People with severe but stable ischemic heart disease (SIHD) don’t benefit any more from invasive CV procedures than they do from optimal medical therapy (OMT) and lifestyle changes alone, according to results from the highly anticipated ISCHEMIA trial.
Results from ISCHEMIA, presented Nov. 16 at the American Heart Association’s Scientific Sessions in Philadelphia, found that SIHD patients who underwent routine procedures like stent implantation or bypass surgery didn’t fare any better in the long-term than those who received OMT and lifestyle advice alone. The trial randomized 5,179 patients in 37 countries to OMT with early cardiac catheterization or OMT alone, with invasive therapy reserved for emergencies.
Patients assigned to the invasive group were treated more proactively, undergoing invasive procedures soon after recording an abnormal stress test. The OMT-alone cohort moved on to invasive therapy only if their symptoms worsened with drug therapy or an emergency, like MI, arose.
Study chair Judith Hochman, MD, of NYU Langone Health, and colleagues reported that patients who were treated more aggressively ultimately didn’t see better outcomes than those treated with OMT alone. ISCHEMIA found no reduction in the rate of occurrence of CV death, MI, or hospitalization for unstable angina or HF with a more invasive approach.
“In line with evidence from prior studies, our results suggest that routine use of heart procedures was not superior in reducing risk for the five-part disease endpoint or death overall compared to treatment only with OMT,” Hochman said in a statement. “On the other hand, patients symptomatic to start that got heart procedures, over the years, had fewer symptoms and felt better.”
By the numbers
Hochman et al. reported an “extremely” low rate of procedure-related stroke and death in ISCHEMIA, though patients who had invasive procedures had a 2% higher event rate at one year than their counterparts (5.3% vs. 3.4%, respectively). The authors said the result might be attributed to the fact that CV procedures carry their own fair share of risks, including death, heart attack and stroke.
At year two, the event rate for the study’s five-pronged endpoint was similar between groups—9% in patients treated with invasive therapy and 9.5% in those treated with OMT alone. The numbers diverged slightly at four years, rising to 13.3% and 15.5% of the groups, respectively, but the investigators stressed that that isn’t a significant difference.
The researchers did find that for patients with symptoms of angina, more invasive treatment resulted in better symptom relief and quality of life through four years of follow-up. They said that among study participants with daily or weekly angina at baseline, 50% of those treated invasively were angina-free at one year compared to 20% of those treated with OMT.
Hochman and colleagues are planning to follow the ISCHEMIA cohort for another five years to determine whether either treatment strategy yields more favorable outcomes over a longer period of time.
A rocky road
ISCHEMIA investigators were on the receiving end of some criticism early last year after they published a paper in Circulation: Cardiovascular Quality & Outcomes defending their addition of several “soft” outcomes to their primary composite endpoint of death and nonfatal MI. The team had decided to tack hospitalization for unstable angina, hospitalization for heart failure and resuscitation after cardiac arrest onto their now five-point composite endpoint, and not all critics were optimistic about the shift.
“We must reflect on whether there is any meaning to the term ‘primary endpoint’ when goalposts are being moved after a trial has begun recruiting despite the best intentions of investigators,” Darrel P. Francis, MD, and colleagues at Imperial College London wrote in a paper published last March. “We must learn to accept the results of trials, even if they are not as we hoped.”
The ISCHEMIA team issued a response two months later claiming the decision to change the study’s primary endpoint was “deliberate and carefully considered,” weighed by experts in the trial’s Leadership Committee and Steering Committee and staff from the National Heart, Lung and Blood Institute, which funneled $84 million into ISCHEMIA.
Hochman’s team said the results of ISCHEMIA—more than a decade in the making—reflect clinical practice, where many patients with abnormal stress tests are referred automatically for invasive procedures.
“Based on our results, we recommend that all patients take medications proven to reduce the risk of a heart attack, be physically active, eat a healthy diet and quit smoking,” ISCHEMIA co-chair David Maron, MD, of Stanford University, said in a statement. “Patients without angina will not see an improvement, but those with angina of any severity will tend to have a greater, lasting improvement in quality of life if they have an invasive heart procedure.”