1. 7/9/08 Priya Pillutla, M.D. Cath Conference

2. History Priya Pillutla, MD HPI – 58 y/o M presented in May ‘08 w/escalating chest pressure at rest and with exertion – Symptoms relieved with NTG; exertional chest pain better with rest – Cath planned but patient eloped; referred back from clinic for persistent chest pain PMH – CAD, DJD – NSTEMI 11/07. Cath showed R dominant system, 90% proximal LAD stenosis s/p PCI (3.5x12mm taxus and 4x18mm driver)

3. History Priya Pillutla, MD Meds – Metoprolol, clopidigrel, simvastatin, lisinopril, NTG as needed, adderal Allergies - ?iodine (no complications 11/07) Social hx - Marginally housed, denies substance abuse – Utox + meth, cannabis Family hx - noncontributory

4. Physical Exam Priya Pillutla, MD VS – BP 128/65, HR 60, RR 13, 98% RA Disheveled JVP 7 cm H20. Neck supple, normal carotid upstrokes PMI nonsustained, nondisplaced. RRR nl s1/s2. No s3/s4. No murmurs. Lungs clear Abdomen soft, nontender No edema 2+ radial, femoral and dorsalis pedis pulses

5. Laboratory Data Priya Pillutla, MD Electrolytes - K 4.5, Cr 0.8 Hematocrit - 40.8 Platelets - 230K INR - 1 Cardiac biomarkers - Troponin neg, CKMB normal x 3

6. Priya Pillutla, MD

7. Cardiac Catheterization Priya Pillutla, MD

8. Summary Priya Pillutla, MD High-grade (95-99%) in-stent restenosis of the proximal LAD and proximal stent 40% stenosis PCI of proximal LAD using cutting balloon (4x10mm) – Probable compliance issues given living situation and +utox Excellent angiographic result with TIMI 3 flow and resolution of chest pain Patient observed overnight and discharged the following day without complications Missed cath f/u appointment

9. In-stent restenosis Priya Pillutla, MD Can be seen in 5-35% 1 of patients after PCI Somewhat lower after DES Mechanisms include: Negative remodeling Elastic recoil Neointimal hyperplasia 1 Stone et al, JAMA, 2005

10. Treatment options Priya Pillutla, MD Angioplasty (PTCA, cutting balloon) High rates of restenosis 1 (39-67%) Mechanical debulking (rotational, laser) Repeat stenting (BMS, DES) Intracoronary radiation (brachytherapy) 1 Scheller et al, NEJM, 2006

11. Priya Pillutla, MD Dauerman, JACC, 2006 (Not shown - TAXUS V, showing that PES is better than brachytherapy)

12. Current effective treatments Brachytherapy Works well but considerable safety, logistical and technical issues Risk of stent-edge restenosis and thrombosis DES Recurrence rates 13-22% 1 DES + DES = higher rate of restenosis 2 (43%) Very small but serious risk of stent thrombosis 1 Scheller et al, NEJM, 2006 2 Lemos et al, Circulation, 2004 Priya Pillutla, MD

13. What’s special about DES? Drug-elution is key Can drug be delivered for a shorter time? Can lower levels of drug still attain antiproliferative effects? Data (cell-culture and swine experiments) suggest that both of the above are true! Priya Pillutla, MD

14. Paclitaxel-Coated Balloon Angioplasty – PACCOCATH ISR NEJM, 2006 (Scheller et al) Hypothesis - Angioplasty using paclitaxel-coated balloons will prevent in-stent restenosis Balloon delivers all of the drug at once and is then withdrawn Priya Pillutla, MD

15. Study design Double-blind, randomized pilot study Inclusion Angina or +functional study Single restenotic lesion Exclusion Recent MI, CKD, allergy Sick or noncompliant Long (>30mm) or small (<2.5mm) lesions <70% stenosis Significant calcification Thrombus Priya Pillutla, MD

16. Study Design Patients randomized to Conventional PTCA PTCA with paclitaxel-coated balloon (3 ug/mm2) Angiography before, after and at 6 months using QCA (quantitative coronary angiography) ASA, plavix x 1 month then ASA alone Endpoints Primary – late luminal loss (lumen at 6 months vs after PTCA) Secondary – restenosis, combined clinical events Priya Pillutla, MD

17. Results 52 patients 26 patients in each group Similar baseline and procedural characteristics Mean age 64 years 71% men Most patients had multi-vessel disease with diffuse ISR Priya Pillutla, MD

18. Angiographic findings – 6 months UncoatedCoatedp value MLD (in-stent)1.6 mm2.3 mm0.004 LLL (in-segment) ** primary endpoint 0.74 mm0.03 mm0.002 Restenosis (%)4350.002 MLD = minimal lumen diameter; LLL = late lumen loss Priya Pillutla, MD

22. Adverse events – related or possibly related to procedure Uncoated group 2 small groin hematomas 6 revascularizations, 1 unstable angina Coated group 3 small groin hematomas 1 MI (possibly related) ** Second MI noted in a patient randomized to uncoated balloon who erroneously received coated balloon, possibly related to balloon Priya Pillutla, MD

23. Limitations Extremely small Not truly blinded – coated balloons had distinct appearance Should be studied in comparison with standard of care (DES) Anti-platelet agents only given for 1 month Was LLL an appropriate parameter? DES trials show that early LLL may not correlate well with restenosis Nevertheless results are encouraging Priya Pillutla, MD

24. Summary In-stent restenosis continues to complicate PCIs Neoproliferation, negative remodeling and elastic recoil are causative factors Therapy Data most strongly supports DES at this time Drug-coated balloon PTCA is likely to be an emerging modality Priya Pillutla, MD