Procedural MIs Have Little Effect on Quality of Life: ISCHEMIA

While spontaneous MIs are associated with worse quality of life both early and late, procedural MIs don’t appear to have a lasting impact on disease-specific quality of life, according to new data from the invasive-management arm of the ISCHEMIA trial.

The findings, published online recently in JACC: Cardiovascular Interventions, add to debate over the prognostic relevance of procedural MI (PMI)—with data from last year showing that many of these events are not predictive of future outcomes—and should largely put any clinical worries over the issue to bed, researchers say.

“This is another example of a nonfatal event that is defined by physicians and measured by physicians but has no effect on patient quality of life [or] well-being,” lead author Mario Gaudino, MD, PhD (NewYork-Presbyterian/Weill Cornell Medicine, New York, NY), told TCTMD. “It’s an event that is of interest to physicians, but it’s not of interest to patients.”

As such, he said, PMI should no longer be used as a clinical endpoint in trials.

“In the end, the patients want to know not only how long they will live after an intervention, but also how well. They don’t really care about perioperative MI, spontaneous MI, or repeat revascularization—those are all metrics that we physicians have created, and we physicians give them relevance,” Gaudino said.

Instead, quality of life (QoL) should be given higher priority by researchers, he urged.

John J. Atherton, MBBS, PhD, and Sandhir B. Prasad, MBBS, PhD (both Royal Brisbane and Women’s Hospital, Herston, Australia), in an accompanying editorial, say that, in their view, the issue of whether PMI matters is not yet settled, but that the new data give more insight.

“Although PMI may be regarded an inevitable complication in some patients, and its prognostic significance continues to be debated, it is reassuring to know that there appear to be no long-term adverse consequences in terms of QoL in a population with an otherwise low event rate,” they write. “These findings should be weighed up in the context of the broader risk-benefit calculus of PCI, in keeping with the Hippocratic tradition of nonmaleficence.”

A History of Controversy

There has been a history of controversy around the clinical significance of PMI outcomes, with some cardiologists and researchers saying the endpoint simply creates a lot of “noise” in trials. It can be defined using the Third Universal Definition, as it was in ISCHEMIA, but there are several others available with different thresholds for cardiac troponin/CK-MB elevations and clinical criteria.

Depending on the definition used, PMI can vary between PCI and CABG. The EXCEL trial, which compared PCI to surgery for patients with left main coronary artery disease, came under intense scrutiny several years ago when the investigators were accused of not reporting the higher rate of procedural events with PCI.    

ISCHEMIA was a large-scale randomized trial that found no difference in outcomes between an invasive strategy with PCI or CABG and optimal medical therapy in patients with stable coronary artery disease. In one analysis, the primary endpoint swung in favor of the conservative strategy depending on the MI definition, with more PMIs seen with the invasive approach. However, more spontaneous MIs (SMIs) were reduced with the invasive strategy. 

To assess the impact of different MI types on quality of life, researchers analyzed 4,375 patients from ISCHEMIA who were randomized to an invasive strategy, with 61% receiving PCI, 20% undergoing CABG, and 20% not having the planned revascularization. These patients were then followed for a median of 36.2 months, over which 84 PMIs and 352 SMIs were recorded.

Quality of life as measured by both the European Quality of Life-5 dimensions visual analog scale (EQ-5D VAS) and Seattle Angina Questionnaire (SAQ-7) summary score decreased following an SMI both within 3 months (early) and after (late). Only the SAQ-7 results dropped in the early period for PMI, with no reductions observed in the late period or at all as measured by the EQ-5D VAS.

QoL Measures Over Time: Adjusted Change in Points (95% CI)

The new data “explore if what we define as a clinical event—in this case, myocardial infarction—has any effect on patient wellbeing and patient quality of life,” Gaudino said. “What we found is that whereas spontaneous or nonprocedural myocardial infarction does in fact affect the quality of life of patients, . . . this is not true for periprocedural myocardial infarction.”

Notably, he added, the ISCHEMIA trial used both the Third Universal Definition of MI as well as a trial-specific definition, “and the findings were consistent” for both.

During the debates around EXCEL, “we all of a sudden realized how difficult it was to define myocardial infarction, and in particular perioperative myocardial infarction,” said Gaudino. “With the new diagnostic tools being available, better imaging, now we can really diagnose even very small changes compared to normal or to baseline.”

What this means for patients, though, is “totally unclear,” he continued. “I still do not have an answer for what is the best definition of PMI.” During the EXCEL controversy, said Gaudino, he and EXCEL principal investigator Gregg Stone, MD, “disagreed on the key points, but we both agreed on the fact that it was really difficult to define a nonfatal event, and that was generating a lot of confusion.”

‘Both Sides’

For C. Noel Bairey Merz, MD (Cedars-Sinai Heart Institute, Los Angeles, CA), however, the new data don’t “really add that much.” The study is biased from the outset, she argued, given that quality of life is inherently worse when patients experience MI symptoms that drive them to seek care compared with being told they had an enzymatic rise during a procedure.

The new study “feathers the nest for the interventional cardiologists” who have argued that these enzymatic, “drive-by MIs” are insignificant to the patient, she told TCTMD. “It’s really supporting their contention that, ‘Hey, this is nothing. We don’t need to worry about these.’”

Still, Bairey Merz said, PMIs come in many permutations, and it remains “controversial” whether the smallest ones are prognostically important.

“You can argue both sides, and there’s data to support it,” she said. While the researchers argue that PMIs don’t lead to reduced quality of life like SMIs do, “a better assessment of this would be: how about undergoing a PCI versus not undergoing a PCI? How is that quality of life? I bet it’s worse with the PCI.”

Because clinical trials have faced increasing difficulty showing significant improvements in mortality rates with revascularization versus optimal medical therapy, which “works very well,” Bairey Merz agreed that it’s “valuable” to look at quality of life.

That discussion, though, can only contribute so much to the decision of whether to undergo an intervention or not, she added. More would be gained reporting quality-of-life outcomes within the ISCHEMIA trial every 3 to 6 months to assess whether there were any noticeable effects before an SMI.

Interventional cardiologists and surgeons should ultimately care about quality of life, but in clinical research, it’s important to pay attention to the “angle” of why it’s included, Bairey Merz cautioned. With trials like ISCHEMIA not showing any difference in hard clinical outcomes, academics now must grapple with whether to move on to other endpoints.

Indeed, Gaudino is currently leading the RECHARGE trial comparing CABG and PCI in underrepresented minority patients. It includes a new primary composite endpoint that combines time-averaged quality of life with mortality and is analyzed using the win ratio.

“The next step for the cardiovascular community is to listen more to patients and try to design trials that provide the information that patients want—and also that patients need—to make an informed decision,” Gaudino said. “If we provide them only with the information that we physicians believe they need, it’s not really an informed decision.”