VIEWS: 29 PAGES: 3 POSTED ON: 9/21/2008
In the COURAGE trial, 2287 patients (mean age, 62; 85% men; 33.5% with diabetes; mean left-ventricular ejection fraction [LVEF] 61%) were randomized to PCI plus optimal medical therapy or to optimal medical therapy alone. All patients had either ³70% stenosis (all underwent angio prior to randomization) with objective evidence of ischemia or ³80% stenosis with classic angina. Patients with a markedly positive stress test, an LVEF <30%, class IV angina were excluded. At the end <10% of screened pts were eligible for enrollment. Of the PCI group, 94% received stents (97% bare-metal). Both groups had high rates of receiving optimal medical therapy and of adhering to healthful lifestyle interventions; they each achieved mean LDLcholesterol levels of just above 70 mg/dL. Median follow-up was 4.6 years. The incidence of death or MI (the primary outcome) was similar in both groups (about 19%), as were the incidences of hospitalization for ACS and stroke. The PCI group had a significantly lower revascularization rate during follow-up (21% vs. 33% with medical therapy alone), and they had a significant advantage in freedom from angina at 1 year (66% vs. 58%) and 3 years (72% vs. 67%) but not at 5 years (74% vs. 72%). Comment: In patients with stable CAD, the roughly 5-year incidence of death or MI was similar with PCI and optimal medical therapy alone, although PCI showed some advantage in relieving angina. As the editorialist notes, fewer than 10% of screened patients were eligible for this trial, and fewer than 75% of eligible patients were enrolled, raising questions about the generalizability of the results. On balance, the data highlight the benefits of optimal medical therapy in patients with stable CAD who do not have stress-test results that suggest high risk for events. The findings confirm the current guideline recommendation that PCI can be safely deferred in these patients. Boden WE et al. for the COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007 Mar 27 - epub ahead of print. Cost-effectiveness: This translated into a cost of $217 000 per quality of life-year gained. Thus, in cost-efficacy analyses, less than 1% of patients treated with PCI would be deemed a cost-effective approach, he said. "Over 99% of estimates of cost effectiveness were in excess of the common benchmark of $50 000," WHY? Boden and colleagues propose that their findings can be explained, in part, by the fact that plaque morphology and vascular remodeling are different in ACS—where stenting has proved superior to medical therapy— than in stable coronary disease. Focal management of stable lesions through PCI would not lead to a reduction of clinical events if the lesions themselves were in no danger of triggering an acute coronary event, they explain; by contrast, systemic medical therapy and riskfactor management may have the effect of reducing plaque vulnerability. "Angina will improve with either PCI plus optimal medical therapy or optimal medical therapy alone," Weintraub stated. "PCI plus optimal medical therapy does offer an incremental benefit over optimal medical therapy alone in treating angina, but compared with optimal medical therapy, PCI plus optimal medical therapy as a first-choice therapy for stable CAD is expensive." Caveats: 1. Not a trial of DES (97% BMS). 2. The optimal degree of medical rx in COURAGE may be hard to reproduce in real life. 3. Astringent screening to be enrolled in the trial with 35000 screened and only 3000 meeting elegibility criteria - more than 90% of those evaluated (also see below: Notes). 4. Among the patients who underwent PCI, 14.5% of the lesions were treated with coronary angioplasty without placement of a stent, a procedure that is subject to rates of revascularization and periprocedural myocardial infarction that are higher than those among patients receiving stents. 5. No quantification of ischemic burden. Recent data (presented at AHA Scient Mtng - see below) suggests that OMT is not enough to reverse ischemia and ischemia by MPI was related to more deaths or MI. 6. Boden et al. (the principal investigators) appropriately analyze their data according to the intention-to-treat principle. However, in the medical-therapy group, 25.5% of patients (32.6% who underwent revascularization minus 7.1% who underwent coronary-artery bypass grafting) underwent PCI by the end of the study for refractory angina or worsening ischemia on noninvasive testing. Moreover, in 4% of the patients in the PCI group, PCI was not attempted. Outcome data for the 848 patients in the medical-therapy group who did not undergo subsequent PCI (74.5%) were not reported separately. Hence, the effect of subsequent PCI on the outcome in the medical-therapy group is unknown. Specifically, calculation of the prevalence of angina needs to take subsequent PCI into account, since PCI was performed for refractory angina. Because of the high rate of crossover, analyzing the data separately according to the treatment actually received would be useful in interpreting the trial results. 7. Boden et al. reaffirm that PCI does not reduce the risk of death or myocardial infarction among patients with stable coronary disease. But the authors mistakenly state that "approximately 85% of all PCI procedures are undertaken electively." This statement misinterprets the cited report by Feldman et al (1) which explicitly counted PCI procedures in patients with unstable angina as "elective" (Table 2 of the report by Feldman et al.). On the basis of data in Tables 1 and 2 of that report, of 82,140 patients who underwent PCI, 10,964 underwent "emergency" procedures and 45,459 had "unstable angina." This leaves 25,717 patients with stable condition who underwent elective procedures (31% rather than the 85% reported by Boden et al.). Moreover, of the 31% of patients who underwent elective procedures, many probably had criteria that would have excluded them from the COURAGE trial: class IV angina, a markedly positive exercise test, refractory heart failure, poor ventricular function, or recent revascularization. (1).Feldman DN, Gade CL, Slotwiner AJ, et al. Comparison of outcomes of percutaneous coronary interventions in patients of three age groups (<60, 60 to 80, and >80 years) (from the New York State Angioplasty Registry). Am J Cardiol 2006;98:1334-1339. 8. If no angio is done in stable angina pts because they will be rx'ed w OMT it is possible to miss LM dz. In COURAGE almost 1000 (940) pts were excluded on the basis of having LM dz. If no angio had been done prior to randomizaion this would have gone unnoticed. ----------------------------FURTHERMORE: Data presented at AHA 2007 Scientific Meetings: - PCI + OMT (as opposed to OMT alone) produced a >5% red in quantitative ischemic chngs by SPECT 33 vs 20% p 0.004. If the analysis is limited to those w mod to sev ischemia at baseline: 78 vs 52% p 0.007. - There was a direct correlation between the extent of residual ischemia at f/u MPI (Myoc Perf Imaging) and % of or MI. (Shaw LJ). - This is highly suggestive that if there is a large ischemic defect or a significant ischemic burden by MPI these pts should be revascularized even if they have stable angina sxs and despite COURAGE findings. - Question remains of what is considered "large" or "siginficant". - It is possible that a much greater benefit had been seen in revascularization if DES were used, particularly in the setting of new data presented (Mass Registry). Major critique by Dean Kereiakes et al, JACC 2007;50:1598. NOTES: - It is probably still wise to cath pts w stable angina to r/o potential LM dz.
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