Coronary Artery Disease: Goodman SG

Harrington RA, Becker RC, Cannon CP, Gutterman D, Lincoff AM, Popma JJ, Steg G, Guyatt GH, Goodman SG, Anonymous00138. · Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705, USA. · Chest. · Pubmed #18574276 links to  free full text

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).

Fitchett DH, Leiter LA, Goodman SG, Langer A. · Division of Cardiology, St. Michael's Hospital, Toronto, Ontario. · Can J Cardiol. · Pubmed #16957800 links to  free full text

Abstract: Recent clinical trials have indicated that lowering low-density lipoprotein cholesterol (LDL-C) levels below currently recommended targets results in favourable surrogate and clinical end points. The Treating to New Targets (TNT) study now confirms that aggressive cholesterol lowering to a mean LDL-C of 2.0 mmol/L with atorvastatin 80 mg daily, compared with the previous target of 2.5 mmol/L with atorvastatin 10 mg daily, results in improved clinical outcomes in high-risk patients with coronary artery disease. A lower LDL-C target of less than 2.0 mmol/L will present therapeutic challenges, because approximately only one-half of high-risk patients will achieve this target using monotherapy with the newer and more powerful statins. Furthermore, registry data show that one-half of these patients are not even achieving the current LDL-C target of 2.5 mmol/L. Causes of the care gap are discussed and possible remedies to achieve the new lower targets are suggested.

Hackam DG, Goodman SG, Anand SS. · Division of Clinical Pharmacology and Toxicology, Sunnybrook & Women's College Health Sciences Centre, Toronto, Canada. · Am Heart J. · Pubmed #16084148 No free full text.

Abstract: Peripheral artery disease (PAD) is a problem frequently encountered by physicians who care for patients with coronary heart disease, diabetes mellitus, renal insufficiency, congestive heart failure, or stroke. Patients with PAD are at heightened risk of myocardial infarction and stroke and are 6 times more likely to die of cardiovascular causes than persons without the disease. There is an urgent need for therapies that reduce the incidence of vascular complications among patients with PAD. In recent years, a number of risk-lowering therapies have been validated by randomized controlled trials enrolling large numbers of patients with PAD. The available evidence supports aggressive lifestyle modification as well as the provision of an antiplatelet agent, an HMGCoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor, and an angiotensin-converting enzyme inhibitor for cardiovascular protection in patients with PAD. As a result of their high baseline risk and the proven effectiveness of these interventions, most patients with PAD will benefit substantially from aggressive medical therapy.

Yan AT, Goodman SG. · Canadian Heart Research Centre, Toronto, Ontario, Canada. · Curr Opin Cardiol. · Pubmed #15218388 No free full text.

Abstract: PURPOSE OF REVIEW: The objective of this review was to summarize the recent developments regarding the use of low-molecular-weight heparins in the management of acute coronary syndromes. RECENT FINDINGS: In the setting of unstable angina and non-ST-elevation myocardial infarction, enoxaparin is superior to unfractionated heparin in reducing death, myocardial infarction, and recurrent ischemia both in the short-term and to 1 year. However, this does not necessarily imply a class effect of low-molecular-weight heparins in general. When combined with glycoprotein IIb/IIIa inhibitors, enoxaparin appears to be effective and safe even for patients treated according to an early invasive strategy. In patients receiving fibrinolytics for ST-elevation myocardial infarction, low-molecular-weight heparins are as effective as unfractionated heparin in maintaining patency of the infarct-related artery and in reducing the composite endpoint of death and reinfarction. However, serious bleeding is more common, especially among the elderly, and the optimal dosing regimen in ST-elevation myocardial infarction remains to be defined. SUMMARY: Low-molecular-weight heparins are safe and effective in the management of unstable angina and non-ST-elevation myocardial infarction, with or without concurrent administration of glycoprotein IIb/IIIa inhibitors. Ongoing studies will clarify the role of low-molecular-weight heparins as adjunctive therapy for fibrinolysis.

Sprecher DL, Goodman SG, Kannampuzha P, Pearce GL, Langer A. · The Cleveland Clinic Foundation and Rehabilitation, Section of Preventive Cardiology, 9500 Euclid Avenue, Desk C51, Cleveland, OH 44195, USA. · Atherosclerosis. · Pubmed #14644394 No free full text.

Abstract: Parallel changes associated with aging found in the vasculature and skin at necropsy, have prompted small preliminary studies to assess the relation between skin tissue cholesterol (SkinTc) and cardiovascular disease. While these studies have been suggestive, no formal investigation is available to test this association. It would, therefore, be valuable to determine whether a relation between SkinTc and angiographic narrowing actually exists, the latter representing one accepted measurement of coronary atherosclerosis. METHODS: Patients at three hospitals undergoing coronary angiography and not on lipid altering agents (n = 649) were examined for skinTc using a non-invasive method. Vessels were evaluated manually (number with stenosis > or = 50%). Clinical characteristics, current medication use, and Framingham global risk score were recorded. RESULTS: SkinTc was significantly higher in patients with angiographic disease (124 +/- 30 vs. 118 +/- 30, P = 0.02). After adjustment for traditional coronary artery disease risk factors, SkinTc provided 7% additional risk (per 10 SkinTc units) for angiographic disease. CONCLUSION: SkinTc, measured with a non-invasive method, is associated with the presence of coronary artery disease as determined by catheterization. Such an assay may eventually help stratify patient risk and target prevention efforts.

Goodman SG, Fitchett D, Armstrong PW, Tan M, Langer A, Anonymous00082. · Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. · Circulation. · Pubmed #12538422 links to  free full text

Abstract: BACKGROUND: Current pharmacotherapeutic options for high-risk non-ST-segment elevation acute coronary syndrome patients include aspirin, clopidogrel, heparin, and platelet glycoprotein IIb/IIIa inhibition. A key issue of uncertainty is the safety and efficacy of combination glycoprotein IIb/IIIa inhibitor and low-molecular-weight heparin therapy. METHODS AND RESULTS: We randomized 746 patients with rest ischemic discomfort within 24 hours after the onset of symptoms and ST-segment deviation and/or elevation of serum cardiac markers to receive open-label enoxaparin (1 mg/kg subcutaneously twice daily) or unfractionated heparin (70-U/kg bolus; 15 U x kg(-1) x h(-1) infusion, titrated to an activated partial thromboplastin time of 1.5 to 2 times control) for 48 hours. All patients received aspirin and eptifibatide (180- microg/kg bolus; 2 microg x kg(-1) x min(-1) infusion). Major non-coronary artery bypass surgery-related bleeding at 96 hours (primary safety outcome) was significantly lower among enoxaparin-treated patients than among heparin-treated patients (1.8% versus 4.6%, P=0.03). Minor bleeding was more frequent in the enoxaparin group (30.3% versus 20.8%, P=0.003). Patients in the enoxaparin group were less likely to experience ischemia as detected by continuous ECG evaluation (primary efficacy outcome) during the initial (14.3% versus 25.4%, P=0.0002) and subsequent (12.7% versus 25.9%, P<0.0001) 48-hour monitoring periods. Death or myocardial infarction at 30 days was significantly lower in the enoxaparin group (5% versus 9%, P=0.031). CONCLUSIONS: When aspirin and eptifibatide are used in high-risk non-ST-segment elevation acute coronary syndrome patients, enoxaparin improves outcomes (determined on the basis of better safety and efficacy) compared with currently recommended unfractionated heparin therapy and provides a useful novel alternative therapeutic strategy.

Goodman SG, Cohen M, Bigonzi F, Gurfinkel EP, Radley DR, Le Iouer V, Fromell GJ, Demers C, Turpie AG, Califf RM, Fox KA, Langer A. · Canadian Heart Research Center, Division of Cardiology, St. Michael's Hospital, University of Toronto, Ontario, Canada. · J Am Coll Cardiol. · Pubmed #10987586 No free full text.

Abstract: OBJECTIVES: We sought to determine whether the observed benefits of enoxaparin were maintained beyond the early phase; a one-year follow-up survey was undertaken for patients enrolled in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events (ESSENCE) study. BACKGROUND: We have previously reported a significant benefit of low molecular weight as compared with unfractionated heparin (UFH) in the 14- and 30-day incidence of a composite end point of death, myocardial infarction (MI) or recurrent angina in patients with unstable angina or non-Qwave MI. METHODS: The study recruited 3,171 patients with recent-onset rest angina and underlying ischemic heart disease. All patients received oral aspirin daily and were randomized to receive enoxaparin subcutaneously every 12 h or UFH (intravenous bolus followed by continuous infusion) in a double-blind, double-dummy fashion for a median of 2.6 days. RESULTS: The incidence of the composite triple end point at one year was lower among patients receiving enoxaparin as compared with those receiving UFH (32.0% vs. 35.7%, p = 0.022), with a trend toward a lower incidence of the secondary composite end point of death or MI (11.5% vs. 13.5%, p = 0.082). At one year, the need for diagnostic catheterization and coronary revascularization was lower in the enoxaparin group (55.8% vs. 59.4%, p = 0.036 and 35.9% vs. 41.2%, p = 0.002, respectively). CONCLUSIONS: In patients with unstable angina or non-Qwave MI, enoxaparin therapy significantly reduced the rates of recurrent ischemic events and invasive diagnostic and therapeutic procedures in the short term with sustained benefit at one year.

Cohen M, Stinnett SS, Weatherley BD, Gurfinkel EP, Fromell GJ, Goodman SG, Fox KA, Califf RM. · Division of Cardiology, MCP-Hahnemann University School of Medicine, Philadelphia, PA 19102, USA. · Am Heart J. · Pubmed #10827375 No free full text.

Abstract: BACKGROUND: Patients with non-Q-wave acute coronary syndromes (ACS) have substantial rates of recurrent ischemic events, but prognostic studies have been small or preceded the routine use of aggressive combination antithrombotic therapy. We sought to identify predictors of these events after antithrombotic treatment of non-Q-wave ACS. METHODS: We assessed 30-day rates of a composite triple end point (death, infarction, or refractory angina) and double end point (death or infarction) among 3171 patients with non-ST-segment elevation ACS randomly assigned to enoxaparin or heparin, plus aspirin, for 2 to 8 days. We created multivariable regression models to predict these end points from baseline factors. RESULTS: Overall, 682 patients (21%) reached the triple end point and 220 (6.8%) reached the double end point. Independent predictors of the triple end point were admission with myocardial necrosis, ST-segment depression, prior angina severity, symptom duration, and allocation to enoxaparin treatment in patients with ST-segment depression (significant interaction). Independent predictors of the double end point were admission with myocardial necrosis, ST-segment depression, enrollment region, age >75 years, prior angina severity, and rales. By deciles, the average predicted risk for the double end point ranged from 2% to 20%: a patient aged <75 years with no risk factors had a 3.5% risk, whereas a patient aged >75 years with 2 additional high-risk features (myonecrosis and ST depression) had a risk of death or reinfarction of 26%. CONCLUSIONS: Patients with non-ST-segment elevation ACS exhibit a broad range of risk of adverse recurrent ischemic events. The predictive power of the model for the triple end point, using baseline variables, was modest. However, a subgroup at very low risk of the double end point (average 2%) can be identified with baseline variables.

Saposnik G, Goodman SG, Leiter LA, Yan RT, Fitchett DH, Bayer NH, Casanova A, Langer A, Yan AT, Anonymous00054, Anonymous00055, Anonymous00056. · Division of Cardiology, Canadian Heart Research Centre and Terrence Donnelly Heart Centre, University of Toronto, Canada. · Stroke. · Pubmed #19213947 No free full text.

Abstract: BACKGROUND AND PURPOSE: The importance of early and aggressive initiation of secondary prevention strategies for patients with both coronary artery disease (CAD) and cerebrovascular disease (CVD) is emphasized by multiple guidelines. However, limited information is available on cardiovascular protection and stroke prevention in an outpatient setting from community-based populations. We sought to evaluate and compare differences in treatment patterns and the attainment of current guideline-recommended targets in unselected high-risk ambulatory patients with CAD, CVD, or both. METHODS: This multicenter, prospective, cohort study was conducted from December 2001 to December 2004 among ambulatory patients in a primary care setting. The prospective Vascular Protection and Guidelines-Oriented Approach to Lipid-Lowering Registries recruited 4933 outpatients with established CAD, CVD, or both. All patients had a complete fasting lipid profile measured within 6 months before enrollment. The primary outcome measure was the achievement of blood pressure (BP) <140/90 mm Hg (or <130/80 mm Hg for patients with diabetes) and LDL cholesterol <2.5 mmol/L (<97 mg/dL) according to the Canadian guidelines in place at that time (similar to the National Cholesterol Education Program's value of 100 mg/dL). Secondary outcomes include use of antithrombotic, antihypertensive, and lipid-modifying therapies. RESULTS: Of the 4933 patients, 3817 (77%) had CAD only; 647 (13%) had CVD only; and 469 (10%) had both CAD and CVD. Mean+/-SD age was 67+/-10 years, and 3466 (71%) were male. Mean systolic and diastolic BPs were 130+/-16 and 75+/-9 mm Hg, respectively. Minor but significant differences were observed on baseline BP, total cholesterol, and LDL cholesterol measurements among the 3 groups. Overall, 83% of patients were taking a statin and 93% were receiving antithrombotic therapy (antiplatelet and/or anticoagulant agents). Compared with patients with CAD, those with CVD only were less likely to achieve the recommended BP (45.3% vs 57.3%, respectively; P<0.001) and lipid (19.4% vs 30.5%, respectively; P<0.001) targets. Among patients with CVD only, women were less likely to achieve the recommended BP and lipid targets compared with their male counterparts (for LDL cholesterol <2.5 mmol/L, 18.7% vs 23.8%, respectively; P=0.048). In multivariable analysis, patients with CVD alone were less likely to achieve treatment success (BP or lipid targets) after adjusting for age, sex, diabetes, and use of pharmacologic therapy. CONCLUSIONS: Despite the proven benefits of available antihypertensive and lipid-lowering therapies, current management of hypertension and dyslipidemia continues to be suboptimal. A considerable proportion of patients failed to achieve guideline-recommended targets, and this apparent treatment gap was more pronounced among patients with CVD and women. Quality improvement strategies should target these patient subgroups.

LaBounty T, Gurm HS, Goodman SG, Montalescot G, Lopez-Sendon J, Quill A, Eagle KA, Anonymous00075. · Weill Cornell Medical College, New York, NY, USA. · Am J Med. · Pubmed #19185091 No free full text.

Abstract: BACKGROUND: Q-waves in ST-elevation acute coronary syndromes carry adverse implications. We sought to determine the frequency, predictors, and implications of Q-waves in the current era that includes primary percutaneous coronary interventions. METHODS: There were 14,916 patients evaluated in a multicenter observational study. They presented with ST-elevation acute coronary syndromes between 1999 and 2006. Clinical variables were compared between patients with versus without presenting Q-waves, with an additional comparison in the latter group between those with versus without subsequent development of Q-waves. RESULTS: ST-elevation myocardial infarction occurred in 88.6% of patients. Q-waves were present on the initial electrocardiogram in 3929 patients and developed later in an additional 3085 patients. The incidence of Q-waves at presentation or during hospitalization decreased from 61% to 39% between 1999 and 2006 (linear trend P<.001). Both presenting and subsequent Q-waves were associated with greater likelihood of coronary occlusions and higher cardiac marker elevations (P <.001). Multivariate analysis showed that presenting Q-waves were associated with male sex (odds ratio [OR] 1.28), increased age (OR 1.06 per 5 years), diabetes (OR 1.26), smoking (OR 1.11), chronic aspirin (OR 0.79), acute aspirin (OR 0.87), other chronic cardiac medications (OR 0.80), prior heart failure (OR 0.67), and prior coronary artery disease (OR 0.61). Presenting Q-waves were independently associated with increased in-hospital mortality (OR 1.46), but Q-waves at presentation or during hospitalization did not impact 6-month mortality. CONCLUSIONS: Q-waves in ST-elevation acute coronary syndromes are decreasing in incidence. Q-waves are a major determinant of in-hospital mortality, and targeted interventions should be directed to these high-risk patients.

Fitchett DH, Goodman SG, Langer A. · Canadian Heart Research Centre and St Michael's Hospital, Toronto, Canada. · Can J Cardiol. · Pubmed #18787721 No free full text.

Abstract: Statin therapy in patients with coronary artery disease or in those at risk for cardiovascular disease is associated with a reduced incidence of ischemic stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial showed treatment with atorvastatin 80 mg daily in patients with a recent stroke or transient ischemic attack (TIA) reduces the incidence of fatal and nonfatal stroke by 16%. In this population with a recent stroke or TIA, coronary artery disease events and the need for revascularization were a frequent occurrence. Furthermore, the relative reduction of noncerebrovascular events and the need for revascularization was greater with atorvastatin than the reduction of stroke. A patient with a recent ischemic stroke or TIA is at high risk for fatal and nonfatal coronary events (approximately 4% per year), and according to most guidelines for the management of coronary artery disease, such patients should be in the high risk category. Consequently, ischemic stroke should be considered to be a coronary risk equivalent with a prognosis similar to that of a patient with coronary artery disease. Furthermore, both the stroke and coronary artery disease prognoses are improved by treatment with atorvastatin 80 mg daily.

Leung S, Gallup D, Mahaffey KW, Cohen M, Antman EM, Goodman SG, Harrington RA, Langer A, Aylward P, Ferguson JJ, Califf RM, Anonymous00272. · University of Kentucky, Lexington, KY, USA. · Am Heart J. · Pubmed #18585514 No free full text.

Abstract: BACKGROUND: Smoking remains a major public health issue. We investigated the incidence of smoking and outcomes in high-risk patients with acute coronary syndromes. Differences in treatment effect of antithrombin therapies were also investigated. METHODS: Using data from SYNERGY, patients were categorized by their self-reported smoking status. They were followed at 30 days and 6 months for death, nonfatal myocardial infarction (MI), revascularization procedures, stroke, and need for rehospitalization, and at 1 year for occurrences of death. RESULTS: Overall, 9,971 patients were evaluated, of whom 2,404 (24%) were current smokers, 3,491 (35%) were former smokers, and 4076 (41%) had never smoked. Current smokers were younger (median age 61 years, interquartile range [IQR] 52-67) than former smokers (median age 69 years, IQR 63-75) and never smokers (median age 70 years, IQR 64-77) and had fewer additional coronary artery disease risk factors (hypertension, diabetes, hypercholesterolemia). The 30-day death/MI rate was similar for former versus never smokers (15% vs 13.6%, P = .079) and for current versus never smokers (14% vs 13.6%, P = .585). Adjusted odds ratios for 30-day death/MI in patients receiving enoxaparin compared with those receiving unfractionated heparin were 1.065 (95% CI 0.883-1.283, P = .51) in never smokers, 1.034 (95% CI 0.853-1.254, P = .733) in former smokers, and 0.742 (95% CI 0.582-0.948, P = .017) in current smokers. A significant interaction for treatment and smoking status was found at 30 days (P = .0215), but not at 6 months (P = .1381) or 1 year (P = .1054). One-year unadjusted mortality rates were higher for former versus never smokers (9.1% vs 6.7%, P = .0002) but were similar for current versus never smokers (6.5% vs 6.7%, P = .7226). On follow-up at 30 days, 62.3% (n =1397) of current smokers reported not smoking. CONCLUSIONS: Smokers with non-ST-segment elevation acute coronary syndrome are generally younger and have fewer cardiac risk factors. A significant interaction of smoking and enoxaparin was seen at 30 days, but not sustained at 6 months and 1 year. More than 60% of smokers quit within 30 days of their cardiac event. There was little difference in outcomes from 30 days to 1 year for these smokers who quit versus those who did not.

Hackam DG, Leiter LA, Yan AT, Yan RT, Mendelsohn A, Tan M, Zavodni L, Chen R, Tsang JL, Kundi A, Lin PJ, Fitchett DH, Langer A, Goodman SG, Anonymous00047. · Department of Medicine, University of Western Ontario, London, Canada. · Can J Cardiol. · Pubmed #18060097 links to  free full text

Abstract: BACKGROUND: Strong evidence supports the use of antithrombotic agents (antiplatelets or oral anticoagulants), statins and angiotensin-converting enzyme inhibitors in patients with atherosclerotic cardiovascular disease; beta-blockers are additionally indicated in patients with coronary artery disease. OBJECTIVES: The investigators sought to determine the extent to which guideline-recommended treatments and target goals are adopted in ambulatory patients with cardiovascular disease in Canada. METHODS: Two large, prospective, community-based registries (the Vascular Protection Registry and the Guideline Oriented Approach to Lipid Lowering Registry) enrolled 9809 outpatients with coronary artery disease, cerebrovascular disease, peripheral vascular disease or multiple cardiovascular risk factors from primary care settings in nine provinces across Canada between 2001 and 2004. This analysis focused primarily on patients with cardiovascular disease (n=6296). RESULTS: At baseline, antithrombotics, statins and angiotensin-converting enzyme inhibitors were used in 92%, 80% and 57% of patients, respectively; beta-blockers were used in 59% of patients with coronary artery disease. The dosing of most drug therapies was suboptimal compared with guideline-recommended dosing derived from clinical trials. Treatment goals for cardiovascular risk factors were suboptimally attained: low-density lipoprotein cholesterol in 50% of patients, total to high-density lipoprotein cholesterol ratio in 51% of patients, systolic and diastolic blood pressure in 58% and 78% of patients, respectively, and waist circumference and body mass index in 45% and 19%, respectively. CONCLUSIONS: These data suggest specific opportunities for improving the care of patients with cardiovascular disease in Canada. The focus must now shift from awareness of treatment gaps to implementation of effective solutions.

Yan AT, Yan RT, Kennelly BM, Anderson FA, Budaj A, López-Sendón J, Brieger D, Allegrone J, Steg G, Goodman SG, Anonymous00290. · Division of Cardiology, St. Michael's Hospital, University of Toronto, and Canadian Heart Research Centre, Toronto, Ontario, Canada. · Am Heart J. · Pubmed #17584554 No free full text.

Abstract: BACKGROUND: 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). METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Cohen M, Mahaffey KW, Pieper K, Pollack CV, Antman EM, Hoekstra J, Goodman SG, Langer A, Col JJ, White HD, Califf RM, Ferguson JJ, Anonymous00147. · HEART Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey 07112, USA. · J Am Coll Cardiol. · Pubmed #17010793 No free full text.

Abstract: OBJECTIVES: The purpose of this study was to compare the effect of receiving pretreatment with antithrombin before randomization as well as overall efficacy and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial. BACKGROUND: The SYNERGY trial results demonstrated noninferiority in outcomes with enoxaparin compared with UFH. Randomized treatment was independent of prerandomization treatment. METHODS: Analyses were first performed on the 4 prerandomization subgroups: patients who received no antithrombin therapy and those who were treated with enoxaparin or UFH or both. Then, we focused on the subgroup of patients who received no pretreatment or were pretreated with and randomized to the same drug. Of the 9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received consistent therapy through randomization. The primary end point was the composite of death and nonfatal myocardial infarction (MI) at 30 days. RESULTS: After adjustment for differences among the subgroups, no significant difference in the association between the 4 pretreatment groups and death or MI remained (p = 0.171). The randomized treatment effect on 30-day death or MI tended to vary with pretreatment (p = 0.055 for interaction test after adjustment). Patients who received consistent therapy with enoxaparin had significantly less death or MI than patients randomized to UFH (adjusted p = 0.041) with a trend toward increased bleeding. CONCLUSIONS: Treatment with antithrombin therapy before randomization had potential impact on comparison of study drug effects. After adjustment for differences in baseline characteristics between subgroups, consistent therapy with enoxaparin might be superior to UFH in reducing death or nonfatal MI, with a modest excess in bleeding.

Hackam DG, Tan MK, Lin PJ, Mehta PG, Jaffer S, Kates M, Oh M, Grima EA, Langer A, Goodman SG, Anonymous00187, Anonymous00188. · Canadian Heart Research Center, Toronto, Canada. · J Vasc Surg. · Pubmed #16930931 No free full text.

Abstract: BACKGROUND: Patients affected by peripheral arterial disease (PAD) incur a heightened risk of adverse cardiovascular events, including stroke, myocardial infarction, and vascular mortality. We examined risk factors, medications, and prognosis of outpatients with PAD enrolled in two national, prospective, practice-based Canadian registries that encompassed 484 physician practices: the Vascular Protection and Guideline Oriented Approach in Lipid Lowering registries. METHODS: The 2 registries were combined to analyze 9810 patients with vascular disease, diabetes mellitus, or age 65 years or older plus at least 2 additional cardiovascular risk factors. Risk factors, medications, and major cardiovascular events were recorded at baseline and again at 6 months' follow-up. RESULTS: Compared with patients without PAD (n = 8303), those with PAD (n = 1507) had substantially worse risk factor profiles and were more likely to have coexisting coronary or cerebrovascular disease. Both groups received high rates of treatment with evidence-based therapies, including antiplatelet drugs, statins, and angiotensin-converting enzyme inhibitors. Despite this, patients with PAD had a nearly twofold higher risk of major cardiovascular events at 6 months than non-PAD patients (7.3% vs 4.1%; P < .0001). After adjustment for multiple confounding factors, the presence of PAD at baseline continued to predict a heightened risk of adverse vascular sequelae (odds ratio, 1.54; 95% confidence interval, 1.18-2.01; P < .0001). CONCLUSIONS: These data support a strong relationship between PAD and worsened vascular prognosis that is independent of both conventional vascular risk factors and concomitant cardiovascular disease. The presence of PAD should therefore provide a clear impetus for intensive risk factor modification and use of preventive medical therapy in affected patients.

Yan AT, Yan RT, Tan M, Hackam DG, Leblanc KL, Kertland H, Tsang JL, Jaffer S, Kates ML, Leiter LA, Fitchett DH, Langer A, Goodman SG, Anonymous00380. · Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, Toronto, Ontario, Canada. · Am J Med. · Pubmed #16887414 No free full text.

Abstract: PURPOSE: Our objective was to evaluate treatment patterns and the attainment of current National Cholesterol Education Program (NCEP)-recommended lipid targets in unselected high-risk ambulatory patients. METHODS: Between December 2001 and December 2004, the prospective Vascular Protection and Guidelines Oriented Approach to Lipid Lowering Registries recruited 8056 outpatients with diabetes, established cardiovascular disease (CVD), or both, who had a complete lipid profile measured within 6 months before enrollment. The primary outcome measure was treatment success, defined as the achievement of LDL-cholesterol<2.6 mmol/L (100 mg/dL) according to NCEP guidelines. We examined patient characteristics and use of lipid-modifying therapy in relation to treatment outcome, which included the recently proposed optional LDL-cholesterol target (<1.8 mmol/L [70 mg/dL]) for very high-risk patients. RESULTS: Overall, 78.2% of patients were treated with a statin and 51.2% had achieved the recommended LDL-cholesterol target. Treatment success rate was highest in diabetic patients with CVD (59.6%), followed by nondiabetic patients with CVD (51.8%), and lowest (44.8%) in diabetic patients without CVD (P<.0001). Compared with untreated patients, those on statins were more likely to achieve target (34.4% vs 55.9%, P<.0001). Of the patients who failed to meet target, only 9.9% were taking high-dose statin, while 29.3% were not prescribed any statin therapy. Among very high-risk patients, 20.8% attained the optional LDL-cholesterol goal. In multivariable analysis, advanced age, male sex, diabetes, coronary artery disease, coronary revascularization, and use of statin were associated with treatment success (all P<.0001). CONCLUSION: Despite the well-established benefits of available lipid-modifying drugs, current management of dyslipidemia continues to be suboptimal, with a substantial proportion of patients failing to achieve guideline-recommended lipid targets. There remains an important opportunity to improve the quality of care for these high-risk patients.

Fox KA, Anderson FA, Dabbous OH, Steg PG, López-Sendón J, Van de Werf F, Budaj A, Gurfinkel EP, Goodman SG, Brieger D, Anonymous00080. · Cardiovascular Research, Division of Medical & Radiological Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK. · Heart. · Pubmed #16757543 No free full text.

Abstract: OBJECTIVE: To determine whether revascularisation is more likely to be performed in higher-risk patients and whether the findings are influenced by hospitals adopting more or less aggressive revascularisation strategies. METHODS: GRACE (Global Registry of Acute Coronary Events) is a multinational, observational cohort study. This study involved 24,189 patients enrolled at 73 hospitals with on-site angiographic facilities. RESULTS: Overall, 32.5% of patients with a non-ST elevation acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI; 53.7% in ST segment elevation myocardial infarction (STEMI)) and 7.2% underwent coronary artery bypass grafting (CABG; 4.0% in STEMI). The cumulative rate of in-hospital death rose correspondingly with the GRACE risk score (variables: age, Killip class, systolic blood pressure, ST segment deviation, cardiac arrest at admission, serum creatinine, raised cardiac markers, heart rate), from 1.2% in low-risk to 3.3% in medium-risk and 13.0% in high-risk patients (c statistic = 0.83). PCI procedures were more likely to be performed in low- (40% non-STEMI, 60% STEMI) than medium- (35%, 54%) or high-risk patients (25%, 41%). No such gradient was apparent for patients undergoing CABG. These findings were seen in STEMI and non-ST elevation ACS, in all geographical regions and irrespective of whether hospitals adopted low (4.2-33.7%, n = 7210 observations), medium (35.7-51.4%, n = 7913 observations) or high rates (52.6-77.0%, n = 8942 observations) of intervention. CONCLUSIONS: A risk-averse strategy to angiography appears to be widely adopted. Proceeding to PCI relates to referral practice and angiographic findings rather than the patient's risk status. Systematic and accurate risk stratification may allow higher-risk patients to be selected for revascularisation procedures, in contrast to current international practice.

Levine GN, Lincoff AM, Ferguson JJ, Mahaffey KW, Goodman SG, Cannon CP, Theroux P, Fox KA. · Baylor College of Medicine and the Houston VA Medical Center, Houston, Texas 77030, USA. · Catheter Cardiovasc Interv. · Pubmed #16152646 No free full text.

Abstract: The degree to which catheterization and revascularization procedures are utilized in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) during hospitalization has broad implications with respect to initial pharmacotherapeutic decisions (upfront therapies), treatment and hospital transfer protocols, guideline recommendations, and allocation of training, material, and financial resources. Analysis of data from multiple trials and registries of patients with NSTE-ACS has the potential to assess more broadly utilization of invasive and revascularization procedures and provide a wide angle or bird's-eye view of the management of such patients, complementing the data obtained from any one trial or registry. We therefore undertook a systematic overview of all large trials and registries of patients with NSTE-ACS conducted over the last decade that were deemed appropriate to provide information on catheterization and revascularization procedures. Although not unexpectedly the percentage of patients with NSTE-ACS managed with cardiac catheterization, percutaneous coronary intervention (PCI), and coronary artery bypass grafting varies in different clinical trials and registries, general findings and trends were still discernable from these studies. During the initial treatment period, the majority of patients were ultimately treated with medical therapy alone (e.g., without revascularization). The percentage of those NSTE-ACS patients undergoing diagnostic cardiac catheterization who were then managed with PCI increased over the last decade and now stands at approximately 50%. Of NSTE-ACS patients who undergo revascularization, the percentage of those patients who are revascularized via PCI similarly increased, and PCI is currently the revascularization procedure utilized in approximately three-fourths of patients undergoing revascularization. The percentages of patients undergoing invasive and revascularization procedures were consistently higher in the U.S. cohorts of study subjects when compared to non-U.S. cohorts of study subjects.

Kaul P, Newby LK, Fu Y, Mark DB, Goodman SG, Wagner GS, Harrington RA, Granger CB, Van de Werf F, Ohman EM, Armstrong PW, Anonymous00139. · University of Alberta, Edmonton, Alberta, Canada. · Heart. · Pubmed #15958353 links to  free full text

Abstract: OBJECTIVES: To examine the interaction between ST segment depression on the baseline ECG and subsequent in-hospital revascularisation on six month mortality among patients with non-ST elevation acute coronary syndromes. To examine whether ST segment depression influenced clinical decision making and whether there was international variation in the use of cardiac procedures across ST segment depression categories. METHODS: 11 453 patients enrolled in GUSTO-IIB (global use of strategies to open occluded coronary arteries), PARAGON (platelet IIb/IIIa antagonism for the reduction of acute coronary syndrome events in a global organisation network) -A, and PARAGON-B were studied. Patients were categorised as having no ST segment depression, 1 mm ST segment depression in two contiguous leads, and ST segment depression > or = 2 mm in two contiguous leads. International practice across four geographic regions was examined: USA, Canada, Europe, and Australia/New Zealand. RESULTS: Revascularisation appeared to have no impact on survival among patients with no ST segment depression; however, revascularisation was associated with a significant survival benefit among patients with ST segment depression > or = 1 mm. There was an inverse relation between the extent of ST segment depression and the use of angiography as well as angioplasty (p < 0.01). However, patients with ST segment depression > or = 2 mm were more likely to undergo bypass surgery. The only significant trend of increasing use of revascularisation procedures with increasing ST segment depression was observed in the USA. CONCLUSIONS: International practice patterns in procedure use appear to be insensitive to the extent of ST segment depression. Major opportunities for more efficient delivery of care exist in all regions.

Fox KA, Goodman SG. · No affiliation provided · Chest. · Pubmed #11834694 links to  free full text

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