer and more effective antithrombotic therapy. This biomimetic antithrombotic system was prepared by one-pot ionic gelation between cationic arginine-glycine-aspartic acid (RGD)-grafted chitosan (RGD-CS) and anionic tripolyphosphate (TPP). The platform exhibited selective binding to activated platelets, leading to efficient release of ASA and subsequent attenuation of platelet functions, including the remarkable inhibition of platelet aggregation through a potent blockage of cyclooxygenase-1 (COX-1). After intravenous administration, ASA-RGD-CS@TPP displayed significantly prolonged circulation time and successful prevention of thrombosis in a mouse model. ASA-RGD-CS@TPP was demonstrated to significantly enhance antithrombotic therapy while showing minimal coagulation and hemorrhagic risks and excellent biocompatibility in vivo as compared to free ASA. This platform provides a simple, safe, effective and targeted strategy for the development of antithrombotic nanomedicines.

Aspirin resistance in patients with ventricular assist devices-A follow-up study.

Despite combined anticoagulation therapy consisting of a vitamin K antagonist and an antiplatelet agent, thromboembolic complications often occur in patients with a left ventricular assist device (LVAD). In addition, bleeding events are also common. Resistance to antiplatelet drugs is a well-known phenomenon; however, the utilization of laboratory chemistry testing for the presence of such resistance, and then switching therapy, is controversial. We tested 132 patients with LVAD (HeartWare n = 57, HeartMate II n = 22, HeartMate 3 n = 53) on acetylsalicylic acid (ASA) therapy for resistance and followed them for a maximum of 7 years regarding pump thrombosis. Light transmission aggregometry (LTA) and impedance aggregometry (IPA) were performed for testing platelet function. We could show that patients with ASA resistance displayed an increased risk of pump thrombosis, regardless of the test used (LTA: OR = 6.20, CI [1.86-20.64], p = 0.003; IPA: OR = 12.14, CI [3.00-49.07], p < 0.001). In patients with a HeartMate 3, we could not detect any pump thrombosis associated with aspirin resistance. Furthermore, there was no significant difference in bleeding events between patients with ASA resistance and ASA responders. Laboratory testing of ASA resistance seems to be a good tool to detect an increased risk of pump thrombosis, at least for patients with a HeartWare or HeartMate II. The extent to which these thromboses can be prevented with a change of medication has to be investigated in further studies. No pump thrombosis was detected in patients with a HeartMate 3, and the question should be asked as to what constellation of underlying and concomitant diseases must be present to justify ASA therapy for these patients.

Варианты патогенетического лечения аспирининдуцированных гастроэнтеропатий у лиц с хронической ишемической болезнью сердца

Aim: Evaluation of Rebamipide treatment efficiency for aspirin-induced gastroduodenopathy in the patients with stable coronary heart disease (CHD). Design: Randomised controlled study. Materials and methods: In the course of the conducted research 340 CHD patients receiving long-term acetylsalicylic acid therapy in cardioprotective doses were studied. All the patients received complete clinical laboratory examination. For CHD verification there was applied selective method of coronary angiography. Gastroduodenopathy was verified by esophagogastroduodenoscopy. In both cases frequency and structure of the aforesaid events were assessed. For aspirin-induced gastroduodenopathy treatment there were applied either endogenic prostaglandin stimulant Rebamipide in combination with proton pump inhibitor (PPI) Pantoprazole (study group, n = 26) or Pantoprazole only (control group, n = 25). Prior to initiating therapy and on completion all the patients were taken blood samples for evaluation of prostaglandin E2 (PGE2) and proinflammatory cytokines (interleukine-1β Il-1β and interleukine-6 Il-6, TNF-α) levels in blood serum for verification of pathogenetic mechanisms in erosive or ulcer-bearing areas developing in gastrointestinal mucosa in association with long-term aspirin therapy. Соntrol group consisted of 26 CHD patients with no evidence of gastroduodenopathy. Statistical processing of the received data was conducted with the software program “Statistics 10.0”. Results. Aspirin-induced gastroduodenopathy was identified in 51 out of 340 (15,0%) cases. According to esophagogastroduodenoscopy data, erosions of the body and antrum of stomach were prevailing (43,1%) over all the erosive damages. CHD patients before the gastroduodenopathy treatment had significantly lower PGE2 levels in comparison with control group (p &lt; 0,01), while proinflammatory cytokines indices were higher (p &lt; 0,001). On the treatment completion 19 patients in the control group did not show endoscopic evidence of gastroduodenopathy, the laboratory findings tended to normalization. Gastric mucosa condition in the study group stabilized in all the cases, which was confirmed by statistically significant PGE2 level positive alterations (p &lt; 0,001) and also cytokine profile alterations (TNF-α: p &lt; 0,001; Il-1β and Il-6: p &lt; 0,01). Conclusion. The presented study demonstrates clinical features of aspirin-induced gastroduodenopathy development in the CHD patients and proposes possible ways of correction. Key words: aspirin-induced gastroduodenopathy, acetylsalicylic acid, prostaglandin E2, proinflammatory cytokines, rebamipide.

Effectiveness of buffered acetylsalicylic acid compared to other drugs in diseases patients in clinical practice: results of the CARDINAL observational retrospective study

Aim. To evaluate the effectiveness of acetylsalicylic acid (ASA) drugs for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in clinical practice and compare the effectiveness of the Cardiomagnyl with other ASA drugs.Material and methods. This observational, non-interventional, retrospective study included data from electronic medical records of 18199 patients with ASCVD who were divided into 2 following groups: patients who received ASA 75-100 mg (n=9784) and patients who did not receive ASA (n=8325). The prescription rate of ASA, the choice of the first drug, the duration of ASA therapy, the frequency of switching ASA during treatment, and the choice of the second ASA drug when changing therapy were assessed. Due to the heterogeneity of patients in the above groups, to assess the clinical outcomes, propensity score matching was performed and comparable groups were selected to evaluate the effectiveness of ASA drugs 75-100 mg in patients with ASCVD (n= 427) in comparison with patients not receiving ASA (n=427) and to assess the effectiveness of Cardiomagnyl 75 mg (n=1308) in comparison with enterosoluble ASA 100 mg (CRA) (n=1308) taking into account 24 parameters.Results. The average proportion of patients with ASCVD taking ASA drugs was 58%. During treatment, 54% of patients underwent a change in drug therapy from one ASA drug to another. The prescription rate of Cardiomagnyl as a first-choice drug was 33%, and as a second drug when changing therapy — 21%. The duration of Cardiomagnyl therapy was the longest compared to other ASA drugs and amounted to 16,3 months. The incidence of ischemic stroke, myocardial infarction and major adverse cardiovascular events in the group of patients who received ACS 75-100 mg was significantly lower than in patients who did not take ASA drugs and amounted to 4,7% vs 8,7%, 0,9% vs 3,3%, 5,6% vs 11,9%, respectively. Significantly lower incidence of unstable angina (0,8% vs 2,0%), myocardial infarction (1,5% vs 3,9%) and major adverse cardiovascular events (5,4% vs 7,8%) in group of patients who received Cardiomagnyl 75 mg as opposed to enterosoluble ASA.Conclusion. Significant advantages of buffered ASA (Cardiomagnyl) were revealed in comparison with enterosoluble ASA in clinical practice.

Acetylsalicylic acid challenge or desensitization in sensitive patients with cardiovascular disease

Abstract Background The use of acetylsalicylic acid (ASA) is problematic in subjects with histories of hypersensitivity reactions (HRs) to it or with cross-reactive types of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Purpose To evaluate the efficacy of low-dose ASA challenge (LDAC) and desensitization to allow ASA therapy at an antiplatelet dose in patients with atherosclerotic cardiovascular disease (ASCVD) or multiple related risk factors and histories of HRs to ASA or ≥ 2 chemically unrelated NSAIDs. Methods We studied prospectively all patients with such histories and ≥ 3 risk factors for ASCVD (group I), chronic coronary syndrome (CCS, group II), and acute coronary syndrome (ACS) with indication for ASA desensitization (group III). Patients from groups I and II underwent LDACs (cumulative dose of 110 mg), while those from group III were desensitized (cumulative dose of 100.1 mg). Results We evaluated 103 patients: 62 from group I, 24 from group II, and 17 from group III. Eighty-two of the 86 patients from the first two groups underwent LDACs and 2 reacted. Subsequently, 22 (27.5%) of the 80 patients with negative LDACs were administered dual antiplatelet therapy with ASA after successful percutaneous coronary interventions, thus sparing desensitizations. The remaining 4 patients with CCS and all 17 patients from group III were successfully desensitized. Conclusions LDAC proved to be a safe and reliable diagnostic tool for identifying patients with histories of HRs to ASA or ≥ 2 different NSAIDs who can tolerate ASA at antiplatelet doses. Routine LDAC is advisable in all patients at high risk for ASCVD or with CCS who report HRs to ASA or ≥ 2 NSAIDs. ASA desensitization remains a safe and effective option in patients with ACS.

Serum uric acid to creatinine ratio and risk of preeclampsia and adverse pregnancy outcomes.

Preeclampsia is one of the most severe diseases among the hypertensive disorders of pregnancy (HDP) and the leading cause of maternal and fetal morbidity and mortality. It is of crucial importance to early identify women at a high risk for preeclampsia to implement appropriate preventive strategies. In our study, we aimed to test the hypothesis that serum uric acid to creatinine ratio (SUA/sCr) is related to the development of preeclampsia and maternal and neonatal complications. We searched for uric acid and creatine values in the medical records of 269 women who consecutively attended our HDP Clinic from December 2018 to December 2022. We compared the baseline characteristics of participants with normotensive pregnancy ( n = 57), to those with HDP without preeclampsia (HDP-non-PE) ( n = 100) and those with preeclampsia ( n = 112), and we performed adjusted logistic regression analysis to test the associations between SUA/sCr and the development of preeclampsia and maternal and neonatal complications. SUA/sCr was consistently higher in women with preeclampsia in all trimesters of pregnancy. Higher SUA/sCr at the third trimester was associated with an increased odd of developing preeclampsia [odds ratio (OR) 1.29, confidence interval (CI) 1.15-1.50, P = 0.001], preterm birth (OR 1.23, CI 1.05-1.45, P = 0.011), and composite neonatal outcome (OR 1.33, CI 1.12-1.59, P = 0.001), after adjustment for age, BMI before pregnancy, nulliparity, antihypertensive therapy, and acetylsalicylic acid therapy during pregnancy. Having higher SUA/sCr during pregnancy is associated with the development of PE and adverse pregnancy outcomes. Controlled prospective studies are warranted to clarify the predictive power of this novel marker during pregnancy.

URIC ACID TO CREATININE RATIO AS A NOVEL PREDICTOR OF PREECLAMPSIA DEVELOPMENT AND SEVERITY

Objective: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality. PE presents with new-onset hypertension after 20 weeks of gestation that can progress rapidly leading to serious complications for both the mother and the fetus. Thus, it is of crucial importance early identifying women at high-risk for PE as early as during the first trimester of pregnancy, to implement the appropriate management and therapeutic strategies. In our study we aimed to assess the associations between serum uric acid to creatinine ratio (SUA/Cr), the development of PE and PE-related maternal and neonatal complications. Design and method: We searched for uric acid and creatine values in the medical records of 269 pregnant women who attended our Hypertensive Disorders in Pregnancy Clinic from December 2015 to December 2021. Two-hundreds and twelve women developed hypertensive disorders of pregnancy (HDP) and 57 had normotensive pregnancies. Of the 201 women with HDP, 112 were diagnosed with PE. After comparing baseline characteristics of the enrolled women, we performed logistic regression analysis models to assess the associations between SUA/Cr, development of PE, and PE-related maternal and neonatal complications. Results: Women who developed PE were more frequently nulliparous and had a higher rate of preterm delivery and maternal and neonatal complications, compared to women with HDP and healthy controls. Serum SUA/Cr was consistently higher in women with PE in all trimesters of pregnancy. Serum uric acid and creatinine alone were higher only during the third trimester in women with PE compared to women with HDP and healthy controls. Third trimester SUA/Cr was associated with an increased risk of developing PE (OR 1.29, CI 1.15 - 1.50, p = 0.001), of preterm birth (OR 1.23, CI 1.05 - 1.45, p = 0.011), and of a composite neonatal outcome (OR 1.33, CI 1.12 - 1.59, p = 0.001), after adjustment for age, BMI before pregnancy, nulliparity, hypertensive therapy, and acetylsalicylic acid therapy during pregnancy. Conclusions: In our study, women who develop PE had elevated SUA/Cr throughout all the trimesters. SUA/Cr at the third trimester of pregnancy was associated with an increased risk of PE development and neonatal complications.

Molecular Ultrasound Imaging Depicts the Modulation of Tumor Angiogenesis by Acetylsalicylic Acid.

Acetylsalicylic acid (ASA) is a well-established drug for heart attack and stroke prophylaxis. Furthermore, numerous studies have reported an anti-carcinogenic effect, but its exact mechanism is still unknown. Here, we applied VEGFR-2-targeted molecular ultrasound to explore a potential inhibitory effect of ASA on tumor angiogenesis in vivo. Daily ASA or placebo therapy was performed in a 4T1 tumor mouse model. During therapy, ultrasound scans were performed using nonspecific microbubbles (CEUS) to determine the relative intratumoral blood volume (rBV) and VEGFR-2-targeted microbubbles to assess angiogenesis. Finally, vessel density and VEGFR-2 expression were assessed histologically. CEUS indicated a decreasing rBV in both groups over time. VEGFR-2 expression increased in both groups up to Day 7. Towards Day 11, the binding of VEGFR-2-specific microbubbles further increased in controls, but significantly (p = 0.0015) decreased under ASA therapy (2.24 ± 0.46 au vs. 0.54 ± 0.55 au). Immunofluorescence showed a tendency towards lower vessel density under ASA and confirmed the result of molecular ultrasound. Molecular US demonstrated an inhibitory effect of ASA on VEGFR-2 expression accompanied by a tendency towards lower vessel density. Thus, this study suggests the inhibition of angiogenesis via VEGFR-2 downregulation as one of the anti-tumor effects of ASA.

Acetylsalicylic acid challenge or desensitization in sensitive patients with cardiovascular disease.

The use of acetylsalicylic acid (ASA) is problematic in subjects with histories of hypersensitivity reactions (HRs) to it or with cross-reactive types of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We sought to evaluate the efficacy of low-dose ASA challenge (LDAC) and desensitization to allow ASA therapy at an antiplatelet dose in patients with atherosclerotic cardiovascular disease (ASCVD) or multiple related risk factors and histories of HRs to ASA or ≥ 2 chemically unrelated NSAIDs. We studied prospectively all patients with such histories and ≥ 3 risk factors for ASCVD (group I), chronic coronary syndrome (CCS, group II), and acute coronary syndrome (ACS) with indication for ASA desensitization (group III). Patients from groups I and II underwent LDACs (cumulative dose of 110mg), while those from group III were desensitized (cumulative dose of 100.1mg). We evaluated 103 patients: 62 from group I, 24 from group II, and 17 from group III. Eighty-two of the 86 patients from the first two groups underwent LDACs and 2 reacted. Subsequently, 22 (27.5%) of the 80 patients with negative LDACs were administered dual antiplatelet therapy with ASA after successful percutaneous coronary interventions, thus sparing desensitizations. The remaining 4 patients with CCS and all 17 patients from group III were successfully desensitized. In this pragmatic study,LDAC proved to be a safe and reliable diagnostic tool for identifying patients with histories of HRs to ASA or ≥ 2 different NSAIDs who can tolerate ASA at antiplatelet doses. Routine LDAC is advisable in all patients at high risk for ASCVD or with CCS who report HRs to ASA or ≥ 2 NSAIDs. ASA desensitization remains a safe and effective option in patients with ACS. Study flow-chart. ASCVD atherosclerotic cardiovascular disease; CCS chronic coronary syndrome; ACS acute coronary syndrome; ASA acetylsalicylic acid; DAPT dual antiplatelet therapy; PCI percutaneous coronary intervention; NSAIDs nonsteroidal anti-inflammatory drugs; NERD NSAID-exacerbated respiratory disease; NECD NSAID-exacerbated cutaneous disease; NIUAA NSAID-induced urticaria-angioedema or anaphylaxis; SNIUAA single NSAID-induced urticaria-angioedema or anaphylaxis; SNIDHR single NSAID-induced delayed hypersensitivity reaction.

Mild Acquired von Willebrand Syndrome and Cholestasis in Pediatric and Adult Patients with Fontan Circulation.

Background: Hemodynamic alterations in Fontan patients (FP) are associated with hemostatic dysbalance and Fontan-associated liver disease. Studies of other hepatopathologies indicate an interplay between cholestasis, tissue factor (TF), and von Willebrand factor (VWF). Hence, we hypothesized a relationship between the accumulation of bile acids (BA) and these hemostatic factors in FP. Methods: We included 34 FP (Phenprocoumon n = 15, acetylsalicylic acid (ASA) n = 16). BA were assessed by mass spectrometry. TF activity and VWF antigen (VWF:Ag) were determined by chromogenic assays. VWF collagen-binding activity (VWF:CB) was assessed via ELISA. Results: Cholestasis was observed in 6/34 FP (total BA ≥ 10 µM). BA levels and TF activity did not correlate (p = 0.724). Cholestatic FP had lower platelet counts (p = 0.013) from which 5/6 FP were not treated with ASA. VWF:Ag levels were increased in 9/34 FP and significantly lower in FP receiving ASA (p = 0.044). Acquired von Willebrand syndrome (AVWS) was observed in 10/34-FP, with a higher incidence in cholestatic FP (4/6) (p = 0.048). Conclusions: Cholestasis is unexpectedly infrequent in FP and seems to be less frequent under ASA therapy. Therefore, ASA may reduce the risk of advanced liver fibrosis. FP should be screened for AVWS to avoid bleeding events, especially in cholestatic states.

Resistance to clopidogrel and acetylsalicylic acid therapy

Resistance to clopidogrel and acetylsalicylic acid therapy

The efficacy and safety of carotid stenting under dual antiplatelet therapy with ticagrelor and acetylsalicylic acid

Aim: To prevent thrombotic complications in carotid artery stenting (CAS), it is recommended to use acetylsalicylic acid (ASA) and clopidogrel for at least one month, followed by single antiplatelet therapy. The number of studies on the use of ticagrelor in CAS is very few. We aimed to evaluate the efficacy and safety of ticagrelor in CAS in this study.Methods: The records of the patients who underwent CAS between January 2020 and January 2022 were scanned and the patients who were treated with the ASA and ticagrelor therapy were included in this study. Demographic data of the patients, vascular risk factors, ipsilateral-contralateral stenosis rates, balloon angioplasty application status, residual stenosis rates, periprocedural ischemic and hemorrhagic events, and vascular events developed during three-month follow-up were noted.Results: Thirteen patients were included in the present study. Their mean age was 69.38±7.1 years. The mean carotid stenosis rate was 82.07±10.44%, and contralateral stenosis rate was 65.07±32.98%. Stent thrombosis was not observed in any patient. After the procedure, minor ischemic stroke that did not cause disability developed in one patient and puncture site bleeding that did not require transfusion in one patient. One patient had &gt;50% restenosis at three months.Conclusion: The findings suggest that dual antiplatelet therapy with ticagrelor + ASA appears to be a safe and effective treatment for CAS. Given that clopidogrel resistance cannot be evaluated in many centers, it may be more accurate to prefer ticagrelor, especially in high-risk patients with bilateral stenosis.

194 THROMBOEMBOLIC ACUTE ST ELEVATION MYOCARDIAL INFARCTION AFTER TRANSCATHETER VALVE IMPLANTATION

Abstract Transcatheter aortic valve implantation (TAVI) is an established treatment of severe symptomatic aortic valve stenosis and is an effective and less invasive treatment option compared with conventional surgical aortic valve replacement (SAVR) for patients considered inoperable or at high surgical risk. Thromboembolic and bleeding complications negatively impact recovery and survival after TAVI. This case describes one of the few reported TAVI-associated myocardial infarction due to thrombosis of the prosthetic aortic valve. A 82-years-old woman, suffering from severe symptomatic aortic stenosis, underwent TAVI. Before the procedure, coronary artery disease was excluded by invasive coronary angiography. Since the time of the discharge the patient didn't assume any therapy with aspirin or other antithrombotic drugs. A month after TAVI she complained persistent epigastric pain and was admitted to our department for anterior ST elevation myocardial infarction. Coronary angiography highlighted a monovascular coronary artery disease with thrombotic occlusion of the first diagonal and of the distal left anterior descending coronary artery. In consideration of the thrombotic load thyrofiban was started and it was performed a chest contrast CT which confirmed the diagnostic suspicion of bioprosthetic valve thrombosis. She was first treated with unfractionated heparin (UFH) and then oral anticoagulant therapy with warfarin was started. Echocardiograms (echo) showed a severely reduced systolic function (EF 25%) and high trans-prosthetic gradients (mean transprosthetic pressure gradient of 30 mmHg). On the 8th day after hospitalization she complained chest pain with evidence of moderate pericardial effusion. Epistenocardica pericarditis was therefore diagnosed and the patient started acetylsalicylic acid therapy with progressive clinical, instrumental and laboratory improvement. After 10 days of anticoagulation therapy, she underwent a transesophageal echocardiogram which turned out negative for bioprosthetic valve thrombosis. The predischarge transthoracic echocardiography showed severely reduced systolic function (EF 30%) with a mean transprothesic gradient of 12 mmHg; the circumferential pericardial effusion was mild-moderate but not haemodynamically significative. Therapy at discharged included warfarin and aspirin. Ten days after an echo showed a reduction of the pericardial effusion, an improved systolic function (EF 42%) and mean transprothesic gradient not changed significantly since discharge. Prosthetic valve thrombosis has been reported in up to 40% of patients after TAVI and this case hightlights the importance of antithrombotic therapy after this procedure. Therapeutic anticoagulation appears to be the only non-invasive treatment for resolving valve thrombosis but it is not clear how long this therapy should last for the prevention of prosthetic valve thrombosis.

A prospective cohort study of sensorineural hearing loss associated with Kawasaki disease.

About 60 cases of sensorineural hearing loss (HL) have been reported in patients with Kawasaki disease (KD), but the current estimate of its prevalence is uncertain. The present study aimed to determine the prevalence and risk factors of sensorineural HL associated with KD. The present, prospective cohort study, conducted from May 2019 to May 2020, evaluated patients with a diagnosis of KD who received the initial therapy and underwent two auditory brainstem response (ABR) tests. HL was defined as a threshold of 40dB or more, and borderline hearing was defined as a threshold of 30dB. In total, 107 patients were enrolled, and 75 underwent two ABR tests. Thirty-one patients (30.0%) received prednisolone with their initial intravenous immune globulin and acetylsalicylic acid therapy. HL was present in only one patient who had congenital conductive HL. Five patients had borderline hearing but had normal hearing behavior. There was no significant difference between the patients with normal hearing and those with borderline hearing in terms of the clinical variables. In Japan, the prevalence of sensorineural HL after KD is not high. It may therefore be unnecessary to perform routine hearing tests for all patients with KD. Association between Kawasaki Disease and Sensorineural Hearing Loss. UMIN000037019 (the date of registration: June 11, 2019).

Clinical, demographic characteristics, and treatment protocols of optic neuropathies: Three-year follow-up experiences from a tertiary hospital in Turkey.

Background: This study was conducted to review the demographic and clinical characteristics, treatment protocols, and visual outcomes of patients with optic neuropathy. Methods: This historical cohort study analyzed the clinical features of 91 patients with optic neuropathy followed up for three years at a university hospital in Turkey. Results: Non-arteritic anterior ischemic optic neuropathy (NA-AION) was the most common group among the optic neuropathy subgroups (47.2%), and optic neuritis (ON) was the second most common group (38.5%). The mean age of symptom onset for NA-AION was 64.97 ± 12.15 years, significantly higher than the mean age of onset for ON (40.28 ± 15.52 years). Most of the patients with NA-AION had at least one systemic disease causing microangiopathy [51.1% had diabetes mellitus (DM), 33.3% had hypertension (HTN)]. Among the patients with ON, 51.4% were idiopathic, and 25.7% were multiple sclerosis (MS)-related ON cases. Patients with ischemic optic neuropathy (ION), ON, and traumatic optic neuropathy received pulse intravenous (IV) corticosteroids, and eleven patients with NA-AION received acetylsalicylic acid (ASA) therapy in addition to corticosteroids. There was a statistically significant increase in visual acuity in NA-AION and ON groups (P = 0.019). It was observed that the cases of ON peaked in the winter months in Turkey. Conclusion: In the differential diagnosis between NA-AION and idiopathic ON, the presence of one or more vascular systemic diseases and mean age may be the main factors. IV steroid treatment given to patients with NA-AION in the acute phase may significantly improve visual acuity.

Personalized allocation of acetylsalicylic acid therapy for secondary prevention of coronary artery disease.

BackgroundA single-daily dose of 75 mg of acetylsalicylic acid inhibits 100% of thromboxane-B2 synthesis within 30–60 min. Thromboxane-B2 synthesis then recovers slowly as new platelets are released from the bone marrow. Normally, only 10% of the platelets are replaced daily by new platelets entering circulation. Hence, 24 h after a dose of acetylsalicylic acid, thromboxane-B2 synthesis is still suppressed by more than 90%. Hence, there is an adequate anti-platelet effect even after 24 h of acetylsalicylic acid intake. However, some patients treated with once-daily acetylsalicylic acid may have an incomplete 24-h suppression of thromboxane-B2 synthesis due to increased platelet turnover. The response could be improved in such patients by twice-daily acetylsalicylic acid administration. This study aimed to identify such a group of patients who would benefit from a twice-daily dose of acetylsalicylic acid.Materials and methodsSerum thromboxane-B2 levels were measured in 79 patients with coronary artery disease receiving 75 mg of acetylsalicylic acid for secondary prophylaxis. Serum levels of thromboxane-B2 were measured after 4 and 24 h of acetylsalicylic acid intake. Patients were then classified into three groups: steady suppression group (serum thromboxane B2 is adequately suppressed at 4 and 24 h), i.e., adequate response to acetylsalicylic acid; fast recovery group (more than 10% rise in serum thromboxane-B2 levels at 24-h when compared to at 4-h) and non-responders (serum thromboxane-B2 levels of >3,100 pg/ml after 4 h of acetylsalicylic acid intake). Patients in the fast recovery group were given twice-daily acetylsalicylic acid and thromboxane-B2 levels were re-measured.ResultsA total of 20 patients (24.3%) had steady suppression of thromboxane-B2 and 11 patients (13.9%) belonged to the fast recovery group, i.e., thromboxane-B2 levels were adequately suppressed at 4 h but had recovered by more than 10% at 24 h; which was adequately suppressed by twice-daily acetylsalicylic acid (p 0.004). A total of 48 patients (60.8%) were non-responders.ConclusionTwice-daily acetylsalicylic acid may be beneficial if serum thromboxane-B2 levels at 4 h are <3,100 and >3,100 pg/ml at 24 h. If thromboxane-B2 levels at 4 and 24 h is <3100 pg/ml but if there is a >10% rise in serum thromboxane B2 at 24 h as compared to that at 4 h, then twice-daily acetylsalicylic acid should be considered. However, if thromboxane-B2 at 4 and 24 h is >3,100 pg/ml consider switching over to a P2Y12 inhibitor.

Study the Association of Nucleotide Polymorphisms in Platelet Receptor and Cytochrome P450 Genes with the Development of Resistance to Antiplatelet Drugs in Patients with Coronary Artery Disease

Aim. To study the association of nucleotide polymorphisms in platelet receptor and cytochrome P450 genes with the development of resistance to antiplatelet drugs in CHD patients.Material and Methods. The study included 243 patients diagnosed with CHD after coronary artery bypass surgery (CABG), including 140 patients in the acetylsalicylic acid (ASA) treatment group and 103 patients in the dual antiplatelet therapy (DAT) group. All patients were tested for platelet aggregation using an optical aggregometer with inducers: 5 mM ADP and 1 mM arachidonic acid (AA). DNA samples were analyzed by allele-specific PCR for the presence of polymorphisms rs2046934, rs1126643, rs5918, rs6065, rs4244285 in the platelet receptor and cytochrome P450 genes.Results. No statistically significant differences were found during comparison of the prevalence of the studied polymorphisms in the platelet receptor and cytochrome P450 genes between the groups of aspirin-sensitive and aspirin-resistant patients, as well as between the groups of clopidogrelsensitive and clopidogrel-resistant patients. No association between carriage of the minor and major alleles of the polymorphisms studied and the development of antiplatelet drug resistance was found. In the group of patients on ASA therapy, carriers of the C allele of the T1565C (rs5918) ITGB3 polymorphism had a higher rate of AA-induced platelet aggregation compared to carriers of the T allele (18,49±25,92 vs 10,43±17,34, р=0,004).Conclusion. Polymorphisms of P2RY12 (rs2046934), ITGA2 (rs1126643), ITGB3 (rs5918), GP1BA (rs6065), CYP2C19*2 (rs4244285) genes are not associated with antiplatelet drug resistance in both patients on ASC therapy and on DAT. The presence of minor alleles of the rs2046934, rs1126643, rs6065, rs4244285 polymorphisms are not associated with increased platelet aggregation activity before CABG.However, in the group of patients on ASA therapy C-allele carriers of the rs5918 polymorphism of the ITGB3 gene had a higher rate of AA-induced platelet aggregation compared to T-allele carriers.

P188 MANAGEMENT OF ANTICOAGULANT AND ANTIPLATELET THERAPY IN THE GREAT ELDERLY: A REAL LIFE CLINICAL CASE

Abstract In daily clinical practice we have often to manage great elderly people with multiple comorbidities. In these cases it is not always easy to apply the guidelines, which must sometimes be adapted to the patient we are treating. We present the case of a 99–year–old hypertensive patient in therapy with oncocarbide and acetylsalicylic acid for polycythemia vera. No cardiological history. It came to our attention for NSTEMI during an episode of persistent atrial fibrillation (AF) with a high ventricular rate. Subsequent spontaneous restoration of sinus rhythm. Significant increase in troponin on blood tests. On the echocardiogram, normal biventricular kinetics and systolic function, no significant valvulopathies. Given the age and hemodynamic stability, a conservative approach was chosen. Therefore, antiplatelet therapy was started with acetylsalicylic acid (ASA) and anticoagulant therapy, initially with low molecular weight heparin and then with oral anticoagulant (NOAC); being the patient over 75 we chose Apixaban 2.5 mg bid, in accordance with weight and renal function (Consensus ESC 2016). At 1 month follow up the patient month was stable in good compensation, the 24h–Holter ECG showed stable sinus rhythm. At this point the question was how to proceed with the therapy: maintain the NOAC, as indicated in the NSTEMI guidelines, or continue with ASA alone, also considering that the risk scores usually used in patients with AF to determine the bleeding and cardioembolic risk (HASBLED and CHADS–VASC) are not validated in such elderly patients. We also hypothesized that the short AF paroxysm was related to ongoing myocardial ischemia (and not vice versa); in the literature, however, the indication for anticoagulant therapy does not take these extreme situations into account. Polycythemia vera also contributes to complicating the situation, exposing the patient to an increased risk of thrombotic events in the absence of antiplatelet therapy. After discussing the case with the haematologist, we decided to suspend the NOAC, also considering the absence of new arrhythmic episodes, and to continue with ASA alone. For now, with a follow–up of 6 months, we have not registered thrombotic / haemorrhagic problems or arrhythmic recurrences. The management of the elderly is always complex and will frequently lead us to adapt and customize the treatments on every single patient.