421 results on '"Udaya S. Tantry"'
Search Results
2. Long-term prognostic implications of brachial-ankle pulse wave velocity in patients undergoing percutaneous coronary intervention
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Byung Sik Kim, Jong-Hwa Ahn, Jeong-Hun Shin, Min Gyu Kang, Kye-Hwan Kim, Jae Seok Bae, Yun Ho Cho, Jin-Sin Koh, Yongwhi Park, Seok-Jae Hwang, Udaya S. Tantry, Paul A. Gurbel, Jin-Yong Hwang, and Young-Hoon Jeong
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coronary artery disease ,arterial stiffness ,pulse wave velocity ,percutaneous coronary intervention ,clinical outcome ,Medicine (General) ,R5-920 - Abstract
ObjectiveThe long-term clinical effect of arterial stiffness in high-risk disease entities remains unclear. The prognostic implications of brachial-ankle pulse wave velocity (baPWV) were assessed using a real-world registry that included patients who underwent percutaneous coronary intervention (PCI).MethodsArterial stiffness was measured using baPWV before discharge. The primary outcome was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or major bleeding. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE: a composite of all-cause death, non-fatal myocardial infarction, or non-fatal stroke), and major bleeding. The outcomes were assessed over a 4-year period.ResultsPatients (n = 3,930) were stratified into high- and low-baPWV groups based on a baPWV cut-off of 1891 cm/s determined through time-dependent receiver operating characteristic curve analysis. baPWV was linearly correlated with 4-year post-PCI clinical events. The high baPWV group had a greater cumulative incidence of NACE, MACCE, and major bleeding. According to multivariable analysis, the high baPWV groups had a significantly greater risk of 4-year NACE (adjusted hazard ratio [HRadj]: 1.44; 95% confidence interval [CI]: 1.12–1.85; p = 0.004), MACCE (HRadj: 1.40; 95% CI: 1.07–1.83; p = 0.015), and major bleeding (HRadj: 1.94; 95% CI: 1.15–3.25; p = 0.012).ConclusionIn PCI-treated patients, baPWV was significantly associated with long-term clinical outcomes, including ischemic and bleeding events, indicating its value for identifying high-risk phenotypes.
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- 2024
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3. The role of viscoelastic testing in assessing peri-interventional platelet function and coagulation
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Udaya S. Tantry, Jan Hartmann, Matthew D. Neal, Herbert Schöechl, Kevin P. Bliden, Seema Agarwal, Dan Mason, Joao D. Dias, Elisabeth Mahla, and Paul A. Gurbel
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bleeding ,critical care ,ischemia ,platelet function ,site-of-care ,trauma ,viscoelastic hemostatic assay ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.
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- 2022
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4. Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases
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Daisuke Katagiri, MD, PhD, FASN, Yusuke Asai, PhD, Norio Ohmagari, MD, PhD, Masahiro Ishikane, MD, PhD, Sayaka Hikida, MD, PhD, Noriko Iwamoto, MD, PhD, Maki Nagashima, MT, Minami Suzuki, MD, PhD, Hideki Takano, MD, PhD, Jin Takasaki, MD, Masayuki Hojo, MD, PhD, Haruhito Sugiyama, MD, PhD, Katsushi Tokunaga, PhD, Yoshihiro Miyashita, MD, Masao Omata, MD, PhD, Keiichi Ohata, MS, Kevin P. Bliden, MBA, Udaya S. Tantry, PhD, Jeffrey R. Dahlen, PhD, Takeshi Sugaya, PhD, Paul A. Gurbel, MD, FACC, and Eisei Noiri, MD, PhD, FASN
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Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
IMPORTANCE:. Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES:. To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN:. Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS:. Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES:. The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient’s severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS:. Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE:. Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).
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- 2023
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5. Prevalence of adverse events during ticagrelor versus clopidogrel treatment and its association with premature discontinuation of dual antiplatelet therapy in East Asian patients with acute coronary syndrome
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Min Gyu Kang, Jong Hwa Ahn, Kyehwan Kim, Jin-Sin Koh, Joeng Rang Park, Seok Jae Hwang, Yongwhi Park, Udaya S. Tantry, Paul A. Gurbel, Jin-Yong Hwang, and Young-Hoon Jeong
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acute coronary syndrome ,ticagrelor ,bleeding ,dyspnea ,adherence ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundClinical evidence raises the issues regarding the high risk of adverse events and serious bleeding in East Asian patients receiving standard-dose ticagrelor treatment. We sought to evaluate the association between adverse events and their associations with premature discontinuation of dual antiplatelet therapy (DAPT).MethodsWe enrolled East Asian patients presented with acute coronary syndrome who took DAPT with 90-mg ticagrelor (n = 270) or 75-mg clopidogrel (n = 674). During 1-month treatment, antiplatelet effect was evaluated with the VerifyNow P2Y12 assay, and the occurrence of Bleeding Academic Research Consortium (BARC) bleeding and modified Medical Research Council (mMRC) dyspnea was assessed with the dedicated questionnaire.ResultsDuring 1-month follow-up, patients on ticagrelor showed the higher risks of bleeding (any BARC type: 45.6% vs. 23.6%; odds ratio [OR], 2.71 and BARC 1 or 2 type: 45.2% vs. 22.1%; OR, 2.90, respectively) and dyspnea (26.3% vs. 13.6%; OR, 2.25) compared with those on clopidogrel. In a receiver-operating characteristics curve analysis to predict bleeding risk, ticagrelor showed a lower cutoff of low platelet reactivity (LPR) (P2Y12 reaction unit [PRU] ≤ 20) than clopidogrel (PRU ≤ 110). Early occurrence of bleeding episode was significantly associated with LPR phenotype (OR, 2.68), not type of P2Y12 inhibitor. In multivariate analysis, type of P2Y12 inhibitor (ticagrelor vs. clopidogrel: OR, 2.19) and bleeding episode (OR, 2.94) were independent predictors for dyspnea occurrence. During 1-year follow-up, DAPT with ticagrelor showed a higher risk of premature discontinuation compared to DAPT with clopidogrel (27.8% vs. 4.7%; adjusted HR, 8.84), which risk appeared frequent during the first month (14.4%) during DAPT with ticagrelor. Early occurrence of bleeding and dyspnea synergistically increased a risk of DAPT non-adherence, irrespective of type of P2Y12 inhibitor.ConclusionThis analysis is the first evidence to show the different cutoff of low platelet reactivity during the reversible (ticagrelor) versus irreversible P2Y12 inhibitor (clopidogrel). Early occurrence of bleeding and dyspnea is very common during standard-dose ticagrelor treatment in East Asian patients, which show a close association with premature DAPT discontinuation.Clinical trial registration[https://www.clinicaltrials.gov], identifier[NCT046 50529].
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- 2022
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6. Measurement of Anticoagulation in Patients on Dabigatran, Rivaroxaban, and Apixaban Therapy by Novel Automated Thrombelastography
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Ramin Artang, Joao D. Dias, Mark Walsh, Kevin Bliden, Jorn D. Nielsen, Maren Anderson, Brian C. Thurston, Udaya S. Tantry, Jan Hartmann, and Paul A. Gurbel
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clinical trials: oral anticoagulants ,coagulation inhibitors ,diagnosis management ,apixaban ,rivaroxaban ,dabigatran ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Direct-acting oral anticoagulants (DOACs) do not require monitoring. Measurement of DOAC effect would be useful in the event of bleeding, trauma, and thromboembolism while on anticoagulation. We evaluated the effectiveness of the investigational DOAC assays on the TEG®6s Hemostasis Analyzer to assess the anticoagulant effect of DOACs in patients treated for atrial fibrillation or deep vein thrombosis (DVT). Methods Patients on treatment for a minimum of 7 days with standard doses of dabigatran, rivaroxaban, and apixaban were included. DOAC plasma concentrations and TEG®6s Reaction (R)-time were measured and correlated. The sensitivity, specificity, and negative predictive value (NPV) of R-time to detect DOAC concentrations of ≥30, ≥50, and ≥100 ng/mL were calculated. Results A total of 189 patients were included, (n = 50) on apixaban, (n = 62) on rivaroxaban, (n = 53) on dabigatran, and (n = 24) on no DOAC were studied. Using the direct thrombin inhibitor (DTI) channel, R-time demonstrated strong linear correlation with dabigatran levels (r = 0.93, p
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- 2021
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7. Race-Related disparities in COVID-19 thrombotic outcomes: Beyond social and economic explanations
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Rahul Chaudhary, Kevin P. Bliden, Rolf P. Kreutz, Young-Hoon Jeong, Udaya S. Tantry, Jerrold H. Levy, and Paul A. Gurbel
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Medicine (General) ,R5-920 - Published
- 2020
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8. Pharmacodynamic effects of a new fixed-dose clopidogrel–aspirin combination compared with separate administration of clopidogrel and aspirin in patients treated with coronary stents: The ACCEL-COMBO trial
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Jin-Sin Koh, Yongwhi Park, Udaya S. Tantry, Jong-Hwa Ahn, Min Gyu Kang, Kyehwan Kim, Jeong Yoon Jang, Hyun Woong Park, Jeong Rang Park, Seok-Jae Hwang, Choong Hwan Kwak, Jin-Yong Hwang, Paul A. Gurbel, and Young-Hoon Jeong
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aspirin ,aggregation ,clopidogrel ,platelet ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open-label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG®). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 ± 52 vs. 207 ± 60 PRU; mean difference, −5 PRU; 90% confidence interval of difference, −23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). “BASE” and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values ≥0.822) and TEG® measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel–aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin.
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- 2017
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9. Current Antiplatelet Treatment Strategy in Patients with Diabetes Mellitus
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Jung Hwa Jung, Udaya S. Tantry, Paul A. Gurbel, and Young-Hoon Jeong
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Aspirin ,Atherothrombosis ,Diabetes ,Platelet ,P2Y inhibitor ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Patients with diabetes mellitus (DM) have accelerated atherosclerosis with an increased risk for atherothrombotic cardiovascular complications. A state of high platelet reactivity and activation, hypercoagulability (prothrombotic state) and a subdued response to standard antiplatelet agents may explain high rate of adverse cardiovascular events in patients with DM. Several antithrombotic treatment strategies have been developed to control the prothrombotic state in patients with DM: dose modification of commonly used agents; use of potent agents; and addition of a third antithrombotic drug (triple therapy) to commonly prescribed dual antiplatelet therapy of aspirin and a P2Y12 inhibitor. The present review aims to provide an overview of the current knowledge on platelet abnormalities in patients with DM, focusing on the challenges and perspectives of antiplatelet treatment strategies in this population.
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- 2015
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10. Relationship of Platelet Reactivity With Bleeding Outcomes During Long‐Term Treatment With Dual Antiplatelet Therapy for Medically Managed Patients With Non‐ST‐Segment Elevation Acute Coronary Syndromes
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Jan H. Cornel, E. Magnus Ohman, Benjamin Neely, Joseph A. Jakubowski, Deepak L. Bhatt, Harvey D. White, Diego Ardissino, Keith A.A. Fox, Dorairaj Prabhakaran, Paul W. Armstrong, David Erlinge, Udaya S. Tantry, Paul A. Gurbel, and Matthew T. Roe
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DAPT ,hemorrhage ,platelet ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundThe relationship between “on‐treatment” low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention. Methods and ResultsWe analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady‐state PRU values could distinguish high versus low bleeding risk using 2‐level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life‐threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non‐CABG Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding. Exploratory analyses used 3‐level composites that incorporated mild and minimal GUSTO and TIMI events. Continuous measures of PRUs (per 10‐unit decrease) were not independently associated with the 2‐level GUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96–1.06) or TIMI composites (1.02; 0.98–1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2‐level composites. However, the PRU cut point of 75 differentiated bleeding risk with the 3‐level composites of GUSTO (26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77–2.94; P
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- 2016
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11. What is the Optimal Duration of Dual Antiplatelet Therapy After Stenting?
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Udaya S. Tantry, Eliano P. Navarese, and Paul A. Gurbel
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The optimal duration of dual antiplatelet therapy (DAPT) of aspirin and a P2Y12 receptor blocker after stenting is still being debated. The current recommendations for DAPT duration are significantly focused on reducing stent thrombosis; a less frequent event with later than earlier generation drug eluting stents (DES). A persistent occurrence of late and very late stent thrombosis with first generation DES supported extended use of DAPT beyond one year. However, recent studies have demonstrated that extended duration DAPT is associated with increased bleeding; an independent predictor for poor outcomes, including long-term mortality. Second-generation DES are associated with less late and very late stent thrombosis. Some recent studies have supported a shorter duration of DAPT for second generation DES. However, these studies were inadequately powered to assess significant differences in stent thrombosis. Furthermore, extended duration DAPT has been associated with a reduced risk of thrombotic events in non-culprit vessels in addition to stent thrombosis in patients with acute coronary syndromes (ACS). The higher risk of bleeding associated with extended DAPT therapy provides a strong rationale for personalized DAPT based on patient risk factors (e.g. ACS vs. non-ACS), type of stents, and cost-benefit analyses.
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- 2016
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12. Prognostic impact of hypercoagulability and impaired fibrinolysis in acute myocardial infarction
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Seung Hun Lee, Hyun Kuk Kim, Jong-Hwa Ahn, Min Gyu Kang, Kye-Hwan Kim, Jae Seok Bae, Sang Young Cho, Jin-Sin Koh, Yongwhi Park, Seok Jae Hwang, Diana A Gorog, Udaya S Tantry, Kevin P Bliden, Paul A Gurbel, Jin-Yong Hwang, and Young-Hoon Jeong
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Cardiology and Cardiovascular Medicine - Abstract
Aims Atherothrombotic events are influenced by systemic hypercoagulability and fibrinolytic activity. The present study evaluated thrombogenicity indices and their prognostic implications according to disease acuity. Methods and results From the consecutive patients undergoing percutaneous coronary intervention (PCI), those with thrombogenicity indices (n = 2705) were grouped according to disease acuity [acute myocardial infarction (AMI) vs. non-AMI]. Thrombogenicity indices were measured by thromboelastography (TEG). Blood samples for TEG were obtained immediately after insertion of the PCI sheath, and TEG tracing was performed within 4 h post-sampling. Major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were evaluated for up to 4 years. Compared with non-AMI patients, AMI patients had higher platelet-fibrin clot strength [maximal amplitude (MA): 66.5 ± 7.8 vs. 65.3 ± 7.2 mm, P < 0.001] and lower fibrinolytic activity [clot lysis at 30 min (LY30): 0.9 ± 1.8% vs. 1.1 ± 1.9%, P < 0.001]. Index AMI presentation was associated with MA [per one-mm increase: odds ratio (OR): 1.024; 95% confidence interval (CI): 1.013–1.036; P < 0.001] and LY30 (per one% increase: OR: 0.934; 95% CI: 0.893–0.978; P = 0.004). The presence of high platelet-fibrin clot strength (MA ≥68 mm) and low fibrinolytic activity (LY30 < 0.2%) was synergistically associated with MACE occurrence. In the multivariable analysis, the combined phenotype of ‘MA ≥ 68 mm’ and ‘LY30 < 0.2%’ was a major predictor of post-PCI MACE in the AMI group [adjusted hazard ratio (HR): 1.744; 95% CI: 1.135–2.679; P = 0.011], but not in the non-AMI group (adjusted HR: 1.031; 95% CI: 0.499–2.129; P = 0.935). Conclusion AMI occurrence is significantly associated with hypercoagulability and impaired fibrinolysis. Their combined phenotype increases the risk of post-PCI atherothrombotic event only in AMI patients. These observations may support individualized therapy that targets thrombogenicity for better outcomes in patients with AMI. Clinical Trial Registration Gyeongsang National University Hospital (G-NUH) Registry, NCT04650529.
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- 2023
13. Post-PCI Risk Assessment by Inflammation Activity According to Disease Acuity and Time from Procedure
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Haegeun Song, Jong-Hwa Ahn, Min Gyu Kang, Kye-Hwan Kim, Jae Seok Bae, Sang Young Cho, Jin-Sin Koh, Yongwhi Park, Seok-Jae Hwang, Eun Jeong Cho, Kyeongmin Byeon, Sang-Wook Kim, Udaya S. Tantry, Paul A. Gurbel, Jin-Yong Hwang, and Young-Hoon Jeong
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Hematology - Abstract
Background High-sensitivity C-reactive protein (hs-CRP) has been proposed as an indicator of inflammation and cardiovascular risk. However, little is known of the comparative temporal profile of hs-CRP and its relation to outcomes according to the disease acuity. Methods We enrolled 4,263 East Asian patients who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) and stable disease. hs-CRP was measured at baseline and 1 month post-PCI. Major adverse cardiovascular events (MACE: the composite occurrence of death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. Result The AMI group (n = 2,376; 55.7%) had higher hs-CRPbaseline than the non-AMI group (n = 1,887; 44.3%) (median: 1.5 vs. 1.0 mg/L; p Conclusion AMI patients have greater inflammation during the early and late phases than non-AMI patients. Risk phenotype of hs-CRPbaseline correlates with 1-month outcomes only in AMI patients. However, the prognostic implications of this risk phenotype appears similar during the late phase, irrespective of the disease acuity.
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- 2023
14. Sex-related differences in clinical outcomes among patients with myocardial infarction with nonobstructive coronary artery disease: A systematic review and meta-analysis
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Rahul, Chaudhary, Michael, Bashline, Enrico M, Novelli, Kevin P, Bliden, Udaya S, Tantry, Oladipupo, Olafiranye, Aref, Rahman, Paul A, Gurbel, and John J, Pacella
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Male ,Stroke ,Sex Factors ,Risk Factors ,Myocardial Infarction ,Humans ,Estrogens ,Female ,Coronary Artery Disease ,Middle Aged ,Coronary Angiography ,Prognosis ,Cardiology and Cardiovascular Medicine - Abstract
Among patients who present with acute myocardial infarction (MI), 2-6% are found to have non-obstructive coronary arteries (NOCA). Patients with MINOCA are more commonly women and present at a younger age (51-59 years). The influence of sex on adverse event rates remains unclear.PubMed, MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), EMBASE, EBSCO, Web of Science and CINAHL databases were searched for trials comparing gender differences in clinical outcomes among patients with MINOCA from inception through April 10, 2022. The primary endpoint of the study was composite major adverse clinical events (MACE) including all-cause mortality, non-fatal MI, stroke, and cardiovascular readmissions, and secondary endpoints were the individual components of the MACE.Seven studies with a total of 28,671 MINOCA patients were included (n = 11,249 men and n = 17,422 women) over a mean follow-up of 2 years. Women had more MACE than men (10.1% vs. 9.1%, OR 1.15, 1.04-1.23, I2 = 44.7%). Among secondary endpoints, only the incidence of stroke was higher in women (3.5% vs. 2.2%, OR 1.3, 1.01-1.68, I2 = 0%). All-cause mortality, non-fatal MI, and cardiovascular readmissions were not significantly different between the two groups.We hypothesize that small vessel disease associated with MINOCA drives MACE in women and the diminishing influence of estrogen, hypercoagulability and underprescribing could contribute to the differences sex-related outcomes.
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- 2022
15. Serial assessment of thrombogenicity and hemodynamics in patients with type II diabetes in a clinical research unit: Evidence for circadian variations in clot formation
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Rahul Chaudhary, Tushar Sharma, Udaya S. Tantry, Juzer Ali Asgar, Parshotam Kundan, Sanchit Duhan, Haroon Gill, Arvind Singh, Yazan Alasadi, Paul A. Gurbel, and Kevin P. Bliden
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Adenosine Diphosphate ,Arachidonic Acid ,Aspirin ,Diabetes Mellitus, Type 2 ,Humans ,Blood Pressure ,Thrombosis ,Hematology ,Cardiology and Cardiovascular Medicine ,Circadian Rhythm - Abstract
Circadian fluctuations in thrombogenicity and hemostasis play a role in acute cardiovascular thrombotic events occurring in the early morning hours. There is a lack of data assessing thrombogenicity, platelet function, and hemodynamics to investigate diurnal variations in a high cardiovascular risk population.This was an exploratory, single-center study conducted in aspirin-treated patients with Type II Diabetes Mellitus (T2DM) (n = 37) with documented vascular disease and/or multiple cardiovascular risk factors. Hemodynamic monitoring and blood sample collection for thromboelastography (TEG) and platelet function testing were done serially at 7-9 AM (morning), 7-9 PM (evening), 11 PM-1 AM (night), and at 5-7 AM (awakening).R-value measured by TEG was shorter during awakening hours than during the night and day hours (p 0.05). There were no changes in platelet reactivity in response to arachidonic acid, adenosine diphosphate, and collagen between time points. Pulse pressure (PP) was highest during awakening hours (p 0.05).Study findings provide a mechanistic explanation for increased thrombotic events observed in the early waking hours among diabetics with multiple cardiovascular risk factors. The role of chronotherapy in reducing coagulability and PP to improve clinical outcomes should be explored.
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- 2022
16. Residual Inflammatory Risk and its Association With Events in East Asian Patients After Coronary Intervention
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Jong-Hwa, Ahn, Udaya S, Tantry, Min Gyu, Kang, Hyun Woong, Park, Jin-Sin, Koh, Jae Seok, Bae, Sang Young, Cho, Kye-Hwan, Kim, Jeong Yoon, Jang, Jeong Rang, Park, Yongwhi, Park, Seok-Jae, Hwang, Choong Hwan, Kwak, Jin-Yong, Hwang, Paul A, Gurbel, and Young-Hoon, Jeong
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Cardiology and Cardiovascular Medicine - Abstract
East Asian population has a low level of inflammation compared with Western population. The prognostic implication of residual inflammatory risk (RIR) remains uncertain in East Asians.This study sought to provide an analysis to estimate early-determined RIR and its association with clinical outcomes in East Asian patients with coronary artery disease (CAD).In an East Asian registry including patients with CAD undergoing percutaneous coronary intervention (PCI) (n = 4,562), RIR status was determined by measuring high-sensitivity C-reactive protein (hsCRP) serially at admission and at 1-month follow-up. Patients were stratified into 4 groups according to hsCRP criteria (≥2 mg/L): 1) persistent low RIR (lowIn our cohort, median levels of hsCRP were significantly decreased over time (1.3 to 0.9 mg/L;Approximately one-fifth of East Asian patients with CAD have persistent high RIR, which shows the close association with occurrence of ischemic and bleeding events. (Gyeongsang National University Hospital Registry [GNUH]; NCT04650529).
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- 2022
17. Monitoring and Reversal of Anticoagulation and Antiplatelet Agents
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Paul A. Gurbel, Amit Rout, and Udaya S. Tantry
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- 2022
18. Peri‐procedural Platelet Function Testing in Risk Stratification and Clinical Decision Making
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Paul A. Gurbel, Eliano P. Navarese, Aung Myat, and Udaya S. Tantry
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- 2022
19. Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens
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Nadia Heramvand, Maryna Masyuk, Johanna M. Muessig, Amir M. Nia, Athanasios Karathanos, Amin Polzin, Marco Valgimigli, Paul A. Gurbel, Udaya S. Tantry, Malte Kelm, and Christian Jung
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Percutaneous Coronary Intervention ,Fibrinolytic Agents ,Tirofiban ,Humans ,Tyrosine ,610 Medicine & health ,European Union ,Platelet Glycoprotein GPIIb-IIIa Complex ,Hematology ,610 Medizin und Gesundheit ,Cardiology and Cardiovascular Medicine ,Platelet Aggregation Inhibitors - Abstract
Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic treatment in patients with acute coronary syndromes (ACS) or high-risk percutaneous coronary interventions (PCI). It is administered intravenously as a bolus followed by continuous infusion. However, the dosage recommendations in the United States (US) and European Union (EU) differ considerably. Furthermore, in routine clinical practice, deviations from the recommendations may occur. The objective of the present study was to investigate the impact of different alterations on tirofiban plasma concentrations in US and EU administration regimens and to give suggestions for delay management in clinical practice. We therefore mathematically simulated the effects of different bolus-infusion delays and infusion interruptions in different scenarios according to the renal function. Here, we provide a systematic assessment of concentration patterns of tirofiban in the US versus EU dosage regimens. We show that differences between the two regimens have important effects on plasma drug levels. Furthermore, we demonstrate that deviations from the proper administration mode affect the concentration of tirofiban. Additionally, we calculated the optimal dosage of a second bolus to rapidly restore the initial concentration without causing overdosage. In conclusion, differences in tirofiban dosing regimens between the U.S and EU and potential infusion interruptions have important effects on drug levels that may impact on degrees of platelet inhibition and thus antithrombotic effects. Thus, the findings of our modelling studies may help to explain differences in clinical outcomes observed in previous clinical trials on tirofiban.
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- 2022
20. Low-Dose Aspirin for Primary Prevention of Cardiovascular Events Comparing East Asian Population with Westerner Population: A Systemic Review and Meta-Analysis
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Rock Bum Kim, Ang Li, Ki-Soo Park, Yune-Sik Kang, Jang-Rak Kim, Eliano P. Navarese, Diana A. Gorog, Udaya S. Tantry, Paul Gurbel, Jin-Yong Hwang, Oh-Young Kwon, and Young-Hoon Jeong
- Published
- 2023
21. Aspirin as an Adjunctive Pharmacologic Therapy Option for COVID-19: Anti-Inflammatory, Antithrombotic, and Antiviral Effects All in One Agent
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Udaya S Tantry, Karsten Schror, Eliano Pio Navarese, Young-Hoon Jeong, Jacek Kubica, Kevin P Bliden, and Paul A Gurbel
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Pharmacology ,Journal of Experimental Pharmacology ,inflammation ,platelets ,Molecular Medicine ,COVID-19 ,Pharmacology (medical) ,acute respiratory syndrome ,acetyl salicylic acid ,lungs ,Original Research - Abstract
Udaya S Tantry,1 Karsten Schror,2 Eliano Pio Navarese,3 Young-Hoon Jeong,4 Jacek Kubica,3 Kevin P Bliden,1 Paul A Gurbel1 1Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, LifeBridge Health, Baltimore, MD, USA; 2Department of Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Düsseldorf, Germany; 3Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Bydgoszcz, Poland; 4Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, South KoreaCorrespondence: Udaya S TantryThrombosis Research Laboratory, Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, LifeBridge Health, Baltimore, MD, 21215, USATel +1 410-367-2590Fax +1 410-367-2596Email utantry@lifebridgehealth.orgIntroduction: Pharmacologic therapy options for COVID-19 should include antiviral, anti-inflammatory, and anticoagulant agents. With the limited effectiveness, currently available virus-directed therapies may have a substantial impact on global health due to continued reports of mutant variants affecting repeated waves of COVID-19 around the world.Methods: We searched articles pertaining to aspirin, COVID-19, acute lung injury and pharmacology in PubMed and provide a comprehensive appraisal of potential use of aspirin in the management of patients with COVID-19. The scope of this article is to provide an overview of the rationale and currently available clinical evidence that supports aspirin as an effective therapeutic option in COVID-19.Results: Experimental and clinical evidence are available for the potential use of aspirin in patients with COVID-19.Discussion: Aspirin targets the intracellular signaling pathway that is essential for viral replication, and resultant inflammatory responses, hypercoagulability, and platelet activation. With these multiple benefits, aspirin can be a credible adjunctive therapeutic option for the treatment of COVID-19. In addition, inhaled formulation with its rapid effects may enhance direct delivery to the lung, which is the key organ damaged in COVID-19 during the critical initial course of the disease, whereas the 150â 325 mg/day can be used for long-term treatment to prevent thrombotic event occurrences. Being economical and widely available, aspirin can be exploited globally, particularly in underserved communities and remote areas of the world to combat the ongoing COVID-19 pandemic.Keywords: COVID-19, acetyl salicylic acid, platelets, inflammation, lungs, acute respiratory syndrome
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- 2021
22. Lack of smoking cessation in patients with coronary artery disease: a common worldwide problem
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Udaya S, Tantry, Parshotam, Kundan, and Paul A, Gurbel
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Risk Factors ,Internal Medicine ,Humans ,Smoking Cessation ,Coronary Artery Disease - Published
- 2022
23. Association Between Thrombogenicity Indices and Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction
- Author
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Young-Hoon Jeong, Jong-Hwa Ahn, Jeong Rang Park, Paul A. Gurbel, Udaya S. Tantry, Hyun Woong Park, Habib Samady, Seok-Jae Hwang, Bon-Kwon Koo, Min Gyu Kang, Jin-Yong Hwang, Kyehwan Kim, and Jin-Sin Koh
- Subjects
medicine.medical_specialty ,Thrombogenicity ,acute myocardial infarction ,Clinical Research ,PRU, P2Y12 reaction units ,Internal medicine ,Medicine ,In patient ,Myocardial infarction ,MA, maximum amplitude ,thrombogenicity ,IMR, index of microcirculatory resistance ,P-FCS, platelet-fibrin clot strength ,Tmn, mean transit time ,Physiologic Test ,LASSO, least absolute shrinkage and selection operator ,medicine.diagnostic_test ,coronary microvascular dysfunction ,business.industry ,CFR, coronary flow reserve ,CMD, coronary microvascular dysfunction ,Odds ratio ,medicine.disease ,cardiovascular event ,Thromboelastography ,AMI, acute myocardial infarction ,Clinical Practice ,OR, odds ratio ,TEG, thromboelastography ,clot strength ,Cardiology ,MACE, major adverse cardiovascular events ,Clot strength ,R, reaction time ,Cardiology and Cardiovascular Medicine ,business ,PCI, percutaneous coronary intervention ,TIMI, Thrombolysis in Myocardial Infarction - Abstract
Visual Abstract, Highlights • Our study supports the feasibility of measuring thrombogenicity in patients with acute myocardial infarction, with intent to predict periprocedural and long-term clinical events, in real-world clinical practice. • Preprocedural assessment of ex vivo thrombogenicity (eg, platelet-fibrin clot strength by thromboelastography) was significantly associated with the risk of coronary microvascular dysfunction. • A combined risk stratification with coronary microvascular dysfunction and platelet-fibrin clot strength increased the prognostic implication to predict the rates of long-term clinical outcomes., Summary The association between thrombogenicity and coronary microvascular dysfunction (CMD) has been poorly explored in patients with acute myocardial infarction (AMI). In our real-world clinical practice (N = 116), thrombogenicity was evaluated with thromboelastography and conventional hemostatic measures, and CMD was defined as index of microcirculatory resistance of >40 U using the invasive physiologic test. High platelet-fibrin clot strength (P-FCS) (≥68 mm) significantly increased the risk of postprocedural CMD (odds ratio: 4.35; 95% CI: 1.74-10.89). Patients with both CMD and high P-FCS had a higher rate of ischemic events compared to non-CMD subjects with low P-FCS (odds ratio: 5.58; 95% CI: 1.31-23.68). This study showed a close association between heightened thrombogenicity and CMD and their prognostic implications after reperfusion in acute myocardial infarction patients.
- Published
- 2021
24. Measurement of Anticoagulation in Patients on Dabigatran, Rivaroxaban, and Apixaban Therapy by Novel Automated Thrombelastography
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Brain Thurston, Kevin P. Bliden, Jan Hartmann, João D. Dias, Udaya S. Tantry, Maren Anderson, Mark Walsh, Paul A. Gurbel, Ramin Artang, and Jørn Dalsgaard Nielsen
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medicine.medical_specialty ,Rivaroxaban ,clinical trials: oral anticoagulants ,business.industry ,diagnosis management ,coagulation inhibitors ,apixaban ,Urology ,Atrial fibrillation ,medicine.disease ,Dabigatran ,Direct thrombin inhibitor ,RC666-701 ,Hemostasis ,medicine ,Diseases of the circulatory (Cardiovascular) system ,Thrombelastography ,Original Article ,dabigatran ,Apixaban ,In patient ,business ,rivaroxaban ,medicine.drug - Abstract
Background Direct-acting oral anticoagulants (DOACs) do not require monitoring. Measurement of DOAC effect would be useful in the event of bleeding, trauma, and thromboembolism while on anticoagulation. We evaluated the effectiveness of the investigational DOAC assays on the TEG®6s Hemostasis Analyzer to assess the anticoagulant effect of DOACs in patients treated for atrial fibrillation or deep vein thrombosis (DVT). Methods Patients on treatment for a minimum of 7 days with standard doses of dabigatran, rivaroxaban, and apixaban were included. DOAC plasma concentrations and TEG®6s Reaction (R)-time were measured and correlated. The sensitivity, specificity, and negative predictive value (NPV) of R-time to detect DOAC concentrations of ≥30, ≥50, and ≥100 ng/mL were calculated. Results A total of 189 patients were included, (n = 50) on apixaban, (n = 62) on rivaroxaban, (n = 53) on dabigatran, and (n = 24) on no DOAC were studied. Using the direct thrombin inhibitor (DTI) channel, R-time demonstrated strong linear correlation with dabigatran levels (r = 0.93, p Conclusion R-time measured by TEG®6s DOAC-specific cartridge has a strong correlation with concentrations of the most commonly used DOACs with high sensitivity and NPV for detecting lower drug levels that are considered clinically relevant for patients in need of antidote, or prior to urgent surgery. Further studies to determine the relation of R-time to clinical outcomes are warranted.
- Published
- 2021
25. The role of viscoelastic testing in assessing peri-interventional platelet function and coagulation
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Jan Hartmann, Seema Agarwal, Elisabeth Mahla, Kevin P. Bliden, Matthew D. Neal, Udaya S. Tantry, João D. Dias, Dan Mason, Paul A. Gurbel, and Herbert Schöechl
- Subjects
Hemostasis ,medicine.medical_specialty ,Neurology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,MEDLINE ,COVID-19 ,Hematology ,General Medicine ,Blood Coagulation Disorders ,Thrombelastography ,Cardiac surgery ,Care setting ,Coagulation ,medicine ,Coagulation testing ,Humans ,Platelet ,Blood Coagulation Tests ,Intensive care medicine ,business ,Blood Coagulation - Abstract
We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.
- Published
- 2021
26. Thrombogenicity markers for early diagnosis and prognosis in COVID-19: a change from the current paradigm?
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Paul A. Gurbel, Udaya S. Tantry, Kevin P. Bliden, Jerrold H. Levy, Nicole Rapista, Christophe Jerjian, Naval Walia, and Alastair Cho
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Male ,Organ Dysfunction Scores ,Comorbidity ,COVID-19 Testing ,Medicine ,Thrombophilia ,Myocardial infarction ,Prospective Studies ,Prospective cohort study ,Stroke ,Aged, 80 and over ,medicine.diagnostic_test ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,Thrombelastography ,Hospitalization ,Treatment Outcome ,Cardiovascular Diseases ,SOFA score ,Female ,Fibrin Clot Lysis Time ,Adult ,medicine.medical_specialty ,Thrombogenicity ,Hyperlipidemias ,White People ,Internal medicine ,Diabetes Mellitus ,Humans ,Obesity ,African--Americans ,Aged ,Fibrin ,L-Lactate Dehydrogenase ,business.industry ,SARS-CoV-2 ,sequential organ failure assessment score ,COVID-19 ,Fibrinogen ,thromboelastography ,Odds ratio ,Original Articles ,medicine.disease ,Thromboelastography ,Black or African American ,Early Diagnosis ,platelet fibrin clot strength ,business ,Biomarkers - Abstract
Standard biomarkers have been widely used for COVID-19 diagnosis and prognosis. We hypothesize that thrombogenicity metrics measured by thromboelastography will provide better diagnostic and prognostic utility versus standard biomarkers in COVID-19 positive patients. In this observational prospective study, we included 119 hospitalized COVID-19 positive patients and 15 COVID-19 negative patients. On admission, we measured standard biomarkers and thrombogenicity using a novel thromboelastography assay (TEG-6s). In-hospital all-cause death and thrombotic occurrences (thromboembolism, myocardial infarction and stroke) were recorded. Most COVID-19 patients were African--Americans (68%). COVID-19 patients versus COVID-19 negative patients had higher platelet-fibrin clot strength (P-FCS), fibrin clot strength (FCS) and functional fibrinogen level (FLEV) (Pâ≤â0.003 for all). The presence of high TEG-6âs metrics better discriminated COVID-19 positive from negative patients. COVID-19 positive patients with sequential organ failure assessment (SOFA) score at least 3 had higher P-FCS, FCS and FLEV than patients with scores less than 3 (Pâ≤â0.001 for all comparisons). By multivariate analysis, the in-hospital composite endpoint occurrence of death and thrombotic events was independently associated with SOFA score more than 3 [odds ratio (OR)â=â2.9, Pâ=â0.03], diabetes (ORâ=â3.3, Pâ=â0.02) and FCSâ>â40âmm (ORâ=â3.4, Pâ=â0.02). This largest observational study suggested the early diagnostic and prognostic utility of thromboelastography to identify COVID-19 and should be considered hypothesis generating. Our results also support the recent FDA guidance regarding the importance of measurement of whole blood viscoelastic properties in COVID-19 patients. Our findings are consistent with the observation of higher hospitalization rates and poorer outcomes for African--Americans with COVID-19.
- Published
- 2021
27. Reply to: Among patients with MINOCA women versus men have the increased risks of MACE and stroke?
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Rahul Chaudhary, Michael Bashline, Enrico M. Novelli, Kevin P. Bliden, Udaya S. Tantry, Oladipupo Olafiranye, Seyed Mehdi Nouraie, Paul A. Gurbel, and John J. Pacella
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2022
28. Clinical validation of AggreGuide A-100 ADP, a novel assay for assessing the antiplatelet effect of oral P2Y12 antagonists
- Author
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Kevin P. Bliden, Paul A. Gurbel, Jeffrey Dahlen, Philip C Speros, Richard Fisher, Sivaprasad Sukavaneshvar, and Udaya S. Tantry
- Subjects
medicine.medical_specialty ,Prasugrel ,Hematology ,business.industry ,030204 cardiovascular system & hematology ,Pharmacology ,Clopidogrel ,03 medical and health sciences ,Adenosine diphosphate ,chemistry.chemical_compound ,0302 clinical medicine ,P2Y12 ,chemistry ,Internal medicine ,medicine ,030212 general & internal medicine ,Platelet activation ,Cardiology and Cardiovascular Medicine ,business ,Ticagrelor ,medicine.drug ,Whole blood - Abstract
In this prospective, 3-arm, repeated-measure multicenter investigation in 280 patients with cardiovascular risk factors, platelet aggregation was measured with the novel AggreGuide A-100 ADP (A-100 ADP) and VerifyNow (VN)-PRU assays at baseline, and after United States Food and Drug Administration approved loading and 7 days maintenance doses of clopidogrel (n = 94), prasugrel (n = 43) or ticagrelor, (n = 143). Based on the predetermined cutoff values of
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- 2021
29. Platelet Reactivity and Coagulation Markers in Patients with COVID-19
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Rinaldo Focaccia Siciliano, Adriadne Justi Bertolin, Felipe G. Lima, Ludhmila Abrahão Hajjar, Roberto R. Giraldez, Rocio Salsoso, Jose C. Nicolau, Alexandra Vieira, Talia Dalcoquio, Cyrillo Cavalheiro-Filho, Remo H.M. Furtado, Esper G. Kallas, Luciano Moreira Baracioli, Celia Maria Cassaro Strunz, Robert P. Giugliano, Roberto Kalil-Filho, Paul A. Gurbel, and Udaya S. Tantry
- Subjects
Blood Platelets ,medicine.medical_specialty ,Platelet Aggregation ,Fibrinogen ,Gastroenterology ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Platelet ,Original Research ,business.industry ,SARS-CoV-2 ,Thromboelastometry ,Case-control study ,COVID-19 ,General Medicine ,Rheumatology ,chemistry ,Plasminogen activator inhibitor-1 ,Case-Control Studies ,Etiology ,Platelet aggregation inhibitor ,Multiplate electrode aggregometry ,business ,Platelet reactivity ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Introdution COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. Methods Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as
- Published
- 2021
30. International COVID-19 thrombosis biomarkers colloquium: COVID-19 diagnostic tests
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Paul A. Gurbel, Robert F. Storey, and Udaya S. Tantry
- Subjects
medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,COVID-19 ,Diagnostic test ,Thrombosis ,Hematology ,medicine.disease ,Article ,COVID-19 Testing ,medicine ,Humans ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business ,Biomarkers - Published
- 2021
31. Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium
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Diana A. Gorog, Robert F. Storey, Paul A. Gurbel, Udaya S. Tantry, Jeffrey S. Berger, Mark Y. Chan, Daniel Duerschmied, Susan S. Smyth, William A. E. Parker, Ramzi A. Ajjan, Gemma Vilahur, Lina Badimon, Jurrien M. ten Berg, Hugo ten Cate, Flora Peyvandi, Taia T. Wang, Richard C. Becker, Interne Geneeskunde, MUMC+: HVC Pieken Trombose (9), MUMC+: MA Alg Interne Geneeskunde (9), MUMC+: HVC Trombosezorg (8), and RS: Carim - B04 Clinical thrombosis and Haemostasis
- Subjects
COMPLICATIONS ,ENDOTHELIITIS ,PROTEASE ,SARS-CoV-2 ,VON-WILLEBRAND-FACTOR ,Consensus Statement ,EXTRACELLULAR VESICLES ,COVID-19 ,Thrombosis ,MECHANISMS ,Prognostic markers ,Thromboembolism ,VENOUS SINUS THROMBOSIS ,MANAGEMENT ,Humans ,Cardiology and Cardiovascular Medicine ,COMPLEMENT ACTIVATION ,Pandemics ,PLATELET ,Biomarkers - Abstract
Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and d-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research., In this Consensus Statement, the authors delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess thrombotic risk in these patients. Consensus recommendations are made about the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombosis and in-hospital mortality.
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- 2022
32. Defining platelet response to acetylsalicylic acid: the relation between inhibition of serum thromboxane B2 and agonist-induced platelet aggregation
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Kevin P. Bliden, Paul A. Gurbel, and Udaya S. Tantry
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Agonist ,medicine.medical_specialty ,medicine.drug_class ,Urinary system ,030204 cardiovascular system & hematology ,Pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Medicine ,Platelet ,030212 general & internal medicine ,Creatinine ,Hematology ,business.industry ,respiratory system ,Thromboxane B2 ,chemistry ,lipids (amino acids, peptides, and proteins) ,Arachidonic acid ,Cardiology and Cardiovascular Medicine ,business ,Salicylic acid ,circulatory and respiratory physiology - Abstract
Arachidonic acid (AA)-induced platelet aggregation (PA) and serum thromboxane B2 (TxB2) inhibition are widely used to indicate cyclooxygenase-1 activity and the antiplatelet effect of acetylsalicylic acid (ASA). Despite decades of investigations, the relation between these measurements remains unclear. We sought to evaluate the relation between AA-PA and serum TxB2 inhibition. We serially measured AA-PA (conventional aggregation), serum TxB2, plasma ASA and salicylic acid (SA) (liquid chromatography-mass spectrometry), and urinary 11-dehydro thromboxane B2 (u11-dh TxB2) (enzyme-linked immunosorbent assay) levels at 10 times over 24 hours in seventeen healthy volunteers receiving a single dose of 162 mg chewed and swallowed ASA (n = 6), 50 mg inhaled ASA (n = 6), or 100 mg inhaled ASA (n = 5) (ClinicalTrials.gov Identifier: NCT04328883, April 1, 2020). Baseline variability was more pronounced with serum TxB2 (31–680 ng/mL) as compared to maximal AA-PA (65–81%) and u11-dh TxB2 (1556–4440 pg/mg creatinine). The relation between serum TxB2 inhibition and AA-PA was stepwise; after 30–40% inhibition of serum TxB2, AA-PA fell to 49% and u11-dh TxB2 49%. Moreover, these results suggest that the definition of > 95% inhibition of serum TxB2 to indicate the level of platelet COX-1 inhibition needed for clinical efficacy may be overestimated and should be re-considered in future translational research investigations that attempt to link the clinical efficacy of ASA with a laboratory measurement cutoff.
- Published
- 2020
33. Targeted pharmacotherapy for ischemia reperfusion injury in acute myocardial infarction
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Ajaypaul Sukhi, Marko Novakovic, Amit Rout, Udaya S. Tantry, and Paul A. Gurbel
- Subjects
medicine.medical_specialty ,Cardiotonic Agents ,Anti-Inflammatory Agents ,Myocardial Infarction ,Ischemia ,Myocardial Reperfusion Injury ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Pharmacotherapy ,Internal medicine ,Animals ,Humans ,Medicine ,Pharmacology (medical) ,Platelet ,Molecular Targeted Therapy ,Myocardial infarction ,Pharmacology ,Anakinra ,business.industry ,General Medicine ,medicine.disease ,chemistry ,030220 oncology & carcinogenesis ,Cardiology ,business ,Reperfusion injury ,Platelet Aggregation Inhibitors ,030217 neurology & neurosurgery ,Oxidative stress ,medicine.drug - Abstract
Achieving reperfusion immediately after acute myocardial infarction improves outcomes; despite this, patients remain at a high risk for mortality and morbidity at least for the first year after the event. Ischemia-reperfusion injury (IRI) has a complex pathophysiology and plays an important role in myocardial tissue injury, repair, and remodeling.In this review, the authors discuss the various mechanisms and their pharmacological agents currently available for reducing myocardial ischemia-reperfusion injury (IRI). They review important original investigations and trials in various clinical databases for treatments targeting IRI.Encouraging results observed in many preclinical studies failed to show similar success in attenuating myocardial IRI in large-scale clinical trials. Identification of critical risk factors for IRI and targeting them individually rather than one size fits all approach should be the major focus of future research. Various newer therapies like tocilizumab, anakinra, colchicine, revacept, and therapies targeting the reperfusion injury salvage kinase pathway, survivor activating factor enhancement, mitochondrial pathways, and angiopoietin-like peptide 4 hold promise for the future.
- Published
- 2020
34. Detailed thrombogenicity phenotyping and 1 year outcomes in patients undergoing WATCHMAN implantation: (TARGET-WATCHMAN) a case–control study
- Author
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Paul A. Gurbel, Ganesh Venkataraman, Rahul Chaudhary, Haroon Rashid, Sharam Yazdani, Leonard Ilkhanoff, Matthew W. Sherwood, Kevin P. Bliden, Wayne Batchelor, Robert McSwain, Adam Strickberger, Udaya S. Tantry, Tracy Plummer, and Eliano Pio Navarese
- Subjects
Male ,medicine.medical_specialty ,Thrombogenicity ,Hemorrhage ,030204 cardiovascular system & hematology ,Thrombin time ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Atrial Fibrillation ,Antithrombotic ,Humans ,Medicine ,Atrial Appendage ,Prospective Studies ,030212 general & internal medicine ,Blood Coagulation ,Aged ,Aged, 80 and over ,Hemostasis ,medicine.diagnostic_test ,business.industry ,Case-control study ,Anticoagulants ,Thrombosis ,Hematology ,medicine.disease ,Thromboelastography ,Clinical trial ,Treatment Outcome ,Case-Control Studies ,Cardiology ,Female ,Heart-Assist Devices ,Cardiology and Cardiovascular Medicine ,business - Abstract
The relation of device related thrombosis (DRT) and major bleeding after left atrial appendage closure (LAAC) to laboratory thrombosis and hemostasis markers has not been studied. We performed a prospective case control study to identify clinical characteristics and laboratory markers in patients who developed DRT and major bleeding following WATCHMAN LAAC. Thromboelastography, platelet aggregation (PA), urinary 11-dehydrothromboxane B2 (UTX), fibrinogen, d-dimer, thrombin time and von Willebrand factor activity were determined at baseline, immediately following, and at 45 and 180 days post-LAAC (n = 32) and outcomes were followed for 1 year. Baseline characteristics and thrombogenic profiles of patients with and without DRT and/or BARC bleeding were compared. Mean age was 76 ± 8 years and CHADS2 VASc score was 4.4 ± 1.4. There were 3 DRTs (2 within 6 months, and 1 at 12 months), 4 Type 3A BARC bleeds, and 2 non-cardiac deaths. Patients with DRT had higher baseline thrombin-induced platelet–fibrin clot strength (68.0 ± 1.8 vs. 62.7 ± 4.7 mm, p = 0.06); FCS (35.6 ± 6.0 vs. 24.4 ± 6.6 mm, p = 0.009); and d-dimer (1712 ± 2330 vs. 283 ± 213 ng/mL, p = 0.001). At baseline, 5 patients had all 3 factors associated with high thrombotic risk and 2 experienced a DRT within 6 months. Patients with Type 3A BARC bleeding had lower baseline collagen-induced and 45-day ADP-induced PA (p
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- 2020
35. Assessing platelet reactivity after drug eluting stent implantation: state of the art
- Author
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Udaya S. Tantry, Kevin P. Bliden, Amit Rout, Paul A. Gurbel, and Saroj Timilsina
- Subjects
Blood Platelets ,Drug ,Acute coronary syndrome ,medicine.medical_specialty ,Platelet Function Tests ,media_common.quotation_subject ,medicine.medical_treatment ,Hemorrhage ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Coronary artery disease ,Platelet reactivity ,03 medical and health sciences ,0302 clinical medicine ,P2Y12 ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Platelet ,030212 general & internal medicine ,Acute Coronary Syndrome ,media_common ,business.industry ,Drug-Eluting Stents ,General Medicine ,medicine.disease ,Clopidogrel ,Drug-eluting stent ,Purinergic P2Y Receptor Antagonists ,Cardiology ,Drug Therapy, Combination ,Cardiology and Cardiovascular Medicine ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Introduction: Platelets play a pivotal role in the occurrence of recurrent ischemic events in coronary artery disease patients who are treated with drug-eluting stents and are on dual antiplatelet therapy (DAPT).Areas covered: High platelet reactivity (HPR) to adenosine diphosphate during clopidogrel therapy is a strong predictor of post-stenting ischemic event occurrences. However, uniform use of potent P2Y12 receptors blockers to overcome HPR is associated with elevated bleeding risk. Selective de-escalation of P2Y12 receptor blocker therapy based on PFT in patients with acute coronary syndrome treated with stenting has been shown to be associated with a similar risk of ischemic event occurrence but with a reduced risk of bleeding. This review aims to discuss the role of PFT in guiding DAPT in patients treated with DES. We searched electronic databases from January 2000 to December 2019 for literatures evaluating the role of platelet function assessment after drug eluting stents.Expert opinion: Platelet function guided therapy improves patient outcomes by lessening bleeding and limiting the overuse of highly potent P2Y12 inhibitors. Interest in this area of de-escalation of therapy will likely grow as the consequences of bleeding are better recognized and the cost of healthcare gains greater focus.
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- 2020
36. Investigational drugs in phase II clinical trials for acute coronary syndromes
- Author
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Udaya S. Tantry, Amit Rout, Kevin P. Bliden, Rahul Chaudhary, Ajaypaul Sukhi, and Paul A. Gurbel
- Subjects
0301 basic medicine ,Drug ,Acute coronary syndrome ,medicine.medical_specialty ,media_common.quotation_subject ,MEDLINE ,Phases of clinical research ,03 medical and health sciences ,chemistry.chemical_compound ,Clinical Trials, Phase II as Topic ,0302 clinical medicine ,Tocilizumab ,Drug Development ,Secondary Prevention ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Acute Coronary Syndrome ,Intensive care medicine ,media_common ,Pharmacology ,Anakinra ,business.industry ,Drugs, Investigational ,General Medicine ,medicine.disease ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Concomitant ,Practice Guidelines as Topic ,Investigational Drugs ,business ,medicine.drug - Abstract
Introduction: Despite current guideline-based, secondary prevention strategies in patients with the acute coronary syndrome, the residual ischemic risk is still at an unacceptable rate, and there is a concomitant high bleeding event rate. These observations mandate investigations of novel treatment strategies to meet the unmet need to improve outcomes in patients with ACS.Areas covered: In this review, the author(s) focus on new agents with ongoing or recently completed phase II trials for the treatment of ACS. We searched MEDLINE and clinicaltrials.org for Phase II trials in ACS patients, and important original investigations are reviewed.Expert opinion: Some of the novel drugs evaluated in the Phase II trials hold promise for future therapies such as AZD5718, anakinra, tocilizumab, CSL112, MEDI 6102, inclisiran, PZ128, selatogrel, and RVX-208. Their efficacy and safety should be evaluated in large scale Phase III trials. The higher cost of the drug will be a major limitation for wide-spread use of novel agents in general practice in future.
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- 2020
37. Effects of vorapaxar on clot characteristics, coagulation, inflammation, and platelet and endothelial function in patients treated with mono‐ and dual‐antiplatelet therapy
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Henry A. Tran, Hamid Taheri, Rahul Chaudhary, Udaya S. Tantry, Arnold Rosenblatt, Athan Kuliopulos, Behnam Tehrani, Kevin P. Bliden, Eliano Pio Navarese, and Paul A. Gurbel
- Subjects
medicine.medical_specialty ,Pyridines ,030204 cardiovascular system & hematology ,Thrombin time ,Fibrinogen ,Gastroenterology ,Article ,Lactones ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,Internal medicine ,medicine ,Humans ,Platelet ,Platelet activation ,Vorapaxar ,Inflammation ,medicine.diagnostic_test ,biology ,business.industry ,Hematology ,Clopidogrel ,Coagulation ,biology.protein ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
BACKGROUND: Vorapaxar is indicated with standard antiplatelet therapy (APT) in patients with a history of myocardial infarction (MI) or peripheral arterial disease (PAD). OBJECTIVES: To evaluate the comparative effects of vorapaxar on platelet-fibrin clot characteristics (PFCC), coagulation, inflammation, and platelet and endothelial function during treatment with daily 81 mg aspirin (A), 75 mg clopidogrel (C), both (C + A), or neither. METHODS: Thrombelastography, conventional platelet aggregation (PA), ex vivo endothelial function by ENDOPAT, coagulation, platelet activation/inflammation marked by urinary 11-dehydrothromboxane B(2) (UTxB(2)) and safety were determined in patients who were APT naïve (n = 21), on C (n = 8), on A (n = 29), and on A + C (n = 23) during 1 month of vorapaxar therapy and 1 month of offset. RESULTS: Vorapaxar had no effect on PFCC, ADP- or collagen-induced PA, thrombin time, fibrinogen, PT, PTT, von Willebrand factor (vWF), D-dimer, or endothelial function (P > .05 in all groups). Inhibition of SFLLRN (PAR-1 activating peptide)-stimulated PA by vorapaxar was accelerated by A + C at 2 hours (P < .05 versus other groups) with nearly complete inhibition by 30 days that persisted through 30 days after discontinuation in all groups (P < .001). SFLLRN-induced PA during offset was lower in APT patients versus APT-naïve patients (P < .05). Inhibition of UTxB(2) was observed in APT-naïve patients treated with vorapaxar (P < .05). Minor bleeding was only observed in C-treated patients. CONCLUSION: Vorapaxar had no influence on PFCC measured by thrombelastography, coagulation, or endothelial function irrespective of APT. Inhibition of protease activated receptor (PAR)-1 mediated platelet aggregation by vorapaxar was accelerated by A + C and offset was prolonged by concomitant APT. Vorapaxar-induced anti-inflammatory effects were observed in non-aspirin-treated patients.
- Published
- 2020
38. Low-dose ticagrelor with or without acetylsalicylic acid in patients with acute coronary syndrome : Rationale and design of the ELECTRA-SIRIO 2 trial
- Author
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Jacek Kubica, Dimitrios Alexopoulos, Piotr Niezgoda, Young-Hoon Jeong, Salvatore Di Somma, Jolanta M. Siller-Matula, Jacek Legutko, Andrzej Budaj, Eliano Pio Navarese, Marcin Gruchała, Agnieszka Tycińska, Bernd Jilma, Giuseppe Specchia, Jarosław D. Kasprzak, Andrzej Kleinrok, Michał Kryjak, Udaya S. Tantry, Dariusz Dudek, Grzegorz J. Horszczaruk, Małgorzata Ostrowska, Robert J. Gil, Wojciech Wojakowski, Piotr Adamski, Aldona Kubica, Miłosz Jaguszewski, Stefan James, Jolita Badarienė, Evangelos Giannitsis, Giuseppe Patti, Katarzyna Buszko, Maciej Lesiak, Mariusz Gąsior, Diana A. Gorog, Janusz Romanek, Paul A. Gurbel, and Paweł Dąbrowski
- Subjects
Ticagrelor ,medicine.medical_specialty ,Acute coronary syndrome ,acute coronary syndrome ,ticagrelor ,Levodopa ,Percutaneous Coronary Intervention ,Internal medicine ,medicine ,Humans ,Cardiac and Cardiovascular Systems ,In patient ,Myocardial infarction ,Acute Coronary Syndrome ,Kardiologi ,Aspirin ,business.industry ,Low dose ,Carbidopa ,General Medicine ,medicine.disease ,de-escalation ,Drug Combinations ,Treatment Outcome ,myocardial infarction ,dose reduction ,Cardiology ,Dose reduction ,Cardiology and Cardiovascular Medicine ,business ,Platelet Aggregation Inhibitors ,De-escalation ,medicine.drug - Published
- 2022
39. HDL3-C is a Marker of Coronary Artery Disease Severity and Inflammation in Patients on Statin Therapy
- Author
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Rahul Chaudhary, Kevin P. Bliden, Rohit Chaudhary, Ajaypaul Sukhi, Udaya S. Tantry, Paul A. Gurbel, and Marija Kinderytė
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,CAD ,030204 cardiovascular system & hematology ,Coronary artery disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Statistical significance ,medicine ,cardiovascular diseases ,030212 general & internal medicine ,Cardiac catheterization ,Receiver operating characteristic ,business.industry ,Cholesterol ,General Medicine ,medicine.disease ,Stenosis ,chemistry ,Cardiology ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,business ,Lipoprotein - Abstract
Introduction Low high-density lipoprotein (HDL-C) and inflammation are risk factors for coronary artery disease (CAD). However, limited data are available determining the role of HDL-C sub-particles HDL2-C and HDL3-C for assessing CAD severity in patients on statin therapy. Methods Blood samples were obtained prior to cardiac catheterization in 304 consecutive patients with suspected CAD on statin therapy in this sub-analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678 ) study. Detailed lipid profiling and oxidized LDL (ox-LDL) were analyzed. CAD severity was angiographically defined as severe CAD (>75% luminal diameter stenosis [LDS]) and non-severe CAD (≤75% LDS). Multi-regression analysis was performed to test for statistical significance. Receiver operator curve (ROC) analysis was performed to determine cut-point for predicting severe CAD. Results Patients with severe CAD had a significantly lower total-HDL-C, lower HDL3-C and higher lipoprotein(a) levels. HDL3-C and lipoprotein(a) cholesterol [Lp(a)-C] retained statistical significance on multiple regression analysis. ROC analysis showed HDL3-C to have a C-statistic of 0.60 (p = 0.003) and Lp(a)-C to have a C-statistic of 0.61 (p = 0.0007). Patients with HDL3-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL were found to have significantly elevated ox-LDL levels. Conclusion In patients on statin therapy, HDL3-C and Lp(a)-C improve prediction of severe CAD compared to a traditional lipid panel. In addition, patients with HDL3-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL have greater inflammation marked by ox-LDL. Further studies are needed to evaluate the utility of these novel biomarkers in predicting CAD severity.
- Published
- 2019
40. In Vitro Evidence for the Role of Cytokine Storm in the Generation of Stent Thrombosis in COVID-19 Patients
- Author
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Paul A. Gurbel and Udaya S. Tantry
- Subjects
SARS-CoV-2 ,COVID-19 ,Humans ,Stents ,Thrombosis ,General Medicine ,Cardiology and Cardiovascular Medicine ,Cytokine Release Syndrome ,Article - Published
- 2021
41. Further evidence for the use of aspirin in COVID-19
- Author
-
Udaya S. Tantry, Paul A. Gurbel, and Kevin P. Bliden
- Subjects
2019-20 coronavirus outbreak ,Aspirin ,Editorial ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Virology ,medicine.drug - Published
- 2021
42. Bedside thromboelastography to rapidly assess the pharmacodynamic response of anticoagulants and aspirin in COVID-19: evidence of inadequate therapy in a predominantly minority population
- Author
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Udaya S. Tantry, Amit Rout, Jaime Barnes, Paul A. Gurbel, Malina Traianova, Nicole Rapista, Rahul Chaudhary, Gordon Ens, Naval Walia, and Kevin P. Bliden
- Subjects
Male ,medicine.medical_specialty ,Platelet Function Tests ,Coronavirus disease 2019 (COVID-19) ,Point-of-care testing ,Population ,Biological Availability ,Biomarkers, Pharmacological ,Article ,medicine ,Humans ,education ,Intensive care medicine ,Hemostasis ,education.field_of_study ,Aspirin ,medicine.diagnostic_test ,Heparin ,SARS-CoV-2 ,business.industry ,Anticoagulants ,COVID-19 ,Hematology ,Middle Aged ,United States ,Thromboelastography ,Thrombelastography ,COVID-19 Drug Treatment ,Black or African American ,Point-of-Care Testing ,Pharmacodynamics ,Platelet aggregation inhibitor ,Female ,Cardiology and Cardiovascular Medicine ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Published
- 2021
43. Is meta-analysis the optimal method to decide the duration of antiplatelet therapy in diabetic patients treated with drug‑eluting stenting?
- Author
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Udaya S. Tantry and Paul A. Gurbel
- Subjects
Drug ,medicine.medical_specialty ,Aspirin ,business.industry ,media_common.quotation_subject ,Text mining ,Treatment Outcome ,Pharmaceutical Preparations ,Internal medicine ,Meta-analysis ,Internal Medicine ,Diabetes Mellitus ,Medicine ,Humans ,Stents ,Duration (project management) ,business ,Platelet Aggregation Inhibitors ,media_common - Published
- 2021
44. Is a personalized pharmacotherapeutic approach closed for acute coronary syndrome?
- Author
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Amit Rout, Kevin P. Bliden, Paul A. Gurbel, and Udaya S. Tantry
- Subjects
Pharmacology ,Acute coronary syndrome ,medicine.medical_specialty ,business.industry ,MEDLINE ,General Medicine ,medicine.disease ,03 medical and health sciences ,Percutaneous Coronary Intervention ,0302 clinical medicine ,Text mining ,Pharmacotherapy ,030220 oncology & carcinogenesis ,medicine ,Humans ,Pharmacology (medical) ,Acute Coronary Syndrome ,business ,Intensive care medicine ,Platelet Aggregation Inhibitors ,030217 neurology & neurosurgery - Abstract
Improvement in reperfusion and pharmacotherapy strategies for the acute coronary syndrome (ACS) had led to a decline in mortality and morbidity; despite this ACS is still associated with substantia...
- Published
- 2021
45. Evolution of Anti-SARS-CoV-2 IgG Antibody and IgG Avidity Post Pfizer and Moderna mRNA Vaccinations
- Author
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Su Zhao, Deepika Sreedhar, Dingying Shan, Tiancheng Liu, Abira Usman, Jessica Hsiung, Christophe Jerjian, Naval Walia, Udaya S. Tantry, Paul A. Gurbel, Alastair Cho, Meijie Tang, Kevin P. Bliden, Jessica Kost, and Hongjie Dai
- Subjects
biology ,Side effect ,business.industry ,Vaccination ,Immune system ,Immunity ,Cohort ,Immunology ,biology.protein ,Medicine ,Avidity ,Antibody ,Receptor ,business - Abstract
Messenger RNA (mRNA) based vaccines (Pfizer/BioNTech and Moderna) are highly effective at providing immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is uncertainty about the duration of immunity, evolution of IgG antibody levels and IgG avidity (an index of antibody-antigen binding strength), and differences in the immune responses between vaccines. Here we performed a prospective pilot study of 71 previously COVID-19 free subjects upon receiving both doses of either the Pfizer (n = 54) or Moderna (n = 17) mRNA vaccine. Anti-spike protein receptor binding domain (RBD) IgG antibodies were measured longitudinally using a qualitative finger stick MidaSpot™ rapid test at the point-of-care for initial screening and a quantitative dry blood spot-based pGOLD™ laboratory test over ∼ four months post-vaccination. The average anti-RBD IgG antibody levels peaked at ∼ two weeks after the second dose of the vaccine and declined thereafter, while antibody avidity increased, suggesting antibody maturation. Moderna vaccine recipients compared to Pfizer vaccine recipients exhibited higher side effect severity, higher peak anti-RBD IgG antibody levels, and higher avidity up to the 90 days period. Differences in antibody levels diminished at ∼ 120 days post-vaccination, in line with the similar efficacy observed in the two vaccines. The MidaSpot™ rapid test detected 100% anti-SARS-CoV-2 RBD positivity for fully vaccinated subjects in both Pfizer and Moderna cohorts post full vaccination but turned negative greater than 90 days post-vaccination for 5.4% of subjects in the Pfizer cohort, whose quantitative anti-IgG were near the minimum levels of the group. Immune responses were found to vary greatly among vaccinees. Personalized longitudinal monitoring of antibodies could be necessary to assess the immunity duration of vaccinated individuals.
- Published
- 2021
46. A New Saliva-Based Lateral-Flow SARS-CoV-2 IgG Antibody Test for mRNA Vaccination
- Author
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Shuanglin Tan, Guoxing Wang, Paul A. Gurbel, Wei Po Yuan, Udaya S. Tantry, Jessica Kost, Hongjie Dai, Jessica Hsiung, Deepika Sreedhar, Dingying Shan, Tiancheng Liu, Tao Liao, Kevin P. Bliden, Su Zhao, Meijie Tang, and Shin Ting Chang
- Subjects
Messenger RNA ,Saliva ,biology ,business.industry ,Dried blood spot ,Vaccination ,Immune system ,Immunity ,Immunology ,biology.protein ,Medicine ,Antibody ,business ,Blood drawing - Abstract
Sensitive detection of IgG antibodies against SARS-CoV-2 is important to assessing immune responses to viral infection or vaccination and immunity duration. Antibody assays using non-invasive body fluids such as saliva could facilitate mass testing including young children, elderly and those who resist blood draws, and easily allowing longitudinal testing/monitoring of antibodies over time. Here, we developed a new lateral flow (nLF) assay that sensitively detects SARS-CoV-2 IgG antibodies in the saliva samples of vaccinated individuals and previous COVID-19 patients. The 25-minute nLF assay detected anti-spike protein (anti-S1) IgG in saliva samples with 100% specificity and high sensitivity from both vaccinated (99.51% for samples ≥ 19 days post 1st Pfizer/BioNTech or Moderna mRNA vaccine dose) and infected individuals. Antibodies against nucleocapsid protein (anti-NCP) was detected only in the saliva samples of COVID-19 patients and not in vaccinated samples, allowing facile differentiation of vaccination from infection. SARS-CoV-2 anti-S1 IgG antibody in saliva measured by nLF demonstrated similar evolution trends post vaccination to that in matching dried blood spot (DBS) samples measured by a quantitative pGOLD lab-test, enabling the nLF to be a valid tool for non-invasive personalized monitoring of SARS-CoV-2 antibody persistence. The new salivary rapid test platform can be applied for non-invasive detection of antibodies against infection and vaccination in a wide range of diseases.
- Published
- 2021
47. Clinical validation of AggreGuide A-100 ADP, a novel assay for assessing the antiplatelet effect of oral P2Y
- Author
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Paul A, Gurbel, Udaya S, Tantry, Kevin P, Bliden, Richard, Fisher, Sivaprasad, Sukavaneshvar, Jeffrey, Dahlen, and Philip C, Speros
- Subjects
Adenosine Diphosphate ,Blood Platelets ,Ticagrelor ,Adenosine ,Platelet Aggregation ,Platelet Function Tests ,Purinergic P2Y Receptor Antagonists ,Humans ,Prospective Studies ,Prasugrel Hydrochloride ,Platelet Aggregation Inhibitors ,Clopidogrel - Abstract
In this prospective, 3-arm, repeated-measure multicenter investigation in 280 patients with cardiovascular risk factors, platelet aggregation was measured with the novel AggreGuide A-100 ADP (A-100 ADP) and VerifyNow (VN)-PRU assays at baseline, and after United States Food and Drug Administration approved loading and 7 days maintenance doses of clopidogrel (n = 94), prasugrel (n = 43) or ticagrelor, (n = 143). Based on the predetermined cutoff values of 4.7 platelet activity index with A-100 ADP assay to indicate antiplatelet response, more than 91% of patients met the criteria following loading and maintenance doses of prasugrel and more than 84% patients met the criteria following loading and maintenance doses of ticagrelor whereas only 32% and 51% of patients met the criteria following loading and maintenance doses of clopidogrel, respectively. The total percent agreement between the A-100 ADP and VN-PRU assays was 89%. The A-100 ADP assay, which includes whole blood in motion, performs comparably to the VN-PRU assay in a study of patients with cardiovascular risk factors treated with P2Y
- Published
- 2021
48. First Experience Addressing the Prognostic Utility of Novel Urinary Biomarkers in Patients with COVID-19
- Author
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Jeffrey Dahlen, Abira Usman, Naval Walia, Christophe Jerjian, Alastair Cho, Paul A. Gurbel, Malina Traianova, Udaya S. Tantry, Gordon Ens, and Kevin P. Bliden
- Subjects
Oncology ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Urinary system ,Urine ,030204 cardiovascular system & hematology ,Fatty acid-binding protein ,urinary 11-dehydro- thromboxane B2 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Deoxyguanosine ,In patient ,030212 general & internal medicine ,liver-type fatty acid binding protein ,Adverse effect ,urinary 8-hydroxy-2' -deoxyguanosine ,business.industry ,Brief Report ,8-Hydroxy-2'-deoxyguanosine ,COVID-19 ,Infectious Diseases ,AcademicSubjects/MED00290 ,chemistry ,lipids (amino acids, peptides, and proteins) ,business - Abstract
Urine 11-dehydro-thromboxane B2 (u11-dh-TxB2), 8-hydroxy-2’-deoxyguanosine (8-OHdG), and liver-type fatty acid binding protein levels (L-FABP) at the time of hospitalization were higher in coronavirus disease 2019 (COVID-19) patients with adverse events vs without events. Higher u11-dh-TxB2 and L-FABP levels were associated with longer hospitalization, more thrombotic events, and greater mortality, providing evidence for potential utility as early prognostic biomarkers for COVID-19.
- Published
- 2021
49. First In-Human Experience With Inhaled Acetylsalicylic Acid for Immediate Platelet Inhibition
- Author
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Paul A. Gurbel, Rahul Chaudhary, Kevin P. Bliden, and Udaya S. Tantry
- Subjects
Aspirin ,Platelet aggregation ,business.industry ,Physiology (medical) ,medicine ,Platelet ,First in human ,Pharmacology ,Platelet inhibition ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Published
- 2020
50. Temporal Variability of Platelet Reactivity in Patients Treated with Clopidogrel or Ticagrelor
- Author
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Paul A. Gurbel, Young-Hoon Jeong, and Udaya S. Tantry
- Subjects
Platelet reactivity ,Text mining ,Editorial ,business.industry ,Internal Medicine ,Medicine ,Platelet ,Cardiology and Cardiovascular Medicine ,Bioinformatics ,business ,Phenotype ,Function (biology) - Published
- 2019
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