Decline in the Use of Drug-Eluting Stents for Patients With NSTEMI Undergoing PCI: Results From the CRUSADE and ACTION Registries Matthew T. Roe, Christopher P. Cannon, Anita Y. Chen, Sunil Rao, John Rumsfeld, Lloyd Klein, E. Magnus Ohman, W. Brian Gibler, Eric D. Peterson on behalf of the CRUSADE and ACTION Registry Participants

Disclosure Statement  Schering-Plough – research grants, consultant, speakers bureau  Bristol Myers-Squibb – research grants, speakers bureau  Sanofi-Aventis – research grants, speakers bureau  Portola Pharmaceuticals – research grants  Lilly – research grants  Daiichi-Sankyo – research grants  Novartis – compensation for Clinical Events Committee adjudication activities

Background Drug eluting stents (DES) approved in 2003 with a rapid uptake in U.S. clinical practice Public debate regarding the risks of stent thrombosis with DES intensified starting in September, 2006 –Numerous registry analyses identified an increased risk of stent thrombosis, especially with “off-label” use –More than 50% of DES use “off-label” in the US FDA Circulatory Systems Devices Advisory Panel reviewed DES data in December, 2006 Both FDA and SCAI released statements in January, 2007 recommending caution with “off-label” DES use

Objective Evaluate trends in DES use among patients with NSTEMI undergoing PCI (an off-label indication) before and after the DES debate and FDA Advisory Panel recommendations

Methods (1) Evaluated temporal patterns of DES vs. Bare Metal Stent (BMS) use among NSTEMI patients undergoing PCI from January, 2006 – December, 2007 in the CRUSADE and ACTION Registries CRUSADE ceased data collection in Dec, 2006 and transitioned to the ACTION registry BMS vs. DES use was analyzed by quarter among hospitals submitting data to the respective registries

Methods (2) Patient Exclusions –Contraindications to catheterization –Transfer out to another hospital –Missing stent type (includes PTCA only) Data were analyzed by quarter among the overall NSTEMI population with trends in BMS vs. DES use analyzed only among the PCI population Patients with both DES and BMS implanted during the same PCI procedure were entered as DES on the data collection form

Patient and Hospital Data CRUSADE: Quarter 1, 2006 – Quarter 4, 2006 –NSTEMI patients = 20,593 –Total Hospitals = 285 ACTION: Quarter 1, 2007 – Quarter 4, 2007 –NSTEMI patients = 23,934 –Total Hospitals = 269

Hospital Characteristics by Quarter Q1 06 N=250 Q2 06 N=252 Q3 06 N=237 Q4 06 N=208 Q1 07 N=219 Q2 07 N=226 Q3 07 N=233 Q4 07 N=215 West Region, % Northwest Region, % Midwest Region, % South Region, % Teaching Hospital, % Median Beds (n)

Patient Clinical Characteristics by Quarter Q1 06 N=5532 Q2 06 N=5575 Q3 06 N=5188 Q4 06 N=4298 Q1 07 N=5746 Q2 07 N=6259 Q3 07 N=6025 Q4 07 N=5904 Median Age, yrs65 Female Sex (%) Diabetes Mellitus (%) Prior MI (%) Prior PCI (%) Prior CHF (%) ST Depression (%)

Acute (< 24 hrs) Medications by Quarter Q1 06 N=5532 Q2 06 N=5575 Q3 06 N=5188 Q4 06 N=4298 Q1 07 N=5746 Q2 07 N=6259 Q3 07 N=6025 Q4 07 N=5904 Aspirin (%)97 Any Heparin (%) Beta-Blocker (%) Clopidogrel (%) GP IIb-IIIa Inhibitor (%)

Use of Invasive Procedures by Quarter Q1 06 N=5532 Q2 06 N=5575 Q3 06 N=5188 Q4 06 N=4298 Q1 07 N=5746 Q2 07 N=6259 Q3 07 N=6025 Q4 07 N=5904 Catheterization (%) Cath < 48 hrs (%) PCI (%) PCI < 48 hrs (%) CABG (%)

Trends in DES vs. BMS Use for PCI for NSTEMI % DES Debate Begins FDA Advisory Panel

In-Hospital Outcomes by Quarter Q1 06 N=5532 Q2 06 N=5575 Q3 06 N=5188 Q4 06 N=4298 Q1 07 N=5746 Q2 07 N=6259 Q3 07 N=6025 Q4 07 N=5904 Death (%) Re-MI (%) CHF (%) Shock (%)

Limitations Hospital participation different in ACTION vs. CRUSADE –~ 75% of hospitals in ACTION previously participated in CRUSADE and hospital characteristics similar Type and number of DES and BMS implanted during PCI were not collected Angiographic lesion characteristics not collected Only in-hospital outcomes analyzed –Could not assess rates of stent thrombosis and other ischemic events post-discharge

Conclusions Public debate regarding the risks of stent thrombosis with DES was associated with a rapid and sustained decline in the proportion of NSTEMI patients undergoing PCI who received a DES – an “off label” indication The magnitude and duration of this temporal change in DES use is still being assessed