Claude Lauzon

Myocardial infarction patients in the 1990s—their risk factors, stratification and survival in Canada: The Canadian assessment of myocardial infarction (CAMI) study

OBJECTIVES This study sought to evaluate the in-hospital and postdischarge mortality of patients with an acute myocardial infarction in the 1990s. BACKGROUND The widespread implementation of therapeutic interventions that modify the natural history of coronary artery disease has led to changes in the profile and survival of patients with an acute myocardial infarction. Although data exist for selected subsets of patients with an acute myocardial infarction, at this time there is little recent prospective information on all patients presenting with an acute myocardial infarction, particularly for survival after hospital discharge. METHODS All patients < or = 75 years old presenting with an acute myocardial infarction between July 1, 1990 and June 30, 1992 at nine Canadian hospitals were prospectively evaluated and followed up for 1 year. From November 1991, patients of all ages were included. In two centers, recruitment continued until December 31, 1992. A total of 3,178 patients were recruited. RESULTS The in-hospital mortality rate of patients < or = 75 years old was 8.4%, and that at 1 year after hospital discharge was 5.3%. For patients of all ages recruited after November 1, 1991, the in-hospital mortality rate was 9.9% and 7.1% for 1 year after hospital discharge. For patients < or = 75 years old, age carried an independent in-hospital but no post discharge risk. Female patients had a twofold greater risk of dying in hospital. After hospital discharge, only 1.7% of patients < or = 75 years old and 1.9% of patients of all ages died of a presumed arrhythmic death. Premature ventricular contractions had no independent prognostic value. The relatively low in-hospital (5.3%) and postdischarge (6.1%) reinfarction rate may have contributed to improved survival. A greater reinfarction rate in patients >75 years old (17.4% vs. 9.6%, p < 0.001) may have contributed to their poorer outcome. CONCLUSIONS One-year mortality after acute myocardial infarction continues to decrease, and changes in the prognostic value of traditional methods of risk stratification have occurred.

Risk Stratification After Myocardial Infarction Using Signal-Averaged Electrocardiographic Criteria Adjusted for Sex, Age, and Myocardial Infarction Location

BACKGROUND The objectives were to investigate the factors influencing signal-averaged ECGs (SAECGs) recorded in patients after myocardial infarction (MI) and to develop criteria for predicting arrhythmic events (AEs) that account for these factors. METHODS AND RESULTS SAECGs were recorded 5 to 15 days after MI in 2461 patients without bundle-branch block. The duration (QRSd), terminal potential (VRMS), and terminal duration (LAS) of the filtered QRS were measured. During follow-up (17 +/- 8 months), AEs (arrhythmic death; ventricular tachycardia, VT; ventricular fibrillation, VF) occurred in 80 patients (3.3%). Receiver operating characteristic curves showed that QRSd discriminated patients with all types of AEs, but VRMS and LAS discriminated only VT patients; QRSd minus LAS also discriminated AE patients. Sex, age, and MI location significantly affected the SAECG; survivors without VT or VF were divided into subgroups (2 sex x 4 age x 2 MI), and QRSd values exceeding the 70th percentile in each subgroup predicted AEs with a sensitivity of 65.4%. An unadjusted QRSd criterion showed the same overall sensitivity and specificity but with less uniform values for each subgroup. A Cox model was constructed by use of multiple prognostic indicators, and in rank order, QRSd, previous MI, and Killip class were predictive of AEs. CONCLUSIONS SAECG adjustments for sex, age, and MI location did not improve sensitivity and specificity but produced a more uniform predictive performance. The proposed criteria are based only on QRSd, because late potentials (VRMS and LAS) did not discriminate patients with sudden death. Duration of high-level activity during QRS (QRSd-LAS) can predict AEs, suggesting that the arrhythmogenic substate involves a large mass of myocardium.

Bupropion for Smoking Cessation in Patients Hospitalized With Acute Myocardial Infarction: A Randomized, Placebo-Controlled Trial

OBJECTIVES The purpose of this study was to examine smoking cessation rates among smokers with AMI to determine whether bupropion, started in-hospital, is safe and can improve cessation rates at 1 year. BACKGROUND Bupropion doubles quit rates in otherwise healthy smokers and patients with stable cardiovascular disease. Although 2 previous trials examined the use of bupropion in patients hospitalized with acute cardiovascular disease, these studies have been inconclusive with respect to its safety and efficacy in patients with acute myocardial infarction (AMI). METHODS We conducted a multicenter, double-blind, placebo-controlled, randomized trial in smokers hospitalized with AMI. Participants received bupropion or placebo for 9 weeks and were followed for 12 months. Both groups received low-intensity counseling. Point prevalence abstinence was assessed by 7-day recall and biochemical validation of expired carbon monoxide. RESULTS A total of 392 patients were randomized (mean age 53.9 ± 10.3 years); 83.5% were male; 64.9% had ST-segment elevation myocardial infarction). Patients smoked a mean of 23.2 ± 10.6 cigarettes/day for a mean of 32.9 ± 12.4 years. At 12 months, point prevalence abstinence rates were 37.2% in the bupropion group and 32.0% in the placebo group (p = 0.33; % difference after adjusting for between center differences 3.9%). Continuous abstinence rates were 26.8% and 22.2%, respectively (p = 0.34). Major adverse cardiac event rates were similar (13.0% vs. 11.0%, respectively; p = 0.64). CONCLUSIONS Two-thirds of patients return to smoking by 12 months after AMI. Bupropion is well tolerated and seems to be safe to use in the immediate post-AMI period. However, bupropion is not effective for smoking cessation in patients post-AMI.

Clinical ResearchClinical TrialBupropion for Smoking Cessation in Patients Hospitalized With Acute Myocardial Infarction: A Randomized, Placebo-Controlled Trial

OBJECTIVES The purpose of this study was to examine smoking cessation rates among smokers with AMI to determine whether bupropion, started in-hospital, is safe and can improve cessation rates at 1 year. BACKGROUND Bupropion doubles quit rates in otherwise healthy smokers and patients with stable cardiovascular disease. Although 2 previous trials examined the use of bupropion in patients hospitalized with acute cardiovascular disease, these studies have been inconclusive with respect to its safety and efficacy in patients with acute myocardial infarction (AMI). METHODS We conducted a multicenter, double-blind, placebo-controlled, randomized trial in smokers hospitalized with AMI. Participants received bupropion or placebo for 9 weeks and were followed for 12 months. Both groups received low-intensity counseling. Point prevalence abstinence was assessed by 7-day recall and biochemical validation of expired carbon monoxide. RESULTS A total of 392 patients were randomized (mean age 53.9 ± 10.3 years); 83.5% were male; 64.9% had ST-segment elevation myocardial infarction). Patients smoked a mean of 23.2 ± 10.6 cigarettes/day for a mean of 32.9 ± 12.4 years. At 12 months, point prevalence abstinence rates were 37.2% in the bupropion group and 32.0% in the placebo group (p = 0.33; % difference after adjusting for between center differences 3.9%). Continuous abstinence rates were 26.8% and 22.2%, respectively (p = 0.34). Major adverse cardiac event rates were similar (13.0% vs. 11.0%, respectively; p = 0.64). CONCLUSIONS Two-thirds of patients return to smoking by 12 months after AMI. Bupropion is well tolerated and seems to be safe to use in the immediate post-AMI period. However, bupropion is not effective for smoking cessation in patients post-AMI.

Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome

Background— Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. Methods and Results— We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low-intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55±9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST-segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21±11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36±12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group (P=0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively (P=0.081; number needed to treat=10.0), and rates of reduction ≥50% in daily cigarette consumption were 67.4% and 55.6%, respectively (P=0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). Conclusions— Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794573.

Treatment and one-year outcome of patients with renal dysfunction across the broad spectrum of acute coronary syndromes.

BACKGROUND There are limited data on the treatment and long-term outcome of patients with renal dysfunction across the broad spectrum of acute coronary syndromes (ACS) in Canada. OBJECTIVES To examine the treatment patterns and outcome of ACS patients with renal dysfunction. METHODS In the prospective, multicentre, Canadian ACS Registry, 3510 patients hospitalized for ACS (including unstable angina, ST and non-ST elevation myocardial infarction) were categorized into four groups: normal renal function (creatinine clearance [CrCl] 90 mL/min or greater; n=1152), mild renal dysfunction (CrCl 60 mL/min to 89 mL/min; n=1253), moderate renal dysfunction (CrCl 30 mL/min to 59 mL/min; n=944) and severe renal dysfunction (CrCl less than 30 mL/min; n=161). Multivariable logistic regression analysis was performed to examine the independent prognostic value of renal dysfunction, and the association of various therapies with one-year survival. RESULTS All-cause mortality at one year was 2.8%, 6.4%, 14.5% and 40.9% in patients with normal renal function, and mild, moderate and severe renal dysfunction, respectively (P for trend<0.001). After adjusting for other prognosticators, moderate (OR 1.82, 95% CI 1.08 to 3.08) and severe (OR 6.29, 95% CI 3.37 to 11.77) renal dysfunction remained independent predictors of one-year death. Patients with renal dysfunction were less likely to receive fibrinolytic therapy, to undergo coronary angiography and revascularization in hospital, and to be treated with acetylsalicylic acid, beta-blockers and lipid-lowering therapy at discharge and at one-year follow-up. The association of in-hospital revascularization, and discharge use of acetylsalicylic acid and beta-blockers with better one-year survival was similar among patients with normal and impaired renal function. CONCLUSIONS Renal dysfunction is prevalent and independently predicts higher mortality in patients with ACS. The current underutilization of effective therapies may contribute to the poor outcome. There remains an important opportunity to improve care in this high-risk population.

Canada Acute Coronary Syndrome Risk Score: A new risk score for early prognostication in acute coronary syndromes

BACKGROUND Despite the availability of several acute coronary syndrome (ACS) prognostic risk scores, there is no appropriate score for early-risk stratification at the time of the first medical contact with patients with ACS. The primary objective of this study is to develop a simple risk score that can be used for early-risk stratification of patients with ACS. METHODS We derived the risk score from the Acute Myocardial Infarction in Quebec and Canada ACS-1 registries and validated the risk score in 4 other large data sets of patients with ACS (Canada ACS-2 registry, Canada-GRACE, EFFECT-1, and the FAST-MI registries). The final risk score is named the Canada Acute Coronary Syndrome Risk Score (C-ACS) and ranged from 0 to 4, with 1 point assigned for the presence of each of these variables: age ≥75 years, Killip >1, systolic blood pressure <100 mm Hg, and heart rate >100 beats/min. The primary end points were short-term (inhospital or 30-day) and long-term (1- or 5-year) all-cause mortality. RESULTS The C-ACS has good predictive values for short- and long-term mortality of patients with ST-segment elevation myocardial infarction and non-ST-segment elevation ACS. The negative predictive value of a C-ACS score ≥1 is excellent at ≥98% (95% CI 0.97-0.99) for short-term mortality and ≥93% (95% CI 0.91-0.96) for long-term mortality. In other words, a C-ACS score of 0 can potentially identify correctly ≥97% short-term survivors and ≥91% long-term survivors. CONCLUSION The C-ACS risk score permits rapid stratification of patients with ACS. Because this risk score is simple and easy to memorize and calculate, it can be rapidly applied by health care professionals without advanced medical training.

Routine functional testing after percutaneous coronary intervention: results of the aggressive diagnosis of restenosis in high-risk patients (ADORE II) trial.

Background — It is unclear whether routine or selective functional testing is optimal following percutaneous coronary intervention (PCI) in high-risk patients. Objectives — The aim of this trial was to compare exercise endurance, functional status, and quality of life (QOL) among high-risk patients randomized to either routine or selective functional testing following PCI. Methods — We randomized 84patients to either routine or selective functional testing. Patients had one or more of the following: multivessel PCI, diabetes mellitus, left ventricular ejection fraction ≤ 35%, and/or PCI of the proximal left anterior descending artery. Patients in the routine arm (n=41) underwent maximum endurance exercise treadmill testing (ETT) with nuclear perfusion imaging at 1.5 and 6months. Patients in the selective arm (n=43) only underwent functional testing for a clinical indication.All patients underwent a maximum endurance ETT at 9months. Exercise endurance, functional status, and QOL were assessed at 9months. Results — Most patients were middle-aged men (58±10years old; 87% male) who underwent PCI with stenting (94%).Among routine functional testing patients, 27.0% and 41.9% had a positive functional test at 1.5 and 6months, respectively. Exercise endurance was improved in the routine vs. selective arm at 9months (metabolic equivalents: 10.3±2.6 vs. 8.6±3.0, P=0.013).There was no difference in improvement from baseline for the Duke Activity Status Index, the Seattle Angina Questionnaire, or the SF-36. Nine-month cumulative incidences of cardiac procedures and clinical events were not significantly different. Conclusions — Routine functional testing following PCI in high-risk patients may lead to improved exercise endurance but not improved QOL.

Effectiveness and safety of glycoprotein IIb/IIIa inhibitors in patients with myocardial infarction undergoing primary percutaneous coronary intervention: A meta-analysis of observational studies

INTRODUCTION Meta-analyses of randomized controlled trials (RCT) showed that glycoprotein IIb/IIIa inhibitors (GPI) are associated with reduced adverse events following primary percutaneous coronary revascularization (PCI). However, the external validity of RCTs is generally limited due to their restricted inclusion of patients. The objective of this study is to evaluate the effectiveness and safety of GPI, as adjuvant therapy for primary PCI in real-life patients with myocardial infarction with ST segment elevation (STEMI) from the general population. METHODS We identified all published peer-reviewed observational studies enrolling STEMI patients who underwent primary PCI. We performed random-effect meta-analyses to determine the association of GPI with major adverse events. RESULTS A total of 11 studies, enrolling 12,253 patients, were retained for this meta-analysis. GPI was associated with approximately 53% reduction in short-term mortality (odds ratio (OR): 0.47, 95% confidence intervals (CI): 0.32-0.68). There was a 62% reduction in long-term mortality associated with GPI (OR: 0.38, 95% CI: 0.30-0.50). GPI was associated with a 62% reduction in 30-day re-infarction (OR: 0.38, 95% CI: 0.24-0.60) and 42% reduction in 30-day repeat PCI (OR: 0.58, 95% CI: 0.36-0.94). A non-significant increase in major bleeding with GPI was observed with an OR of 1.55 (95% CI: 0.92-2.62). CONCLUSIONS GPI is associated with significant reductions in short-term mortality, re-infarction and repeat PCI, long-term mortality and an inconclusive increase in major bleeding. These results provide evidence for the safety and effectiveness of GPI as adjuvant therapy for primary PCI in real-life STEMI patients.

Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital

BACKGROUND: Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks. METHODS: The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking. RESULTS: Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI −0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI −3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI −7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference −0.7%, 95% CI −7.8% to 6.5%). INTERPRETATION: Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573