Impact of ischemia and scar on therapeutic benefit of myocardial revascularization.

The question of how to optimally manage coronary artery disease (CAD) has been a challenge for the cardiology community. The results of early, large randomized clinical trials (RCTs) comparing strategies of medical therapy alone versus revascularization plus medical therapy in patients with stable CAD suggested a survival advantage for a revascularization strategy in the setting of more advanced, higher-risk CAD (left main, three-vessel CAD), but a superiority of medical therapy in patients with more limited, relatively lower-risk CAD (one vessel, limited two-vessel CAD). The results of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials redefined the management of CAD, supporting the concept that the impact of aggressively applied modern "medical therapy" on patient survival and patient-reported outcomes is not further improved by the addition of percutaneous intervention. On the other hand, RCTs incorporating fractional flow reserve have shown that this physiologic metric can help identify which patients will benefit from a revascularization strategy. This paradigm has been extended to the use of myocardial perfusion imaging-identified ischemia to determine which patients may have enhanced survival with early revascularization versus medical therapy. Although data from a series of observational studies suggest that inducible ischemia on myocardial perfusion scintigraphy can identify revascularization candidates, several studies, including substudies from major RCTs, do not support this idea. Until RCTs comparing revascularization with medical therapy strategies are performed, many questions remain open. The correct thresholds for treatment, the metric to guide treatment, and how revascularization should be performed are as yet undefined.