Does Myocardial Ischemia Matter in Stable CAD?

— Long-term outcomes the same regardless of stress-test results in MASS II trial

Last Updated July 23, 2019
MedicalToday

For people with stable multivessel coronary artery disease (CAD) who subsequently received treatment, long-term cardiovascular outcomes were the same whether or not myocardial ischemia was confirmed with exercise stress testing, a study found.

Combined death, MI, and revascularization for refractory angina (adjusted HR 1.00, 95% CI 0.80-1.27) did not differ according to stress-test results among participants recruited with proximal multivessel coronary stenoses greater than 70% on angiography.

Positive and negative findings alike were followed by a similar magnitude of decline in left ventricular ejection fraction (LVEF) over more than a decade of follow-up, Whady Hueb, MD, PhD, of Brazil's Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, and collaborators reported in .

MASS II randomized participants at one center to medical therapy alone or revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in 1995-2000.

"Although the present study did not have data about high-risk findings in EST [exercise stress testing], more than 50% of the studied patients had triple-vessel disease and almost 90% had proximal left anterior descending coronary artery involvement, which characterize a higher-risk population," the authors noted.

"Despite this high risk, the results of this study suggest that, in patients with stable CAD, documented ischemia observed by ischemic changes during EST was not associated with different 10-year cardiovascular outcomes and worsening of ventricular function compared with that in patients with nonischemic EST," they concluded.

From these results, the take-home message should be that therapy is beneficial and that even in patients with ischemia you can't say whether revascularization or medical therapy is better for them -- not that stress testing is not useful, cautioned Christopher Kramer, MD, of the University of Virginia Heart and Vascular Center in Charlottesville, who was not involved with the study.

The usefulness of stress testing is controversial, and it would take an "impossible-to-do, ethically difficult" trial where some patients are randomized to treatment or no treatment to really understand the importance of ischemia, Kramer told .

The , with participants who have moderate or severe ischemia on stress testing, is expected to shed some light on the question next year, he noted.

Included in the present retrospective analysis of were 535 patients who got baseline exercise stress testing (69.7% men, mean age 59.7 years). No matter the assigned treatment, people stayed on medical therapy throughout follow-up averaging 11.4 years.

This cohort was roughly split between those with and without documented ischemia during stress testing.

"You could flip it and say that the angiogram lied: half of these patients with 70% stenosis didn't have ischemia," Kramer pointed out. "This study raises more questions than it answers."

One explanation for the main results may be that functional information about myocardial stress-induced ischemia does not actually describe atherosclerotic plaque instability, Hueb's group suggested. "Since myocardial ischemia is associated with the degree of stenosis and atherosclerotic burden, we must consider that its presence, even if significant, may remain stable for a long time while the plaque stability persists."

Ultimately, patients with established coronary disease need to be on preventative medications, eat healthier, exercise more, and stop smoking regardless of whether they have documented ischemia, commented Joseph Ladapo, MD, PhD, of UCLA School of Medicine.

"The other important point to make is that there is growing data that advanced PCI techniques such as fractional flow reserve can improve cardiovascular outcomes by targeting ischemic lesions. So ultimately, it's possible that techniques like this may have improved outcomes in the patients in this study, had they been used," he told .

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    Nicole Lou is a reporter for , where she covers cardiology news and other developments in medicine.

Disclosures

The study was funded by a grant from the Zerbini Foundation.

Hueb disclosed no conflicts of interest.

Primary Source

JAMA Internal Medicine

Garzillo CL, et al "Association between stress testing-induced myocardial ischemia and clinical events in patients with multivessel coronary artery disease" JAMA Intern Med 2019; DOI: 10.1001/jamainternmed.2019.2227.