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Mehran_PARIS_30-day presentation- TCT- final

VIEWS: 10 PAGES: 33

									         PARIS Registry
 Patterns of Non-Adherence to
Anti-Platelet Regimens In Stented
   Patients: An Observational
        Single Arm Study
            Roxana Mehran, MD
      on behalf of PARIS Investigators
      Background and Rationale
• Anti-platelet agents are the cornerstone of
  therapy in pts with ACS and in those undergoing
  PCI.
• Current ACC/AHA guidelines recommend 30
                               1



  days DAPT following placement of a BMS and 1
  year following placement of a DES. (In patients
  with ACS 12 months of DAPT is recommended
  regardless of stent type.)
• Premature discontinuation of DAPT (within the
  first 6 months after DES) has been associated
  with an increased risk of stent thrombosis, but
  the optimal duration of DAPT has not yet been
  precisely determined, especially with regard to
  second generation DES.
                              1. Wright et al. JACC 10 May 2011
     Background and Rationale
• The mode and circumstances around non-
  adherence to DAPT has not been previously
  studied.
• Whether or not discontinuation of DAPT
  secondary to bleeding or other events (ie: non-
  cardiac surgery) may lead to subsequent
  ischemic events has not been systematically
  studied.
• Previous studies have only addressed patients
  “on” or “off” DAPT at specific follow-up points or
  at the time of events.
              Study Design

• Multicenter, multinational, observational study

• 5033 subjects to be followed for approximately
  24 months post stent implantation


• Includes bare metal and drug eluting stents
       Modes of Non-adherence

• Discontinuation: subjects have discontinued
  use of DAPT as per recommendation of their
  physician who felt subject no longer needed
  therapy.
• Interruption: subjects have interrupted DAPT
  use on a voluntary basis and under guidance
  and recommendation of their physician due to
  need for surgery. DAPT will be reinstituted
  within 14 days.
• Disruption: subjects have disrupted DAPT use
  due to bleeding or non-compliance. Includes
  use of DAPT at lower dose levels than
  prescribed.
     Eligibility for Enrollment (1)

Inclusion Criteria
• Successful stent placement in one or more
  lesions in native coronary arteries using an
  approved coronary stent, and intent to
  discharge on DAPT
• Diagnosis of Acute Coronary Syndrome,
  Stable Angina, or Documented Silent
  Ischemia
• Subject is over 18 years old, provides
  consent, and agrees to follow-up
    Eligibility for Enrollment (2)

Exclusion Criteria
• Evidence of stent thrombosis during
 baseline procedure
• Subject is participating in an
 investigational device or drug study
                Objectives

Primary Objectives
• To examine the modes of non-adherence to
  dual anti-platelet therapy (DAPT) following
  stenting
• To evaluate subsequent clinical outcomes and
  the relation to non-adherence to DAPT
Secondary Objectives
• To examine factors associated with non-
  adherence
• To examine the relationship of major & minor
  bleeding to stent thrombosis & MACE
                Study Organization

•   Principal Investigators:   Roxana Mehran, MD
                               Antonio Colombo, MD


•   Steering Committee:        Roxana Mehran, MD (Chair); Antonio
                               Colombo, MD (Co-Chair); Alaide
                               Chieffo, MD; David J. Cohen, MD, MSc;
                               C. Michael Gibson, MD; Mitchell W.
                               Krucoff, MD; David J. Moliterno, MD;
                               Ph. Gabriel Steg, MD; Giora Weisz,
                               MD; Bernhard Witzenbichler, MD
             Study Organization


• Sponsor:                  Mount Sinai School of Medicine

• Grant Support:            Sanofi-Aventis and Bristol-Myers
                            Squibb

• Data Coordinating Center: Mount Sinai School of Medicine
• Clinical Event Committee: Dr. Steven Marx (Chair)
• Site and Data Monitoring: Medical Devices Consultancy Ltd
• EDC:                      Study Manager
       Investigators and Site Name

    PI Name                      Site name
1   James Hermiller, MD          Heart Center of Indiana, IN

2   Annapoorna Kini, MD          Mount Sinai Medical Center, NY

3   Fayaz Shawl, MD              Washington Adventist Hospital, MD

4   Giora Weisz, MD              Columbia University Medical Center, NY

5   Bernhard Witzenbichler, MD   Charité, Germany
    Antonio Colombo, MD
6   Alaide Chieffo, MD           San Raffaele Hospital, Italy

7   David J. Cohen, MD, MSc      Saint Luke's Mid-America Heart Institute, MO

8   David J. Moliterno, MD       University of Kentucky, KY
       Investigators and Site Name
                  (cont.)
     PI Name                    Site name
9    David Antoniucci, MD       Careggi Hospital, Italy

10   Ph. Gabriel Steg, MD       Hopital Bichat, France

11   Peter B. Berger, MD        Geisinger Medical Center, PA

12   Thomas Stuckey, MD         LeBauer Cardiovascular Research Foundation, NC

13   Ron Waksman, MD            Washington Hospital Center, DC

14   Timothy D. Henry, MD       Minneapolis Heart Institute Foundation, MN

15   Ioannis Iakovou, MD, PhD   Onassis Cardiac Surgery Center, Greece
                 Paris Enrollment - Patients
5,033 pts enrolled at 15 centers in 5 countries




         USA [10]
        n=3,666, 72,9%



 •   Columbia University Medical Center (n=927, 18,5%)
 •   Minneapolis Heart Institute Foundation (n=704, 14%)
 •   Mount Sinai Medical Center (n=555, 11%)
 •   LeBauer Cardiovascular Research Foundation/ Moses Cone Heart and
     Vascular Center (n=344, 6,8%)
 •   St. Luke's Hospital/ Mid-America Heart Institute (n=318 , 6,3%)
 •   Geisinger Medical Center (n=276, 5,5%)
 •   Washington Adventist Hospital (n=199, 4%)
 •   University of Kentucky (n=143, 2,8%)
 •   Heart Center of Indiana/ St. Vincent's/ The Care Group (n= 125, 2,5% )
 •   Washington Hospital Center (n=75, 1,5%)

                                  July 1st, 2009 and October 29th, 2010
        Paris Enrollment - Patients
5,033 pts enrolled at 15 centers in 5 countries

                                     Germany [1]
               EUROPE [5]              n=720, 14,3%
                  n=1,367, 27,1%

              France [1]                    Greece [1]
              n=160, 3,2%                    n=180, 3,6%

                      Italy [2]
                     n=307, 6%




              •     Charité Hospital, Germany (n=720, 14,3%)
              •     San Raffaele Hospital, Italy (n=221 , 4,4%)
              •     Onassis Cardiac Surgery Center, Greece (n= 180, 3,5%)
              •     Hospital Bichat, France (n=160, 3,2%)
              •     Careggi Hospital, Italy (n=86, 1,7%)




                      July 1st, 2009 and October 29th, 2010
                               Enrollment Over Time

6000


5000


4000


3000


2000


1000


   0
   Jul-09   Aug-09   Sep-09   Oct-09   Nov-09   Dec-09   Jan-10   Feb-10   Mar-10   Apr-10   May-10   Jun-10   Jul-10   Aug-10   Sep-10   Oct-10
                   Baseline Characteristics
Enrolled: n= 5033
Complete 30 Day Follow-Up Available: 5023 (99.3%)

                        Variable                    Patients (n=5033)
      Age, years                                      63.96 ± 11.32
      Body mass index, kg/m2                          29.26 ± 5.63
      Male, n (%)                                      3750 (74.5)
      Acute coronary syndrome, n (%)                   2047 (40.9)
      Current smoker, n (%)                             984 (19.6)
      Diabetes Mellitus, n (%)                         1663 (33.0)
      Insulin-requiring DM, n (%)                       547 (10.9)
      Dyslipidemia, n (%)                              3810 (75.7)
      Hypertension, n (%)                              4020 (79.9)
      Peripheral Vascular Disease, n (%)                 396 (7.9)
      Prior coronary artery disease, n (%)             1613 (32.1)
      Prior MI, n (%)                                  1220 (24.2)
      Prior PCI with stenting, n (%)                   1853 (36.8)
      Prior CABG, n (%)                                 691 (13.7)
      Prior stroke, n (%)                                174 (3.5)
                    Medication Usage

           6000

           5000
Patients




           4000

           3000

           2000

           1000

             0
                                                Proton-
                             Thienopyridi                                      Triple
                  Aspirin                        Pump           DAPT
                                 ne                                           Therapy
                                               Inhibitor
                   (71.1%)
 Pre-Procedure 35823582           (40.0%)
                             2014 2014      991 (19.7%)
                                                  991            (37.6%)
                                                            1894 1894      47 (0.9%)
                                                                                  47
 At Discharge 50125012
                   (99.6%)   5031 5031
                                  (100%)    1177 1177
                                                  (23.4%)   5012 5012
                                                                 (99.6%)         311
                                                                           311 (6.2%)
              Procedural Information


      Number of Stents                         Stent Type
                                                   2%

      16%                                               16%
                                                              BMS alone
                           One (n = 2792)
                                                              (n = 817)

                           Two (n = 1417)                     DES alone
28%                  56%
                                                              (n = 4141)
                           > Two (n = 824)   82%
                                                              BMS & DES
                                                              (n = 70)
               Stents by Type

• Total # of stents used: 8434 (1.68 stents/pt)
               Stents by Type
                                            BMS (n = 1258)
                    1%
                                            PES (n = 662)
                         15%
                                8%
                                       3%   SES (n = 289)

        62%                      11%
                                            ZES (n = 920)

                                            EES (n = 5226)

                                            Other DES (n = 79)
Thienopyridine at Discharge

           2%
      6%


                      Clopidogrel (n = 4647)


                      Prasugrel (n = 315)


                      Ticlopidine (n = 69)

                92%
           Rates of Non-Adherence
                (Patient-level)
Incidence of Non-Adherence          Non-Adherence by Mode



    2%                               12%
                 Adherent (4929)                    Disruption (72)
                                   19%              Interruption (20)
                 Non-Adherent
                                            69%
                 (104)
     98%                                            Discontinuation
                                                    (12)
Incidence of Non-Adherence

Any Non-Adherence

        Variable            Patients Episodes
Any Non-adherence           104 (2.1)     147

   Disruption, n (%)        72 (69)     102 (70)

   Interruption, n (%)      20 (19)     27 (18)

   Discontinuation, n (%)   12 (12)     18 (12)
      Incidence of Non-Adherence
                 (Cont.)
Non Adherence to Thienopyridine:

        Variable            Patients Episodes
Any Non-adherence, n (%) 66 (1.3)       69

   Disruption, n (%)        43 (65)   46 (67)

   Interruption, n (%)      12 (18)   12 (17)

   Discontinuation, n (%)   11 (17)   11 (16)
      Incidence of Non-Adherence
                (Cont.)

Non Adherence to Aspirin:

        Variable            Patients Episodes
Any Non-adherence, n (%) 70 (1.4)       78

   Disruption, n (%)        51 (73)   56 (72)

   Interruption, n (%)      12 (17)   15 (19)

   Discontinuation, n (%)    7 (10)    7 (9)
                           Reasons for Disruption

                                                           Thienopyridine
                        Aspirin
                                                   Other
                Other                               4%
                 7%

                              Bleeding                               Bleeding
                                32%                                    31%

     Non-                                         Non-
   Compliance                                   compliance
     61%                                           65%




                                   Bleeding   Non-Compliance                Other
ASA                                   18            34                        4
Thienopyridine                        14            30                        2
                  Reasons for Interruption

                  Aspirin                                                     Thienopyridine
       Coumadin
         13%

                            Surgery                                           Allergy
        Allergy                                                                          Surgery
                             34%                                               33%
                                                                                          42%
         20%

             GI Upset                      Other
               20%                        Medical
                                         Procedure
                                            13%                    Other
                                                                  Medical
                                                                 Procedure
                                                                    25%




                                          Other Medical
                                           Procedure
                  Surgery         (epidural, catheter removal, GI Scope)   GI Upset     Allergy    Coumadin
ASA                  5                              2                          3           3          2
Thienopyridine          5                           3                         0           4           0
Non-Adherence guided by healthcare professionals



                            Recommended By


                                                 Cardiologist (n = 31)
                16%
                                   38%           Primary Care Physician (n = 15)
      10%
    5%                                           ER Physician (n = 11)

         13%
                                                 GI Specialist (n = 4)
                          18%
                                                 Other (n = 8)


                                                 Unknown (n = 13)



         Total episodes of “Recommended” DAPT non-adherence: 82
               Baseline Characteristics


                                        Adherent       Non-adherent
Variable                                                               p-value
                                         n=4929           n=104
Age, years                             63.94 [11.33]   64.83 [11.31]    0.42
Male, n (%)                             3676 (74.6)      74 (71.2)      0.43
Acute coronary syndrome, n (%)          1987 (40.5)      60 (58.3)     <0.0001
Diabetes Mellitus, n (%)                1627 (33.0)      36 (34.6)      0.73
Dyslipidemia, n (%)                     3744 (76.0)      66 (63.5)      0.003
Hypertension, n (%)                     3944 (80.0)      76 (73.1)      0.08
Peripheral Vascular Disease, n (%)       387 (7.9)        9 (8.7)       0.76
Prior coronary artery disease, n (%)    1987 (40.5)      60 (58.3)     <0.0001
Prior MI, n (%)                         1201 (24.4)      19 (18.3)      0.15
            Rates of 30-Day non-adherence
                 in Similar Registries

                                                                                           DAPT
                                                                                    Discontinuation at 30
      Study        Timeframe            Population                      N                days (%)
Airoldi et al1     2002 – 2004          PCI with DES                  3021                            2.4%

PREMIER            2003 – 2004            DES for MI                  500                             13.6%
Registry2
MATRIX Registry3   2004-2006            PCI with SES                  1504                            5.8%

E-Five Registry4   2005-2007            PCI with ZES                  7988                            2.1%

E-SELECT           2006-2008            PCI with SES                14,365                             2%
Registry5



                                        1. Airoldi F et al. Circulation. 2007 Aug 14;116(7):745-54.
                                    2. Spertus J et al. Circulation 2006 June 20; 113(24):2803-9.
                                            3. Claessen B et al. Am J Cardiol 2011;107:528-534.
                                 4. Lotan C et al. J Am Coll Cardiol Interv 2009; 2(12), 1227-1235.
                                            5. Urban P et al J Am Coll Cardiol 2011;57:1445-54.
                    Adverse Event Rates
                                          Adherent    Non-adherent
                               Total      (n=4929)      (n=104)
Ischemic
MACE, n (%)                    78 (1.5)    67 (1.4)      11 (10.6)
Death, all-cause, n(%)         17 (0.3)    15 (0.3)       2 (1.9)
Cardiac Death, n (%)           15 (0.3)    14 (0.3)       1 (1.0)
Myocardial Infarction, n (%)   54 (1.1)    46 (0.9)       8 (7.7)
Stent Thrombosis, n (%)        26 (0.5)    23 (0.5)       3 (2.9)
TVR, n (%)                     30 (0.6)    25 (0.5)       5 (4.8)
TLR, n (%)                     23 (0.5)    19 (0.4)       4 (3.8)

Bleeding
TIMI major, n (%)              9 (0.2)     6 (0.1)        3 (2.9)
ACUITY Major, n (%)            35 (0.7)    23 (0.5)      12 (11.5)
BARC ≥ 3, n (%)                30 (0.6)    18 (0.4)      12 (11.5)
             BARC Bleeding Scale                                               1




BARC Classification                            N (% of total population)
Type 1 (not actionable)                        26 (0.5)
Type 2 (requiring medical attention)           37 (0.7)
Type 3                                         30 (0.6)
  3a                                           15 (0.3)
  3b                                           15 (0.3)
  3c                                           0
Type 4 (CABG related)                          0
BARC Type 5 (Fatal)                            0



                   1. Mehran et al. Circulation 2011 Jun 14;123(23):2736-47.
             Stent Thrombosis
                    Stent Thrombosis
                          (n=26)


   Probable (n=9)                      Definite (n=17)


                         Adherent (n=14)          Non-adherent (n=3)



                                          Disrupted ASA      Disrupted
                                               (n=2)      Clopidogrel (n=1)




Odds Ratio (95% CI) for stent thrombosis associated with
non-adherence: 6.3 (1.9-21.4)
  Relative Risk of Non-Adherence on
     30 Day Stent Thrombosis in
       Contemporary Registries

                                      Adherent               Non-Adherent      RR

PARIS Registry                             0.5%                        2.9%    5.8

Airoldi et al1                             0.9%                        4.2%    4.7

eSELECT Registry2                          0.5%                        4.6%    9.2



                 1. Airoldi F et al. Circulation. 2007 Aug 14;116(7):745-54.
                 2. Urban P et al. J Am Coll Cardiol 2011;57:1445-54.

								
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