While revascularization in acute coronary syndromes (ACS) and myocardial infarction (MI) decreases mortality and recurrent MI, outcomes in stable ischemic heart disease (SIHD) are less well understood. Funded by the National Heart, Lung, and Blood Institute, the ISCHEMIA-EXTEND study is the long-term follow-up of randomized, participants in the ISCHEMIA and ISCHEMIA-CKD trials.
“Initial results from ISCHEMIA showed durable improvements in angina control and quality of life with initial invasive management—but no differences in major adverse cardiac events and mortality,” says Judith S. Hochman, MD, the Harold Snyder Family Professor of Cardiology and a leader of many complex international clinical trials.
Building Upon Earlier Results
The ISCHEMIA and ISCHEMIA-CKD investigators and their global partners presented the initial findings at the American Heart Association (AHA) Scientific Sessions in November 2019 and published the results of both trials in The New England Journal of Medicine in April 2020.
VIDEO: Dr. Judith S. Hochman discusses interim results of the landmark ISCHEMIA study at the American Heart Association’s 2022 Scientific Sessions.
Among patients with stable coronary disease and moderate or severe ischemia, the researchers did not find evidence that an initial invasive management strategy, as compared with an initial conservative management strategy, lowered the risk of ischemic cardiovascular events or death from any cause. In ISCHEMIA-CKD, they observed similar results among patients with advanced chronic kidney disease. Moreover, there was an early excess of peri-procedural MI and a late reduction in spontaneous MI in both studies.
Building upon these results, ISCHEMIA-EXTEND was pioneered to assess whether an initial invasive strategy reduces long-term all-cause mortality as compared with an initial conservative strategy over an extended period of follow-up. At its launch, more than 5,000 participants worldwide entered the trial.
“It is imperative to assess long-term all-cause mortality following these two different management strategies.”Judith S. Hochman, MD
“Prior evidence shows that spontaneous MI has a larger impact on subsequent death than most peri-procedural MIs,” Dr. Hochman explains. “Thus, it is imperative to assess long-term all-cause mortality following these two different management strategies.”
A Continued Investigation
At AHA Scientific Sessions 2022, that took place November 5 to 7 in Chicago, Illinois, and virtually, Dr. Hochman presented the interim results of ISCHEMIA-EXTEND on behalf of the research group. After a median follow-up of 5.7 years, the researchers found that initial invasive management compared with initial conservative management resulted in no difference in all-cause mortality, but there was a lower risk of cardiovascular mortality and higher risk of non-cardiovascular mortality.
“These findings provide important evidence for whether to add invasive management to guideline-directed medical therapy.”
“The previously observed excess of non-cardiovascular mortality with initial invasive strategy persisted,” Dr. Hochman says. “These findings provide important evidence for whether to add invasive management to guideline-directed medical therapy.”
What Lies Ahead
Dr. Hochman emphasizes that these findings are consistent with prior randomized trials of revascularization versus medical therapy alone, which have reported similar rates of all-cause mortality between groups.
Next, the researchers will continue to follow surviving participants into 2025 for a projected median of approximately 10 years to increase the precision around these mortality estimates.
“We believe these data will add to the evidence base for shared decision-making between patients and their physicians,” Dr. Hochman explains. “Providers should engage in shared decision-making with patients to discuss treatment preferences.”