Sibrafiban

Obesity is a coronary disease risk factor, but its independent effect on clinical outcomes following acute coronary syndromes has not been quantified. We evaluated the relationship between elevated body mass index (BMI) and 30-day, 90-day, and 1-year clinical outcomes postacute coronary syndromes.

Using 15 071 patients (normal weight [BMI = 18.5-24.9 kg/m(2)], overweight [BMI = 25-29.9 kg/m(2)], obese [BMI = 30-34.9 kg/m(2)] or very obese [BMI > or =35 kg/m(2)]) randomized from 1997-1999 in the SYMPHONY (Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes) and 2nd SYMPHONY trials, we evaluated the relationships between BMI and 30-day, 90-day, and 1-year mortality and 30-day and 90-day death or myocardial infarction.

Increasing BMI was associated with younger age, multiple comorbidities, and greater cardiac medication and procedure use; however, systolic function and coronary disease extent were similar for all BMI categories. Unadjusted Kaplan-Meier mortality estimates were higher for normal-weight patients than for all other BMI groups. After multivariable adjustment, the 30-day mortality hazard ratios (95% confidence interval [CI]) were: overweight, 0.66 (95% CI: 0.47 to 0.94); obese, 0.61 (95% CI: 0.39 to 0.97); very obese, 0.89 (95% CI: 0.48 to 1.64). Adjusted hazard ratios were similar for 90-day and 1-year mortality. There were no statistically significant differences among BMI groups in 30-day and 90-day death or myocardial infarction (unadjusted or adjusted).

Overweight and obese BMI classifications were associated with better intermediate-term survival after acute coronary syndromes than normal weight and very obese, but death or myocardial infarction rates were similar. Further study is required to understand the apparent association of overweight and moderate obesity with better intermediate-term outcomes.

R emarkable advances in cardiovascular care have been substantially mediated by large-scale, randomized clinical trials.These trials not only have identified treatments resulting in major improvements in patient outcomes but also have enhanced our understanding of the natural history of contemporary disease and the impact of risk factors and complications.The process by which phase III clinical trials in cardiovascular medicine are created, implemented, completed, analyzed, presented, and published has evolved dramatically over the past decade.Historically, government and academic alliances took center stage in this process because of their intellectual equity, opinion leadership, access to patients, and allocation of public interest-related research tax dollars.This axis has now shifted.Community practitioners and groups of physicians, often organized regionally, now provide the majority of subjects for clinical trials.Furthermore, substantial scientific expertise, at both the basic and clinical levels, resides within multinational pharmaceutical firms.Additionally, contract research organizations have seized the business opportunity afforded by the need for timely and efficient operational aspects of clinical trials.Although communitybased trials, efficiency, and expertise are prerequisites for a major clinical trial, the extraordinary costs of completing them squarely places the sponsor in a dominant position. 1ur participation in the failed large-scale attempt to develop a novel oral glycoprotein IIb/IIIa inhibitor, sibrafiban, for secondary prevention of coronary heart disease has stimulated us to reflect on issues that arose in the design and conduct of this trial. 2,3Using the Sibrafiban Versus Aspirin to Yield Maximum Protection From ischemic Heart Events Post-Acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials as examples, we review issues here that should be of interest to investigators, clinical practitioners, participating institutions, sponsors, data and safety monitoring boards (DSMBs), and the patients whom we serve. 4Our purpose is to encourage discussion so that standards can be enhanced for this form of collaborative science.