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 GRACE2 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet ...drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This full document has been summarized in an Executive Summary published in the Canadian Journal of Cardiology and may be found at http://www.ccs.ca/ . Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital following acute coronary syndromes, post–percutaneous coronary intervention, post–coronary artery bypass grafting, patients with a history of transient cerebral ischemic events or strokes, and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy/lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel and proton-pump inhibitors, or acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objectives We sought to compare outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) with or without previous coronary ...artery bypass grafts (CABG). Background Limited information exists regarding procedural success and clinical outcomes of STEMI patients with CABG undergoing primary PCI. Methods The APEX-AMI (Assessment of Pexelizumab in Acute Myocardial Infarction) trial was a randomized, placebo-controlled trial of pexelizumab in STEMI patients with planned primary PCI: 128 of 5,745 (2.2%) patients had prior CABG. Clinical/procedural characteristics, culprit vessel (infarct-related artery IRA), and 90-day clinical outcomes were compared. Results Patients with previous CABG were more frequently men, older, had a higher incidence of comorbidities and multivessel disease. In patients with versus without prior CABG, PCI was performed less frequently, that is, 78.9% versus 93.9%; of those with prior CABG receiving PCI, Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was also restored less often, that is, 82.5% versus 91.6% (both p < 0.001). In prior CABG, there was a nearly even designation of the IRA as a bypass graft (n = 63) versus a native vessel (n = 55): IRA post-PCI TIMI flow grade 3 was achieved in 66.7% versus 88.0%, respectively (p = 0.043). Prior CABG patients had increased 90-day death and composite 90-day death/congestive heart failure/shock. Excess death remained significant after multivariable adjustment (hazard ratio: 1.9, 95% confidence interval: 1.08 to 3.33, p = 0.025). When prior CABG patients were stratified by the type of IRA, there was further discrimination of the increased 90-day death, that is, 19% bypass graft (n = 63) versus 5.7% native vessel (n = 55, p = 0.05), respectively. Conclusions Prior CABG patients with STEMI are less likely to undergo acute reperfusion, have worse angiographic outcomes following primary PCI, and higher 90-day mortality. These findings are especially applicable when the IRA was a bypass graft.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Current guideline-based recommendations for oral dual-antiplatelet therapy in an acute coronary syndrome (ACS) include the use of newer adenosine diphosphate receptor inhibitor (ADPri) ...regimens and agents. The Canadian ACS Reflective Program is a multicenter observational quality-enhancement project that compared the use of ADPri therapy in 2 phases (November 2011-March 2013 and April 2013-November 2013) and also compared ADPri use with previous national data from the Canadian Global Registry of Acute Coronary Events (2000-2008). Of 3099 patients with ACS, 30.6% had ST-segment elevation myocardial infarction (STEMI), 52.3% had non-STEMI, and 17% had unstable angina. There was high use of dual-antiplatelet therapy for ≤ 24 hours, with important increases noted when compared with previous national experience ( P for trend, < 0.0001). Clopidogrel was the most commonly used ADPri (82.2%), with lower use of the newer agents ticagrelor (9.0%) and prasugrel (3.1%). Ticagrelor and prasugrel use was most frequent in patients with STEMI undergoing percutaneous coronary intervention PCI (34.3%). There was relatively lower use of ADPri therapy at discharge; it was given mainly to patients who did not undergo PCI (68.2%) and to those with non-ST–elevation ACS (82%). When comparing the 2 consecutive phases of data collection in the ACS Reflective, there was an approximate 3- and 2-fold increase in the early and discharge use of the newer ADPri agents, respectively. In conclusion, there has been a temporal increase in ADPri use compared with previous national experience and an increased uptake of newer ADPri agents. Additional work is needed to identify and address barriers limiting optimal implementation of these newer guideline-recommended agents into routine Canadian practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Since the introduction of newer, more potent P2Y12 receptor inhibitors (P2Y12 ris), practice patterns and associated clinical outcomes in patients with myocardial infarction (MI) ...undergoing percutaneous coronary intervention (PCI) and also requiring oral anticoagulation (OAC) have not been fully characterized. Methods The Canadian Observational Antiplatelet Study was a prospective, multicenter, longitudinal, observational study (26 hospitals, Dec/11-May/13) describing P2Y12 ri treatment patterns and outcomes in patients with ST-elevation and non-ST-elevation MI undergoing PCI. We describe the clinical characteristics, treatment patterns, bleeding and ischemic outcomes over the 15-month follow-up within and between the subgroups of patients discharged on either dual antiplatelet therapy (DAPT; ASA + P2Y12 ri) or triple therapy (ASA + P2Y12 ri + OAC). Results Of the 2034 patients at discharge, 86% (n = 1757) were on DAPT, while 14% (n = 277) were on triple therapy (50% warfarin, 50% non-vitamin K oral anticoagulant NOAC). The frequency of newer P2Y12 ri use (prasugrel or ticagrelor) was similar in the DAPT and triple therapy groups (28% vs 26%, respectively). In the triple therapy group, NOAC use was higher in those receiving a new P2Y12 ri compared to those receiving clopidogrel (75% vs 41%, respectively, P < .0001). The unadjusted and adjusted events of MACE and bleeding were higher in the triple therapy group. For patients on triple therapy, the bleeding or MACE events were not significantly different between those on clopidogrel versus those on ticagrelor or prasugrel. Conclusion In this observational study of MI patients requiring PCI, 1 in 8 were discharged on triple antithrombotic therapy, of whom 26% were on newer P2Y12 ris. Patients on triple therapy had higher risk at baseline, with higher unadjusted and adjusted MACE and bleeding events compared to those on DAPT alone. Amongst triple therapy-treated patients, there was no difference in the MACE and bleeding events regardless of the P2Y12 ri used.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Despite current dual-antiplatelet therapy with aspirin and clopidogrel, adverse clinical events continue to occur during and after percutaneous coronary intervention (PCI). The failure of clopidogrel ...to provide optimal protection may be related to delayed onset of action, interpatient variability in its effect, and an insufficient level of platelet inhibition. Furthermore, the irreversible binding of clopidogrel to the P2Y12 receptor for the life span of the platelet is associated with increased bleeding risk especially during urgent or emergency surgery. Novel antiplatelet agents are required to improve management of patients undergoing PCI. Elinogrel is a potent, direct-acting (ie, non-prodrug), selective, competitive, and reversible P2Y12 inhibitor available in both intravenous and oral formulations. The INNOVATE-PCI study is a phase 2 randomized, double-blind, clopidogrel-controlled trial to evaluate the safety, tolerability, and preliminary efficacy of this novel antiplatelet agent in patients undergoing nonurgent PCI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Contemporary use of dual antiplatelet therapy and consistency with guideline recommendations in acute coronary syndrome (ACS) patients undergoing percutaneous coronary ...intervention (PCI) has not been well characterized. Methods The Canadian Observational AntiPlatelet sTudy (COAPT) was a prospective, observational, multicenter, longitudinal study of patients with myocardial infarction (MI) undergoing PCI. Baseline characteristics, treatment patterns, processes of care, factors associated with switching to and from novel adenosine diphosphate receptor inhibitors (ADPris), and in-hospital outcomes are described. Results Among 2179 MI patients undergoing PCI during their index hospitalisation, 1328 (60.9%) had ST elevation. Initial ADPri use included clopidogrel in 1812 (83.2%), prasugrel in 125 (5.7%), and ticagrelor in 242 (11.1%). At discharge, 1597 patients (73.4%) were prescribed clopidogrel, 220 (10.1%) prasugrel and 358 (16.5%) ticagrelor. Switching between ADPri therapies during the index hospitalisation occurred in 15.3%, 22.4%, and 25.2% of patients initially started on clopidogrel, prasugrel, and ticagrelor, respectively. The majority of switches over the 15 month study period occurred during the index admission (16.8% of patients vs. 4.4% switches post-discharge). Major adverse cardiovascular events (MACE) occurred in 7.5% of patients during the index hospitalisation. In-hospital bleeding events occurred in 6.0% of patients and the majority were mild. Conclusions Despite randomized trial evidence and guideline recommendations, only a minority of Canadian MI patients undergoing PCI initially received or were discharged on one of the newer ADPri agents. These findings suggest an opportunity to improve upon the appropriate selection of the ADPris at index hospitalisation and discharge in Canadian MI patients undergoing PCI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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/GRACE2 /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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract 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 (GRACE2 )/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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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