This interview was recorded on November 16, 2019, at the American Heart Association Scientific Sessions and is a collaboration between MDedge and Medscape. It is published on both websites.
This transcript has been edited for clarity.
Tricia Ward: Hi. This is Tricia Ward from Medscape, and I'm here at the American Heart Association with Dr Sripal Bangalore, who just presented ISCHEMIA-CKD. Could you tell us the top-line findings from the trial?
Sripal Bangalore, MD, MHA: Absolutely. We enrolled a group of patients who had advanced chronic kidney disease (CKD), defined as having an estimated glomerular filtration rate < 30 mL/min/1.73 m² or on dialysis and also having moderate or severe ischemia. We randomized them to an invasive or conservative strategy. Our primary endpoint was death or myocardial infarction (MI). We found no statistically significant difference between the invasive versus conservative strategy, either for the primary endpoint of death or MI, or for the major secondary endpoint which was a five-point composite. And in fact, this was true for many of the secondary individual components of the primary endpoint.
Ward: In the invasive strategy group there was quite a number of people who did not get revascularization. Could you speak to that?
Bangalore: In the invasive strategy, 50% of them underwent revascularization. This number is interesting. In the main ISCHEMIA trial, 20% of patients with moderate or severe ischemia who underwent coronary CT angiography (CCTA) were excluded because of nonobstructive disease. We did not have the CCTA requirement so we didn't have that filter.
A number of studies have shown that the sensitivity and specificity of stress testing in advanced CKD is lower, so there are both false positives and false negatives. It's not surprising, therefore, that in patients who underwent cath, 26% had zero-vessel disease, and it's not surprising that patients without coronary artery disease (CAD) were not revascularized. We saw 50%, but we have to keep that number [in perspective] by looking at other trials. In prior trials of acute coronary syndromes—patients coming in with an MI who were randomized prior to defining anatomy—the rate of revascularization was not very high, at 44%-76%. So, 50% [revascularization] is in line with what you would expect if anatomy is not defined upfront.
Ward: One of the other novel aspects of ISCHEMIA-CKD was that you didn't just randomize them to any center for revascularization; you did some initial training to try to minimize the risk for acute kidney injury.
Bangalore: The centers were handpicked to make sure that they had the best quality of revascularization technique, and before they could start enrolling patients, they had to go through a training process. This involved learning strategies for adequate hydration for the patients and for minimal-contrast cath and percutaneous coronary intervention (PCI), so ultra-low volume and zero-contrast PCI.
Ward: In the session, one of the discussants, Dr Glenn Levine, said that maybe we should not look too hard for ischemia, or even CAD, in patients with CKD. What do you think about that?
Bangalore: That is a very interesting perspective which I would tend to concur with if the patient had no symptoms. If they don't have symptoms, maybe we should not look too hard for ischemia or CAD. That being said, we still need to be giving them secondary prevention. Many of these patients do have risk factors: hypertension, hyperlipidemia, diabetes.
Ward: Speaking of prevention, do you still think there is room for improvement in the optimal medical therapy arm?
Bangalore: There is always room, but this is a very challenging population for a number of reasons. We just don't have the evidence base for optimal medical therapy in this group of patients. When we were running the trial, even promoting high-intensity statins was met with a lot of resistance, because for high-intensity statins or statins in dialysis patients, there just aren't robust data. We had to literally convince sites. Our thresholds were different—we said moderate- or high-intensity statins [for patients] on dialysis. And that applies to many of our secondary prevention strategies because there are no data to support saying that 100% of patients should be on it.
Even if we had data saying that we need to optimize their medical therapy, this is a group of patients who have many comorbidities, so it's extremely hard to add on different agents and get their risk factors under control. It's a challenging group of patients. We can always try, but the first step is to start with developing a better evidence base to make sure that the medicines we are giving actually work in this group of patients.
Ward: Do you think we need more clinical trials that enroll patients with CKD or on dialysis?
Bangalore: Absolutely. That is very much needed. Otherwise, we'll continue to do what we have been doing, which is take data from non-CKD patients, apply it to CKD, and hope that it works.
Ward: What do you think are the messages for nephrologists or those who might be referring patients to cardiology?
Bangalore: There are a couple of things to take home from our trial. One is that we enrolled stable patients who were minimally symptomatic, and in those types of patients revascularization or medical therapy did not make a difference. But we showed that upfront procedural risk was low if you have the right expertise. So, it was not patients who are very symptomatic or a patient who comes in with an MI. A common thing in this field is what we call "renalism," where patients who have advanced CKD are being denied what they need because of fear that it will worsen their kidneys. I hope that this trial does not fuel the flames of renalism such that people start withholding therapies in patients who really need them.
Ward: Thank you very much for your time.
Bangalore: Thank you.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: ISCHEMIA-CKD PI Hopes Study Doesn't Fuel the Flames of Renalism - Medscape - Nov 22, 2019.