New data presented at EuroPCR from the much debated ORBITA trial may provide some modest temporary lessening of the pain felt by interventional cardiologists in response to the initial negative ORBITA findings.
But the pain relief is likely to be only temporary, and might even be fairly compared to a placebo effect, since the major finding of ORBITA, that PCI for stable angina almost certainly sparks a large placebo effect, remains unchanged. In their efforts to prop up the flow of PCI potentially clogged by the ORBITA findings, the interventional cardiology community is still seeking to avoid the new reality that the placebo effect in stents is real and must be taken into consideration both in clinical practice and in future trials.
At EuroPCR Rasha Al-Lamee (Imperial College London) presented a series of secondary analyses from ORBITA. (The findings were published simultaneously in Circulation.) The analyses were designed to provide more context to the most striking main finding of the placebo-controlled ORBITA trial, which was that although PCI in single vessel stable angina resulted in a significant improvement in blood flow as measured by stress echocardiography, this did not result in a significant improvement in symptoms, as measured by exercise time.
The new analysis presented by Al-Lamee addressed one of the main criticisms of ORBITA, which was that patients were randomized without regard to the physiologic status of their vessel. ORBITA did obtain FFR and iFR measurements in study patients but operators were blinded to these results, since one goal of the trial was to obtain a cut-point for angina relief. (The patients had already been found to have clinical indications for PCI and had angiographically significant lesions.) Critics of the trial predicted that the trial would have been positive in a patient population with low FFR/iFR values.
But PCI defenders could only find small relief in the physiology-stratified analysis of ORBITA presented by Al-Lamee. One positive finding in favor of PCI was that FFR and iFR were able to predict the placebo-controlled effect of PCI on stress echocardiography. However, FFR and iFR were unable to predict the effect of PCI on exercise time or symptoms, thereby dashing the hope that FFR/iFR might “save” stents from ORBITA.
In another secondary analysis, PCI-treated patients were more likely to report that they were angina free than placebo-treated patients (49.5% versus 31.5%, p=0.006), though Al-Lamee cautioned that this was not a prespecified analysis, and no significant difference was found in the Seattle Angina Questionnaire score, which was a prespecified secondary endpoint.
In an interview, Al-Lamee said it was reasonable for physicians to tell their patients that PCI for stable angina can “improve blood flow to the heart.” But, she emphasized, the trial found no evidence that FFR or iFR can be used to identify patients who are most likely to benefit from PCI.
In a series of tweets Robert Yeh tweeted that the message of ORBITA is not that “PCI doesn’t work.” Instead, he offered a more nuanced perspective: “PCI improves angina, but it’s effect is a combination of reality and perception. Patients will be more likely to be angina-free after PCI.”
Yeh also noted the significance of the FFR/iFR findings: “There’s no clifff!!!!” The finding means that “FFR will not help identify who’s going to feel better with PCI.” Further, he advised, “measuring an FFR is not a substitute for a careful history.”
Finally, Yeh pointed to what is likely to be an active area of research in the next few years. “Symptoms are tricky,” he wrote. “They don’t correlate with our tests for ischemia, and don’t go away the most when we relieve the most ischemia.”
This article has been republished from Larry’s blog CardioBrief as part of a licensing agreement between Everyday Health and the limbic.