Publications by authors named "Udaya S Tantry"

253 Publications

Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes.

J Thromb Thrombolysis 2022 Jan 18. Epub 2022 Jan 18.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Lifebridge Health, Baltimore, MD, 21215, USA.

Diabetes mellitus (DM) is associated with a greater risk of COVID-19 and an increased mortality when the disease is contracted. Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear. Our aim was to explore the effects of metformin on markers of inflammation, oxidative stress, and hypercoagulability, and on clinical outcomes. Patients with DM on metformin (n = 34) and metformin naïve (n = 41), and patients without DM (n = 73) were enrolled within 48 h of hospital admission for COVID-19. Patients on metformin compared to naïve patients had a lower white blood cell count (p = 0.02), d-dimer (p = 0.04), urinary 11-dehydro thromboxane B (p = 0.01) and urinary liver-type fatty acid binding protein (p = 0.03) levels and had lower sequential organ failure assessment score (p = 0.002), and intubation rate (p = 0.03), fewer hospitalized days (p = 0.13), lower in-hospital mortality (p = 0.12) and lower mortality plus nonfatal thrombotic event occurrences (p = 0.10). Patients on metformin had similar clinical outcomes compared to patients without DM. In a multiple regression analysis, metformin use was associated with less days in hospital and lower intubation rate. In conclusion, metformin treatment in COVID-19 patients with DM was associated with lower markers of inflammation, renal ischemia, and thrombosis, and fewer hospitalized days and intubation requirement. Further focused studies are required to support these findings.
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http://dx.doi.org/10.1007/s11239-022-02631-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764325PMC
January 2022

Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium.

Nat Rev Cardiol 2022 Jan 13. Epub 2022 Jan 13.

Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

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.
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http://dx.doi.org/10.1038/s41569-021-00665-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757397PMC
January 2022

Measurement of Anticoagulation in Patients on Dabigatran, Rivaroxaban, and Apixaban Therapy by Novel Automated Thrombelastography.

TH Open 2021 Oct 9;5(4):e570-e576. Epub 2021 Nov 9.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, Maryland, United States.

 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).  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.  A total of 189 patients were included, (  = 50) on apixaban, (  = 62) on rivaroxaban, (  = 53) on dabigatran, and (  = 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,  < 0.0001). Using the antifactor Xa (AFXa) channel, R-time demonstrated strong nonlinear correlation with rivaroxaban and apixaban levels (  = 0.92 and 0.84, respectively,  < 0.0001 for both). R-time revealed strong sensitivity and NPV in detecting low DOAC levels for the predefined concentrations.  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.
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http://dx.doi.org/10.1055/a-1692-1415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718262PMC
October 2021

Aspirin as an Adjunctive Pharmacologic Therapy Option for COVID-19: Anti-Inflammatory, Antithrombotic, and Antiviral Effects All in One Agent.

J Exp Pharmacol 2021 7;13:957-970. Epub 2021 Dec 7.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, LifeBridge Health, Baltimore, MD, USA.

Introduction: 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 150-325 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.
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http://dx.doi.org/10.2147/JEP.S330776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665864PMC
December 2021

In vitro evidence for the role of cytokine storm in the generation of stent thrombosis in COVID -19 patients.

Cardiovasc Revasc Med 2021 Dec 2. Epub 2021 Dec 2.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Lifebridge Health, Baltimore, MD, USA.

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http://dx.doi.org/10.1016/j.carrev.2021.11.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635684PMC
December 2021

Is clopidogrel as the P2Y inhibitor a wise choice for long-term monotherapy in patients undergoing stenting?

EuroIntervention 2021 Dec 3;17(11):e865-e866. Epub 2021 Dec 3.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA.

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http://dx.doi.org/10.4244/EIJV17I11A144DOI Listing
December 2021

Further evidence for the use of aspirin in COVID-19.

Int J Cardiol 2022 01 12;346:107-108. Epub 2021 Nov 12.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Lifebridge Health, Baltimore, MD, USA.

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http://dx.doi.org/10.1016/j.ijcard.2021.11.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585554PMC
January 2022

Association Between Thrombogenicity Indices and Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction.

JACC Basic Transl Sci 2021 Sep-Oct;6(9-10):749-761. Epub 2021 Oct 25.

Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, South Korea.

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.
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http://dx.doi.org/10.1016/j.jacbts.2021.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559320PMC
October 2021

The role of viscoelastic testing in assessing peri-interventional platelet function and coagulation.

Platelets 2021 Aug 9:1-11. Epub 2021 Aug 9.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA.

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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http://dx.doi.org/10.1080/09537104.2021.1961709DOI Listing
August 2021

Thrombogenicity markers for early diagnosis and prognosis in COVID-19: a change from the current paradigm?

Blood Coagul Fibrinolysis 2021 Dec;32(8):544-549

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Lifebridge Health, Baltimore, Maryland.

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) (P ≤ 0.003 for all). The presence of high TEG-6 s 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 (P ≤ 0.001 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) = 2.9, P = 0.03], diabetes (OR = 3.3, P = 0.02) and FCS > 40 mm (OR = 3.4, P = 0.02). 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.
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http://dx.doi.org/10.1097/MBC.0000000000001069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630843PMC
December 2021

First Experience Addressing the Prognostic Utility of Novel Urinary Biomarkers in Patients With COVID-19.

Open Forum Infect Dis 2021 Jul 26;8(7):ofab274. Epub 2021 May 26.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Lifebridge Health, Baltimore, Maryland, USA.

Urine 11-dehydro-thromboxane B (u11-dh-TxB), 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-TxB 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.
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http://dx.doi.org/10.1093/ofid/ofab274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194603PMC
July 2021

Effects of Monotherapy with Clopidogrel vs. Aspirin on Vascular Function and Hemostatic Measurements in Patients with Coronary Artery Disease: The Prospective, Crossover I-LOVE-MONO Trial.

J Clin Med 2021 Jun 20;10(12). Epub 2021 Jun 20.

Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon 51472, Korea.

Objectives: To evaluate the effect of clopidogrel vs. aspirin monotherapy on vascular function and hemostatic measurement.

Background: Monotherapy with P2Y receptor inhibitor vs. aspirin can be a useful alterative to optimize clinical efficacy and safety in high-risk patients with coronary artery disease (CAD).

Methods: We performed a randomized, open-label, two-period crossover study in stented patients receiving at least 6-month of dual antiplatelet therapy (DAPT). Thirty CAD patients with moderate-to-high ischemic risk were randomly assigned to receive either 75 mg of clopidogrel or 100 mg of aspirin daily for 4 weeks, and were crossed over to the other strategy for 4 weeks. Vascular function was evaluated with reactive hyperemia-peripheral arterial tonometry (RH-PAT) and brachial-ankle pulse wave velocity (baPWV). Hemostatic profiles were measured with VerifyNow and thromboelastography (TEG). The primary endpoint was the reactive hyperemia index (RHI) during clopidogrel or aspirin monotherapy.

Results: Clopidogrel vs. aspirin monotherapy was associated with better endothelial function (RHI: 2.11 ± 0.77% vs. 1.87 ± 0.72%, = 0.045), lower platelet reactivity (130 ± 64 vs. 214 ± 50 P2Y12 reaction unit [PRU], < 0.001) and prolonged reaction time (TEG R: 5.5 ± 1.2 vs. 5.1 ± 1.1 min, = 0.037). In multivariate analysis, normal endothelial function (RHI ≥ 2.1) was significantly associated with clot kinetics (TEG angle ≤ 68 degree) and 'PRU ≤ 132'. 'PRU ≤ 132' was achieved in 46.2% vs. 3.8% during clopidogrel administration vs. aspirin monotherapy (odds ratio 21.4, 95% confidence interval 2.7 to 170.1, < 0.001).

Conclusions: In CAD patients, clopidogrel vs. aspirin monotherapy was associated with better endothelial function, greater platelet inhibition and lower coagulation activity, suggesting pleiotropic effects of clopidogrel on endothelial function and hemostatic profiles.
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http://dx.doi.org/10.3390/jcm10122720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235752PMC
June 2021

Clinical validation of AggreGuide A-100 ADP, a novel assay for assessing the antiplatelet effect of oral P2Y antagonists.

J Thromb Thrombolysis 2021 Jul 18;52(1):272-280. Epub 2021 Jun 18.

PCS Houston LLC, Houston, TX, USA.

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 inhibitors possessing known differences in antiplatelet potencies. Trial registration ClinicalTrials.gov Identifier: NCT3111420.
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http://dx.doi.org/10.1007/s11239-021-02498-0DOI Listing
July 2021

Platelet Reactivity and Coagulation Markers in Patients with COVID-19.

Adv Ther 2021 07 4;38(7):3911-3923. Epub 2021 Jun 4.

Faculdade de Medicina, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil.

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 < 53 AUC), arachidonic acid (MEA-ASPI, low PR < 86 AUC) and thrombin receptor-activating peptide 6 (MEA-TRAP, low PR < 97 AUC) in both groups.

Results: The rates of low PR with MEA-ADP were 27.5% in the COVID-19 group and 21.7% in the control group (OR = 1.60, p = 0.20); with MEA-ASPI, the rates were, respectively, 37.5% and 22.5% (OR = 3.67, p < 0.001); and with MEA-TRAP, the incidences were 48.5% and 18.8%, respectively (OR = 9.58, p < 0.001). Levels of D-dimer, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) were higher in the COVID-19 group in comparison with the control group (all p < 0.05). Thromboelastometry was utilized in a subgroup of patients and showed a hypercoagulable state in the COVID-19 group.

Conclusion: Patients hospitalized with non-severe COVID-19 had lower PR compared to healthy controls, despite having higher levels of D-dimer, fibrinogen, and PAI-1, and hypercoagulability by thromboelastometry.

Trial Registration: ClinicalTrials.gov identifier, NCT04447131.
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http://dx.doi.org/10.1007/s12325-021-01803-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176448PMC
July 2021

International COVID-19 thrombosis biomarkers colloquium: COVID-19 diagnostic tests.

J Thromb Thrombolysis 2021 Nov 22;52(4):992-998. Epub 2021 May 22.

Cardiovascular Research Unit, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.

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http://dx.doi.org/10.1007/s11239-021-02465-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140326PMC
November 2021

Ethnic Difference of Thrombogenicity in Patients with Cardiovascular Disease: a Pandora Box to Explain Prognostic Differences.

Korean Circ J 2021 Mar;51(3):202-221

Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Korea.

Arterial and venous atherothrombotic events are finely regulated processes involving a complex interplay between vulnerable blood, vulnerable vessel, and blood stasis. Vulnerable blood ('thrombogenicity') comprises complex interactions between cellular components and plasma factors (inflammatory, procoagulant, anticoagulant, and fibrinolytic factors). The extent of thrombogenicity may determine the progression of atheroma and the clinical manifestation of atherothrombotic events, with the highest thrombogenicity in African Americans and lowest in East Asians. Inherent thrombogenicity may influence clinical efficacy and safety of specific antithrombotic treatments in high-risk patients, which may in part explain the observation that East Asian patients have reduced anti-ischemic benefits and elevated bleeding risk with antithrombotic therapy compared to Caucasian patients. In this review, we discuss available evidence regarding the racial differences in thrombogenicity and its impact on clinical outcomes among patients with atherosclerotic cardiovascular disease.
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http://dx.doi.org/10.4070/kcj.2020.0537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925962PMC
March 2021

Is a personalized pharmacotherapeutic approach closed for acute coronary syndrome?

Expert Opin Pharmacother 2021 Apr 31;22(5):527-529. Epub 2021 Jan 31.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA.

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http://dx.doi.org/10.1080/14656566.2021.1877659DOI Listing
April 2021

Pharmacodynamic Profile and Prevalence of Bleeding Episode in East Asian Patients with Acute Coronary Syndromes Treated with Prasugrel Standard-Dose versus De-escalation Strategy: A Randomized A-MATCH Trial.

Thromb Haemost 2021 Oct 5;121(10):1376-1386. Epub 2021 Jan 5.

Division of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.

Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg ( = 255) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group ( = 85) compared with the 5-mg ( = 83) and PFT-guided groups ( = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30-1.14 and 0.28-1.09, respectively). "PRU < 127" was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543-0.689;  = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28-3.03;  = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes. REGISTRATION:  URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.
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http://dx.doi.org/10.1055/a-1346-3300DOI Listing
October 2021

Race-Related disparities in COVID-19 thrombotic outcomes: Beyond social and economic explanations.

EClinicalMedicine 2020 Dec 20;29:100647. Epub 2020 Nov 20.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, United States.

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http://dx.doi.org/10.1016/j.eclinm.2020.100647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678450PMC
December 2020

The East Asian Paradox: An Updated Position Statement on the Challenges to the Current Antithrombotic Strategy in Patients with Cardiovascular Disease.

Thromb Haemost 2021 Apr 10;121(4):422-432. Epub 2020 Nov 10.

Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, South Korea.

East Asian patients have reduced anti-ischemic benefits and increased bleeding risk during antithrombotic therapies compared with Caucasian patients. As potent P2Y receptor inhibitors (e.g., ticagrelor and prasugrel) and direct oral anticoagulants are commonly used in current daily practice, the unique risk-benefit trade-off in East Asians has been a topic of emerging interest. In this article, we propose updated evidence and future directions of antithrombotic treatment in East Asian patients.
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http://dx.doi.org/10.1055/s-0040-1718729DOI Listing
April 2021

Defining platelet response to acetylsalicylic acid: the relation between inhibition of serum thromboxane B and agonist-induced platelet aggregation.

J Thromb Thrombolysis 2021 Feb 10;51(2):260-264. Epub 2020 Nov 10.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, 21215, USA.

Arachidonic acid (AA)-induced platelet aggregation (PA) and serum thromboxane B (TxB) 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 TxB inhibition. We serially measured AA-PA (conventional aggregation), serum TxB plasma ASA and salicylic acid (SA) (liquid chromatography-mass spectrometry), and urinary 11-dehydro thromboxane B (u11-dh TxB) (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 TxB (31-680 ng/mL) as compared to maximal AA-PA (65-81%) and u11-dh TxB (1556-4440 pg/mg creatinine). The relation between serum TxB inhibition and AA-PA was stepwise; after 30-40% inhibition of serum TxB, AA-PA fell to < 5%. By receiver operating characteristic curve analysis using AA-PA < 5% to define aspirin responsiveness, serum TxB2 inhibition > 49% and u11-dh TxB2 < 1520 pg/mg creatinine met the definition. Our study demonstrates a non-linear relation between serum TxB inhibition and AA-PA. Aggregation was nil once TxB inhibition reached > 49%. Moreover, these results suggest that the definition of > 95% inhibition of serum TxB 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.
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http://dx.doi.org/10.1007/s11239-020-02334-xDOI Listing
February 2021

Quantification of antibody avidities and accurate detection of SARS-CoV-2 antibodies in serum and saliva on plasmonic substrates.

Nat Biomed Eng 2020 12 29;4(12):1188-1196. Epub 2020 Oct 29.

Department of Chemistry and Bio-X, Stanford University, Stanford, CA, USA.

Accurate assays for the detection of antibodies to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) are essential for the control of the COVID-19 (coronavirus disease 2019) pandemic. Here, we report antibody and antibody-avidity assays, relying on near-infrared-fluorescence amplification by nanostructured plasmonic gold substrates, for the simultaneous detection of antibodies to the S1 subunit of the spike protein and to the receptor binding domain of SARS-CoV-2 in human serum and saliva, and for quantifying immunoglobulin avidities against coronavirus antigens from SARS-CoV-2, SARS-CoV-1 and the common-cold viruses OC43, HKU1, NL63 and 229E. The antibody assay detected immunoglobulin M in 87% (52 of 60) COVID-19-positive serum samples collected 6 or more days after symptom onset (and the immunoglobulins M and G in all 33 samples collected at least 15 days after symptom onset), and correctly classified 456 out of the 457 COVID-19-negative serum samples tested (424 of them collected before the pandemic, including 73 that were positive for other viruses). We used the antibody-avidity assay to study antibody-maturation patterns, anamnestic responses, and cross-immunity to the common-cold coronaviruses.
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http://dx.doi.org/10.1038/s41551-020-00642-4DOI Listing
December 2020

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines.

Cardiol J 2020 19;27(6):661-676. Epub 2020 Oct 19.

Pavia, Italy.

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.
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http://dx.doi.org/10.5603/CJ.a2020.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079117PMC
September 2021

First In-Human Experience With Inhaled Acetylsalicylic Acid for Immediate Platelet Inhibition: Comparison With Chewed and Swallowed Acetylsalicylic Acid.

Circulation 2020 09 28;142(13):1305-1307. Epub 2020 Sep 28.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047477DOI Listing
September 2020

Viscoelastic properties of clot formation and their clinical impact in East Asian versus Caucasian patients with stable coronary artery disease: a COMPARE-RACE analysis.

J Thromb Thrombolysis 2021 Feb;51(2):454-465

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, 21215, USA.

Compared with Caucasian patients, East Asian patients with coronary artery disease (CAD) have demonstrated better clinical outcomes. We sought to compare the viscoelastic properties of clot formation and their impact on clinical outcomes in East Asian vs. Caucasian patients. We analyzed age- and sex-matched East Asian and Caucasian patients with stable CAD (n = 249 each). Viscoelastic properties of clot formation were assessed with thromboelastography (TEG), and 3-year clinical outcomes were recorded. Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular death, myocardial infarction, or stroke. Compared with Caucasians, East Asians showed lower platelet-fibrin clot strength (PFCS) (maximum amplitude [MA]: 61.8 ± 7.9 vs. 65.4 ± 5.0 mm, p < 0.001). In a multivariate analysis, high PFCS (defined as MA ≥ 68 mm) was significantly associated with MACE occurrence (odds ratio 6.27, 95% CI 2.41 to 16.30, p < 0.001). East Asians vs. Caucasians had lower prevalence of high PFCS (odds ratio 0.50, 95% CI 0.27 to 0.93, p = 0.028). In conclusion, this is the first study to demonstrate different viscoelastic properties of clot between East Asian and Caucasian patients with stable CAD. The platelet-fibrin clot strength was significantly associated with MACE in these patients and was significantly lower in East Asians. Future studies are warranted to further explore the mechanistic explanation and clinical importance of these findings.
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http://dx.doi.org/10.1007/s11239-020-02240-2DOI Listing
February 2021

Another Unmet Need against Residual Risk of Atherosclerotic Cardiovascular Disease: Can "Thrombin Pathway" Be a New Target for Therapy?

Korean Circ J 2020 Sep;50(9):817-821

Department of Internal Medicine, Gyeongsang National University School of Medicine and Cardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, Korea.

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http://dx.doi.org/10.4070/kcj.2020.0287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440994PMC
September 2020

Meta-Analysis of the Usefulness of Therapeutic Hypothermia After Cardiac Arrest.

Am J Cardiol 2020 10 24;133:48-53. Epub 2020 Jul 24.

Department of Medicine, Sinai Hospital of Baltimore, Baltimore, Maryland; Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland.

Despite current guidelines recommending therapeutic hypothermia (TH) for post cardiac arrest comatose patient, its use remains limited. Randomized controlled trials (RCTs) have also reported conflicting results on the efficacy of TH. Therefore, we conducted an updated meta-analysis to evaluate the effect of TH in post cardiac arrest patients. We searched electronic databases for RCTs comparing TH (32°C to 34°C) with controls (normothermia or temperature ≥36°C) in comatose patients who sustained cardiac arrest. Mortality and neurological outcomes were the outcomes of interest. We used random effect meta-analysis to estimate risk ratio (RR) with 95% confidence interval (CI). Eight RCTs with a total of 2,026 patients (TH n = 1,025 and control n = 1,001) were included. Irrespective of initial rhythm, TH was associated with significant reduction in poor neurological outcomes (RR 0.87, 95% CI 0.77 to 0.98; p = 0.02) without any difference in mortality (RR 0.94, 95% CI 0.85 to 1.03; p = 0.17). In patients with initial shockable rhythm compared with control, TH reduced mortality (RR 0.85, 95% CI 0.73 to 0.99; p = 0.04) and poor neurological outcomes (RR 0.81, 95% CI 0.67 to 0.99; p = 0.04). Whereas, in patients with initial nonshockable rhythm, TH was associated with decreased poor neurological outcomes after excluding one trial (RR 0.95 95% CI 0.91 to 1.00; p = 0.05). In conclusion, TH is associated with improved neurological outcomes in all patients sustaining cardiac arrest and with decreased mortality in patients with initial shockable rhythm.
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http://dx.doi.org/10.1016/j.amjcard.2020.07.038DOI Listing
October 2020
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