Intermediate Left Main Disease Linked to Worse Outcomes: ISCHEMIA

Even an intermediate degree of left main (LM) disease puts patients with stable, moderate-to-severe CAD at greater risk of adverse events compared with no left main involvement, a subanalysis of the ISCHEMIA trial shows.

ISCHEMIA, presented at last year’s American Heart Association Scientific Sessions, showed that an invasive strategy on top of optimal medical therapy offers no advantage over optimal medical therapy alone in preventing a range of major cardiovascular events, but does improve quality of life and angina symptoms. The trial, however, excluded patients with a LM stenosis of 50% or greater on coronary CT angiography (CTA).

In a report released at last week’s Society for Cardiovascular Angiography and Interventions (SCAI) virtual meeting, investigators focused on patients with intermediate LM stenosis (defined as 25% to 49%) as compared to patients with < 25% LM stenosis, representing three-quarters of the trial participants.

Importantly, “the invasive strategy was associated with significantly better quality of life compared with the conservative strategy regardless of the left main stenosis severity,” Sripal Bangalore, MD (Bellevue Hospital, New York, NY), told SCAI attendees in his virtual presentation. “As was seen in the main results, the impact of the invasive strategy was dependent on baseline angina status, such that the invasive strategy was associated with better angina relief in those with daily/weekly or monthly angina compared to no angina.”

B. Hadley Wilson, MD (Sanger Heart and Vascular Institute, Charlotte, NC), an American College of Cardiology spokesperson, told TCTMD that intermediate LM disease hasn’t been looked at so closely in the past. “I think the prevailing previous opinion was that if it was less than that 50% cut mark then those patients were probably okay and could be followed in the usual pool of our coronary artery disease patients,” he said.

This subanalysis, Wilson commented, “really tells us that we can’t just have blinders on until someone reaches a cut point of 50% left main stenosis before we actually need to pay attention to them. We need to heighten our guard, and this is an important category to follow. I’m going to think about that in my own practice.”

Invasive, Conservative Strategies Similar

Within the no-LM and intermediate-LM groups, there were no differences in demographics or clinical history between the invasive and conservative arms. Nor were there any related to the results of stress testing or CTA. Patients with intermediate LM tended to be older and to have more risk factors like hypertension and diabetes, more moderate-to-severe ischemia, more-extensive CAD, and a higher likelihood of proximal LAD disease. Among the patients with intermediate LM disease on CTA, invasive angiography identified 7% as having severe LM stenosis.

Compared to no LM disease, the presence of intermediate LM on CTA was associated with a 31% increase in the risk of the study’s primary endpoint, defined as CV death, MI, resuscitated cardiac arrest, hospitalization for unstable angina, and hospitalization for heart failure (adjusted HR 1.31; 95% CI 1.06-1.61). For the trial’s original primary endpoint—CV death and MI—risk also was elevated but not to a statistically significant degree (adjusted HR 1.24; 95% CI 0.99-1.55). Overall, though, outcomes were worse among the intermediate-LM patients as compared with those with no LM disease.

As in the main trial, most outcomes were similar within each LM subgroup regardless of the patients’ assigned treatment. There was more procedural MI and less nonprocedural MI among patients randomized to invasive treatment, a difference that was slightly more pronounced in the intermediate-LM group. The effect of treatment on quality of life on the SAQ-7 summary and angina frequency scores did not differ based on the degree of LM disease.

Panelist Timothy Henry, MD (The Christ Hospital, Cincinnati, OH), said these ISCHEMIA data suggest “an intermediate lesion on CTA might make us be more aggressive. I think these are really important results.”

In response, Bangalore said, “Many times, we are looking at results as binary, whether patients have left main disease or not. And here we are showing it’s not black or white, there are shades of gray. If a patient has intermediate left main disease, their prognosis is worse.”

That intermediate left main disease should be taken seriously is a point that must be conveyed to referring physicians, he urged. “Many times, they may just look at the bottom line and say, ‘Oh, there is no left main disease.’”

Here we are showing it’s not black or white, there are shades of gray. If a patient has intermediate left main disease their prognosis is worse. Sripal Bangalore

Cindy Grines, MD (Northside Hospital Cardiovascular Institute, Atlanta, GA), also a panelist, observed that left main disease is often accompanied by multivessel disease, and asked: “Were you able to sort it out in terms of the core outcomes? Do you think it was due to borderline left main? Or was it due to the higher prevalence of three-vessel disease and proximal LAD disease?”

What the left main findings suggest overall is a “greater burden of atherosclerosis,” Bangalore replied. “Even though we did adjust for many of these baseline differences, it still panned out to be independently predictive. My guess is that we can’t capture the extent of atherosclerosis just by, for example, looking at the number of diseased vessels.”

Hadley, too, said that intermediate left main disease may itself not be the problem but rather may be a “marker for the total coronary disease or atherosclerotic burden.” He also questioned whether or not these left main lesions actually were treated in the trial’s invasive arm.

What’s clear, though, is that “this is a higher-risk group that needs to be followed more closely,” he continued. “And if they develop any sign of instability or progression and symptoms, this would be a group that one needs to take note of and act quickly.”