Patterns of Non-Adherence to Dual Anti-Platelet Regimen In Stented Patients

NCT ID: NCT00998127

Last Updated: 2016-02-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 5031 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2013-03-31

Brief Summary

The purpose of this observational research study is to determine when and why patients discontinue, interrupt, or disrupt the regimen of anti-platelet medications prescribed following stent implantation, and to examine the relationship between specific patterns of non-adherence and patient outcomes.

Detailed Description

Anti-platelet medicines are the cornerstone of therapy in patients who present with acute coronary syndromes, including unstable angina, non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarction (STEMI). Multiple clinical trials have demonstrated the efficacy of dual anti-platelet therapy (DAPT) for the prevention of thrombotic events in patients who present with unstable coronary symptoms; in particular, patients who are to receive percutaneous coronary intervention (PCI). Dual anti-platelet therapy consists of a combination of aspirin and a thienopyridine (such as clopidogrel or ticlopidine). While premature discontinuation (within the first 6 months) of such therapy is associated with an increased risk of stent thrombosis, the optimal duration of DAPT has not yet been precisely determined.

Although studies suggest an increased risk of stent thrombosis and adverse events within days after thienopyridine discontinuation, no study has collected detailed data as to the exact dates and reasons that anti-platelet agents were discontinued - thus, the true risks of premature early or even scheduled late discontinuation are unknown.

Furthermore, there are multiple modes that impact subject adherence to DAPT. These include non-compliance and cost issues.

We have determined three modes why subjects may not adhere to DAPT. These include:

• Discontinuation - These subjects have discontinued the use of DAPT (aspirin or thienopyridines) as per recommendation of their physician who has felt that the subject no longer needs this therapy.
• Interruption - These subjects have interrupted their DAPT use on a voluntary basis and under the guidance and recommendation of their physician due to the need for a surgical procedure, and will reinstitute the use of DAPT within 14 days of stopping the therapy. Interruptions must be guided by the physician/cardiologist taking care of the subject and not by other health care professionals.
• Disruption - These subjects have disrupted their DAPT use, either because of a bleeding episode (minor or major) or non-compliance. Non-compliance will include continued use of DAPT at lower dose levels than prescribed either through smaller daily doses or less frequent than daily use.

These modes have not previously been systematically collected and correlated with adverse clinical events such as stent thrombosis. Furthermore, the relation of events to subsequent disruption of DAPT has not been studied prospectively. Subjects enrolled in this registry will be followed for approximately 24 months to determine the incidence of adherence according to the above classification. All patients will have their events and DAPT use monitored during the follow-up period. The assumption is that most subjects will discontinue their therapy voluntarily (usually according to their physician's advice) and that it is only those with disrupted therapy who are at risk for major adverse cardiac events (MACE). This registry will examine the predictors of DAPT disruption based on subject's demographics and determine the relationship of bleeding versus MI in these subjects using a time-dependent covariate adjusted analysis. Finally, since there are two completely different categories within the disrupted group, (non-compliance vs. event driven disruption), we will examine these patients separately as well, as a secondary endpoint.

Conditions

Medication Non-adherence; Stent Thrombosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• The subject has been informed of the nature of the study, agrees to its provisions, and has signed and been provided an "Informed Consent Form" approved by the appropriate Medical Ethics Committee (MEC) or Institutional Review Board (IRB).
• The subject must be ≥18 of age (or minimum age as required by local regulations) at the time of enrollment with successful stent placement in one or more lesions in native coronary arteries using an approved coronary stent.
• Diagnosis of angina pectoris as defined by Canadian Cardiovascular Society Classification (CCS I, II, III, IV), OR unstable angina pectoris (Braunwald Classification B&C, I-II-III), OR subjects with documented silent ischemia, OR acute myocardial infarction.
• The subject is willing and able to cooperate with the study procedures and required follow-ups.

Exclusion Criteria

• Subjects with hypersensitivity or allergies to anti-platelet therapy.
• Subjects in whom anti-platelet and/or anticoagulation therapy is contraindicated.
• Pregnant or nursing subjects and those who plan pregnancy in the period up to 1 year following the index procedure.
• The subject is participating in an investigational device or drug study. Subject must have completed the follow-up phase of any previous study at least 30 days prior to enrollment in this study.
• Subject has a history of bleeding diathesis or coagulopathy.
• Subject has other medical illness (e.g., cancer, known malignancy or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin, etc.) that may cause non-compliance with the followups as defined by the protocol or confound the data interpretation.
• Evidence of stent thrombosis by visual angiographic assessment during the index procedure.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roxana Mehran, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Antonio Colombo, MD

Role: PRINCIPAL_INVESTIGATOR

San Raffaele Hospital (Milan, Italy)

Locations

Washington Hospital Center

Washington D.C., District of Columbia, United States

Heart Center of Indiana

Indianapolis, Indiana, United States

University of Kentucky

Lexington, Kentucky, United States

Washington Adventist Hospital

Takoma Park, Maryland, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Saint Luke's/ Mid-America Heart Institute

Kansas City, Missouri, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

LeBauer Cardiovascular Research Foundation

Greensboro, North Carolina, United States

Geisinger Medical Center Clinic

Danville, Pennsylvania, United States

Hopital Bichat

Paris, , France

Charite - Campus Benjamin Franklin

Berlin, , Germany

Onassis Cardiac Surgery Center

Athens, , Greece

Careggi Hospital

Florence, , Italy

San Raffaele Hospital

Milan, , Italy

Countries

United States; France; Germany; Greece; Italy

References

Baber U, Leisman DE, Cohen DJ, Gibson CM, Henry TD, Dangas G, Moliterno D, Kini A, Krucoff M, Colombo A, Chieffo A, Sartori S, Witzenbichler B, Steg PG, Pocock SJ, Mehran R. Tailoring Antiplatelet Therapy Intensity to Ischemic and Bleeding Risk. Circ Cardiovasc Qual Outcomes. 2019 Jan;12(1):e004945. doi: 10.1161/CIRCOUTCOMES.118.004945.

Reference Type: DERIVED

PMID: 30606052 (View on PubMed)

Shah B, Baber U, Pocock SJ, Krucoff MW, Ariti C, Gibson CM, Steg PG, Weisz G, Witzenbichler B, Henry TD, Kini AS, Stuckey T, Cohen DJ, Iakovou I, Dangas G, Aquino MB, Sartori S, Chieffo A, Moliterno DJ, Colombo A, Mehran R. White Blood Cell Count and Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention in the Contemporary Era: Insights From the PARIS Study (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients Registry). Circ Cardiovasc Interv. 2017 Sep;10(9):e004981. doi: 10.1161/CIRCINTERVENTIONS.117.004981.

Reference Type: DERIVED

PMID: 28916600 (View on PubMed)

Baber U, Mehran R, Giustino G, Cohen DJ, Henry TD, Sartori S, Ariti C, Litherland C, Dangas G, Gibson CM, Krucoff MW, Moliterno DJ, Kirtane AJ, Stone GW, Colombo A, Chieffo A, Kini AS, Witzenbichler B, Weisz G, Steg PG, Pocock S. Coronary Thrombosis and Major Bleeding After PCI With Drug-Eluting Stents: Risk Scores From PARIS. J Am Coll Cardiol. 2016 May 17;67(19):2224-2234. doi: 10.1016/j.jacc.2016.02.064. Epub 2016 Apr 11.

Reference Type: DERIVED

PMID: 27079334 (View on PubMed)

Mehran R, Baber U, Steg PG, Ariti C, Weisz G, Witzenbichler B, Henry TD, Kini AS, Stuckey T, Cohen DJ, Berger PB, Iakovou I, Dangas G, Waksman R, Antoniucci D, Sartori S, Krucoff MW, Hermiller JB, Shawl F, Gibson CM, Chieffo A, Alu M, Moliterno DJ, Colombo A, Pocock S. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet. 2013 Nov 23;382(9906):1714-22. doi: 10.1016/S0140-6736(13)61720-1. Epub 2013 Sep 1.

Reference Type: DERIVED

PMID: 24004642 (View on PubMed)

Other Identifiers

09-367

Identifier Type: -

Identifier Source: secondary_id

09-0421-F2L

Identifier Type: -

Identifier Source: secondary_id

717/DG

Identifier Type: -

Identifier Source: secondary_id

AAAE0348

Identifier Type: -

Identifier Source: secondary_id

GCO 10-1196

Identifier Type: -

Identifier Source: org_study_id