Raúl García-Rinaldi, MD, PhD, FACS

Professor of Surgery Ponce School of MedicineProfessor of Surgery Ponce School of Medicine

Director Cardiovascular Surgery

Mayagüez Medical Center

Mayagüez, Puerto RicoMayagüez, Puerto Rico

Presented at The Houston Aortic SymposiumFebruary 23-24-25, 2017February 23-24-25, 2017

Houston, Texas

Receive support for ongoing researchReceive support for ongoing researchfromfrom CryolifeCryolife (On(On--X Prosthesis)X Prosthesis)fromfrom CryolifeCryolife (On(On--X Prosthesis)X Prosthesis)

Thromboembolism from aortic prosthesis isdue to platelet activation and aggregationdue to platelet activation and aggregationsecondary to shear forces from the valve andrelease of ADP.release of ADP.

Becker R.C., Eisenberg P., Turpie AGG. Pathobiologic features and Prevention of thrombotic complications associatedBecker R.C., Eisenberg P., Turpie AGG. Pathobiologic features and Prevention of thrombotic complications associatedwith Prosthetic Valves: Fundamental principles and the contribution of platelet and thrombin. Am Heart J2001; 141:1025-37.

Experimental Basis- Pigs implanted with St. Jude MechanicalValve in Thoracic Dacron® graftsValve in Thoracic Dacron® grafts

Mckellar SH, Thompson III, JL., Garcia-Rinaldi R, MacDonald RJ, Sundt III TM, Schaff HV. Short and long-term efficacy ofaspirin and clopidogrel from thromboprophylaxis for mechanical heart valves: an In-Vivo study in swine. JThorac Cardiovasc Surg. 2008 Oct; 136(4):908-14.

a) Dalteparin (Surrogate for Warfarin)

b) Aspirin

c) Clopidogrelc) Clopidogrel

d) Clopidogrel plus aspirin

Clot Formation:Clot Formation:

Patients loaded with antiplatelet agents the first day after surgery:Clopidogrel 300mg and ASA 325mg and tested for platelet inhibition.Clopidogrel 300mg and ASA 325mg and tested for platelet inhibition.Non responsive patients receive 60mg prasugrel.

Tested by Accumetrics® Assay or Thromboelastography(TEG) to insurepatients respond to treatment (>50% platelet inhibition) which ismandatory.

Patients retested at 1 month and every 6 months.

Patients and/or physicians requesting tissue valves for their patients orpatients who refuse to enter study are excluded. Also excludedpatients who require a mitral prosthesis, have a history ofpatients who require a mitral prosthesis, have a history ofhypercoagulability or a previous CVA.

Day 1 Day 2

Clopidogrel 300mg

Aspirin 325mg

Accumetrics - TEG

Accumetrics

TEG

> 50% Inhibition < 50% Inhibition < 50% Inhibition > 50% Inhibition> 50% Inhibition < 50% Inhibition

Reload

< 50% Inhibition

Prasugrel 60mg

> 50% Inhibition

Clopidogrel 300mg All Respond

>50% Inhibition

Maintenance: Clopidogrel 75mg +81mg ASA or Prasugrel 10mg + 81mg ASA

Number of Patients: 264Number of Patients: 264

Age: 21 - 86 Average 64.5 ± 12.0

Male 171 (65%) Female 93 (35%)Male 171 (65%) Female 93 (35%)

Coexistant Disease

Diabetes Mellitus 107 (41%)

Hypertension 203 (77%)Hypertension 203 (77%)

Diabetes + hypertension 91 (34%)

Operation # Patients

AVR 264

AVR + Coronary Artery Bypass 104 (39%)

AVR + Resection of Ascending Aorta and Coronary reimplantation 15 (6%)

Resection of ascending aortic aneurysm 10 (4%)

AVR + Enlargement of Aortic Root 9 (3.4%)

AVR + Mitral Valve Repair 6 (2.3%)

AVR (Redo) 5 (2%)AVR (Redo) 5 (2%)

AVR + Resection of Ascending Aorta and Portions of Transverse Arch 3 (1.1%)

AVR + Carotid Endarterectomy 1 (0.4%)

AVR + Carotid Endarterectomy + CAB 1 (0.4%)

AVR + Femoro Femoral Bypass 1 (0.4%)

AVR + Alfieri Mitral Valve Repair, Septoplasty, Resection of Left Ventricular Aneurysm 1 (0.4%)AVR + Alfieri Mitral Valve Repair, Septoplasty, Resection of Left Ventricular Aneurysm 1 (0.4%)

2001 -20162001 -2016

Months at risk: 11688.8 (974.1 patient/years)Months at risk: 11688.8 (974.1 patient/years)

Average Follow up: 47.3 ± 44.3 months

Deaths: 51 (19%)Deaths: 51 (19%)

Medical Deaths: 48 (18%)

Valve Related Mortality 3 (1.1%, 0.3% pt-yrs)

GI Bleeding: 13 PatientsGI Bleeding: 13 Patients

Other significant bleeding: 2

1. Post colonic polypectomy

2. Nasal Bleed (patient with CA of the lung)2. Nasal Bleed (patient with CA of the lung)

Total patients 15 (1.5% pt/yr)

Sub Arachnoid Hemorrhage: 3 patients

A. TIA: (Secondary to carotid disease) 2

10 patients underwent Carotid Endarterectomy

B. ISCHEMIC STROKES: 12 (1.2 % pt/yr)

Cause:Cause:

1. OFF Clopidogrel 10/12

2. Non responder to Clopidogrel 12. Non responder to Clopidogrel 1

3. Never tested 1

C. Valve Thrombosis 1 (small clot between leaflets, in aC. Valve Thrombosis 1 (small clot between leaflets, in a

non compliant patient)

No episodes of early or late valve, thrombosis in compliant patients.

C. Hemorrhagic strokes 3

Compliant, responsive patients have not had ischemic strokesCompliant, responsive patients have not had ischemic strokes

Total Deaths: 51 (19%) Medical Deaths: 48 (18%)

Causes of Death

Cause Number of patients

Myocardial Infarction 22 (43%)

Pulmonary Failure 5 (10%)

Total Deaths: 51 (19%) Medical Deaths: 48 (18%)

Pulmonary Failure 5 (10%)

Aspiration pneumonia 4 (8%)

Endocarditis* 2 (4%)

Hemorrhagic stroke 3 (6%)

Perinephric abscess failure 1 (2%)Perinephric abscess failure 1 (2%)

Pannus formation* 1 (2%)

Liver Disease 2 (4%)

Ischemic Stroke* (patient never tested) 1 (2%)

Sepsis 1 (2%)

Cardiac Arrest after Carotid Endarterectomy 1 (2%)

Cardiac Arrhythmia not valve related 1 (2%)

Head trauma 1 (2%)

Drug Abuse 1 (2%)

Car Accident 1 (2%)

Colon Carcinoma 2 (4%)

Breast Carcinoma 1 (2%)

CVA (patient on Warfarin) 1 (2%)

*valve related mortality 3/264 = 1.1% 0.3%/pt-yr

1. Platelet Inhibition due to dual antiplatelet therapy prevents1. Platelet Inhibition due to dual antiplatelet therapy preventsthromboembolism in patients with mechanic aortic valves.

2. During 16 years: 51 patients died primarily of myocardialinfarctions (43%).infarctions (43%).

3. Patients who had strokes were off ClopidogrelASA(completely or non compliant with therapy).

4. Strokes occurred in the early part of the study when some4. Strokes occurred in the early part of the study when somephysicians took the patients off Clopidogrel ASA.

5. There have been no cases of early or late valve thrombosis.5. There have been no cases of early or late valve thrombosis.

15 Atrial Fibrillation

10 Unilateral decision without valid reason

3 DVT3 DVT

3 Redo AVR

5 Patient decision

1 Unable to active satisfactory platelet1 Unable to active satisfactory plateletinhibition

1 CA Prostate

1 Hypercoagulable syndrome1 Hypercoagulable syndrome