Marc Cohen

Beth Israel Medical Center, New York City, New York, United States

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Publications (145)1210.96 Total impact

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    ABSTRACT: Carotid Duplex Ultrasonography (CDUS) is one of the non-invasive imaging modalities used to evaluate for carotid artery stenosis. However, it is often used in patients with coronary artery disease (CAD), peripheral artery disease (PAD), before heart surgery, syncope and non-specific neurological symptoms although its value is unclear. Our study aimed to further investigate the yield of CDUS in these conditions. A retrospective analysis was conducted on 827 consecutive carotid ultrasounds ordered between March 2013 and August 2013 at Newark Beth Israel Medical Center. Clinical characteristics such as age, sex, smoking status, systemic hypertension, diabetes mellitus, CAD, PAD, carotid bruit and indications for carotid ultrasound were included. Significant cerebrovascular disease (sCBVD) was defined as greater than or equal to 50% diameter reduction in internal carotid arteries (ICA) or any degree of occlusion in vertebrobasilar system. Only 88 out of 827 (10.6%) patients had sCBVD. Using logistic regression analysis we identified age greater than 65 years (OR 2.1, 95% CI 1.2 to 3.7; P = 0.006), carotid bruit (OR 7.8, 95% CI 3.6 to 16.6; P <0.001) and history of prior carotid endarterectomy or carotid artery stenting (OR 5.8, 95% CI 2.3 to 14.8; P <0.001) as significant predictors of sCBVD. Significant carotid artery stenosis is more likely in patients 65 years and older, presence of carotid bruit and prior CEA. On the other hand, it has low diagnostic yield in less than 65-year-old individuals, syncope and non-focal neurological symptoms. This highlights the need for better risk prediction models in order to promote optimal utilization.
    Cardiovascular Ultrasound 11/2014; 12(1):48. · 1.28 Impact Factor
  • Marc Cohen, Deepa Iyer
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    ABSTRACT: Acute coronary syndrome (ACS) is a medical emergency often associated with an occlusive coronary event with consequent myocardial underperfusion. Patients require immediate antiplatelet therapy and long-term antithrombotic prophylaxis to reduce the risk of recurrence. Acetylsalicylic acid alone or in combination with a platelet P2Y12 inhibitor (dual antiplatelet therapy) has become the clinically accepted antithrombotic prophylaxis for patients post ACS. Historically, studies assessing the utility of adding oral anticoagulants have not demonstrated a clinical benefit with regard to acceptable bleeding risk. Studies with vitamin K antagonists such as warfarin demonstrated a potential to reduce the risk for subsequent death by reinfarction but this benefit was offset by increases in bleeding. Results from studies of two targeted non-vitamin K antagonist oral anticoagulants also proved disappointing, with little or no apparent reduction in the rate of ischemic events seen. However, the recent ATLAS studies assessing rivaroxaban (an oral Factor Xa inhibitor) in patients with ACS demonstrated a reduction in the composite endpoint of deaths from cardiovascular causes, myocardial infarction, or stroke, and a reduction in the rate of stent thrombosis. This review provides an overview of the pivotal studies in which the addition of oral anticoagulants to antiplatelet therapy (the so-called 'dual-pathway' approach) has been investigated for the management of patients post ACS, and considers the results of the ATLAS studies and their potential impact on the management of patients after an acute event. This article is protected by copyright. All rights reserved.
    Cardiovascular Therapeutics 06/2014; · 2.85 Impact Factor
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    ABSTRACT: P2Y12 receptor antagonist therapy is recommended in addition to ASA for up to 1 year after acute coronary syndrome to reduce ischemic events. In contrast, the benefit of long-term dual antiplatelet therapy beyond 1 year remains unclear. Ticagrelor is a potent, reversibly binding P2Y12 receptor-antagonist that has been shown to be superior to clopidogrel in patients with acute coronary syndromes for up to 1 year. PEGASUS-TIMI 54 is a randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor in addition to aspirin (75-150 mg) for the prevention of major adverse cardiovascular events in patients with a history of myocardial infarction and risk factors. Patients with a history of spontaneous myocardial infarction within 1 to 3 years are randomized in a 1:1:1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or matching placebo, all with low dose ASA, until the end of the study. The primary endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. Recruitment began in October 2010 and completed in April 2013 with a sample size of over 21,000 patients. The trial is planned to continue until the latest of either 1,360 adjudicated primary end points are accrued or the last patient randomized has been followed for at least 12 months. PEGASUS-TIMI 54 is investigating whether the addition of intensive antiplatelet therapy with ticagrelor to low-dose aspirin reduces major adverse cardiovascular events in high-risk patients with a history of myocardial infarction.
    American heart journal 04/2014; 167(4):437-444.e5. · 4.56 Impact Factor
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    ABSTRACT: Intravenous enoxaparin did not reduce significantly the primary end point (p = 0.06) compared with unfractionated heparin (UFH) in the randomized Acute Myocardial Infarction Treated with primary angioplasty and intravenous enoxaparin Or unfractionated heparin to Lower ischemic and bleeding events at short- and Long-term follow-up (ATOLL) trial. We present the results of the prespecified per-protocol analysis excluding patients who did not receive the treatment allocated by randomization or received both enoxaparin and UFH. We evaluated all-cause mortality, complication of myocardial infarction, procedural failure, or major bleeding (primary end point) and all-cause mortality, recurrent acute coronary syndrome, or urgent revascularization (main secondary end point). Baseline and procedural characteristics were well balanced between the 2 treatment groups. Of 910 randomized patients, 795 patients (87.4%) were treated according to the protocol with consistent anticoagulation using intravenous enoxaparin (n = 400) or UFH (n = 395). Enoxaparin reduced significantly the rates of the primary end point (relative risk [RR] 0.76, 95% confidence interval [CI] 0.62 to 0.94, p = 0.012) and the main secondary end point (RR 0.37, 95% CI 0.22 to 0.63, p <0.0001). There was less major bleeding with enoxaparin (RR 0.46, 95% CI 0.21 to 1.01, p = 0.050) contributing to the significant improvement of the net clinical benefit (RR 0.46, 95% CI 0.3 to 0.74, p = 0.0002). All-cause mortality was also reduced with enoxaparin (RR 0.36, 95% CI 0.18 to 0.74, p = 0.003). In conclusion, in the per-protocol analysis of the ATOLL trial, pertinent to >87% of the study population, enoxaparin was superior to UFH in reducing ischemic end points and mortality.
    The American journal of cardiology 09/2013; 112(9). · 3.58 Impact Factor
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    ABSTRACT: IMPORTANCE The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial. OBJECTIVE To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, active-controlled superiority trial that enrolled 13 229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection. INTERVENTIONS Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURES The primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7. RESULTS Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P = .93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P < .001). Results were consistent across prespecified subgroups. CONCLUSIONS AND RELEVANCE Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention. TRIAL REGISTRATION Identifier: NCT01076764.
    JAMA The Journal of the American Medical Association 09/2013; · 29.98 Impact Factor
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    ABSTRACT: OBJECTIVES: To determine if rivaroxaban is associated with a reduction in stent thrombosis among ACS subjects in the ATLAS ACS 2-TIMI 51 trial. BACKGROUND: Dual antiplatelet therapy has been the mainstay of efforts to prevent stent thrombosis. Since thrombin is a potent stimulant of platelet activation, we hypothesized that inhibition of thrombin generation via factor Xa inhibition may further reduce the risk of stent thrombosis. METHODS: ATLAS ACS 2-TIMI 51 was a placebo-controlled trial that randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. RESULTS: Among subjects who had a stent placed prior to or at the time of the index event, rivaroxaban significantly reduced independently adjudicated Academic Research Consortium (ARC) definite and probable stent thrombosis in the pooled (1.9% vs. 1.5%, HR 0.65, p=0.017) and the 2.5 mg BID (1.9% vs. 1.5%, HR 0.61, p=0.023) treatment groups when compared to placebo, with a trend toward a reduction in the 5 mg BID treatment group (1.9% vs. 1.5%, HR 0.70, p=0.089). Among subjects who received both aspirin and a thienopyridine (Stratum 2), the benefit of rivaroxaban emerged during the period of active treatment with dual antiplatelet therapy (HR 0.68, 95% CI 0.50-0.92, combined rivaroxaban group vs. placebo). Among stented subjects who were treated with dual antiplatelet therapy, there was a mortality reduction among those treated with 2.5 mg BID of rivaroxaban (HR 0.56, 95% CI 0.35-0.89, p=0.014). CONCLUSIONS: Among stented ACS patients treated with dual antiplatelet therapy, the administration of 2.5 mg BID of rivaroxaban is associated with a reduction in stent thrombosis and mortality. CLINICAL TRIAL ID: NCT00809965.
    Journal of the American College of Cardiology 04/2013; · 15.34 Impact Factor
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    ABSTRACT: The use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) in high-risk patients with acute coronary syndromes has been associated with reductions in ischemic events but increases in bleeding complications. The role of GPIs in patients who undergo primary percutaneous coronary intervention (PCI) by the transradial approach (TRA) is not well studied. The aim of this post hoc analysis from the randomized prospective Acute Myocardial Infarction Treated With Primary Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin to Lower Ischemic and Bleeding Events at Short- and Long-Term Follow-Up (ATOLL) trial was to assess the safety and efficacy of GPIs in primary PCI performed using the TRA. A total of 910 patients were enrolled in ATOLL; 522 patients (67%) underwent PCI using the TRA. Two comparative analyses were performed. First, patients who underwent PCI using the TRA who received GPIs were compared with those who did not receive GPIs. Second, patients who underwent PCI using the TRA who received GPIs were compared with those who underwent PCI using a nonradial route and received GPIs. Composite end points of net clinical benefit, ischemic outcomes, and safety consisting of bleeding and transfusion at 1 month were analyzed. A propensity score was constructed, and weight adjustment were made for variables, including but not limited to age, weight, gender, renal function, concomitant use of other medications, Killip class, and medical history, when analyzing the end points. There was no significant difference in net clinical benefit or ischemic outcomes between either TRA patients with versus without GPIs or TRA patients with GPIs versus non-TRA patients with GPIs. Additionally, there were significantly fewer major bleeding events and blood transfusions in TRA patients with GPIs compared with non-TRA patients with GPIs. In conclusion, the addition of GPIs in the setting of primary PCI using the TRA was not associated with bleeding liability. The use of GPIs with TRA was associated with safer outcomes than using GPIs with a nontransradial approach. This study was limited in that it was a nonrandomized retrospective analysis.
    The American journal of cardiology 03/2013; · 3.58 Impact Factor
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    ABSTRACT: BACKGROUND: Vascular access complications remain the leading cause of morbidity after cardiac catheterization procedures. Fluoroscopy-guided vascular access has been recommended to reduce these complications. However, the use of current recommendations still results in arterial access above the inferior epigastric artery (IEA) (high stick) or below the common femoral artery (CFA) bifurcation (low stick). OBJECTIVES: The goal of our study was to evaluate the influence of patient characteristics like age, body mass index, and pelvic anatomy on current recommendations. METHODS: We prospectively collected clinical, anatomic, and angiographic data on 631 consecutive patients who underwent coronary and noncoronary procedures via CFA access. Anatomic location of IEA loop, CFA bifurcation, public tubercle (PT), and anterior superior iliac spine were identified in relationship to the femoral head Location of IEA loop was used as a surrogate for inguinal ligament (IL). RESULTS: Approximately 12% of patients had a low-lying IEA loop (group B). These patients had a significantly higher BMI compared with patients with IEA loop above the centerline of femoral head (group A) (P = 0.018). The anatomic location of PT was below the lower border of femoral head significantly more frequently in group B compared to group A (P < 0.0001). Fifteen percent of patients had a high CFA bifurcation. On clinical follow-up during index hospitalization, there was no significant difference between the two groups, in terms of complications including retroperitoneal hemorrhage, access site hematoma >5 cm, bleeding requiring transfusion or pseudoaneurysm. CONCLUSIONS: Anatomic location of PT on fluoroscopy can be used as an additional surrogate to predict the location of IL. Patients with high BMI have a low lying IL, which may predispose them to "high sticks." The location of IEA cannot be used as a surrogate for IL in all patients. © 2012 Wiley Periodicals, Inc.
    Catheterization and Cardiovascular Interventions 01/2013; · 2.51 Impact Factor
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    Zafar Iqbal, Gurinder Rana, Marc Cohen
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    ABSTRACT: Managing coronary thrombus is a challenging task and requires adequate knowledge of the various antithrombotic agents available. In this article, we will briefly analyze the risk-benefit profile of antithrombotic agents, with critical analysis of the scientific evidence available to support their use. Since thrombus consists of platelets and coagulation cofactors, an effective antithrombotic strategy involves using one anticoagulant with two or more antiplatelet agents. Unfractionated heparin traditionally has been the most commonly used anticoagulant but is fast being replaced by relatively newer agents like LMWH, direct thrombin inhibitors, and Factor Xa inhibitors. In recent years, the antiplatelet landscape has changed significantly with the availability of more potent and rapidly acting agents, like prasugrel and ticagrelor. These agents have demonstrated a sizeable reduction in ischemic outcomes in patients with ACS, who are treated invasively or otherwise, with some concern for an increased bleeding risk. Glycoprotein IIb/IIIa inhibitors have an established role in high risk NSTE ACS patients pretreated with dual antiplatelets, but its role in STEMI patients, treated with invasive approach and dual antiplatelets, has not been supported consistently across the studies. Additionally, in recent years, its place as a directly injected therapy into coronaries has been looked into with mixed results. In conclusion, a well-tailored antithrombotic strategy requires taking into account each patient's individual risk factors and clinical presentation, with an effort to strike balance between not only preventing ischemic outcomes but also reducing bleeding complications.
    Current Cardiology Reviews 08/2012;
  • Marc Cohen
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    ABSTRACT: Acute coronary syndrome (ACS) is a major health burden, resulting in increased hospital admissions and significant morbidity and mortality. Platelet activation, which leads to thrombin generation, is highly implicated in ACS, and antiplatelet agents represent the current standard of care. Established antiplatelet agents include acetylsalicylic acid (ASA), thienopyridines (clopidogrel, ticlopidine), and glycoprotein IIb/IIIa inhibitors. Recently, antiplatelet therapy for ACS has evolved to include more potent inhibitors (e.g., prasugrel, cangrelor, and ticagrelor). During the acute phase of an acute coronary event, both anticoagulation and dual antiplatelet therapy with aspirin and a thienopyridine are guideline recommended as first-line treatment. While anticoagulation is usually limited to the acute in-patient phase, dual antiplatelet therapy is recommended for 12 months. Despite the efficacy of antiplatelet agents in ACS, in many patients the residual risk of death from cardiac events, myocardial infarction, stroke, and refractory ischemia remains high. Dual therapy (i.e., ASA or clopidogrel plus a vitamin K antagonist [VKA]), and triple therapy (two antiplatelets plus a VKA) are associated with increases in bleeding complications. New oral anticoagulants that offer a novel mechanism of action may, when added to the current standard of care, provide a more comprehensive response to thrombin generation. In this review, we examine the pathology of ACS, investigate antiplatelet therapies and describe emerging anticoagulants that may be of benefit when used as combination therapy with antiplatelet agents for secondary prevention in ACS patients. (J Interven Cardiol 2012;25:425-432).
    Journal of Interventional Cardiology 05/2012; 25(5):425-32. · 1.50 Impact Factor
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    ABSTRACT: Our objective was to determine the association of activated partial thromboplastin time (aPTT) with recurrent ischemic events and non-coronary artery bypass surgery-related thrombolysis in myocardial infarction major bleeding. We studied 4,985 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) participating in SYNERGY, a prospective, randomized, international trial designed to emulate contemporary practice wherein unfractionated heparin (UFH) is given intravenously and titrated according to a weight-adjusted dosing nomogram to a target aPTT of 1.5-2 times the upper limit of normal (approximately 50-70 s). Aspirin was administered to 95% of patients, clopidogrel to 63%, and glycoprotein IIb/IIIa receptor inhibitors to 58%. More than 90% of patients underwent early coronary angiography, and 69% were revascularized. Used as a time-dependent covariate, aPTT was evaluated as a predictor of time to ischemic or major hemorrhagic events in proportional hazards regression models. Using discrete variable analysis, aPTT was categorized as persistently below a lower threshold of anticoagulation (<50 vs. ≥50 s) for recurrent ischemic events and above an upper threshold (>70 vs. ≤70 s) for major hemorrhagic events. UFH treatment lasted a median of 42 (30, 78) h. At >6-12 (n = 3,021), >12-24 (n = 3,406), and >24-48 (n = 2,497) h, 34, 41, and 46% of patients achieved the target aPTT range, respectively. Both before and after adjusting for baseline predictors of anticoagulant response and risk score (age, hypertension, diabetes, smoking, ST depression, and renal function), no significant relationship between aPTT values and recurrent ischemic events or major bleeding was found. No relationship was observed between clinical outcomes and aPTT values persistently above or below the designated thresholds. Measurements of aPTT were not associated with clinical outcomes among patients with NSTE ACS treated with UFH. The required intensity of anticoagulation for benefit may be relatively modest when UFH is administered concomitantly with dual or triple platelet-directed therapy, particularly in patients undergoing early coronary revascularization.
    Journal of Thrombosis and Thrombolysis 02/2012; 34(1):114-9. · 1.99 Impact Factor
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    ABSTRACT: To determine the efficacy and safety of enoxaparin compared with unfractionated heparin during percutaneous coronary intervention. Systematic review and meta-analysis. Medline and Cochrane database of systematic reviews, January 1996 to May 2011. Randomised and non-randomised studies comparing enoxaparin with unfractionated heparin during percutaneous coronary intervention and reporting on both mortality (efficacy end point) and major bleeding (safety end point) outcomes. Sample size, characteristics, and outcomes, extracted independently and analysed. 23 trials representing 30,966 patients were identified, including 10,243 patients (33.1%) undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction, 8750 (28.2%) undergoing secondary percutaneous coronary intervention after fibrinolysis, and 11,973 (38.7%) with non-ST elevation acute coronary syndrome or stable patients scheduled for percutaneous coronary intervention. A total of 13,943 patients (45.0%) received enoxaparin and 17,023 (55.0%) unfractionated heparin. Enoxaparin was associated with significant reductions in death (relative risk 0.66, 95% confidence interval 0.57 to 0.76; P<0.001), the composite of death or myocardial infarction (0.68, 0.57 to 0.81; P<0.001), and complications of myocardial infarction (0.75, 0.6 to 0.85; P<0.001), and a reduction in incidence of major bleeding (0.80, 0.68 to 0.95; P=0.009). In patients who underwent primary percutaneous coronary intervention, the reduction in death (0.52, 0.42 to 0.64; P<0.001) was particularly significant and associated with a reduction in major bleeding (0.72, 0.56 to 0.93; P=0.01). Enoxaparin seems to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention and particularly in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction.
    BMJ (online) 02/2012; 344:e553. · 16.38 Impact Factor
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    ABSTRACT: Low-molecular-weight heparins (LMWHs) have shown equivalent or superior efficacy and safety to unfractionated heparin as antithrombotic therapy for patients with acute coronary syndromes. Each approved LMWH is a pleotropic biological agent with a unique chemical, biochemical, biophysical and biological profile and displays different pharmacodynamic and pharmacokinetic profiles. As a result, LMWHs are neither equipotent in preclinical assays nor equivalent in terms of their clinical efficacy and safety. Previously, the US Food and Drug Administration (FDA) cautioned against using various LMWHs interchangeably, however recently, the FDA approved generic versions of LMWH that have not been tested in large clinical trials. This paper highlights the bio-chemical and pharmacological differences between the LMWH preparations that may result in different clinical outcomes, and also reviews the implications and challenges physicians face when generic versions of the original/innovator agents are approved for clinical use.
    Journal of Thrombosis and Thrombolysis 01/2012; 33(3):230-8. · 1.99 Impact Factor
  • Marc Cohen, Catalin Boiangiu
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    ABSTRACT: The pharmacologic management of atrial fibrillation (AF) includes rate and rhythm control strategies. Antiarrhythmic agents (eg, amiodarone, flecainide, and propafenone) are limited by serious toxicities (including proarrhythmic effects and pulmonary toxicity), which may lead to a reduced net clinical efficacy of rhythm control strategies. Dronedarone, a new antiarrhythmic agent, is effective in the maintenance of sinus rhythm. Dronedarone has also been shown to reduce ventricular rate and the incidence of hospitalization due to cardiovascular events. Dronedarone is recommended by the 2011 American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society guidelines update for the management of AF patients with no or minimal heart disease, coronary artery disease, and hypertension with no left ventricular hypertrophy. Dronedarone is contraindicated in patients with New York Heart Association (NYHA) class IV heart failure or NYHA class II-III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic.
    Advances in Therapy 12/2011; 28(12):1059-77. · 2.44 Impact Factor
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    ABSTRACT: Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome. In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04). In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 number, NCT00809965.).
    New England Journal of Medicine 11/2011; 366(1):9-19. · 54.42 Impact Factor
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    ABSTRACT: Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction has traditionally been supported by unfractionated heparin, which has never been directly compared with a new anticoagulant using consistent anticoagulation and similar antiplatelet strategies in both groups. We compared traditional heparin treatment with intravenous enoxaparin in primary PCI. In a randomised open-label trial, patients presenting with ST-elevation myocardial infarction were randomly assigned (1:1) to receive an intravenous bolus of 0·5 mg/kg of enoxaparin or unfractionated heparin before primary PCI. Wherever possible, medical teams travelling in mobile intensive care units (ambulances) selected, randomly assigned (using an interactive voice response system at the central randomisation centre), and treated patients. Patients who had received any anticoagulant before randomisation were excluded. Patients and caregivers were not masked to treatment allocation. The primary endpoint was 30-day incidence of death, complication of myocardial infarction, procedure failure, or major bleeding. The main secondary endpoint was the composite of death, recurrent acute coronary syndrome, or urgent revascularisation. Analysis was by intention to treat. This trial is registered at, number NCT00718471. 910 patients were assigned to treatment with enoxaparin (n=450) or unfractionated heparin (n=460). The primary endpoint occurred in 126 (28%) patients after anticoagulation with enoxaparin versus 155 (34%) patients on unfractionated heparin (relative risk [RR] 0·83, 95% CI 0·68-1·01, p=0·06). The incidence of death (enoxaparin, 17 [4%] vs heparin, 29 [6%] patients; p=0·08), complication of myocardial infarction (20 [4%] vs 29 [6%]; p=0·21), procedure failure (100 [26%] vs 109 [28%]; p=0·61), and major bleeding (20 [5%] vs 22 [5%]; p=0·79) did not differ between groups. Enoxaparin resulted in a significantly reduced rate of the main secondary endpoint (30 [7%] vs 52 [11%] patients; RR 0·59, 95% CI 0·38-0·91, p=0·015). Death, complication of myocardial infarction, or major bleeding (46 [10%] vs 69 [15%] patients; p=0·03), death or complication of myocardial infarction (35 [8%] vs 57 [12%]; p=0·02), and death, recurrent myocardial infarction, or urgent revascularisation (23 [5%] vs 39 [8%]; p=0·04) were all reduced with enoxaparin. Intravenous enoxaparin compared with unfractionated heparin significantly reduced clinical ischaemic outcomes without differences in bleeding and procedural success. Therefore, enoxaparin provided an improvement in net clinical benefit in patients undergoing primary PCI. Direction de la Recherche Clinique, Assistance Publique-Hôpitaux de Paris; Sanofi-Aventis.
    The Lancet 08/2011; 378(9792):693-703. · 39.21 Impact Factor
  • American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado; 05/2011
  • Zafar Iqbal, Marc Cohen
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    ABSTRACT: INTRODUCTION: Both arterial and venous thromboembolism constitute a significant disease burden worldwide, leading to major use of healthcare resources. As anticoagulants play a pivotal role in the treatment of these disorders, it is vital for healthcare providers to have sufficient knowledge of their biochemical and clinical attributes. AREAS COVERED: Enoxaparin is one of the most commonly used low-molecular-weight heparins in a wide variety of thromboembolic disorders and has several advantages over unfractionated heparin. An analysis of its biophysical profile, with special emphasis on pharmacokinetic and pharmacodynamic properties, is undertaken in this article. In addition, most recent major clinical studies elucidating its role in common thromboembolic conditions are discussed, while keeping the historical perspective at hand. Readers will be able to understand the pharmacologic properties of enoxaparin with their clinical relevance for day-to-day use and critically analyze the amount and weight of scientific evidence behind its use in various disorders. EXPERT OPINION: In summary, enoxaparin has been shown, by a vast amount of scientific data, to be a safe and effective agent in the treatment of a whole spectrum of acute coronary syndromes, with similar efficacy and safety in the prevention and treatment of venous thromboembolism.
    Expert Opinion on Pharmacotherapy 04/2011; 12(7):1157-70. · 2.86 Impact Factor
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    ABSTRACT: Engagement of the brachiocephalic vessels during carotid angiography is performed using a JR-4, Vitek, or other catheters with variable success. These catheters require additional training for safe manipulation. In this study, we evaluated the feasibility of using the 3D RCA catheter which requires less manipulation in the aorta, and less training, to engage the brachiocephalic vessels. We prospectively studied consecutive high-risk patients undergoing carotid angiography and stenting from August 2005 to March 2009 at our institution. A baseline aortogram was performed to define the arch type in all patients. Engagement of the brachiocephalic vessels was initially attempted using the 3D RCA catheter using the following approach: The 3D RCA catheter is positioned in the ascending aorta beyond the brachiocephalic vessels take off. The natural curve of the catheter usually makes it point cephalad spontaneously in most patients and as it is gently withdrawn it engages the aortic arch vessels without much manipulation. Clinical follow-up with a neurological exam was performed at one month and six months. A total of 52 patients were enrolled in this study. Baseline demographics and aortic arch types encountered are listed in Table I. The 3D RCA catheter readily engaged the brachiocephalic vessels in 50/52 patients (96.0 %) in our cohort of patients undergoing carotid angiography. Of the 52 patients, 43 subsequently underwent carotid stenting and shuttle sheath placement was facilitated by initial engagement of the relevant common carotid artery with the 3D RCA catheter. There was one transient neurologic complication that resolved by 5 days in a patient that underwent carotid stenting. The 3D RCA catheter can be used with a high success rate to engage the brachiocephalic vessels in all 3 arch types, including a bovine arch during carotid angiography and facilitates shuttle sheath placement for carotid stenting. It requires less manipulation and therefore may be a more operator friendly approach. © 2010 Wiley-Liss, Inc.
    Catheterization and Cardiovascular Interventions 04/2011; 77(5):742-5. · 2.51 Impact Factor
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    ABSTRACT: Cardiac transplantation, a procedure nearly abandoned in the 1970s, has evolved into the standard of care for appropriate patients with end-stage heart failure. Much of this success has been due to improvements in immunosuppression, including the introduction of a triple-drug regimen. Retrospective reports suggested that single-drug immunosuppression with tacrolimus was feasible. As such, a prospective, randomized trial was conducted to test this approach. One hundred fifty adult de novo heart transplant recipients were enrolled in a prospective, randomized, controlled, open-label trial comparing tacrolimus monotherapy (MONO) with tacrolimus and mycophenolate mofetil therapy (COMBO). Corticosteroids were used in the early postoperative period but discontinued in all patients over 8 to 9 weeks. The primary end point was the composite biopsy score at 6 months after transplant. Patients were followed for 1 to 5 years. The composite biopsy score was similar between groups at 6 and 12 months: 6-month MONO, 0.70 ± 0.44 (95% confidence interval, 0.60 to 0.80) versus COMBO, 0.65 ± 0.40 (95% confidence interval, 0.55 to 0.74; P=0.44). Allograft vasculopathy was assessed by angiography and intravascular ultrasound, with no significant differences noted. Three-year survival was also similar (92.4% MONO versus 97% COMBO; P=0.58, log-rank). Addition of mycophenolate to single-agent immunosuppression did not provide an advantage over single-agent immunosuppression in terms of rejection, allograft vasculopathy, or 3-year survival. Corticosteroids, which have traditionally been a mainstay of therapy, were successfully discontinued in all patients. These conclusions are tempered by the limited statistical power associated with a sample size of only 150 patients. Clinical Trial Registration- URL: Unique identifier: NCT00299221.
    Circulation Heart Failure 03/2011; 4(2):129-37. · 6.68 Impact Factor

Publication Stats

4k Citations
1,210.96 Total Impact Points


  • 2003–2014
    • Beth Israel Medical Center
      • • Department of Medicine
      • • Cardiac Catheterization Lab
      New York City, New York, United States
    • Philadelphia University
      Philadelphia, Pennsylvania, United States
    • The Children's Hospital of Philadelphia
      Philadelphia, Pennsylvania, United States
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Cardiology and Cardio-thoracic Surgery
      Amsterdam, North Holland, Netherlands
  • 2007–2013
    • Beth Israel Deaconess Medical Center
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2012
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
  • 2004–2011
    • Duke University Medical Center
      • Duke Clinical Research Institute
      Durham, NC, United States
  • 2009
    • Auckland City Hospital
      Окленд, Auckland, New Zealand
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      San Paulo, São Paulo, Brazil
  • 2006–2009
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
    • University of Toronto
      • Division of Cardiology
      Toronto, Ontario, Canada
  • 1998–2009
    • University of the Sciences in Philadelphia
      • Department of Pharmacy Practice and Pharmacy Administration
      Philadelphia, PA, United States
  • 2008
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
    • University of Kentucky
      Lexington, Kentucky, United States
  • 2000–2007
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Center for Brain Mind Medicine
      Boston, MA, United States
  • 2002
    • Partners HealthCare
      Boston, Massachusetts, United States
    • Tenet HealthSystem Medical, Inc.
      Dallas, Texas, United States
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 1999–2000
    • Allegheny University
      Worcester, Massachusetts, United States
  • 1994
    • Miramar Polyclinic
      Palma, Balearic Islands, Spain
  • 1992
    • Mount Sinai Hospital
      New York City, New York, United States
  • 1987–1989
    • CUNY Graduate Center
      New York City, New York, United States
    • New York State
      New York City, New York, United States