Hospitalists New options for DVT Treatment Beyond the

Hospitalists are the frontline providers that diagnose and manage hospital-acquired VTEs in hospitalized patients. Nearly half of all venous thromboembolism (VTE) events occur during or soon after hospitalizations © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 2

What Is Deep Vein Thrombosis (DVT)? DVT is a blood clot that forms in a vein deep in the body Most often occurs in the deep veins of the legs, either above the knee or below it © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 The blood clot or part of it can break free (called embolism) and become lodged in the blood vessels of the lung, causing pulmonary embolism (PE) 3

VTE: A Major Source of Mortality and Morbidity Over 200, 000 deaths per year due to PE annually in the U. S. alone. More than HIV, MVAs & Breast Cancer combined Over 600, 000 patients diagnosed with DVT annually in the US alone 10% of Hospital Deaths most common preventable death Huge Costs and Morbidity Recurrence of DVT, postthrombotic syndrome and chronic PE / PAH are long term sequelae Some Causes of Death in the US Annual Number of Deaths PE Up to 200, 000 AIDS 16, 371 Breast Cancer 40, 580 © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 4

DVT Development Risks VTE prophylaxis has already made The Joint Commission's list of Patient Safety Goals, which call for anticoagulation to be managed by protocol. Using unfractionated heparin and even low-molecularweight heparin, we're going to have a guideline to manage those patients. Several studies, including last year's Million Women Study, have shown that patients who have surgery for abdominal and pelvic cancers face a clot risk for at least a month. In the @RISTOS trial, 40% of surgical cancer patients' VTEs occurred after discharge, and the risk factors were the same, whether the clot appeared early or late. © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 5

DVT: What we know Venous thromboembolism (VTE) is manifested clinically by deep venous thrombosis (DVT) and pulmonary embolism (PE). DVT, usually of the lower extremity, nearly always precedes PE. The risk of VTE increases greatly after age 50. Other Risk Factors • Age • Trauma • Immobilization, • Surgery • Anti-estrogen tamoxifen also increases the risk of VTE • Inherited conditions that increase risk (thrombophilia) usually present before age 40, although it is not unusual to see the first episode of VTE in a patient with factor V Leiden appear after total hip replacement at age 65 © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 Occurrence The disease most often occurs in hospitalized patients, particularly those with cancer or following surgical procedures, but also occurs sporadically in the community. In both settings, multiple risk factors are usually present. 6

Risk of DVT in Hospitalized Patients No prophylaxis + routine objective screening for DVT Patient Group DVT Incidence Medical patients 10 - 26 % Major gyne/urol/gen surgery 15 - 40 % Neurosurgery 15 - 40 % Stroke 11 - 75 % Hip/knee surgery 40 - 60 % Major trauma 40 - 80 % Spinal cord injury 60 - 80 % Critical care patients 15 - 80 % Heit – Mayo Clin Proc 2001; 76: 1102 © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 7

VTE is a Disease of Hospitalized and Recently Hospitalized Patients Cases per 10, 000 person-years 1000 100 Recently hospitalized 10 1 Hospitalized patients Community residents Heit – Mayo Clin Proc 2001; 76: 1102 © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 8

VTE According to Service (N=384) Patients Total VTE (%) 44 Medical 16 General surgery 10 Medical oncology Total VTE PE DVT Orthopaedic surgery 9 8 Thoracic surgery 14 Other 0 25 50 75 100 125 150 175 Number of VTE events Goldhaber SZ et al. Chest 2000; 118: 1680 -4. © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 9

DVT and the risk our patients face: Stasis Hypercoagulability Age > 40 Immobility CHF Stroke Paralysis Spinal Cord injury Hyperviscosity Polycythemia Severe COPD Anesthesia Obesity Varicose Veins Cancer High estrogen states Inflammatory Bowel Nephrotic Syndrome Sepsis Smoking Pregnancy Thrombophilia Endothelial Damage Surgery Prior VTE Central lines Trauma Most hospitalized patients have at least one risk factor for DVT © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 10

Hospital Performance for Pharmacologic Venous Thromboembolism Prophylaxis and Rate of Venous Thromboembolism: A Cohort JAMA Intern Med. 2014; 174(10): 1577 -1584. doi: 10. 1001/jamainternmed. 2014. 3 384 Figure Legend: Flow Diagram of Patient Progress Through the 90 -Day Observation Period -- ICU indicates intensive care unit; VTE, venous thromboembolism. Studies continue to identify the risks showing the need for DVT awareness in the ICU 2015 American Medical Association. © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 11

Icoper: Cumulative Mortality After Diagnosis of PE 25 17. 5% At 90 days Mortality (%) 20 15 10 5 0 7 14 30 60 90 Days From Diagnosis Lancet. 1999; 353: 1386 -1389. © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 12

Associated Illnesses that are a Consequence of VTE events Chronic thromboembolic pulmonary hypertension Post thrombotic Syndrome Mean pulmonary artery pressure greater than 25 mm Hg that persists 6 months after PE 2 -4% of patients after PE Calf swelling and skin pigmentation; venous ulceration in severe cases Up to 43% of patients develop PTS within 2 years Goldhaber SZ, Bounameaux H. Lancet. 2012 May 12; 379: 1835 -46 © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 13

Venous Thromboembolism (VTE) remains a major health problem In addition to the risk of sudden death 30% of survivors 28% of survivors develop recurrent VTE within 10 years develop venous stasis syndrome within 20 years © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 14

DVT and the Risks DVT risk and prophylaxis in the hospitalized patient Low Risk Moderate Risk High Risk Ambulatory patient without additional VTE Risk Factors All other patients. Most patients (not LOW or HIGH category) Elective major lower extremity arthroplasty Ambulatory patient with expected LOS ≤ 2 days, or same day/minor surgery Hip, pelvic, or sever lower extremity fractures Only a few patients! Acture spinal cord injury with paresis Multiple major trauma Abdominal or pelvic surgery for cancer Ambulation and Education LMWH or UFH 5000 units SQ q 8 h LMWH or Arixtra or Coumadin Physicians at UCSD use these checklists to assess all adult inpatients when they are admitted, transferred between units, or post-op © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 15

DVT and the Risks DVT risk factors Low Moderate High Age > 50 years Prior History of VTE Acture or chronic lung disease Myeloproliferative disorder Impaired mobility Obesity Dehydration Inflammatory bowel disease Known thrombophilic state CHF Active rheumatic disease Varicose veins/chronic stasis Active malignancy Sickel cell disease Recent post-partum w/ immobility Hormonal replacement Estrogen-based contraceptives Nephrotic syndrome Moderate to Major surgery Central venous catheter Myocardial infarction Physicians at UCSD use these checklists to assess all adult inpatients when they are admitted, transferred between units, or post-op © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 16

DVT and Your Cancer Patients with cancer who develop VTE are at higher risk of both recurrence and death than other patients with VTE. Because of improved treatment and longer survival, patients with cancer account for an increasing proportion of those with VTE. • VTE can occur before cancer is evident, at the time of the cancer diagnosis and at any point in the clinical course of patients with known cancer. • VTE is particularly likely to occur during intensive chemotherapy and as a complication of cancer surgery. • For years, clinicians have been aware of so-called "warfarin failure"-the tendency to develop recurrent VTE despite an INR between 2. 0 and 3. 0 -in patients with VTE and cancer. Recent clinical trials have shown that long-term LMWH in a treatment dose reduces the recurrence rate of VTE in cancer patients by 50% compared with warfarin (INR 2. 0 -3. 0). © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 17

Strategies to Improve Thromboprophylaxis Success • • Excellent quality guidelines • • Local written policy (care pathway) for the hospital / program / patient care unit Multidisciplinary team Goals and Measures Standardized risk assessment and order sets National body endorsement Hospital accreditation (JCAHO) Pay for performance (CMS) © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 18

National Recommendations American College of Chest Physicians (ACCP) “We recommend that every hospital develop a formal strategy that addresses the prevention of thromboembolic complications. ” © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 19

The Real Question: What do we do with those patients that develop a DVT? Prompt diagnosis and treatment of deep vein thrombosis (DVT) is essential to decrease both the risk of recurrence and a potentially fatal pulmonary embolism (PE) © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 20

In-Hospital DVT Is Current in-hospital treatment adequate? Anticoagulation Compression Stockings We can do better for these patients? Using multidisciplinary team approach Understanding the options for thrombus removal Setting a goal of quickly removing the thrombus Offering minimally invasive solutions © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 21

Treating DVT Once It Has Occurred Interventional Treatment of DVT can help reduce the risk of complications, such as PE The current goals in treating DVT support: Stop the clot from progressing and getting larger Reduce the chance of having another clot develop Prevent the clot from breaking off in your vein and moving to your lungs © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 22

Treating DVT Once It Has Occurred The best strategy once a DVT has been diagnosed is clot removal The option of “clot removal” Dissolving and/or Mechanical removal Restores flow decreases risk of clot Allows venous valves to return to normal function Can decrease long term anticoagulation © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 23

A New Option For Venous Thrombus Removal New options exist for minimally invasive treatment to remove the venous clot © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 • Infusion of clot busting medication to assist in removal • Followed by thrombus removal using a mechanical device to remove the clot from the vessel and body 24

DVT Clot Removal We Believe We Can Efficiently remove thrombus Provide quick restoration of venous flow Decrease risk of embolic complications Assist in restoring normal venous valve function © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 25

DVT Clot Removal Interventional Treatment offers Patient's A minimally invasive procedure Potential to minimize treatment time Possibly eliminate or decrease dose and duration of thrombolytic Potential for quick resolution of signs and symptoms Improved short-term & long-term outcomes © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 26

An option for DVT thrombus Removal ANGIOJET™ ULTRA Thrombectomy System MECHANISM OF ACTION 1. The Angio. Jet Ultra Console monitors and controls the system. 2. The Console energizes the pump which sends pressurized saline to the catheter tip. 3. Saline Jets travel backwards to create a low pressure zone causing a vacuum effect. 4. Thrombus is drawn into the in-flow windows and the jets push the thrombus back down the catheter. © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 5. Thrombus is evacuated from the body and into the collection bag. 27

There is an indication and data behind thrombus removal Outcomes – Interventional Approach To Remove DVT Thrombus 97% 84% had venographic improvement had freedom from re-thrombosis at 1 year Improved quality of life score for mental and physical baseline out to 1 year Patients treated: 67% acute, 19% sub-acute and 14% Chronic thrombus age Bleeding complication rate was 4. 5%, however not related to the use of Angio. Jet The PEARL Registry looked at 371 DVT patients treated using an interventional approach © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 28

There is an indication and data behind thrombus removal PEARL Registry data demonstrates that mechanical thrombectomy treatment of DVT is safe and effective and can potentially reduce the need for concomitant catheter directed lytic and intensive care stay. The PEARL Registry looked at 371 DVT patients treated using an interventional approach © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 29

There Is An Indication And Data Behind Thrombus Removal Using an interventional approach for DVT results showed Overall, 75% cases completed in < 24 hours 38% of DVT treatment times were completed in < 6 hours 87% had two or less interventional treatments The PEARL Registry looked at 371 DVT patients treated using an interventional approach © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 30

Moving Forward Consults available for your patients that have developed a DVT Offer a multidisciplinary team approach to in-hospital DVT Create best practice model Develop treatment pathways to benefit patients for quicker recovery Reduce the potential risks for those that develop DVT Decrease hospital stay and cost associated with DVT Potential to improve short and long term outcomes © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 31

Case Example © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802

Questions Thank you © 2016 Boston Scientific Corporation or its affiliates. All rights reserved.

Solent Catheters combined w/console CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician. Rx only. Prior to use, please see the complete “Instructions for Use” for more information on Indications, Contraindications, Warnings, Precautions, Adverse Events, and Operator’s Instructions. INDICATIONS AND USAGE The Angio. Jet SOLENT proxi & omni Thrombectomy Sets are intended for use with the Angio. Jet Ultra Console to break apart and remove thrombus from: • upper and lower extremity peripheral arteries ≥ 3. 0 mm in diameter, • upper extremity peripheral veins ≥ 3. 0 mm in diameter, • ileofemoral and lower extremity veins ≥ 3. 0 mm in diameter, • A-V access conduits ≥ 3. 0 mm in diameter and • for use with the Angio. Jet Ultra Power Pulse technique for the control and selective infusion of physician specified fluids, including thrombolytic agents, into the peripheral vascular system. The Angio. Jet SOLENT dista Thrombectomy Set is intended for use with the Angio. Jet Ultra Console to break apart and remove thrombus from: • upper and lower extremity peripheral arteries and • for use with the Angio. Jet Ultra Power Pulse technique for the control and selective infusion of physician specified fluids, including thrombolytic agents, into the peripheral vascular system. The minimum vessel diameter for each Thrombectomy Set model is listed in Table 1 (in the IFU). CONTRAINDICATIONS Do not use the catheter in patients: • Who are contraindicated for endovascular procedures • Who cannot tolerate contrast media • In whom the lesion cannot be accessed with the guide wire WARNINGS AND PRECAUTIONS • The Thrombectomy Set has not been evaluated for treatment of pulmonary embolism. There are reports of serious adverse events, including death, associated with cases where the catheter was used in treatment of pulmonary embolism. • The Thrombectomy Set has not been evaluated for use in the carotid or cerebral vasculature. • The Thrombectomy Set has not been evaluated for use in the coronary vasculature (unless accompanied by a separate coronary IFU). • Operation of the catheter may cause embolization of some thrombus and/or thrombotic particulate debris. Debris embolization may cause distal vessel occlusion, which may further result in hypoperfusion or tissue necrosis. • Cardiac arrhythmias during catheter operation have been reported in a small number of patients. Cardiac rhythm should be monitored during catheter use and appropriate management, such as temporary pacing, be employed, if needed. • Use of the catheter may cause a vessel dissection or perforation. • Do not use the Angio. Jet Ultra System in patients who have a nonhealed injury due to recent mechanical intervention, in the vessel to be treated, to avoid further injury, dissection, or hemorrhage. • Do not use the Thrombectomy Set in vessels smaller than minimum vessel diameter for each Thrombectomy Set model as listed in Table 1 (in the IFU); such use may increase risk of vessel injury. • Systemic heparinization is advisable to avoid pericatheterization thrombus and acute rethrombosis. This is in addition to the heparin added to the saline supply bag. • Operation of the Angio. Jet System causes transient hemolysis which may manifest as hemoglobinuria. Table 1 (in the IFU) lists maximum recommended run times in a flowing blood field and total operating time for each Thrombectomy Set. Evaluate the patient’s risk tolerance for hemoglobinemia and related sequelae prior to the procedure. Consider hydration prior to, during, and after the procedure as appropriate to the patient’s overall medical condition. • Large thrombus burdens in peripheral veins and other vessels may result in significant hemoglobinemia which should be monitored to manage possible renal, pancreatic, or other adverse events. • Monitor thrombotic debris/fluid flow exiting the Thrombectomy Set via the waste tubing during use. If blood is not visible in the waste tubing during Angio. Jet Ultra System activation, the catheter may be occlusive within the vessel; verify catheter position, vessel diameter and thrombus status. Operation under occlusive conditions may increase risk of vessel injury. • Do not exchange the guide wire. Do not retract the guide wire into the catheter during operation. The guide wire should extend at least 3 cm past the catheter tip at all times. If retraction of the guide wire into the Thrombectomy Set occurs, it may be necessary to remove both the Thrombectomy Set and the guide wire from the patient in order to re-load the catheter over the guide wire. (Dista only ) • Use of a J-tip guide wire is not recommended as it is possible for the tip of the guide wire to exit through a side window on the distal end of the catheter. (Omni, Proxi only) • Do not pull the catheter against abnormal resistance. If increased resistance is felt when removing the catheter, remove the catheter together with the sheath or guide catheter as a unit to prevent possible tip separation. • If resistance is felt during the advancement of the Thrombectomy Set to lesion site, do not force or torque the catheter excessively as this may result in deformation of tip components and thereby degrade catheter performance. • Obstructing lesions that are difficult to cross with the catheter to access thrombus may be balloon dilated with low pressure (≤ 2 atm). Failure to pre-dilate difficult-to-cross lesions prior to catheter operation may result in vessel injury. • The potential for pulmonary thromboembolism should be carefully considered when the Thrombectomy Sets are used to break up and remove peripheral venous thrombus. . (Below is Omni, Proxi only) • Hand injection of standard contrast medium may be delivered through the thrombectomy catheter via the manifold port stopcock. Follow the steps to remove air from the catheter when delivering fluid through the catheter stopcock. • Fluids should be injected only under the direction of a physician and all solutions prepared according the manufacturer instructions. • The Thrombectomy Set waste lumen is rated for 50 psi. Delivering a hand injection of contrast medium with excessive force can create injection pressures greater than 50 psi, potentially causing leaks in the waste lumen of the catheter. • Do not use a power injector to deliver contrast medium through the catheter stopcock. Power injectors can deliver pressures greater than 50 psi, potentially causing leaks in the waste lumen of the catheter. • Some fluids, such as contrast agents, can thicken in the catheter lumen and block proper catheter operation if left static too long. The catheter should be operated to clear the fluid within 15 minutes of injection. Console WARNINGS and PRECAUTIONS: • Use the Angio. Jet Ultra Console only with an Angio. Jet Ultra Thrombectomy Set. This Console will not operate with a previous model pump set and catheter. • Do not attempt to bypass any of the Console safety features. • If the catheter is removed from the patient and/or is inoperative, the waste tubing lumen, guide catheter, and sheath should be flushed with sterile, heparinized solution to avoid thrombus formation and maintain lumen patency. Reprime the catheter by submerging the tip in sterile, heparinized solution and operating it for at least 20 seconds before reintroduction to the patient. • Refer to the individual Angio. Jet Ultra Thrombectomy Set Information for Use manual for specific warnings and precautions. • Do not move the collection bag during catheter operation as this may cause a collection bag error. • Monitor thrombotic debris/fluid flow exiting the catheter through the waste tubing during use. If blood is not visible during console activation, the catheter may be occlusive within the vessel or the outflow lumen may be blocked. • Ensure adequate patient anticoagulation to prevent thrombus formation in outflow lumen. • Refer to individual Thrombectomy Set Instructions for Use manual for specific instructions regarding heparinization of the Thrombectomy Set. • The Console contains no user-serviceable parts. Refer service to qualified personnel. • Removal of outer covers may result in electrical shock. • This device may cause electromagnetic interference with other devices when in use. Do not place Console near sensitive equipment when operating. • Equipment not suitable for use in the presence of flammable anesthetic mixture with air or with oxygen or nitrous oxide. • To avoid the risk of electric shock, this equipment must only be connected to a supply mains with protective earth. • Where the “Trapping Zone Hazard for Fingers” symbol is displayed on the console, there exists a risk of trapping or pinching fingers during operation and care must be exercised to avoid injury. • Do not reposition or push the console from any point other than the handle designed for that purpose. A condition of overbalance or tipping may ensue. • The Angio. Jet Ultra Console should not be used adjacent to or stacked with other equipment, and if adjacent or stacked use is necessary, the Angio. Jet Ultra Console should be observed to verify normal operation in the configuration in which it will be used. • Portable and mobile RF communications equipment can affect MEDICAL ELECTRICAL EQUIPMENT. • The use of accessories and cables other than those specified, with the exception of accessories and cables sold by Bayer Health. Care as replacement parts for internal components, may result in increased EMISSIONS or decreased IMMUNITY of the Ultra Console. • MEDICAL ELECTRICAL EQUIPMENT needs special precautions regarding Electro-Magnetic Compatibility (EMC) and needs to be installed and put into service according to the EMC information provided in the tables provided in the IFU. ADVERSE EVENTS Potential adverse events which may be associated with use of the Angio. Jet Ultra Thrombectomy System are similar to those associated with other interventional procedures and include, but are not limited to : • abrupt closure of treated vessel • acute myocardial infarction • acute renal failure • bleeding from access site • cerebrovascular accident • death • dissection • embolization, proximal or distal • hematoma • hemolysis • hemorrhage, requiring transfusion • hypotension/hypertension • infection at the access site • pain • pancreatitis • perforation • pseudoaneurysm • reactions to contrast medium • thrombosis/occlusion • total occlusion of treated vessel • vascular aneurysm • vascular spasm • vessel wall or valve damage Final PEARL Data Aug 2013; Presented by Dr. Mark Garcia at CIRSE 2013; Angio. Jet, Solent, AVX, Power Pulse and Cross-Stream are trademarks of Boston Scientific. © 2016 Boston Scientific Corporation or its affiliates. All rights reserved. PI-368802 -AB MAR 2016 34