David J. Maron, M.D., Judith S. Hochman, et al, ISCHEMIA Research Group*

April 9, 2020  N Engl J Med 2020; 382:1395-1407

COMMENTARY . . . . . . . . .   by Ronald Peters, MD, MPH

Stable coronary artery disease is the term used by doctors for patients with known cardiovascular disease but have no cardiac symptoms. Angina and heart attack are examples of unstable heart disease.  Reduced blood flow, or ischemia, is the key pathology in angina and heart attack because the coronary arteries are blocked with cholesterol deposits that limit the flow of blood to the heart. Due to the dire consequences of severe coronary ischemia, Cardiologists do coronary angiograms to evaluate blockage in the coronary arteries, which can be treated with stents and possible coronary artery bypass surgery.  However, there are other metabolic causes for ischemia which can be treated medially.  Also, it is possible to have a heart attack without coronary artery blockage, which is called a “silent heart attack” and is due to severe coronary artery spasm usually due to severe anger and the intense release of stress hormones.  Severe emotional stress can have a deadly effect on the heart.  There are other risk factors, such as increased blood clotting, which need evaluation and treatment.  The ISCHEMIA research Group has shown that enhancing health in the body and mind (stress reduction), which they call “conservative therapy” is just as effective in the treatment of stable coronary artery disease as interventions such as stents and bypass surgery.



Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.


We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.


Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, −1.8 percentage points; 95% CI, −4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).


Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used.