BOSTON — In the ongoing debate over whether patients with chronic, stable angina are better served by revascularization with percutaneous coronary intervention in addition to drug treatment or optimal medical therapy alone, the key variable appears to be ischemic burden, Dr. Daniel S. Berman reported at the annual meeting of the American Society of Nuclear Cardiology.
Last year, investigators in the Clinical Outcomes Using Revascularization and Aggressive Drug Evaluation (COURAGE) trial reported that adding percutaneous coronary intervention (PCI) to optimal medical therapy in patients with stable coronary artery disease did not improve clinical end points, compared with optimal medical therapy alone (N. Engl. J. Med. 2007;356:1503–16). The results sparked a controversy that led some experts to conclude that PCI is overused and unnecessary in stable coronary disease.
More recently, however, a substudy of the COURAGE trial comprising 314 patients equally distributed between groups treated with PCI plus optical medical therapy and optimal medical therapy alone showed that the PCI strategy produced a greater ischemia reduction than the optimal medical therapy-only (OMT-only) intervention—particularly among patients with moderate to severe ischemia at baseline.
“Importantly, patients in both groups who experienced ischemia reduction had a significantly lower risk for death or myocardial infarction than patients without ischemia reduction, and the magnitude of residual ischemia was proportional to the overall risk of subsequent cardiac event,” said Dr. Berman, chief of cardiac imaging and nuclear cardiology at Cedars-Sinai Heart Center in Los Angeles.
The main COURAGE trial included 2,287 patients, with a history of angina or documented myocardial ischemia and at least one significant coronary lesion, who were stable on medical therapy. Participants were randomized to continue their medication alone or with PCI, and the study's combined end points were death or nonfatal myocardial infarction. The composite rates of death or nonfatal myocardial infarction over 4.6 years of follow-up were statistically similar in both groups, at 19.0% for the PCI group and at in18.5%, the patients who received only optimal medical therapy, showing no benefit of PCI over optical medical therapy in stable coronary artery disease.
In the nuclear imaging substudy, the 314 patients were equally distributed between the PCI and OMT groups and they were well matched with respect to demographics and risk factors, said Dr. Berman.
All of the patients were on medication for a mean 374 days from baseline and all underwent serial myocardial perfusion single-photon emission computed tomography (SPECT-MPI) studies 6–18 months following the baseline examination to assess the extent and severity of the perfusion defect in the global myocardium, he said.
With myocardial ischemia defined as the total perfusion deficit at stress minus the perfusion deficit at rest, 33% of patients in the PCI group and 20% in the OMT-only group showed a 5% or greater reduction in ischemia.
Among the patients in the imaging substudy with moderate to severe pretreatment ischemia, defined as a perfusion defect involving 10% or more of myocardium, “78% of the PCI patients demonstrated 5% improvement or greater, compared to 52% of the [OMT-only] patients,” Dr. Berman reported.
In considering these changes in terms of their relationship to subsequent outcomes, “we looked at the myocardial infarction rates in patients with and without ischemia reduction and determined that patients in both groups with 5% improvement in ischemia had approximately 50% lower cardiac event rate,” he said.
A similarly reduced cardiac event rate was observed in the 105 patients from both groups with moderate to severe ischemia and a greater than 5% reduction in ischemia observed post treatment, he said.
Although the substudy was not sufficiently powered to generalize that reducing ischemia will prevent later cardiac events, “we did see a striking relationship between amount of residual ischemia and the subsequent death or myocardial infarction rate,” Dr. Berman stated.
This observation is “definitely a hypothesis generator,” warranting a controlled trial comparing the PCI-based strategy with optimal medical therapy alone in patients with chronic stable angina who would be randomized based on the presence of moderate to severe ischemia, he said.
“We should be studying patients with 10% or more ischemia to determine if there is a subset of patients who would have improved angina and quality-of-life outcomes with revascularization.” The findings would be especially important to those patients with documented large amounts of jeopardized myocardia in whom medical therapy does not provide adequate relief, he concluded.
The COURAGE nuclear imaging substudy was supported by Bristol-Myers Squibb Medical Imaging and Astellas Healthcare.
COURAGE patients with moderate to severe ischemia showed greater improvement after PCIthan after OMT only. DR. BERMAN