[Show abstract][Hide abstract] ABSTRACT: The Silences of the Archives, the Reknown of the Story.
The Martin Guerre affair has been told many times since Jean de Coras and Guillaume Lesueur published their stories in 1561. It is in many ways a perfect intrigue with uncanny resemblance, persuasive deception and a surprizing end when the two Martin stood face to face, memory to memory, before captivated judges and a guilty feeling Bertrande de Rols. The historian wanted to go beyond the known story in order to discover the world of the heroes. This research led to disappointments and surprizes as documents were discovered concerning the environment of Artigat’s inhabitants and bearing directly on the main characters thanks to notarial contracts. Along the way, study of the works of Coras and Lesueur took a new direction. Coming back to the affair a quarter century later did not result in finding new documents (some are perhaps still buried in Spanish archives), but by going back over her tracks, the historian could only be struck by the silences of the archives that refuse to reveal their secrets and, at the same time, by the possible openings they suggest, by the intuition that almost invisible threads link here and there characters and events.
The Canadian journal of cardiology 11/2013; 29(11):1429-1435. DOI:10.1016/j.cjca.2013.04.035 · 3.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Randomized trials have established the efficacy of antianginal medications in the treatment of chronic stable coronary disease. Using data from the Global Registry of Acute Coronary Events (GRACE) and Canadian Registry of Acute Coronary Events (CANRACE), we examined the temporal trends in antianginal use (beta blockers, calcium antagonists, and nitrates) before non-ST-elevation acute coronary syndrome presentation from 1999 to 2008 in 10,019 patients. The relationships among previous antianginal use, clinical characteristics on presentation, and in-hospital management and outcomes were examined. Beta blockers were the most commonly used agents, and there was a significant decline in the use of nitrates over time. Compared with patients not on any antianginal therapy before presentation, those on treatment were more likely to be older, female, and have a history of hypertension, diabetes, previous angina, and myocardial infarction; they were less likely to present with positive biomarkers (all p <0.001). Patients not on antianginal therapy before presentation were more likely to undergo coronary angiography and percutaneous coronary intervention and less likely to have recurrent ischemia during hospitalization (all p <0.001). In multivariable analysis, previous antianginal use was independently associated with lower use of coronary angiography in hospital (p = 0.034) but not with in-hospital mortality. In conclusion, there has significant temporal decline in nitrate use before non-ST-elevation acute coronary syndrome. Patients receiving antianginal therapy before presentation more frequently had preexisting cardiovascular disease and previous revascularization and were less likely to present with non-ST-segment elevation MI compared with patients on no antianginal therapies. Previous antianginal use was independently associated with a lower use of coronary angiography in hospital.
The American journal of cardiology 07/2013; 112(1):51–56. DOI:10.1016/j.amjcard.2013.02.053 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
International journal of cardiology 04/2013; 168(3). DOI:10.1016/j.ijcard.2013.03.020 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examine the clinical characteristics and outcomes of ST-elevation myocardial infarction (STEMI) patients receiving various reperfusion therapies in 2 contemporary Canadian registries.
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.
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, β-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).
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.
The Canadian journal of cardiology 11/2011; 28(1):40-7. DOI:10.1016/j.cjca.2011.09.011 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of acetylsalicylic acid (ASA [aspirin]) and warfarin in secondary prevention after acute coronary syndromes (ACS) is well established. However, there are sparse data comparing the presentation and outcomes of patients who present with ACS while on ASA and/or warfarin therapy and those on neither.
Using data from the Canadian Global Registry of Acute Coronary Events (GRACE), we stratified 14,090 ACS patients into 4 groups according to prior use of antithrombotic therapies and compared in-hospital management and outcomes.
Among 14,090 ACS patients, 7411 (52.6%) were not on prior ASA or warfarin therapy, 5724 (40.6%) were on ASA only, 593 (4.2%) were on warfarin only, and 362 (2.6%) were on both ASA and warfarin. ACS patients taking ASA and/or warfarin were older with more comorbidities than the patients on neither drug. Patients receiving prior warfarin only or ASA and warfarin were less likely to receive guideline-recommended therapies. Patients who were taking prior warfarin only had higher unadjusted rates of death, death and/or reinfarction (re-MI), congestive heart failure (CHF), and major bleeding as compared with patients on no prior therapy. Furthermore, patients who were taking ASA and warfarin had higher unadjusted rates of death and/or re-MI and CHF than patients on prior ASA only.
ACS patients on prior warfarin are a high-risk population, yet they receive less guideline-recommended therapies and have higher unadjusted adverse event rates during their index hospitalization. With the increasing use of oral anticoagulants, clinical trials are needed to guide the optimal management of these ACS patients.
The Canadian journal of cardiology 11/2011; 28(1):48-53. DOI:10.1016/j.cjca.2011.09.003 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 <0.001). 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.
The American journal of cardiology 11/2010; 106(10):1389-96. DOI:10.1016/j.amjcard.2010.06.070 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
American heart journal 09/2010; 160(3):420-7. DOI:10.1016/j.ahj.2010.05.036 · 4.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 <0.001), 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 <0.001). 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 <0.001), 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.
The American journal of cardiology 04/2010; 105(8):1083-9. DOI:10.1016/j.amjcard.2009.12.005 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Current guidelines support an early invasive strategy in the management of high-risk non-ST elevation acute coronary syndromes (NSTE-ACS). Although studies in the 1990s suggested that highrisk patients received less aggressive treatment, there are limited data on the contemporary management patterns of NSTE-ACS in Canada.
To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS.
Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE2) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment.
While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and highrisk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization.
Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada.
The Canadian journal of cardiology 11/2009; 25(11):e370-6. DOI:10.1016/S0828-282X(09)70163-1 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
American heart journal 09/2009; 158(3):392-9. DOI:10.1016/j.ahj.2009.06.010 · 4.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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. Demographic information, clinical features, and treatment were recorded. We examined the early use of clopidogrel over time and in relation to the type of ACS, clinical features on presentation, and the mode of reperfusion therapy.
Of the 11,177 patients with ACS, 3,091 (27.7%) had ST-elevation myocardial infarction (STEMI), 5,194 (46.5%) had non-STEMI, and 2,892 (25.9%) had unstable angina; the rates of early clopidogrel administration were 63.0%, 66.6%, and 57.2%, respectively (P < .001). Overall, there was a significant increase in clopidogrel use over the period studied (P for trend < .001). In patients with non-ST-elevation ACS (non-STEMI and unstable angina), clopidogrel use was higher among those with positive cardiac biomarkers compared to those without (67.1% vs 59.8%, P < .001) but similar in the groups with and without ST deviation. There was an inverse relationship between GRACE risk score and rates of early clopidogrel administration. In patients with STEMI receiving fibrinolytic therapy, only 55.7% of patients <65 years old received clopidogrel compared with 47.0% and 42.6% of patients 65 to 74 and >75 years old, respectively (P for trend < .001).
Although early use of clopidogrel therapy has increased over time across the spectrum of ACS, a significant proportion of eligible patients still do not receive this evidence-based therapy. There is a need to optimize the use of proven antiplatelet therapies to improve clinical outcome.
American heart journal 05/2009; 157(4):642-50.e1. DOI:10.1016/j.ahj.2009.01.002 · 4.46 Impact Factor