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Coronary Artery Disease: HELP
Articles by Marc S. Sabatine
Based on 21 articles published since 2008
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Between 2008 and 2019, Marc Sabatine wrote the following 21 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 Guideline 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 2016

Levine, Glenn N / Bates, Eric R / Bittl, John A / Brindis, Ralph G / Fihn, Stephan D / Fleisher, Lee A / Granger, Christopher B / Lange, Richard A / Mack, Michael J / Mauri, Laura / Mehran, Roxana / Mukherjee, Debabrata / Newby, L Kristin / O'Gara, Patrick T / Sabatine, Marc S / Smith, Peter K / Smith, Sidney C / Halperin, Jonathan L / Levine, Glenn N / Al-Khatib, Sana M / Birtcher, Kim K / Bozkurt, Biykem / Brindis, Ralph G / Cigarroa, Joaquin E / Curtis, Lesley H / Fleisher, Lee A / Gentile, Federico / Gidding, Samuel / Hlatky, Mark A / Ikonomidis, John S / Joglar, José A / Pressler, Susan J / Wijeysundera, Duminda N. · ·J Thorac Cardiovasc Surg · Pubmed #27751237.

ABSTRACT: -- No abstract --

2 Guideline 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 2016

Levine, Glenn N / Bates, Eric R / Bittl, John A / Brindis, Ralph G / Fihn, Stephan D / Fleisher, Lee A / Granger, Christopher B / Lange, Richard A / Mack, Michael J / Mauri, Laura / Mehran, Roxana / Mukherjee, Debabrata / Newby, L Kristin / O'Gara, Patrick T / Sabatine, Marc S / Smith, Peter K / Smith, Sidney C. · ·J Am Coll Cardiol · Pubmed #27036918.

ABSTRACT: -- No abstract --

3 Guideline Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures. 2009

Becker, Richard C / Scheiman, James / Dauerman, Harold L / Spencer, Frederick / Rao, Sunil / Sabatine, Marc / Johnson, David A / Chan, Frances / Abraham, Neena S / Quigley, Eamonn M M / Anonymous1490644 / Anonymous1500644. ·Duke University Medical Center, Duke Clinical Research Institute, Durham, NC 27705, USA. becke021@mc.duke.edu ·J Am Coll Cardiol · Pubmed #19942393.

ABSTRACT: The periprocedural management of patients with atherosclerotic coronary heart disease, including those who have heart disease and those who are undergoing percutaneous coronary intervention and stent placement who might require temporary interruption of platelet-directed pharmacotherapy for the purpose of an elective endoscopic gastrointestinal procedure, is a common clinical scenario in daily practice. Herein, we summarize the available information that can be employed for making management decisions and provide general guidance for risk assessment.

4 Editorial Using Aptamer-Based Technology to Probe the Plasma Proteome for Cardiovascular Disease Prediction. 2016

Sabatine, Marc S. ·TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. ·JAMA · Pubmed #27327798.

ABSTRACT: -- No abstract --

5 Review 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. 2016

Levine, Glenn N / Bates, Eric R / Bittl, John A / Brindis, Ralph G / Fihn, Stephan D / Fleisher, Lee A / Granger, Christopher B / Lange, Richard A / Mack, Michael J / Mauri, Laura / Mehran, Roxana / Mukherjee, Debabrata / Newby, L Kristin / O'Gara, Patrick T / Sabatine, Marc S / Smith, Peter K / Smith, Sidney C. ·Focused Update writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ACC/AHA Representative. Evidence Review Committee Chair. American Society of Anesthesiologists/Society of Cardiovascular Anesthesiologists Representative. American Association for Thoracic Surgery/Society of Thoracic Surgeons Representative. Society for Cardiovascular Angiography and Interventions Representative. ·Circulation · Pubmed #27026020.

ABSTRACT: -- No abstract --

6 Review Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group on current status and future directions. 2012

Fleg, Jerome L / Stone, Gregg W / Fayad, Zahi A / Granada, Juan F / Hatsukami, Thomas S / Kolodgie, Frank D / Ohayon, Jacques / Pettigrew, Roderic / Sabatine, Marc S / Tearney, Guillermo J / Waxman, Sergio / Domanski, Michael J / Srinivas, Pothur R / Narula, Jagat. ·Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA. flegj@nhlbi.nih.gov ·JACC Cardiovasc Imaging · Pubmed #22974808.

ABSTRACT: The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis.

7 Review Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures. 2009

Becker, Richard C / Scheiman, James / Dauerman, Harold L / Spencer, Frederick / Rao, Sunil / Sabatine, Marc / Johnson, David A / Chan, Frances / Abraham, Neena S / Quigley, Eamonn M M / Anonymous270644. ·Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina 27705, USA. becke021@mc.duke.edu ·Am J Gastroenterol · Pubmed #19935784.

ABSTRACT: The periprocedural management of patients with atherosclerotic coronary heart disease, including those who have heart disease and those who are undergoing percutaneous coronary intervention and stent placement who might require temporary interruption of platelet-directed pharmacotherapy for the purpose of an elective endoscopic gastrointestinal procedure, is a common clinical scenario in daily practice. Herein, we summarize the available information that can be employed for making management decisions and provide general guidance for risk assessment.

8 Article Potent P2Y 2017

Lau, Emily S / Braunwald, Eugene / Murphy, Sabina A / Wiviott, Stephen D / Bonaca, Marc P / Husted, Steen / James, Stefan K / Wallentin, Lars / Clemmensen, Peter / Roe, Matthew T / Ohman, E Magnus / Harrington, Robert A / Mega, Jessica L / Bhatt, Deepak L / Sabatine, Marc S / O'Donoghue, Michelle L. ·Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. · TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Cardiology, Århus University Hospital, Århus, Denmark. · Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany; Department of Medicine, Nykoebing F Hospital, University of Southern Denmark, Odense, Denmark. · Division of Cardiology, Duke Clinical Research Institute, Durham, North Carolina. · Department of Medicine, Stanford University, Stanford, California. · Verily Life Sciences, Mountain View, California. · TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: modonoghue@partners.org. ·J Am Coll Cardiol · Pubmed #28335837.

ABSTRACT: BACKGROUND: Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain. OBJECTIVES: The study investigated the efficacy and safety of the potent P2Y METHODS: A collaborative sex-specific meta-analysis was conducted of phase III or IV randomized trials of potent P2Y RESULTS: Potent P2Y CONCLUSIONS: In randomized trials, the efficacy and safety of the potent P2Y

9 Article Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction: Insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54). 2016

Bonaca, Marc P / Goto, Shinya / Bhatt, Deepak L / Steg, P Gabriel / Storey, Robert F / Cohen, Marc / Goodrich, Erica / Mauri, Laura / Ophuis, Ton Oude / Ruda, Mikhail / Špinar, Jindřich / Seung, Ki-Bae / Hu, Dayi / Dalby, Anthony J / Jensen, Eva / Held, Peter / Morrow, David A / Braunwald, Eugene / Sabatine, Marc S. ·From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) · Tokai University School of Medicine · Institute of Medical Science, Isehara, Japan (S.G.) · FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) · University of Sheffield, United Kingdom (R.F.S.) · Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) · Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) · CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) · Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) · Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) · Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) · Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) · Life Fourways Hospital, Randburg, South Africa (A.J.D.) · and AstraZeneca, Mölndal, Sweden (E.J., P.H.). ·Circulation · Pubmed #27576775.

ABSTRACT: BACKGROUND: In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. METHODS: Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. RESULTS: Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). CONCLUSIONS: High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562.

10 Article Focus on PCSK9 Inhibitors: From Genetics to Clinical Practice. 2016

Sabatine, Marc S / Underberg, James A / Koren, Michael / Baum, Seth J. ·a Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine , Brigham and Women's Hospital. · b Department of Medicine , Harvard Medical School , Boston , MA. · c NYU Medical School, NYU Center for CVD Prevention , Bellevue Hospital Lipid Clinic , New York , NY. · d Jacksonville Center for Clinical Research. · e Academy of Physicians in Clinical Research , Jacksonville , FL. · f MB Clinical Research. · g American Society for Preventive Cardiology. · h The FH Foundation. ·Postgrad Med · Pubmed #27422124.

ABSTRACT: Elevation of low-density lipoprotein cholesterol (LDL-C) is an important cause of atherosclerotic cardiovascular disease (ASCVD). Over the years, clinical outcome studies with LDL-C lowering agents have revealed that reducing LCL-C levels is effective in reducing rates of major ASCVD events. Although secondary factors play a role in clinical expression, severe lipid disorders often have a strong genetic component. Genetic revelations have provided novel targets for improving LDL-C management in high-risk individuals. Most recently, researchers have explored how the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) alters LDL metabolism and lowers LDL-C levels to achieve lipid goals and potentially reduce ASCVD risk in patients with severe lipid disorders, including familial hypercholesterolemia (FH). This CMHC Spotlight article summarizes the clinical evidence demonstrating the safety, tolerability, and efficacy of PCSK9 inhibitors in lowering LDL-C levels. Reductions in LDL-C levels by PCSK9 inhibitors alone in patients who are statin intolerant or combined with maximally tolerated statins in patients with severe lipid disorders demonstrate the potential for reduced morbidity and mortality associated with ASCVD.

11 Article Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel. Insights from the ELEVATE-TIMI 56 Trial. 2016

Carreras, Edward T / Hochholzer, Willibald / Frelinger, Andrew L / Nordio, Francesco / O'Donoghue, Michelle L / Wiviott, Stephen D / Angiolillo, Dominick J / Michelson, Alan D / Sabatine, Marc S / Mega, Jessica L. ·Edward T. Carreras, MD, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA, Tel.: +1 617 732 5500, E-mail: ecarreras@partners.org. · Marc S. Sabatine, MD, MPH, Brigham & Women's Hospital, 75 Francis Street, Boston, MA 02115, USA, E-mail: msabatine@partners.org. ·Thromb Haemost · Pubmed #27009617.

ABSTRACT: Both diabetes mellitus (DM) and carriage of the CYP2C19*2 allele are associated with a reduced response to clopidogrel. The relative contributions of these factors and whether higher clopidogrel doses can overcome both factors remain unknown. The objective of this study was to test the ability of clopidogrel doses up to 300 mg daily to decrease platelet reactivity in patients with DM and/or CYP2C19*2. ELEVATE-TIMI 56 randomised 333 patients with coronary artery disease to different maintenance doses of clopidogrel in four treatment periods, each lasting approximately 14 days. On-treatment platelet reactivity was compared between patients stratified by DM, CYP2C19*2 status and clopidogrel dose. Both DM and CYP2C19*2 were independently associated with elevated on-treatment platelet reactivity with clopidogrel 75 mg daily (p<0.0001 for each). With 75 mg, mean on-treatment PRU was progressively higher (p trend <0.001) when evaluating patients: with neither DM nor CYP2C19*2 (150.7; 95 % CI 140.5-162.6), with only DM (187.2; 95 % CI, 171.3-206.9), with only CYP2C19*2 (227.9; 95 % CI, 205.1-250.8), and with both DM and CYP2C19*2 (239.9; 95 % CI, 209.7-270.1). Notably, with 75 mg, patients with only CYP2C19*2 had higher on-treatment platelet reactivity than those with only DM (p=0.0068). To achieve on-treatment platelet reactivity similar to that seen with clopidogrel 75 mg in patients with neither DM nor CYP2C19*2, the following doses were required: 150 mg with only DM, 225 mg with only CYP2C19*2, and 300 mg with both DM and CYP2C19*2. Patients with both DM and CYP2C19*2 required a four-fold increase in clopidogrel maintenance dose as compared to patients without these factors to achieve a similar antiplatelet response.

12 Article Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial. 2016

Magnani, Giulia / Storey, Robert F / Steg, Gabriel / Bhatt, Deepak L / Cohen, Marc / Kuder, Julia / Im, Kyungah / Aylward, Philip / Ardissino, Diego / Isaza, Daniel / Parkhomenko, Alexander / Goudev, Assen R / Dellborg, Mikael / Kontny, Frederic / Corbalan, Ramon / Medina, Felix / Jensen, Eva C / Held, Peter / Braunwald, Eugene / Sabatine, Marc S / Bonaca, Marc P. ·TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA. · Department of Cardiovascular Science, University of Sheffield, Sheffield, UK. · Cardiology Department, DHU-FIRE, Hôpital Bichat, Paris, France Université Paris-Diderot, Paris, France INSERM U1148, Paris, France. · Cardiovascular Division, Department of Medicine, Rutgers-New Jersey Medical School, New York, USA. · Division of Medicine, Cardiac & Critical Care Services, Flinders University and Medical Centre, Adelaide, Australia. · Cardiovascular Division, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. · Fundacion CardioInfantil, Bogota, Colombia. · Ukranian Strazhesko Institute of Cardiology, Kiev, Ukraine. · Department of Cardiology, Queen Giovanna University Hospital, Sofia, Bulgaria. · Department of Molecular and Clinical Medicine/Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · Department of Cardiology, Stavanger University Hospital, Stavanger, Norway. · Cardiovascular Division, Pontificia Universidad Católica de Chile, Santiago, Chile. · Hospital Nacional Cayetano Heredia, San Martin de Porres, Lima, Peru. · AstraZenecaAZ R&D, Molndal, Sweden. · TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, USA mbonaca@partners.org. ·Eur Heart J · Pubmed #26443023.

ABSTRACT: AIMS: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). METHODS AND RESULTS: Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). CONCLUSION: In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor.

13 Article Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial. 2014

Hochholzer, Willibald / Ruff, Christian T / Mesa, Robert A / Mattimore, John F / Cyr, John F / Lei, Lanyu / Frelinger, Andrew L / Michelson, Alan D / Berg, David D / Angiolillo, Dominick J / O'Donoghue, Michelle L / Sabatine, Marc S / Mega, Jessica L. ·Universitaets Herzzentrum Freiburg, Klinik für Kardiologie und Angiologie II, Bad Krozingen, Germany. · TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Harvard Clinical Research Institute, Boston, Massachusetts. · Center for Platelet Research Studies, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. · University of Florida College of Medicine-Jacksonville, Jacksonville, Florida. · TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: jmega@partners.org. ·J Am Coll Cardiol · Pubmed #25060370.

ABSTRACT: BACKGROUND: The degree of antiplatelet response to clopidogrel has been associated with clinical outcomes. Studies have investigated whether adjustment of antiplatelet therapies based on a single platelet function test is beneficial. OBJECTIVES: The aim of the study was to test the stability of platelet reactivity measurements over time among patients treated with standard and double doses of clopidogrel. METHODS: The ELEVATE-TIMI 56 (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56) investigators genotyped 333 patients with coronary artery disease and randomized them to various clopidogrel regimens. Patients with at least 2 platelet function results on the same maintenance dose of clopidogrel (75 mg or 150 mg) were analyzed. Platelet aggregation was measured using P2Y12 reaction units (PRU). RESULTS: In total, the mean platelet reactivity and the total number of nonresponders (PRU ≥230) with clopidogrel did not change between 2 periods for the 75-mg (22.4% vs. 21.9%; p = 0.86) and 150-mg doses of clopidogrel (11.5% vs. 11.5%; p = 1.00). In contrast, when evaluating each patient individually, 15.7% of patients taking clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their responder status when tested at 2 different time points (p < 0.001). Despite being treated with the same dose of clopidogrel, >40% of patients had a change in PRU >40 on serial sampling, which approximates the average PRU difference caused by increasing the clopidogrel dose from 75 mg to 150 mg. CONCLUSIONS: Measurements of platelet reactivity vary over time in a significant proportion of patients. Thus, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy in clinical or research settings. (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56 [ELEVATE-TIMI 56]; NCT01235351).

14 Article Lipoprotein(a) for risk assessment in patients with established coronary artery disease. 2014

O'Donoghue, Michelle L / Morrow, David A / Tsimikas, Sotirios / Sloan, Sarah / Ren, Angela F / Hoffman, Elaine B / Desai, Nihar R / Solomon, Scott D / Domanski, Michael / Arai, Kiyohito / Chiuve, Stephanie E / Cannon, Christopher P / Sacks, Frank M / Sabatine, Marc S. ·TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: modonoghue@partners.org. · TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. · Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California. · Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine; Center for Outcomes Research and Evaluation, Yale-New Haven Health System, New Haven, Connecticut. · Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. · Mount Sinai School of Medicine, Cardiovascular Division, New York, New York. · Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California; Division of Cardiology, Tokyo Women's Medical University, Tokyo, Japan. · Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Channing Laboratory and Cardiology Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. ·J Am Coll Cardiol · Pubmed #24161323.

ABSTRACT: OBJECTIVES: The purpose of this study was to assess the prognostic utility of lipoprotein(a) [Lp(a)] in individuals with coronary artery disease (CAD). BACKGROUND: Data regarding an association between Lp(a) and cardiovascular (CV) risk in secondary prevention populations are sparse. METHODS: Plasma Lp(a) was measured in 6,708 subjects with CAD from 3 studies; data were then combined with 8 previously published studies for a total of 18,978 subjects. RESULTS: Across the 3 studies, increasing levels of Lp(a) were not associated with the risk of CV events when modeled as a continuous variable (odds ratio [OR]: 1.03 per log-transformed SD, 95% confidence interval [CI]: 0.96 to 1.11) or by quintile (Q5:Q1 OR: 1.05, 95% CI: 0.83 to 1.34). When data were combined with previously published studies of Lp(a) in secondary prevention, subjects with Lp(a) levels in the highest quantile were at increased risk of CV events (OR: 1.40, 95% CI: 1.15 to 1.71), but with significant between-study heterogeneity (p = 0.001). When stratified on the basis of low-density lipoprotein (LDL) cholesterol, the association between Lp(a) and CV events was significant in studies in which average LDL cholesterol was ≥130 mg/dl (OR: 1.46, 95% CI: 1.23 to 1.73, p < 0.001), whereas this relationship did not achieve statistical significance for studies with an average LDL cholesterol <130 mg/dl (OR: 1.20, 95% CI: 0.90 to 1.60, p = 0.21). CONCLUSIONS: Lp(a) is significantly associated with the risk of CV events in patients with established CAD; however, there exists marked heterogeneity across trials. In particular, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear.

15 Article Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease. 2013

Omland, Torbjørn / Pfeffer, Marc A / Solomon, Scott D / de Lemos, James A / Røsjø, Helge / Šaltytė Benth, Jūratė / Maggioni, Aldo / Domanski, Michael J / Rouleau, Jean L / Sabatine, Marc S / Braunwald, Eugene / Anonymous2860750. ·Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway. torbjorn.omland@medisin.uio.no ·J Am Coll Cardiol · Pubmed #23414791.

ABSTRACT: OBJECTIVES: The aims of this study were to assess the prognostic value of cardiac troponin I levels, measured with a new high-sensitivity assay, in low-risk patients with stable coronary artery disease (CAD) and to contrast its determinants and prognostic merit with that of high-sensitivity cardiac troponin T (hs-TnT). BACKGROUND: New, highly sensitive cardiac troponin assays permit evaluation of the association between troponin levels and outcomes in patients with stable CAD. METHODS: High-sensitivity cardiac troponin I (hs-TnI) levels at baseline were assessed in 3,623 patients with stable CAD and preserved systolic function enrolled in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy) trial. RESULTS: In total, 98.5% of patients had hs-TnI concentrations higher than the detection level (1.2 pg/ml). hs-TnI correlated moderately with hs-TnT (r = 0.44) and N-terminal pro-B-type natriuretic peptide (r = 0.39) but only weakly with age (r = 0.17) and estimated glomerular filtration rate (r = -0.11). During a median follow-up period of 5.2 years, 203 patients died of cardiovascular causes or were hospitalized for heart failure, and 209 patients had nonfatal myocardial infarctions. In analyses adjusting for conventional risk markers, N-terminal pro-B-type natriuretic peptide, and hs-TnT, hs-TnI levels in the fourth compared with the 3 lower quartiles were associated with the incidence of cardiovascular death or heart failure (hazard ratio: 1.84; 95% confidence interval: 1.30 to 2.61; p < 0.001). [corrected]. There was a [corrected] weaker association with nonfatal myocardial infarction (hazard ratio: 1.37; 95% confidence interval: 0.98 to 1.92; p = 0.066). [corrected]. In the same models, hs-TnT concentrations were associated with the incidence of cardiovascular death or heart failure but not of myocardial infarction. CONCLUSIONS: In patients with stable CAD, hs-TnI concentrations are associated with cardiovascular risk independently of conventional risk markers and hs-TnT. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy [PEACE]; NCT00000558).

16 Article Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy. 2011

Hochholzer, Willibald / Trenk, Dietmar / Mega, Jessica L / Morath, Tanja / Stratz, Christian / Valina, Christian M / O'Donoghue, Michelle L / Bernlochner, Isabell / Contant, Charles F / Guo, Jianping / Sabatine, Marc S / Schömig, Albert / Neumann, Franz-Josef / Kastrati, Adnan / Wiviott, Stephen D / Sibbing, Dirk. ·TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. whochholzer@partners.org ·Am Heart J · Pubmed #21884870.

ABSTRACT: BACKGROUND: Pharmacodynamic studies reported an amplified on-clopidogrel platelet inhibition in smokers potentially caused by an increased metabolic drug activation via induction of cytochrome P450 1A2. The aims of this analysis were to evaluate the impact of smoking on the antiplatelet effect of clopidogrel and prasugrel and to test the potential interaction of smoking with the treatment effect of these drugs. METHODS: A variety of platelet function results was analyzed from 2 large cohorts of patients undergoing coronary intervention after loading with clopidogrel 600 mg (n = 2,533 and n = 1,996), a cohort of patients undergoing dose adaptation from 75 to 150 mg according to response to clopidogrel (n = 117) and a crossover trial comparing clopidogrel 150 mg with prasugrel 10 mg (n = 87). Linear regression analyses were used to test the impact of smoking on platelet function and to identify independent predictors of on-treatment platelet reactivity. The potential interaction of smoking with the clinical effect of clopidogrel versus prasugrel was analyzed in the TRITON-TIMI 38 cohort (n = 13,608). RESULTS: No significant association of smoking with platelet reactivity on clopidogrel was seen in unadjusted and adjusted analyses. The variables most consistently associated with on-clopidogrel platelet function were age, sex, diabetes, and body mass index. There was no significant interaction of smoking status at presentation with the clinical efficacy of prasugrel versus clopidogrel (P for interaction = .39). CONCLUSIONS: Smoking does not impact on platelet reactivity in patients after loading or on different maintenance doses of clopidogrel. The clinical treatment effect of clopidogrel versus prasugrel is not affected by smoking status at presentation.

17 Article Myocardial ischemia induced by rapid atrial pacing causes troponin T release detectable by a highly sensitive assay: insights from a coronary sinus sampling study. 2011

Turer, Aslan T / Addo, Tayo A / Martin, Justin L / Sabatine, Marc S / Lewis, Gregory D / Gerszten, Robert E / Keeley, Ellen C / Cigarroa, Joaquin E / Lange, Richard A / Hillis, L David / de Lemos, James A. ·Department of Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas 75230-9047, USA. aslan.turer@utsouthwestern.edu ·J Am Coll Cardiol · Pubmed #21658559.

ABSTRACT: OBJECTIVES: The purpose of this study was to assess whether: 1) very small increases in troponin T, measured by a new highly sensitive cardiac troponin T (hs-cTnT), may reflect ischemia without necrosis; and 2) serial changes can discriminate ischemia from other causes of cardiac troponin T (cTnT) release. BACKGROUND: A new hs-cTnT assay offers greater sensitivity than current assays. METHODS: Nineteen patients referred for diagnostic catheterization underwent cannulation of the coronary sinus (CS). Serial CS and peripheral plasma samples were obtained at multiple time points during and after incremental rapid atrial pacing. cTnT was quantified using both a standard and a pre-commercial highly sensitive assay. Ischemia was determined by the presence of significant coronary artery disease (CAD) and myocardial lactate release with pacing. RESULTS: cTnT concentrations in CS blood increased from a median of 6.8 pg/ml prior to pacing to 15.6 pg/ml 60 min after termination of rapid atrial pacing (p < 0.0001), changes that were mirrored at 180 min in peripheral blood (5.1 to 11.8 pg/ml, p < 0.0001). Although peripheral cTnT concentrations tended to be higher at 180 min following pacing for patients with CAD and lactate elution (n = 7) when compared with those without either marker (n = 5) (25.0 pg/ml vs. 10.2 pg/ml, p = 0.10), relative (1.7-fold vs. 5.2-fold) and absolute (6.8 pg/ml vs. 8.8 pg/ml, p = 0.50) changes were not different between groups. CONCLUSIONS: Brief periods of ischemia, without frank infarction, cause low-level cTnT release, and small increases are common after periods of increased myocardial work, even among patients without objective evidence of myocardial ischemia or obstructive CAD. Additional research is needed before hs-cTnT assays are widely adopted in the management of subjects with chest pain syndromes.

18 Article A sensitive cardiac troponin T assay in stable coronary artery disease. 2009

Omland, Torbjørn / de Lemos, James A / Sabatine, Marc S / Christophi, Costas A / Rice, Madeline Murguia / Jablonski, Kathleen A / Tjora, Solve / Domanski, Michael J / Gersh, Bernard J / Rouleau, Jean L / Pfeffer, Marc A / Braunwald, Eugene / Anonymous1881162. ·Division of Medicine, Akershus University Hospital, Lørenskog, Norway. torbjorn.omland@medisin.uio.no ·N Engl J Med · Pubmed #19940289.

ABSTRACT: BACKGROUND: In most patients with stable coronary artery disease, plasma cardiac troponin T levels are below the limit of detection for the conventional assay. The distribution and determinants of very low circulating troponin T levels, as well as their association with cardiovascular events, in such patients are unknown. METHODS: We used a new, high-sensitivity assay to determine the concentration of cardiac troponin T in plasma samples from 3679 patients with stable coronary artery disease and preserved left ventricular function. Results of the assay were analyzed in relation to the incidence of cardiovascular events during a median follow-up period of 5.2 years. RESULTS: With the highly sensitive assay, concentrations of cardiac troponin T were at or above the limit of detection (0.001 microg per liter) in 3593 patients (97.7%) and at or above the 99th percentile for apparently healthy subjects (0.0133 microg per liter) in 407 patients (11.1%). After adjustment for other independent prognostic indicators, there was a strong and graded increase in the cumulative incidence of cardiovascular death (adjusted hazard ratio per unit increase in the natural logarithm of the troponin T level, 2.09; 95% confidence interval [CI], 1.60 to 2.74; P<0.001) and of heart failure (adjusted hazard ratio, 2.20; 95% CI, 1.66 to 2.90; P<0.001) in this study group. Increased risk associated with higher levels of troponin T was evident well below the limit of detection of conventional cardiac troponin T assays and below the 99th percentile of values in a healthy population. There was no association between troponin T levels as measured with the highly sensitive assay and the incidence of myocardial infarction (adjusted hazard ratio, 1.16; 95% CI, 0.97 to 1.40; P=0.11). CONCLUSIONS: After adjustment for other independent prognostic indicators, cardiac troponin T concentrations as measured with a highly sensitive assay were significantly associated with the incidence of cardiovascular death and heart failure but not with myocardial infarction in patients with stable coronary artery disease.

19 Article Predictors of initial nontherapeutic anticoagulation with unfractionated heparin in ST-segment elevation myocardial infarction. 2009

Cheng, Susan / Morrow, David A / Sloan, Sarah / Antman, Elliott M / Sabatine, Marc S. ·Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ·Circulation · Pubmed #19237657.

ABSTRACT: BACKGROUND: Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging. METHODS AND RESULTS: In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low (<1.25 times); and 16.3% were markedly high (> or =2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio [RR(adj)], 1.14 per decade; P=0.001), were female (RR(adj), 1.46; P<0.001), were of lower weight (RR(adj), 1.19 per 10-kg decrease; P<0.001) or had renal dysfunction (RR(adj), 1.08 per 0.2-mg/dL increase in serum creatinine; P=0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P=0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P=0.057). CONCLUSIONS: Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy.

20 Article Efficacy and safety of clopidogrel pretreatment before percutaneous coronary intervention with and without glycoprotein IIb/IIIa inhibitor use. 2008

Sabatine, Marc S / Hamdalla, Hussam N / Mehta, Shamir R / Fox, Keith A A / Topol, Eric J / Steinhubl, Steven R / Cannon, Christopher P. ·Cardiovascular Division, Department of Medicine, Thrombolysis in Myocardial Infarction Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. msabatine@partners.org ·Am Heart J · Pubmed #18440341.

ABSTRACT: BACKGROUND: Clopidogrel pretreatment before percutaneous coronary intervention (PCI) has been shown to reduce the risk of death and ischemic complications after PCI. However, the need for clopidogrel pretreatment is debated in patients receiving a glycoprotein IIb/IIIa inhibitor (GPI). METHODS: We performed a collaborative meta-analysis of the results of 3 randomized trials of clopidogrel pretreatment: PCI-CURE, CREDO, and PCI-CLARITY. Patients were stratified based on GPI use at the time of PCI (a postrandomization subgroup analysis). Odds ratios (ORs) and 95% CIs for the effect of clopidogrel pretreatment versus placebo pretreatment on the incidence of cardiovascular death, myocardial infarction (MI), or stroke for up to 30 days after PCI were calculated for each trial within each GPI stratum and were combined using a random effects model. RESULTS: Six thousand three hundred twenty-five patients were included, 32.4% of whom received a GPI. There was a consistent benefit of clopidogrel pretreatment in reducing the incidence of cardiovascular death, MI, or stroke after PCI both in patients who did not receive a GPI (OR 0.72, 95% CI 0.53-0.98, P = .03) and in those who did (OR 0.69, 95% CI 0.47-1.00, P = .05). There was no evidence of heterogeneity in the benefit of clopidogrel pretreatment between GPI use strata (P = .85 for heterogeneity). Clopidogrel pretreatment was not associated with a significant excess of TIMI major or minor bleeding, either in those who did not receive a GPI (OR 1.20, 95% CI 0.76-1.92) or in those who did (OR 1.22, 95% CI 0.71-2.09) (P = .97 for heterogeneity). CONCLUSION: Clopidogrel pretreatment before PCI is beneficial and safe regardless of whether a GPI is used at the time of PCI.

21 Article Sudden cardiac death in patients with stable coronary artery disease and preserved left ventricular systolic function. 2008

Hsia, Judith / Jablonski, Kathleen A / Rice, Madeline Murguia / Sabatine, Marc S / Zabalgoitia, Miguel / Maggioni, Aldo / Cuddy, Thomas E / Domanski, Michael J / Geller, Nancy L / Flaker, Greg / Solomon, Scott / Omland, Torbjørn / Rouleau, Jean L / Anonymous5630593. ·Department of Medicine, George Washington University, Washington, DC, USA. judith.hsia@astrazeneca.com ·Am J Cardiol · Pubmed #18312757.

ABSTRACT: Although sudden cardiac death (SCD) has been extensively studied in patients with coronary artery disease (CAD) and low ejection fraction, prediction of SCD among individuals with preserved left ventricular systolic function is less well understood. We randomized 8,290 patients with stable CAD with preserved left ventricular systolic function to trandolapril or placebo in a secondary coronary prevention trial, and we used Cox proportional hazards models to identify independent baseline predictors of SCD during 4.8 year follow-up (median). Using a risk scoring algorithm based on simple clinical characteristics, we were able to distinguish individuals at higher risk for SCD. Independent determinants of SCD included age (p <0.001), current angina pectoris (p = 0.002), ejection fraction >40% to <50% (as opposed to >50%) (p <0.001), and diuretic (p <0.001) and digitalis use (p <0.001). Negative predictors included having prior coronary revascularization (p = 0.01) and being female (p = 0.02) or Caucasian (p = 0.006). Trandolapril neither increased nor decreased SCD. Thus, among patients with stable CAD with preserved left ventricular systolic function receiving current standard-of-care including coronary revascularization, clinical characteristics can identify individuals at higher risk for SCD.