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C Michael Gibson,
Anjan K Chakrabarti,
Jessica Mega,
Christophe Bode, Jean-Pierre Bassand,
Freek W A Verheugt,
Deepak L Bhatt,
Shinya Goto,
Marc Cohen,
Satishkumar Mohanavelu,
Paul Burton,
Gregg Stone,
Eugene Braunwald
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ABSTRACT: OBJECTIVES: To determine if rivaroxaban is associated with a reduction in stent thrombosis among ACS subjects in the ATLAS ACS 2-TIMI 51 trial. BACKGROUND: Dual antiplatelet therapy has been the mainstay of efforts to prevent stent thrombosis. Since thrombin is a potent stimulant of platelet activation, we hypothesized that inhibition of thrombin generation via factor Xa inhibition may further reduce the risk of stent thrombosis. METHODS: ATLAS ACS 2-TIMI 51 was a placebo-controlled trial that randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. RESULTS: Among subjects who had a stent placed prior to or at the time of the index event, rivaroxaban significantly reduced independently adjudicated Academic Research Consortium (ARC) definite and probable stent thrombosis in the pooled (1.9% vs. 1.5%, HR 0.65, p=0.017) and the 2.5 mg BID (1.9% vs. 1.5%, HR 0.61, p=0.023) treatment groups when compared to placebo, with a trend toward a reduction in the 5 mg BID treatment group (1.9% vs. 1.5%, HR 0.70, p=0.089). Among subjects who received both aspirin and a thienopyridine (Stratum 2), the benefit of rivaroxaban emerged during the period of active treatment with dual antiplatelet therapy (HR 0.68, 95% CI 0.50-0.92, combined rivaroxaban group vs. placebo). Among stented subjects who were treated with dual antiplatelet therapy, there was a mortality reduction among those treated with 2.5 mg BID of rivaroxaban (HR 0.56, 95% CI 0.35-0.89, p=0.014). CONCLUSIONS: Among stented ACS patients treated with dual antiplatelet therapy, the administration of 2.5 mg BID of rivaroxaban is associated with a reduction in stent thrombosis and mortality. CLINICAL TRIAL ID: NCT00809965.
Journal of the American College of Cardiology 04/2013; · 14.16 Impact Factor
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Kristian Thygesen,
Joseph S Alpert,
Allan S Jaffe,
Maarten L Simoons,
Bernard R Chaitman,
Harvey D White,
Hugo A Katus,
Fred S Apple,
Bertil Lindahl,
David A Morrow, [......],
Karl B Kern,
David J Moliterno,
Christian Mueller,
Aleksandar N Neskovic,
Burkert Mathias Pieske,
Steven P Schulman,
Robert F Storey,
Kathryn A Taubert,
Pascal Vranckx,
Daniel R Wagner
European Heart Journal 10/2012; 33(20):2551-2567. · 10.48 Impact Factor
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ABSTRACT: To determine the relationship between the number of CD14(+) cells, myocardial infarct (MI) size and left ventricular (LV) volumes in ST segment elevation MI (STEMI) and non-ST segment elevation MI (NSTEMI) patients.
A total of 62 patients with STEMI (n=34) or NSTEMI (n=28) were enrolled. The number of CD14(+) cells was assessed at admission. Infarct size, left ventricular ejection fraction (LVEF) and LV volumes were measured using magnetic resonance imaging five days after MI and six months after MI.
In STEMI patients, the number of CD14(+) cells was positively and significantly correlated with infarct size at day 5 (r=0.40; P=0.016) and after six months (r=0.34; P=0.047), negatively correlated with LVEF at day 5 (r=-0.50; P=0.002) and after six months (r=-0.46; P=0.005) and positively correlated with end-diastolic (r=0.38; P=0.02) and end-systolic (r=0.49; P=0.002) volumes after six months. In NSTEMI patients, no significant correlation was found between the number of CD14(+) cells and infarct size, LVEF or LV volumes at day 5 or after six months.
The number of CD14(+) cells at admission was associated with infarct size and LV remodelling in STEMI patients with large infarct size, whereas in NSTEMI patients, no relationship was observed between numbers of CD14(+) cells and LV remodelling.
Experimental and clinical cardiology 09/2012; 17(3):131-5. · 0.58 Impact Factor
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Christian W Hamm, Jean-Pierre Bassand,
Stefan Agewall,
Jeroen Bax,
Eric Boersma,
Hector Bueno,
Pio Caso,
Dariusz Dudek,
Stephan Gielen,
Kurt Huber,
Magnus Ohman,
Mark C Petrie,
Frank Sonntag,
Miguel Sousa Uva,
Robert F Storey,
William Wijns,
Doron Zahger
Giornale italiano di cardiologia (2006) 03/2012; 13(3):171-228.
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Ajay K Kakkar,
Iris Mueller, Jean-Pierre Bassand,
David A Fitzmaurice,
Samuel Z Goldhaber,
Shinya Goto,
Sylvia Haas,
Werner Hacke,
Gregory Y H Lip,
Lorenzo G Mantovani,
Freek W A Verheugt,
Waheed Jamal,
Frank Misselwitz,
Sophie Rushton-Smith,
Alexander G G Turpie
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ABSTRACT: Atrial fibrillation (AF) is associated with high rates of morbidity and mortality. Patients with AF carry a fivefold increased risk of stroke and the risk of death from AF-related stroke is doubled. Current management is often inadequate, leaving patients at risk for a potentially fatal or disabling event. The purpose of the GARFIELD registry is to evaluate the management and outcomes of patients with newly diagnosed non-valvular AF at risk for stroke.
The GARFIELD registry is an observational, multicenter, prospective study of patients with newly diagnosed AF and one or more additional risk factors for stroke. The aim is to enroll 55,000 patients at >1,000 centers in 50 countries. Enrollment will take place in five independent, sequential, prospective cohorts. An additional retrospective validation cohort of 5,000 patients with established AF and at least one additional risk factor for stroke will be conducted in parallel with cohort one. The study started in December 2009, with a planned recruitment period of 4 years and a minimum of 2-year follow-up for each patient.
The GARFIELD registry will provide valuable insights into the clinical management and related outcomes of AF patients throughout many regions of the world and across the spectrum of healthcare systems. By capturing data from unselected patients treated in everyday practice, the registry has the potential to identify best practices as well as deficiencies in available treatment options for specific patient populations and to describe how therapeutic strategies, patient care, and outcomes will evolve over time.
American heart journal 01/2012; 163(1):13-19.e1. · 4.65 Impact Factor
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ABSTRACT: To evaluate the potential value of intravascular ultrasound (IVUS) imaging in the diagnosis of aortic intramural hematoma (AIH).
From September 2002 to May 2005, a consecutive series of 15 patients with suspected aortic dissection (AD) underwent both IVUS imaging and spiral computed tomography (CT). Six patients diagnosed as acute type B AIH by CT or IVUS composed the present study group.
The study group consisted of five males and one female with mean age of 66 years old. All of them had chest or back pain. In one patient, CT omitted a localized AIH and an associated penetrating atherosclerotic ulcer (PAU), which were detected by IVUS. In another patient, CT mistaken a partly thrombosed false lumen as an AIH, whereas IVUS detected a subtle intimal tear and slow moving blood in the false lumen. In the four rest patients, both CT and IVUS made the diagnosis of AIH, however, IVUS detected three PAUs in three of them, only one of them was also detected by CT, and two of them escaped initial CT and were confirmed by follow up CT or magnetic resonance imaging.
IVUS imaging is a safe examination and has high accuracy in the diagnosis of AIH, particularly for diagnosing localized AIH, distinguishing AIH with thrombosed classic AD and detecting accompanied small PAUs.
Journal of Geriatric Cardiology 12/2011; 8(4):224-9.
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Richard C Becker, Jean Pierre Bassand,
Andrzej Budaj,
Daniel M Wojdyla,
Stefan K James,
Jan H Cornel,
John French,
Claes Held,
Jay Horrow,
Steen Husted,
Jose Lopez-Sendon,
Riitta Lassila,
Kenneth W Mahaffey,
Robert F Storey,
Robert A Harrington,
Lars Wallentin
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ABSTRACT: AIMS More intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal bleeding complications in the PLATO study. METHODS AND RESULTS PLATO was a randomized, double-blind, active control international, phase 3 clinical trial in patients with acute ST elevation and non-ST-segment elevation ACS. A total of 18 624 patients were randomized to either ticagrelor, a non-thienopyridine, reversibly binding platelet P2Y(12) receptor antagonist, or clopidogrel in addition to aspirin. Patients randomized to ticagrelor and clopidogrel had similar rates of PLATO major bleeding (11.6 vs. 11.2%; P = 0.43), TIMI major bleeding (7.9 vs. 7.7%, P = 0.56) and GUSTO severe bleeding (2.9 vs. 3.1%, P = 0.22). Procedure-related bleeding rates were also similar. Non-CABG major bleeding (4.5 vs. 3.8%, P = 0.02) and non-procedure-related major bleeding (3.1 vs. 2.3%, P = 0.05) were more common in ticagrelor-treated patients, primarily after 30 days on treatment. Fatal bleeding and transfusion rates did not differ between groups. There were no significant interactions for major bleeding or combined minor plus major bleeding between treatment groups and age ≥75 years, weight <60 kg, region, chronic kidney disease, creatinine clearance <60 mL/min, aspirin dose >325 mg on the day of randomization, pre-randomization clopidogrel administration, or clopidogrel loading dose. CONCLUSION Ticagrelor compared with clopidogrel was associated with similar total major bleeding but increased non-CABG and non-procedure-related major bleeding, primarily after 30 days on study drug treatment. Fatal bleeding was low and did not differ between groups.
European Heart Journal 11/2011; 32(23):2933-44. · 10.48 Impact Factor
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Jessica L Mega,
Eugene Braunwald,
Stephen D Wiviott, Jean-Pierre Bassand,
Deepak L Bhatt,
Christoph Bode,
Paul Burton,
Marc Cohen,
Nancy Cook-Bruns,
Keith A A Fox,
Shinya Goto,
Sabina A Murphy,
Alexei N Plotnikov,
David Schneider,
Xiang Sun,
Freek W A Verheugt,
C Michael Gibson
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ABSTRACT: Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome.
In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke.
Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04).
In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.).
New England Journal of Medicine 11/2011; 366(1):9-19. · 53.30 Impact Factor
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ABSTRACT: Endothelial colony-forming cells (ECFCs) are known to increase after acute myocardial infarction (AMI). We examined whether the presence of ECFCs is associated with preserved microvascular integrity in the myocardium at risk by reducing microvascular obstruction (MVO). We enrolled 88 patients with a first ST elevation AMI. ECFC colonies and circulating progenitor cells were characterized at admission. MVO was evaluated at 5 days and infarct size at 5 days and at 6-month follow-up by magnetic resonance imaging. ECFC colonies were detected in 40 patients (ECFC(pos) patients). At 5 days, MVO was of greater magnitude in ECFC(neg) versus ECFC(pos) patients (7.7 ± 5.3 vs. 3.2 ± 5%, p = 0.0002). At 6 months, in ECFC(pos) patients, there was a greater reduction in infarct size (-32.4 ± 33 vs. -12.8 ± 24%; p = 0.003) and a significant improvement in left ventricular (LV) volumes and ejection fraction. Level of circulating CD34+/VEGF-R2+ cells was correlated with the number of ECFC colonies (r = 0.54, p < 0.001) and relative change in infarct size (r = 0.71, p < 0.0001). The results showed that the presence of ECFC colonies is associated with reduced MVO after AMI, leading to reduced infarct size and less LV remodelling and can be considered a marker of preserved microvascular integrity in AMI patients.
Archiv für Kreislaufforschung 09/2011; 106(6):1397-410. · 7.35 Impact Factor
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Christian W Hamm, Jean-Pierre Bassand,
Stefan Agewall,
Jeroen Bax,
Eric Boersma,
Hector Bueno,
Pio Caso,
Dariusz Dudek,
Stephan Gielen,
Kurt Huber, [......],
Franz-Josef Neumann,
Ludwig Neyses,
Joep Perk,
Marco Roffi,
Francesco Romeo,
Mikhail Ruda,
Eva Swahn,
Marco Valgimigli,
Christiaan Jm Vrints,
Petr Widimsky
European Heart Journal 08/2011; 32(23):2999-3054. · 10.48 Impact Factor
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ABSTRACT: The greater mortality observed in women compared to men after acute myocardial infarction remains unexplained. Using an analysis of pairs, matched on a conditional probability of being male (propensity score), we assessed the effect of the baseline characteristics and management on 30-day mortality. Consecutive patients were included from January 2006 to December 2007. Two propensity scores (for being male) were calculated, 1 from the baseline characteristics and 1 from both the baseline characteristics and treatment. Two matched cohorts were composed using 1:1 matching and computed using the best 8 digits of the propensity score. Paired analyses were performed using conditional regression analysis. During the study period, 3,510 patients were included in the registry; 1,119 (32%) were women. Compared to the men, the women were 10 years older, had more co-morbidities, less often underwent angiography and reperfusion, and received less medical treatment. The 30-day mortality rate was 12.3% (130 of 1,060) for the women and 7.2% (167 of 2,324) for the men (p <0.001). The 2 matched populations represented 1,298 and 1,168 patients. After matching using the baseline characteristics, the only difference in treatment was a lower rate of angiography and reperfusion, with a trend toward greater 30-day mortality in women. After matching using both baseline characteristics and treatment, the 30-day mortality was similar for the men and women, suggesting that the increased use of invasive procedures in women could potentially be beneficial. In conclusion, compared to men, the 30-day mortality is greater in women and explained primarily by differences in baseline characteristics and to a lesser degree by differences in management. The difference in the use of invasive procedures persisted after matching by characteristics. In contrast, after matching using the baseline characteristics and treatment, the 30-day mortality was comparable across the genders.
The American journal of cardiology 07/2011; 108(6):789-98. · 3.58 Impact Factor
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Philippe Gabriel Steg,
Kurt Huber,
Felicita Andreotti,
Harald Arnesen,
Dan Atar,
Lina Badimon, Jean-Pierre Bassand,
Raffaele De Caterina,
John A Eikelboom,
Dietrich Gulba,
Martial Hamon,
Gérard Helft,
Keith A A Fox,
Steen D Kristensen,
Sunil V Rao,
Freek W A Verheugt,
Petr Widimsky,
Uwe Zeymer,
Jean-Philippe Collet
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ABSTRACT: Bleeding has recently emerged as an important outcome in the management of acute coronary syndromes (ACS), which is relatively frequent compared with ischaemic outcomes and has important implications in terms of prognosis, outcomes, and costs. In particular, there is evidence that patients experiencing major bleeding in the acute phase are at higher risk for death in the following months, although the causal nature of this relation is still debated. This position paper aims to summarize current knowledge regarding the epidemiology of bleeding in ACS and percutaneous coronary intervention, including measurement and definitions of bleeding, with emphasis on the recent consensus Bleeding Academic Research Consortium (BARC) definitions. It also provides an European perspective on management strategies to minimize the rate, extent, and consequences of bleeding. Finally, the research implications of bleeding (measuring and reporting bleeding in trials, the importance of bleeding as an outcome measure, and bleeding as a subject for future research) are also discussed.
European Heart Journal 06/2011; 32(15):1854-64. · 10.48 Impact Factor
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Claes Held,
Nils Asenblad, Jean Pierre Bassand,
Richard C Becker,
Christopher P Cannon,
Marc J Claeys,
Robert A Harrington,
Jay Horrow,
Steen Husted,
Stefan K James,
Kenneth W Mahaffey,
José C Nicolau,
Benjamin M Scirica,
Robert F Storey,
Marius Vintila,
Joseph Ycas,
Lars Wallentin
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ABSTRACT: The purpose of this study is to evaluate the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome undergoing coronary artery bypass graft surgery (CABG), as a post-randomization strategy.
Ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y(12)-receptor antagonist. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized 18,624 patients with acute coronary syndromes, ticagrelor compared with clopidogrel significantly reduced the risk of the primary composite end point of cardiovascular (CV) death, myocardial infarction, or stroke (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.77 to 0.92; p < 0.001). This report investigated the outcomes of patients treated with CABG during the trial.
In total, 1,899 patients underwent CABG post-randomization. The protocol recommended ticagrelor/placebo to be withheld for 24 to 72 h and clopidogrel/placebo for 5 days preoperatively. In all, 1,261 patients underwent CABG and were receiving study drug treatment <7 days before surgery. The statistical analysis was based on events occurring from the CABG procedure until the end of the study, excluding 3 patients with CABG after study end.
In the 1,261 patient cohort, the relative reduction of primary composite end point at 12 months (10.6% [66 of 629] with ticagrelor versus 13.1% [79 of 629] with clopidogrel; HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.29) was consistent with the results of the whole trial. Total mortality was reduced from 9.7% (58 of 629) to 4.7% (29 of 629; HR: 0.49; 95% CI: 0.32 to 0.77; p < 0.01), CV death from 7.9% (47 of 629) to 4.1% (25 of 629; HR: 0.52; 95% CI: 0.32 to 0.85; p < 0.01), and non-CV death numerically from 2.0% to 0.7% (p = 0.07). There was no significant difference in CABG-related major bleeding between the randomized treatments.
In the subgroup of patients undergoing CABG within 7 days after the last study drug intake, ticagrelor compared with clopidogrel was associated with a substantial reduction in total and CV mortality without excess risk of CABG-related bleeding.
Journal of the American College of Cardiology 02/2011; 57(6):672-84. · 14.16 Impact Factor
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ABSTRACT: The rate and type of reperfusion, as well as time delays to reperfusion are directly associated with mortality and are established as performance measures (PMs) in the treatment of ST elevation myocardial infarction (STEMI). To date, little information exists about PMs for reperfusion in clinical practice in Europe and their temporal changes.
Using the Euro Heart Survey ACS-III data set (2 years of inclusions between 2006 and 2008, 138 centres in 21 countries), we selected patients with STEMI eligible for reperfusion therapy. Recorded variables corresponded to the CARDS data set. The rate and type of reperfusion, as well as door to needle and door to artery times were assessed and compared between periods. Timely reperfusion was defined as a door to needle time < 30 min, or a door to artery time < 90 min. We assessed changes in PMs for reperfusion over the 2 years of recruitment. Among 19 205 patients included in the registry, 7655 had STEMI, and 6481 were admitted within the first 12 h and eligible for reperfusion. The rate of patients who underwent reperfusion increased from 77.2 to 81.3%, with an increase in the use of primary percutaneous coronary intervention (P-PCI). The door to needle and door to artery times decreased significantly during the study period, from 20 to 15 min (P = 0.0011) and from 60 to 45 min (P < 0.0001) respectively. As a result, the number of eligible patients receiving reperfusion therapy in a timely manner increased from 53.1 to 63.5% (P < 0.0001). In parallel, over the 2-year period, in-hospital mortality decreased from 8.1 to 6.6% (P = 0.047).
In centres participating in the Euro Heart Survey ACS III, PMs for reperfusion in STEMI improved significantly between 2006 and 2008, with greater use of PCI. Similarly, the rate of patients reperfused in a timely manner also increased, with a significant reduction in door to needle and door to artery times.
European Heart Journal 11/2010; 31(21):2614-24. · 10.48 Impact Factor
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Shamir R Mehta,
Jean-Francois Tanguay,
John W Eikelboom,
Sanjit S Jolly,
Campbell D Joyner,
Christopher B Granger,
David P Faxon,
Hans-Jurgen Rupprecht,
Andrzej Budaj,
Alvaro Avezum, [......],
Gilles Montalescot,
Carlos Macaya,
Giuseppe Di Pasquale,
Kari Niemela,
Andrew E Ajani,
Harvey D White,
Susan Chrolavicius,
Peggy Gao,
Keith A A Fox,
Salim Yusuf
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ABSTRACT: Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention (PCI). We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI.
The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries. 25,086 individuals with acute coronary syndromes and intended early PCI were randomly assigned to double-dose (600 mg on day 1, 150 mg on days 2-7, then 75 mg daily) versus standard-dose (300 mg on day 1 then 75 mg daily) clopidogrel, and high-dose (300-325 mg daily) versus low-dose (75-100 mg daily) aspirin. Randomisation was done with a 24 h computerised central automated voice response system. The clopidogrel dose comparison was double-blind and the aspirin dose comparison was open label with blinded assessment of outcomes. This prespecified analysis is of the 17,263 individuals who underwent PCI. The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. Analyses were by intention to treat, adjusted for propensity to undergo PCI. This trial is registered with ClinicalTrials.gov, number NCT00335452.
8560 patients were assigned to double-dose and 8703 to standard-dose clopidogrel (8558 and 8702 completed 30-day follow-up, respectively), and 8624 to high-dose and 8639 to low-dose aspirin (8622 and 8638 completed 30-day follow-up, respectively). Compared with the standard dose, double-dose clopidogrel reduced the rate of the primary outcome (330 events [3·9%] vs 392 events [4·5%]; adjusted hazard ratio 0·86, 95% CI 0·74-0·99, p=0·039) and definite stent thrombosis (58 [0·7%] vs 111 [1·3%]; 0·54 [0·39-0·74], p=0·0001). High-dose and low-dose aspirin did not differ for the primary outcome (356 [4·1%] vs 366 [4·2%]; 0·98, 0·84-1·13, p=0·76). Major bleeding was more common with double-dose than with standard-dose clopidogrel (139 [1·6%] vs 99 [1·1%]; 1·41, 1·09-1·83, p=0·009) and did not differ between high-dose and low-dose aspirin (128 [1·5%] vs 110 [1·3%]; 1·18, 0·92-1·53, p=0·20).
In patients undergoing PCI for acute coronary syndromes, a 7-day double-dose clopidogrel regimen was associated with a reduction in cardiovascular events and stent thrombosis compared with the standard dose. Efficacy and safety did not differ between high-dose and low-dose aspirin. A double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI.
Sanofi-Aventis and Bristol-Myers Squibb.
The Lancet 10/2010; 376(9748):1233-43. · 38.28 Impact Factor
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Jean-Pierre Bassand
European Heart Journal 03/2010; 31(6):640-1. · 10.48 Impact Factor
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ABSTRACT: Fondaparinux has recently been approved in patients with acute coronary syndromes. The primary aim of this study was to describe the changes in use of anticoagulants between January 2006 and December 2007. The secondary aim was to compare 30-day mortality and rate of a combined end point (30-day death or major bleeding) according to the initial and final anticoagulant agent used.
The rates of use of unfractionated heparin (UFH), enoxaparin, and fondaparinux were compared by periods of 1 month in a multicenter registry. The initial anticoagulant (first used at admission), the final anticoagulant (last used during hospitalization), and switches in anticoagulation were recorded. Temporal trends in monthly use of each anticoagulant were assessed; 30-day mortality rates and the combined end point were compared according to initial and final anticoagulant.
Among 2,874 patients included, the first anticoagulant used was UFH in 26%, enoxaparin in 59%, and fondaparinux in 15%. Respective figures for final anticoagulant were 17%, 56%, and 27%. Although 3 centers did not use fondaparinux (community centers with catheterization laboratory), the overall rate of use of fondaparinux, as initial and final anticoagulant, increased at the expense of the use of enoxaparin. We observed a growing proportion of patients with a switch from UFH to either enoxaparin or fondaparinux, ranging from 5% at the beginning to 25% at the end of the study. Patients treated with UFH were older, had more comorbidities, were at higher risk, and received fewer guidelines-recommended treatments. In patients submitted to angioplasty and treated with fondaparinux, a bolus of 60 IU/kg of UFH was added. After adjustment, 30-day mortality and combined end point rates were higher in patients treated with UFH. Irrespective of the type of acute coronary syndromes, patients treated with enoxaparin or fondaparinux had similar outcomes.
Between 2006 and 2007, the use of fondaparinux in patients with acute coronary syndromes increased considerably, either because it was used instead of enoxaparin or because of a switch from UFH. Adjusted mortality in patients treated with fondaparinux was lower than with UFH and similar to enoxaparin.
American heart journal 02/2010; 159(2):190-8. · 4.65 Impact Factor
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Sunil V Rao,
John Eikelboom,
Ph Gabriel Steg,
A Michael Lincoff,
William S Weintraub, Jean-Pierre Bassand,
A Koneti Rao,
C Michael Gibson,
John L Petersen,
Roxana Mehran,
Steven V Manoukian,
Richard Charnigo,
Kerry L Lee,
Mauro Moscucci,
Robert A Harrington
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ABSTRACT: Clinical trials of antithrombotic agents for the treatment of ACS routinely assess bleeding as a safety endpoint, but variation in bleeding definitions makes comparison of the relative safety of these agents difficult.
The ABC Multidisciplinary Working Group, an informal working group comprising clinical researchers and representatives from the US Food and Drug Administration, the National Institutes of Health, and the pharmaceutical industry, sought to develop a consensus approach to measuring the incidence and severity of bleeding complications during clinical trials of acute coronary syndromes (ACS). A meeting of the ABC was convened in April 2008 in Washington, DC, with the goal of developing a consensus approach to measuring the incidence and severity of hemorrhagic complications during clinical trials of ACS. Relevant literature on bleeding was reviewed through a series of short lectures and intensive group discussion.
Using existing evidence on bleeding and outcomes as well as clinical judgment, criteria for the assessment of bleeding were developed through expert consensus. This consensus statement divides bleeding-related data elements into three categories: essential, recommended, and optional.
The ABC Group recommendations for collection and reporting of bleeding complications provide a framework for consistency in the collection of information on hemorrhagic complications in trials of ACS. Widespread adoption of the statement recommendations will facilitate understanding of the mechanisms of adverse outcomes after bleeding and comparisons of the relative safety of antithrombotic agents, as well as the interpretation of safety results from future studies.
American heart journal 12/2009; 158(6):881-886.e1. · 4.65 Impact Factor
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Jean-Pierre Bassand,
Rizwan Afzal,
John Eikelboom,
Lars Wallentin,
Ron Peters,
Andrzej Budaj,
Keith A A Fox,
Campbell D Joyner,
Susan Chrolavicius,
Christopher B Granger,
Shamir Mehta,
Salim Yusuf
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ABSTRACT: In patients with acute coronary syndromes (ACS), the negative impact of baseline haemoglobin levels on ischaemic events, particularly death, is well established, but the association with bleeding risk is less well studied. The aim of this study was to assess the impact of baseline haemoglobin levels on major bleeding complications.
Pooled analysis of OASIS 5 and 6 data involving 32 170 patients with ACS with and without ST-segment elevation was performed. The association between baseline haemoglobin and major bleeding or ischaemic events was examined using multiple regression model.
were 30-day rates of major bleeding, death, and death/myocardial infarction (MI) analysed according to baseline haemoglobin levels. Baseline haemoglobin level independently predicted the risk of overall, procedure-related, and non-procedure-related major bleedings at 30 days [odds ratio (OR) 0.94, 95% CI 0.90-0.98; OR 0.94, 95% CI 0.90-0.99; and OR 0.89, 95% CI 0.83-0.95, respectively, per 1 g/dL haemoglobin increment above 10 g/dL]. In addition, a curvilinear relationship between baseline haemoglobin levels and death at 30 days was observed with a 6% decrease in the risk for every 1 g/dL haemoglobin increment above 10 g/dL up to 15.9 g/dL (OR 0.94, 95% CI 0.90-0.98) and a 19% increase above this value (OR 1.19, 95% CI, 0.98-1.43). A similar relationship for the composite outcome of death/MI was observed.
A low baseline haemoglobin level is an independent predictor of the risk of major bleeding in ACS as well as of the risk of death and death and MI. Among other predictors of bleeding risk, baseline haemoglobin should be taken into account in patients presenting with ACS. Clinical trial registration: ClinicalTrials.gov number, NCT00139815. http://clinicaltrials.gov/ct2/show/NCT00139815?term=NCT00139815&rank=1.
European Heart Journal 10/2009; 31(1):50-8. · 10.48 Impact Factor
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ABSTRACT: Elevated C-reactive protein level is a risk marker in patients with acute coronary syndromes (ACSs), but current risk score systems do not consider this factor. We studied the incremental predictive value of adding C-reactive protein to the Global Registry of Acute Coronary Events (GRACE) risk score.
Characteristics, treatments and 30-day mortality were recorded for 1408/1901 consecutive ACS patients. Changes in global model fit, discrimination, calibration, and reclassification were evaluated upon addition of C-reactive protein to the GRACE risk score. High-C-reactive protein patients (C-reactive protein >22 mg/L, 4th quartile of C-reactive protein) were older, had more comorbidities and worse haemodynamic conditions, received less recommended treatment, and had a four-fold higher 30 day mortality. Multivariable analysis demonstrated high-C-reactive protein as an important and independent predictor of mortality. Addition of high-C-reactive protein in the GRACE model modestly improved global fit, discriminatory capacity (c-statistic from 0.795 to 0.823), and calibration. Patients were divided into four groups according to GRACE risk score prediction: <1, 1 to <5, 5 to <10, and >or=10%. The model with high-C-reactive protein allowed adequate reclassification in 12.2%.
Elevated C-reactive protein level is a modest but independent predictive factor of 30-day mortality in ACS patients, even after adjustment for co-morbidities, haemodynamic conditions, and treatment. Combined with the GRACE risk score, C-reactive protein information improves risk classification.
European Heart Journal 08/2009; 31(3):290-7. · 10.48 Impact Factor
