Kaleida Global Vascular Center UB Translational Research Center Jacobs Institute UB Translational Research Center

Travis Dumont MD Shady Jansen L. N. Hopkins MD Symptomatic Intracranial Stenosis: Why Did SAMPRAS Fail, and How Do We Manage the Refractory Patient? Travis Dumont MD Shady Jansen L. N. Hopkins MD

LN Hopkins, MD I disclose the following financial relationship(s): Consultant/Honoraria - Abbott, BARD, Boston Scientific, Cordis, Toshiba, Gore, Medtronic Financial Interest - Access Closure, Boston Scientific, Claret, Osteal, Vascular Dynamics, Square One Director - Access Closure, Claret, Osteal University Grants/Research Support - Boston Scientific, Cordis, Micrus, Toshiba, St Jude

Intracranial Stenosis Common … Dangerous…Treatable with Risk 7-10% of Ischemic CVA’s 70-90,000 CVA’s 15% Recurr Rate Warning TIA- 20% Natural Hx (Sx stenosis) is Poor Med therepy 12-24% 1 Yr M&M Coumadin is dangerous (WASID) Primary Stenting high risk Restenosis is common (25-40% BMS)

WASID trial Enrollment stopped due to increased adverse events in warfarin group incidence of ischemic stroke 22% in both groups Conclusion: Warfarin has significantly higher adverse events and no benefit over aspirin

Aggressive Medical Management alone Study Design 450 patients Angioplasty and Stenting (Wingspan System) + Aggressive Medical Management vs. Aggressive Medical Management alone

SAMMPRIS Trial stopped due to increased complications in surgical arm 30 day stroke or death 14.7% in Surgical arm 5.8% in Medical arm p = 0.002 Note: incidence of stroke events lower than treatment with aspirin or warfarin in WASID

Aggressive Medical Management Aspirin 325 mg / day for entire follow-up Clopidogrel 75mg per day for 90 days Aggressive, protocol driven risk factor management primarily targeting systolic blood pressure < 140 mm Hg (130 mm Hg diabetics) and low density cholesterol < 70 mg / dl Intervent USA – a lifestyle modification program

30-day results Among 33 strokes in PTAS group, Primary Endpoint AMM n = 227 PTAS n = 224 Ischemic stroke in randomized vessel territory 10 23 Ischemic stroke in other vessel territory 2 Symptomatic brain hemorrhage (5 reperfusion) (4 wire perforation) Non-stroke related death 1 Totals 13 (5.8%) 33(14.7%) Among 33 strokes in PTAS group, 25 within 1 day of the procedure, 8 within 2-6 days

SAMMPRIS Results >30 days Beyond 30 days, the rates of stroke in the territory of the stenotic artery are similar in the two groups (13 in each group) *fewer than half the patients have been followed for one year (results as of April 28, 2011)

SAMMPRIS Results: Current 1-Yr Rate 1-year rate of the primary endpoint 20.0% in PTAS group 12.2% in AMM group 30-day rate of the primary endpoint 14.7% PTAS vs. 5.8% AMM

SAMMPRIS: What went wrong “Hot Plaques” (within 30 days of sx) Plaque snowplow effect = perforator infarction Too much revascularization = reperfusion hge Cheese grater effect = embolization, art injury Wire perforation, vessel rupture Wingspan (1st gen- open cell) ?? wrong technology

What Went “Right” With SAMMPRIS 12.2 % 1 year end point Not so great… ?? 2 yrs WASID > 20% “Aggressive medical management” FU every 2 weeks Free meds Lifestyle coach Is this realistic and achievable ??

What about MORI 1998 Study Not Headed A cerebral arteriographic classification for intracranial stenosis Lesson: Long complex, angulated hot lesions can not be treated aggressively safely

MORI Classification Type A: short (5 mm ), concentric or moderately eccentric, and less than totally occlusive. Type B, tubular (5–10 mm ), extremely eccentric, and moderately angulated (curved), or chronic and totally occlusive for less than 3 months. Type C, diffuse (>10 mm ), extremely angulated (>90°) with an excessively tortuous proximal segment, or chronic and totally occlusive for 3 months or longer.

Mori Results The clinical success rates for type were: A- 92% , B- 86% , C- 33% Angiographic restenosis: A- 0% , B- 33% , C- 100% Ipsilateral ischemic stroke: A- 8%, B- 12%, C - 56%, at 1 year

How we do it???

Endovascular Treatment Intracranial Atherosclerotic Disease Staged Angioplasty and Stent Submaximal Angioplasty Allow Healing Delayed Stent (undresized) PRN

Could the answer come from an old solution?

Submaximal Angioplasty: UBNS Experience 2007-2011 41 patients: 1 year stroke-free survival 93% 2 perioperative complications Vessel perforation: pt died POD 4 Reperfusion hemorrhage: MRS 3 -> 4 1 30 day – 1year ischemic event

CASE 45 year old man presents with left hand numbness TIA. Cardioembolic workup was negative, but angiography confirmed right MCA near-occlusive stenosis.

Angioplasty Pre-plasty Post-plasty 1.5MM Balloon

6 months post-plasty: no symptoms

Hypothesis Patients with symptomatic intracranial stenosis treated with sub maximal angioplasty will fare better than patients treated with medical management alone due to improved blood flow and limited perioperative morbidity. Do No HARM !

Approved and Awaiting Enrollment of First Patient Prospective registry (planned 120 patients at 10 centers) Same as SAMMPRIS: entry criteria follow-up endpoints

“Don’t hurt my brain, its my second favorite organ.” Woody Allen