Unstable angina is generally considered to encompass a spectrum of symptomatic manifestations of ... more Unstable angina is generally considered to encompass a spectrum of symptomatic manifestations of ischemic heart disease, intermediate between stable angina and acute myocardial infarction. Approximately 75,000 Canadians are hospitalized yearly with unstable angina. The pathophysiology of unstable angina is still imperfectly understood, but is related to the same pathophysiological factors underlying myocardial infarction and sudden cardiac death. In March 1995 a group of Canadian cardiologists met to review the current understanding of unstable angina and to define a Canadian approach to this common problem. Important issues and questions regarding the diagnosis and management of unstable angina were defined. The objective was to outline approaches to the management of unstable angina that would be appropriate in Canada. Topics discussed included definition, incidence, clinical presentations, pathophysiology, initial diagnostic and risk stratification approaches, acute medical manag...
Strong evidence supports the concept that earlier application of fibrinolytic treatment can maxim... more Strong evidence supports the concept that earlier application of fibrinolytic treatment can maximize the benefits derived. The results of two level I trials have shown that prehospital thrombolysis is feasible and safe. Although the trials have not proven that prehospital thrombolysis improves prognosis, they have shown that early identification of eligible patients can greatly accelerate the process of drug administration.
Histological sections performed 24 h after coronary occlusion in eight pigs displayed compact inf... more Histological sections performed 24 h after coronary occlusion in eight pigs displayed compact infarcts extending transmurally with well-defined edges; reconstruction and inspection of the area of necrosis showed a geometric distribution of the infarcts with very irregular, interdigitating edges always in continuity with the main mass of necrosis. Reperfusion in 32 pigs after periods of coronary occlusion of 90, 60, 45, and 30 min exponentially reduced infarct size and transmural extension of the infarct but did not modify its geometry. The two-dimensional size, progression, and geometry of the infarcts could be reproduced by a computer model. In the simulated infarcts, each myocardial cell within the area at risk was represented by a pixel. The algorithm included an inner loop, which determined at random at each iteration a status of reversible or irreversible damage to all pixels. The number of iterations could reproduce infarct of various sizes. With the addition of an index of tr...
European heart journal. Acute cardiovascular care, 2014
Limited data exist concerning outcomes of patients with non-ST-segment elevation acute coronary s... more Limited data exist concerning outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) with no angiographically obstructive coronary artery disease (non-obstructive CAD). We assessed the frequency of clinical outcomes among patients with non-obstructive CAD compared with obstructive CAD. We pooled data from eight NSTE ACS randomized clinical trials from 1994 to 2008, including 37,101 patients who underwent coronary angiography. The primary outcome was 30-day death or myocardial infarction (MI). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for 30-day death or MI for non-obstructive versus obstructive CAD were generated for each trial. Summary ORs (95% CIs) across trials were generated using random effects models. Overall, 3550 patients (9.6%) had non-obstructive CAD. They were younger, more were female, and fewer had diabetes mellitus, previous MI or prior percutaneous coronary intervention than patients with obstructive CAD. Thirty-day ...
Little is known about how physicians make decisions when the evidence is incomplete or controvers... more Little is known about how physicians make decisions when the evidence is incomplete or controversial. While thrombolysis improves survival following acute myocardial infarction (AMI), conflicting evidence exists as to any specific agent's superiority, particularly if cost-effectiveness is considered. Using a Bayesian hierarchical model, the authors examined the patient, physician, and hospital characteristics that are related to the decision-making process concerning the choice of thrombolytic agent in a prospective registry of 1,165 AMI patients receiving thrombolysis. Tissue plasminogen activator (t-PA) was administered to 432 patients (31.8%) and streptokinase (SK) to the remainder. The presence of an anterior infarction, a previous myocardial infarction, low blood pressure, a cardiologist decision maker, younger age, and receiving treatment within six hours after the start of symptoms were independent predictors of receiving t-PA. The levels of importance that physicians accorded to these patient characteristics differed according to their practicing institutions. Generally, they followed evidence-based medicine and reasonably targeted high-risk patients to receive the more expensive t-PA. However, they also preferentially treated younger patients, where only a small absolute advantage appears to exist.
In order to assess if coronary artery disease progression occurs as a slow, continuous process or... more In order to assess if coronary artery disease progression occurs as a slow, continuous process or at bouts, the coronary angiograms of 44 patients catheterized three times were reviewed. A previously developed logistic model, taking into account time interval between the angiograms, age, occurrence of unstable angina, and extent score of coronary artery disease, was used to compute a probability of progression from the second to the third angiogram. Two groups of patients were considered: those with (n = 15) and those without (n = 29) progression from the first to the second angiogram (PROGRESSION 1-2). A simulation provided in each group the distribution of the expected number of patients with progression from the second to the third catheterization. In the group without PROGRESSION 1-2, the observed number of progressions from the second to the third angiogram was in agreement with the expected one. However, in the group with PROGRESSION 1-2, the progression from the second to the third angiogram was more frequent than expected (p = 0.068). These results suggest that, in many patients, coronary artery disease progression is continuous over several years.
Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary synd... more Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We aimed to identify predictors of stroke within 30 days in patients who suffered NSTE-ACS. We pooled data from six trials (n=31 402) that randomized NSTE-ACS patients either to platelet glycoprotein (GP) IIb/IIIa receptor blockers or to placebo/control therapy. Potential predictors of stroke included treatment, demographic, and clinical characteristics. We identified predictors using univariable and multivariable logistic models, and their performance was evaluated with calibration (Hosmer-Lemeshow test) and discrimination (c-statistic). We found 228 (0.7%) all-cause strokes: 155 (0.5%) non-haemorrhagic, 20 (0.06%) haemorrhagic, and 53 without computed tomography (CT) confirmation. Patients with any type of stroke had a 30-day mortality of 25%. Randomization to GP IIb/IIIa receptor blockers was not significantly associated with all-cause stroke [OR (95% CI) 1.08 (0.83-1.41)]. Older age [OR per 10-year increase 1.5 (1.3-1.7)], prior stroke [2.1 (1.4-3.1)], and elevated heart rate [per 10-beat increase 1.1 (1.0-1.2)] were the strongest predictors of 30-day all-cause stroke. Similar predictors were found for non-haemorrhagic and haemorrhagic strokes. Smoking, previous myocardial infarction, diabetes, and hypertension were not independent predictors of all-cause stroke. The multivariable model to predict all-cause stroke was well calibrated, but its discrimination was only moderate [c-statistic 0.69 (0.65-0.72)]. Stroke is a rare complication occurring early after NSTE-ACS, but is associated with high mortality. We found no evidence that GP IIb/IIIa receptor blockers increase stroke risks. A few clinical characteristics predicted higher stroke risks. Thus, incident strokes in NSTE-ACS patients remain largely unexplained.
Pexelizumab, a monoclonal antibody inhibiting C5, reduced 90 day mortality and shock in the COMpl... more Pexelizumab, a monoclonal antibody inhibiting C5, reduced 90 day mortality and shock in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial without apparent reductions in infarct size. Inflammation is a critical component of ST-elevation myocardial infarction (STEMI); this substudy examines prognostic values of selected markers and treatment effects. C-reactive protein, interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) serum levels were assessed in 337 patients enrolled in either the placebo or the pexelizumab 24 h infusion group. Higher C-reactive protein and IL-6 levels at baseline, 24 h, and 72 h were strongly associated with increased subsequent death (P<0.002 at baseline and 24 h, P<0.02 at 72 h); and all baseline marker levels with death or cardiogenic shock (P<0.03) within 90 days. C-reactive protein and IL-6 levels were similar at baseline, but significantly lower 24 h later with pexelizumab, when compared with placebo (17.1 vs. 25.5 mg/L, P=0.03 and 51.0 vs. 63.8 pg/mL, P=0.04, respectively). At 72 h, corresponding levels were similar, whereas TNF-alpha was slightly higher (P=0.04) in the treated group. Inflammation markers and their serial changes predict death and shock in patients with STEMI undergoing primary angioplasty. Pexelizumab reduced C-reactive protein and IL-6, suggesting treatment benefits mediated through anti-inflammatory effects.
Unstable angina is generally considered to encompass a spectrum of symptomatic manifestations of ... more Unstable angina is generally considered to encompass a spectrum of symptomatic manifestations of ischemic heart disease, intermediate between stable angina and acute myocardial infarction. Approximately 75,000 Canadians are hospitalized yearly with unstable angina. The pathophysiology of unstable angina is still imperfectly understood, but is related to the same pathophysiological factors underlying myocardial infarction and sudden cardiac death. In March 1995 a group of Canadian cardiologists met to review the current understanding of unstable angina and to define a Canadian approach to this common problem. Important issues and questions regarding the diagnosis and management of unstable angina were defined. The objective was to outline approaches to the management of unstable angina that would be appropriate in Canada. Topics discussed included definition, incidence, clinical presentations, pathophysiology, initial diagnostic and risk stratification approaches, acute medical manag...
Strong evidence supports the concept that earlier application of fibrinolytic treatment can maxim... more Strong evidence supports the concept that earlier application of fibrinolytic treatment can maximize the benefits derived. The results of two level I trials have shown that prehospital thrombolysis is feasible and safe. Although the trials have not proven that prehospital thrombolysis improves prognosis, they have shown that early identification of eligible patients can greatly accelerate the process of drug administration.
Histological sections performed 24 h after coronary occlusion in eight pigs displayed compact inf... more Histological sections performed 24 h after coronary occlusion in eight pigs displayed compact infarcts extending transmurally with well-defined edges; reconstruction and inspection of the area of necrosis showed a geometric distribution of the infarcts with very irregular, interdigitating edges always in continuity with the main mass of necrosis. Reperfusion in 32 pigs after periods of coronary occlusion of 90, 60, 45, and 30 min exponentially reduced infarct size and transmural extension of the infarct but did not modify its geometry. The two-dimensional size, progression, and geometry of the infarcts could be reproduced by a computer model. In the simulated infarcts, each myocardial cell within the area at risk was represented by a pixel. The algorithm included an inner loop, which determined at random at each iteration a status of reversible or irreversible damage to all pixels. The number of iterations could reproduce infarct of various sizes. With the addition of an index of tr...
European heart journal. Acute cardiovascular care, 2014
Limited data exist concerning outcomes of patients with non-ST-segment elevation acute coronary s... more Limited data exist concerning outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) with no angiographically obstructive coronary artery disease (non-obstructive CAD). We assessed the frequency of clinical outcomes among patients with non-obstructive CAD compared with obstructive CAD. We pooled data from eight NSTE ACS randomized clinical trials from 1994 to 2008, including 37,101 patients who underwent coronary angiography. The primary outcome was 30-day death or myocardial infarction (MI). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for 30-day death or MI for non-obstructive versus obstructive CAD were generated for each trial. Summary ORs (95% CIs) across trials were generated using random effects models. Overall, 3550 patients (9.6%) had non-obstructive CAD. They were younger, more were female, and fewer had diabetes mellitus, previous MI or prior percutaneous coronary intervention than patients with obstructive CAD. Thirty-day ...
Little is known about how physicians make decisions when the evidence is incomplete or controvers... more Little is known about how physicians make decisions when the evidence is incomplete or controversial. While thrombolysis improves survival following acute myocardial infarction (AMI), conflicting evidence exists as to any specific agent's superiority, particularly if cost-effectiveness is considered. Using a Bayesian hierarchical model, the authors examined the patient, physician, and hospital characteristics that are related to the decision-making process concerning the choice of thrombolytic agent in a prospective registry of 1,165 AMI patients receiving thrombolysis. Tissue plasminogen activator (t-PA) was administered to 432 patients (31.8%) and streptokinase (SK) to the remainder. The presence of an anterior infarction, a previous myocardial infarction, low blood pressure, a cardiologist decision maker, younger age, and receiving treatment within six hours after the start of symptoms were independent predictors of receiving t-PA. The levels of importance that physicians accorded to these patient characteristics differed according to their practicing institutions. Generally, they followed evidence-based medicine and reasonably targeted high-risk patients to receive the more expensive t-PA. However, they also preferentially treated younger patients, where only a small absolute advantage appears to exist.
In order to assess if coronary artery disease progression occurs as a slow, continuous process or... more In order to assess if coronary artery disease progression occurs as a slow, continuous process or at bouts, the coronary angiograms of 44 patients catheterized three times were reviewed. A previously developed logistic model, taking into account time interval between the angiograms, age, occurrence of unstable angina, and extent score of coronary artery disease, was used to compute a probability of progression from the second to the third angiogram. Two groups of patients were considered: those with (n = 15) and those without (n = 29) progression from the first to the second angiogram (PROGRESSION 1-2). A simulation provided in each group the distribution of the expected number of patients with progression from the second to the third catheterization. In the group without PROGRESSION 1-2, the observed number of progressions from the second to the third angiogram was in agreement with the expected one. However, in the group with PROGRESSION 1-2, the progression from the second to the third angiogram was more frequent than expected (p = 0.068). These results suggest that, in many patients, coronary artery disease progression is continuous over several years.
Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary synd... more Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We aimed to identify predictors of stroke within 30 days in patients who suffered NSTE-ACS. We pooled data from six trials (n=31 402) that randomized NSTE-ACS patients either to platelet glycoprotein (GP) IIb/IIIa receptor blockers or to placebo/control therapy. Potential predictors of stroke included treatment, demographic, and clinical characteristics. We identified predictors using univariable and multivariable logistic models, and their performance was evaluated with calibration (Hosmer-Lemeshow test) and discrimination (c-statistic). We found 228 (0.7%) all-cause strokes: 155 (0.5%) non-haemorrhagic, 20 (0.06%) haemorrhagic, and 53 without computed tomography (CT) confirmation. Patients with any type of stroke had a 30-day mortality of 25%. Randomization to GP IIb/IIIa receptor blockers was not significantly associated with all-cause stroke [OR (95% CI) 1.08 (0.83-1.41)]. Older age [OR per 10-year increase 1.5 (1.3-1.7)], prior stroke [2.1 (1.4-3.1)], and elevated heart rate [per 10-beat increase 1.1 (1.0-1.2)] were the strongest predictors of 30-day all-cause stroke. Similar predictors were found for non-haemorrhagic and haemorrhagic strokes. Smoking, previous myocardial infarction, diabetes, and hypertension were not independent predictors of all-cause stroke. The multivariable model to predict all-cause stroke was well calibrated, but its discrimination was only moderate [c-statistic 0.69 (0.65-0.72)]. Stroke is a rare complication occurring early after NSTE-ACS, but is associated with high mortality. We found no evidence that GP IIb/IIIa receptor blockers increase stroke risks. A few clinical characteristics predicted higher stroke risks. Thus, incident strokes in NSTE-ACS patients remain largely unexplained.
Pexelizumab, a monoclonal antibody inhibiting C5, reduced 90 day mortality and shock in the COMpl... more Pexelizumab, a monoclonal antibody inhibiting C5, reduced 90 day mortality and shock in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial without apparent reductions in infarct size. Inflammation is a critical component of ST-elevation myocardial infarction (STEMI); this substudy examines prognostic values of selected markers and treatment effects. C-reactive protein, interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) serum levels were assessed in 337 patients enrolled in either the placebo or the pexelizumab 24 h infusion group. Higher C-reactive protein and IL-6 levels at baseline, 24 h, and 72 h were strongly associated with increased subsequent death (P<0.002 at baseline and 24 h, P<0.02 at 72 h); and all baseline marker levels with death or cardiogenic shock (P<0.03) within 90 days. C-reactive protein and IL-6 levels were similar at baseline, but significantly lower 24 h later with pexelizumab, when compared with placebo (17.1 vs. 25.5 mg/L, P=0.03 and 51.0 vs. 63.8 pg/mL, P=0.04, respectively). At 72 h, corresponding levels were similar, whereas TNF-alpha was slightly higher (P=0.04) in the treated group. Inflammation markers and their serial changes predict death and shock in patients with STEMI undergoing primary angioplasty. Pexelizumab reduced C-reactive protein and IL-6, suggesting treatment benefits mediated through anti-inflammatory effects.
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Papers by P. Theroux