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Sripal Bangalore, Gabriel Steg,
Prakash Deedwania,
Kevin Crowley,
Kim A Eagle,
Shinya Goto,
E Magnus Ohman,
Christopher P Cannon,
Sidney C Smith,
Uwe Zeymer,
Elaine B Hoffman,
Franz H Messerli,
Deepak L Bhatt
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ABSTRACT: β-Blockers remain the standard of care after a myocardial infarction (MI). However, the benefit of β-blocker use in patients with coronary artery disease (CAD) but no history of MI, those with a remote history of MI, and those with only risk factors for CAD is unclear.
To assess the association of β-blocker use with cardiovascular events in stable patients with a prior history of MI, in those with CAD but no history of MI, and in those with only risk factors for CAD.
Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14,043), known CAD without MI (n = 12,012), or those with CAD risk factors only (n = 18,653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009.
The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure.
Among the 44,708 patients, 21,860 were included in the propensity score-matched analysis. With a median follow-up of 44 months (interquartile range, 35-45 months), event rates were not significantly different in patients with β-blocker use compared with those without β-blocker use for any of the outcomes tested, even in the prior MI cohort (489 [16.93%] vs 532 [18.60%], respectively; hazard ratio [HR], 0.90 [95% CI, 0.79-1.03]; P = .14). In the CAD without MI cohort, the associated event rates were not significantly different in those with β-blocker use for the primary outcome (391 [12.94%]) vs without β-blocker use (405 [13.55%]) (HR, 0.92 [95% CI, 0.79-1.08]; P = .31), with higher rates for the secondary outcome (1101 [30.59%] vs 1002 [27.84%]; odds ratio [OR], 1.14 [95% CI, 1.03-1.27]; P = .01) and for the tertiary outcome of hospitalization (870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30]; P = .01). In the cohort with CAD risk factors only, the event rates were higher for the primary outcome with β-blocker use (467 [14.22%]) vs without β-blocker use (403 [12.11%]) (HR, 1.18 [95% CI, 1.02-1.36]; P = .02), for the secondary outcome (870 [22.01%] vs 797 [20.17%]; OR, 1.12 [95% CI, 1.00-1.24]; P = .04) but not for the tertiary outcomes of MI (89 [2.82%] vs 68 [2.00%]; HR, 1.36 [95% CI, 0.97-1.90]; P = .08) and stroke (210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P = .06). However, in those with recent MI (≤1 year), β-blocker use was associated with a lower incidence of the secondary outcome (OR, 0.77 [95% CI, 0.64-0.92]).
In this observational study of patients with either CAD risk factors only, known prior MI, or known CAD without MI, the use of β-blockers was not associated with a lower risk of composite cardiovascular events.
JAMA The Journal of the American Medical Association 10/2012; 308(13):1340-9. · 30.03 Impact Factor
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Ahmed Krimly,
Raymond T Yan,
Andrew T Yan,
J Paul DeYoung,
Richard Gallo, Gabriel Steg,
John Eikelboom,
Joel M Gore,
Keith A A Fox,
David Fitchett,
Mackenzie A Quantz,
Shaun G Goodman
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ABSTRACT: Randomized trials have established the efficacy of clopidogrel in acute coronary syndromes (ACS). The benefit of clopidogrel has also been observed in the subgroup of ACS patients who subsequently undergo coronary artery bypass surgery (CABG); however, this therapy is discontinued preoperatively and the frequency with which clopidogrel is restarted post-CABG is unknown.
We examined the pattern of clopidogrel use in the Canadian Global Registry of Acute Coronary Events (GRACE), GRACE2, and CANRACE (2003-2008) post-CABG ACS patients. We stratified the patients according to whether they underwent CABG during their index hospitalization for ACS and whether they were prescribed clopidogrel at discharge.
Among those patients in whom clopidogrel status at discharge was known, 5904 (60%) of 9841 were discharged from hospital on clopidogrel. Use of clopidogrel at discharge was observed in 2222 (40.8%) of 5443 patients who were medically managed (ie, did not undergo percutaneous coronary intervention [PCI] or CABG) and in 3585 (90.1%) of 3980 patients who underwent in-hospital PCI. Overall, 455 (3.3%) of 13,776 patients underwent CABG during the index hospitalization; 255 (56%) patients were started on clopidogrel during the first 24 hours, and 66 of these patients (25.9%) were discharged on clopidogrel. In contrast, 5681 (61.3%) of the 9262 patients who did not undergo in-hospital CABG were discharged on clopidogrel.
Although current guidelines recommend the use of clopidogrel post-CABG in patients with ACS, our observations suggest that only 1 in 4 or 5 Canadian patients are discharged on this therapy.
The Canadian journal of cardiology 08/2011; 27(6):711-5. · 3.36 Impact Factor
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Olivier Barthélémy,
Tobias Limbourg,
Jean Philippe Collet,
Farzin Beygui,
Johanne Silvain,
Anne Bellemain-Appaix,
Guillaume Cayla,
Thomas Chastre,
Iris Baumgartner,
Joachim Röther,
Uwe Zeymer,
Deepak L Bhatt, Gabriel Steg,
Gilles Montalescot
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ABSTRACT: BACKGROUND: We aimed to assess whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events in stable patients with established atherothrombosis or multiple risk factors. METHODS: We analysed the 23,728 European patients of the REACH Registry; 20,588 (86.8%) had established atherothrombotic disease and 3140 (13.2%) had multiple risk factors only. Aspirin (ASA) and/or NSAIDs use was determined at enrolment and ischemic events were recorded over two years of follow-up. cMACCE was defined as the composite of CV death, MI or stroke. Bleeding was defined as any bleeding leading to both hospitalisation and transfusion. RESULTS: The mean age of population was 67.2±9.8years. At baseline, 1573 patients (6.6%) received NSAIDs and 15,395 (64.9%) received ASA. Four groups were defined: 1) no ASA/no NSAIDs, 2) ASA only, 3) NSAIDs only, 4) NSAIDs+ASA, with 7722 (32.5%), 14,433 (60.8%), 611 (2.6%) and 962 (4.1%) patients in these groups, respectively. Among the 22,028 (92.8%) with complete 2-year follow-up, 683 (3.2%) died from CV causes, while 395 (1.9%) had MI, 665 (3.1%) stroke, 1651 (7.6%) cMACCE and 199 (1.0%) bleeding. After adjustment, NSAID use was independently associated with an increased risk of stroke (OR 1.635; 95% CI 1.239-2.159, p<0.001), and a trend towards an increased bleeding rate (OR 1.554; CI 95% 0.960-2.51, p=0.07). No association was found between NSAID use and MI or MACCE. CONCLUSIONS: In stable atherothrombosis patients, the use of NSAIDs appears to be independently associated with an increased cerebrovascular event risk.
International journal of cardiology 06/2011; · 7.08 Impact Factor
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ABSTRACT: Accurate estimation of bleeding risk in patients undergoing elective percutaneous coronary intervention (PCI) is difficult and not based on widely accepted scores or characteristics. We developed and validated a simple prediction model for major bleeding using the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial, which demonstrated the superior safety of enoxaparin over unfractionated heparin (UFH) in 3528 patients undergoing elective PCI.
Independent predictors of non-coronary artery bypass graft (CABG)-related major bleeding events were determined using stepwise multivariate logistic regression analysis from a development dataset using bootstrap resampling. These predictors were assigned an integer coefficient (risk score) proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. Female sex, use of unfractionated heparin (vs. enoxaparin), and use of a glycoprotein IIb/IIIa inhibitor (vs. nonuse) were the strongest independent predictors of bleeding. Extensive testing found that the final model performed well with bootstrap resampling in the development set (c-statistic 0.75; 95% CI: 0.70-0.82; Hosmer-Lemeshow p = 0.29), validation set (c-statistic 0.67; Hosmer-Lemeshow p = 0.12), and subgroups of high-risk patients analysed from the validation set (c-statistic ≥ 0.67).
Our model for evaluating the risk of non-CABG-related major bleeding in patients undergoing elective PCI identified sex, the type of antithrombin used, and glycoprotein IIb/IIIa inhibitor use as important indicators of bleeding risk, and accurately predicted the incidence of non-CABG-related major bleeding in patients undergoing elective PCI in the STEEPLE trial.
International journal of cardiology 03/2010; 150(1):79-83. · 7.08 Impact Factor
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ABSTRACT: Major bleeding significantly impacts outcomes in patients undergoing percutaneous coronary intervention (PCI). No uniform definitions exist for major and minor bleeding. Hematomas > or =5 cm at the femoral puncture site are considered major bleeding events in some trials and minor in others. Limited information is available on the incidence and clinical relevance of hematomas > or =5 cm in PCI patients.
Data from the STEEPLE trial in patients undergoing elective PCI were used to assess the impact of hematomas > or =5 cm on ischemic outcomes (mortality, nonfatal myocardial infarction, or urgent target vessel revascularization) up to day 30 and all-cause 1-year mortality. Hematoma data were available for 3,342 of 3,528 patients in STEEPLE. Patients with (n = 103) and without (n = 3,239) hematomas > or =5 cm were evenly distributed across treatment groups.
No differences were observed in 30-day ischemic outcomes between patients with and without hematomas (5.8% vs 5.9%, respectively; P = .96). No transfusions were observed in patients with hematomas as compared with patients without hematomas (0% and 0.4%, respectively; P = .52). A greater reduction in hemoglobin was observed (pre- vs post-PCI) in patients with hematomas as compared with patients without hematomas (-0.84 vs -0.35 g/L, P < or = .001). No significant difference in all-cause 1-year mortality was observed between patients with and without hematomas (0.0% vs 1.7%, P = .98).
After PCI, hematomas > or =5 cm had no effect on 30-day ischemic events or 1-year mortality. Although there is no agreed classification for large hematomas, the lack of a relationship between hematomas > or =5 cm and clinical outcome after PCI justifies the classification of these hematomas as minor bleeds in STEEPLE.
American heart journal 01/2010; 159(1):110-6. · 4.65 Impact Factor
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ABSTRACT: The Global Registry of Acute Coronary Events (GRACE) risk model provides a simple method for determining the probability of hospital death in acute coronary syndrome (ACS). The aim of this study was to explore the impact of modeling techniques on the risk model when generating predictions.
Patients with ACS (n = 48,023) with or without ST-segment elevation myocardial infarction (STEMI) were enrolled (123 hospitals, 14 countries) between April 1999 and June 2006. The original GRACE model did not include terms to account for possible differences in outcomes between patients with STEMI, non-STEMI, and unstable angina, nor did it account for changing risk across continuous measures.
In this cohort, the influence on outcome of region of hospitalization and cardiac arrest at presentation changed over the 7-year study. Other interactions included previous percutaneous coronary intervention and age with type of ACS. However, these interactions were insufficient to affect the final risk score. The same variables as in the original score comprise the new score. Inclusion of nonlinearity and differential effects did little to change the model's discrimination but influenced predictions for patients at extremes of risk.
Irrespective of the inclusion of nonlinear and interaction terms, the updated GRACE risk model provides an excellent means to discriminate risk of death in patients with ACS and can be used as a simple nomogram to estimate risk in patients seen in clinical practice.
American heart journal 07/2009; 157(6):1097-105. · 4.65 Impact Factor
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ABSTRACT: This chapter about antithrombotic therapy for coronary artery disease is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicans Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggestions are weaker as there is uncertainty regarding the benefits, risks and costs such that individual patients' values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation for Antithrombotic Agents" chapter by Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations are the following: for all patients presenting with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS), without a clear allergy to aspirin, we recommend immediate aspirin (162 to 325 mg po) and then daily oral aspirin (75 to 100 mg) [Grade 1A]. For NSTE ACS patients who are at at least moderate risk for an ischemic event and who will undergo an early invasive management strategy, we recommend "upstream" treatment either with clopidogrel (300 mg po bolus, followed by 75 mg/d) or a small-molecule IV glycoprotein (GP) IIb/IIIa inhibitor (eptifibatide or tirofiban) [Grade 1A]. For NSTE ACS patients who are at least moderate risk for an ischemic event and for whom an early conservative or a delayed invasive strategy of management is to be used, we recommend "upstream" treatment with clopidogrel (300 mg oral bolus, followed by 75 mg/d) [Grade 1A]. For NSTE ACS patients who undergo PCI, we recommend treatment with both clopidogrel and an IV GP IIb/IIIa inhibitor (Grade 1A). We recommend a loading dose of 600 mg of clopidogrel given at least 2 h prior to planned PCI followed by 75 mg/d (Grade 1B). For all patients presenting with NSTE ACS, we recommend anticoagulation with UFH or LMWH or bivalirudin or fondaparinux over no anticoagulation (Grade 1A). For NSTE ACS patients who will undergo an early invasive strategy of management, we recommend UFH (with a GP IIb/IIIa inhibitor) over either LMWH or fondaparinux (Grade 1B). For NSTE ACS patients in whom an early conservative or a delayed invasive strategy of management is to be used, we recommend fondaparinux over enoxaparin (Grade 1A) and LMWH over UFH (Grade 1B). We recommend continuing LMWH during PCI treatment of patients with NSTE ACS when it has been started as the "upstream" anticoagulant (Grade 1B). In low- to moderate-risk patients with NSTE ACS undergoing PCI, we recommend either bivalirudin with provisional ("bail-out") GP IIb/IIIa inhibitors or UFH plus a GP IIb/IIIa inhibitor over alternative antithrombotic regimens (Grade 1B).
Chest 06/2008; 133(6 Suppl):670S-707S. · 5.25 Impact Factor
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ABSTRACT: This chapter about fibrinolytic, antiplatelet, and antithrombin treatment for acute ST-segment elevation (STE) myocardial infarction (MI) is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the chapter by Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with ischemic symptoms characteristic of acute MI of < or = 12 h in duration and persistent STE, we recommend that all undergo rapid evaluation for reperfusion (primary percutaneous coronary intervention [PCI] or fibrinolytic) therapy and have a reperfusion strategy implemented promptly after contact with the health-care system (Grade 1A). For patients with ischemic symptoms characteristic of acute MI of < or = 12 h in duration and persistent STE, we recommend administration of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over no fibrinolytic therapy (all Grade 1A). For patients with symptom duration < or = 6 h, we recommend the administration of alteplase or tenecteplase over streptokinase (both Grade 1A). We recommend aspirin over no aspirin therapy followed by indefinite therapy (Grade 1A); we also recommend clopidogrel in addition to aspirin for up to 28 days (Grade 1A). In addition to aspirin and other antiplatelet therapies, we recommend the use of antithrombin therapy (eg, unfractionated heparin (UFH), enoxaparin, or fondaparinux) over no antithrombin therapy (Grade 1A), including for those patients receiving fibrinolysis (and regardless of which lytic agent is administered), primary PCI, or patients not receiving reperfusion therapy.
Chest 06/2008; 133(6 Suppl):708S-775S. · 5.25 Impact Factor
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ABSTRACT: Limited data suggest that ST elevation (ST elevation) in aVR is associated with higher mortality and more extensive coronary artery disease in the setting of non-ST elevation acute coronary syndromes (ACS).
In the prospective Global Registry of Acute Coronary Events (GRACE) electrocardiographic substudy, the admission electrocardiograms were analyzed by a blinded core laboratory. We performed multivariable analysis to determine (1) the independent prognostic significance of ST elevation in aVR and (2) its association with significant (> or = 50% stenosis) left main or 3-vessel disease (LM/3-vd).
Among 5064 patients with non-ST elevation ACS, 4696 had no ST elevation in aVR, 292 (5.8%) had minor (0.5-1 mm) ST elevation in aVR, and 76 (1.5%) had major (>1 mm) ST elevation in aVR; their in-hospital mortality rates were 4.2%, 6.2%, and 7.9%, respectively (P for trend =.03). At 6 months follow-up, the cumulative mortality rates were 7.6%, 12.7%, and 18.3%, respectively (log-rank P for trend <.001). However, minor and major ST elevation in aVR were not independent predictors of in-hospital or 6-month death after adjusting for other validated prognosticators in the GRACE risk model. Of the 2416 patients without prior coronary bypass surgery who underwent cardiac catheterization, the prevalence of LM/3-vd was 26.1%, 36.2%, and 55.9% for the groups with no, minor, and major ST elevation in aVR, respectively (P for trend <.001). After adjusting for other clinical characteristics, major ST elevation in aVR remained an independent predictor of LM/3-vd (adjusted odds ratio, 2.68; 95% confidence interval, 1.29-5.58; P = .008).
ST elevation in aVR is less prevalent than reported in previous smaller studies. Although it is associated with higher unadjusted in-hospital and 6-month mortality, it does not provide incremental prognostic value beyond comprehensive risk stratification using the validated GRACE risk model. However, ST elevation greater than 1 mm in aVR may be useful in the early identification of LM/3-vd in ACS patients with ST depression.
American heart journal 08/2007; 154(1):71-8. · 4.65 Impact Factor
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Debabrata Mukherjee,
Hitinder Gurm,
W H Wilson Tang,
Marco Roffi,
Kathy Wolski,
David J Moliterno,
Victor Guetta,
Diego Ardissinio,
Christopher Bode, Gabriel Steg,
A Michael Lincoff,
Eric J Topol
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ABSTRACT: ST-segment elevation acute myocardial infarction (AMI) in patients who have undergone previous coronary artery bypass grafting (CABG) is associated with low reperfusion rates and poor outcome after fibrinolytic therapy. The efficacy of a combination strategy (reduced fibrinolytic plus platelet glycoprotein IIb/IIIa agent) in this setting is unknown. In the Global Use of Streptokinase and TPA for Occluded coronary arteries V (GUSTO V) trial, 553 patients with a history of CABG were treated with standard-dose reteplase (n = 273), or half-dose reteplase and full-dose abciximab (n = 280) in the first 6 hours of evolving ST-segment elevation MI. Mortality at 30 days was significantly higher in patients who underwent prior CABG compared with patients with no prior CABG (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.21 to 2.24, p = 0.001). In patients who underwent prior CABG, mortality at 7 days was reduced 15% with combination therapy compared with reteplase alone, which was not statistically significant (OR 0.85, 95% CI 0.40 to 1.81, p = 0.66). Patients who underwent prior CABG treated with the combination therapy had fewer episodes of recurrent ischemia (OR 0.60, 95% CI 0.37 to 0.96, p = 0.02), high degree atrioventricular block (OR 0.17, 95% CI 0.02 to 0.82, p = 0.01), and ventricular tachycardia (OR 0.29, 95% CI 0.07 to 0.96, p = 0.04). There was a trend toward reduced urgent revascularization (OR 0.61, 95% CI 0.36 to 1.03, p = 0.06) but no significant difference in reinfarction (OR 0.61, 95% CI 0.31 to 1.52, p = 0.40). In the GUSTO V trial, patients who underwent prior CABG had significantly higher event rates compared with patients without CABG. As in the overall trial, combination therapy in patients who underwent prior CABG led to a consistent reduction in key secondary complications of AMI, including recurrent ischemia and a trend toward reduced urgent revascularization.
The American Journal of Cardiology 01/2003; 90(11):1198-203. · 3.37 Impact Factor
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John W Eikelboom,
Graeme J Hankey,
Jim Thom,
L. Deepa,
P. Bhatt, Gabriel Steg,
Gilles Montalescot,
S Claiborne Johnston,
Steven R Steinhubl,
Koon-Hou Mak,
Christian Hamm,
Tingfei Hu,
Keith A A Fox,
Eric J Topol,
Philip J. Walker
