Atlantic Cardiovascular Patient Outcomes Research Team CPORT- E Trial Randomized trial comparing outcomes of non-primary PCI at hospitals with and without on-site cardiac surgery

Motivation for Trial Sustain primary PCI program at no-SOS hospitals Improve access to PCI services Reduce pressure to create additional cardiac surgery programs Need for research to inform healthcare policy decisions by state and national organizations

C-PORT Elective No Consent Registry Patient for Diagnostic Cath Not Approached Patient for Diagnostic Cath Refuse Informed consent Consent Registry Catheterization Exclusion criteria Meets inclusion criteria Patients entered the CPORT E project through the community hospital where diagnostic catheterization was performed. Prior to diagnostic catheterization, patients signed informed consent. For those patients who were either not approached for consent or were approached but refused, a registry of baseline characteristics was developed. For those patients who signed consent but were excluded from participation, a consent registry was developed. Those patients meeting inclusion criteria and having no exclusion criteria were randomized. Randomization was asymmetric (3:1) so that for every 4 study subjects, 3 remained at the hospital without surgery on-site (no SOS) and 1 was transferred to a tertiary hospital (SOS) for PCI. 3:1 Randomization PCI no SOS PCI with SOS

Study Endpoints Non-inferiority trial Primary Endpoints All-cause mortality at 6 weeks MACE at 9 months All-cause mortality Q-wave myocardial infarction Target vessel revascularization Assuming 6 week mortality to be 0.8%, a sample size of 18360 was selected to define a non-inferiority margin of 0.4% with a one-sided test for non-inferiority using α=0.05 and β=0.80 for both primary endpoints. This report concerns only the first primary endpoint, mortality at 6 weeks.

Inclusion and Exclusion Criteria Patient Devices Institution Inclusion Age > 18 years Informed consent > 50% stenosis All target lesions approachable at no-SOS hospital Exclusion Unprotected LM EF < 20% MD-judged high risk Inclusion Balloon, stent Distal protection Covered stent Cutting balloon - in-stent restenosis Exclusion Atherectomy Cutting balloon- de novo lesion Inclusion > 200 PCI/year 24/7 Primary PCI Complete formal development program Interventionalist meets AHA/ACC competency

Participating Centers Center Annual PCI Procedure Volume 150 (99,216) median (25th,75th percentile) Median Participation Duration 2.2 years Note that if a center did 100 cases in the first year and 200 in the second, the average center volume would be 150 cases per year.

99479 Visits 23805 No Consent 75674 Consented 18867 PCI Randomized 56807 Not Randomized There were nearly 100,000 cath lab visits among the 60 participating centers. 75% of all patients were consented for the study. 2298 PCI Excluded (12%)

Lesion Not Significant 18867 PCI Randomized No PCI 299 (1.6%) PCI 18568 (98.4% CABG Lesion Not Significant Withdrawal Medical Tx Overall SOS 0.73% 0.79% 0.68% 0.51% 3.68% No-SOS 0.14% 0.27% 0.12% 0.09% 0.86% Assigned 18496 Unassigned 72 SOS 0.73% No-SOS 0.28% No-SOS 13981 SOS 4515

No-SOS SOS p-value Age (years) (mean+/-SD) 64+/-12 0.42 Male Gender (%) 64.0 63.2 0.37 Race/Ethnicity (%) Caucasian 79.1 80.2 0.33 Africa-American 11.8 11.3 Hispanic 5.6 Asian 2.1 1.9 Hypertension (%) 84.6 85.3 0.29 Hypercholesterolemia (%) 82.2 0.95 Smoking (Current & Former) (%) 61.6 62.7 0.20 Diabetes (%) 39.0 39.7 0.41 Family History of CAD (%) 56.7 57.9 0.17 Heart Failure (%) 8.6 8.8 0.64 Prior MI (%) 42.5 43.3 0.35 Prior PCI (%) 31.9 30.4 0.06 Prior CABG (%) 13.1 13.5 0.47 Prior Stroke or PVD (%) 17.3 18.4 0.09 Creatinine (mg/dl) 1.15+/-0.88 1.15+/-0.87 0.63 GFR ml/min/1.73 m2 76.5+/-34.1 76.3+/-27.1 BMI kg/m2 32.7+/-21.9 33.2+/-24.5 0.22

Presentation Clinical Characteristics Procedure Status No-SOS (%) ACS 63.8 64.1 Stable 36.1 36.0 No-SOS (%) SOS (%) Elective 76.7 79.4 Urgent 22.9 20.1 Emergency 0.36 0.57 * P < 0.001

Baseline Diagnostic Catheterization No-SOS (%) SOS (%) p-value One vessel CAD 36.1 34.7 0.22 Two vessel CAD 35.9 37.2 Three vessel CAD 28.0 Left main disease 3.2 3.7 0.13 Graft disease 9.4 9.7 0.44 LV function (EF) 54.2 +/- 10.6 54.3 +/- 10.7 0.72 Underlying CAD severity and LV function are similar in both groups Totals add up to >100% because Left Main and Graft disease are in addition to disease in the three major circulations

Procedure Characteristics No-SOS (%) SOS (%) P- Value Staged 25.7 67.7 <0.0001 Lab Visits /Index PCI 1.28 1.73 Single Vessel PCI 79 78 Multi-Vessel PCI 21 22 The number of staged procedures – defined as multiple catheterization laboratory visits required to complete index PCI – is significantly greater in the SOS group, primarily because of the need to transfer patients to an alternative facility after diagnostic catheterization, frequently requiring a procedure on a subsequent day. Staged Index PCI procedure requires one or more catheterization laboratory visit dates in addition to the diagnostic catheterization date

PCI Success No-SOS (%) SOS (%) Complete Success 90.8 91.9* Partial Success 5.7 5.5 Failure 3.4 2.5* Patient Success P=0.0096 There are no differences in PCI success when success is classified by lesion. When classified by patient, there are slightly but significantly more PCI’ patients classified as “failure” at no-SOS hospitals. However, the complete success rates are comparable and not significantly different. Complete Success: all treated lesions successful Partial Success: some treated lesions successful, others failure Failure: no treated lesion successful No-SOS (%) SOS (%) Success 93.4 94.1 Failure 6.6 5.9 Lesion Success P=0.0474 PCI Success: <20% residual stenosis and TIMI 3 flow

Mortality 6- Weeks No-SOS (%) SOS (%) P-value Death 0.91 0.93 0.94 The difference in 6 week mortality is -0.014% with a 90% confidence interval of -0.26% to 0.28%. The upper bound is <0.4%, so that the hypothesis of inferior 6 week mortality for the no-SOS hospitals is rejected at the one-sided P<0.05 level.

Adverse Events - 6-Weeks No-SOS (%) SOS (%) P-value Death 0.91 0.93 0.94 Bleeding 3.41 3.00 0.18 Vascular repair 0.38 0.40 0.86 Stroke 0.27 0.15 0.16 Renal Failure 0.50 0.37 0.28

Unplanned Procedures No-SOS (%) SOS (%) P-value CABG 0.48 0.68 0.10 Emergency CABG 0.22 0.05 Unplanned Cath 4.41 3.35 0.002 Unplanned PCI 2.11 1.32 0.001

Summary Angiographic Outcomes PCI Success > 90% in both groups but lower in hospitals without surgery on-site (success rate difference of 1.1% on per patient basis; 0.7% on per lesion basis) Number of catheterization laboratory visits required to complete the index PCI is greater in patients randomized to hospitals with surgery on-site (1.3 versus 1.7 visits/patient) Unplanned procedure outcomes Unplanned catheterization and PCI procedures were uncommon but occurred more frequently in patients randomized to hospitals without surgery on-site (4.4% no-SOS vs 3.4% SOS) Emergency coronary CABG was rarely required, but was utilized more among patients at hospitals with surgery on-site (0.1% no-SOS vs 0.2% SOS) Patient Outcomes Mortality is similar in both groups (0.91% no-SOS vs 0.93% SOS) The incidence of bleeding, vascular repair, stroke and renal failure is similar in both groups

Conclusion In hospitals without on-site cardiac surgery that complete a formal PCI development program, adhere to C-PORT participation requirements, and whose outcomes are monitored, non-primary PCI is safe and associated with similar rates of adverse events including mortality. Long-term, quality outcome data are currently being collected on these study subjects and will be reported early in 2012.