Revascularization Shows Benefit at 4 years in ISCHEMIA

Key Points:

• ISCHEMIA trial patients in the invasive management arm were assessed for completeness in revascularization.
• Patients who achieved complete revascularization were found to have better outcomes at 4 years than those who did not.
• If all patients in the invasive arm were to have achieved complete revascularization, the primary endpoint of ISCHEMIA would have favored invasive management even more strongly at 4 years.

Complete revascularization has been associated with improved outcomes in patients presenting with acute coronary syndrome. For those with chronic coronary disease, many observational data support complete revascularization after PCI and CABG, as the strategy has been associated with improved survival. In a Focused Clinical Research session at the 2021 American College of Cardiology Scientific Sessions today, Dr. Gregg Stone and his team from the ISCHEMIA trial, took the strategy one step forward, and compared patients undergoing complete revascularization to those undergoing conservative management for chronic coronary disease.

This retrospective analysis of the ISCHEMIA trial had two objectives:

• Assess the frequency and outcomes of anatomic complete revascularization and functional complete revascularization compared to incomplete revascularization when patients are treated with an invasive strategy.
• Assess the impact that achieving complete revascularization in all patients randomized to an invasive strategy might have had when compared to conservative management.

It is important to remember that in ISCHEMIA patients with stable disease were randomized to either undergo an invasive strategy for optimal revascularization at the discretion of the operators, or conservative management, for which optimal medical therapy alone was encouraged. All films were analyzed by an angiographic core laboratory, which compared pre and postprocedural angiograms to determine the level of completeness in the revascularization. In review of those angiograms, the authors found, that of 1825 evaluable patients, 43.3% achieved complete revascularization when assess anatomically, and 58.3% achieved it when assessed functionally.

For the primary endpoint of cardiovascular death, MI or cardiac hospitalization, anatomic complete revascularization was associated with 4.5% fewer events at 4 years when compared to incomplete revascularization. A similar finding of 3.7% fewer events was seen in patients assessed for functional complete revascularization. After adjusting for covariates, however, these findings did not reach statistical significance.

Dr. Stone then continued to explain the results of his secondary objective of comparing all 2296 patients who underwent complete revascularization to 2498 patients treated conservatively in the trial. To do so, the authors first estimated the hypothetical ideal treatment effect had all patients received complete revascularization, then compared those to the patients who underwent conservative management using inverse probability weighting to try and adjust for confounding. The hypothetical modeling showed that had all invasive patients achieved anatomic complete revascularization, there would have been a 3.5% reduction in the primary endpoint at 4 years, favoring invasive strategy (compared to 2.2% in the original trial).  These differences were driven by cardiovascular death and MI, which remained significant even after adjusting for covariates.

“When we decide on an invasive versus a conservative strategy, whether it is from a CT scan or an angiogram, we must be honest with ourselves as to whether complete revascularization is achievable,” explained Dr. Stone when referring to the results of the study. “If we cannot achieve complete revascularization, the benefit of an invasive strategy is attenuated, and those patients may fare better with coronary artery bypass surgery.”

The authors report the limitations of the study, namely that their results represent associations, given the observational design. Furthermore, the results are limited to patients enrolled in the ISCHEMIA trial, and are only applicable to those who met inclusion criteria.