1. Late Open Artery Hypothesis Jason S. Finkelstein, M.D. Tulane University Medical Center 2/24/03

2. Acute Myocardial infarction Early Reperfusion Benefits Early Reperfusion Benefits –Infarct size reduction –Preservation of LV function –Increased survival

3. Post Myocardial infarction Late reperfusion benefits Late reperfusion benefits –Beyond the window of myocardial salvage remains controversial and inconclusive –However, despite lack of consensus, late mechanical reperfusion after MI seems to be a common treatment strategy

4. Hypothesis That late mechanical reperfusion in patients with asymptomatic occluded IRA’s will improve long-term clinical outcomes That late mechanical reperfusion in patients with asymptomatic occluded IRA’s will improve long-term clinical outcomes Remains to be proved by clinical trials Remains to be proved by clinical trials

5. The Open Artery Trial (TOAT)

6. Objective To conduct a randomized trial comparing late revascularization with conservative therapy in symptom-free patients after AMI To conduct a randomized trial comparing late revascularization with conservative therapy in symptom-free patients after AMI

7. Methods Patient selection criteria Patient selection criteria –Age < 75 –Uncomplicated hospital course –Sinus rhythm without BBB –Ejection fraction 3 pathological Q waves in 3 precordial leads –Absence of chest pain or hemodynamic disturbance during modified Bruce treadmill exercise testing

8. Angiography Screening Screening –Coronary angiography was performed between 3 days and 4 weeks of MI –Patients with an occluded LAD and non- significant disease elsewhere (< 50% stenosis) were randomized (< 50% stenosis) were randomized

9. Randomization 223 patients enrolled with Q-wave anterior MI 223 patients enrolled with Q-wave anterior MI 66 patients with isolated occlusion of LAD were randomized to 2 groups 66 patients with isolated occlusion of LAD were randomized to 2 groups –Medical therapy ( n=34) –Late PCI plus stent to the LAD + medical therapy ( n=32) –Very similar baseline characteristics in both groups

10. Medical therapy ASA ASA B-blockers B-blockers ACE-I ACE-I Lipid-lowering agents Lipid-lowering agents Stented patients received plavix for 2 weeks post procedure Stented patients received plavix for 2 weeks post procedure

11. End Points To compare To compare –LV function –LV size –Quality of Life –Exercise Tolerance Between the 2 groups at 12 months post AMI Between the 2 groups at 12 months post AMI

12. Patient Follow-up 6 weeks 6 weeks 3 months 3 months 6 months 6 months 12 months 12 months For 2-D echo estimates of LV function, size, assessments of exercise tolerance and quality of life For 2-D echo estimates of LV function, size, assessments of exercise tolerance and quality of life

13. Results LV ESV, EDV, and EF were similar in both groups at 6 weeks post MI LV ESV, EDV, and EF were similar in both groups at 6 weeks post MI No significant changes were observed in the medical therapy group over 12 months, but the LV ESV significantly increased in the open artery group No significant changes were observed in the medical therapy group over 12 months, but the LV ESV significantly increased in the open artery group LV ESV (106+ 37.5 ml vs. 79.7+34.4 ml) p<0.01 LV ESV (106+ 37.5 ml vs. 79.7+34.4 ml) p<0.01 –LV EDV (162.0 + 51.4 ml vs. 130.1 + 46.1 ml) p<0.01

14. Results Exercise tolerance Exercise tolerance –Exercise duration increased in both groups, but was greater in the open artery group at 12 months Quality of life Quality of life –At 12 months, late intervention was associated with less functional impairment

15. Discussion Late intervention to open occluded IRA’s is associated with greater LV dilation than a non-invasive strategy Late intervention to open occluded IRA’s is associated with greater LV dilation than a non-invasive strategy However, late PCI may lead to an improved quality of life and exercise tolerance However, late PCI may lead to an improved quality of life and exercise tolerance

16. Possible adverse effects of Late PCI Distal micro-circulation has high resistance leading to low-reflow and stasis within the epicardial vessel Distal micro-circulation has high resistance leading to low-reflow and stasis within the epicardial vessel Collateral circulation may become embolized contributing to the regression of collateral support Collateral circulation may become embolized contributing to the regression of collateral support

17. Limitations Small study, only 66 patients Small study, only 66 patients Did not assess microinfarction by routinely checking cardiac enzymes Did not assess microinfarction by routinely checking cardiac enzymes Study population was highly selected, limiting the generalizability of the findings Study population was highly selected, limiting the generalizability of the findings Role of microvascular circulation was inadequately addressed Role of microvascular circulation was inadequately addressed

18. Clinical implications Late PCI after MI is technically feasible and compelling Late PCI after MI is technically feasible and compelling Associated with an adverse effect on LV remodeling when compared to medical therapy Associated with an adverse effect on LV remodeling when compared to medical therapy Patients may not derive objective benefits from late PCI Patients may not derive objective benefits from late PCI More ongoing clinical trials are needed More ongoing clinical trials are needed

19. Occluded Artery Trial (OAT)

20. OAT Sponsored by the National Heart, Lung, and Blood Institute Sponsored by the National Heart, Lung, and Blood Institute Currently recruiting patients for an ongoing trial Currently recruiting patients for an ongoing trial Not yet published Not yet published

21. Purpose To determine whether opening an occluded infarcted artery 3-28 days post AMI in high risk asymptomatic patients reduces the composite endpoint of mortality, recurrent MI, and hospitalization for Class IV CHF over a 3 year follow up To determine whether opening an occluded infarcted artery 3-28 days post AMI in high risk asymptomatic patients reduces the composite endpoint of mortality, recurrent MI, and hospitalization for Class IV CHF over a 3 year follow up

22. Design Multi-center randomized, controlled trial Multi-center randomized, controlled trial 3200 patients are allocated to 2 treatment groups 3200 patients are allocated to 2 treatment groups –Medical therapy: ASA, B- blockers, ACE-I, and risk factor modification –PCI plus stent with medical therapy

23. Endpoint Primary composite endpoint is mortality, recurrent MI, and hospitalization of Class IV CHF Primary composite endpoint is mortality, recurrent MI, and hospitalization of Class IV CHF Costs of the 2 treatments Costs of the 2 treatments Health related quality of life Health related quality of life

24. Clinical Implication To Late PCI or Not to Late PCI? We shall see!!!!