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. We stratified the study population according to prior coronary revascularization status into 4 groups and compared their clinical characteristics, in-hospital use of medications, and cardiac procedures. RESULTS: Of the 12,483 NSTE-ACS patients, 71.2% had no prior revascularization, 14.2% had percutaneous coronary intervention (PCI) only, 9.5% had coronary artery bypass graft surgery (CABG) only, and 5% had both PCI and CABG. Compared to their counterparts without prior revascularization, patients with previous PCI and/or CABG were more likely to be male, to have diabetes, myocardial infarction, and heart failure but less likely to have ST-segment deviation or positive cardiac biomarker on presentation. Early use of evidence-based medications was higher among patients with previous PCI only and lower among patients with previous CABG only. After adjusting for possible confounders including GRACE risk score, prior PCI was independently associated with in-hospital use of cardiac catheterization (adjusted odds ratio [OR] 1.18, 95% CI 1.04-1.34, P = .008). In contrast, previous CABG was an independent negative predictor (adjusted OR .77, 95% CI 0.68-0.87, P \u3c .001). There was no significant interaction (P = .93) between previous PCI and CABG. CONCLUSIONS: The NSTE-ACS patients with previous PCI were more likely to be treated invasively. Conversely, patients with prior CABG less frequently received invasive therapy. Future studies should determine the appropriateness of this treatment discrepancy

RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

AIMS: To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS). METHODS: In a 26-week, multi-centre, double-blind, randomized, parallel-group study, 1279 patients with recent high-risk non-ST-segment or ST-segment elevation ACS received one of six darexaban regimens: 5 mg b.i.d., 10 mg o.d., 15 mg b.i.d., 30 mg o.d., 30 mg b.i.d., or 60 mg o.d. or placebo, on top of dual antiplatelet treatment. Primary outcome was incidence of major or clinically relevant non-major bleeding events. The main efficacy outcome was a composite of death, stroke, myocardial infarction, systemic thromboembolism, and severe recurrent ischaemia. RESULTS: Bleeding rates were numerically higher in all darexaban arms vs. placebo (pooled HR: 2.275; 95% CI: 1.13–4.60, P = 0.022). Using placebo as reference (bleeding rate 3.1%), there was a dose–response relationship (P = 0.009) for increased bleeding with increasing darexaban dose (6.2, 6.5, and 9.3% for 10, 30, and 60 mg daily, respectively), which was statistically significant for 30 mg b.i.d. (P = 0.002). There was no decrease (indeed a numerical increase in the 30 and 60 mg dose arms) in efficacy event rates with darexaban, but the study was underpowered for efficacy. Darexaban showed good tolerability without signs of liver toxicity. CONCLUSIONS: Darexaban when added to dual antiplatelet therapy after ACS produces an expected dose-related two- to four-fold increase in bleeding, with no other safety concerns but no signal of efficacy. Establishing the potential of low-dose darexaban in preventing major cardiac events after ACS requires a large phase III trial. ClinicalTrials.gov Identifier: NCT0099429

Evaluation of left ventricular ejection fraction in non-ST-segment elevation acute coronary syndromes and its relationship to treatment

BACKGROUND: In-hospital assessment of left ventricular ejection fraction (LVEF) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is emphasized in current practice guidelines. There are limited data regarding the evaluation of LVEF and clinical characteristics and in-hospital management in the real world. METHODS: Registries including the Canadian Acute Coronary Syndrome (ACS) I and II, Global Registry of Acute Coronary Events (main GRACE/expanded GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 13,703 NSTE-ACS patients across Canada between 1999 and 2008. Patients were stratified by in-hospital LVEF measurement, and LVEF was categorized as normal, mildly, or moderately to severely impaired. We compared clinical characteristics, cardiac procedures, and clinical outcomes across these groups. Multivariable logistic regression identified factors independently associated with the assessment of LVEF. RESULTS: Overall, 8,116 patients (59.2%) had LVEF measurement, and of the 7,667 patients with available LVEF data, 4,470 (58.3%) had normal, 1,916 (25%) mildly impaired, and 1,281 (16.7%) moderately to severely impaired LVEF. Patients with LVEF assessment more frequently (all P \u3c .001) underwent cardiac catheterization, percutaneous coronary intervention or coronary bypass surgery, and had higher (both P \u3c .001) rates of myocardial (re) infarction and heart failure. In-hospital reinfarction, higher Killip class, abnormal biomarker, hospital stay \u3e10 days, and on-site cardiac catheterization facility were independently associated with LVEF assessment. Despite increasing LVEF assessment over time (P for trend \u3c .001), 31.2% of patients in the most recent registry (2008) had no in-hospital LVEF assessment. CONCLUSIONS: In-hospital LVEF assessment is not performed in many NSTE-ACS patients. The LVEF assessment, associated with increased use of evidence-based therapies and invasive cardiac procedures, was obtained more frequently in patients with myocardial (re) infarction, heart failure on presentation, and prolonged hospital stay

Relation of timing of cardiac catheterization to outcomes in patients with non-ST-segment elevation myocardial infarction or unstable angina pectoris enrolled in the multinational global registry of acute coronary events

We assessed whether timing of catheterization is associated with the type of non-ST-segment elevation acute coronary syndrome and/or outcome in patients who were enrolled in the Global Registry of Acute Coronary Events. Overall, 8,853 patients who had unstable angina pectoris or non-ST-elevation myocardial infarction were categorized according to timing of catheterization: expeditive (48 hours). Patients in the delayed group were older, more frequently had previous myocardial infarction or stroke, and had a higher risk score compared with those in the expeditive and early groups (all

Disparities in management patterns and outcomes of patients with non-ST-elevation acute coronary syndrome with and without a history of cerebrovascular disease

Cerebrovascular (CVD) disease is commonly associated with coronary artery disease and adversely affects outcome. The goal of the present study was to examine the temporal management patterns and outcomes in relation to previous CVD in a contemporary real-world spectrum of patients with acute coronary syndrome (ACS). From 1999 to 2008, 14,070 patients with non-ST-segment elevation ACS were recruited into the Canadian Acute Coronary Syndrome I (ACS I), ACS II, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) prospective multicenter registries. We stratified the study patients according to a history of CVD and compared their treatment and outcomes. Patients with a history of CVD were older, more likely to have pre-existing coronary artery disease, elevated creatinine, higher Killip class, and ST-segment deviation on admission. Despite presenting with greater GRACE risk scores (137 vs 117, p \u3c0.001), patients with previous CVD were less likely to receive evidence-based antiplatelet and antithrombin therapies during the initial 24 hours of hospital admission. They were also less likely to undergo in-hospital coronary angiography and revascularization. These disparities in medical and invasive management were preserved temporally across all 4 registries. Patients with concomitant CVD had worse in-hospital outcomes. Previous CVD remained an independent predictor of in-hospital mortality (adjusted odds ratio 1.43, 95% confidence interval 1.06 to 1.92, p = 0.019) after adjusting for other powerful prognosticators in the GRACE risk score. However, it was independently associated with a lower use of in-hospital coronary angiography (adjusted odds ratio 0.70, 95% confidence interval 0.60 to 0.83, p \u3c0.001). Underestimation of patient risk was the most common reason for not pursuing an invasive strategy. Revascularization was independently associated with lower 1-year mortality (adjusted odds ratio 0.48, 95% confidence interval 0.33 to 0.71, p \u3c0.001), irrespective of a history of CVD. In conclusion, for patients presenting with non-ST-segment elevation-ACS, a history of CVD was independently associated with worse outcomes, which might have been, in part, because of the underuse of evidence-based medical and invasive therapies

Temporal Patterns of Lipid Testing and Statin Therapy in Acute Coronary Syndrome Patients (from the Canadian GRACE Experience)

Current guidelines recommend the measurement of fasting lipid profile and use of statins in all patients with acute coronary syndrome (ACS). However, the temporal trends of lipid testing and statin therapy in real-world patients with ACS are unclear. From January 1999 through December 2008, the prospective, multicenter, Global Registry of Acute Coronary Events (GRACE/GRACE(2)/CANRACE) enrolled 13,947 patients with ACS in Canada. We stratified the study population based on year of presentation into 3 groups (1999 to 2004, 2005 to 2006, and 2007 to 2008) and compared the use of lipid testing and use of statin therapy in hospital. Overall, 70.8% of patients underwent lipid testing and 79.4% received in-hospital statin therapy; these patients were younger and had lower GRACE risk scores (p 130 mg/dl (3.4 mmol/L) were more likely to be treated with in-hospital statins. In conclusion, there has been a significant temporal increase in the use of in-hospital statin therapy but only a minor increase in lipid testing. Lipid testing was strongly associated with in-hospital statin use. A substantial proportion of patients with ACS, especially those at higher risk, still do not receive these guideline-recommended interventions in contemporary practice

Cardiovascular Risk Factors and In-Hospital Mortality in Acute Coronary Syndromes: Insights From the Canadian Global Registry of Acute Coronary Events

BACKGROUND: There are conflicting data regarding the relationship between the number of modifiable traditional risk factors and prognosis in acute coronary syndromes (ACS). This controversy might in part be explained by the differential use of prehospital medications. METHODS: Using data from the Canadian, multicentre Global Registry of Acute Coronary Events (GRACE) (1999-2008), we stratified 13,686 ACS patients into 3 groups (0, 1-2, vs 3-4 risk factors) and compared their baseline characteristics, in-hospital treatments, and outcomes. Multivariable logistic regressions were performed to adjust for the components of the GRACE risk score and preadmission statin and acetylsalicylic acid (ASA) use. RESULTS: Among these patients (ST-elevation myocardial infarction 28.3%), 14.5%, 62.6%, and 22.9% had 0, 1-2, and 3-4 risk factors, respectively. Patients with fewer risk factors were less likely to be on ASA, statin, and other prehospital medications. Unadjusted in-hospital mortality was significantly different across risk factor groups (4.9%, 3.0%, and 3.1% for 0, 1-2, and 3-4 risk factor groups, respectively, P for trend = 0.002). This difference was no longer significant after adjusting for the components of the GRACE risk score (P for trend = 0.088) and further adjusting for preadmission statin and ASA use (P for trend = 0.96). For in-hospital mortality, there was no significant interaction between risk factor categories and ACS type (P = 0.26). CONCLUSIONS: The lower mortality observed in patients with ACS with more risk factors may be partially attributed to the protective effect of prehospital ASA and statin use. The number of risk factors does not provide incremental prognostic value beyond the validated GRACE risk score

Management and Outcome of Acute Coronary Syndrome Patients in Relation to Prior History of Atrial Fibrillation

BACKGROUND: The prognostic impact of atrial fibrillation (AF) in the setting of acute coronary syndrome (ACS) is controversial. Furthermore, there are limited real-world data on the management of ACS patients with history of AF. METHODS: The Global Registry of Acute Coronary Events (GRACE/GRACE2) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 14,285 patients across Canada between 1999 and 2008. Patients were stratified by the presence of history of AF. We compared clinical characteristics, medical therapies, cardiac procedures, and clinical outcomes between the 2 groups. RESULTS: Overall, 1333 of the enrolled patients (9.3%) had history of AF, of whom 51.5% presented with non-ST-segment elevation myocardial infarction, 29.5% with unstable angina, and 19.1% with ST-segment elevation myocardial infarction. Compared with the group without, patients with a history of AF less frequently received evidence-based antiplatelet and antithrombin therapies, left ventricle ejection fraction assessment, and coronary angiography (all P \u3c 0.001); they also had higher unadjusted rates of in-hospital death, myocardial (re)infarction, and heart failure. However, in multivariable analysis, history of AF was not found to be independently associated with in-hospital mortality (adjusted odds ratio [OR] = 1.12; 95% confidence interval (CI), 0.73-1.73; P = 0.61) or death and/or myocardial reinfarction (adjusted OR = 1.15; 95% CI, 0.87-1.5; P = 0.34). CONCLUSIONS: History of AF is common among ACS patients. They received less evidence-based medical and invasive therapies than ACS patients without history of AF. History of AF is a negative independent predictor of in-hospital coronary angiography but was not found to be independently associated with adverse outcomes. All rights reserved

Comparison of baseline characteristics, management and outcome of patients with non-ST-segment elevation acute coronary syndrome in versus not in clinical trials

Previous studies have questioned the external validity of randomized controlled trial results of acute coronary syndrome (ACS) because of potential selection bias toward healthier patients. We sought to evaluate differences in clinical characteristics and management of patients admitted with non-ST-elevation ACS according to participation in clinical trials over the previous decade. The Canadian ACS I (1999 to 2001), ACS II (2002-2003), GRACE (2004-2007), and CANRACE (2008) were prospective, multicenter registries of patients admitted to hospitals with ACS. We examined 13,556 patients with non-ST-elevation ACS, of whom 1,126 (8.3%) participated in clinical trials. Data were collected on baseline characteristics, medication use at admission and discharge, in-hospital procedures, and in-hospital adverse events. Patients enrolled in clinical trials were younger, more likely to be men, and had fewer co-morbidities. They were significantly more likely to be on several guideline-recommended medications and were significantly more likely to undergo invasive procedures, including coronary angiography, percutaneous coronary intervention, and coronary bypass surgery (all p values \u3c0.001). Unadjusted in-hospital (2.1% vs 0.7%, p = 0.001) and 1-year (8.9% vs 6.3%, p = 0.037) mortality rates were higher in non-enrolled patients. In multivariable analysis, patients who were older, women, had a history of heart failure, and increased creatinine levels on presentation were less likely to be enrolled into clinical trials. In conclusion, significant differences persist in baseline characteristics, treatment, and outcomes between patients enrolled and those not enrolled in clinical trials. Consequently, generalization of ACS clinical trials over the previous decade to the real-world patient may remain in question

Influence of age on use of cardiac catheterization and associated outcomes in patients with non-ST-elevation acute coronary syndromes

Randomized controlled trials support the use of an early invasive strategy in high-risk patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). Although risk increases with age, limited data are available to support this strategy in older patients. The aims of this study were to examine temporal trends in the management and outcomes of NSTE ACS in elderly patients and to explore reasons for the lower use of early angiography in the aged population. Data from 11,732 patients with NSTE ACS were collected from 3 consecutive Canadian registries (ACS I, ACS II, and Global Registry of Acute Coronary Events [GRACE]/GRACE2) from 1999 to 2007. Rates of in-hospital cardiac catheterization, revascularization, infarction or reinfarction, and death were stratified by age (\u3c65, 65 to 74, and \u3e or = 75 years). Although overall, rates of in-hospital catheterization and revascularization increased over time (p \u3c0.001), the largest increase occurred in patients aged \u3c65 years. The strongest independent negative predictor of the use of cardiac catheterization was age \u3e or = 75 years (adjusted odds ratio 0.45, 95% confidence interval 0.37 to 0.56, p \u3c0.001). Use of an early invasive approach was associated with a reduction in 1-year mortality across all age groups, but the absolute difference was greatest in patients aged \u3e or = 75 years. The underestimation of risk by physicians (ascertained in ACS II) was the most common reason for choosing a conservative strategy. In conclusion, despite an overall increased use of an early invasive strategy, elderly patients with NSTE ACS remain significantly less likely to undergo cardiac catheterization and revascularization and are often erroneously perceived to be at low risk by their physicians. Future studies should determine whether more aggressive treatment of these high-risk elderly patients improves outcomes