Temporal changes in the management and outcome of Canadian diabetic patients hospitalized for non-ST-elevation acute coronary syndromes.

Background: There are limited data on the contemporary management and outcomes of non-ST-elevation acute coronary syndrome (NSTE-ACS) patients with diabetes in the "real world." We sought to evaluate (1) the temporal changes in the medical and invasive management and (2) in-hospital outcome of NSTE-ACS patients with and without diabetes.

Methods: We included Canadian patients hospitalized for NSTE-ACS enrolled in 4 consecutive, prospective, multicenter registries: Canadian ACS-I (n = 3259; 1999-2001), ACS-II (n = 1,956; 2002-2003), Global Registry of Acute Coronary Events (GRACE/GRACE2 [n = 7,561; 2004-2007]) and Canadian Registry of Acute Coronary Events (n = 1,326; 2008).

Prognostic significance of electrocardiographic-determined left ventricular hypertrophy and associated ST-segment depression in patients with non-ST-elevation acute coronary syndromes.

Background: Left ventricular hypertrophy (LVH) is frequently associated with ST depression (STD) on the electrocardiogram (ECG), a so-called strain pattern. Although STD is a well-established adverse prognosticator in non-ST-elevation acute coronary syndrome (NSTE-ACS), the relative prognostic importance of LVH and associated STD has not been elucidated.

Methods: A total of 7,761 patients with NSTE-ACS in the Global Registry of Acute Coronary Events (GRACE) and ACS-I registries had admission ECGs analyzed at a core laboratory.

Management patterns of non-ST segment elevation acute coronary syndromes in relation to prior coronary revascularization.

Background: Contemporary guidelines support an early invasive strategy for non-ST elevation acute coronary syndrome (NSTE-ACS) patients who had prior coronary revascularization. However, little is known about the management pattern of these patients in "real world."

Methods: We analyzed 3 consecutive Canadian registries (ACS I, ACS II, and Global Registry of Acute Coronary Events [GRACE]/expanded-GRACE) that recruited 12,483 NSTE-ACS patients from June 1999 to December 2007.

Prognostic utility of quantifying evolutionary ST-segment depression on early follow-up electrocardiogram in patients with non-ST-segment elevation acute coronary syndromes.

Aims: Although ST-segment depression (STD) on the admission electrocardiogram (ECG) confers adverse prognosis in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), the implications of STD on follow-up ECG remain uncertain. We determined the prognostic significance of STD on follow-up ECG performed within 12-24 h of admission and whether its quantitative evaluation can further refine risk stratification.

Methods And Results: The admission and follow-up ECGs of 3877 patients in the SYNERGY trial were analysed for the presence (>or=1 mm) and extent (maximum magnitude on any single lead) of STD.

Underutilization of clopidogrel and glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute coronary syndrome patients: the Canadian global registry of acute coronary events (GRACE) experience.

Background: There are limited contemporary data on the early use of clopidogrel or glycoprotein (Gp) IIb/IIIa inhibitors, alone versus combination therapies, in non-ST-elevation acute coronary syndrome (NSTE-ACS).

Methods: This study included 5,806 Canadian NSTE-ACS patients with elevated cardiac biomarker and/or ST deviation on presentation in the prospective GRACE between 2003-2007. We stratified the study population according to the management strategy (non-invasive vs invasive) and into low-(GRACE risk score or=141).

The expanded Global Registry of Acute Coronary Events: baseline characteristics, management practices, and hospital outcomes of patients with acute coronary syndromes.

Background: The Global Registry of Acute Coronary Events (GRACE)-a prospective, multinational study of patients hospitalized with acute coronary syndromes (ACSs)-was designed to improve the quality of care for patients with an ACS. Expanded GRACE aims to test the feasibility of a simplified data collection tool and provision of quarterly feedback to index individual hospital management practices to an international reference cohort.

Methods: We describe the objectives; study design; study and data management; and the characteristics, management, and hospital outcomes of patients > or =18 years old enrolled with a presumptive diagnosis of ACS.

Recurrent ischemia across the spectrum of acute coronary syndromes: prevalence and prognostic significance of (re-)infarction and ST-segment changes in a large contemporary registry.

Background: There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era.

Methods: The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS.

Temporal trends and patterns of early clopidogrel use across the spectrum of acute coronary syndromes.

Background: Randomized trials have established efficacy of clopidogrel in various types of acute coronary syndromes (ACS). The objective of this study was to examine the temporal trends and patterns of early clopidogrel use (within the first 24 hours of hospitalization) across the spectrum of patients with ACS in Canada.

Methods: Using the multinational, prospective GRACE (Global Registry of Acute Coronary Events) and GRACE(2), we identified 11,177 patients who were admitted for ACS from January 2003 to December 2007 in Canada.

Applying the evidence: do patients with stroke, coronary artery disease, or both achieve similar treatment goals?

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.

Ischemic stroke: a cardiovascular risk equivalent? Lessons learned from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

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.

Acute ST-segment elevation myocardial infarction: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

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).

Usefulness of quantitative versus qualitative ST-segment depression for risk stratification of non-ST elevation acute coronary syndromes in contemporary clinical practice.

This aim of this study was to assess the clinical utility of quantitative ST-segment depression (STD) for refining the risk stratification of non-ST elevation acute coronary syndromes in the prospective, multinational Global Registry of Acute Coronary Events (GRACE). Quantitative measurements of STD on admission electrocardiograms were evaluated independently by a core laboratory, and their predictive value for in-hospital and cumulative 6-month mortality was examined. Although more severe STD is a marker of increased short- and long-term mortality, it is also associated with higher risk clinical features and biomarkers.

Optimal medical therapy at discharge in patients with acute coronary syndromes: temporal changes, characteristics, and 1-year outcome.

Background: There are limited data on the recent trend in the use of optimal evidence-based medical therapies after acute coronary syndromes (ACSs). We sought to evaluate (1) the temporal changes in medical management of patients discharged after an ACS; (2) patient and practice characteristics associated with optimal medical therapy at discharge; and (3) the association between discharge medication use and 1-year outcome.

Methods: The Canadian ACS I (September 1999-June 2001) and ACS II (October 2002-December 2003) Registries were prospective, multicenter, observational studies of 6853 patients admitted for ACS.

Paradoxical use of invasive cardiac procedures for patients with non-ST segment elevation myocardial infarction: an international perspective from the CRUSADE Initiative and the Canadian ACS Registries I and II.

Background: Practice guidelines support an early invasive strategy in patients with non-ST segment elevation acute coronary syndromes, particularly in those at higher risk.

Objectives: To compare North American rates of invasive cardiac procedure use stratified by risk.

Methods: Use of invasive cardiac procedures and other care patterns in patients with non-ST segment elevation acute coronary syndromes from the United States (US) Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) National Quality Improvement Initiative (n=88,097; 465 hospitals) and Canadian ACS Registries I (n=1270; 51 hospitals) and II (n=1473; 36 hospitals) were compared after dividing patients into different risk categories based on predicted risk of in-hospital mortality.

Differences between local hospital and core laboratory interpretation of the admission electrocardiogram in patients with acute coronary syndromes and their relation to outcome.

In the prospective, multinational Global Registry of Acute Coronary Events (GRACE), patients diagnosed with non-ST-elevation acute coronary syndromes had their admission electrocardiogram independently evaluated by a central core laboratory, and its interpretation by the core laboratory and enrolling site were compared. One in 6 of these patients had clinically important features of left-bundle branch block or ST-segment deviation diagnosed by the core laboratory that were apparently not recognized at the local sites; this subgroup of patients was less likely to undergo risk stratification and revascularization. Importantly, failure to recognize these features as confirmed by the core laboratory in routine clinical practice was independently associated with higher mortality and recurrent myocardial infarction at 6 months (adjusted odds ratio 1.

Relationship of ST elevation in lead aVR with angiographic findings and outcome in non-ST elevation acute coronary syndromes.

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).

Risk scores for risk stratification in acute coronary syndromes: useful but simpler is not necessarily better.

Aims: Our objectives were (i) to compare the discriminatory performance of the Thrombolysis in Myocardial Infarction risk score (TIMI RS), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy risk score (PURSUIT RS), and Global Registry of Acute Cardiac Events risk score (GRACE RS) for in-hospital and 1 year mortality across the broad spectrum of non-ST-elevation acute coronary syndromes (ACS) and (ii) to determine their incremental prognostic utility beyond overall risk assessment by physicians.

Methods And Results: We calculated the TIMI RS, PURSUIT RS, and GRACE RS for 1,728 patients with non-ST-elevation ACS in the prospective, multicentre, Canadian ACS II Registry. Discriminatory performance was measured by the c-statistic (area under receiver-operating characteristic curve) and compared by the method described by DeLong.

Long-term prognostic value and therapeutic implications of continuous ST-segment monitoring in acute coronary syndrome.

Background: In patients with acute coronary syndromes (ACS), recurrent ischemia detected by continuous electrocardiographic monitoring portends a poor outcome. We sought to investigate (1) the additional long-term prognostic value of ST-segment monitoring beyond the validated Global Registry of Acute Coronary Events (GRACE) risk score in ACS and (2) whether ST-segment monitoring can identify patients who benefit from early revascularization.

Methods: We determined the GRACE risk score (a validated predictor of inhospital mortality) in 681 non-ST-elevation ACS patients enrolled in the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment trial.

Bedtime administration of graded-release diltiazem in patients with inadequate BP control: a tolerability and efficacy study.

Background: Achievement of target BP is a challenge in patients attending family practice. The long duration between administration of the last bedtime dose of antihypertensive medication and the physiologic early morning surge in BP makes it difficult to achieve satisfactory BP control.

Objective: To determine whether a new graded-release preparation of diltiazem (diltiazem XC), taken once daily at bedtime, will show an acceptable adverse-effect profile as well as improved BP control.

Contemporary management of dyslipidemia in high-risk patients: targets still not met.

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.

The prognostic value of the admission and predischarge electrocardiogram in acute coronary syndromes: the GUSTO-IIb ECG Core Laboratory experience.

Background: Prior research suggests that patients may be entered into clinical trials with different electrocardiographic (ECG) findings than specified by study protocol criteria; the extent and impact of this variability in a large-scale trial have not been previously described.

Methods: We evaluated the relationship between case report form (CRF) categorization of the admission ECG and a Core Laboratory and subsequent outcome in a retrospective analysis of a trial of patients with acute ischemia and a broad spectrum of ECG changes (the GUSTO-IIb trial).

Results: In 11,037 patients with CRF information and an interpretable ECG, there was agreement in 89.

ST-segment depression in non-ST elevation acute coronary syndromes: quantitative analysis may not provide incremental prognostic value beyond comprehensive risk stratification.

Background: It is unclear whether quantitative ST-segment assessment can improve risk stratification of unselected acute coronary syndrome (ACS) patients using the validated Global Registry of Acute Cardiac Events (GRACE) risk model.

Methods: In the prospective, multicenter, Canadian ACS Registry, the admission electrocardiogram was evaluated centrally at a blinded core laboratory. Patients with ST-elevation myocardial infarction and other electrocardiogram confounders were excluded.

The greatest benefit of enoxaparin over unfractionated heparin in acute coronary syndromes is achieved in patients presenting with ST-segment changes: the Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) Electrocardiogram Core Laboratory Substudy.

Background: We undertook a prospective electrocardiogram (ECG) substudy in the ESSENCE trial and hypothesized that patient subgroups with ST-segment deviation would experience greater benefit from enoxaparin, as compared with unfractionated heparin (UFH).

Methods: Of the 3171 patients in the trial, 3087 had a qualifying ECG available for analysis by the core laboratory. Patients were divided into 4 mutually exclusive groups based upon the qualifying ECG: (1) ST-segment elevation, (2) ST-segment depression, (3) T-wave inversions, or (4) others.

The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: lessons from the Global Registry of Acute Coronary Events (GRACE).

Background: The impact and prognostic value of the redefinition of myocardial infarction (MI) with more sensitive markers have not been evaluated prospectively in a large, less selected population with acute coronary syndrome (ACS).

Methods: We evaluated the attack and case-fatality rates of MI based on initial and/or peak creatine kinase (CK), creatine kinase-MB (CK-MB), and cardiac troponin (the upper limit of normal [ULN] was defined according to the local hospital's standard) in a prospective observational registry of 26,267 patients with ACS admitted to 106 hospitals in 14 countries.

Results: The addition of cardiac troponin-positive status to CK status as a criterion for the diagnosis of MI resulted in as many as 1 in 4 additional patients meeting the redefined criteria.