Coronary Artery Disease: Steg PG

Daemen J, Simoons ML, Wijns W, Bagust A, Bos G, Bowen JM, Braunwald E, Camenzind E, Chevaliers B, DiMario C, Fajadeto J, Gitt A, Guagliumi G, Hillege HL, James S, Jüni P, Kastrati A, Kloth S, Kristensen SD, Krucoff M, Legrand V, Pfisterer M, Rothman M, Serruys PW, Silber S, Steg PG, Tariah I, Wallentin L, Windecker SW, Aimonetti A, Allocco D, Berenger M, Boam A, Calle JP, Campo G, Carlier S, de Schepper J, Di Bisceglie G, Dobbels H, Farb A, Ghislain JC, Hellbardt S, ten Hoedt R, Isaia C, de Jong P, Lekehal M, LeNarz L, Mhullain FN, Nagai H, Patteet A, Paunovic D, Potgieter A, Purdy I, Raveau-Landon C, Ternstrom S, Van Wuytswinkel J, Waliszewski M, Anonymous00071. · Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands. · EuroIntervention. · Pubmed #19284063 No free full text.

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Patrono C, Bachmann F, Baigent C, Bode C, De Caterina R, Charbonnier B, Fitzgerald D, Hirsh J, Husted S, Kvasnicka J, Montalescot G, García Rodríguez LA, Verheugt F, Vermylen J, Wallentin L, Priori SG, Alonso Garcia MA, Blanc JJ, Budaj A, Cowie M, Dean V, Deckers J, Fernández Burgos E, Lekakis J, Lindahl B, Mazzotta G, Morais J, Oto A, Smiseth OA, Morais J, Deckers J, Ferreira R, Mazzotta G, Steg PG, Teixeira F, Wilcox R, Anonymous00086. · ESC Task Force on Antiplatelets, University of Rome La Sapienza, II Facoltà di Medicina e Chirurgia, Via di Grottarossa, 1035, 00189 Roma, Italy. · Eur Heart J. · Pubmed #14720534 links to  free full text

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Steg PG, Feldman LJ. · No affiliation provided · Eur Heart J. · Pubmed #12208218 No free full text.

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Fox K, Borer JS, Camm AJ, Danchin N, Ferrari R, Lopez Sendon JL, Steg PG, Tardif JC, Tavazzi L, Tendera M, Anonymous00190. · Royal Brompton Hospital, Sydney Street, London SW3 6NP, England. · J Am Coll Cardiol. · Pubmed #17719466 No free full text.

Abstract: The importance of resting heart rate (HR) as a prognostic factor and potential therapeutic target is not yet generally accepted. Recent large epidemiologic studies have confirmed earlier studies that showed resting HR to be an independent predictor of cardiovascular and all-cause mortality in men and women with and without diagnosed cardiovascular disease. Clinical trial data suggest that HR reduction itself is an important mechanism of benefit of beta-blockers and other heart-rate lowering drugs used after acute myocardial infarction, in chronic heart failure, and in stable angina pectoris. Pathophysiological studies indicate that a relatively high HR has direct detrimental effects on the progression of coronary atherosclerosis, on the occurrence of myocardial ischemia and ventricular arrhythmias, and on left ventricular function. Studies have found a continuous increase in risk with HR above 60 beats/min. Although it may be difficult to define an optimal HR for a given individual, it seems desirable to maintain resting HR substantially below the traditionally defined tachycardia threshold of 90 or 100 beats/min. These findings suggest that the potential role of HR and its modulation should be considered in future cardiovascular guidance documents.

Camenzind E, Steg PG, Wijns W. · University of Geneva, 1 rue Michel-Servet, 1211 Geneva, Switzerland. · Circulation. · Pubmed #17344324 links to  free full text

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Steg PG, Karila-Cohen D, Feldman LJ. · Hôpital Bichat, Service de cardiologie, 46 rue Henri Huchard, 75877 Paris. · Arch Mal Coeur Vaiss. · Pubmed #11296458 No free full text.

Abstract: Diabetes mellitus is one of the main risk factors of coronary atherosclerosis. The relative risk of cardiovascular disease is 2 to 4 times higher in type II diabetes than in the general population. The number of cases, especially type II, is increasing, especially as the definition of diabetes has been changed recently by the specialist scientific societies (American Diabetic Association, World Health organisation and ALFEDIAM) to include all patients with fasting glucose levels > or = 7 mmol/L on two occasions. Therefore, in the next 25 years, the number of diabetic patients will probably double, not only because of this new definition but also because of the combined effects of an ageing population, dietary changes (with an increase in obesity) and a progressively more sedentary and urbanized life-style in the so-called "emerging" countries.

Steg PG, Karila-Cohen D. · Service de Cardiologie, Hôpital Bichat, Paris, France. · Diabetes Metab. · Pubmed #10421994 links to  free full text

Abstract: Diabetes mellitus is associated with increased risk of short and long-term complications after balloon angioplasty. In patients with multivessel disease, there may be a substantial increase in long-term mortality when percutaneous transluminal coronary angioplasty (PTCA) is preferred over surgery in patients who are amenable to both techniques, which should lead to caution in selecting PTCA as a routine revascularization method for these patients. However, many diabetic patients will still require revascularization with PTCA, either for single-vessel disease or because they are poor surgical candidates. Finally, the impact of recent advances, such as stents and glycoprotein IIb/IIIa inhibitors, on the short and long-term results of percutaneous interventions is still not fully defined and deserves further study.

Steg PG, Thuaire C, Himbert D, Carrié D, Champagne S, Coisne D, Khalifé K, Cazaux P, Logeart D, Slama M, Spaulding C, Cohen A, Tirouvanziam A, Montély JM, Rodriguez RM, Garbarz E, Wijns W, Durand-Zaleski I, Porcher R, Brucker L, Chevret S, Chastang C, Anonymous00030. · Department of Cardiology, Hôpital Bichat, 46 rue Henri Huchard, 75877 Paris Cedex 18, France. · Eur Heart J. · Pubmed #15589635 links to  free full text

Abstract: AIM: To determine whether late recanalization of an occluded infarct artery after acute myocardial infarction is beneficial. METHODS AND RESULTS: Two hundred and twelve patients with a first Q-wave myocardial infarction (MI) and an occluded infarct vessel were enrolled. After coronary and left ventricular contrast angiography, patients were randomized to percutaneous revascularization (PTCA, n=109), carried out 2-15 days after symptom onset or medical therapy (n=103). The primary endpoint was a composite of cardiac death, non-fatal MI, or ventricular tachyarrhythmia. The majority had single-vessel disease and less than one-third had involvement of the left anterior descending artery. The use of pharmacological therapy was high in both groups. At six months, left ventricular ejection fraction was 5% higher in the invasive compared with the medical group (P=0.013) and more patients had a patent artery (82.8% vs 34.2%, P<0.0001). Restenosis was seen in 49.4% of patients in the PTCA group. At a mean of 34 months of follow-up, the occurrence of the primary endpoint was similar in the medical and PTCA groups (8.7% vs 7.3% respectively, P=0.68), but the overall costs were higher for PTCA. The secondary endpoint combining the primary endpoint with admission for heart failure was also similar between groups (12.6% vs 10.1% in the medical and PTCA groups, respectively, P=0.56). CONCLUSIONS: Systematic late PTCA of the infarct vessel was associated with a higher left ventricular ejection fraction at six months, no difference in clinical outcomes, and higher costs than medical therapy. These results must be interpreted with caution given the small size and low risk of the population.

Carrié D, Khalifé K, Citron B, Izaaz K, Hamon M, Juiliard JM, Leclercq F, Fourcade J, Lipiecki J, Sabatier R, Boulet V, Rinaldi JP, Mourali S, Fatouch M, El Mokhtar E, Aboujaoudé G, Elbaz M, Grolleau R, Steg PG, Puel J, Anonymous00143. · Cardiology Department, Purpan Hospital, Toulouse, France. carrié · Am J Cardiol. · Pubmed #11249885 No free full text.

Abstract: The purpose of this study was to compare the effects of stent placement with and without balloon predilatation on duration of the procedure, reduction of procedure-related costs, and clinical outcomes. Although preliminary trials of direct coronary stenting have demonstrated promising results, the lack of randomized studies with long-term follow-up has limited the critical evaluation of the role of direct stenting in the treatment of obstructive coronary artery disease. Between January and September 1999, 338 patients were randomly assigned to either direct stent implantation (DS+; 173 patients) or standard stent implantation with balloon predilatation (DS-; 165 patients). Baseline clinical and angiographic characteristics were similar in the 2 groups. Procedural success was achieved in 98.3% of patients assigned to DS+ and 97.5% of patients assigned to DS- (p = NS), with a crossover rate of 13.9%. Compared with DS-, DS+ conferred a dramatic reduction in procedure-related cost ($956.4 +/- $352.2 vs $1,164.6 +/- $383.9, p <0.0001) and duration of the procedure (424.2 +/- 412.1 vs 634.5 +/- 390.1 seconds, p < 0.0001). At 6-month follow-up, the incidence of major adverse cardiac events including death, angina pectoris, myocardial infarction, congestive heart failure, repeat angioplasty, or coronary artery bypass graft surgery was 5.3% in DS+ and 11.4% in DS- (p = NS). Multivariate analysis demonstrated that major adverse cardiac events rates were related to stent length of 10 mm (relative risk [RR] 3.25, 95% confidence intervals [CI] 1.36 to 7.78; p = 0.008), stent diameter of 3 mm (RR 2.69, 95% CI 1.03 to 7.06; p = 0.043), and complex lesion type C (RR 2.83, 95% CI 1.02 to 7.85; p = 0.045). Thus, in selected patients, this prospective randomized study shows the feasibility of DS+ with reduction in procedural cost and length, and without an increase in in-hospital clinical events and major adverse cardiac events at 6-month follow-up.

Dumaine RL, Montalescot G, Steg PG, Ohman EM, Eagle K, Bhatt DL, Anonymous00098. · Pitié-Salpêtrière University Hospital, Paris, France. · Am Heart J. · Pubmed #19540404 No free full text.

Abstract: BACKGROUND: Although prior data showed an association between chronic kidney disease (CKD) and atherothrombotic events, little is known about the risk profile and specific outcomes of atherothrombotic outpatients with CKD. METHODS: More than 69,000 outpatients at risk of atherothrombotic events were enrolled in the REACH Registry. Creatinine clearance (CrCl) was available for 51,208 patients divided into 4 groups: normal (CrCl > or =90 mL/min, n = 13,949), mild (60-89 mL/min, n = 19,474), moderate (30-59 mL/min, n = 15,883), and severe CKD (CrCl <30 mL/min, n = 1902). Baseline characteristics, number of arterial beds overtly affected, medications, overall mortality, cardiovascular death, myocardial infarction, stroke, congestive heart failure, peripheral arterial events, and bleeding events were assessed according to renal function. RESULTS: The number of arterial beds affected increased with severity of CKD. However, patients with severe CKD were less likely to receive medications of proven benefit. Severe CKD was an independent correlate of all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, peripheral arterial revascularization, or amputation. CONCLUSION: One third of outpatients at risk for atherothrombotic events have moderate to severe CKD. They are less likely to receive beneficial therapies despite a higher atherothrombotic burden and worse outcomes.

Eagle KA, Hirsch AT, Califf RM, Alberts MJ, Steg PG, Cannon CP, Brennan DM, Bhatt DL, Anonymous00086. · University of Michigan Cardiovascular Center, Ann Arbor, MI 48109, USA. · Crit Pathw Cardiol. · Pubmed #19417637 No free full text.

Abstract: BACKGROUND: Atherothrombosis, defined as coronary artery, cerebrovascular, and peripheral arterial disease, is the leading cause of death in the United States. Limited data are available from outpatient populations to describe contemporary cardiovascular ischemic event rates and associated use of risk reduction treatments in patients with clinically manifest, or at risk for, atherothrombosis. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective, observational study of patients with either documented atherothrombotic syndromes or 3 or more risk factors designed to fill this knowledge gap. METHODS: Baseline demographics and 1-year outcomes were evaluated for US patients enrolled in the REACH Registry. Multivariate analytic models were constructed using baseline characteristics to determine independent predictors of 1-year event rates. RESULTS: In the United States, 25,686 patients were enrolled into the registry. Among symptomatic patients (n = 19,069), 19% had disease in >or=1 arterial bed. As of July 2006, 1-year outcomes were available for 93.4% (n = 23,985) of patients. The composite cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke event rate was 4.3% for the overall population and highest in patients with triple bed disease (9.9%). There was a relatively high use of risk reduction medications among symptomatic patients. However, opportunity for improvement remains. Approximately 9% of symptomatic patients were not using any antithrombotic, 7% were not using any antihypertensive agents, and 17% were not taking a lipid-lowering agent, whereas >80% of patients suffered from hypertension or dyslipidemia. CONCLUSIONS: US patients with established atherothrombotic disease continue to experience high cardiovascular ischemic event rates; these rates increase in close association with polyvascular disease. Despite the use of risk reduction interventions, ideal secondary prevention of ischemic events has not been achieved.

Ethgen M, Boutron L, Steg PG, Roy C, Ravaud P. · Institut National de la Santé et la Recherche Médiale, INSERM U738, Paris, France. · BMC Med Res Methodol. · Pubmed #19358717 links to  free full text

Abstract: BACKGROUND: Stents are commonly used to treat patients with coronary artery disease. However, the quality of reporting internal and external validity data in published reports of randomised controlled trials (RCTs) of stents has never been assessed.The objective of our study was to evaluate the quality of reporting internal and external validity data in published reports of RCTs assessing the stents for percutaneous coronary interventions. METHODS: A systematic literature review was conducted. Reports of RCTs assessing stents for percutaneous coronary interventions indexed in MEDLINE and the Cochrane Central Register of Controlled Trials and published between January 2003 and September 2008 were selected. A standardized abstraction form was used to extract data. All analyses were adjusted for the effect of clustering articles by journal. RESULTS: 132 articles were analyzed. The generation of the allocation sequence was adequate in 58.3% of the reports; treatment allocation was concealed in 34.8%. Adequate blinding was reported in one-fifth of the reports. An intention-to-treat analysis was described in 79.5%. The main outcome was a surrogate angiographic endpoint in 47.0%. The volume of interventions per center was described in two reports. Operator expertise was described in five (3.8%) reports. The quality of reporting was better in journals with high impact factors and in journals endorsing the CONSORT statement. CONCLUSION: The current reporting of results of RCTs testing stents needs to be improved to allow readers to appraise the risk of bias and the applicability of the results.

Anyfantakis ZA, Baron G, Aubry P, Himbert D, Feldman LJ, Juliard JM, Ricard-Hibon A, Burnod A, Cokkinos DV, Steg PG. · Institut National de la Santé et de la Recherche Médicale, Université Paris, Groupe Hospitalier Bichat-Claude Bernard, Paris, France. · Am Heart J. · Pubmed #19185639 No free full text.

Abstract: BACKGROUND: Diagnosis of acute coronary artery disease in survivors of out-of-hospital cardiac arrest (OHCA) is difficult. The role of emergency coronary angiography and percutaneous coronary intervention (PCI) in this setting is debated. The objective of this study was to assess the prevalence of coronary lesions on emergency angiography in survivors of OHCA. METHODS: Seventy-two consecutive OHCA survivors underwent systematic emergency coronary angiography. Patients with critical stenoses or occlusion underwent ad hoc PCI. RESULTS: Most (63.9%) OHCA survivors had angiographic coronary artery disease (> or =1 lesion >50%), but only a minority (37.5%) had clinical or angiographic evidence of an acute coronary syndrome due to either an acute occlusion (16.7%) or an irregular lesion suggestive of ruptured plaque or thrombus (25.0%). A final diagnosis of myocardial infarction was assigned in 27 patients (37.5%). Percutaneous coronary intervention was attempted and successful in 33.3% of the total cohort (n = 24). Hospital survival was 48.6%. By multivariable analysis, use of PCI was not an independent correlate of survival. ST-segment elevation on admission was an independent correlate of acute myocardial infarction (odds ratio 64.2, 95% CI 7.6-544.2, P = .0001), with high positive (82.6%) and negative (83.7%) predictive values. CONCLUSIONS: A minority of OHCA patients has angiographic evidence of an acute coronary syndrome and one-third undergo PCI, but PCI is not an independent correlate of survival. The presence of ST elevation on admission was a strong independent correlate of acute myocardial infarction and may be used to triage OHCA patients to emergency angiography with a view to PCI.

Goto S, Bhatt DL, Röther J, Alberts M, Hill MD, Ikeda Y, Uchiyama S, D'Agostino R, Ohman EM, Liau CS, Hirsch AT, Mas JL, Wilson PW, Corbalán R, Aichner F, Steg PG, Anonymous00007. · Department of Medicine and Metabolic Disease Center, Tokai University School of Medicine, Tokai University, Kanagawa, Japan. · Am Heart J. · Pubmed #19061698 No free full text.

Abstract: BACKGROUND: Atrial fibrillation (AF) is a major risk factor (RF) for ischemic stroke. Its prevalence and prognostic impact in patients with atherothrombosis are unclear. METHODS: Risk factors, drug usage, and 1-year cardiovascular (CV) outcomes (CV death, myocardial infarction [MI], and stroke) were compared in AF and non-AF patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of 68,236 stable outpatients with established atherothrombosis or>or=3 atherothrombotic RFs. RESULTS: Atrial fibrillation and 1-year follow-up data are available for 63,589 patients. The prevalence of AF was, 12.5%, 13.7%, 11.5%, and 6.2% among coronary artery disease, CV disease, peripheral artery disease, and RF-only patients, respectively. Of the 6,814 patients with AF, 6.7% experienced CV death, nonfatal MI, or nonfatal stroke within a year. The annual incidence of nonfatal stroke (2.4% vs 1.6%, P<.0001) and unstable angina (6.0% vs 4.0%, P<.00001) was higher, and CV death was more than double (3.2% vs 1.4%, P<.0001), in AF versus non-AF patients. In these patients with or at high risk of atherothrombosis, most patients with AF received antiplatelet agents, but only 53.1% were treated with oral anticoagulants. Even with high CHADS2 (congestive heart failure, hypertension, aging, diabetes mellitus, and stroke) scores, anticoagulant use did not exceed (59%). The rate of bleeding requiring hospitalization was higher in AF versus non-AF patients (1.5% vs 0.8%, P<.0001), possibly related to the more frequent use of anticoagulants (53.1% vs 7.1%). CONCLUSIONS: Atrial fibrillation is common in patients with atherothrombosis, associated with more frequent fatal and nonfatal CV outcomes, and underuse of oral anticoagulants.

Cacoub PP, Abola MT, Baumgartner I, Bhatt DL, Creager MA, Liau CS, Goto S, Röther J, Steg PG, Hirsch AT, Anonymous00101. · Pierre and Marie Curie University-Paris 6, and AP HP, Hospital La Pitié-Salpêtrière, Paris, France. · Atherosclerosis. · Pubmed #19054514 No free full text.

Abstract: OBJECTIVES: To examine differences in risk factor (RF) management between peripheral artery disease (PAD) and coronary artery (CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major 1-year cardiovascular (CV) event rates. METHODS: The REACH Registry recruited >68000 outpatients aged >or=45 years with established atherothrombotic disease or >or=3 RFs for atherothrombosis. The predictors of RF control that were evaluated included: (1) patient demographics, (2) mode of PAD diagnosis, and (3) concomitant CAD and/or CVD. RESULTS: RF control was less frequent in patients with PAD (n=8322), compared with those with CAD or CVD (but no PAD, n=47492) [blood pressure; glycemia; total cholesterol; smoking cessation (each P<0.001)]. Factors independently associated with optimal RF control in patients with PAD were male gender (OR=1.9); residence in North America (OR=3.5), Japan (OR=2.5) or Latin America (OR=1.5); previous coronary revascularization (OR=1.3); and statin use (OR=1.4); whereas prior leg amputation was a negative predictor (OR=0.7) (P<0.001). Optimal RF control was associated with fewer 1-year CV ischemic symptoms or events. CONCLUSIONS: Patients with PAD do not achieve RF control as frequently as individuals with CAD or CVD. Improved RF control is associated with a positive impact on 1-year CV event rates.

Mehta RH, Bhatt DL, Steg PG, Goto S, Hirsch AT, Liau CS, Röther J, Wilson PW, Richard AJ, Eagle KA, Ohman EM, Anonymous00040. · Duke Clinical Research Institute, 2400 Pratt Street, PO Box 17969, Durham, NC, USA. · Eur Heart J. · Pubmed #18996953 links to  free full text

Abstract: AIMS: To evaluate the influence of achieving secondary prevention target treatment goals for cardiovascular (CV) risk factors on clinical outcomes in patients with prior coronary artery bypass surgery (CABG). METHODS AND RESULTS: Accordingly, we analysed treatment to target goals in patients with prior CABG and atherothrombotic disease or known risk factors (diabetes, hypertension, hypercholesterolaemia, smoking, obesity) enrolled in the global REduction in Atherothrombosis for Continued Health (REACH) Registry, and their association with 1 year outcomes. A total of 13 907 of 68 236 patients (20.4%) in REACH had a history of prior CABG, and 1 year outcomes data were available for 13 207 of these. At baseline <25, 25-<50, 50-<75, and > or =75% risk factors were at goal in 3.7, 12.9, 31.7, and 51.7% of patients, respectively. One-year composite rates of CV death, non-fatal MI, non-fatal stroke were inversely related to the proportion of risk factors at goal at baseline (age, gender, and region adjusted rates 6.1, 5.6, 5.2, and 4.3% of patients with <25, 25-<50, 50-<75, and >75% risk factors at goal, respectively; P for trend 0.059). CONCLUSION: Risk-factor control varied greatly in CABG patients. Although CABG patients are frequently treated with appropriate therapies, these treatments fail to achieve an adequate level of prevention in many. This failure was associated with a trend for worse age-, gender-, and region-adjusted clinical outcomes. Thus, perhaps secondary prevention after CABG needs to focus on more comprehensive modification of risk factors to target goals in the hope of preventing subsequent CV events, and represents an opportunity to improve CV health.

Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R, Anonymous00005. · Royal Brompton Hospital, London, UK. · Lancet. · Pubmed #18757091 No free full text.

Abstract: BACKGROUND: The BEAUTIFUL study assessed the morbidity and mortality benefits of the heart rate-lowering agent ivabradine. The placebo arm of the BEAUTIFUL trial was a large cohort of patients with stable coronary artery disease and left-ventricular dysfunction. We did a subanalysis of this placebo group to test the hypothesis that elevated resting heart rate at baseline is a marker for subsequent cardiovascular death and morbidity. METHODS: The association of baseline resting heart rate with cardiovascular outcomes was analysed using Cox proportional hazard models for groups with a heart rate of 70 beats per min (bpm) or greater (2693 patients) versus less than 70 bpm (2745 patients). Additional analyses were done with finer categorisation of heart rate, and with heart rate as a continuous variable. FINDINGS: After adjustment for baseline characteristics, patients with heart rates of 70 bpm or greater had increased risk for cardiovascular death (34%, p=0.0041), admission to hospital for heart failure (53%, p<0.0001), admission to hospital for myocardial infarction (46%, p=0.0066), and coronary revascularisation (38%, p=0.037). For every increase of 5 bpm, there were increases in cardiovascular death (8%, p=0.0005), admission to hospital for heart failure (16%, p<0.0001), admission to hospital for myocardial infarction (7%, p=0.052), and coronary revascularisation (8%, p=0.034). The analysis of fine-groupings of heart rate suggests that the increase in mortality and heart failure outcomes rises continuously above 70 bpm, whereas the relation is less pronounced for coronary outcomes. For heart failure outcomes, the predictive value of resting heart rate was stronger for earlier events than for later events. INTERPRETATION: In patients with coronary artery disease and left-ventricular systolic dysfunction, elevated heart rate (70 bpm or greater) identifies those at increased risk of cardiovascular outcomes, with a differential effect on outcomes associated with heart failure and outcomes associated with coronary events.

Fox K, Ford I, Steg PG, Tendera M, Ferrari R, Anonymous00009. · Royal Brompton Hospital, London, UK. · Lancet. · Pubmed #18757088 No free full text.

Abstract: BACKGROUND: Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. METHODS: Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. FINDINGS: Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). INTERPRETATION: Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.

Baumgartner I, Hirsch AT, Abola MT, Cacoub PP, Poldermans D, Steg PG, Creager MA, Bhatt DL, Anonymous00053. · Department of Clinical and Interventional Angiology, Swiss Cardiovascular Centre, Angiology Division, University Hospital, Bern, Switzerland. · J Vasc Surg. · Pubmed #18639426 No free full text.

Abstract: OBJECTIVE: Datasets regarding patients with abdominal aortic aneurysm (AAA) have almost universally been restricted to single geographic regions. We aimed to obtain data on the risk factor profile and cardiovascular (CV) co-morbidity among multi-ethnic patients with known AAA in the global REACH (REduction of Atherothrombosis for Continued Health) Registry. METHODS: The REACH Registry is an international, prospective, observational out-patient registry enrolling out-patients >/=45 years of age with established coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral arterial disease (PAD) or with at least three atherothrombotic risk factors. This report includes observations pertaining to 68,236 out-patients enrolled in 44 countries. MAIN OUTCOME MEASURES: Gender, ethnic origin, CV risk factors, established atherosclerotic disease (CAD, CVD and PAD) at baseline, and CV outcome events at 1-year were compared in patients with and without AAA. RESULTS: An AAA was reported in 1722 (2.5%) of 68,236 out-patients enrolled in the REACH Registry. Older age (73 +/- 8 vs 68 +/- 10, P < .0001), male gender (81% vs 63%, P < .0001), White ethnicity (79% vs 67%, P < .0001) and a history of smoking (81% vs 55%, P < .0001) were independently related to the diagnosis of AAA. There was a weaker association with hypertension or hypercholesterolemia, and an inverse relation with diabetes. Fatal and non-fatal coronary and cerebrovascular event rates were not different between the AAA and non-AAA cohorts, but individuals with AAA suffered increased rates of other cardiovascular deaths (1.39% vs 0.94%, P = .0135), hospitalizations for atherothrombotic events (14.1% vs 9.3%, P < .0001) due to increased rates of revascularization procedures, and new or worsening PAD (3.7% vs 1.3%, P < .0001) at 1-year follow-up. CONCLUSION: This study, the largest published to date, presents the CV risk profile and outcome of patients with an established diagnosis of AAA from a cohort of patients with either overt manifestations of CV disease or multiple risk factors, and further defines these patients in a multi-ethnic, global context.

Anonymous00383, Ferrari R, Ford I, Fox K, Steg PG, Tendera M. · Royal Brompton Hospital, London, UK. · Cardiology. · Pubmed #18595216 No free full text.

Abstract: OBJECTIVES: Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. METHODS: BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). RESULTS: A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). CONCLUSIONS: Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients.

Danchin N, Coste P, Ferrières J, Steg PG, Cottin Y, Blanchard D, Belle L, Ritz B, Kirkorian G, Angioi M, Sans P, Charbonnier B, Eltchaninoff H, Guéret P, Khalife K, Asseman P, Puel J, Goldstein P, Cambou JP, Simon T, Anonymous00198. · Division of Coronary Artery Disease and Intensive Cardiac Care, Hôpital Européen Georges Pompidou, Assistance-Publique des Hôpitaux de Paris and Faculté René Descartes, Université Paris 5, 20 rue Leblanc, 75015 Paris, France. · Circulation. · Pubmed #18591434 links to  free full text

Abstract: BACKGROUND: Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. METHODS AND RESULTS: This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (P=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. CONCLUSIONS: When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.

Dey S, Flather MD, Devlin G, Brieger D, Gurfinkel EP, Steg PG, Fitzgerald G, Jackson EA, Eagle KA, Anonymous00046. · University of Michigan Medical School, Ann Arbor, Missouri, USA. · Heart. · Pubmed #18463200 No free full text.

Abstract: OBJECTIVE: To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). METHODS: The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999-2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as >or=one vessel with >or=50% stenosis. RESULTS: Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. CONCLUSIONS: Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.

Röther J, Alberts MJ, Touzé E, Mas JL, Hill MD, Michel P, Bhatt DL, Aichner FT, Goto S, Matsumoto M, Ohman EM, Okada Y, Uchiyama S, D'Agostino R, Hirsch AT, Wilson PW, Steg PG, Anonymous00103. · Department of Neurology, Klinikum Minden, Hannover Medical School, Minden, Germany. · Cerebrovasc Dis. · Pubmed #18337635 No free full text.

Abstract: BACKGROUND: Cerebrovascular disease (CVD) is a global public health problem. CVD patients are at high risk of recurrent stroke and other atherothrombotic events. Prevalence of risk factors, comorbidities, utilization of secondary prevention therapies and adherence to guidelines all influence the recurrent event rate. We assessed these factors in 18,992 CVD patients within a worldwide registry of stable outpatients. METHODS: The Reduction of Atherothrombosis for Continued Health Registry recruited >68,000 outpatients (44 countries). The subjects were mainly recruited by general practitioners (44%) and internists (29%) if they had symptomatic CVD, coronary artery disease, peripheral arterial disease (PAD) and/or >or=3 atherothrombotic risk factors. RESULTS: The 18,992 CVD patients suffered a stroke (53.7%), transient ischemic attack (TIA) (27.7%) or both (18.5%); 40% had symptomatic atherothrombotic disease in >or=1 additional vascular beds: 36% coronary artery disease; 10% PAD and 6% both. The prevalence of risk factors at baseline was higher in the TIA subgroup than in the stroke group: treated hypertension (83.5/82.0%; p = 0.02), body mass index >or=30 (26.7/20.8%; p < 0.0001), hypercholesterolemia (65.1/52.1%; p < 0.0001), atrial fibrillation (14.7/11.9%; p < 0.0001) and carotid artery disease (42.3/29.7%; p < 0.0001). CVD patients received antiplatelet agents (81.7%), oral anticoagulants (17.3%), lipid-lowering agents (61.2%) and antihypertensives (87.9%), but guideline treatment targets were frequently not achieved (54.5% had elevated blood pressure at baseline, while 4.5% had untreated diabetes). CONCLUSIONS: A high percentage of CVD patients have additional atherothrombotic disease manifestations. The risk profile puts CVD patients, especially the TIA subgroup, at high risk for future atherothrombotic events. Undertreatment is common worldwide and adherence to guidelines needs to be enforced.

Huisse MG, Lanoy E, Tcheche D, Feldman LJ, Bezeaud A, Anglès-Cano E, Mary-Krause M, de Prost D, Guillin MC, Steg PG. · AP-HP, Hôpital Bichat, Paris, France. · Thromb Haemost. · Pubmed #17721626 links to  free full text

Abstract: We tested the hypothesis that selected prothrombotic biomarkers might be associated with early spontaneous coronary recanalization in patients with ST-segment elevation acute myocardial infarction (STEMI). We prospectively enrolled 123 patients with STEMI including 53 patients with spontaneous coronary recanalization (cases) and 70 patients with persistent occlusion (controls) at the time of emergent coronary angiography and before angioplasty. All had received aspirin and heparin. Blood samples were collected immediately before angioplasty to measure soluble P-selectin, circulating microparticles originating from platelets (PMPs), granulocytes (GMPs), endothelial cells (EMPs); tissue factor-associated MP (TF-MP); soluble platelet glycoprotein V (sGPV) and prothrombin F1 + 2; tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and plasmin-antiplasmin (PAP). A sub-group of 70 patients (35 cases, 35 controls) was available for flow cytometry analysis of platelet P-selectin and activated GPIIb-IIIa. Baseline clinical characteristics did not differ between groups except for more frequent hypertension and dyslipidemia in controls. Platelet activation markers and PMP did not differ between the two groups. Controls had higher numbers of EMPs and GMPs compared to cases, but the difference was no longer significant when corrected for risk factors. Controls differed from cases by higher plasma levels of sGPV [64 (47-84) ng/ml vs. 53 (44-63) ng/ml] and PAP [114(65-225) ng/ml vs. 88 (51-147) ng/ml]. The difference persisted after adjustment for risks factors (p = 0.031 and 0.037, respectively). Persistent occlusion of the infarct related artery is associated with some markers related to higher thrombin (sGPV) and plasmin (PAP) production but is not associated with markers of platelet activation.

Steinberg BA, Steg PG, Bhatt DL, Fonarow GC, Zeymer U, Cannon CP, Anonymous00360. · Thrombolysis In Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Am J Cardiol. · Pubmed #17478144 No free full text.

Abstract: To evaluate current compliance with recommendations for medical therapy in patients with coronary artery disease (CAD), the relation between previous revascularization and use of guideline-recommended therapies was investigated. From 5,400 outpatient practices in 44 countries, we compared baseline characteristics and medical therapy of 40,450 patients with documented CAD (all with previous myocardial infarction, percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], or angina pectoris) by previous revascularization status. Approximately 33% of patients had previous CABG, 33% had previous PCI, and 33% had no previous revascularization. Patients with previous CABG were older and often men and diabetic. Patients with previous PCI were the youngest. Guideline-recommended medical therapy use was significantly higher in those with previous revascularization. Antiplatelet therapy in medically managed patients was 80% versus 86% and 91% for those with previous CABG or PCI, respectively. Use of any lipid-lowering agent in those with previous CABG or PCI was 86% in the 2 groups versus 70% in patients who were medically managed. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were used in similar ratios among groups. Previous revascularization appears to be associated with better use of guideline-recommended medical treatment. These trends were similar for patients from the United States versus everywhere else. In conclusion, use of evidence-based, guideline-recommended therapies in outpatients with CAD needs to improve, especially in medically managed patients.