November 18, 2019 11:25 AM

‘It Did Live Up to the Hype’: Reflections on ISCHEMIA

A highly anticipated clinical trial found no advantage to an invasive strategy for patients with stable coronary artery disease.

Ischemia image

 

ISCHEMIA data isn’t yet published in a scientific journal, but it’s already leading to questioning about when – if ever – patients with stable ischemic heart disease should be taken to the cardiac catheterization lab or the operating room, or if they’ll do as well with medication.

According to the investigators, who presented their results at the November 16 late-breaking science session at the annual American Heart Association meeting: “The trial showed that heart procedures added to taking medicines and making lifestyle changes did not reduce the overall rate of heart attack or death compared with medicines and lifestyle changes alone.

“However, for people with chest pain symptoms, heart procedures improved symptoms better than medicines and lifestyle changes alone. The more chest pain to begin with, the more symptoms improved after getting a stent or bypass surgery.”

Experts from the Michigan Medicine Frankel Cardiovascular Center reflected on the news.

What’s your takeaway from the study?

Kim Eagle, M.D., cardiologist: “In patients with good heart muscle, no or mild symptoms, and no left main coronary disease, optimal medical therapy is very efficacious. Doing coronary intervention has a mild early hazard by two years and similar late benefit at two to four years, and overall survival is good. If the patient has angina symptoms, then intervention reduces that at a cost of slight early hazard.”

Brahmajee Nallamothu, M.D., interventional cardiologist: “I agree with Dr. Eagle. ISCHEMIA is really a testament to how far we’ve come along with guidelines-directed medical therapy. It also gives us clearer guidance before a patient ends up in the cath lab. COURAGE taught me that not every blockage needs to be stented. ISCHEMIA teaches me that not every positive stress test needs to go to the cath lab.”

Nadia Sutton, M.D., M.P.H., interventional cardiologist: “Overall, the findings support current practice and an individualized approach to patient care. To me the major question is how to rule out high-risk anatomy. We typically have done this invasively, but perhaps we should be doing more non-invasive screening for anatomic high risk anatomy in the future.”

How will ISCHEMIA change clinical practice?

Eagle: “They will provide further confidence that either approach is reasonable and should be driven by the degree of symptoms and informed decision making.”

Nallamothu: “I agree. It should give clinicians and patients new information on how to proceed if poor blood flow is detected on a stress test. It should reassure those who want to try a more conservative approach upfront with medications. It also should give patients an idea of what to expect in terms of a benefit for symptom control. The big thing for me is that we don’t have to rush through these decisions.”

"ISCHEMIA teaches me that not every positive stress test needs to go to the cath lab. "
Brahmajee Nallamothu, M.D.

Did ISCHEMIA live up to the hype?

Eagle: “Yes!”

Sutton: “Yes. The study was beautifully designed and conducted, and the authors should be congratulated for contributing this seminal work to the literature.”

Nallamothu: “I think it did live up to the hype. The answer wasn’t a clear win for an invasive approach. But it also wasn’t a clear loss. The answer was messy. But that’s OK, because sometimes biology and medicine are messy.

“I think it provides us with confidence that patients like those in the study can do well with a conservative approach upfront and that we can take our time. As Dr. Eagle noted, both are reasonable options with no ‘right’ answer for all patients.”

What details stick out to you?

Sutton: “I would like to emphasize that study protocol mandated ruling out left main disease (high risk anatomy) with a CT scan. This ruled out 1/20 of every enrolled patient (434/8518). If this was implemented on a routine basis for patients, it would result in an unprecedented increase in the number of coronary CT scans performed on patients.

“It also is noted 23% of patients assigned to the conservative therapy arm had undergone revascularization by four years (cross-over).”

Nallamothu: “I’m curious as to how they’ll handle the crossing survival curves in their analysis. This can be complicated and might shed some light on key factors – e.g., was this benefit due to longer dual antiplatelet therapy in the invasive approach arm?”

Eagle: “The extended endpoints possibly diluted the observed late benefit (two to four years) which might have swayed overall results. If the trial results were extended beyond four years, it is possible that the intervention group might look a little better than the medical only arm.”

What do you still want to know?

Sutton: “The primary endpoint showed no difference in the primary endpoint at four years, but the curves do appear to show some divergence which favor an invasive strategy, and longer term follow up with the full study cohort will be necessary to determine if there is any potential long-term benefit in the primary outcome.”

Eagle: “I’d like to see a substudy of patients with both more ischemia by imaging and symptoms...Is there a benefit trend in that group?”

Nallamothu: “The role of coronary computed tomography angiography (CCTA) to rule-out left main disease will be discussed a lot. Whether or not every patient will need a CCTA is unclear. I’m hopeful that the ISCHEMIA investigators can help us learn if certain patient features can predict who might benefit from a CCTA to rule out left main disease. This will be an important substudy that I’ll be on the lookout for.”