The management of patients with stable coronary artery disease is one of the most challenging situations in cardiology. It is necessary to decide whether to maintain a conservative strategy, with only a medical therapy, or to proceed with hemodynamic study and, if possible, revascularization.
Whatever the decision, the aim must be to reduce mortality, the risk of acute ischemic events and, last but not least, improve quality of life, reducing symptoms.
In the past, different studies have tried to provide an answer to this dilemma, but unfortunately the results were contrasting. Now this answer seems to be arrived, by the ISCHEMIA Trial, recently published in the New England Journal of Medicine.
Object of this study were patients with stable coronary artery disease, with evidence of at least moderate ischemia, revealed with stress tests, SPECT/PET, magnetic resonance imaging and echocardiogram with pharmacological stress.
Patients with left ventricular ejection fraction less than or equal to 35% and those with a previous angiographic finding of unprotected left main stenosis of at least 50% were excluded from the study.
The 5,179 subjects recruited, at 320 centers, in 37 countries, were randomized to two treatment strategies: invasive strategy, with medical therapy, angiography and, if possible, revascularization; conservative strategy, with medical therapy alone.
The main endpoint of the study was a composite of cardiovascular death, myocardial infarction or hospitalization for unstable angina, heart failure or cardiac arrest.
Secondary endpoints were a composite of cardiovascular death or myocardial infarction, and angina-related quality of life.
The median follow-up of the study was long, exceeding three years. During this period, the primary endpoint occurred in 318 patients in the invasive strategy group and in 352 patients in the conservative strategy group.
The 6-month event analysis showed a cumulative event rate of 5.3% in the invasive strategy group and 3.4% in the conservative strategy group, whereas at 5 years the rate was 16.4% and 18.2% respectively.
Secondary endpoints also occurred with similar proportions between the two treatment groups.
There were 145 deaths in the invasive strategy group and 144 deaths in the conservative strategy group.
The ISCHEMIA Trial along its course has adopted two different definitions of myocardial infarction, thus obtaining different results depending on the criteria adopted.
The primary definition was based on the third universal definition of myocardial infarction, with higher biomarker thresholds for confirmation of procedural events.
The second definition for procedural infarctions were similar to those of the universal definition but
with additional criteria based on elevations of biomarker levels alone.
These different criteria led to a greater number of procedural infarcts with the second definition, affecting results.
With the adoption of the new criterion, the 6-month cumulative event rate for the main endpoint of the study was 10.2% in the invasive strategy group and 3.7% in the conservative strategy group, while the 5-years rate was 21.2% and 19% respectively.
The authors simply conclude that patients with stable coronary artery disease, and moderate or severe ischemia, do not appear to benefit from an invasive strategy.
However, a trend in favor of non-invasive strategy seems to emerge, at least in the short-term.
For sure, this is a very important study, with accurate data quality and long follow-up, which could have “historical” consequences on the approach to the patient with stable coronary artery disease. Based on its results, the use of interventional procedures could be substantially reduced, returning to medical treatment the importance it has played for many years.
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