August 9th, 2011
Will ISCHEMIA Tell Us More than COURAGE? PART II: Banking on Eight Years of Equipoise
Judith Hochman, L. David Hillis, MD and Richard A. Lange, MD, MBA
(Continued from Part I: Aiming to Beat Bias with Blinding)
On August 1, 2011, the Langone Medical Center at New York University announced that the National Heart, Lung, and Blood Institute has provided a grant to fund the ISCHEMIA study of an invasive strategy versus optimal medical management in patients with stable coronary artery disease and moderate-to-severe ischemia. We welcome the members of the study Executive Committee, chaired by Dr. Judith Hochman, to answer questions posed by L. David Hillis and Richard Lange, the co-moderators of the Interventional Cardiology blog on CardioExchange. The other members of the committee are William Boden, Gregg Stone, Bob Harrington, Bruce Ferguson, David Williams, and David Maron.
Hillis and Lange: How will you assess the accuracy of the noninvasive studies (nuclear imaging, stress echo, cardiac MR perfusion) for determining the presence and extent of ischemia?
ISCHEMIA Executive Committee: It is critical to the success of this trial that patients who are enrolled have a sufficient degree of ischemia to test the study hypothesis. Therefore, all stress imaging studies will be initially reviewed by a core laboratory prior to confirmation that the patient is eligible to participate in the trial. Once a site has demonstrated its concordance with core lab interpretations, it will be able to enroll patients before core lab confirmation, although we will continue to monitor the accuracy of site interpretations during enrollment.
Hillis and Lange: “Optimal” medical therapy is often in the eye of the beholder. Will it be prescribed for all patients? What will it be?
ISCHEMIA Executive Committee: We use the term optimal medical therapy (OMT) to indicate lifestyle and pharmacologic interventions that are intensive and evidence-based. OMT in ISCHEMIA will be very similar to what was delivered in COURAGE. It will be applied in both the invasive and conservative treatment strategies. Bill Boden and David Maron co-chair the optimal medical therapy committee. Behavioral interventions will focus on smoking cessation, nutrition, physical activity, weight control, and medication adherence. Pharmacologic interventions will be anti-atherosclerotic and anti-ischemic, in keeping with ACC/AHA/ESC guidelines.
Hillis and Lange: What are the participation criteria for the 150 medical centers in the U.S. and hundreds of sites in 33 countries worldwide that will be enrolling patients? Are there criteria regarding revascularization outcomes?
ISCHEMIA Executive Committee: The most important criterion is that cardiologists at a participating site have clinical equipoise and are therefore able to enroll adequate numbers of patients with at least moderate ischemia. The other important considerations are volume and mortality statistics for PCI (≥400/year per site; in-hospital mortality <1.5%) and CABG (≥125/year per site; non–risk‐adjusted in‐hospital mortality <3.0%), access to a coronary CT angiography facility, and the ability to transmit images electronically. We invite primary care and cardiology practices to contact us if they want to participate as enrolling sites.
Hillis and Lange: What is a realistic time for enrollment, and when should we expect to see results?
ISCHEMIA Executive Committee: We anticipate that enrollment will begin in 1 year and will continue for approximately 4 years. The average duration of follow-up will be 4 years. Results will be available in 8 years.
4 Responses to “Will ISCHEMIA Tell Us More than COURAGE? PART II: Banking on Eight Years of Equipoise”
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What is the „sufficient degree of ischemia to test the study hypothesis”? How is it defined? My question comes from http://blogs.jwatch.org/cardioexchange/journal-club/have-the-courage-to-critique-a-substudy/ where Sanjay Kaul expertly refers to clinical importance of various ischemic thresholds. Will it be >10% ischemia or something else? Is there any role for FFR measurement in the study?
On behalf of the ISCHEMIA Study Leadership:
The threshold severity of ischemia is defined as ≥10% on nuclear perfusion imaging, ≥12% on cardiac MR perfusion imaging, and ≥3/16 segments with stress-induced severe hypokinesis or akinesis on echo or cardiac MR. FFR will be required when PCI is considered for a stenosis <70% by visual estimate when there is no ischemia in the lesion distribution on stress imaging. Revascularization will be recommended in this circumstance if FFR ≤0.80
I am interested to know whether there would be a CABG arm in the trial, as well. Moreover, it would be nice if within the PCI group, patients would randomly receive PCI with, versus without intravascular ultrasound guidance (to see if detection of vulnerable plaques could be of clinical help).
Competing interests pertaining specifically to this post, comment, or both:
None
On behalf of the ISCHEMIA Study Leadership:
There will not be a CABG arm per se, but CABG will be considered by the local Heart Team for patients with multivessel disease. An algorithm, based largely on SYNTAX, was developed with recommendations for best method of revascularization. We are very interested in the research question about vulnerable plaques and are considering non-randomized study designs to answer this question.