Cooperate! A paradigm shift for health equity.

The role of competition and cooperation in relation to the goal of health equity is examined in this paper. The authors explain why the win-lose mentality associated with avoidable competition is ethically questionable and less effective than cooperation in achieving positive outcomes, particularly as it relates to health and health equity. Competition, which differentiates winners from losers, often with the winner-takes-all reward system, inevitably leads to a few winners and many losers, resulting in social inequality, which, in turn, engenders and perpetuates health inequity.Competitive market-driven approaches to healthcare-brought about by capitalism, neo-liberalization, and globalization, based primarily on a competitive framework-are shown to have contributed to growing inequities with respect to the social determinants of health, and have undermined equal opportunity to access health care and achieve health equity. It is possible to redistribute income and wealth to reduce social inequality, but globalization poses increasing challenges to policy makers. John Stuart Mill provided a passionate, philosophical defense of cooperatives, followed by Karl Polanyi who offered an insightful critique of both state socialism and especially the self-regulating market, thereby opening up the cooperative way of shaping the future. We cite Hannah Arendt's "the banality of evil" to characterize the tragic concept of "ethical fading" witnessed in business and everyday life all over the world, often committed (without thinking and reflecting) by ordinary people under competitive pressures.To promote equity in health for all, we recommend the adoption of a radically new cooperation paradigm, applied whenever possible, to everything in our daily lives.

Influence of particle surface roughness on creeping granular motion.

A core is formed at the center of a quasi-two-dimensional rotating drum filled more than half with granular material. The core rotates slightly faster than the drum (precession) and decreases in radius over time (erosion) due to the granular creeping motion that occurs below the freely flowing layer. This paper focuses on the effect of the surface roughness of particles on core dynamics, core precession, and core erosion. Two different surface roughness of glass particles having the same diameter were used in the experiments. The surface structures of the particles were quantitatively compared by measuring the coefficients of friction and using a simple image contrast method. The experiments were performed with five different filling levels in a 50-cm-diameter rotating drum. According to the results, core precession and core erosion are both dependent on the particle surface roughness. Core precession becomes weaker and erosion becomes stronger when using particles having a rough surface in the experiments. To explain the physics of core dynamics, the particles' surface roughness effect on the freely flowing layer and the creeping motion region were also investigated. The granular bed velocity field, maximum flowing layer depth δ, shear rate in the flowing layer γ[over ̇], and the creeping region decay constant y_{0} were also calculated in this paper. The effect of the particles' surface roughness on these physical variables well illustrates the physics of core dynamics and creeping granular motion.

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.

No prognostic significance of chronic infection with Chlamydia pneumoniae in acute coronary syndromes: insights from the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial.

BACKGROUND: Although relationships between chronic Chlamydia pneumoniae (Cpn) infection and the risk of coronary events in stable coronary artery disease patients have been reported, a similar link in acute coronary syndrome (ACS) patients has not been consistently observed. METHODS: In a nested case-control substudy of the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial, 295 cases (30-day death/myocardial infarction [MI]) were matched by age, sex, baseline creatine kinase-myocardial kinase, and smoking status with 295 control subjects. To test the hypothesis on 1-year mortality, another subset (n = 276) was drawn from the 590-patient cohort; 138 patients who died at 1 year plus the matching controls who survived at 1 year. We measured Cpn IgG and IgA antibody titers in baseline serum with microimmunofluorescence. Conditional logistic regression was used to quantify the prognostic relevance seropositivity (IgG > or = 1:32; IgA > or = 1:16) and elevated titer levels. RESULTS: The prevalence of Cpn IgG and IgA was similar between cases and controls (30-day death/MI: IgG, 80% vs 85%, P = .126; IgA, 45% vs 37%, P = .079), and were not statistically significant predictors of 30-day death/MI after baseline adjustment. Likewise, the 1-year death cohort had comparable proportions of Cpn IgG and IgA among cases and controls (86% vs 91% [P = .265] and 49% vs 43% [P = .334], respectively), and did not add prognostic value. CONCLUSIONS: These findings are in concert with study results suggesting that chronic Cpn infection is not associated with 30-day death/MI or 1-year mortality in non-ST elevation ACS.

Effects of socioeconomic status on mortality after acute myocardial infarction.

PURPOSE: To assess the effects of socioeconomic status on mortality in patients with acute myocardial infarction. MATERIAL AND METHODS: We studied a retrospective cohort of 5622 patients who presented to a hospital emergency department with an initial episode of acute myocardial infarction between April 1998 and March 2002 in the Province of Alberta, Canada. Our main outcome measure was 1-year all-cause mortality following the index emergency department visit; we used socioeconomic status (measured by neighborhood median household income) as our main predictor after controlling for patient and hospital characteristics and revascularization. RESULTS: Socioeconomic status profoundly affected the rate of emergency department presentation and the process and outcome of acute myocardial infarction care. In patients belonging to the lowest versus the highest socioeconomic status quartile, the risk of presenting to the emergency department was 72% higher (P <.001); at 1 year, revascularization was lower (36% vs 48%, P <.001), and mortality higher (19.1% vs 9.1%, P <.001). Socioeconomic status was independently associated with 1-year mortality after adjustment for baseline characteristics and 1-year revascularization, and socioeconomic status was especially influential in non-revascularized patients. CONCLUSIONS: Given the influence of socioeconomic status on mortality after acute myocardial infarction and the key role of revascularization in modulating this relationship, our study has important implications for access to and process of cardiac care.

Efficacy and safety of unfractionated heparin versus enoxaparin: a pooled analysis of ASSENT-3 and -3 PLUS data.

BACKGROUND: The optimal antithrombotic therapy to accompany tenecteplase in cases of acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We undertook a prespecified pooled analysis of data from the ASSENT-3 and ASSENT-3 PLUS trials. METHODS: We created a combined database of the 2040 and 818 patients who received enoxaparin in ASSENT-3 and ASSENT-3 PLUS, respectively, and compared them with the 2038 and 821 patients who received unfractionated heparin. RESULTS: The efficacy end point (a composite of 30-day mortality, reinfarction or refractory ischemia) was 12.2% with enoxaparin versus 16.0% with unfractionated heparin (p < 0.001); the combined end point of efficacy plus safety (a composite of 30-day mortality, reinfarction, refractory ischemia, intracranial hemorrhage [ICH] or major systemic bleeding) was 15.0% versus 18.0%, respectively (p = 0.003) [corrected] The 1049 patients urgently revascularized had greater benefit from enoxaparin (15.4% v. 10.1%, p = 0.013), yet the excess in major systemic bleeding evident with enoxaparin (3.3% v. 2.4%, p = 0.01) was largely confined to the 3492 patients without or before revascularization. Although ICH rates in the groups were similar (1.3% v. 0.9%, p = 0.26), an excess of ICH occurred among those administered enoxaparin during the ASSENT-3 PLUS trial (6.7% v. 0.8%, p = 0.013), especially among women over 75 years of age. INTERPRETATION: These data demonstrated the benefit of enoxaparin used in conjunction with tenecteplase, but raised caution about its prehospital use to treat STEMI in elderly women.

Optimizing use of revascularization and clinical outcomes in ST-elevation myocardial infarction: insights from the GUSTO-V trial.

AIMS: To examine the relationship between revascularization within 7 days and 1-year mortality among ST-elevation myocardial infarction patients enrolled in GUSTO-V trial (n=13 451). To examine the relative contribution of system and patient level factors to the variation in international revascularization rates, and their impact on mortality outcomes. METHODS AND RESULTS: Patients from North America (USA, Canada), Australia, and Europe (UK, France, Germany, Italy, Spain, Poland, Norway, The Netherlands, Belgium, Finland) were included in the study. Revascularization was associated with lower 1-year mortality. Norway, Belgium, Spain, Poland, and Italy also had lower than expected revascularization rates but higher than expected mortality rates. France and USA had almost two times the expected rate of 7-day revascularization, which was associated with modest mortality benefits. Patients' propensity for revascularization based on clinical factors alone was associated with lower 1-year mortality (OR 0.97, 95% CI: 0.96-0.99). Country-level factors had an impact on propensity for revascularization but no impact on 1-year mortality. CONCLUSION: Our study reveals the potential for some countries with lower than expected 7-day revascularization rates to improve their clinical outcomes. Also highlighted is the possibility for more economically efficient delivery of care in USA and France.

Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction.

BACKGROUND: The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial previously demonstrated an unexpected dose-dependent reduction in 90-day mortality after bolus/infusion of pexelizumab despite no reduction in the primary end point of myocardial infarction (MI) size. We examined whether the mortality benefit was related to established modulators of clinical benefit such as baseline demographics, time to treatment from symptom onset, myocardial perfusion post-percutaneous coronary intervention (PCI), and extent of ST resolution. METHODS AND RESULTS: Eight hundred fourteen patients were randomized into 3 groups; (1) placebo, (2) pexelizumab bolus 2.0 mg/kg and placebo infusion for 20 hours, and (3) pexelizumab bolus 2.0 and 0.05 mg/kg per hour infusion for 20 hours commencing 4 hours after the bolus. Subjects presented with ST elevation MI within 6 hours of symptom onset and underwent PCI, creatine kinase (CK), and CK-MB measurements taken sequentially to define CK-MB area under the curve (AUC) and sequential ECG's defined ST resolution and QRS infarct size. Whereas mortality for both placebo and bolus pexelizumab groups rose during later time after presentation, it remained low and did not change appreciably during the 6-hour randomization window when patients received pexelizumab bolus infusion. Amplification of the mortality benefit was evident in patients with the highest quartile of hemodynamic compromise, that is, heart rate > or = 90 beat/min and systolic blood pressure < or = 118 mm Hg (3.2% vs 11.3% P = .004). A significant interaction between treatment assignment and hemodynamic status (P = .013) existed after adjusting for age, race, and MI location. Clinical benefit was not related to infarct size, extent of ST elevation, or evidence of angiographic or electrocardiographic reperfusion. CONCLUSIONS: These data raise the possibility that the clinical benefit of pexelizumab is mediated through novel pathways such as reduction in apoptosis or other mechanisms.

Forecasting mortality: dynamic assessment of risk in ST-segment elevation acute myocardial infarction.

AIMS: To demonstrate the feasibility and clinical utility of developing dynamic risk assessment models for ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: In 6066 STEMI patients enrolled in the Assessment of the Safety and Efficacy of a New Thrombolytic-3 (ASSENT-3) trial with complete electrocardiographic data, we assessed the probability of 30-day mortality over the following forecasting periods beginning at day 0 (baseline), 3 h, day 2, and day 5 using multiple-logistic regression. These models were validated and simplified in independent samples of 1622 similar fibrinolytic-treated patients from the ASSENT-3 PLUS trial and in 814 STEMI patients undergoing primary percutaneous coronary intervention in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial. The discriminatory power of these predictive models, from baseline to day 5, was excellent (c-statistics 0.80 to 0.87); and their predictive ability was supported by strong gradients in mortality outcomes as the risk score increased. Dynamic modelling also provided information on the change in prognosis over time which may be used to advise more appropriate therapeutic decisions, e.g. the identification of high-risk patients for possible co-interventions. CONCLUSION: Dynamic modelling for STEMI patients enhances the risk assessment and stratification and should provide valuable ongoing guidance for their management.

Secular trends in coronary heart disease mortality, hospitalization rates, and major cardiovascular risk factors in Taiwan, 1971-2001.

BACKGROUND: While mortality from coronary heart disease (CHD) has declined substantially in most developed countries in recent decades, discordant rising trends have been observed in many developing and newly developed countries. In this study, we examined the trends of CHD mortality and its hospitalization rate, and correlated the trends with changes in major cardiovascular risk factors in Taiwan. METHODS: Mortality data during the period 1971-2001 were obtained from official vital statistics. Hospitalization rates were calculated using information extracted from the National Health Insurance Database, which was available from 1996 to 2001. Changes in major cardiovascular risk factors were obtained from official statistics and review of previous epidemiologic studies. RESULTS: In 2001, the age-standardized CHD mortality in Taiwan was 28.7 per 100,000 for men and 15.5 per 100,000 for women. For both men and women, age-adjusted CHD mortality increased slowly but steadily from 1971 to 1992, but after that, a downward trend was observed. Hospitalization rates for CHD, however, increased substantially from 1996 to 2001. Levels of per-capita cigarette consumption, dietary fat intake, body mass index, and prevalence of hypertension and diabetes had all increased over the past three decades. CONCLUSIONS: The overall cardiovascular risk profile has worsened in the general population in Taiwan. The decline in CHD mortality observed in recent years was most likely attributable to the improvement in acute cardiac care and medical treatment among patients with CHD. We anticipated that CHD incidence and prevalence would continue to rise in Taiwan.

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.

Meal composition and shift work performance.

Research indicates that the ability to perform a task can be affected by the composition of the meal preceding the task. This study investigated the effect of shift workers' consumption of a medium-fat, medium-carbohydrate meal on alertness scores. Six subjects (four men, two women) aged 19 to 44 recorded food intake, sleep, and quality of sleep for two weeks, and measured their body temperature and performed cognitive tests during two night shifts at baseline and in test periods. The Stanford Sleepiness Scale (SSS) was used to quantify sleepiness, and a Paced Auditory Serial Addition Test (PASAT) was used to measure cognitive performance. In comparison with the score at baseline, when subjects had a low-fat, high-carbohydrate dietary intake (1,335 kcal/5,588 kJ, 56% carbohydrate, 28% fat), the 1.6-second PASAT score improved significantly (p=0.042) during night shifts when subjects consumed a test meal (987 kcal/4,131 kJ, 46% carbohydrate, 42% fat). No statistically significant difference in SSS was found between baseline and test periods. The reduced body temperature between 2400 hours and 0530 hours was similar for both baseline and test periods. Meal composition and size during night shifts may affect cognitive performance.

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.

Six-month outcomes of percutaneous coronary balloon angioplasty in acute coronary syndromes: Results from the PURSUIT trial.

BACKGROUND: Potent inhibition of the platelet glycoprotein IIb/IIIa receptor has improved the acute outcome of patients presenting with acute coronary syndromes (ACS). For patients with ACS undergoing percutaneous balloon angioplasty without coronary stenting in the era of platelet glycoprotein IIb/IIIa blockade, the long-term prognosis is less clear. OBJECTIVE: To examine the six-month outcome of patients who received eptifibatide within a randomized clinical trial and subsequently underwent balloon angioplasty. METHODS: Patients included in this substudy were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, a randomized study evaluating the efficacy of eptifibatide in reducing the incidence of death or nonfatal myocardial infarction (MI) in non-ST segment elevation ACS. During the index hospitalization, 1151 (12.2%) of the PURSUIT patients underwent percutaneous balloon angioplasty without coronary stenting. RESULTS: Eptifibatide was associated with a significant reduction in the adjudicated composite end point of death or MI at six months after randomization in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) (P=0.037). A trend toward a beneficial effect was evident before the procedure (4.7% versus 6.9%; P=0.13) and at 30 days (12.1% versus 15.3%; P=0.12). The incidence of repeat revascularization was relatively low for patients undergoing PTCA, with no difference observed between the eptifibatide and placebo groups (16.3% versus 14.8%; P=0.51). CONCLUSIONS: Eptifibatide was associated with a sustained beneficial effect to six months in patients with ACS undergoing PTCA. It reduced the incidence of preprocedural MI. The rate of repeat revascularization at six months was low and was not significantly altered by eptifibatide.

Dynamic prognostication in non-ST-elevation acute coronary syndromes: insights from GUSTO-IIb and PURSUIT.

BACKGROUND: Risk assessment in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) traditionally focuses on and is limited to admission findings. The objective of the current study was to develop an approach to predicting outcome in NSTE-ACS that could account for the changing nature of risk. METHODS: In 7294 of 8010 patients with NSTE-ACS and complete electrocardiographic data in the GUSTO-IIb trial, we predicted the mortality probability at days 0-2, 0-30, 3-30, 5-30, and 7-30 using multiple logistic regression. Resulting risk estimates were incorporated into a composite, dynamic model to estimate the effects of changing probabilities over time. These models were validated against an independent sample of 9461 patients from the PURSUIT trial. RESULTS: As time passed after admission, the risk of 30-day death declined in stable patients. This risk, which was 3.72% at baseline, declined to 1.92% in 6-day survivors, and the risk reduction was greatest for those with the highest baseline risk. Importantly, however, the development of inhospital complications modified these trends. The use of dynamic models not only allowed us to estimate early (<48 h) mortality with a high degree of accuracy (C-index of 0.87), but also to continuously update the longer-term prognosis with increasing accuracy: the C-index increased from 0.75 for the day 0-30 model to 0.81 and 0.82 for the composite and day 7-30 models, respectively. CONCLUSIONS: Dynamic risk assessment is feasible and reliable. This approach can improve risk assessment and provide valuable guidance for management of patients with NSTE-ACS.

Do evidence-based treatments provide incremental benefits to patients with congestive heart failure already receiving angiotensin-converting enzyme inhibitors? A secondary analysis of one-year outcomes from the Assessment of Treatment with Lisinopril and Survival (ATLAS) study.

BACKGROUND: In patients with congestive heart failure (CHF), use of submaximal doses of angiotensin-converting enzyme (ACE) inhibitors (ie, low-dose ACE inhibitors) represents usual care in routine clinical practice, whereas high-dose ACE inhibitors, beta-blockers, and digoxin have each been shown to improve outcomes. OBJECTIVE: We examined whether treatment with high dose-ACE inhibitors, beta-blockers, and digoxin would each provide incremental benefits over that achieved with usual care and whether concurrent use of high-dose ACE inhibitors, beta-blockers, and digoxin would provide maximal benefits. METHODS: We conducted a secondary analysis of a randomized, controlled, active-comparator trial. Specifically, we studied 1-year outcomes data from the Assessment of Treatment with Lisinopril and Survival trial (ATLAS), which assessed high-dose ACE inhibitors (mean dosage, 33.2 mg daily lisinopril) versus low-dose ACE inhibitors (mean dosage, 4.5 mg daily lisinopril) in patients of any age with advanced CHF in 287 centers in 19 countries in the 1990s. In our analysis, patients were classified by their use of low-dose or high-dose ACE inhibitors, beta-blockers, and/or digoxin at the time of randomization. The primary outcome of interest was the ATLAS composite end point of all-cause mortality or hospitalization for any reason at 1 year. Multiple logistic regression analyses were used to adjust for baseline differences in patient characteristics. RESULTS: The 3164 patients in the ATLAS study had a mean (SD) age of 64 (10) years; 2516 patients (80%) were men and 648 (20%) were women; mean (SD) left-ventricular ejection fraction was 23% (6%); and 2671 patients (84%) had New York Heart Association class III or IV symptoms. At 1 year, the mortality rate was 13% (408 patients); 43% (1369 patients) had > or =1 hospitalization; and the composite end point of mortality or hospitalization was 47% (1489 patients). Most patients (2873; 91%) remained on their initial treatment regimen. Compared with low-dose ACE inhibitors (n = 471), the composite end point decreased incrementally with the use of high-dose ACE inhibitors (n = 475) (adjusted odds ratio [aOR], 0.93; P = NS), high-dose ACE inhibitors plus beta-blockers (n = 72) (aOR, 0.89; P = NS), and high-dose ACE inhibitors plus beta-blockers plus digoxin (n = 77) (aOR, 0.47; P = 0.006). In absolute proportions, patients receiving high-dose ACE inhibitors plus beta-blockers plus digoxin for 1 year had 12% fewer deaths and hospitalizations than patients receiving low-dose ACE inhibitors alone. CONCLUSIONS: Compared with usual care for patients with CHF, in this analysis, an evidence-based strategy that incorporated high-dose ACE inhibitors plus beta-blockers plus digoxin was associated with incrementally greater reductions in morbidity and mortality. These findings support treatment guidelines that recommend the concurrent use of all available proven efficacious treatment in patients with advanced CHF.

Differential treatment benefit of platelet glycoprotein IIb/IIIa inhibition with percutaneous coronary intervention versus medical therapy for acute coronary syndromes: exploration of methods.

BACKGROUND: Although many believe that platelet glycoprotein IIb/IIIa inhibitors should be used only in acute coronary syndrome patients undergoing percutaneous coronary intervention, supporting data from randomized clinical trials are tenuous. The assumption that these agents are useful only in conjunction with percutaneous coronary intervention is based primarily on inappropriate subgroup analyses performed across the glycoprotein IIb/IIIa inhibitor trials. METHODS AND RESULTS: We describe the problems with these analytical techniques and demonstrate that different approaches to the question can result in opposing answers. CONCLUSIONS: Clinical-practice decisions and practice guidelines should be based on overall trial results and not analyses of post-randomization subgroups.

International variation in the use of evidence-based medicines for acute coronary syndromes.

AIMS: We sought to evaluate international patterns of use and factors influencing use of evidence-based medications early after ACS. METHODS AND RESULTS: Using a database of 15904 ACS patients enrolled in the SYMPHONY and 2nd SYMPHONY trials in 37 countries, we performed descriptive and logistic regression analyses. After controlling for other factors, region was significantly associated with the use of every class of evidence-based medication, most pronounced for intravenous unfractionated heparin (IV UFH), low-molecular-weight heparin (LMWH), angiotensin II converting enzyme inhibitors (ACEI) and discharge use of lipid-lowering agents. Latin America and Eastern Europe were among the highest users of early ACEI, yet the lowest users of discharge lipid-lowering therapy. Relative to the United States, all regions except Canada had greater use of LMWH and lower use of IV UFH. Compared with patients with acute myocardial infarction, those with unstable angina less often received aspirin, beta-blockers, ACEI, or IV UFH. Older age was associated with lower use of aspirin, beta-blockers, IV UFH, and lipid-lowering agents. CONCLUSIONS: Use of evidence-based therapies for management of ACS patients is strongly associated with region. To improve patient outcomes, more research is needed to understand this variation, and to institute appropriate solutions.

International variation in the use of evidence-based medicines for acute coronary syndromes

Aims We sought to evaluate international patterns of use and factors influencing use of evidence-based medications early after ACS. Methods and results Using a database of 15 904 ACS patients enrolled in the SYMPHONY and 2nd SYMPHONY trials in 37 countries, we performed descriptive and logistic regression analyses. After controlling for other factors, region was significantly associated with the use of every class of evidence-based medication, most pronounced for intravenous unfractionated heparin (IV UFH), low- molecular-weight heparin (LMWH), angiotensin II converting enzyme inhibitors (ACEI) and discharge use of lipid-lowering agents. Latin America and Eastern Europe were among the highest users of early ACEI, yet the lowest users of discharge lipid-lowering therapy. Relative to the United States, all regions except Canada had greater use of LMWH and lower use of IV UFH. Compared with patients with acute myocardial infarction, those with unstable angina less often received aspirin, beta-blockers, ACEI, or IV UFH. Older age was associated with lower use of aspirin, beta-blockers, IV UFH, and lipid-lowering agents. Conclusion Use of evidence-based therapies for management of ACS patients is strongly associated with region. To improve patient outcomes, more research is needed to understand this variation, and to institute appropriate solutions.