The challenge of assessing the cardiovascular safety of the recently approved naltrexone-bupropion combination for treatment of obesity originates in the complex issues involving the LIGHT trial, published in this issue of JAMA.1
In 2011, in response to concerns regarding the cardiovascular effects of this combination medication, including elevations in blood pressure, the US Food and Drug Administration (FDA) asked the sponsor, Orexigen, to support a definitive safety study.2 Investigators designed the LIGHT study to randomize approximately 9000 patients to receive treatment with naltrexone-bupropion vs placebo and follow them up for about 5 years until approximately 400 major adverse cardiovascular events had occurred. With a noninferiority design, the study was powered to exclude a 1.4-fold increase in cardiovascular risk associated with the medication.
Sharfstein JM, Psaty BM. Evaluation of the Cardiovascular Risk of Naltrexone-BupropionA Study Interrupted. JAMA. 2016;315(10):984-986. doi:10.1001/jama.2016.1461