Swain 23 Oct Embol-X Clinical Reviewers Wolf Sapirstein M.D. Julie Swain M.D. (Cardiothoracic Surgery)

Swain 23 Oct Study Design Randomized, multicenter Control 644 patients, Filter 645 patients Control arm = patients without filter Interim data analysis at 50% of patients

Swain 23 Oct Investigational Plan “If the hypothesis tests performed at the interim are statistically significant, indicating emboli capture and equivalent safety, the study will be terminated” The study was continued to completion to attempt to show safety superiority (which was not shown)

Swain 23 Oct Inclusion/Exclusion Criteria Elective operations Isolated CAB or valve Age >60 Total 24 exclusion criteria – Neurological deficit – Hx major stroke (as defined by a clinical history of fixed, focal neurological deficit attributable to stroke) – Redo operations – Renal failure on dialysis

Swain 23 Oct Neurological Evaluation (Gross Neurologic Testing) History, Physical Exam NIH Stroke Score No neuropsychological testing

Swain 23 Oct Endpoints Efficacy: >75% of filters trap at least one particle Composite Primary Safety: 12 items (Not worse than control group with an equivalency delta of 5%) Secondary Safety: Aortic Injury (not part of composite safety endpoint)

Swain 23 Oct Patient Demographics No statistical differences in baseline characteristics between treatment and control group Treatment group: – 73% male –91% Caucasian –Average age 71 years

Swain 23 Oct Types of operations CABG AVR MVR/R 8% 6% 84%

Swain 23 Oct Composite Safety Endpoint (12 clinical events) Death Neurological Stroke TIA Non-metabolic coma Renal Creatinine >2.0 or increased 50% (non-dialysis) Dialysis Gastrointestinal Bleeding requiring transfusion Pancreatitis Cholecystitis Mesenteric ischemia Cardiac Q-wave MI Non Q-wave MI Limb threatening periph. embolism Diminished pulse Altered pallor Pain

Swain 23 Oct Number of Particles Trapped % filters >20 Maximum number trapped = 25 (38 in roll-in) Total number of particles embolized unknown Mean 5.6 particles/filter

Swain 23 Oct Selected Events % patients * * P <.001

Swain 23 Oct Manipulation-Related Aortic Injury Filter Roll In Filter Control % patients * * p<0.001 vs control 7/7842/456 9/454

Swain 23 Oct Manipulation-Related Aortic Injury Occurred in 9.2% of filter patients (42/456 patients) 3 filter patients required aortic repair Study protocol follow-up: 30 day or hospital discharge, whichever occurred first (median follow-up 7.0 days) Post hoc designed telephone follow-up of 43/49 aortic injury patients (roll in + randomized), 18/49 had > 1 year follow-up No apparent training effect Not associated with increase in Adverse Events

Swain 23 Oct Post-Hoc Data Analysis These analyses were not planned prospectively in the investigational plan Statistical treatment of post hoc analyses is not straight-forward  Nominal p-values do not account for multiplicity  No way to know how much adjustment should be applied when judging "significance"

Swain 23 Oct Selected Adverse Events (Higgins score >5) % patients p = N.S. for all points

Swain 23 Oct Summary Embol-XControlp value Trapped at least one particle 97% Composite safety endpoint 17.1%18.9%n.s. Individual safety eventsn.s. Aortic injuries9.2%2.0%<.001

Swain 23 Oct Conclusions The filter traps particles A correlation with clinical improvement was not shown Additional concerns were raised by the occurrence of aortic injuries