In-hospital management and outcomes of acute coronary syndromes in relation to prior history of heart failure.

INTRODUCTION: The prognostic significance of prior heart failure in acute coronary syndromes has not been well studied. Accordingly, we evaluated the baseline characteristics, management patterns and clinical outcomes in patients with acute coronary syndromes who had prior heart failure. METHODS AND RESULTS: The study population consisted of acute coronary syndrome patients in the Global Registry of Acute Coronary Events, expanded Global Registry of Acute Coronary Events and Canadian Registry of Acute Coronary Events between 1999 and 2008. Of the 13,937 eligible patients (mean age 66±13 years, 33% female and 28.3% with ST-elevation myocardial infarction), 1498 (10.7%) patients had a history of heart failure. Those with prior heart failure tended to be older, female and had lower systolic blood pressure, higher Killip class and creatinine on presentation. Prior heart failure was also associated with significantly worse left ventricular systolic function and lower rates of cardiac catheterization and coronary revascularization. The group with previous heart failure had significantly higher rates of acute decompensated heart failure, cardiogenic shock, myocardial (re)infarction and mortality in hospital. In multivariable analysis, prior heart failure remained an independent predictor of in-hospital mortality (odds ratio 1.48, 95% confidence interval 1.08-2.03, p=0.015). CONCLUSIONS: Prior heart failure was associated with high risk features on presentation and adverse outcomes including higher adjusted in-hospital mortality in acute coronary syndrome patients. However, acute coronary syndrome patients with prior heart failure were less likely to receive evidence-based therapies, suggesting potential opportunities to target more intensive treatment to improve their outcome.

Use and timing of coronary angiography and associated in-hospital outcomes in Canadian non-ST-segment elevation myocardial infarction patients: insights from the Canadian Global Registry of Acute Coronary Events.

BACKGROUND: Although an early invasive approach has become standard strategy for the management of non-ST-segment elevation myocardial infarction (NSTEMI), the frequency and timing in Canada is uncertain. METHODS: We examined the use and timing of coronary angiography, revascularization, and cardiovascular outcomes of NSTEMI patients: (1) admitted on weekdays vs weekends; and (2) stratified according to presentation risk level, in the Canadian Global Registry of Acute Coronary Events (GRACE)/Expanded GRACE (GRACE(2))/Canadian Registry of Acute Coronary Events (CANRACE) population. RESULTS: Of 6711 NSTEMI patients, 1956 (29.1%) were admitted on the weekend. The median (interquartile range) wait time for coronary angiography was 58 (32-106) and 70 (50-112) hours for weekday and weekend patients, respectively (P = 0.32). Compared with lower-intermediate risk, higher-risk patients were less likely to undergo angiography (44.7% vs 69.7% for weekdays and 45.2% vs 69.6% for weekends; both P < 0.0001) and waited longer for angiography (median 71 vs 61 hours; P < 0.0001). Weekend admission was independently associated with higher mortality (adjusted odds ratio [OR], 1.52; 95% confidence interval [CI], 1.15-2.01; P = 0.004), recurrent ischemia (adjusted OR, 1.16; 95% CI, 1.01-1.32; P = 0.03), and heart failure (adjusted OR, 1.28; 95% CI, 1.00-1.63; P = 0.048) but not with reinfarction. CONCLUSIONS: Median wait time for angiography in Canadian NSTEMI patients admitted on the weekend was not significantly longer than for those who presented on a weekday. Patients admitted on weekends had higher adjusted mortality and cardiovascular event rates. Higher-risk patients were less likely to undergo angiography and waited longer, with higher observed in-hospital event rates. Systematic, guideline-recommended risk stratification should be considered to ensure that optimal management strategies (eg, timely coronary angiography in higher-risk patients) are matched to level of risk.

Pre-hospital cardiac arrest in acute coronary syndromes: insights from the global registry of acute coronary events and the canadian registry of acute coronary events.

OBJECTIVES: Cardiac arrest in acute coronary syndromes (ACS) is associated with high morbidity and mortality. We examined the clinical characteristics, contemporary management patterns and outcomes of ACS patients with pre-hospital cardiac arrest. METHODS: The Global Registry of Acute Coronary Events and the Canadian Registry of Acute Coronary Events enrolled 14,010 ACS patients in 1999-2008. We compared the clinical characteristics, in-hospital treatment and outcomes between patients with and without pre-hospital cardiac arrest. RESULTS: Overall, 206 (1.4%) patients had cardiac arrest prior to hospital presentation. ACS patients with pre-hospital cardiac arrest were less frequently treated with aspirin, ß-blocker, angiotensin-converting enzyme inhibitors, and statins within the first 24 h of presentation, but the use of cardiac procedures was similar compared to the group without cardiac arrest. Patients with pre-hospital cardiac arrest had significantly higher rates of in-hospital adverse events. Factors independently associated with pre-hospital cardiac arrest included male gender, current smoker status, tachycardia, higher Killip class and ST-segment deviation. CONCLUSION: ACS patients with pre-hospital cardiac arrest continue to have more in-hospital complications and higher mortality. Their use of evidence-based medical therapies was lower but the use of cardiac procedures was similar compared to the group without cardiac arrest. Better utilization of evidence-based therapies in these patients may translate into improved outcomes.

Treatment and outcomes of non-ST elevation acute coronary syndromes in relation to burden of pre-existing vascular disease.

BACKGROUND: Patients with atherosclerotic disease in one territory often have disease in other vascular territories. However, the relationships between pre-existing vascular disease and the treatment and outcome of acute coronary syndrome (ACS), have not been well characterized. METHODS: The Canadian ACS2, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) were used to obtain data on 10,667 non-ST segment elevation acute coronary syndrome (NSTEACS) patients between 2002 and 2008. Multivariable analysis was used to examine the relationships between the number of vascular beds affected and both in-hospital coronary angiography and in-hospital mortality. The ACS2 registry (2002-2003) included physician-reported reasons for non-invasive management, which were stratified by vascular disease burden. RESULTS: Patients with more vascular disease had higher GRACE risk scores at presentation, but less frequently received antiplatelet agents and angiography. The most common reason in the ACS2 registry for patients who did not undergo angiography was "not high enough risk." There was an independent inverse relationship between the extent of vascular disease and in-hospital angiography. Patients with higher vascular disease burden had higher unadjusted in-hospital mortality. In multivariable analysis, patients with 1 vascular territory affected had the lowest and those with 3 vascular beds affected had the highest adjusted in-hospital mortality. In the ACS2 registry, patients with more extensive vascular disease had higher rates of 1-year mortality and death/re-infarction (both p for trend <0.001). CONCLUSIONS: NSTEACS patients with more vascular disease received less intensive treatment, with an associated worse outcome. This undertreatment might be partly mediated by physicians' underestimation of patient risk. More aggressive risk factor modification and intensive ACS therapies may improve the outcome of these high-risk patients.

Improved survival associated with pre-hospital triage strategy in a large regional ST-segment elevation myocardial infarction program.

OBJECTIVES: This study sought to compare the 1-year survival of patients diagnosed with ST-segment elevation myocardial infarction (STEMI) and transferred via pre-hospital triage strategy for primary percutaneous coronary intervention (PCI) with those transferred via inter-hospital transfer within a large suburban region in Canada. BACKGROUND: Primary angioplasty is the preferred therapy for STEMI if it is done within 90 min of door-to-balloon time by an experienced team in a high-volume center. METHODS: Patients identified to have STEMI on the ambulances equipped with electrocardiography bypassed the local hospitals and were sent directly to the PCI center, whereas other patients that were picked up by ambulances without electrocardiographic equipment were transported to the local hospitals where the diagnosis of STEMI was made and were re-routed to the PCI center. Patient demographic data, clinical presentation, procedural data, in-hospital course, and vital statistics were prospectively recorded in a provincial cardiac registry. RESULTS: A total of 167 patients were brought into the PCI center via pre-hospital triage strategy, and 427 patients were brought in via inter-hospital transfer during a 2-year study period. Baseline demographic data, infarct location, cardiovascular history, and hemodynamic status were similar between the 2 groups. When compared with the inter-hospital transfer group, a significantly higher proportion of pre-hospital triaged patients achieved the 90-min door-to-balloon time benchmark (80.4% vs. 8.7%, p < 0.001) and post-procedural Thrombolysis In Myocardial Infarction flow grade 3 after the emergency procedure (97.6% vs. 91.4%, p = 0.02). In addition, the pre-hospital triage strategy was associated with a significantly lower 30-day (5.4% vs. 13.3%, p = 0.006) and 1-year (6.6% vs. 17.5%, p = 0.019) mortality. Pre-hospital triage was an independent predictor for survival at 1 year (hazard ratio: 0.37, 95% confidence interval: 0.18 to 0.75, p = 0.006). CONCLUSIONS: Pre-hospital triage strategy was associated with improved survival rate in patients undergoing primary PCI in a regional STEMI program.

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 <0.001 for the 2 comparisons) compared to those who did not. Over time there was a significant increase in rates of in-hospital statin therapy (70% in 1999 to 2004 to 84.5% in 2007 to 2008, p for trend < 0.001) but only a minor increase in rates of lipid testing (69.4% in 1999 to 2004 to 72.4% in 2007 to 2008, p for trend = 0.003). After adjusting for confounders, this increasing temporal trend remained statistically significant for statin therapy (p <0.001) but not for lipid testing. Lipid testing was independently associated with in-hospital statin use (adjusted odds ratio 1.62, 95% confidence interval 1.27 to 2.08, p <0.001). In patients who did have lipid testing, those with low-density lipoprotein cholesterol level >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.

Reperfusion strategies and outcomes of ST-segment elevation myocardial infarction patients in Canada: observations from the Global Registry of Acute Coronary Events (GRACE) and the Canadian Registry of Acute Coronary Events (CANRACE).

BACKGROUND: We examine the clinical characteristics and outcomes of ST-elevation myocardial infarction (STEMI) patients receiving various reperfusion therapies in 2 contemporary Canadian registries. METHODS: Of 4045 STEMI patients, 2024 received reperfusion therapy and had complete data on invasive management. They were stratified by reperfusion strategy used: primary percutaneous coronary intervention (PCI) (n = 716); fibrinolysis with rescue PCI (n = 177); fibrinolysis with urgent/elective PCI (n = 210); and fibrinolysis without PCI (n = 921). Data were collected on clinical and laboratory findings, and outcomes. RESULTS: Compared with fibrinolytic-treated patients, patients treated with primary PCI were younger and had higher Killip class, had longer time to delivery of reperfusion therapy, and utilized more antiplatelet therapy but less heparin, ß-blockers and angiotensin-converting enzyme inhibitors. In-hospital death occurred in 2.7% of patients treated with primary PCI, 1.7% fibrinolysis-rescue PCI, 1.0% fibrinolysis-urgent/elective PCI, and 4.8% fibrinolysis-alone (P = 0.009); the rates of death/reinfarction were 3.9%, 4.0%, 4.3%, and 7.1% (P = 0.032), respectively. The rate of shock was highest in the primary PCI group. Rates of heart failure or major bleeding were similar in the 4 groups. In multivariable analysis, no PCI during hospitalization was associated with death and reinfarction (adjusted odds ratio = 1.66; 95% confidence interval, 1.03-2.70; P = 0.04). CONCLUSIONS: Clinical features, time to reperfusion, and medication utilization differed with respect to the reperfusion strategy. While low rates of re-infarction/death were observed, these complications occurred more frequently in those who did not undergo PCI during index hospitalization.

Has the ClOpidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) of early ß-blocker use in acute coronary syndromes impacted on clinical practice in Canada? Insights from the Global Registry of Acute Coronary Events (GRACE).

BACKGROUND: The COMMIT/CCS-2 trial, published in 2005, demonstrated no net benefit of early ß-blocker (BB) therapy in acute coronary syndromes (ACS). We sought to assess the short-term impact of this landmark trial by comparing the use of early BB therapy in patients with a broad spectrum of ACS before and after 2005. METHODS: Using data from the Global Registry of Acute Coronary Events and Canadian Registry of Acute Coronary Events, we compared the rates of BB use within the first 24 hours of presentation in the periods 1999 to 2005 and 2006 to 2008, after stratifying patients by the type of ACS (ST-segment elevation myocardial infarction [STEMI] and non-ST-segment elevation ACS [NSTEACS]) and clinical presentation. RESULTS: Of the 14,231 patients with ACS, 77.7% received BB therapy within 24 hours of presentation (78.5% and 77.4% in the STEMI and NSTEACS groups, respectively). The early use of BB declined in the STEMI group (80.3% to 76.7%, P = .005) but increased in the NSTEACS group (75.4% to 78.9%, P < .001) after 2005. Long-term BB use, higher systolic blood pressure, and higher heart rate were independent predictors of early BB use. Conversely, patients who were female, older, Killip class >1, and had cardiac arrest at presentation were less likely to receive early BB. Multivariable analysis showed a trend toward lower use of BB among patients with STEMI (adjusted odds ratio 0.76, 95% CI 0.57-1.00, P = .055) and a trend toward more frequent BB use among patients with NSTEACS (adjusted odds ratio 1.22, 95% CI 0.96-1.55, P = .11) after 2005. The temporal trends in the early use of BB differed between patients with STEMI and patients with NSTEACS (P for interaction with period <.001). CONCLUSIONS: Most patients with STEMI or NSTEACS were treated with early BB therapy. In accordance with the COMMMIT/CCS-2 trial, patients with lower systolic blood pressure and higher Killip class in the "real world" less frequently received early BB therapy. Since the publication of COMMIT/CCS-2, there has been no significant change in the use of BB in patients with STEMI or NSTEACS after controlling for their clinical characteristics.

Temporal trend of in-hospital major bleeding among patients with non ST-elevation acute coronary syndromes.

BACKGROUND: Although randomized controlled trials support the use of intensive medical and invasive therapies for non-ST segment elevation acute coronary syndromes (NSTE-ACS), major bleeding is a serious treatment complication. We sought to determine the temporal trend of in-hospital major bleeding among patients with NSTE-ACS, in relation to the evolving management pattern. METHODS: We identified 14 111 NSTE-ACS patients enrolled in 4 successive, prospective, multicenter registries (ACS I, 1999-2001; ACS II, 2002-2003; GRACE, 2004-2007; and CANRACE, 2008) in Canada between 1999 and 2008. We collected data on patient characteristics, use of cardiac medications and procedures on standardized case report forms. In all registries, major bleeding was defined a priori as life threatening or fatal bleeding, bleeding requiring transfusion of ≥2 U of packed red cells, or resulting in an absolute decrease in hemoglobin of >30g/L. RESULTS: A total of 14 111 patients had a final diagnosis of NSTE-ACS and were included in this study (3294 in the ACS-I registry, 1956 in the ACS-II registry, 7543 in GRACE, and 1318 in CANRACE). Over time, there was a substantial increase in the use of dual anti-platelet (aspirin and thienopyridine) therapy (P for trend <.001), and in rates of in-hospital cardiac catheterization and percutaneous coronary intervention (both Ps for trend <.001). Overall, major bleeding was relatively infrequent (1.7%). There was no significant increase in the unadjusted rates of major bleeding over time (P for trend = .19). In multivariable analysis adjusting for GRACE risk score and intensive treatment, enrolment period was not an independent predictor of bleeding (P for trend = .98). There was no interaction between the enrolment period and the use of intensive medical and invasive management. CONCLUSION: Despite more widespread use of dual anti-platelet therapies and invasive cardiac procedures in the management of NSTE-ACS, the rate of major bleeding remains relatively low and has not increased significantly over time. Our findings suggest that physicians selectively target treatment for their patients, and these evidence-based therapies can be safely administered to ACS patients in clinical practice.

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 < .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.

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). RESULTS: Overall, 3,893 patients (67.1%) received early (

Validation of the Global Registry of Acute Coronary Event (GRACE) risk score for in-hospital mortality in patients with acute coronary syndrome in Canada.

BACKGROUND: The Global Registry of Acute Coronary Event (GRACE) risk score was developed in a large multinational registry to predict in-hospital mortality across the broad spectrum of acute coronary syndromes (ACS). Because of the substantial regional variation and temporal changes in patient characteristics and management patterns, we sought to validate this risk score in a contemporary Canadian population with ACS. METHODS: The main GRACE and GRACE(2) registries are prospective, multicenter, observational studies of patients with ACS (June 1999 to December 2007). For each patient, we calculated the GRACE risk score and evaluated its discrimination and calibration by the c statistic and the Hosmer-Lemeshow goodness-of-fit test, respectively. To assess the impact of temporal changes in management on the GRACE risk score performance, we evaluated its discrimination and calibration after stratifying the study population into prespecified subgroups according to enrollment period, type of ACS, and whether the patient underwent coronary angiography or revascularization during index hospitalization. RESULTS: A total of 12,242 Canadian patients with ACS were included; the median GRACE risk score was 127 (25th and 75th percentiles were 103 and 157, respectively). Overall, the GRACE risk score demonstrated excellent discrimination (c statistic 0.84, 95% CI 0.82-0.86, P < .001) for in-hospital mortality. Similar results were seen in all the subgroups (all c statistics >/=0.8). However, calibration was suboptimal overall (Hosmer-Lemeshow P = .06) and in various subgroups. CONCLUSIONS: GRACE risk score is a valid and powerful predictor of adverse outcomes across the wide range of Canadian patients with ACS. Its excellent discrimination is maintained despite advances in management over time and is evident in all patient subgroups. However, the predicted probability of in-hospital mortality may require recalibration in the specific health care setting and with advancements in treatment.

Temporal management patterns and outcomes of non-ST elevation acute coronary syndromes in patients with kidney dysfunction.

AIMS: To examine: (i) the temporal changes in the management pattern; (ii) the reasons for any treatment disparities; (iii) the relationship between invasive treatment and outcome, among acute coronary syndrome (ACS) patients with vs. without kidney dysfunction. METHODS AND RESULTS: Canadian ACS I, ACS II registries and Global Registry of Acute Coronary Events (GRACE) were prospective, multi-centre, observational studies of patients with ACS. From 1999 to 2007, non-ST elevation (NSTE) ACS patients were recruited in ACS I (n = 3295; 1999-2001), ACS II (n = 1956; 2002-2003), and GRACE (n = 6491; 2004-2007) in Canada. Using the four-variable Modified Diet in Renal Disease equation, we stratified the study population (n = 11,377) into three groups based on their estimated glomerular filtration rate (eGFR), and examined their treatment and outcome. While in-hospital use of coronary angiography and revascularization increased over time in all groups (P < 0.001), patients with kidney dysfunction were less likely to undergo invasive management (P < 0.001). Unadjusted 1 year mortality was lower among patients receiving in-hospital coronary angiography within all eGFR categories (> or =60 mL/min/1.73 m(2): 2.5 vs. 7.6%, P < 0.001; 30-59 mL/min/1.73 m(2): 8.0 vs. 14.6%, P < 0.001; <30 mL/min/1.73 m(2): 27.5 vs. 41.5%, P = 0.043). In-hospital revascularization was independently associated with lower 1-year mortality (adjusted OR = 0.52, 95% CI 0.36-0.77, P = 0.001), irrespective of eGFR (P for heterogeneity = 0.39). Underestimation of patient risk was the most common barrier to an invasive treatment strategy. CONCLUSION: Despite temporal increases in invasive management of NSTE-ACS, patients with kidney dysfunction are more commonly treated conservatively, with an associated worse outcome. In-hospital revascularization was independently associated with improved survival, irrespective of eGFR. Randomized controlled trials involving patients with kidney dysfunction are needed to confirm whether more aggressive treatment will improve their poor outcome.

A multicenter disease management program for hospitalized patients with heart failure.

BACKGROUND: Despite the availability of proven therapies, outcomes in patients with heart failure (HF) remain poor. In this 2-stage, multicenter trial, we evaluated the effect of a disease management program on clinical and economic outcomes in patients with HF. METHODS AND RESULTS: In Stage 1, a pharmacist or nurse assessed each patient and made recommendations to the physician to add or adjust angiotensin-converting enzyme (ACE) inhibitors and other HF medications. Before discharge (Stage 2), patients were randomized to a patient support program (PSP) (education about HF, self-monitoring, adherence aids, newsletters, telephone hotline, and follow-up at 2 weeks, then monthly for 6 months after discharge) or usual care. In Stage 1 (766 patients) ACE inhibitor use increased from 58% on admission to 83% at discharge (P < .0001), and the daily dose (in enalapril equivalents) increased from 11.3 +/- 8.8 mg to 14.5 +/- 8.8 mg (P < .0001). In Stage 2 (276 patients) there was no difference in ACE inhibitor adherence, but a reduction in cardiovascular-related emergency room visits (49 versus 20, P = .030), hospitalization days (812 versus 341, P = .003), and cost of care (2,531 Canadian dollars less per patient) in favor of the PSP. CONCLUSION: Simple interventions can improve ACE inhibitor use and patient outcomes.