SPECT Substudy of COURAGE shows Improved Perfusion with PCI at Follow-Up

November 6, 2007 By Alexandra M. Palmer [mailto:apalmer@perfuse.org]

Orlando, FL: Results from a substudy of the Clinical Outcomes Using Revascularization and Aggressive Drug Evaluation (COURAGE) Trial demonstrate greater improvements in follow-up stress myocardial perfusion ischemia when patients undergo both percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) as compared with OMT alone. The substudy data was presented by Leslee J. Shaw at the American Heart Association 2007 Scientific Sessions.

The COURAGE trial, conducted from 1999-2004, was a multicenter study which enrolled 2,287 patients at 50 centers in the U.S. and Canada. The inclusion criteria selected patients who were stable on medical therapy and had a history of angina or documented myocardial ischemia with at least one significant coronary lesion. 1,138 patients were randomized to OMT alone and 1,149 to OMT+PCI. The duration of follow-up was a median of 4.6 years (minimum of 2.5 and a maximum of 7 years).

A total of 313 patients from the COURAGE trial were selected to participate in the myocardial perfusion imaging substudy. Ischemia was assessed by myocardial perfusion single photon emission computed tomography (myocardial perfusion SPECT or MPS). The substudy included 155 patients randomized to OMT alone and 159 to OMT+PCI. The duration of clinical follow-up for events was a median of 1 year after the SPECT study.

Patients with stable chest pain and stress-induced ischemia before treatment benefited more from PCI + OMT and experienced a greater reduction in ischemia by one year when compared to OMT alone. The proportion of patients with a reduction in ischemia greater than or equal to 5% was significantly greater in the PCI+OMT group vs OMT alone group (33.3% vs 19.8%, p=0.004). Among patients who had severe ischemia at baseline before PCI, a reduction in ischemia was again greater for the PCI+OMT strategy (78% (n=54) vs 52% (n=51) in the OMT group, p=0.007).

Among patients with CCS class > 1, there was a greater improvement in the angina class in the PCI+OMT group when compared to the OMT group (70% vs. 63%, p=0.0077).

Improvement in SPECT ischemia was associated with a lower rate of death and MI. Among 105 patients with severe ischemia before treatment, a 5% or greater reduction in ischemia was associated with lower rates of death or MI when compared to no reduction in ischemia (16.2% vs. 32.4% p=0.001).

The fact that this was a substudy and drew upon select patients from the COURAGE study limits the broad applicability of the results (14% of total COURAGE population were enrolled in the substudy). These observations pertain to a non-randomized group of population. The follow-up MPS was performed at 6 to 18 months, and the possibility of a delayed improvement associated with medical therapy cannot be excluded. The analysis was underpowered but was generated for exploratory purposes.

This substudy extends prior results from COURAGE which indicate no statistical difference between the PCI and the OMT group.

This substudy was supported by Bristol Myers-Squibb Medical Imaging and Astellas Healthcare.

| View the slides here

References 1. Leslee J. Shaw, Daniel S. Berman, David J. Maron, G.B. John Mancini, Sean W. Hayes, Pamela M. Hartigan, William S. Weintraub, Robert A. O’Rourke, Marcin Dada, John A. Spertus, Bernard R. Chaitman, John Friedman, Piotr Slomka, Gary V. Heller, Guido Germano, Gilbert Gosselin, Peter Berger, William J. Kostuk, Ronald Schwartz, Merill Knudtson, Emir Veledar, Eric R. Bates, Benjamin McCallister, Koon K. Teo, William E. Boden. COURAGE Nuclear Substudy II, Optimal Medical Therapy With or Without PCI to Reduce Ischemic Burden: Results from Clinical Outcomes Utilizing Revascularization and Aggessive Guideline-Driven Drug Evaluation Trial Nuclear Substudy. As presented at AHA 2007.