Person: Korjian, Serge
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Korjian
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Serge
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Korjian, Serge
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Publication Comparison of Fatal or Irreversible Events With Extended‐Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely Ill Medical Patients: An APEX Trial Substudy(John Wiley and Sons Inc., 2017) Gibson, Charles; Korjian, Serge; Chi, Gerald; Daaboul, Yazan; Jain, Purva; Arbetter, Douglas; Goldhaber, Samuel; Hull, Russel; Hernandez, Adrian F.; Lopes, Renato D.; Gold, Alex; Cohen, Alexander T.; Harrington, Robert A.Background: Extended‐duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. Methods and Results: This was a post hoc analysis of the APEX trial—a multicenter, double‐blind, randomized controlled trial comparing extended‐duration betrixaban versus standard‐of‐care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time‐to‐first event analysis. In patients with positive D‐dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). Conclusions: Among hospitalized medically ill patients, extended‐duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard‐duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.Publication d-Dimer elevation and adverse outcomes(Springer US, 2014) Halaby, Rim; Popma, Christopher J.; Cohen, Ander; Chi, Gerald; Zacarkim, Marcelo Rodrigues; Romero, Gonzalo; Goldhaber, Samuel; Hull, Russell; Hernandez, Adrian; Mentz, Robert; Harrington, Robert; Lip, Gregory; Peacock, Frank; Welker, James; Martin-Loeches, Ignacio; Daaboul, Yazan; Korjian, Serge; Gibson, Charlesd-Dimer is a biomarker of fibrin formation and degradation. While a d-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated d-dimer with adverse outcomes has received far less emphasis. An elevated d-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated d-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the d-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.Publication Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I)(Lippincott Williams & Wilkins, 2016) Michael Gibson, C.; Korjian, Serge; Tricoci, Pierluigi; Daaboul, Yazan; Yee, Megan; Jain, Purva; Alexander, John; Steg, P. Gabriel; Lincoff, A. Michael; Kastelein, John J.P.; Mehran, Roxana; D’Andrea, Denise M.; Deckelbaum, Lawrence I.; Merkely, Bela; Zarebinski, Maciej; Ophuis, Ton Oude; Harrington, Robert A.Background: Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein–mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction. Methods: The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy). Results: A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar. Conclusions: Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02108262.Publication Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy(Lippincott Williams & Wilkins, 2016) Gibson, Charles; Pinto, Duane; Chi, Gerald; Arbetter, Douglas; Yee, Megan; Mehran, Roxana; Bode, Christoph; Halperin, Jonathan; Verheugt, Freek W.A.; Wildgoose, Peter; Burton, Paul; van Eickels, Martin; Korjian, Serge; Daaboul, Yazan; Jain, Purva; Lip, Gregory Y.H.; Cohen, Marc; Peterson, Eric D.; Fox, Keith A.A.Background: Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable impact on all-cause mortality and the need for rehospitalization. Methods: Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y12 inhibitor for 12 months (group 1); rivaroxaban 2.5 mg twice daily with stratification to a prespecified duration of DAPT of 1, 6, or 12 months (group 2); or the reference arm of dose-adjusted VKA daily with a similar DAPT stratification (group 3). The present post hoc analysis assessed the end point of all-cause mortality or recurrent hospitalization for an adverse event, which was further classified as the result of bleeding, a cardiovascular cause, or another cause blinded to treatment assignment. Results: The risk of all-cause mortality or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95% confidence interval, 0.66–0.94; P=0.008 versus group 3; number needed to treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62–0.90; P=0.002 versus group 3; number needed to treat=10), and 41.9% in group 3 (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from bleeding (group 1=8.6% [P=0.032 versus group 3], group 2=8.0% [P=0.012 versus group 3], and group 3=12.4%) and all-cause death plus rehospitalization potentially resulting from a cardiovascular cause (group 1=21.4% [P=0.001 versus group 3], group 2=21.7% [P=0.011 versus group 3], and group 3=29.3%) were reduced in the rivaroxaban arms compared with the VKA arm, but other forms of rehospitalization were not. Conclusions: Among patients with atrial fibrillation undergoing intracoronary stenting, administration of either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy or 2.5 mg rivaroxaban twice daily plus DAPT was associated with a reduced risk of all-cause mortality or recurrent hospitalization for adverse events compared with standard-of-care VKA plus DAPT. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830543.Publication Medical education in a foreign language and history-taking in the native language in Lebanon – a nationwide survey(BioMed Central, 2016) Abi Raad, Vanda; Raad, Kareem; Daaboul, Yazan; Korjian, Serge; Asmar, Nadia; Jammal, Mouin; Aoun Bahous, SolaBackground: With the adoption of the English language in medical education, a gap in clinical communication may develop in countries where the native language is different from the language of medical education. This study investigates the association between medical education in a foreign language and students’ confidence in their history-taking skills in their native language. Methods: This cross-sectional study consisted of a 17-question survey among medical students in clinical clerkships of Lebanese medical schools. The relationship between the language of medical education and confidence in conducting a medical history in Arabic (the native language) was evaluated (n = 457). Results: The majority (88.5%) of students whose native language was Arabic were confident they could conduct a medical history in Arabic. Among participants enrolled in the first clinical year, high confidence in Arabic history-taking was independently associated with Arabic being the native language and with conducting medical history in Arabic either in the pre-clinical years or during extracurricular activities. Among students in their second clinical year, however, these factors were not associated with confidence levels. Conclusions: Despite having their medical education in a foreign language, the majority of students in Lebanese medical schools are confident in conducting a medical history in their native language.Publication Etiology of End-Stage Renal Disease and Arterial Stiffness among Hemodialysis Patients(Hindawi Publishing Corporation, 2017) El Ghoul, Balsam; Daaboul, Yazan; Korjian, Serge; El Alam, Andrew; Mansour, Anthony; Hariri, Essa; Samad, Salam; Salameh, Pascale; Dahdah, Georges; Blacher, Jacques; Safar, Michel E.; Aoun Bahous, SolaBackground:. Prior studies have demonstrated that conventional and emerging CV risk factors are associated with worsening arterial stiffness among end-stage renal disease (ESRD) patients on hemodialysis. The present cross-sectional study evaluates the association between the etiology of ESRD and arterial stiffness among a cohort of hemodialysis patients. Methods. Etiology of ESRD was identified from patients' medical records and classified as either vascular renal disease, diabetic nephropathy, nondiabetic glomerulopathy, tubular interstitial nephropathy, hereditary nephropathy, or ESRD of unconfirmed etiology. Results. A total of 82 subjects were enrolled. cfPWV was independently associated with the composite of either diabetic nephropathy or vascular renal disease (p = 0.022), pulse pressure (p = 0.001), and a history of CV events (p = 0.025), but not history of hypertension or diabetes mellitus alone. The median cfPWVs in diabetic nephropathy and vascular renal disease were comparable and significantly higher than median cfPWVs in other etiologies of ESRD. Conclusion. The study suggests that the etiology of ESRD is independently associated with arterial stiffness among hemodialysis patients. Furthermore, arterial stiffness was higher among patients who developed renal sequelae of either diabetes mellitus or hypertension as compared with those who have a history of either diabetes mellitus or hypertension alone.