PARIS RegistryPatterns of Non-Adherence to Anti-Platelet Regimens In Stented Patients: An Observational Single Arm StudyRoxana Mehran, MDon behalf of PARIS Investigators PARIS Registry
Background and Rationale • Anti-platelet agents are the cornerstone of therapy in pts with ACS and in those undergoing PCI. • Current ACC/AHA guidelines1 recommend 30 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.
PARIS Registry 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
PARIS Registry 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.
PARIS Registry 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
PARIS Registry Eligibility for Enrollment (2) Exclusion Criteria • Evidence of stent thrombosis during baseline procedure • Subject is participating in an investigational device or drug study
PARIS Registry 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 PARIS Registry
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 PARIS Registry
PARIS Registry Investigators and Site Name
PARIS Registry Investigators and Site Name(cont.)
PARIS Registry Paris Enrollment - Patients 5,033 pts enrolled at 15 centers in 5 countries USA  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 Registry Paris Enrollment - Patients 5,033 pts enrolled at 15 centers in 5 countries Germany  n=720, 14,3% EUROPE  n=1,367, 27,1% Greece  n=180, 3,6% France  n=160, 3,2% Italy  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
PARIS Registry Enrollment Over Time
PARIS Registry Baseline Characteristics Enrolled: n= 5033 Complete 30 Day Follow-Up Available: 5023 (99.3%)
PARIS Registry Medication Usage
PARIS Registry Procedural Information
Total # of stents used: 8434 (1.68 stents/pt) PARIS Registry Stents by Type
PARIS Registry Thienopyridine at Discharge
PARIS Registry Rates of Non-Adherence (Patient-level)
PARIS Registry Incidence of Non-Adherence
PARIS Registry Incidence of Non-Adherence (Cont.)
PARIS Registry Incidence of Non-Adherence(Cont.)
PARIS Registry Reasons for Disruption
PARIS Registry Reasons for Interruption
Non-Adherence guided by healthcare professionals PARIS Registry Total episodes of “Recommended” DAPT non-adherence: 82
PARIS Registry Baseline Characteristics
PARIS Registry Rates of 30-Day non-adherence in Similar Registries • Airoldi F et al. Circulation. 2007 Aug 14;116(7):745-54. • Spertus J et al. Circulation 2006 June 20; 113(24):2803-9. • Claessen B et al. Am J Cardiol 2011;107:528-534. • Lotan C et al. J Am Coll Cardiol Interv 2009; 2(12), 1227-1235. • Urban P et al J Am Coll Cardiol 2011;57:1445-54.
PARIS Registry Adverse Event Rates
BARC Bleeding Scale1 1. Mehran et al. Circulation 2011 Jun 14;123(23):2736-47.
PARIS Registry Stent Thrombosis Stent Thrombosis (n=26) Probable (n=9) Definite (n=17) Adherent (n=14) Non-adherent (n=3) Disrupted Clopidogrel (n=1) Disrupted ASA (n=2) Odds Ratio (95% CI) for stent thrombosis associated with non-adherence: 6.3 (1.9-21.4)
PARIS Registry Relative Risk of Non-Adherence on 30 Day Stent Thrombosis in Contemporary Registries • Airoldi F et al. Circulation. 2007 Aug 14;116(7):745-54. • Urban P et al. J Am CollCardiol 2011;57:1445-54.