Author + information
As cumulative therapies improve over time, composite primary endpoints have been utilized to increase the chance of detecting a positive treatment outcome in cardiovascular clinical trials. This study seeks to assess the success of this strategy over the past 2 decades.
A systematic review was performed of the 3 major general medical journals, JAMA, NEJM and the Lancet from 1986 to the present to find reports of randomized CV clinical trials with expected follow up of greater than 1 year with at least 400 patients in the study. Data was then abstracted from these reports on: demographics of the studies, components of the primary endpoint, and results of the primary endpoint and the reporting of the frequency of major CV endpoints (MACE) of death, CV death, MI, and stroke. Calculations for change in risk with the intervention for the primary endpoint and the MACE were performed utilizing standard methods.
There were 385 studies identified. Over time, the median age enrolled increased from 61 to 64, the percentage male decreased (76% to 70%), length of study increased (2.3 to 3 years) and the number enrolled ncreased (1600 to 4000). The median number of endpoints in the primary endpoint increased from 1 to 3. The median number of events in the primary endpoint increased from 277 to 464. The number of deaths, MIs, and strokes recorded all increased over time. Despite this, the rate of positive studies decreased from 40% to 23%. The chance of a study showing a statistically positive result for mortality decreased from 25% to 5%, for CV mortality from 22% to 5%, for MI from 35% to 15% and for stroke from 33% to 17%. Age and gender adjusted mortality rates decreased by up to 70% over time.
The use of composite endpoints has increased markedly over the past 25 years. This has been associated with larger studies with older patients followed for a longer period of time. Despite these trends, the chance of a study demonstrating a positive result has diminished markedly. Better understanding of how the use of composite endpoints affects the outcome of trials is clearly needed.
Poster Sessions, Expo North
Saturday, March 09, 2013, 3:45 p.m.-4:30 p.m.
Session Title: AMI and PCI
Abstract Category: 28. Quality of Care and Outcomes Assessment
Presentation Number: 1158-104
- 2013 American College of Cardiology Foundation