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Post-ISCHEMIA: Focus Turns to Testing for Stable Angina

— Stress test no longer enough to send most stable cases to cath lab?

Last Updated December 13, 2019
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PHILADELPHIA -- After the ISCHEMIA trial delivered its clear determination that early revascularization isn't better than medication alone for moderate-to-severe, but stable, heart disease, cardiologists saw little "reperfusion injury" for their practice overall.

"Everyone sees what the they want to see," Gregg Stone, MD, of the Icahn School of Medicine at Mount Sinai in New York City, , while Robert Yeh, MD, MBA, of Beth Israel Deaconess Medical Center in Boston , "Everything I believed yesterday, I believe even more strongly today."

Still, there were many others here at the American Heart Association (AHA) meeting who concluded from the seminal trial that important changes are needed in the upstream testing that leads patients to this juncture in their care and in how aggressively to proceed.

"We have real proof that revascularization does not appear to have a marked effect on the natural history of stable ischemic heart disease," said James de Lemos, MD, of UT Southwestern Medical Center in Dallas. "I think the downstream implications of this with regard to noninvasive testing are massive."

"I think that is more where we will see it in our practice. Many of us as, a result of [Orbita] and COURAGE, have become more conservative inherently, but this will have major effects on cardiac testing," he stated.

The Best Gatekeeper?

The trial included 5,179 stable patients who had moderate or severe ischemia on clinically-indicated nuclear, echo, cardiac MRI, or exercise tolerance testing confirmed by coronary CT angiogram (CTA), which also ruled out unprotected left main disease.

Of the 3,339 screen failures, more than half were due to insufficient ischemia and most of the rest were due to no obstructive coronary artery disease found on CTA.

Since randomization to routine early revascularization or continued optimal medical care alone didn't make a difference on outcome, "it does beg the question of whether the stress test as a gatekeeper is that useful," said Athena Poppas, MD, of Brown University in Providence, Rhode Island.

"Are we doing too many stress tests on these patients who have moderate or mild symptoms -- one episode of angina per month? That's a big question. Maybe it's more important to rule out left main with CTA," said Roxana Mehran, MD, also of Mount Sinai.

"This will change practice, because at the moment most of these patients are landing in the cath lab and we're expected to fix them," she added.

Stress tests are still needed to screen whether symptoms are coming from ischemia, but shouldn't be enough to send patients to the cath lab, even in high risk cases, concluded Poppas.

"We all worry about patients who have a very positive stress test dropping dead or having a heart attack in short order," noted Judith Hochman, MD, of NYU Langone Medical Center in New York City, in discussing the main findings she presented at the AHA meeting. "The point here is these patients were treated with medication. Between the stress test and enrollment, they were treated, which means that stabilizing the plaque is really, really important."

"Trying to get patients to actually comply with risk factor modification and medications is absolutely our goal, should be our goal, in terms of the medical community going forward," she stated.

With this strategy, only 28% of the patients in the conservative group got cardiac catheterization and only 23% got revascularization by 4 years in the trial.

"Watchful waiting is as good," Poppas concluded.

The trial did show a quality of life (QoL) advantage to early invasive management but only for those with angina, as the revascularization arm had greater freedom from angina.

"After you optimize the medicines, if it bothers them, or they don't even like taking the medicines...at least the patient understands the trade-off, they want to be relieved of the angina, that's great," said John Spertus, MD, MPH, of St. Luke's Mid America Heart Institute in Kansas City, who presented the QoL data at the AHA meeting. "You could never have done that with confidence without these data to support that really there's no difference in death out to 4 years plus."

"The practice pattern seems simple and we should not lose the forest for the trees here," he added. "Health status and quality of life is important to our patients."

Left Main Disease

The only conundrum is how to ensure that patients don't wait on revascularization if they have left main disease, which has been shown to clearly benefit from it, noted Alice Jacobs, MD, of Boston University.

Based on the number of people excluded from ISCHEMIA, taking all-comers would leave about 5% with prognostically significant left main disease, noted Darshan Doshi, MD, of Massachusetts General Hospital in Boston.

Changing practice patterns to incorporate CTA upfront "if that's available might be reasonable" to rule it out, Jacobs said.

Another possibility, Poppas suggested: "It may be in the future that, on the heels of or PROMISE, that coronary CT with fractional flow reserve would answer a lot of questions."

U.K. groups , noted Ajay Kirtane, MD, of of New York-Presbyterian/Columbia University in New York City.

Cost and access are issues, commented E. Magnus Ohman, MBBS, of Duke Clinical Research Institute in Durham, North Carolina. "The other fear in this country is the radiation exposure. Even though that's been mitigated, it's a concern especially in women. Repeated CT test is a driver. There is some downside."

New U.S. guidelines are underway, said Glenn Levine, MD, of Baylor College of Medicine in Houston. The American College of Cardiology and American Heart Association chest pain writing group, and the revascularization guideline writing group, have documents in the works that will presumably incorporate ISCHEMIA, he suggested.

Another next step is to expedite a tool for shared decision-making to explain the findings to patients, noted Elliott Antman, MD, of Brigham and Women's Hospital in Boston.

Long-Term Perspective

High on the priority list, too, is ensuring funding to continue to follow ISCHEMIA patients, a number of cardiologists at the AHA meeting said.

For both the primary composite of cardiac events and the key secondary of MI and cardiovascular death, the curves crossed over at about 2 years, with an absolute 1.9% more events in the first 6 months and 2.2% fewer at 4 years compared with optimal medical therapy alone.

The early difference looked like it was primarily driven by periprocedural MI, whereas "it looked like they were continuing to diverge in favor of an invasive approach," commented Doshi. "If patients were actually followed out longer, perhaps at statistically significant difference in favor of an invasive approach might be reached."

A similar pattern has been seen before, noted Kirtane, pointing to STICH, STICHES, and EXCEL.

"Any randomized trial of bypass surgery versus medical therapy, they all show exactly the same curves: early risk, later benefit," Ohman agreed.

"The late change makes me believe wholeheartedly that we cannot walk away without understanding what's next," Mehran said. "'ISCHEMIA LATE' now becomes the most important trial we must absolutely get done."

Hochman "There's been a lot on social media about the $100 million spent. We calculate that if asymptomatic patients didn't get PCI, we would save over $500 million every year. ...I believe it was money well invested."