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Universitäts-Herzzentrum Freiburg - Bad KrozingenUniversitäts-Herzzentrum Freiburg - Bad Krozingen

Working group: Clinical aspects of antiplatelet therapy and cardiovascular biomarkers


Platelets play a central role in development and progression of atherosclerotic diseases. Thus, antiplatelet treatment strategies are a major cornerstone in treatment of these syndromes. However, antiplatelet effects of different drugs such as clopidogrel show a significant interindividual variability which is linked to worse clinical outcome (e.g., acute myocardial infarction) as demonstrated in a large cohort of our center. Further key results of our research are the identification of genetic and clinical factors associated with low response to clopidogrel and the research of potential treatment strategies to achieve an optimized antiplatelet effect. Another target of our research is the identification of cellular mechanism leading to impaired antiplatelet response to drugs. In this context, we are currently focusing on immature platelets. Two prospective randomized trials are currently evaluating novel therapeutic strategies for a more rapid and consistent periinterventional platelet inhibition.

Another focus of our research is the identification cardiovascular biomarkers such as cardiac troponin and soluble fms-like tyrosine kinase-1 for diagnosis and prognosis in stable patients. Results of several large cohorts did show among other things that the prognostic effect of cardiac troponin is independent of obstructive coronary heart or structural heart disease. A current large prospective study is evaluating biomarker based algorithms for diagnosis of acute myocardial infarction.

Team members
Dr. med. Christian M. Valina

Dr. med. Christian M. Valina
E-Mail: christian.valina@universitaets-herzzentrum.de

Dr. med. Michael Amann
E-Mail: michael.amann@universitaets-herzzentrum.de

Dr. med. Felix Gaiser
E-Mail: Felix.Gaiser@universitaets-herzzentrum.de

Dr. med. Sebastian Merz
E-Mail: Sebastian.Merz@universitaets-herzzentrum.de

Dr. med. Sherif Abdelrazek
E-Mail: Sherif.Abdelrazek@universitaets-herzzentrum.de

Dr. med. Julia Schlosser
E-Mail: Julia.Schlosser@universitaets-herzzentrum.de

Study Nurses

Stefanie Waldmann-Kittler
Ulrike Maier
Cordula Jarvers

Doctoral fellows
Alexander Titow

Alexander Titow

Jasmin Stöckle

Sandra Schwenk

Alexander Kille

Past members of our group

  • Dr. med. Timo Bömicke
  • Dr. med. Valentin Wennekes-Neagu
  • Dr. med. Christian Stratz
  • Dr. med. Pascal Kleiner
  • Devine Frundi
  • Philipp Blanke
  • Benjamin Fischer
  • Katharina Andris
  • Barbara Müller
  • Pascal Kleiner
Iris Younas

Iris Younas

ELEVATE-TIMI 56 (2010-2011, conducted at the TIMI Study Group, Harvard Medical School, Boston)

  • ELEVATE-TIMI 56 investigated if patients with a genetic polymorphism associated with a reduced antiplatelet response to clopidogrel (CYP2C19*2 polymorphism) can achieve a similar platelet inhibition as compared to patients without this polymorphism by increasing the dose of clopidogrel. The central finding of this trial was that heterozygote carriers of the CYP2C19*2 polymorphism can achieve this goal by increasing the maintenance dose of clopidogrel to 225mg daily. Homozygous carriers of the polymorphism did not reach the same level of platelet inhibition even when increasing the maintenance dose of clopidogrel to 300mg daily.

    Trial design and results

ExcelsiorLOAD (2014-2015)

  • ExcelsiorLOAD investigated randomized to what extent loading with various doses of prasugrel can provide a more rapid peri-interventional antiplatelet effect than clopidogrel 600mg. From 30min onwards, prasugrel 60mg achieved a stronger platelet inhibition than clopidogrel loading in stable patients undergoing PCI. Compared with clopidogrel, prasugrel 60mg was associated with a twice as fast onset of platelet inhibition. Prespecified subgroup analyses did analyze the impact of immature platelets on the antiplatelet effects of the study medication.

    Trial design and results

ExcelsiorLOAD2 (2015-2016)

  • ExcelsiorLOAD2 was a randomized comparison of different transitioning strategies from an intravenous to an oral P2Y12-receptor inhibitor. The key finding was that, despite the known interaction of active metabolites of prasugrel and cangrelor, loading with prasugrel 60 mg given at the start of a 2-hour infusion of cangrelor can provide a sufficient platelet inhibition post cangrelor. Prespecified subgroup analyses did analyze the impact of immature platelets on the antiplatelet effects of the study medication.

    Trial design and results

FastMI (2016 - aktuell)

  • The FastMI study evaluates in cooperation with the German Heart Foundation the 1-hour troponin diagnosis algorithm for acute myocardial infarction of the European Society of Cardiology in a high-risk setting. We are currently enrolling approximately 1500 patients into this study at our center.

ProRadial (coming soon)

  • TIMI Study Group, Boston, USA (Prof. Braunwald, Dr. Mega, Prof. Sabatine, Prof. Wiviott, Prof. Giugliano)
  • Medizinische Klinik und Poliklinik I, Ludwig-Maximilians Universität München (PD Dr. Sibbing)
  • Universitätsspital Basel, Schweiz (Prof. Müller)
  • Institut für Mikro- und Informationstechnik der Hahn-Schickard-Gesellschaft e.V., University of Freiburg
  • Trois-Chêne Hospital, Geneva University Hospitals, Switzerland (Prof. Dr. Jean-Luc Reny)
  • Center for Medical Biometry and Medical Informatics, University of Freiburg (Prof. Dr. Hauschke)
  • Institute of Experimental and Clinical Pharmacology, University of Erlangen-Nuremberg (Prof. Dr. Fromm)
  • Department of Cardiovascular Surgery, University of Freiburg (Prof. Siepe)
  • Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg • Bad Krozingen (Prof. Kohl)
  • University Hospital Heidelberg (Prof. Dr. Giannitsis)
  • Clinical Translation Sciences Institute, University of Maryland, Baltimore, USA (Prof. Alan R. Shuldiner)
  • University of Florida College of Medicine-Jacksonville, Jacksonville, USA (Prof. Angiolillo)
  • TAmiRNA GmbH, Vienna, Austria (Dr. Hackl)
  • 2007 AstraZeneca Fonds grant
  • 2007 August Wilhelm und Lieselotte Becht award
  • 2009 Stipend of the German Heart Foundation
  • 2010 Early Career Investigator Award of the 6th Annual Platelet Colloquium
  • 2011 W.Proctor-Harvey Award of the Albert-Ludwigs-Universität Freiburg
  • 2014 Research grant of the German Heart Foundation/German Foundation of Heart Research
  • 2017 Research grant of the German Heart Foundation
  • 2017 Andreas-Grünzig-Award oft he German Cardiac Society

Neumann FJ, Hochholzer W, Pogatsa-Murray G, Schömig A, Gawaz M:
Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting.
Journal of the American College of Cardiology 2001; 37: 1323-28.

Hochholzer W, Trenk D, Frundi D, Blanke P, Fischer B, Andris K, Bestehorn HP, Büttner HJ, Neumann FJ:
Time dependence of platelet inhibition after a 600 mg loading dose of clopidogrel in a large unselected cohort of candidates for percutaneous coronary intervention.
Circulation 2005; 111: 2560-2564.

Hochholzer W, Trenk D, Bestehorn HP, Fischer B, Valina CM, Ferenc M, Gick M, Caputo A, Büttner HJ, Neumann FJ:
Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement.
Journal of the American College of Cardiology 2006; 48: 1742-1750.

Mueller C, Neumann FJ, Hochholzer W, Trenk D, Zeller T, Perruchoud AP, Buettner HJ:The impact of platelet count on mortality in unstable angina/non-ST-segment elevation myocardial infarction.
American Heart Journal 2006; 151: 1214.e1-7

Wermuth J, Staub D, Laule-Kilian K, Nusbaumer C, Breidthardt T, Hochholzer W, Christ M, Mueller C:
Neurohormonal activation and left ventricular ejection fraction in patients with suspected myocardial ischemia.
International Journal of Cardiology 2007; 120: 248-253.

Breidthardt T, Christ M, Matti M, Schrafl D, Laule K, Noveanu M, Boldanova T, Klima T, Hochholzer W, Perruchoud AP, Mueller C:
QRS and QTc interval prolongation in the prediction of long-term mortality of patients with acute destabilised heart failure.
Heart 2007; 93:1093-1097.

Christ M, Thuerlimann A, Laule K, Klima T, Hochholzer W, Perruchoud AP, Mueller C:
Long-term prognostic value of B-type natriuretic peptide in cardiac and non-cardiac causes of acute dyspnoea.
European Journal of Clinical Investigation 2007; 37: 834-841.

Hochholzer W, Trenk D, Frundi D, Neumann FJ:
Whole blood aggregometry for evaluation of the antiplatelet effects of clopidogrel.
Thrombosis Research 2007; 119: 285-291.

Hochholzer W, Schlittenhardt D, Arentz T, Stockinger J, Weber R, Bürkle G, Kalusche D, Trenk D, Neumann FJ:
Platelet activation and myocardial necrosis in patients undergoing radiofrequency and cryoablation of isthmus-dependent atrial flutter.
Europace 2007; 9: 490-495.

Hochholzer W, Buettner HJ, Trenk D, Laule K, Christ M, Neumann FJ, Mueller C:
New definition of myocardial infarction: impact on long-term mortality.
American Journal of Medicine 2008; 121: 399-405.

Hochholzer W, Buettner HJ, Trenk D, Breidthardt T, Noveanu M, Laule K, Christ M, Schindler C, Neumann FJ, Mueller C:
Percutaneous coronary intervention versus coronary artery bypass grafting as primary revascularization in patients with acute coronary syndrome.
American Journal of Cardiology 2008; 102: 173-179.

Trenk D, Hochholzer W, Frundi D, Stratz C, Valina CM, Bestehorn HP, Büttner HJ, Neumann FJ:
Impact of cytochrome P450 3A4-metabolized statins on the antiplatelet effect of a 600-mg loading dose clopidogrel and on clinical outcome in patients undergoing elective coronary stent placement.
Thrombosis Haemostasis 2008; 99: 174-181.

Christ M, Laule K, Klima T, Hochholzer W, Breidthardt T, Perruchoud AP, Mueller C:
Multimarker strategy for risk prediction in patients presenting with acute dyspnea to the emergency department.
International Journal of Cardiology 2008; 126: 73-78.

Trenk D, Hochholzer W, Fromm MF, Chialda LE, Pahl A, Valina CM, Stratz C, Schmiebusch P, Bestehorn HP, Büttner HJ, Neumann FJ:
Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents.
Journal of the American College of Cardiology 2008; 51: 1925-1934.

Breidthardt T, Noveanu M, Cayir S, Viglino M, Laule K, Hochholzer W, Reichlin T, Potocki M, Christ M, Mueller C:
The use of B-type natriuretic peptide in the management of patients with atrial fibrillation and dyspnea.
International Journal of Cardiology 2009; 136: 193-9.

Trenk D, Hochholzer W, Müller B, Stratz C, Valina CM, Schmiebusch P, Büttner HJ, Neumann FJ:
Antiplatelet response to the 150-mg maintenance dose of clopidogrel in patients with insufficient platelet inhibition after clopidogrel loading for elective coronary stent placement.
EuroIntervention 2008; 4: 214-21.

Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG, Bergmann A, Potocki M, Noveanu M, Breidthardt T, Christ A, Boldanova T, Merki R, Schaub N, Bingisser R, Christ M, Mueller C:
Incremental value of copeptin for rapid rule out of acute myocardial infarction.
Journal of the American College of Cardiology 2009; 54: 60-8.

Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, Biedert S, Schaub N, Buerge C, Potocki M, Noveanu M, Breidthardt T, Twerenbold R, Winkler K, Bingisser R, Mueller C:
Early diagnosis of myocardial infarction with sensitive cardiac troponin assays.
New England Journal of Medicine 2009; 361: 858-67.

Hochholzer W, Trenk D, Fromm MF, Valina CM, Stratz C, Bestehorn HP, Büttner HJ,
Neumann FJ:
Impact of cytochrome P450 2C19 loss-of-function polymorphism and of major demographic characteristics on residual platelet function after loading and maintenance treatment with clopidogrel in patients undergoing elective coronary stent placement.
Journal of the American College of Cardiology 2010; 55: 2427-34.

Hochholzer W, Giugliano RP:
Lipid lowering goals: back to nature?
Therapeutic Advances in Cardiovascular Disease 2010; 4: 185-91.

Hochholzer W, Morrow DA, Giugliano RP:
Novel biomarkers in cardiovascular disease: update 2010.
American Heart Journal 2010; 160: 583-94.

Hochholzer W, Berg DD, Giugliano RP:
The Facts Behind Niacin.
Therapeutic Advances in Cardiovascular Disease 2011; 5: 227-40.

Wiviott SD, Hochholzer W:
On-clopidogrel platelet reactivity: a target in sight?
Journal of the American College of Cardiology 2011; 58: 1955-7.

Hochholzer W, Reichlin T, Stelzig C, Hochholzer K, Meissner J, Breidthardt T, Reiter M,
Duehsler B, Freidank H, Winkler K, Twerenbold R, Mueller C:
Impact of soluble fms-like tyrosine kinase 1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction.
European Heart Journal 2011; 32: 326-35.

Hochholzer W, Wiviott SD, Antman EM, Contant CF, Guo J, Giugliano RP, Dalby AJ,
Montalescot G, Braunwald E:
Predictors of Bleeding and Time Dependence of Association of Bleeding With Mortality: Insights From the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel--Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38).
Circulation 2011; 123: 2681-9.

Hochholzer W, Reichlin T, Twerenbold R, Stelzig C, Hochholzer K, Meissner J, Haaf P, Schaub N, Steuer S, Bassetti R, Reiter M, Roost K, Freidank H, Winkler K, Mueller C:
Incremental Value of High-Sensitivity Troponin T for Risk Prediction in Patients with Suspected Acute Myocardial Infarction.
Clinical Chemistry 2011; 57: 1318-26.

Hochholzer W, Trenk D, Mega JL, Morath T, Stratz C, Valina CM, O'Donoghue ML, Bernlochner I, Contant CF, Guo J, Sabatine MS, Schömig A, Neumann FJ, Kastrati A, Wiviott SD, Sibbing D:
Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy.
American Heart Journal 2011; 162: 518-526.

Mega JL, Hochholzer W, Frelinger AL, Kluk MJ, Angiolillo DJ, Kereiakes DJ, Isserman S, Rogers WJ, Ruff CT, Contant C, Pencina MJ, Scirica BM, Longtine JA, Michelson AD, Sabatine MS:
Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease.
The Journal of the American Medical Association 2011; 306: 2221-8.

Reiter M, Twerenbold R, Reichlin T, Haaf P, Peter F, Meissner J, Hochholzer W, Stelzig C, Freese M, Heinisch C, Breidthardt T, Freidank H, Winkler K, Campodarve I, Gea J, Mueller C:
Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays.
European Heart Journal 2011; 32: 1379-89.

Trenk D, Hochholzer W, Fromm MF, Zolk O, Valina CM, Stratz C, Neumann FJ:
Paraoxonase-1 Q192R Polymorphism and Antiplatelet Effects of Clopidogrel in Patients Undergoing Elective Coronary Stent Placement.
Circulation: Cardiovascular Genetics 2011; 4: 429-36.

Reichlin T, Irfan A, Twerenbold R, Reiter M, Hochholzer W, Burkhalter H, Bassetti S, Steuer S, Winkler K, Peter F, Meissner J, Haaf P, Potocki M, Drexler B, Osswald S, Mueller C:
Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction.
Circulation 2011; 124: 136-45.

Haaf P, Balmelli C, Reichlin T, Twerenbold R, Reiter M, Meissner J, Schaub N, Stelzig C, Freese M, Paniz P, Meune C, Drexler B, Freidank H, Winkler K, Hochholzer W, Mueller C:
N-terminal Pro B-type Natriuretic Peptide in the Early Evaluation of Suspected Acute Myocardial Infarction.
American Journal of Medicine 2011; 124: 731-9.

Reiter M, Twerenbold R, Reichlin T, Benz B, Haaf P, Meissner J, Hochholzer W, Stelzig C, Freese M, Heinisch C, Balmelli C, Drexler B, Freidank H, Winkler K, Campodarve I, Gea J, Mueller C:
Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays.
European Heart Journal 2012; 33: 988-97.

Fiebich BL, Collado JA, Stratz C, Valina C, Hochholzer W, Muñoz E, Bellido LM: Pseudoephedrine inhibits T-cell activation by targeting NF-κB, NFAT and AP-1 signaling pathways.
Immunopharmacology and Immunotoxicology 2012: 34: 98-106.

Schaub N, Reichlin T, Meune C, Twerenbold R, Haaf P, Hochholzer W, Niederhauser N, Bosshard P, Stelzig C, Freese M, Reiter M, Gea J, Buser A, Mebazaa A, Osswald S, Mueller C:
Markers of plaque instability in the early diagnosis and risk stratification of acute myocardial infarction.
Clinical Chemistry 2012; 58: 246-56.

Meune C, Reichlin T, Irfan A, Schaub N, Twerenbold R, Meissner J, Reiter M, Lüthi A, Haaf P, Balmelli C, Drexler B, Winkler K, Hochholzer W, Osswald S, Mueller C:
How safe is the outpatient management of patients with acute chest pain and mildly increased cardiac troponin concentrations?
Clinical Chemistry 2012; 58: 916-24.

Irfan A, Twerenbold R, Reiter M, Reichlin T, Stelzig C, Freese M, Haaf P, Hochholzer W, Steuer S, Bassetti S, Zellweger C, Freidank H, Peter F, Campodarve I, Meune C, Mueller C:
Determinants of high-sensitivity troponin T among patients with a noncardiac cause of chest pain.
American Journal of Medicine 2012; 125: 491-49.

Rowley JW, Finn AV, French PA, Jennings LK, Bluestein D, Gross PL, Freedman JE, Steinhubl SR, Zimmerman GA, Becker RC, Dauerman HL, Smyth SS; 2011 Platelet Colloquium Participants.
Cardiovascular devices and platelet interactions: understanding the role of injury, flow, and cellular responses.
Circulation Cardiovasc Interventions 2012; 5: 296-304.

Haaf P, Drexler B, Reichlin T, Twerenbold R, Reiter M, Meissner J, Schaub N, Stelzig C, Freese M, Heinzelmann A, Meune C, Balmelli C, Freidank H, Winkler K, Denhaerynck K, Hochholzer W, Osswald S, Mueller C:
High-sensitivity cardiac troponin in the distinction of acute myocardial infarction from acute cardiac noncoronary artery disease.
Circulation 2012; 126: 31-40.

Stratz C, Nührenberg TG, Binder H, Valina CM, Trenk D, Hochholzer W, Neumann FJ, Fiebich BL:
Micro-array profiling exhibits remarkable intra-individual stability of human platelet micro-RNA.
Thrombosis and Haemostasis 2012; 107: 634-41.

Stratz C, Amann M, Berg DD, Morrow DA, Neumann FJ, Hochholzer W:
Novel biomarkers in cardiovascular disease: research tools or ready for personalized medicine?
Cardiology in Review 2012; 20: 111-7.

Trenk D, Zolk O, Fromm MF, Neumann FJ, Hochholzer W:
Personalizing antiplatelet therapy with clopidogrel.
Clinical Pharmacology & Therapeutics 2012; 92: 476-85.

Trenk D, Kristensen SD, Hochholzer W, Neumann FJ:
High on-treatment platelet reactivity and P2Y12 antagonists in clinical trials.
Thrombosis and Haemostasis 2012109: 834-45.

Sibbing D, Hochholzer W, Kastrati A:
Influence of smoking on treatment with clopidogrel.
The Journal of the American Medical Association 2012; 308: 1322-3.

Hochholzer W, Giugliano RP:
Does it Make Sense to Combine Statins with Other Lipid-Altering Agents Following
Current Atherosclerosis Reports 2013; 15: 290.

Nührenberg TG, Trenk D, Leggewie S, Ristau I, Amann M, Stratz C, Hochholzer W, Valina CM, Neumann FJ:
Clopidogrel pretreatment of patients with ST-elevation myocardial infarction does not affect platelet reactivity after subsequent prasugrel-loading: Platelet reactivity in an observational study.
Platelets 2013; 24: 549-53.

Stratz C, Nührenberg T, Fiebich BL, Amann M, Kumar A, Binder H, Hoffmann I, Valina C, Hochholzer W, Trenk D, Neumann FJ:
Controlled type II diabetes mellitus has no major influence on platelet micro-RNA expression. Results from micro-array profiling in a cohort of 60 patients.
Thrombosis and Haemostasis 2014; 111: 902-11.

Trenk D, Hochholzer W:
Genetics of platelet inhibitor treatment.
British Journal of Clinical Pharmacology 2014; 77: 642-53.

Hochholzer W, Ruff CT, Mesa RA, Mattimore JF, Cyr JF, Lei L, Frelinger AL, Michelson AD, Berg DD, Angiolillo DJ, O'Donoghue ML, Sabatine MS, MegaJL:
Variability of individual platelet reactivity over time in patients treated with clopidogrel – insights from the ELEVATE-TIMI 56 trial
Journal of the American College of Cardiology 2014; 64: 361-8.

Hochholzer W, Valina CM, Stratz C, Amann M, Schlittenhardt D, Büttner HJ, Trenk D, Neumann FJ:
High-sensitivity cardiac troponin for risk prediction in patients with and without coronary heart disease.
International Journal of Cardiology 2014: 176: 444-9.

Jander N, Hochholzer W, Kaufmann BA, Bahlmann E, Gerdts E, Boman K, Chambers JB, Nienaber CA, Ray S, Rossebo A, Pedersen TR, Wachtell K, Gohlke-Bärwolf C, Neumann FJ, Minners J:
Velocity ratio predicts outcomes in patients with low gradient severe aortic stenosis and preserved EF.
Heart 2014; 100: 1946-53.

Dorfs S, Zeh W, Hochholzer W, Jander N, Kienzle RP, Pieske B, Neumann FJ:
Pulmonary capillary wedge pressure during exercise and long-term mortality in patients with suspected heart failure with preserved ejection fraction.
European Heart Journal 2014; 35: 3103-12.

Hochholzer W, Valina CM, Bömicke T, Amann M, Stratz C, Nührenberg T, Trenk D, Neumann FJ:
Intrinsic platelet reactivity before start with clopidogrel as predictor for on-clopidogrel platelet function and long-term clinical outcome.
Thrombosis and Haemostasis 2015; 114: 109-14.

Nührenberg TG, Stratz C, Leggewie S, Hochholzer W, Valina CM, Gick M, Kirtane AJ, Stone GW, Neumann FJ, Trenk D:
Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation. An ADAPT-DES substudy.
Thrombosis and Haemostasis 2015; 114: 1020-7.

Reny JL, Fontana P, Hochholzer W, Neumann FJ, Ten Berg J, Janssen PW, Geisler T, Gawaz M, Marcucci R, Gori AM, Cuisset T, Alessi MC, Berdagué P, Gurbel PA, Yong G, Angiolillo DJ, Aradi D, Beigel R, Campo G, Combescure C:
Vascular risk levels affect predictive value of platelet reactivity for the occurrence of MACE in clopidogrel treatment. Systematic review and collaborative meta-analysis of individual patient data.
Thrombosis and Haemostasis 2015; 115: 844-55.

Hochholzer W, Amann M, Titov A, Younas I, Löffelhardt N, Riede F, Potocnik C, Stratz C, Hauschke D, Trenk D, Neumann FJ, Valina CM:
Randomized comparison of different thienopyridine loading strategies in patients undergoing elective coronary intervention – the ExcelsiorLOAD trial.
JACC: Cardiovascular Interventions 2016; 9: 219-227.

Valina CM, Amann M, Stratz C, Trenk D, Löffelhardt N, Ferenc M, Neumann FJ, Hochholzer W:
Predictors of high-sensitivity cardiac troponin in stable patients undergoing coronary angiography.
Eurointervention 2016: 12: 329-36.

Carreras ET, Hochholzer W, Frelinger AL 3rd, Nordio F, O'Donoghue ML, Wiviott SD, Angiolillo DJ, Michelson AD, Sabatine MS, Mega JL:
Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel. Insights from the ELEVATE-TIMI 56 Trial.
Thrombosis and Haemostasis 2016; 116: 69-77.

Hochholzer W, Neumann FJ:
The new 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.
Deutsche Medizinische Wochenschrift 2016; 141: 782-5.

Stratz C, Bömicke T, Younas I, Kittel A, Amann M, Valina CM, Nührenberg T, Trenk D, Neumann FJ, Hochholzer W:
Comparison of Immature Platelet Count to Established Predictors of Platelet Reactivity During Thienopyridine Therapy.
Journal of the American College of Cardiology 2016; 68: 286-29.  

Stratz C, Nührenberg T, Amann M, Cederqvist M, Kleiner P, Valina CM, Trenk D, Neumann FJ, Hochholzer W:
Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.
Thrombosis and Haemostasis 2016; 116: 941-948.

Ferenc M, Gick M, Comberg T, Rothe J, Valina C, Toma A, Löffelhardt N, Hochholzer W, Riede F, Kienzle RP, Achtari A, Neumann FJ:
Culotte stenting vs. TAP stenting for treatment of de-novo coronary bifurcation lesions with the need for side-branch stenting: the Bifurcations Bad Krozingen (BBK) II angiographic trial.
European Heart Journal 2016; 37: 3399-3405.

Amann M, Ferenc M, Valina CM, Bömicke T, Stratz C, Leggewie S, Trenk D, Neumann FJ, Hochholzer W:
Validation of a P2Y12-receptor specific whole blood platelet aggregation assay.
Platelets 2016; 27: 668-672.

Biener M, Giannitsis E, Kuhner M, Zelniker T, Mueller-Hennessen M, Vafaie M, Trenk D, Neumann FJ, Hochholzer W, Katus HA:
Prognostic Value of High-Sensitivity Cardiac Troponin T Compared with Risk Scores in Stable Cardiovascular Disease.
American Journal of Medicine 2017; 130: 572-582.

Hochholzer W, Kleiner P, Younas I, Valina CM, Löffelhardt N, Amann M, Bömicke T, Ferenc M, Hauschke D, Trenk D, Neumann FJ, Stratz C:
Randomized Comparison of Oral P2Y12-Receptor Inhibitor Loading Strategies for Transitioning From Cangrelor: The ExcelsiorLOAD2 Trial.
JACC: Cardiovascular Interventions 2017; 10: 121-129.

Bömicke T, Valina CM, Stratz C, Amann M, Neumann FJ, Hochholzer W:
On-clopidogrel platelet reactivity as predictor for long-term clinical outcome in patients after planned discontinuation of clopidogrel.
Thrombosis and Haemostasis 2017; 117: 1644-1650.

Krankenberg H, Zeller T, Ingwersen M, Schmalstieg J, Gissler HM, Nikol S, Baumgartner I, Diehm N, Nickling E, Müller-Hülsbeck S, Schmiedel R, Torsello G, Hochholzer W, Stelzner C, Brechtel K, Ito W, Kickuth R, Blessing E, Thieme M, Nakonieczny J, Nolte T, Gareis R, Boden H, Sixt S:
Self-Expanding Versus Balloon-Expandable Stents for Iliac Artery Occlusive Disease: The Randomized ICE Trial.
JACC: Cardiovascular Interventions 2017; 10: 1694-1704.

Angiolillo DJ, Rollini F, Storey RF, Bhatt DL, James S, Schneider DJ, Sibbing D, So DYF, Trenk D, Alexopoulos D, Gurbel PA, Hochholzer W, De Luca L, Bonello L, Aradi D, Cuisset T, Tantry US, Wang TY, Valgimigli M, Waksman R, Mehran R, Montalescot G, Franchi F, Price MJ:
International Expert Consensus on Switching Platelet P2Y12 Receptor-Inhibiting Therapies.
Circulation 2017; 136: 1955-1975.

Valina CM, Merz S, Löffelhardt N, Amann M, Ferenc M, Stratz C, Neumann FJ, Hochholzer W:
Risk of discontinuation of clopidogrel after 1 month following bare-metal stents: a propensity-score adjusted comparison with continued administration of clopidogrel after drug-eluting stents.
Journal of Thrombosis and Thrombolysis 2018; 45: 432-439.

Pingpoh C, Siepe M, Burger K, Zietak T, Valina CM, Ferenc M, Beyersdorf F, Neumann FJ, Hochholzer W:
Impact of proximal radiopaque coronary bypass graft markers on postbypass surgery coronary angiography.
Journal of Thoracic and Cardiovascular Surgery 2018; 155: 1565-1572.

Stratz C, Nührenberg T, Valina CM, Löffelhardt N, Mashayekhi K, Ferenc M, Trenk D, Neumann FJ, Hochholzer W.
Impact of Reticulated Platelets on the Antiplatelet Effect of the Intravenous P2Y12-Receptor Inhibitor Cangrelor.
Thrombosis and Haemostasis 2018; 118: 362-368.

Bergmeijer TO, Reny JL, Pakyz RE, Gong L, Lewis JP, Kim EY, Aradi D, Fernandez-Cadenas I, Horenstein RB, Lee MTM, Whaley RM, Montaner J, Gensini GF, Cleator JH, Chang K, Holmvang L, Hochholzer W, Roden DM, Winter S, Altman RB, Alexopoulos D, Kim HS, Déry JP, Gawaz M, Bliden K, Valgimigli M, Marcucci R, Campo G, Schaeffeler E, Dridi NP, Wen MS, Shin JG, Simon T, Fontana P, Giusti B, Geisler T, Kubo M, Trenk D, Siller-Matula JM, Ten Berg JM, Gurbel PA, Hulot JS, Mitchell BD, Schwab M, Ritchie MD, Klein TE, Shuldiner AR; ICPC Investigators:
Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points-Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC).
American Heart Journal 2018; 198: 152-159.

Nührenberg TG, Hochholzer W, Mashayekhi K, Ferenc M, Neumann FJ:
Efficacy and safety of bivalirudin for percutaneous coronary intervention in acute coronary syndromes: a meta-analysis of randomized-controlled trials.
Clinical Research in Cardiology 2018; 107: 807-815.

Biener M, Giannitsis E, Kuhner M, Zelniker T, Mueller-Hennessen M, Vafaie M, Stoyanov KM, Neumann FJ, Katus HA, Hochholzer W, Valina CM.
Risk prediction in stable cardiovascular disease using a high-sensitivity cardiac troponin T single biomarker strategy compared to the ESC-SCORE.
Open Heart 2018; 5: e000710.

Ferenc M, Banholzer N, Hochholzer W, Mashayekhi K, Comberg T, Rothe J, Valina CM, Toma A, Löffelhardt N, Gick M, Neumann FJ, Nührenberg TG:
Long-term results after PCI of unprotected distal left main coronary artery stenosis: the Bifurcations Bad Krozingen (BBK)-Left Main Registry.
Clinical Research in Cardiology 2018; in press.

Valina C, Bömicke T, Abdelrazek S, Eltaweel S, Stratz C, Ferenc M, Trenk D, Chafai A, Neumann FJ, Hochholzer W:
Pharmacodynamic safety of clopidogrel monotherapy in patients under oral anticoagulation with a vitamin K antagonist undergoing coronary stent implantation.
Platelets 2018; in press.

Mashayekhi K, Nührenberg TG, Toma A, Gick M, Ferenc M, Hochholzer W, Comberg T, Rothe J, Valina CM, Löffelhardt N, Ayoub M, Zhao M, Bremicker J, Jander N, Minners J, Ruile P, Behnes M, Akin I, Schäufele T, Neumann FJ, Büttner HJ:
A Randomized Trial to Assess Regional Left Ventricular Function After Stent Implantation in Chronic Total Occlusion: The REVASC Trial.
JACC: Cardiovascular Interventions 2018; 11: 1982-1991.

Team leader
Prof. Dr. Willibald Hochholzer

Prof. Dr. Willibald Hochholzer
Senior physician
Head of clinical research

Fon: +49 7633 402-4285
Fax: +49 7633 402-2489
E-Mail: willibald.hochholzer@