Novel Trial Design Focus - Left Main and “All Comers” DES Studies: All-Comers Studies. Interventional View Jeffrey J. Popma, MD Director, Innovations in Interventional Cardiology Senior Attending Physician Beth Israel Deaconess Medical Center Associate Professor of Medicine Harvard Medical School Boston, MA

Jeffrey J. Popma, MD DISCLOSURES Grants/Contracted Research Honoraria Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson company, Medtronic CardioVascular, Inc. Honoraria Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson company I intend to reference unlabeled/unapproved uses of drugs or devices in my presentation. I intend to reference transcatheter aortic valves.

How the heck did we get here? PCI v. Device Indications Left Main and “All Comers” Studies: Our Preoccupation with “On-Label” Indications Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. How the heck did we get here? PCI v. Device Indications Opportunity Lost Final Suggestions

The Predicate – Predicate Device Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. 8/2/1994 Palmaz-Schatz Stent FDA Approval “Focal, de novo lesions in native coronaries 3.0-4.0 mm”

Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. 8/12/1998 The NIR Premounted Stent System . . . . is indicated for use in: patients with symptomatic ischemic disease due to discrete de novo lesions in native coronary arteries (length < 25 mm with a reference vessel diameter of 3.0 to 4.0 mm); treatment of abrupt or threatening closure in patients with failed interventional therapy (in lesions with reference diameters in the range of 2.5 to 4.0 mm); and patients with symptomatic ischemic heart disease due to lesions in saphenous vein bypass grafts (with lesion length < 30 mm and reference vessels diameter in the range of 3.0 to 4.0 mm). ACS Multi-Link (RX and OTW) Duet™ Coronary Stent Systems (CSS) . .. approval for additional stent sizes 2.5 mm diameter or 35mm length) and ACS Multi-Link (RX and OTW) Duet (stents with 2.5mm diameter or 38mm length) CSS. 2/18/1999 The SCIMED RADIUS™ Coronary Stent (14 mm and 20 mm lengths) with Delivery System is indicated for use in patients with symptomatic ischemic heart disease due to discrete de novo native coronary artery and saphenous vein bypass graft lesions (length <30mm) with reference vessel diameter ranging from 2.75 to 4.25 mm and is intended to improve coronary luminal diameter. 2/11/1999

“On Label Use” – Single lesion – De novo lesion – Native coronary Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. – Single lesion – De novo lesion – Native coronary - Patients with stable CAD only. - Cypher: 2.5-3.5 mm vessel, <30 mm long. - Taxus: 2.5-3.75 mm vessel, <28 mm long. - Endeavor: 2.5-3.5 mm vessel, <28 mm long.

Off Label Use • Vessel size: Cypher < 2.5 mm or > 3.5mm, Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. • Vessel size: Cypher < 2.5 mm or > 3.5mm, Taxus <2.5mm or >3.75mm. • Unstable syndromes, all MI’s. • Bifurcation • CTO • Ostial lesions • Long lesions (> 28 or 30 mm). • Bypass grafts. • In-stent restenosis lesions. • Multiple lesions or multiple vessels. • Left main coronary artery.

How the heck did we get here? PCI v. Device Indications Left Main and “All Comers” Studies: Our Preoccupation with “On-Label” Indications Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. How the heck did we get here? PCI v. Device Indications Opportunity Lost Final Suggestions

ACC-AHA Appropriateness” Criteria Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Patel et al JACC 2009 53 (February): 530-553

Appropriateness: High Risk Stable CAD Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. Patel et al JACC 2009 53 (February): 530-553

How the heck did we get here? PCI v. Device Indications Left Main and “All Comers” Studies: Our Preoccupation with “On-Label” Indications Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. How the heck did we get here? PCI v. Device Indications Opportunity Lost Final Suggestions

Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning.

Outcomes Following Coronary Stenting: A National Study of Long Term, Real-World Outcomes of Bare-Metal and Drug-Eluting Stents Pamela S. Douglas, J. Matthew Brennan, Kevin J. Anstrom, Eric L. Eisenstein, David Dai, Ghazala Haque, David F. Kong, Ralph Brindis, Art Sedrakyan, David Matchar, Eric D. Peterson Duke Clinical Research Institute Duke University Medical Center

Landmark Display: Mortality Consistent in all subgroups & across time

2009 ACC-AHA Guidelines Marroquin OC, Selzer F, Mulukutla SR, et al. A comparison of bare-metal and drug-eluting stents for off-label indications. N Engl J Med. 2008;358:342–52. Garg P, Normand SL, Silbaugh TS, et al. Drug-eluting or bare-metal stenting in patients with diabetes mellitus: results from the Massachusetts Data Analysis Center Registry. Circulation. 2008;118:2277– 85.

How the heck did we get here? PCI v. Device Indications Left Main and “All Comers” Studies: Our Preoccupation with “On-Label” Indications Control is required for study validity, to avoid the fallacy of post hoc ergo propter hoc reasoning. How the heck did we get here? PCI v. Device Indications Opportunity Lost Final Suggestions