Should We enCOURAGE Stress Testing on Medications?

Dear Editor,

The recent Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial1 has generated substantial concern in the lay as well as medical presses regarding potential excesses in percutaneous coronary interventions (PCI). Boden et al had randomized 2,287 patients with chronic stable angina (CSA) to optimal medical therapy (OMT) with or without PCI. No differences were found for the primary endpoint of death or acute myocardial infarction (p = 0.62) during the median 4.6-year follow-up period. Subjects randomized to the PCI arm, however, did enjoy less recurrent angina.

This finding, however, is quite consistent with existing cardiologic practices and principles. As the prognosis in patients with true CSA is usually benign, PCI trials have demonstrated symptomatic improvements, but never survival advantages. Indeed, aside from primary PCI during ST-elevation myocardial infarctions, percutaneous coronary revascularization is not associated with mortality reduction in any subgroups. Additionally, in COURAGE, there were numerous crossovers into the PCI arm, thereby possibly improving the control results, based upon an intention-to-treat analysis.

Nonetheless, there may be yet another, perhaps unintended, lesson to be learned here. In the nuclear substudy, Shaw and colleagues2 evaluated 314 patients with serial rest/stress myocardial perfusion studies at baseline and at 6–18 months post randomization. Achievement of significant ischemia reduction was greater with the PCI arm (33% versus 19%, p = 0.0004). Moreover, in patients with moderate-to-severe baseline ischemia, the reductions were 78% versus 52% in the PCI/OMT versus OMT groups, respectively. Consistent with the total study group, there was again no difference in mortality.

Could we, then, take these findings even a step further? Perhaps stress tests can be performed with OMT as an initial evaluation for patients with symptoms of CSA. Those individuals without demonstrable ischemia on OMT are likely to have mild ischemia adequately treated by the medication regimen. OMT would unlikely “mask” severe or life-threatening (“surgical”) coronary stenoses.

Conversely, if significant reversible perfusion defects are detected on OMT, then subsequent invasive evaluation and potentially revascularization may be indicated to further unburden the significant ischemia not treatable by OMT alone.

Current practice for exercise testing, with or without imaging, is to withhold beta-blockers to allow adequate pulse acceleration. However, if a patient on OMT (including beta-blockade) achieves a lower peak heart rate with maximal exercise, is he/she not in fact thus protected by the medical regimen? That is, if that patient, while on OMT, attains 75% of the age-adjusted maximal predicted heart rate at peak exercise, he/she is unlikely to surpass that workload during other strenuous activities. The absence of demonstrable ischemia at that heart rate and workload may thus indicate adequate OMT protection for that individual patient.

Moreover, interruption of anti-anginal medications (usually for 48 hours) can be problematic in some cases. Patients with tachyarrhythmias may have rebound increases in heart rate with beta-blockade cessation. If beta-blockers are serving a dual function as antihypertensive therapy, undesirable blood pressure elevations may also result. On rare occasions, patients may experience destabilization of their previous CSA symptoms while these medications are withheld.

Clearly, there are, at present, no data to support such clinical practices. Nonetheless, if validated by future evaluations, ischemia testing on OMT may help reduce the frequency of borderline studies which result in therapeutic dilemmas, especially in light of the COURAGE results.

Sincerely,

Jack P. Chen, MD, FACC, FSCAI, FCCP
Director of Cardiac Translational Research
Saint Joseph’s Translational Research Institute
Saint Joseph’s Hospital of Atlanta
and Chairman, Department of Cardiology
Northside Hospital, Atlanta, GA  30342
E-mail: chenjackapollo@yahoo.com
 

J INVASIVE CARDIOL 2008;20: 492