Results of the ISCHEMIA trial were revealed at AHA 2019 and revealed little overall benefit of an invasive approach but saw improved angina control in patients with previous angina.
Results of the highly anticipated ISCHEMIA trial presented at the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia are offering cardiologists revolutionary insight on how to best manage patients with stable ischemic heart disease.
The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, which was supported by the National Heart, Lung, and Blood Institute, compared invasive treatments including surgery versus optimal medical therapy, such as lifestyle advice and medications, based on a composite endpoint of cardiovascular events.
A total of 5179 patients from 37 countries with moderate to severe ischemia were included in the study, which began in 2012 and was led by a team of investigators from NYU Grossman School of Medicine and Stanford University. For inclusion, patients needed to be 21 years of age or older and have 50% or greater stenosis in a major epicardial vessel—as measured by stress imaging—and 70% or greater stenosis in a proximal or mine vessel—as measured by exercise tolerance test.
Investigators noted a number of exclusion criteria for the trial, including NYHA Class 3 or 4 heart failure, estimated glomerular filtration rate less than 30 mL/min, ejection fraction less than 35%, and percutaneous coronary intervention or coronary artery bypass grafting.
The primary endpoint of ISCHEMIA was time to cardiovascular death, myocardial infarction, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. Secondary endpoints included time to cardiovascular death and quality of life.
OF the 5179 patients included in the study, 2588 were randomized to receive invasive therapies and 2591 were randomized to conventional therapy. In the invasive treatment group, 99.4% completed the trial while that figure was 99.7% in the optimal medical therapy arm. Median follow-up time for survivors was 3.3 across both arms.
Baseline characteristics were similar between both groups. Values including median age (64; 58, 70), hypertension (73%), previous myocardial infarction (19%), and systolic (130; 120, 142) and diastolic blood pressure (77; 70, 81) were similar in both groups.
Results of the trial revealed an adjusted hazard ratio of 0.93 (0.80, 1.08) with a P-value for the primary outcome of cardiovascular death, myocardial infarction, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. Additionally, at 6 months there was a 1.9% difference favoring the optimal medical therapy arm and that switched at 4 years, with a 2.2% difference in favor of invasive treatment (15.5% versus 13.6%).
In regard to the secondary endpoints of cardiovascular death or myocardial infarction, a similar effect was seen. At 6 months, optimal medical therapy had a 1.9% lower rate but this switched and patients receiving optimal medical therapy had a 2.2% higher rate of the secondary endpoint.
Investigators pointed out procedural myocardial infarctions were increased with an invasive strategy while this approach led to decreases in spontaneous myocardial infarction.
"Overall, an initial invasive strategy as compared with initial conservative strategy did not demonstrate a reduced risk over a median 3.3 years for the primary endpoint or the major secondary endpoint. The probability of at least a 10% benefit of invasive on all-cause mortality was low,” said Judith Hochman, MD, study presenter and cardiologist at NYU Langone.
When examining only quality of life outcomes, investigators observed patients with stable CAD had significant, durable improvement from 3 months out to 3 years in angina control and quality of life with an invasive strategy if they had an angina. In patients without angina, investigators saw minimal symptom or quality of life benefits compared with an optimal medical therapy arm.
These studies, “International Study of Comparative Health Effectiveness With Medical and Invasive Approaches: Primary Report of Clinical Outcomes,” and “International Study of Comparative Health Effectiveness With Medical and Invasive Approaches: Primary Report of Quality of Life Outcomes,” were presented at AHA 2019 by Judith Hochman, MD, and John Spertus, MD, respectively.