Scripps Evaluation of Antiplatelet Therapies for Intermediate Duration With the Endeavor Stent (Seaside) (SEASIDE)
Despite the benefit of drug-eluting stents (DES) to reduce the need for repeat revascularization procedures, concerns regarding late stent thrombosis (ST) have led to recent guidelines advocating extended prescription of dual antiplatelet therapy (DAPT) with aspirin and a thienopyridine (clopidogrel or ticlopidine]) beyond that described in the product labeling. Specifically, an advisory has recommended at least 1 year DAPT following treatment with DES in patients without contraindications. However, this recommendation was largely empiric and not based on any trial showing reductions in ST with long-term DAPT, nor are potential safety differences between DES considered. Further, no study has examined the balance in potential efficacy with long-term DAPT relative to an increased bleeding risk.
A consistency across clinical trials involving the Endeavor DES has been very low rates of late myocardial infarction, cardiac death and ST. Unlike other DES, recent studies indicate that the Endeavor stent may permit more rapid and complete healing over stent struts in addition to restoring normal blood vessel function. Further, in patients treated with the Endeavor stent, long-term safety outcomes are similar through 3 years follow-up irrespective of whether patients were adherent to DAPT for durations of ≤ 6 months, 12 months or 24 months.
In this study, long-term safety and effectiveness will be examined for patients treated with the Endeavor stent and assigned to DAPT for reduced duration of 6 months. If the study demonstrates safety and efficacy, it could influence treatment guidelines in favor of an abbreviated duration of DAPT for patients treated with the Endeavor stent. This would mean that should a bleeding complication or need or surgery arise less than 12 months post-PCI, patients treated with the Endeavor stent could stop DAPT after 6 months with reasonable estimate of safety. Furthermore, it is possible that patients who are currently denied DES due to known need for elective surgery could be treated with the Endeavor stent in cases where surgery can be temporarily delayed. Finally, it could be an additional option for patients who forgo treatment with DES in favor of bare metal stent (BMS) out of fear of possible bleeding with long-term DAPT.
Finally, it is recognized that not all patients respond the same way to anti-platelet therapy. Recent studies have indicated that inherited genetic variations in the way the body metabolizes anti-platelet medications may be important determinants of responsiveness to thienopyridine therapy, and that such differences may also confer a higher likelihood of adverse outcome. Patients agreeing to the additional genetic sub-study will have a DNA sample taken at baseline to test for the presence of such genes related to antiplatelet therapy metabolism and effectiveness. The results of these tests could help the medical community to better understand individual variation in response to anti-platelet therapy and the role that genetics may play in determining the response. It is possible that the information gained could help physicians tailor DAPT on a patient by patient basis.
Coronary Artery Disease
Device: Medtronic Endeavor Stent
Drug: Reduced duration (6 months) DAPT
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Clinical Evaluation of Dual Antiplatelet Therapy Duration Following Treatment With the Medtronic Endeavor Zotarolimus-eluting Coronary Stent|
- Composite endpoint of all-cause death/myocardial infarction (MI)/stroke/definite and probable stent thrombosis (ST) at 1 year post-procedure (Hierarchal) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2009|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: Six months DAPT
All patients will be assigned to 6 months of DAPT
Device: Medtronic Endeavor Stent
The study population was to consist of 900 consecutive, eligible patients with ischemic heart disease scheduled to undergo elective percutaneous coronary revascularization and amenable to treatment with an Endeavor drug-eluting stent with reference vessel diameter between 2.5 and 4.0 mm. Patients will be assigned to 6 month duration of post-procedure thienopyridine treatment with indefinite aspirin (minimum 81 mg daily) according to protocol. Recruitment was terminated early due to difficulty recruiting patients and difficulty achieving patient compliance with the six month anti-platelet protocol.Drug: Reduced duration (6 months) DAPT
|United States, California|
|La Jolla, California, United States, 92037|
|Principal Investigator:||David E Kandzari, MD||Scripps Clinic|
|Principal Investigator:||Paul S. Teirstein, MD||Scripps Clinic|
|Principal Investigator:||Eric J. Topol, MD||Scripps Clinic and Scripps Translational Science Institute|