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FT. LAUDERDALE -- Clinical trial researchers tend to give equal weight to the components of a composite endpoint, but patients see things differently, researchers found.
In the SYNTAX trial, for example, the composite endpoint included death, stroke, nonfatal myocardial infarction (MI), and target vessel revascularization (TVR), Peter K. Smith, MD, from Duke University Medical Center, explained at the annual meeting of the Society of Thoracic Surgeons.
If a patient experienced any one of them, it counted toward the major adverse cardiac and cerebrovascular events (MACCE) rate.
But if those individual components do not carry equal importance to patients, any data that rely on this assumption could be faulty, Smith said.
So he and his colleagues surveyed 244 people (62% men) to see whether they would rank some of the components of the SYNTAX composite higher than others if deciding between coronary artery bypass grafting (CABG) and stenting. They also asked about two non-MACCE factors that might impact one's choice: extent of procedure, hospitalization, and recovery time; and potential for increased longevity.
The patients, it turned out, were far more concerned about the risk of death than any other outcome, giving it a relative weight of 0.23. Stroke came in second (relative weight 0.18) and even long-term outcome and recovery time (each 0.17) counted more than MI or TVR.
In fact, the composite factor that least concerned those surveyed was TVR (relative weight 0.11), even though the number of TVRs in the SYNTAX trial -- which found coronary artery bypass grafting (CABG) superior to stenting -- propelled its high MACCE rate, Smith, told MedPage Today.
Despite the positive results for CABG, many people focused on the higher rate of stroke associated with CABG and concluded that percutaneous coronary intervention (PCI) was equally as good.
The survey was an online questionnaire, and the scenario presented would make respondents eligible for the SYNTAX three-vessel disease cohort.
Nearly half of the respondents reported a known history of coronary artery disease and MI. Three-quarters had hypercholesterolemia and hypertension. Other risk factors included arrhythmias, angina, and peripheral vascular disease.
Nearly two-thirds had undergone cardiac catheterization, 43% had undergone PCI, 28% had undergone CABG, and 12% had undergone PCI and CABG.
The researchers applied the relative weights of the MACCE elements to the results of the SYNTAX trial. They then calculated a normalized adjustment factor for each of the MACCE elements. When they recalculated the MACCE using the normalized adjustment factor, the difference in MACCE decreased from 8.6% to 5.9%, co-author Betty C. Tong, MD, MHS, reported.
"This is due to the relatively lower importance of repeat revascularization, which accounts for much of the difference in MACCE between CABG and PCI," she said.
Recalculating the SYNTAX three-year outcomes also resulted in a decrease in MACCE between CABG and PCI from 13% to 10.1%. Tong noted that the 10.1% difference is still greater than the trial's noninferiority margin and 95% confidence interval of 8.3%.
"This reinforces the conclusion that CABG is superior to PCI for patients with three-vessel disease," she said.
Another interesting result of the survey was that respondents overwhelmingly chose "CABG" over "PCI" even when those procedures were not given specific labels (87% versus 13%). Their choice was based on the reduced risk of death and MI associated with CABG, as well as an expected one-year longer life expectancy compared with no change in life expectancy after PCI.
The stroke rate presented to them was three out of 100 patients for CABG and two out of 100 patients for PCI.
But when researchers spelled out "coronary bypass procedure" and "coronary stent procedure," the choice for CABG dropped to 73%, while that for PCI increased to 27%.
"There is a bias against CABG in the population," Smith said.
Overall, the investigators concluded that "assigning relative weights to the elements of the composite endpoint strengthens the validity of the statistical analysis and conclusions."
They added that future use of these relative weights may "obviate the need for establishing noninferiority margins and provide a more accurate comparison of treatment modalities."
The study was sponsored by the National Heart, Lung, and Blood Institute.
The authors reported they had no relevant conflicts of interest.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Society of Thoracic SurgeonsSource Reference: Tong B, et al "Patient preferences in coronary revascularization: Redefining clinical trial endpoints" STS 2001.