Wei-Ching Chang

Acute Coronary Syndromes in the GUSTO-IIb Trial Prognostic Insights and Impact of Recurrent Ischemia

Background—Recurrent ischemia after an acute coronary syndrome portends an unfavorable outcome and has major resource-use implications. This issue has not been studied systematically among the spectrum of patients with acute coronary presentations, encompassing those with and without ST-segment elevation. Methods and Results—We assessed the 1-year prognosis of the 12 142 patients enrolled in the GUSTO-IIb trial by the presence (n54125) or absence (n58001) of ST-segment elevation. This latter group was further categorized into those with baseline myocardial infarction (n53513) or unstable angina (n54488). We also assessed the incidence of recurrent ischemia and its impact on outcomes. Recurrent ischemia was significantly rarer in those with ST-segment elevation (23%) than in those without (35%; P,0.001). Mortality at 30 days was greater among patients with ST-segment elevation (6.1% versus 3.8%; P,0.001) but less so at 6 months; by 1 year, mortality did not differ significantly (9.6% versus 8.8%). Patients with non‐ST-segment-elevation infarction had higher rates of reinfarction at 6 months (9.8% versus 6.2%) and higher 6-month (8.8% versus 5.0%) and 1-year mortality rates (11.1% versus 7.0%) than such patients who had unstable angina. Conclusions—Refractory ischemia was associated with an approximate doubling of mortality among patients with ST-segment elevation and a near tripling of risk among those without ST elevation. This study highlights not only the substantial increase in late mortality and reinfarction with non‐ST-segment-elevation infarction but also the opportunities for better triage and application of therapeutic strategies for patients with recurrent ischemia. (Circulation. 1998;98:1860-1868.)

Prognostic value of ST segment depression in acute coronary syndromes: insights from PARAGON-A applied to GUSTO-IIb ☆

Objectives Our objectives were to develop a risk-stratification model addressing the importance of the magnitude and distribution of ST segment depression in predicting long-term outcomes and to validate the model in an analogous patient population. Background Although patients without ST segment elevation presenting with acute coronary syndromes represent an increasingly frequent population admitted to coronary care units, little attention has been paid to quantifying their ST segment abnormalities. Methods ST segment depression was categorized into three groups: 1) no ST segment depression; 2) 1-mm ST segment depression in two contiguous leads; and 3) ST segment depression > or =2 mm in two contiguous leads. A logistic regression model was developed using Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A) data to assess the prognostic value of the extent and distribution of ST segment depression in predicting one-year mortality. The model was validated using the non-ST segment elevation population in Global Use of Strategies To Open occluded arteries in acute coronary syndromes (GUSTO-IIb). Results ST segment depression was the strongest predictor of one-year mortality, accounting for 35% of the models predictive power. Patients with ST segment depression > or =2 mm were approximately 6 times (odds ratio [OR] 5.73, 95% confidence interval [CI] 2.8 to 11.6) more likely to die within one year than patients with no ST segment depression. On validation, the model showed good discriminatory power (c-index = 0.75). Patients with ST segment depression > or =2 mm in more than one region were almost 10 times more likely to die within one year than patients with no ST segment depression. Conclusions These data provide new evidence supporting the powerful prognostic value of the baseline electrocardiogram and, in particular, the magnitude and distribution of ST segment depression in predicting unfavorable events.

Long-Term Mortality of Patients With Acute Myocardial Infarction in the United States and Canada Comparison of Patients Enrolled in Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I

Background—In a previous substudy of the GUSTO-I trial, we observed better functional and quality-of-life outcomes among patients in the United States (US patients) compared with patients in Canada. Rates of invasive therapy were significantly higher in the United States and were associated with a small mortality benefit (0.4%, adjusted P=0.02). We sought to determine whether Canadian–US differences in practice patterns in GUSTO-I had an impact on 5-year mortality. Methods and Results—Mortality data for 23 105 US and 2898 Canadian patients enrolled in GUSTO-I were obtained from national mortality databases. Median follow-up was 5.46 years in the US and 5.33 years in the Canadian cohort. Five-year mortality rate was 19.6% among US and 21.4% among Canadian patients (P=0.02). After baseline adjustment, enrollment in Canada was associated with a higher hazard of death (1.17; 95% confidence interval, 1.07 to 1.28, P=0.001). Revascularization rates during the index hospitalization in the United States were almost 3 times those in Canada: 30.5% versus 11.4% for angioplasty and 13.1% versus 4.0% for bypass surgery (P<0.01 for both). After accounting for revascularization status as a time-dependent covariate, country was no longer a significant predictor of long-term mortality. These results were confirmed in a propensity-matched analysis. Conclusions—Our results suggest, for the first time, that the more conservative pattern of care with regard to early revascularization in Canada for ST-segment elevation acute myocardial infarction may have a detrimental effect on long-term survival. Our results have important policy implications for cardiac care in countries and healthcare systems wherein use of invasive procedures is similarly conservative.

International differences in in-hospital revascularization and outcomes following acute myocardial infarction A multilevel analysis of patients in ASSENT-2

BACKGROUND Revascularization rates vary substantially between countries in patients with acute ST-elevation myocardial infarction (STEMI). The impact of early revascularization on clinical outcomes in such patients remains uncertain. The ASSENT-2 fibrinolytic trial provides the opportunity to compare revascularization rates following STEMI in patients across 29 countries, and to explore the relationship between revascularization and clinical outcome. METHODS Countries participating in ASSENT-2 were grouped into tertiles according to their in-hospital revascularization rates (<15%, 15-39%, >39%). Baseline characteristics, medication and procedure use, and clinical outcomes of the 16949 patients enrolled were compared. Multiple Cox regressions were used to assess the relationship between the tertiles and 30-day mortality, the primary endpoint of the ASSENT-2 trial. Multilevel logistic regression models were developed to validate and further extend the findings from the single-level analyses. RESULTS Patients in highest tertile countries were younger, heavier, and more often diabetic or hypertensive. They were more likely to have had a previous myocardial infarction or revascularization procedure. Time to treatment and hospital length of stay were shorter in the highest tertile, and beta-blocker use was more frequent. Stroke rates were low and similar across tertiles, with no statistically significant difference in rates of intracranial haemorrhage. Recurrent ischaemia and reinfarction were less common in the highest tertile. Mortality rates at 30 days were lower for countries with the highest revascularization rates (5.1% vs 6.9% vs 6.5% for the lower two tertiles, P<0.001). At 1 year, mortality remained significantly lower in the highest tertile countries (8.4% vs 10.6% vs 9.9%, P=0.001). Following adjustment for baseline patient characteristics, Cox regression analysis confirmed an excess of 30-day and 1-year mortality in the lowest and intermediate tertiles compared to the highest tertile. The multilevel analyses validated these findings, and demonstrated that a countrys life expectancy and the hospital volume were inversely related to both 30-day and 1-year mortality. CONCLUSIONS The highest rate of in-hospital revascularization following fibrinolytic therapy for acute myocardial infarction in this international study was associated with a reduction in recurrent ischaemia, reinfarction, and improved survival at both 30 days and at 1 year. The optimal rates of revascularization in this setting remain to be determined.

Differences in admission rates and outcomes between men and women presenting to emergency departments with coronary syndromes

Background: Previous studies examining sex-related differences in the treatment of coronary artery disease have focused on patients in hospital. We sought to examine sex-related differences at an earlier point in care — presentation to the emergency department. Methods: We collected data on ambulatory care and hospital admissions for 54 134 patients (44% women) who presented to an emergency department in Alberta between July 1998 and March 2001 because of acute myocardial infarction, unstable angina, stable angina or chest pain. We used logistic regression and Cox regression analyses to determine sex-specific associations between the likelihood of discharge from the emergency department or coronary revascularization within 1 year and 1-year mortality after adjusting for age, comorbidities and socioeconomic factors. Results: Following the emergency department visit, 91.3% of patients with acute myocardial infarction, 87.4% of those with unstable angina, 40.7% of those with stable angina and 19.8% of those with chest pain were admitted to hospital. Women were more likely than men to be discharged from the emergency department: adjusted odds ratio (and 95% confidence interval [CI]) 2.25 (1.75–2.90) for acute myocardial infarction, 1.71 (1.45–2.01) for unstable angina, 1.33 (1.15–1.53) for stable angina and 1.46 (1.36–1.57) for chest pain. Women were less likely than men to undergo coronary revascularization within 1 year: adjusted odds ratio (and 95% CI) 0.65 (0.57–0.73) for myocardial infarction, 0.39 (0.35–0.44) for unstable angina, 0.35 (0.29–0.42) for stable angina and 0.32 (0.27–0.37) for chest pain. Female sex had no impact on 1-year mortality among patients with acute myocardial infarction; it was associated with a decreased 1-year mortality among patients with unstable angina, stable angina and chest pain: adjusted hazard ratio (and 95% CI) 0.60 (0.46–0.78), 0.60 (0.46–0.78) and 0.74 (0.63–0.87) respectively. Interpretation: Women presenting to the emergency department with coronary syndromes are less likely than men to be admitted to an acute care hospital and to receive coronary revascularization procedures. These differences do not translate into worse outcomes for women in terms of 1-year mortality.

The meaning and goals of equity in health

The meaning and implications of “equity in health” are discussed. A conceptual framework is proposed to delineate the roles of empirical and normative research in determining when inequalities in health are equitable.

Canadian-American Differences in the Management of Acute Coronary Syndromes in the GUSTO IIb Trial One-Year Follow-Up of Patients Without ST-Segment Elevation

BackgroundLittle information exists concerning practice patterns between Canada and the United States in the management of myocardial infarction (MI) patients without ST-segment elevation and unstable angina. Methods and ResultsWe examined the practice patterns and 1-year outcomes of 2250 US and 922 Canadian patients without ST-elevation acute coronary syndromes in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial. The US hospitals more commonly had on-site facilities for angiography and revascularization. These procedures were performed more often and sooner in the United States than Canada, whereas Canadian patients were more likely to undergo noninvasive stress testing. The length of initial hospital stay was 1 day longer for Canadian than US patients. Recurrent and refractory ischemia was more common in Canada. One-year mortality was comparable between the 2 countries. However, at 6 months, even after baseline differences were accounted for, the (re)MI rate was significantly higher in Canadian than US patients with unstable angina (8.8% versus 5.8%, P =0.039), as was the composite rate of death or (re)MI (13.1% versus 9.1%, P =0.016). ConclusionsOne-year mortality was comparable between Canada and the United States in both MI and unstable angina cohorts despite higher intervention rates in the United States. However, outcomes at 6 months among patients with unstable angina differed. Whereas more frequent coronary interventions were not associated with reduced recurrent MI or death among MI patients without ST elevation, they may favorably affect outcomes in patients with unstable angina.

Time to treatment and the impact of a physician on prehospital management of acute ST elevation myocardial infarction: insights from the ASSENT-3 PLUS trial

Objectives: To assess the impact of variation in prehospital care across distinct health care environments in ASSENT (assessment of the safety and efficacy of a new thrombolytic) -3 PLUS, a large (n  =  1639) contemporary multicentred international trial of prehospital fibrinolysis. Specifically, the objectives were to assess predictors of time to treatment, whether components of time to treatment vary across countries, and the impact of physician presence before hospitalisation on time to treatment, adherence to protocol, and clinical events. Methods: Patient characteristics associated with early treatment (⩽ 2 hours), comparison of international variation in time to treatment, and components of delay were assessed. Trial specific patient data were linked with site specific survey responses. Results: Younger age, slower heart rate, lower systolic blood pressure, and prior percutaneous coronary intervention were associated with early treatment. Country of origin accounted for the largest proportion of variation in time. Intercountry heterogeneity was shown in components of elapsed time to treatment. Physicians in the prehospital setting enrolled 63.8% of patients. The presence of a physician was associated with greater adherence to protocol mandated treatments and procedures but with delay in time to treatment (120 v 108 minutes, p < 0. 001). Conclusion: Country of enrolment accounted for the largest proportion of variation in time to treatment and intercountry heterogeneity modulated components of delay. The effectiveness and safety of prehospital fibrinolysis was not influenced by the presence of a physician. These data, acquired in diverse health care environments, provide new understanding into the components of prehospital treatment delay and the opportunities to further reduce time to fibrinolysis for patients with ST elevation myocardial infarction.

Are international differences in the outcomes of acute coronary syndromes apparent or real? A multilevel analysis

Study objective: International variation in the outcomes of patients with acute coronary syndromes (ACS) has been well reported. The relative contributions of patient, hospital, and country level factors on clinical outcomes, however, remain unclear, and thus, was the objective of this study. Design: Multilevel logistic regression models were developed for death/(re)infarction (MI) at 30 days and death in one year, with patients (1st level) nested in hospitals (2nd level) and hospitals in countries (3rd level). Settings: The GUSTO IV ACS clinical trial was carried out at 458 hospital sites in 24 countries. Patients: 7800 non-ST segment elevation (NSTE) ACS patients. Main results: There were substantial variations among countries in the processes and outcomes of care at 30 days, ranging from 5.4% to 50.0% for percutaneous coronary intervention, 4.3% to 21.2% for coronary artery bypass graft surgery, 5.0% to 13.9% for 30 day death/(re)MI, and 4.9% to 14.8% for one year mortality. However, the residual inter-country variations in 30 day death/(re)MI and one year mortality became non-significant and nearly disappeared (p>0.500 for both) after adjusting for key baseline patient characteristics and hospital factors, which became significant (p<0.01 for both). Patient level factors accounted for 96%–99% of total variation in these end points, leaving the remaining 1% and 4% of variance attributable to hospital level factors. Conclusion: The international differences in clinical outcomes in this study of NSTE ACS are primarily accounted for by the patient level factors, with hospital level factors playing a minor part, and the country level factors a negligible one. These findings have significant policy and research implications involving international collaboration and comparisons.

Do the investigative sites that take part in a positive clinical trial translate that evidence into practice

PURPOSE The earliest awareness of new evidence should beat the trial sites that first generated the evidence. We hypothesized that sites that had taken part in the Survival and Ventricular Enlargement (SAVE) trial, which demonstrated that angiotensin-converting enzyme (ACE) inhibitors were beneficial following myocardial infarction, would be more likely to adopt their use in this group of patients. SUBJECTS AND METHODS We performed a cross-sectional analysis of data collected for the 25,886 North American patients with myocardial infarction enrolled in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) study from 1990 to 1993. Patients were treated at 659 hospitals, 22 of which had also taken part in SAVE. One third of patients were enrolled after SAVE was published in 1992. The primary outcome was use of an ACE inhibitor at discharge. We analyzed the data using hierarchical models and multivariate regression. RESULTS Patients treated at sites that had taken part in SAVE were not more likely to receive an ACE inhibitor at discharge than were patients treated at non-SAVE sites (226/1415 [16%] vs. 3671/24,471 [15%]; odds ratio [OR] = 1.1; 95% confidence interval [CI]: 0.8 to 1.4; P = 0.67). Although patients with heart failure were more likely to receive ACE inhibitors than were those without heart failure, there was no difference between SAVE and non-SAVE sites (90/297 [30%] vs. 1322/4405 [30%]; P = 0.75). Use of ACE inhibitors increased following the publication of the SAVE trial, but again there was no significant difference in adoption of the drug between SAVE and non-SAVE sites. CONCLUSION Sites that had taken part in SAVE were no more likely to adopt ACE inhibitors for patients with myocardial infarction than were sites that had not taken part. If those who generated the evidence are slow to translate it into practice, it is unlikely that passive forms of dissemination can improve the quality of care. To accelerate adoption of new evidence, we need to understand factors other than knowledge and awareness that influence practice.