Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial.
BACKGROUND
Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI.


RESULTS
In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72).


CONCLUSIONS
Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae.
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minn 55905, USA.
David R
DR
Holmes
Michael
M
Savage
J-M
JM
LaBlanche
Lars
L
Grip
P W
PW
Serruys
Peter
P
Fitzgerald
David
D
Fischman
Sheldon
S
Goldberg
Jeffrey A
JA
Brinker
A M
AM
Zeiher
Leonard M
LM
Shapiro
James
J
Willerson
Barry R
BR
Davis
James J
JJ
Ferguson
Jeffrey
J
Popma
Spencer B
SB
King
A Michael
AM
Lincoff
James E
JE
Tcheng
Robert
R
Chan
Jeffrey R
JR
Granett
Marcia
M
Poland
D000284:Administration, Oral; D015906:Angioplasty, Balloon, Coronary; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D016896:Treatment Outcome; D014463:Ultrasonography; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D002317:Cardiovascular Agents; D062367:ortho-Aminobenzoates; C012293:tranilast