ISCHEMIA Trial baseline data

ISCHEMIA Trial baseline data: International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial was sponsored by the New York University School of Medicine. Collaborators include National Heart, Lung, and Blood Institute (NHLBI), Stanford University, Duke University, Emory University, Harvard University and several other leading institutions.

ISCHEMIA trial randomized 5179 patients with stable ischemic heart disease with moderate to severe degree of inducible ischemia on stress testing. Blinded CT coronary angiogram was used to exclude those with significant unprotected left main coronary artery disease or obstructive stenosis in all major coronary arteries, in those with eGFR of 60 mL/min/1.73 sq m. There were 341 enrolling sites from 38 countries of which 320 sites finally randomized patients into the trial.

Randomization was to either routine invasive strategy with coronary angiography and revascularization plus optimal medical therapy OR conservative strategy with optimal medical therapy and revascularization in only those who fail medical management.

Primary composite endpoint included cardiovascular death, myocardial infarction, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure. Average follow up period is around 3.5 years.

ISCHEMIA trial baseline data [1] had a median age of 64 years with 22.6% females, 41% had diabetes mellitus, 19% previous myocardial infarction, and 90% with previous angina.

Stress myocardial imaging was the qualifying test in three fourth of the patients. Imaging modalities included nuclear imaging, stress echocardiography and magnetic resonance imaging. Cut off points were 10% or ischemic myocardium on stress nuclear imaging, three or more segments out of 16 with worsening wall motion abnormalities on stress echocardiography and more than 12% ischemic myocardium on stress magnetic resonance perfusion study.

One quarter of patients were enrolled based on non imaging exercise tolerance test in the form of exercise electrocardiogram (ECG). This was included to boost enrollment from countries where stress imaging is not routinely done.

The degree of ischemia on stress imaging classified by the core laboratory was:

1. 44.8% severe
2. 41.0% moderate
3. 8.1% mild
4. 6.1% non existent or uninterpretable

Corresponding degree of ischemia in those randomized after exercise ECG was:

1. 83.0% severe
2. 8.0% moderate
3. 2.7% mild
4. 6.3% non existent or uninterpretable

CT angiography showed multivessel disease in 79%, left anterior descending coronary artery (LAD) disease in 87% and proximal LAD disease in 47%.

Those enrolled after exercise ECG had greater frequency of three vessel disease, LAD disease and proximal LAD disease than those enrolled after stress myocardial imaging.

As one of the criticisms against the two previous trials in stable ischemic heart disease (COURAGE and BARI 2D) was that many had milder ischemia, this trial tried to enroll patients with more severe documented ischemia who are more likely to benefit from early revascularization.

The current paper reports only the baseline data. We can look forward to the outcome data presentation and publication soon.

Reference

1. Hochman JS, Reynolds HR, Bangalore S, O’Brien SM, Alexander KP, Senior R, Boden WE, Stone GW, Goodman SG, Lopes RD, Lopez-Sendon J, White HD, Maggioni AP, Shaw LJ, Min JK, Picard MH, Berman DS, Chaitman BR, Mark DB, Spertus JA, Cyr DD, Bhargava B, Ruzyllo W, Wander GS, Chernyavskiy AM, Rosenberg YD, Maron DJ; ISCHEMIA Research Group. Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial. JAMA Cardiol. 2019 Feb 27. doi: 10.1001/jamacardio.2019.0014. [Epub ahead of print]