Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation (ISAR-TRIPLE)

Intracoronary Stenting and Antithrombotic Regimen: Testing of a Six-week Versus a Six-month Clopidogrel Treatment Regimen in Patients With Concomitant Aspirin and Oral Anticoagulant Therapy Following Drug-eluting Stenting

The investigators hypothesize that reducing the duration of clopidogrel therapy from 6 months to 6 weeks after DES implantation is associated with improved clinical outcomes in patients on ASA and an oral anticoagulant.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Atrial Fibrillation
• Intervention / Treatment: Drug: aspirin; Drug: clopidogrel; Drug: oral anticoagulation

Detailed Description

The introduction of drug-eluting stents (DES) was associated not only with a widening of the indication for percutaneous coronary intervention (PCI) but also with longer antithrombotic therapy duration. Dual antiplatelet therapy with ASA and a thienopyridine is very efficient in preventing adverse events after coronary stenting but it is inferior to oral anticoagulation (OAC) to reduce the risk of stroke in patients with atrial fibrillation. OAC is also superior to antiplatelet therapy in patients with mechanical heart valves and the therapy of choice for the treatment of deep vein thrombosis and pulmonary embolism. OAC is also administered for left ventricular thrombi and low ejection fraction. There is an increasing number of patients undergoing coronary stenting who are in need of life-long anticoagulation therapy and would therefore require a triple therapy consisting of aspirin, clopidogrel and oral anticoagulation. As oral anticoagulation and antithrombotic therapy impair primary and secondary hemostasis there are concerns that adding warfarin to dual antiplatelet therapy might cause increased bleeding rates. Several studies have retrospectively assessed efficacy and safety in patients receiving a triple therapy with various results: major bleeding rates varied from 3,1%-14,9% with total bleeding rates up to 27,5%. Prospective randomized data on this topic are not available. Therefore the aim of this study is to compare a 6 week versus a 6 month triple therapy after DES implantation.

• Study Type: Interventional
• Enrollment (Actual): 614
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
• Germany
  • Munich, Germany, 80636
    • Deutsches Herzzentrum München
  • München, Germany, 81675
    • 1. Medizinische Klinik, Klinikum rechts der Isar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Patients with an indication for oral anticoagulation and a DES implantation.
2. Informed, written consent by the patient or her/his legally-authorized representative for participation in the study.

Key Exclusion Criteria:

1. Age ≤18 years
2. Previous stent thrombosis
3. DES in left main

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short triple; 6 weeks triple therapy	Drug: aspirin; 6 weeks triple therapy with aspirin, clopidogrel and oral anticoagulation; Drug: clopidogrel; 6 months triple therapy with aspirin, clopidogrel and oral anticoagulation; Drug: oral anticoagulation
Active Comparator: Long triple; 6 months triple therapy	Drug: aspirin; 6 weeks triple therapy with aspirin, clopidogrel and oral anticoagulation; Drug: clopidogrel; 6 months triple therapy with aspirin, clopidogrel and oral anticoagulation; Drug: oral anticoagulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of death, myocardial infarction, definite stent thrombosis, stroke or major bleeding.	9 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Ischemic complications (composite of cardiac death, myocardial infarction, stent thrombosis or ischemic stroke)	9 months
Bleeding complications (Major bleeding)	9 months

Collaborators and Investigators

• Sponsor: Deutsches Herzzentrum Muenchen
• Investigators: Study Chair: Adnan Kastrati, MD, Deutsches Herzzentum München; Principal Investigator: Stefanie Schulz, MD, Deutsches Herzzentrum Muenchen

Publications and helpful links

General Publications

• Rubboli A, Halperin JL, Airaksinen KE, Buerke M, Eeckhout E, Freedman SB, Gershlick AH, Schlitt A, Tse HF, Verheugt FW, Lip GY. Antithrombotic therapy in patients treated with oral anticoagulation undergoing coronary artery stenting. An expert consensus document with focus on atrial fibrillation. Ann Med. 2008;40(6):428-36. doi: 10.1080/07853890802089786.
• Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, Richardt G, Alt E, Schmitt C, Ulm K. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996 Apr 25;334(17):1084-9. doi: 10.1056/NEJM199604253341702.
• Fiedler KA, Maeng M, Mehilli J, Schulz-Schupke S, Byrne RA, Sibbing D, Hoppmann P, Schneider S, Fusaro M, Ott I, Kristensen SD, Ibrahim T, Massberg S, Schunkert H, Laugwitz KL, Kastrati A, Sarafoff N. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015 Apr 28;65(16):1619-1629. doi: 10.1016/j.jacc.2015.02.050.
• Fiedler KA, Byrne RA, Schulz S, Sibbing D, Mehilli J, Ibrahim T, Maeng M, Laugwitz KL, Kastrati A, Sarafoff N. Rationale and design of The Intracoronary Stenting and Antithrombotic Regimen-Testing of a six-week versus a six-month clopidogrel treatment Regimen In Patients with concomitant aspirin and oraL anticoagulant therapy following drug-Eluting stenting (ISAR-TRIPLE) study. Am Heart J. 2014 Apr;167(4):459-465.e1. doi: 10.1016/j.ahj.2014.01.005. Epub 2014 Jan 14.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2013
• Study Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: October 20, 2008
• First Submitted That Met QC Criteria: October 20, 2008
• First Posted (Estimate): October 21, 2008

Study Record Updates

• Last Update Posted (Estimate): August 30, 2016
• Last Update Submitted That Met QC Criteria: August 29, 2016
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: phenprocoumon; clopidogrel; warfarin; aspirin; drug eluting stent; oral anticoagulation
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Arrhythmias, Cardiac; Coronary Disease; Coronary Artery Disease; Atrial Fibrillation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: GE IDE No. A01508