1. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview A comprehensive review of safety, procedural, short and long term benefits of Aspiration therapy

2. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview This presentation is intended to provide a comprehensive review of the available safety, procedural, short and long term data comparing aspiration therapy versus conventional PCIThis presentation is intended to provide a comprehensive review of the available safety, procedural, short and long term data comparing aspiration therapy versus conventional PCI There is some evidence that the clinical effect of routine intracoronary thrombus aspiration before primary percutaneous intervention (PCI) in ST-elevation myocardial infarction (STEMI) is beneficial.There is some evidence that the clinical effect of routine intracoronary thrombus aspiration before primary percutaneous intervention (PCI) in ST-elevation myocardial infarction (STEMI) is beneficial. –However more data and longer follow-up are needed to support use of aspiration, paired with PCI, as a consistent choice. This deck highlights the clinical outcomes from largest aspiration/PCI clinical trials conducted to date and with follow up in progress:This deck highlights the clinical outcomes from largest aspiration/PCI clinical trials conducted to date and with follow up in progress: Due to inconsistencies in study results related to clinical outcome data, a number of meta-analyses were carried out. The data from the most current meta-analysis is also discussed here.Due to inconsistencies in study results related to clinical outcome data, a number of meta-analyses were carried out. The data from the most current meta-analysis is also discussed here. Current Clinical Evidence Supporting Aspiration TAPAS Trial TASTE trial INFUSE-AMI Meta-Analysis 6 1 Vlaar PJ, et al. Lancet. 2008; 371:1915-20. 2 Svilaas T, et al. N Engl J Med. 2008;358:557-67. 3 Fröbert O, et al. NEJM 2013: Epub ahead of print 4 Stone G, et al. JAMA. 2012;307(17):1817-1826 5 clinicaltrials.gov NCT01149044 6 Kumbhani DJ, et al. J Am Coll Cardiol. 2013;Epub ahead of print 3 5 4 1,2

3. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Procedural Safety Data Thrombus Aspiration (N=535) Conventional PCI (N=536) P-Value Side branch occlusion no. (%)5/502 (1.0)4/503 (0.8)1.00 Flow-limiting dissections no. (%)001.00 Emergency CABG no. (%)1/502 (0.2)1/503(0.2)1.00 Randomized in TASTE Thrombus Aspiration (N = 3621) PCI Only (N = 3623) P-Value Stroke or Neurological complication; no. (%)19 (0.5)18 (0.5)0.87 Perforation or tamponade; no. (%)13 (0.4)14 (0.4)0.85 TAPAS Trial In the TAPAS trial, none of the complications were thought to be related to the aspiration device used, there were no intraprocedural deaths or strokes. TASTE trial In the TASTE trial, there was no statistically significant difference in rates of stroke or neurological complications between groups. The TAPAS 1, TASTE 3 and INFUSE AMI 1, trials showed that manual thrombus aspiration (MTA) used as an adjunctive therapy to PCI showed no difference in procedural safety compared to PCI alone. 1 Svilaas T, et al. N Engl J Med. 2008;358:557-67. 2 Fröbert O, et al. NEJM 2013: Epub ahead of print.

4. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Procedural Data In the TASTE Trial there was a significant difference in favor of aspiration related to direct stenting. The aspiration group used less stents per procedure (P = 0.02) and had shorter total stent length (P = 0.5) than conventional PCI only.In the TASTE Trial there was a significant difference in favor of aspiration related to direct stenting. The aspiration group used less stents per procedure (P = 0.02) and had shorter total stent length (P = 0.5) than conventional PCI only. Randomized in TASTE Thrombus Aspiration (N = 3621) PCI Only (N = 3623) P Value Direct Stenting1388 (38.3)843 (23.3)<0.001 Stent no. per procedure; Mean ± SD 1.35 (0.77)1.39 (0.81)0.02 Total Stent Length; Mean ± SD 27.7 (15.9)28.5 (16.4)0.05 Manual thrombus aspiration (MTA) used as an adjunctive therapy to PCI may offer procedural advantages compared to PCI alone (ability to better size the stent, better stent apposition).Manual thrombus aspiration (MTA) used as an adjunctive therapy to PCI may offer procedural advantages compared to PCI alone (ability to better size the stent, better stent apposition). TASTE trial Fröbert O, et al. NEJM 2013: Epub ahead of print

5. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Manual thrombus aspiration (MTA) used as an adjunctive therapy to PCI may result in improved myocardial perfusion and clinical outcomesManual thrombus aspiration (MTA) used as an adjunctive therapy to PCI may result in improved myocardial perfusion and clinical outcomes Myocardial Perfusion – Blush Grade TAPAS showed that aspiration in STEMI patients results in improved myocardial perfusion and clinical outcome as compared with conventional PCI, irrespective of clinical and angiographic characteristics at baseline. 1TAPAS showed that aspiration in STEMI patients results in improved myocardial perfusion and clinical outcome as compared with conventional PCI, irrespective of clinical and angiographic characteristics at baseline. 1 Myocardial Blush Grade (immediately post-procedure) 45.7 32.2 41.4 26.3 Conventional PCI 0 10 20 50 60 70 100 30 40 80 90 Percent Thrombus Aspiration P < 0.001 37.1 17.1 MBG 3 MBG 2 MBG 0/1 TAPAS Trial 1 Svilaas T, et al. N Engl J Med. 2008;358:557-67. 2 Stone G, et al. JAMA. 2012;307(17):1817-1826. Thrombus Aspiration (N=229) PCI Only (N=223) P-Value MBG 0/1 no. (%)38/229 (16.6)46/222 (20.7)0.26 MGB 2/3 no. (%)191/229 (83.4)176/222 (79.3)0.26 Complete ST-segment resolution no. (%) 101/199 (50.8)108/190 (56.8)0.23 INFUSE-AMI In the INFUSE AMI Trial, there were no significant differences for myocardial blush grade (0/1, 2/3) or complete ST-segment resolution. 2In the INFUSE AMI Trial, there were no significant differences for myocardial blush grade (0/1, 2/3) or complete ST-segment resolution. 2

6. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Myocardial Perfusion – Meta-Analysis Meta-Analysis Even with the exclusion of TAPAS from the meta-analysis, TIMI 3 blush (P<0.0001) and ST-segment resolution (P<0.0001) were still significantly improved with aspiration thrombectomy over conventional primary PCI aloneEven with the exclusion of TAPAS from the meta-analysis, TIMI 3 blush (P<0.0001) and ST-segment resolution (P<0.0001) were still significantly improved with aspiration thrombectomy over conventional primary PCI alone Immediate Myocardial Reperfusion at 1Yr Thrombus Aspiration (N=1944) Conventional PCI (N=2811) P Value TIMI Blush Grade63.6%48.5%<0.0001 Complete ST-segment resolution55.8%44.4%<0.0001 The latest meta-analysis looked at 3936 patients with AMI undergoing primary angioplasty from 25 randomized trialsThe latest meta-analysis looked at 3936 patients with AMI undergoing primary angioplasty from 25 randomized trials 1 Kumbhani DJ, et al. J Am Coll Cardiol. 2013;Epub ahead of print

7. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview 30-Day Data TAPAS Trial 1 At 30-days there were no significant differences between the aspiration group and the conventional PCI group related to: major bleeding (P = 0.11), death (P = 0.07), re-infarction (P = 0.11), TVR (P = 4.5%), MACE (P = 0.12) At 30-days there were no significant differences between the aspiration group and the conventional PCI group related to death (P = 0.81), re-infarction (P = 0.55), new- onset severe heart failure (P = 0.77), re-hospitalization for heart failure (P = 0.15), stent thrombosis (Def/Prob) (P = 0.33), MACCE (P = 0.31), MACHFE (P = 0.80) INFUSE-AMI 2 At 30 days, there were no significant differences in all cause mortality between the aspiration group and the conventional PCI group All cause mortality at 30 days. 1 Svilaas T, et al. N Engl J Med. 2008;358:557-67. 2 Stone G, et al. JAMA. 2012;307(17):1817-1826 3 Fröbert O, et al. NEJM 2013: Epub ahead of print TASTE trial 3

8. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Longer term follow up The INFUSE-AMI Trial showed that the mortality difference between aspiration therapy and conventional PCI, though numerically lower for aspiration, was not significant.The INFUSE-AMI Trial showed that the mortality difference between aspiration therapy and conventional PCI, though numerically lower for aspiration, was not significant. A significant difference in favor of aspiration therapy over conventional PCI was seen related to new onset of severe heart failure and re- hospitalization for heart failure.A significant difference in favor of aspiration therapy over conventional PCI was seen related to new onset of severe heart failure and re- hospitalization for heart failure. INFUSE-AMI Longer Term Follow-up at 1Yr Thrombus Aspiration (N=229) Conventional PCI (N=223) P Value Death4.9%7.0%0.35 Reinfarction0.5%1.4%0.30 New onset of severe heart failure3.5%8.1%0.05 Rehospitalization for heart failure0.9%5.4%0.008 Stent Thrombosis (Def/Prob)1.4%1.9%0.66 MACCE7.6%10.3%0.31 MACHFE8.4%12.5%0.17 Stone G, et al. JAMA. 2012;307(17):1817-1826

9. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Longer Term Follow-up The TAPAS Trial showed a statistically significant reduction of all-cause mortality in favor of thrombus aspiration group at 1 year (-38%).The TAPAS Trial showed a statistically significant reduction of all-cause mortality in favor of thrombus aspiration group at 1 year (-38%). All-Cause Mortality (%) 060360380240180120 Time (days) 0 2 4 6 8 10 Conventional PCI Thrombus aspiration Log-rank P = 0.040 536 535 1071 506 519 1025 489 505 994 494 506 1000 495 510 1005 499 514 1013 501 517 1018 Number at risk Conventional PCI Thrombus aspiration Total TAPAS Trial Manual thrombus aspiration (MTA) used as an adjunctive therapy to PCI may provide improved long term clinical outcomes such as all- cause mortality vs. conventional PCI alone.Manual thrombus aspiration (MTA) used as an adjunctive therapy to PCI may provide improved long term clinical outcomes such as all- cause mortality vs. conventional PCI alone. Vlaar PJ, et al. Lancet. 2008; 371:1915-20. 4.7% 7.6%

10. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Longer term follow up Although no benefit in clinical outcomes was noted at 30 days, a benefit is seen at the 6-12 month time pointAlthough no benefit in clinical outcomes was noted at 30 days, a benefit is seen at the 6-12 month time point Meta-Analysis 1 Long Term Clinical Outcomes 6-12M Thrombus Aspiration (N=1944) Conventional PCI (N=2811) P Value All-Cause Death 2.7%3.9%0.049 Reinfarction1.6%2.4%0.11 TVR6.9%8.7%0.06 MACE10.8%14%0.006 Although no benefit in clinical outcomes was noted at 30 days, it will be important to see the longer term data out to 1 YearAlthough no benefit in clinical outcomes was noted at 30 days, it will be important to see the longer term data out to 1 Year 1 Kumbhani DJ, et al. J Am Coll Cardiol. 2013;Epub ahead of print 2 Fröbert O, et al. NEJM 2013: Epub ahead of print TASTE trial 2

11. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Longer term follow up The TOTAL Trial is an international randomized controlled trial with an event-driven design that will recruit 6700 STEMI patients referred to primary PCI within 12 hours – –The primary outcome is the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock or new or worsening New York Heart Association class IV heart failure up to 180 days. – –Follow up occurs at 30 days, 180 days, and 1 yr The long-term follow-up of the TOTAL Trial will continue to build on the existing body of data for the long-term clinical evidence of aspiration, with results presented in 2014. 1. clinicaltrials.gov NCT01149044 The TOTAL Trial is a Randomized Trial of Routine Aspiration ThrOmbecTomy with Percutaneous Coronary Intervention (PCI) vs. PCI ALone in Patients with STEMI Undergoing Primary PCI 1

12. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Current Reperfusion Treatment Guidelines While primary PCI is the preferred MI treatment, clinical evidence has led to guideline recommendations for manual thrombus aspiration during primary PCI.While primary PCI is the preferred MI treatment, clinical evidence has led to guideline recommendations for manual thrombus aspiration during primary PCI. For Acute MI in patients presenting with ST-elevation Both guidelines are evidence Class IIa, Level B. This means that the recommendation is in favor of treatment or procedure being useful/effective, however, some conflicting evidence from single randomized trial or nonrandomized studies may exist.Both guidelines are evidence Class IIa, Level B. This means that the recommendation is in favor of treatment or procedure being useful/effective, however, some conflicting evidence from single randomized trial or nonrandomized studies may exist. 2013 American College of Cardiology Foundation/American Heart Association Guidelines for STEMI Circ 2013 2012 European Society of Cardiology Guidelines for STEMI EJH 2012

13. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Single center using surrogate endpointsSingle center using surrogate endpoints Not all patients underwent stenting with balloon predilationNot all patients underwent stenting with balloon predilation While designed to detect differences, had limited power to investigate magnitudeWhile designed to detect differences, had limited power to investigate magnitude Meta-Analysis Study Limitations TAPAS Trial TASTE trial INFUSE-AMI No independent adjudication of events or monitoring of dataNo independent adjudication of events or monitoring of data Inclusion of late presenters (>12 and 12 and <24) potentially minimizes benefit of aspiration Is 30-day endpoint appropriate?Is 30-day endpoint appropriate? Highly selected patient population (only 7.2% of screened STEMI patients were randomized)Highly selected patient population (only 7.2% of screened STEMI patients were randomized) Not powered for clinical eventsNot powered for clinical events Did not include patient level dataDid not include patient level data Not all measures of infarct size were included due to inconsistent reportingNot all measures of infarct size were included due to inconsistent reporting 1 Vlaar PJ, et al. Lancet. 2008; 371:1915-20. 2 Svilaas T, et al. N Engl J Med. 2008;358:557-67. 3 Fröbert O, et al. NEJM 2013: Epub ahead of print 4 Stone G, et al. JAMA. 2012;307(17):1817-1826 5 Kumbhani DJ, et al. J Am Coll Cardiol. 2013;Epub ahead of print 1,2 3 4 5

14. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Early restoration of blood flow minimizes the extent of heart muscle damage and preserves the pumping function of the heart – –Current evidence shows aspiration of thrombus prior to PCI for STEMI is safe and has been associated with improved myocardial perfusion and long term clinical outcomes. 1,2,3,4,5 While no clinical benefits have been seen at 30-days in most studies, long-term data suggest that aspiration used as an adjunctive therapy to PCI improves clinical outcomes compared to PCI alone 1,2,4,5 The long-term follow-up of the two largest studies to date, TASTE and TOTAL, will continue to build on the existing body of evidence for the long-term clinical evidence of aspiration 2,6 – –The TASTE study 1-year follow-up is in progress and should be available within the next year – –The TOTAL study primary composite endpoint will be evaluated at 6 months with results presented in 2014. Discussion 1 Vlaar PJ, et al. Lancet. 2008; 371:1915-20. 2 Svilaas T, et al. N Engl J Med. 2008;358:557-67. 3 Fröbert O, et al. NEJM 2013: Epub ahead of print 4 Stone G, et al. JAMA. 2012;307(17):1817-1826 5 Kumbhani DJ, et al. J Am Coll Cardiol. 2013;Epub ahead of print 6 clinicaltrials.gov NCT01149044

15. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview The following slides provide additional background Information

16. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview Worldwide, coronary artery disease (CAD) is the single most frequent cause of death.Worldwide, coronary artery disease (CAD) is the single most frequent cause of death. –Over 7 million people die each year from CAD, accounting for 12.8% of all deaths. 1 Timely diagnosis of STEMI is key to successful management and early provision of reperfusion therapy, is critical to its benefit. 1Timely diagnosis of STEMI is key to successful management and early provision of reperfusion therapy, is critical to its benefit. 1 Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy in patients with STEMI, provided it can be performed expeditiously. 1, 2Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy in patients with STEMI, provided it can be performed expeditiously. 1, 2 CAD Prevalence and Treatment 1 ESC Guidelines, European Heart Journal 2012 33, 2569-2619 2. Svilaas et al. NEJM, 2008, vol358, No. 6

17. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All rights reserved. UC201402424ML 08/2013 Aspiration Overview The main goal of primary percutaneous coronary intervention (PPCI) is to restore blood flow and re- perfuse the myocardial tissue 1The main goal of primary percutaneous coronary intervention (PPCI) is to restore blood flow and re- perfuse the myocardial tissue 1 Microvascular obstruction with diminished myocardial perfusion occurs in a large proportion of patients with a patent epicardial vessel after primary PCIMicrovascular obstruction with diminished myocardial perfusion occurs in a large proportion of patients with a patent epicardial vessel after primary PCI –This event is associated with an increased infarct size, reduced recovery of ventricular function, and increased mortality 2 Thrombus aspiration during PCI has been proposed to prevent embolizationThrombus aspiration during PCI has been proposed to prevent embolization –Several different thrombectomy devices have been demonstrated to be well tolerated and effective in improving surrogate markers of myocardial reperfusion 1 Thrombus Aspiration to Prevent Embolization 1 Picchi, A. Limbruno, U. Journal of Cardiovascular Medicine, 2012 Jan;13(1):16-23. 2. Svilaas et al. NEJM, 2008, vol358, No. 6