CPORT- E Trial Randomized trial comparing medical, economic and quality of life 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 Patient for Diagnostic Cath Informed consent Catheterization Meets inclusion criteria PCI no SOS PCI with SOS Exclusion criteria Consent Registry Refuse No Consent Registry Not Approached 3:1 Randomization Analysis by intention-to-treat

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 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.

Inclusion and Exclusion Criteria Patient 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 Devices 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 60 Centers Center Annual PCI Procedure Volume 150 (99,216) median (25 th,75 th percentile) Median Participation Duration 2.2 years

99479 Visits Consented No Consent PCI Randomized Not Randomized 2298 PCI Excluded (12%)

18867 PCI Randomized No PCI 299 (1.6%) PCI (98.4% CABG Lesion Not SignificantWithdrawal Medical TxOverall SOS0.73%0.79%0.68%0.51%3.68% No-SOS0.14%0.27%0.12%0.09%0.86% Assigned Unassigned 72 SOS 0.73% No-SOS 0.28% No-SOS SOS 4515

No-SOSSOSp-value Age (years) (mean+/-SD) 64+/ Male Gender (%) Race/Ethnicity (%) Caucasian Africa-American Hispanic 5.6 Asian Hypertension (%) Hypercholesterolemia (%) Smoking (Current & Former) (%) Diabetes (%) Family History of CAD (%) Heart Failure (%) Prior MI (%) Prior PCI (%) Prior CABG (%) Prior Stroke or PVD (%) Creatinine (mg/dl) 1.15+/ / GFR ml/min/1.73 m / / BMI kg/m / /

Presentation Clinical CharacteristicsProcedure Status No-SOS (%) SOS (%) Elective Urgent Emergency No-SOS (%) SOS (%) ACS Stable * P < 0.001

Baseline Diagnostic Catheterization No-SOS (%) SOS (%) p-value One vessel CAD Two vessel CAD Three vessel CAD28.0 Left main disease Graft disease LV function (EF)54.2 +/ / 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 < Lab Visits /Index PCI < Single Vessel PCI7978 Multi-Vessel PCI2122 Staged Index PCI procedure requires one or more catheterization laboratory visit dates in addition to the diagnostic catheterization date

PCI Success Patient Success P= Lesion Success P= PCI Success: <20% residual stenosis and TIMI 3 flow

Mortality 6- Weeks No-SOS (%) SOS (%) P-value Death The difference in 6 week mortality is % 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 Bleeding Vascular repair Stroke Renal Failure

Unplanned Procedures No-SOS (%) SOS (%) P-value CABG Emergency CABG Unplanned Cath Unplanned PCI

Summary PCI success is greater than 90% in both groups but lower in patients randomized to hospitals without surgery on-site (success rate difference of 1.1% on per patient basis; 0.7% on per lesion basis) Number of cath lab 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 catheterization and PCI procedures are uncommon but occur more frequently in patients randomized to hospitals without surgery on-site (4.4% no-SOS vs 3.4% SOS) Emergency CABG procedures are rare, but occur more frequently in patients randomized to hospitals with surgery on-site (0.1% no-SOS vs 0.2% SOS) 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.

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

Summary No SOS (%) SOS (%) Relative Difference Absolute Difference PCI Success %204 Number procedures / index PCI %5570 Unplanned cath or PCI %184 Unplanned emergency CABG %22 Mortality %4 Bleeding %76

Summary - 1 Historical, angiographic and clinical characteristics of study subjects are similar at hospitals with and without on-site surgery Acute coronary syndrome is the most frequent clinical presentation in both groups Fewer procedures are classified as “elective” at hospitals without surgery on-site PCI success rate differs by less than 1% in the two groups, but is statistically lower at hospitals without on-site surgery In patients assigned to hospitals with on-site surgery there are more staged procedures and more catheterization laboratory visits are required to complete the index PCI.

Six weeks after index PCI Mortality is similar at hospitals with and without SOS Incidence of bleeding, renal failure and stroke are similar at hospitals with and without SOS Unplanned CABG, particularly emergency CABG, are more frequent at hospitals with SOS Unplanned catheterization and PCI procedures are more frequent in patient assigned to no-SOS hospitals Summary - 2

Catheterization Laboratory Visits No-SOSSOS Diagnositic Cath Visits Visits to Complete Index PCI Visits/PCI Unplanned Visits Total Visits/PCI

Reason No PCI – consented, not randomized

Consented But Not Randomized PCI at alternate site Exclusion Criteria Need Excluded Device36816% Left Main2189% Poor LV Function1617% High Risk High Risk Anatomy53723% Calcification45220% High Risk (other)41018% Tortuous27012% Co-morbidity2009% Bifurcation1979% Thrombus703% Total > 100 % because of multiple reasons for some patients

PCI Success PCI Success: <50% residual stenosis and TIMI 3 flow * Kutcher MA et al. J Am Coll Cardiol, 2009, 54:16-24

No-SOSSOSOff-Site*On-Site* Age (years) (mean+/-SD) 64+/ Male Gender (%) Race/Ethnicity (%) Caucasian Africa-American Hispanic 5.6 Asian Hypertension (%) Hypercholesterolemia (%) Smoking (Current & Former) (%) Diabetes (%) Family History of CAD (%) Heart Failure (%) Prior MI (%) Prior PCI (%) Prior CABG (%) Prior Stroke or PVD (%) Creatinine (mg/dl) 1.15+/ /-0.87 GFR ml/min/1.73 m / /-27.1 BMI kg/m / /-24.5 * Kutcher MA et al. J Am Coll Cardiol, 2009, 54:16-24

Adverse Events - 6-Weeks No-SOS (%) SOS (%) Off-Site* (%) On-Site* (%) Death Bleeding Vascular repair Stroke Renal Failure * Kutcher MA et al. J Am Coll Cardiol, 2009, 54:16-24

Unplanned Procedures No-SOS (%) SOS (%) Off-Site* (%) On-Site* (%) CABG Emergency CABG Unplanned Cath Unplanned PCI * Kutcher MA et al. J Am Coll Cardiol, 2009, 54:16-24

Disclosure Participating sites supported study infrastructure and personnel at Johns Hopkins – Clinical Coordinating Center Duke – Economics and Quality of Life Clinical Trials and Survey Corporation – Data Analysis