Peter R Sinnaeve

Publications (15)151.37 Total impact

• Article: Do Ingredients Make the Difference? Finding the Best Cocktail of an Anticoagulant with Antiplatelets.

  Peter R Sinnaeve, Frans Van de Werf
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  ABSTRACT: In clinical practice, the need for adding one or two antiplatelet agents to an oral anticoagulant (OAC) often arises in patients with atrial fibrillation (AF). The indications can be diverse, from primary prevention in patients at high risk for an ischemic atherosclerotic event, over secondary prevention after an acute coronary syndrome (ACS) to prevention of stent thrombosis.(1,2) Unfortunately, adding antiplatelet agents to oral anticoagulants increases bleeding risk, and although this risk is highest early after initiation of combination therapy, there appears to be no safe therapeutic window.(1) The difficulty lies in balancing thromboembolic risk versus bleeding risk in the individual patient. Since many new agents came on the market recently, there are a wide variety of possible strategies not only with regard the number and type of agents but also the intensity of anticoagulation and the duration of the combination treatment.
  Circulation 12/2012; · 14.74 Impact Factor
• Article: Routine invasive versus conservative management in non-ST-elevation acute coronary syndromes.

  Peter R Sinnaeve
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  ABSTRACT: Coronary angiography as part of the management of non-ST-segment-elevation acute coronary syndrome (ACS) patients has several advantages but also carries some risks if done routinely. The advantage of a planned early invasive approach in moderate to high-risk patients appears to be clear and is recommended by guidelines. This is often not mirrored by real world practice; however, only about 50% to 70% of ACS patients do undergo a diagnostic catheterization. In addition, the optimal timing of an angiography or intervention in relation to contemporary antithrombotic regimens remains unclear. In this paper, the current evidence for routine invasive management as well as the timing of catheterization in non-ST-ACS is reviewed.
  Journal of Cardiovascular Translational Research 02/2012; 5(1):22-9. · 2.61 Impact Factor
• Source

  Available from: Giuseppe Ambrosio

  Article: Thrombin-receptor antagonist vorapaxar in acute coronary syndromes.

  Pierluigi Tricoci, Zhen Huang, Claes Held, David J Moliterno, Paul W Armstrong, Frans Van de Werf, Harvey D White, Philip E Aylward, Lars Wallentin, Edmond Chen, [......], Juan Carlos Prieto, Witold Ruzyllo, Peter R Sinnaeve, Robert F Storey, Marco Valgimigli, David J Whellan, Petr Widimsky, John Strony, Robert A Harrington, Kenneth W Mahaffey
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  ABSTRACT: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
  New England Journal of Medicine 11/2011; 366(1):20-33. · 53.30 Impact Factor
• Source

  Available from: Uwe Zeymer

  Article: Prediction of cardiogenic shock using plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone [corrected] concentrations in ST elevation myocardial infarction: an analysis from the ASSENT-4 Percutaneous Coronary Intervention Trial.

  Rudolf Jarai, Kurt Huber, Kris Bogaerts, Peter R Sinnaeve, Justin Ezekowitz, Allan M Ross, Uwe Zeymer, Paul W Armstrong, Frans J Van de Werf
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  ABSTRACT: Cardiogenic shock is a major cause of death in ST elevation myocardial infarction. We investigated whether determination of plasma [corrected] B-type natriuretic peptide and the N-terminal fragment of its pro-hormone in the acute phase of ST elevation myocardial infarction could identify patients prone to development of cardiogenic shock. Retrospective analysis of a multicenter, randomized open-label trial (ASSENT-4 PCI; ClinicalTrials.gov Identifier: NCT00168792). Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone were determined in available stored samples of 1016 ST elevation myocardial infarction patients without signs of cardiogenic shock at randomization to primary percutaneous coronary intervention or to full-dose tenecteplase before percutaneous coronary intervention. The end point of the present analysis was in-hospital cardiogenic shock. None. In total, 57 (5.6%) patients had cardiogenic shock during index hospitalization. In-hospital cardiogenic shock increased precipitously with higher baseline concentrations of plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone (B-type natriuretic peptide and the N-terminal fragment of its pro-hormone < or =67 pg/mL: 1.9%; 68-1482 pg/mL: 5.9%; >1482 pg/mL: 14.9%; p < .001). Higher plasma [corrected] B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations were predictors of in-hospital shock, especially among those patients with relatively low clinical risk (no requirement of inotropic support before angiography, systolic blood pressure >100 mm Hg, heart rate <100 bpm, Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score of <122). In multivariate Cox regression analysis, higher plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations remained significant predictors of shock, in addition to age, systolic blood pressure, heart rate, and randomization to facilitated percutaneous coronary intervention and Killip classification. Furthermore, plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone significantly predicted in-hospital shock independently of the validated Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score (p = .014). Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations measured early in the acute phase of ST elevation myocardial infarction are useful in predicting the development of in-hospital cardiogenic shock.
  Critical care medicine 09/2010; 38(9):1793-801. · 6.37 Impact Factor
• Article: Plasma N-terminal fragment of the prohormone B-type natriuretic peptide concentrations in relation to time to treatment and Thrombolysis in Myocardial Infarction (TIMI) flow: a substudy of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial.

  Rudolf Jarai, Kurt Huber, Kris Bogaerts, Walter Droogne, Justin Ezekowitz, Christopher B Granger, Peter R Sinnaeve, Allan M Ross, Uwe Zeymer, Paul W Armstrong, Frans J Van de Werf
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  ABSTRACT: We investigated the prognostic significance of plasma N-terminal fragment of the prohormone B-type natriuretic peptide (Nt-proBNP) concentrations in addition to time to reperfusion and Thrombolysis in Myocardial Infarction (TIMI) flow before and after coronary intervention in patients with ST elevation myocardial infarction (STEMI) from the database of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial. Plasma Nt-proBNP was available in 1,037 patients with STEMI. Patients were randomized either to primary (p-PCI) or to full-dose tenecteplase before PCI (f-PCI).The study end point was the composite of death, cardiogenic shock, or congestive heart failure at 90 days. According to classification tree analysis, patients with Nt-proBNP levels >694 pg/mL had the highest primary end point rates (33.8% vs 11%, P < .001). In Cox regression analysis, Nt-proBNP >694 pg/mL strongly predicted 90-day survival even among patients with short treatment delay (f-PCI < or =3 hours: hazard ratio [HR] 2.63, P = .002 and p-PCI < or =3 hours: HR 4.87, P < .001, respectively). Patients with TIMI 3 flow after coronary intervention were at significantly higher risk of the primary end point if admission Nt-proBNP exceeded 694 pg/mL (f-PCI: HR 2.88, P < .001 and p-PCI: HR 3.84, P < .001, respectively). In multivariable analysis, Nt-proBNP >694 pg/mL significantly (P = .001) predicted 90-day survival in addition to age (P < .001), TIMI flow after PCI (P < .001), body mass index (P = .026), anterior wall infarction (P = .035), and systolic blood pressure at randomization (P = .036), respectively. Elevated plasma concentrations of Nt-proBNP in the early phase of STEMI determine in-hospital and 90-day outcome after infarction irrespective of time to treatment and pre- or postinterventional TIMI flow.
  American heart journal 01/2010; 159(1):131-40. · 4.65 Impact Factor
• Article: Reperfusion before percutaneous coronary intervention in ST-elevation myocardial infarction patients is associated with lower N-terminal pro-brain natriuretic peptide levels during follow-up, irrespective of pre-treatment with full-dose fibrinolysis.

  Peter R Sinnaeve, Justin A Ezekowitz, Kris Bogaerts, Walter Droogne, Rudolf Jarai, Kurt Huber, Christopher B Granger, Walter J Desmet, Paul W Armstrong, Frans J Van de Werf
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  ABSTRACT: N-terminal pro-brain natriuretic peptide (NT-proBNP) levels predict outcomes in ST-elevation myocardial infarction patients treated with fibrinolysis or primary percutaneous coronary intervention (PCI). However, its role in facilitated PCI has not yet been assessed; it may be a tool to evaluate the lower event rates with primary PCI in ASSENT-4. In ASSENT-4, 1667 patients were randomized to tenecteplase (TNK) followed by PCI or primary PCI alone. Baseline, discharge/Day 7, and 90-day NT-proBNP levels were available for 1008, 971, and 813 patients. Increasing quartiles of baseline NT-proBNP levels were associated with a higher risk of the combined endpoint of death, heart failure, and shock at 90 days and 1-year mortality (P < 0.001). Events were more common with TNK + PCI, regardless of baseline NT-proBNP quartile. When analysing baseline NT-proBNP as a continuous variable, no treatment interaction was observed for the primary endpoint (P = 0.17) or 1-year mortality (P = 0.08). Overall, NT-proBNP levels at Day 7 or 90 were not different between the two treatments. In patients with TIMI 2-3 flow before PCI, NT-proBNP at Day 90 was lower in PCI-only patients (P = 0.01), although no interaction was observed (P = 0.14). In TNK-pre-treated patients without reperfusion (TIMI 0-1) after PCI, NT-proBNP levels at Day 7 or 90 were not significantly higher than in PCI patients. Baseline NT-proBNP predicts outcome at 90 days and 1 year in patients undergoing PCI with or without facilitation with TNK. A higher rate of reperfusion in lytic-pre-treated patients did not result in lower NT-proBNP during follow-up. Thus, baseline and subsequent NT-proBNP levels do not explain the lower mortality rate with PCI alone seen in this trial.
  European Heart Journal 08/2009; 30(18):2213-9. · 10.48 Impact Factor
• Source

  Available from: Frederick A Anderson

  Article: Association of elevated fasting glucose with increased short-term and 6-month mortality in ST-segment elevation and non-ST-segment elevation acute coronary syndromes: the Global Registry of Acute Coronary Events.

  Peter R Sinnaeve, P Gabriel Steg, Keith A A Fox, Frans Van de Werf, Gilles Montalescot, Christopher B Granger, Elias Knobel, Frederick A Anderson, Omar H Dabbous, Alvaro Avezum
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  ABSTRACT: Elevated blood glucose level at admission is associated with worse outcome after a myocardial infarction. The impact of elevated glucose level, particularly fasting glucose, is less certain in non-ST-segment elevation acute coronary syndromes. We studied the relationship between elevated fasting blood glucose levels and outcome across the spectrum of ST-segment elevation and non-ST-segment elevation acute coronary syndromes in a large multicenter population broadly representative of clinical practice. Fasting glucose levels were available for 13 526 patients in the Global Registry of Acute Coronary Events. A multivariate logistic regression analysis was used for assessing the association between admission or fasting glucose level and in-hospital or 6-month outcome, adjusted for the variables from the registry risk scores. Higher fasting glucose levels were associated with a graded increase in the risk of in-hospital death (odds ratios [95% confidence intervals] vs <100 mg/dL: 1.51 [1.12-2.04] for 100-125 mg/dL, 2.20 [1.64-2.60] for 126-199 mg/dL, 5.11 [3.52-7.43] for 200-299 mg/dL, and 8.00 [4.76-13.5] for > or =300 mg/dL). When taken as a continuous variable, higher fasting glucose level was related to a higher probability of in-hospital death, without detectable threshold and irrespective of whether patients had a history of diabetes mellitus. Higher fasting glucose levels were found to be associated with a higher risk of postdischarge death up to 6 months. The risk of postdischarge death at 6 months was significantly higher with fasting glucose levels between 126 and 199 mg/dL (1.71 [1.25-2.34]) and 300 mg/dL or greater (2.93 [1.33-6.43]), but not within the 200- to 299-mg/dL range (1.08 [0.60-1.95]). Short-term and 6-month mortality was increased significantly with higher fasting glucose levels in patients across the spectrum of acute coronary syndromes, thus extending this relation to patients with non-ST-segment elevation myocardial infarction. The relation between fasting glucose level and risk of adverse short-term outcomes is graded across different glucose levels with no detectable threshold for diabetic or nondiabetic patients.
  Archives of internal medicine 03/2009; 169(4):402-9. · 11.46 Impact Factor
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  Available from: William E Kraus

  Article: Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.

  Peter R Sinnaeve, Mark P Donahue, Peter Grass, David Seo, Jacky Vonderscher, Salah-Dine Chibout, William E Kraus, Michael Sketch, Charlotte Nelson, Geoffrey S Ginsburg, Pascal J Goldschmidt-Clermont, Christopher B Granger
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  ABSTRACT: Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall. Patients were selected according to their coronary artery disease index (CADi), a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from blood of 120 patients with at least a stenosis greater than 50% (CADi > or = 23) and from 121 controls without evidence of coronary stenosis (CADi = 0). 160 individual genes were found to correlate with CADi (rho > 0.2, P<0.003). Prominent differential expression was observed especially in genes involved in cell growth, apoptosis and inflammation. Using these 160 genes, a partial least squares multivariate regression model resulted in a highly predictive model (r(2) = 0.776, P<0.0001). The expression pattern of these 160 genes in aortic tissue also predicted the severity of atherosclerosis in human aortas, showing that peripheral blood gene expression associated with coronary atherosclerosis mirrors gene expression changes in atherosclerotic arteries. In conclusion, the simultaneous expression pattern of 160 genes in whole blood correlates with the severity of coronary artery disease and mirrors expression changes in the atherosclerotic vascular wall.
  PLoS ONE 01/2009; 4(9):e7037. · 4.09 Impact Factor
• Article: The good, the bad, and the ugly: triple therapy after PCI in patients requiring chronic anticoagulation.

  Peter R Sinnaeve
  European Heart Journal 04/2007; 28(6):657-8. · 10.48 Impact Factor
• Source

  Available from: Lars Wallentin

  Article: Age, outcomes, and treatment effects of fibrinolytic and antithrombotic combinations: findings from Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-3 and ASSENT-3 PLUS.

  Peter R Sinnaeve, Yao Huang, Kris Bogaerts, Alec Vahanian, Jennifer Adgey, Paul W Armstrong, Lars Wallentin, Frans J Van de Werf, Christopher B Granger
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  ABSTRACT: Elderly patients with acute myocardial infarction are at particularly high risk for death and bleeding complications. The efficacy and safety of antithrombotic strategies in these patients remain unclear. To provide more insight into the risk and benefit of antithrombotic strategies in the elderly, we examined patients from the ASSENT-3 and ASSENT-3 PLUS trials with STEMI who were treated with tenecteplase (TNK) and unfractionated heparin (UFH) or enoxaparin, or half-dose TNK with abciximab and reduced-dose UFH. Older patients had a higher risk profile, and lower use of concomitant therapies and revascularization procedures. We found an interaction between age and treatment effect for the efficacy end point (P = .0007) and the efficacy plus safety end point (P < .0001). Younger patients (<65 years) had a lower risk of the composite efficacy plus safety end point with enoxaparin (relative risk [RR] 0.84, 95% CI 0.74-0.94) or abciximab (RR 0.79, 95% CI 0.69-0.90) compared with UFH. In patients >65 years of age, the benefit of enoxaparin appeared to be offset by an increased risk of bleeding complications. The risk of the efficacy plus safety end point tended to be higher in elderly patients receiving abciximab and half-dose TNK (RR 1.18, 95% CI 0.91-1.51 for 76-85 years of age and RR 1.48, 95% CI 0.88-2.49 for >85 years of age). Although TNK with either enoxaparin or abciximab appeared to be more effective than with standard UHF in younger patients, these combinations tended to be less effective and even may be unsafe in the elderly. Development of new combination strategies and dosing schemes of fibrinolytics and antithrombotics with improved efficacy and safety in the elderly remains a high priority.
  American heart journal 11/2006; 152(4):684.e1-9. · 4.65 Impact Factor
• Article: Simultaneous triple kissing stenting in an unprotected left main coronary artery.

  Christophe L Dubois, Peter R Sinnaeve, Walter J Desmet
  European Heart Journal 08/2006; 27(16):1897. · 10.48 Impact Factor
• Article: Direct thrombin inhibitors in acute coronary syndromes: effect in patients undergoing early percutaneous coronary intervention.

  Peter R Sinnaeve, John Simes, Salim Yusuf, Jyotsna Garg, Shamir Mehta, John Eikelboom, John A Bittl, Patrick Serruys, Eric J Topol, Christopher B Granger
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  ABSTRACT: We evaluated the effect of direct thrombin inhibitors (DTIs) in patients undergoing early percutaneous coronary intervention (PCI), using the DTI Trialists' Collaboration database of 35,970 patients from 11 randomized trials of DTIs vs. heparin. We performed a Cox proportional hazards regression analysis with PCI as a time-dependent covariate to assess the independent impact of DTIs according to the performance of early PCI. PCI was performed in 7049 patients in the first 72 h after randomization. In trials in which PCI was not planned, DTIs were associated with a 10% relative risk reduction in death or myocardial infarction at 30 days (HR=0.90, 95% CI: 0.84-0.97). This benefit was found to be greater in patients undergoing early PCI (HR=0.66, 95% CI: 0.48-0.91) than those undergoing non-early PCI (HR=0.94, 95% CI: 0.86-1.03). After adjustment for baseline characteristics and propensity to undergo PCI, the risk of death or myocardial infarction remained lower with DTI (HR=0.62, 95% CI: 0.44-0.89). After adjustment for baseline differences and propensity to undergo early PCI, DTIs appeared to be more effective than heparin in reducing death or re-infarction among patients undergoing early PCI.
  European Heart Journal 12/2005; 26(22):2396-403. · 10.48 Impact Factor
• Article: Genetics and coronary artery disease.

  Peter R Sinnaeve
  Acta cardiologica 01/2005; 59(6):581-93. · 0.61 Impact Factor
• Article: Global patterns of health care for acute coronary syndromes.

  Peter R Sinnaeve, Frans J Van de Werf
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  ABSTRACT: Despite similar guidelines, remarkable global differences exist in the management of acute coronary syndromes. This review describes recent insights in global patterns of patient baseline characteristics, treatment strategies, medication use, and outcome in acute coronary syndromes. Results from recent registries and randomized clinical trials suggest that the arrival of many novel medications and treatment options for acute coronary syndromes has led to interregional heterogeneity in the management and treatment of patients with acute coronary syndromes. These differences in health care and adherence to national and international guidelines appear to be influenced by geographical, social, cultural, and economic factors, resulting in regional variation in hospital characteristics, physician attitude, access to resources or advanced cardiovascular care, access to the literature, and the availability of drugs. Significant differences in diagnosis and treatment of acute coronary syndrome patients can be observed globally, despite similar guidelines based on the same randomized clinical trials. Guidelines are not adapted promptly worldwide, influencing outcome and health care expenditure.
  Current Opinion in Cardiology 12/2004; 19(6):625-30. · 2.33 Impact Factor
• Article: Efficacy of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: one-year follow-up results of the Assessment of the Safety of a New Thrombolytic-3 (ASSENT-3) randomized trial in acute myocardial infarction.

  Peter R Sinnaeve, John H Alexander, Kris Bogaerts, Ann Belmans, Lars Wallentin, Paul Armstrong, Jennifer A A Adgey, Michal Tendera, Rafael Diaz, Leopoldo Soares-Piegas, Alec Vahanian, Christopher B Granger, Frans J Van De Werf
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  ABSTRACT: In the ASsessment of the Safety of a New Thrombolytic 3 (ASSENT-3) study, full-dose tenecteplase plus enoxaparin or half-dose tenecteplase plus abciximab reduced the frequency of ischemic complications of acute myocardial infarction, when compared to full-dose tenecteplase plus unfractionated heparin. The aim of the present study was to determine the effect of these fibrinolytic regimens on 1-year mortality. Vital status at 1 year was available for 5942 patients (97.5%) of the 6095 initially enrolled in the study. At 1 year, 515 patients (8.7%) had died. Elderly or female patients and patients with low body weight, previous myocardial infarction, anterior wall myocardial infarction, and diabetes were at increased risk for death at 1 year. Mortality at 1 year was 7.9 % (n = 161) in the heparin group, 8.1% (n = 166) in the enoxaparin group, and 9.3% (n = 188) in the abciximab group (P =.226). Overall, pairwise comparisons did not show a significant difference among treatment regimens: relative risk 1.03 (95% CI 0.82-1.30) for enoxaparin versus heparin (P =.794) and relative risk 1.18 (95% CI 0.95-1.47) for abciximab versus heparin (P =.144). However, 1-year outcome tended to be worse with abciximab in diabetic patients. Mortality at 1 year after acute myocardial infarction remains high. Despite a reduction in ischemic complications after acute myocardial infarction with the use of full-dose tenecteplase plus enoxaparin or half-dose tenecteplase plus abciximab, mortality at 1 year was similar in these treatment groups.
  American heart journal 07/2004; 147(6):993-8. · 4.65 Impact Factor