From the Guidelines
The primary purpose of an ischemia trial is to determine whether an initial invasive strategy of cardiac catheterization and optimal revascularization, plus optimal medical therapy (OMT), reduces the primary composite endpoint of cardiovascular death or nonfatal myocardial infarction in patients with stable ischemic heart disease (SIHD) and moderate or severe ischemia, as compared with an initial conservative strategy of OMT alone.
Key Objectives
- To compare the effectiveness of an initial invasive strategy versus a conservative strategy in patients with SIHD and moderate or severe ischemia
- To evaluate the impact of revascularization on cardiovascular death, nonfatal myocardial infarction, and angina-related quality of life
- To assess health resource utilization, costs, and cost-effectiveness of the two strategies
Study Design
The ISCHEMIA trial is a randomized controlled trial that enrolled patients with SIHD and moderate or severe ischemia, with a primary aim to determine the optimal approach to managing these patients 1. The trial has a parallel substudy for patients with advanced chronic kidney disease.
Evidence and Rationale
The ISCHEMIA trial aims to address the limitations of previous strategy trials by enrolling patients before catheterization, enrolling a higher-risk group with at least moderate ischemia, minimizing crossovers, and using contemporary revascularization techniques and physiologically guided decision making 1. The results of the ISCHEMIA trial will have important implications for global guidelines for performance and reimbursement of revascularization procedures in patients with SIHD 1.
Recent Findings
Extended follow-up of the ISCHEMIA trial population up to 7 years (ISCHEMIA-EXTEND) revealed a significant 2.2% absolute decrease in cardiovascular mortality favoring the initial invasive strategy, although this benefit was offset by a significant 1.2% absolute increase in non-cardiac mortality 1. A post hoc analysis of the ISCHEMIA trial indicated that coronary artery disease severity was associated with a higher risk of all-cause death, MI, and the primary endpoint of the trial 1.
From the Research
Purpose of an Ischemia Trial
The purpose of an ischemia trial, such as the ISCHEMIA trial, is to compare the effectiveness of different treatment strategies for patients with stable coronary artery disease and moderate to severe myocardial ischemia. The trial aims to determine whether an early invasive strategy with revascularization plus optimal medical therapy is more effective than initial optimal medical therapy alone with revascularization reserved for cases where symptom control is insufficient 2, 3.
Key Objectives
The key objectives of the ISCHEMIA trial include:
- Comparing the outcomes of patients with stable coronary artery disease and moderate to severe myocardial ischemia who receive an early invasive strategy versus those who receive initial optimal medical therapy alone 2
- Evaluating the effectiveness of revascularization procedures, such as coronary artery bypass grafting or percutaneous coronary intervention, in improving symptoms of angina and preventing new myocardial infarction events and cardiovascular death 3
- Assessing the benefits of disease-modifying optimal medical treatment for stable coronary artery disease patients 3
Methodology
The ISCHEMIA trial is a large, multicentric trial that enrolled over 5,000 patients with stable coronary artery disease and moderate to severe myocardial ischemia. The trial compared coronary revascularization and optimal medical treatment versus optimal medical treatment alone, with a median follow-up of 3.2 years 2, 3.
Findings
The findings of the ISCHEMIA trial indicate that there is no significant difference in clinical outcomes, including all-cause mortality, cardiovascular death, myocardial infarction, and stroke, between the early invasive strategy and the initial optimal medical therapy alone 2, 4. However, the trial did find that angina control was better in patients with severe symptomatic angina who received the early invasive strategy 2.
Implications
The implications of the ISCHEMIA trial are still being debated, with some studies suggesting that the findings may challenge current diagnostic approaches for stable angina patients 3 and others arguing that the results should not be used to downgrade recommendations for the benefits of coronary artery bypass grafting 5. Further studies are needed to evaluate the optimal modality of therapy in patients with stable coronary disease and moderate or severe ischemia 4.