Actinomycin-eluting stent for coronary revascularization: a randomized feasibility and safety study: the ACTION trial.
OBJECTIVE
We sought to demonstrate the safety and performance of the actinomycin D-coated Multilink-Tetra stent(Guidant Corp., Santa Clara, California) in the treatment of patients with single de novo native coronary lesions.


BACKGROUND
Drug-eluting stents (DES) releasing sirolimus or paclitaxel dramatically reduce restenosis. The anti-proliferative drug, actinomycin D, which is highly effective in reducing neointimal proliferation in preclinical studies, was selected for clinical evaluation.


METHODS
The multi-center, single-blind, three-arm ACTinomycin-eluting stent Improves Outcomes by reducing Neointimal hyperplasia (ACTION) trial randomized 360 patients to receive a DES (2.5 or 10 microg/cm(2) of actinomycin D) or metallic stent (MS). The primary end points were major adverse cardiac events (MACE) at 30 days, diameter stenosis by angiography, tissue effects, and neointimal volume by intravascular ultrasound (IVUS) at six months. When early monitoring revealed an increased rate of repeat revascularization, the protocol was amended to allow for additional follow-up for DES patients. Angiographic control of MS patients was no longer mandatory.


RESULTS
The biased selection of DES patients undergoing IVUS follow-up invalidated the interpretation of the IVUS findings. The in-stent late lumen loss and that at the proximal and distal edges were higher in both DES groups than in the MS group and resulted in higher six-month and one-year MACE (34.8% and 43.1% vs. 13.5%), driven exclusively by target vessel revascularization without excess death or myocardial infarction.


CONCLUSIONS
The results of the ACTION trial indicate that all anti-proliferative drugs will not uniformly show a drug class effect in the prevention of restenosis.
Serruys
Patrick W
PW
Erasmus Medical Center, Rotterdam, The Netherlands. p.w.j.c.serruys@erasmusmc.nl <p.w.j.c.serruys@erasmusmc.nl>
Ormiston
John A
JA
Sianos
Georgios
G
Sousa
J Eduardo
JE
Grube
Eberhard
E
den Heijer
Peter
P
de Feyter
Pim
P
Buszman
Pawel
P
Schömig
Albert
A
Marco
Jean
J
Polonski
Lech
L
Thuesen
Leif
L
Zeiher
Andreas M
AM
Bett
J H Nicholas
JH
Suttorp
Maarten J
MJ
Glogar
Helmut D
HD
Pitney
Mark
M
Wilkins
Gerard T
GT
Whitbourn
Robert
R
Veldhof
Susan
S
Miquel
Karine
K
Johnson
Rachel
R
Coleman
Leslie
L
Virmani
Renu
R
D000368:Aged; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000628:therapy*; D023903:Coronary Restenosis / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects*; D003609:Dactinomycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D009204:Myocardial Revascularization / Q000379:methods*; D011446:Prospective Studies; D015983:Selection Bias; D016037:Single-Blind Method; D015607:Stents / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects; D018084:Ultrasonography, Interventional
D003609:Dactinomycin