Best Strategy Questioned for NSTE ACS Patients With Prior CABG

Patients who’ve undergone CABG and go on to develop non-ST-segment elevation ACS may do just as well with medical therapy as they do with an invasive strategy, but the question won’t be settled unless a larger, randomized trial is done, say the authors of a pilot study.

Matthew M.Y. Lee, MBChB (Golden Jubilee National Hospital, Glasgow, Scotland), and colleagues assert that despite the challenges of studying this group, their findings highlight the need to identify the best treatment approach in these patients, who are typically older with multiple comorbidities and whose acute presentation may not ultimately benefit from PCI.

Both European and American guidelines for the management of NSTE ACS give invasive management a class I (level of evidence A) recommendation, but patients with prior CABG were typically excluded from the trials that support that guidance, senior author Colin Berry, PhD (British Heart Foundation Glasgow Cardiovascular Research Centre), told TCTMD.

“The standard of care for these patients is invasive management, and my observation as a practicing clinician in cardiology wards and also in the cath labs is that these patients are referred for invasive management, they undergo invasive management, and in at least half of those procedures, PCI is not performed, and certainly not redo CABG,” Berry said. “So that calls into question whether invasive management should be the default approach.”

Lee, Berry, and colleagues reported the findings from the CABG-ACS pilot study online July 31, 2019, in Circulation: Cardiovascular Interventions.

How Care Plays Out

The CABG-ACS trial prospectively screened 217 patients with NSTE ACS and prior CABG at four hospitals in Scotland, ultimately randomizing 60 patients to invasive management or medical therapy. The sheer number of patients not randomized—now being followed in a registry—is itself telling, Berry noted. In all, 73 “potentially eligible patients” were not randomized because either the physician or patient had “preheld views” as to which was the better strategy.

“The attending physician would say no, in my opinion this patient needs an angiogram or in my opinion this patient should not have an angiogram,” he said. In some cases, the patients would decline to participate. “Patients and physicians have views as to how care should play out.”

Commenting on the results for TCTMD, Tracy Wang, MD (Duke Clinical Research Institute, Durham, NC), also noticed the high proportion of patients never randomized in what she characterized as a feasibility study. “I think the key knowledge gap here is the group of patients who were excluded from the trial [but were] in the registry because of either physician or clinician preference. This is more than half of screen successes, suggesting a strong lack of equipoise, and it would have been interesting to see their revascularization patterns and outcomes in comparison to each of the randomized groups,” she explained.

To TCTMD, Berry confirmed that he and his colleagues have also done an analysis of outcomes among the nonrandomized patients and have submitted the results for publication.

That calls into question whether invasive management should be the default approach. Colin Berry

At 2 years, the composite outcome for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, or hospitalization for heart failure) had occurred in 13 patients in each group, while a full 55% in both groups met the composite endpoint for safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function).

The event curves, said Berry, were “completely overlapping” over the course of the 2-year follow-up.

Of note, a culprit lesion was identified in only half of the invasively managed patients and just one-third proceeded to PCI. The choice to not intervene in some of these cases likely relates to the complexity of the coronary disease or the burden of comorbidities in these older patients—mean age 71, Berry said. Nearly 70% of the patient population had had a prior MI and the cause of their NSTE ACS may be the “eventual occlusion of a chronically diseased graft or a mismatch in myocardial blood supply,” the authors write.

The fact that so few patients headed to PCI may to some extent reflect the fact that this study was launched in 2012, Berry acknowledged to TCTMD. Today, he continued, “we might see a higher proportion of patients being revascularized with optimal PCI, CHIP techniques, but in this real-world study, only one in three of these invasively managed patients actually received PCI.”

The lack of crossovers is also worth noting, Berry said. Only one patient crossed over in 30 days (at day 30) and that patient was ultimately not treated percutaneously. “In this patient population, focused on older patients with multimorbidity, which is in fact the population of postbypass patients who are presenting, they did well with medical management and there were no crossovers. So that speaks to success of the noninvasive strategy.”

So, would the findings be relevant today, given advances in techniques and devices over the last 7 years?

“They absolutely, definitely remain current,” Berry said. “My friends in the CHIP community have to demonstrate the benefits of those advances, and at this time, [they’re] not proven. I do hope, in the interests of patient well-being, that [research] will demonstrate benefits from an interventional approach. I'm all for that.”

Commenting on the study for TCTMD, Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY)—emailing en route to the CHIP meeting in Seattle—said it was “hard to draw any conclusions” from the study, given the sample size, geographical differences in practices, the high event rates, and the delay between randomization and first procedure in the invasive-management group (a median of 13 days). “In addition, the lack of an identifiable culprit lesion in almost half of the patients is surprising,” Kirtane wrote. “I suspect that the outcomes would be different in patients with culprit graft lesions, which would be very difficult to randomize.”

Patients with prior CABG, Kirtane continued, are among some of the highest-risk patients to treat. “I find it very hard to establish equipoise in the treatment of such patients who are presenting acutely with true MIs and a degenerating vein graft, for example. The natural history of SVG disease is very different from that of native coronary lesions, with much higher event rates through progression to occlusion, which can often result in large MIs and subsequent ventricular dysfunction,” he said.

Wang, for her part, called the 2-year outcomes between the two randomized groups in CABG-ACS “difficult to interpret as the study was not powered to assess these.”

She added: “I agree with the authors that a large randomized trial of prior CABG patients will be logistically challenging, as there is very little equipoise.”

A Tough Trial

Speaking with TCTMD, Berry acknowledged he had been “anxious about doing this study,” given the widely held views that these patients need urgent interventions.

Funding for this pilot trial, for example, was denied on the grounds that randomizing these patients was unethical, which reinforced the lack of equipoise as to the best management strategy for these elderly, often very ill patients.

But the fact that so few patients proceeded to revascularization, and that there were no differences in outcomes between groups, supports the need to move forward with a larger trial, said Berry. “This was an engaging study to deliver and I had to spend a lot more time with patients and their families than one might normally do, and that just reflects the age and chronic health problems of this population,” Berry told TCTMD. “It was not by any means a straight shot to deliver this trial. I describe it as a labor of love.”

And if a future trial confirms no difference in outcomes between a conservative versus an invasive approach, potentially sparing these patients an invasive test, that would justify the difficulty of doing such a trial, he insisted. “That's what our study is saying, but we still believe there's a definite place for an intervention in those patients that need it. A large trial would allow us to deep dive to try to risk stratify and give clinicians and patients the knowledge they need to identify the person who really does need a cath and is likely to need PCI.”