Canadian Heart Research Center

Toronto, Canada

Canadian Heart Research Center

Toronto, Canada
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Alexander J.H.,Duke University | Lopes R.D.,Duke University | James S.,Uppsala Clinical Research Center | Kilaru R.,Duke University | And 30 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. RESULTS: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. CONCLUSIONS: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 number, NCT00831441.) Copyright © 2011 Massachusetts Medical Society. All rights reserved.

PubMed | University of Ottawa, University of Oslo, Hospital General Universitario Gregorio Maranon, Imperial College London and 6 more.
Type: Journal Article | Journal: Cardiovascular revascularization medicine : including molecular interventions | Year: 2016

To investigate the relationship between arterial access site choice (radial versus femoral) and clinical outcomes among STEMI patients undergoing routine PCI after fibrinolysis.Patient-level data from trials of STEMI patients evaluating routine PCI after fibrinolysis were included. The primary endpoint was 30-day major bleeding; secondary endpoints included 30-day death and re-infarction.1891 patients underwent PCI (trans-radial n=338, trans-femoral n=1553). Trans-radial PCI patients were less likely to be >75years (2% vs. 8%, p=0.0001), heavier (median weight 82 [72-90] vs. 80 [70-90] kg, p=0.0013) and more likely in Killip class I at presentation (87% vs. 82%, p=0.03). At 30days, trans-radial PCI was associated with a similar unadjusted risk for major bleeding (3.7% vs. 1.2%, Odds Ratio [OR] 0.43 [95% CI 0.13-1.48], p=0.18), mortality (3.4% vs. 1.2%, OR 0.34 [0.09-1.28], p=0.11) and re-infarction (3.9% vs. 4.7%, OR 1.25 [0.60-2.58], p=0.56). In multivariable analysis, radial access was associated with similar estimates for bleeding and death/reinfarction risk.In STEMI patients treated with fibrinolysis and undergoing an early routine invasive strategy, radial compared to femoral PCI is chosen in younger, less ill patients and is independently associated with similar risk of bleeding, re-infarction, and mortality.This study evaluated the relationship between arterial access choice (radial versus femoral) and in-hospital and 30-day outcomes in patients undergoing routine PCI after fibrinolysis for STEMI. We included patient-level data from trials evaluating a strategy of routine PCI after fibrinolysis for STEMI. Of 1891 patients undergoing PCI, trans-radial access (n=338) was chosen in younger, lower risk patients. At 30days, trans-radial access was associated with a similar unadjusted and adjusted risk of major bleeding, re-infarction and mortality.

McLaughlin V.V.,University of Michigan | Langer A.,Canadian Heart Research Center | Tan M.,Canadian Heart Research Center | Clements P.J.,University of California at Los Angeles | And 4 more authors.
Chest | Year: 2013

Background: The Pulmonary Arterial Hypertension-Quality Enhancement Research Initiative (PAHQuERI) was created to help clinicians to implement a guidelines-based approach to the diagnosis and management of pulmonary arterial hypertension (PAH). Patients with PAH represent a heterogeneous population, and physician evaluation and treatment paradigms may vary considerably. Methods: Using an electronic data management system, participating physicians recorded data on diagnostic workup, disease management, and outcomes of patients with PAH. Queries were generated automatically following each follow-up visit if the tests recommended by the American College of Chest Physicians (ACCP) were not performed at least once. Results: Of 791 patients enrolled in PAH-QuERI, 77% were women; 64% received a diagnosis . 3 months prior to enrollment; 9% were in New York Heart Association functional class I, 39% in II, 48% in III, and 5% in IV; and the median age was 55 years (interquartile range, 45-66 years). At enrollment, all ACCP-recommended tests had been performed in only 6% of patients. The automated program generated 1,530 reminders for 642 patients (81%) with validated enrollment data. The proportion of recommended tests performed was 91% for CBC count, 91% for liver function test, 50% for connective tissue disease screen, 29% for HIV screen, 88% for chest radiograph, 82% for ECG, 97% for two-dimensional echocardiogram, 83% for pulmonary function tests, 41% for oximetry, 57% for ventilation/perfusion scan, 79% for 6-min walk distance, and 90% for right-sided heart catheterization. Regarding management, 78% of patients were on diseasespecifi c therapy, and the use of these therapies tended to increase with the functional disability of the patient. One hundred seventy patients were taking calcium channel blockers, 91 specifi - cally for PAH. Only six of 91 patients (7%) who received calcium channel blockers specifi cally for PAH had met the current guideline for acute vasoreactivity. Conclusions: When comparing reported clinical practice with ACCP guidelines-recommended strategies, a diagnostic care gap is apparent such that certain essential and recommended diagnostic tests may be underused despite the availability of detailed guidelines and reminders. © 2013 American College of Chest Physicians.

Clements P.J.,University of California at Los Angeles | Tan M.,Canadian Heart Research Center | McLaughlin V.V.,University of Michigan | Oudiz R.J.,University of California at Los Angeles | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objective: The objective of this report is to compare baseline, management and survival characteristics in idiopathic pulmonary arterial hypertension (IPAH) with systemic sclerosis-associated pulmonary arterial hypertension (SSc-APAH) using data from the prospectively enrolled PAH Quality Enhancement Research Initiative. Methods: Between August 2005 and July 2007, patients with IPAH and SSc-APAH were enrolled across 60 US sites and followed up for 3 years. Data on diagnostic tests, clinical variables, pulmonary arterial hypertension (PAH) medication and outcomes were recorded. Results: With some exceptions, baseline clinical and laboratory characteristics were similar between the 279 patients with IPAH and the 228 with SSc-APAH. Patients with SSc-APAH were older at the time of PAH diagnosis, were more likely to be female and were antinuclear antibody positive. Patients with SSc-APAH had poorer spirometric results. During the 3-year follow-up, both groups were managed with prostacyclin and prostacyclin analogue treatment, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors (PDE5i) singly or in combination. At 3 years, patients with SSc-APAH were more likely to be treated with PDE5i alone or with an endothelin receptor antagonist. Patients with SSc-APAH had a significantly lower survival rate compared to patients with IPAH (60% vs 77%, p<0.0001). Conclusions: The cohort with SSc-APAH was older, was more severely ill, was more likely to be female, was managed with PDE5i and had reduced 3-year survival compared with the cohort with IPAH.

Taljaard M.,Ottawa Hospital Research Institute | Taljaard M.,University of Ottawa | Ward M.R.,University of Toronto | Kutryk M.J.B.,St Michaels Hospital | And 8 more authors.
American Heart Journal | Year: 2010

Background: Despite the widespread use of pharmacological and/or interventional reperfusion therapies, recovery of cardiac function in myocardial infarction (MI) patients is often modest or even absent. Unlike classical pharmacological treatments, the use of progenitor cells could potentially restore functional tissue in regions that otherwise would form only scar. However, a major limitation of autologous cell therapy is the deleterious influence of age and cardiac risk factors on progenitor cell activity. Trial Design: The ENACT-AMI trial is a phase IIb, double-blind, randomized placebo-controlled trial, using transplantation of autologous early endothelial progenitor cells (EPCs) for patients who have suffered large MI. Circulating mononuclear cells (MNCs) are obtained by apheresis and subjected to differential culture for 3 days to select a population of highly regenerative, endothelial-like, culture modified MNCs (E-CMMs), often referred to as "early EPCs." A total of 99 patients will be randomized to placebo (Plasma-Lyte A), autologous E-CMMs, or E-CMMs transfected with human endothelial nitric oxide synthase delivered by coronary injection into the infarct-related artery. The primary efficacy end point is change from baseline to 6 months in global left ventricular ejection fraction by cardiac MRI; secondary endpoints include regional wall motion, wall thickening, infarct volume, time to clinical worsening, and quality of life. Conclusions: This will be the first clinical trial to include a strategy designed to enhance the function of autologous progenitor cells by overexpressing endothelial nitric oxide synthase, and the first to use combination gene and cell therapy for the treatment of cardiac disease. © 2010 Mosby, Inc. All rights reserved.

Rizvi S.J.,University of Toronto | Grima E.,Canadian Heart Research Center | Tan M.,Canadian Heart Research Center | Rotzinger S.,University of Toronto | And 5 more authors.
Canadian Journal of Psychiatry | Year: 2014

Objective: Treatment-resistant depression (TRD) represents a considerable global health concern. The goal of the InSight study was to investigate the prevalence of TRD and to evaluate its clinical characterization and management, compared with nonresistant depression, in primary care centres. Methods: Physicians completed a case report on a consecutive series of patients with major depressive disorder (n = 1212), which captured patient demographics and comorbidity, as well as current and past medication. Results: Using failure to respond to at least 2 antidepressants (ADs) from different classes as the definition of TRD, the overall prevalence was 21.7%. There were no differences in prevalence between men and women or among ethnicities. Patients with TRD had longer episode duration, were more likely to receive polypharmacy (for example, psychotropic, lipid-lowering, and antiinflammatory agents), and reported more AD related side effects. Higher rates of disability and comorbidity (axes I to III) were associated with treatment resistance. Obesity and being overweight were also associated with treatment resistance. While the selection and sequencing of pharmacotherapy by family physicians in this sample was in line with recommendations from evidence-based treatment guidelines, the wait time to make a change in treatment was 6 to 8 weeks in both groups, which exceeds guideline recommendations. Conclusions: These real-world data demonstrate the high prevalence of TRD in primary care settings, and underscore the substantial burden of illness associated with TRD.

PubMed | University of New South Wales, University of Edinburgh, University of Alberta, Canadian Heart Research Center and 3 more.
Type: Journal Article | Journal: Heart (British Cardiac Society) | Year: 2016

To assess the relationship between the evolution of T wave inversion (TWI) on the 24-48h postadmission ECG and the patient characteristics, management and clinical outcomes among those with non-ST elevation acute coronary syndrome (NSTE-ACS).We evaluated admission and 24-48h follow-up ECGs of 7201 patients with NSTE-ACS from the prospective, multicentre Global Registry of Acute Coronary Events (GRACE) and Canadian ACS Registry I. We performed multivariable analyses to determine the association between new TWI (on follow-up ECG only), resolved TWI (on admission ECG only) and persistent TWI (on both admission and follow-up ECG) and inhospital and cumulative 6-month all-cause mortality.Patients with TWI were older, more likely to have cardiovascular risk factors, higher Killip class and GRACE risk scores. After adjustment for known prognostic factors, compared with patients presenting without TWI, new TWI was associated with significantly lower inhospital mortality (OR=0.60, 95% CI 0.38 to 0.95, p=0.029), whereas resolved (OR=1.06, 95% CI 0.65 to 1.75, p=0.81) and persistent (OR=0.73, 95% CI 0.48 to 1.11, p=0.14) TWI did not predict inhospital mortality. No TWI pattern independently predicted inhospital adverse cardiovascular events or cumulative 6-month mortality. In contrast, ST depression on the admission and follow-up ECG were independent predictors of inhospital and 6-month mortality.Across the spectrum of NSTE-ACS, TWI within 48h of presentation was associated with high-risk clinical features, but its presence or dynamic change did not provide additional prognostic value beyond other established clinical predictors.

PubMed | Eli Lilly and Company, London Health Sciences Center, University of Alberta, McMaster University and 9 more.
Type: | Journal: American heart journal | Year: 2016

Since the introduction of newer, more potent P2Y12 receptor inhibitors (P2Y12ris), 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.The Canadian Observational Antiplatelet Study was a prospective, multicenter, longitudinal, observational study (26 hospitals, December 2011 to May 2013) describing P2Y12ri 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) (acetyl salicylic acid [ASA]+P2Y12ri) or triple therapy (ASA+P2Y12ri+OAC).Of the 2,034 patients at discharge, 86% (n = 1,757) were on DAPT, whereas 14% (n = 277) were on triple therapy (50% warfarin, 50% non-vitamin K OAC [NOAC]). The frequency of newer P2Y12ri 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 P2Y12ri compared to those receiving clopidogrel (75% vs 41%, respectively, P < .0001). The unadjusted and adjusted events of major cardiovascular event (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.In this observational study of MI patients requiring PCI, 1 in 8 were discharged on triple antithrombotic therapy, of whom 26% were on newer P2Y12ris. Patients on triple therapy had higher risk at baseline, with higher unadjusted and adjusted MACE and bleeding events compared to those on DAPT alone. Among triple therapy-treated patients, there was no difference in the MACE and bleeding events regardless of the P2Y12ri used.

PubMed | University of Western Ontario, Oakville Hospital, Canadian Heart Research Center, Sunnybrook Research Institute and 3 more.
Type: Journal Article | Journal: The Canadian journal of cardiology | Year: 2016

We examined whether the efficacy of an early invasive strategy after fibrinolysis in ST-segment elevation myocardial infarction (STEMI) differs in relation to the initial troponin status.In the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), patients with STEMI presenting to a non-percutaneous coronary intervention (PCI)-capable hospital who received fibrinolysis were randomized to either a pharmacoinvasive or standard strategy for subsequent angiography and PCI. In this post hoc subgroup analysis, we compared the efficacy of these strategies in relation to the initial troponin status at hospital presentation for the primary composite end point of mortality, reinfarction, recurrent ischemia, heart failure, and cardiogenic shock at 30 days. We assessed the heterogeneity of treatment effect with initial troponin status using the Breslow-Day test and tested for interaction after adjustment for baseline Global Registry of Acute Coronary Events (GRACE) risk score.Among 1059 patients, those with abnormal initial troponin levels (n= 514 [48.5%]) were older with worse Killip class, had a longer time from symptom onset to fibrinolysis, and had higher GRACE and Thrombolysis In Myocardial Infarction risk scores. Patients with abnormal troponin levels had higher rates of the primary end point (17.5% vs 10.8%; P= 0.002) and cumulative mortality or reinfarction at 1 year (14.0% vs 8.1%; P= 0.003). In stratified analyses, pharmacoinvasive management reduced the primary end point only among patients with normal initial troponin status. However, there was no significant treatment heterogeneity (all P 0.10) and no interaction between initial troponin status and treatment assignment after adjusting for GRACE risk score.Patients with STEMI and abnormal initial troponin levels had worse short-term and long-term outcomes. Accounting for overall baseline risk with the GRACE risk score, troponin status did not modulate the efficacy of pharmacoinvasive management.

Wijeysundera H.C.,Toronto Health Economics and Technology Assessment Collaborative | Wijeysundera H.C.,University of Toronto | Machado M.,Toronto Health Economics and Technology Assessment Collaborative | Farahati F.,Toronto Health Economics and Technology Assessment Collaborative | And 14 more authors.
JAMA - Journal of the American Medical Association | Year: 2010

Context: Coronary heart disease (CHD) mortality has declined substantially in Canada since 1994. Objective: To determine what proportion of this decline was associated with temporal trends in CHD risk factors and advancements in medical treatments. Design, Setting, and Patients: Prospective analytic study of the Ontario, Canada, population aged 25 to 84 years between 1994 and 2005, using an updated version of the validated IMPACT model, which integrates data on population size, CHD mortality, risk factors, and treatment uptake changes. Relative risks and regression coefficients from the published literature quantified the relationship between CHD mortality and (1) evidence-based therapies in 8 distinct CHD subpopulations (acute myocardial infarction [AMI], acute coronary syndromes, secondary prevention post-AMI, chronic coronary artery disease, heart failure in the hospital vs in the community, and primary prevention for hyperlipidemia or hypertension) and (2) population trends in 6 risk factors (smoking, diabetes mellitus, systolic blood pressure, plasma cholesterol level, exercise, and obesity). Main Outcome Measures: The number of deaths prevented or delayed in 2005; secondary outcome measures were improvements in medical treatments and trends in risk factors. Results: Between 1994 and 2005, the age-adjusted CHD mortality rate in Ontario decreased by 35% from 191 to 125 deaths per 100 000 inhabitants, translating to an estimated 7585 fewer CHD deaths in 2005. Improvements in medical and surgical treatments were associated with 43% (range, 11% to 124%) of the total mortality decrease, most notably in AMI (8%; range, -5% to 40%), chronic stable coronary artery disease (17%; range,7%to 35%), and heart failure occurring while in the community (10%; range,6%to 31%). Trends in risk factors accounted for 3660 fewer CHD deaths prevented or delayed (48% of total; range, 28% to 64%), specifically, reductions in total cholesterol (23%; range, 10% to 33%) and systolic blood pressure (20%; range, 13% to 26%). Increasing diabetes prevalence and body mass index had an inverse relationship associated with higher CHD mortality of 6% (range, 4% to 8%) and 2% (range, 1% to 4%), respectively. Conclusion: Between 1994 and 2005, there was a decrease in CHD mortality rates in Ontario that was associated primarily with trends in risk factors and improvements in medical treatments, each explaining about half of the decrease. ©2010 American Medical Association. All rights reserved.

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