To the Editor: In the STRADIVARIUS trial, Dr Nissen and colleagues1 studied the effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease. We would like to raise a number of issues about this trial.
From an ethical perspective, new treatments should be tested when possible against an established treatment with proven benefits, rather than against placebo. Medications other than rimonabant have been shown to be superior to placebo for weight reduction in obese patients,2 - 3 but in the STRADIVARIUS trial the interventions studied were either rimonabant (20 mg daily) or placebo.
The primary end point used was percent atheroma volume (PAV), determined using intravascular ultrasound. Decrease in body weight is associated with favorable changes in the metabolic profile, which may reduce progression of atherosclerotic disease. The strategy of using a primary end point of PAV rather than weight reduction in this study seems to be a way to avoid the need for comparing rimonabant with an active antiobesity medication. In the STRADIVARIUS trial, more than 80% of the included patients were obese (BMI >30).
In addition, PAV is a nonvalidated surrogate end point for cardiovascular outcomes, and measurement of PAV requires an invasive procedure. Diagnostic cardiac catheterization is not a risk-free procedure, with 1 study finding a 1.9% major complication rate and a mortality rate of 0.12%.4 It is not clear how many cardiac catheterizations were conducted solely to evaluate PAV, and no data were presented about complications resulting from the procedure.
The high rates of adverse events resulting from rimonabant itself were discussed in the accompanying Editorial by Drs Rumsfeld and Nallamothu.5 Our main concerns are whether it is acceptable to compare an active drug against placebo when another therapy has already shown proven benefits for the condition, and whether it is ethical to submit patients to a risky invasive procedure to evaluate a nonvalidated end point.
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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