PCI for Preventing Death in Unstable vs Stable CAD: New Data, More Soul-searching

For all subtypes of unstable coronary artery disease, PCI prevents death, cardiac death, and MI, according to a comprehensive, updated meta-analysis—one that incorporates new data from the ISCHEMIA and COMPLETE trials. But for patients with stable CAD, “PCI shows no evidence of an effect on any of these outcomes,” write Liza Chacko, MBBS (Imperial College London, England) and colleagues.

The aim of the study, according to senior author Yousif Ahmad, BMBS (Columbia University Irving Medical Center, New York, NY and Imperial College, London), was to clarify the different categories of unstable CAD as they’ve been defined in prior academic and clinical scenarios, and to distinguish the impact of PCI in these settings from “truly” stable CAD, he said.

This is particularly important given some of the confusing headlines in the lay press that reported on trials like ISCHEMIA and ORBITA. Some stable CAD trials in the past have also included patients that today are accepted as unstable, such as STEMI patients who don’t get immediate revascularization but are treated in the outpatient setting. “We wanted to lay things out as simply as possible and try and make the different categories very clear, to give physicians and patients a bit of a framework for how to proceed.”

Published this week in Circulation: Cardiovascular Quality and Outcomes, the paper by Chacko et al is accompanied by four intersecting commentaries that drive home the nuances of extrapolating clinical trial data to individual patients. The first, a patient perspective by renowned investigative journalist Bob Dreyfuss, describes the speed with which Dreyfuss’s own diagnosis of stable, mostly asymptomatic heart disease saw him heading for urgent CABG, leaving him no time for research and second opinions. The viewpoint, entitled “It Happened So Fast . . . I Guess, Yes, I Was Lucky,” is accompanied by two clinical commentaries taking opposing views and a perspective by the journal’s editor, Brahmajee K. Nallamothu, MD, MPH (University of Michigan Medical School, Ann Arbor).

Speaking with TCTMD, Nallamothu explained that the journal received the Dreyfuss perspective around the time that ISCHEMIA came out at the American Heart Association 2019 Scientific Sessions. The Chacko analysis, updated with the (unpublished) ISCHEMIA trial data, came in shortly thereafter. With Dreyfuss’s blessing, editors solicited the two clinical commentaries as well as Dreyfuss’s clinical records to verify parts of his viewpoint, ultimately deciding to package all five pieces together.

“I don’t think the findings [of the meta-analysis] are a shock,” Nallamothu said. “There are earlier studies that suggest the same thing, but in light of ISCHEMIA we felt it was such an important study that updating the current level of evidence with a systematic review was warranted. Then when we saw these commentaries come together, we thought it would be nice to put all of these in the same issue.”

Updated Meta-analysis

For their analysis, Chacko, Ahmad, and colleagues combined data from 46 randomized, controlled trials of PCI versus medical therapy for a total of 37,757 patients. Unstable CAD patients were further subcategorized as patients post–MI who did not undergo revascularization, patients who had undergone primary PCI for STEMI but had other nonculprit coronary lesions, or patients with NSTE ACS. Patients with truly stable CAD and no recent infarct made up the fourth category.

For the primary endpoint of all-cause mortality, PCI significantly reduced deaths in all three unstable categories combined (RR 0.84; 95% CI 0.75-0.93), but had no significant impact on patients with stable CAD (RR 0.98; 95% CI 0.87-1.11). PCI also reduced cardiac death (RR 0.69; 95% CI 0.53-0.90) and MI (RR 0.74; 95% CI 0.62-0.90) in the unstable CAD patients. Again, no reduction was seen for either secondary endpoint in the stable CAD group.

“I think this reemphasizes what we have known for a few years, which is for stable coronary disease, PCI—with the exception of left main disease revascularization—should be reserved for symptomatic benefit,” Ahmad said. “We've seen that in COURAGE, we've seen that in ISCHEMIA (and all of these trials have caveats), but if you look at the totality of data, there's not a sign that PCI improves these hard outcomes in what is truly stable disease. But you have to be sure that the patient in front of you falls into that category and does have truly stable disease: for those patients, we have to be a bit more circumspect and we can't offer PCI on the assumption it's going to improve prognosis.”

Urgency is Scary

It’s that needed circumspection that Nallamothu highlights in his editorial, making the point that ISCHEMIA, like other trials before it, has already fallen victim to the Rashomon effect, wherein different groups of people have interpreted the same results in conflicting ways. “Whether you favored an initial invasive approach or a conservative approach before the ISCHEMIA trial, there is something in these results for you to hang on to in your clinical practice,” he writes.

Moreover, the debate about the trial and its interpretation has occasionally turned rancorous online, Nallamothu notes. In the pages of the journal, by contrast, the counterpoint commentaries—one by William Boden, MD (VA New England Healthcare System, Boston, MA), and John Mancini, MD (University of British Columbia, Vancouver, Canada), and the other by Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, NY), hint that there is more common ground between the typically polarized stances on ISCHEMIA than social media might suggest. “Many of you,” writes Nallamothu, “will nod along with several parts of both Clinical Commentaries.”

While Boden and Mancini argue for better systems that allow for more-informed, shared decision-making, Kirtane makes the case that applying the ISCHEMIA trial in practice is not as straightforward as it seems, with the Dreyfuss viewpoint serving as a sobering reminder.

We need to change the conversation around stable coronary artery disease: we need to make it less about a sense of urgency and more about decision-making, because otherwise all our attempts to try and involve patients in these really complex choices will consistently fail. Brahmajee K. Nallamothu

“I have to be honest,” Nallamothu told TCTMD, “Mr. Dreyfuss asked me a couple times, ‘What would you have done if you had seen my case?’ And I think, with this extent of CAD, I would have recommended revascularization almost invariably unless he had suggested otherwise. The reason I think the paper by Ahmad and colleagues is important is that for too long we’ve been almost scaring people towards some kind of urgency that’s really affected our ability to do good, fair decision-making in chronic stable coronary artery disease.”

Ahmad noted that the findings of the meta-analysis are already supported by international guidelines and, in the case of revascularization for nonculprit lesions in STEMI, are already expected to get a stronger endorsement in the next update. The subcategory of patients with STEMI who don’t get urgent revascularization is “an odd group,” he acknowledged, mostly represented in outdated clinical trials and not seen today in clinical practice. The bigger unknown, he added, is what further information will come out of the in-depth analysis of MI subtypes in ISCHEMIA. Their meta-analysis, he noted, did not differentiate between periprocedural and spontaneous MI, but that data are eagerly awaited.

Nallamothu hopes people will read all five of these articles in this month’s issue, starting with Dreyfuss, who writes with a compelling mix of wonder and uncertainty about the events that quickly befell him last year. Then, said Nallamothu, there are two lessons he hopes physicians take with them when they’ve finished all five.

“One lesson is that we need to change the conversation around stable coronary artery disease: we need to make it less about a sense of urgency with decision-making, because otherwise all our attempts to try and involve patients in these really complex choices will consistently fail,” Nallamothu told TCTMD. “So we need to really understand that there is a difference between stable CAD and unstable CAD and we need to have those conversations more broadly as a society.”

The second lesson, he continued, is that these kinds of discussions can be tough. “I think there’s a role for social media in the kind of rapid discussion about trials, but there is also a role for more-thoughtful discussion. And sometimes when you can find patients who are brave enough to share these stories, this creates a kind of respectful tone, allowing for some longer forms of dialogue and conversation. I think [that] can really make us move forward because I’m not sure our differences are as stark as they sometimes seem on Twitter.”