COURAGE substudy: Anatomic burden predicted outcomes

Findings from a post-hoc analysis of the COURAGE trial indicated that anatomic burden, but not ischemic burden, predicted outcomes in this patient population. However, neither determination predicted which patients would benefit from a more invasive approach.

The researchers aimed to assess the prognostic capability of both the anatomic and ischemic burden of CAD in clinical decision-making for revascularization in a cohort of 621 patients from the COURAGE trial.

Participants included those with baseline quantitative nuclear single-photon emission CT and quantitative coronary angiography.

Death, MI and non-ST-segment elevation ACS served as the primary outcome measure. The investigators also assessed ischemic burden during single-photon emission CT, anatomic burden derived from angiography and LV ejection fraction. Patients were assigned optimal medical therapy plus PCI or optimal medical therapy alone.

Adjusted and unadjusted results indicated that anatomic burden and LV ejection fraction consistently prognosticated the primary outcome measures. Ischemic burden and treatment assignment failed to predict those outcomes.

The investigators reported that the interaction term of anatomic and ischemic burden was a moderate predictor of clinical outcome (P=.03). However, when anatomy or ischemia was observed separately or in combination with one another, they failed to interact with the therapeutic strategy and achieve a prognostic capability.

Spencer B. King III, MD, of the cardiology department at Emory Saint Joseph’s Hospital and the Emory University School of Medicine in Atlanta, wrote in an accompanying editorial that the impact of the quantitative anatomic burden “form” and the ischemic burden “function” were interesting.

“The degree of ischemia did not predict the clinical outcome, whereas the extent of anatomic obstruction of the coronary arteries did,” King wrote. “[LV] dysfunction was, as expected, also a predictor of adverse events.”

Spencer B. King III

King suggested that the findings establish two points. “First, neither the coronary anatomy nor myocardial ischemia nor the combination of the [two] interacted with the therapeutic assignment to predict outcome,” he wrote. “Second, which is perhaps more interesting, was that [LV] ejection fraction and the anatomic burden of disease at baseline were predictors of the combined endpoints of death, [MI] or non-ST-segment elevation [ACS], but the ischemic burden was not.”

King added that the findings of the current substudy may have implications for the ISCHEMIA trial.

“The purpose of this study is to eliminate patients with left main disease who would have not been suitable for medical therapy alone and to eliminate patients without significant stenoses,” he wrote, and suggested that the study raises some relevant clinical questions.

“Should angiograms be restricted to patients with higher risk scores from noninvasive evaluations of ischemia, or should some be considered for angiography?” King wrote. “What will be the future role of computed tomographic angiography be in these patients? Although this substudy of the COURAGE trial does not answer all of these questions, it certainly raises the possibility that form may sometimes trump function in predicting cardiovascular events.”

For more information:

Mancini GBJ. J Am Coll Cardiol Intv. 2013;doi.10.1016/j.jcin.2013.10.017.

King SB. J Am Coll Cardiol Intv. 2013;doi.10.1016/j.jcin.2013.10.018.

Disclosure: The researchers report financial relationships with companies including AstraZeneca, Astellas Healthcare, Bayer Healthcare, Bristol-Myers Squibb, Datascope, Eli Lilly, EvaHeart, Forest, GE Healthcare, Genentech, Gilead, GlaxoSmithKline, Janssen, Lantheus Medical Imaging, Merck, Novartis, Pfizer and Sanofi-Aventis. King reports associations with Celonova Biosciences, Merck and Wyeth Pharmaceuticals. See the study and editorial for a full list of disclosures.