Glycoprotein IIB/IIIA inhibitor to reduce postpercutaneous coronary intervention myonecrosis and improve coronary flow in diabetics: the 'OPTIMIZE-IT' pilot randomized study.
BACKGROUND
Subgroup analyses of trials enrolling acute coronary syndrome patients suggest that inhibition of glycoprotein IIb/IIIa can improve the outcome of diabetic patients undergoing percutaneous coronary interventions (PCIs), possibly by improving microvascular perfusion. However, the efficacy of small-molecule IIb/IIIa receptor inhibitors to improve microvascular perfusion in stable diabetic patients undergoing elective PCI has not been specifically investigated.


METHODS
We randomized consecutive stable diabetic patients, undergoing elective PCI, to tirofiban or placebo groups along with double antiplatelet therapy. High-dose bolus (25 microg/kg per 3 min) of tirofiban was administered immediately before PCI followed by 8 h continuous infusion (0.15 microg/kg per min). Postprocedural myonecrosis was assessed prospectively by measurement of cardiac troponin T (cTnT) at 6 and 24 h after PCI. The primary end-points were post-PCI coronary flow estimated by corrected thrombolysis in myocardial infarction frame count and post-PCI myocardial infarction. Platelet aggregation was measured by platelet function analyser-100 values.


RESULTS
Forty-six patients entered the study (22 randomized to placebo and 24 randomized to tirofiban). The study drug was associated with a significant increase of platelet function analyser-100 values that peaked immediately after PCI and was maintained at 6 h (pre-PCI: 131 +/- 65 s; post-PCI: 222 +/- 49 s; after 6 h: 219 +/- 55 s).Post-PCI corrected thrombolysis in myocardial infarction frame count was similar in tirofiban and in placebo groups (10.2 +/- 3.6 vs. 12.0 +/- 7.6, P = 0.30, respectively). The prevalence of raised cTnT levels was similar in the two groups (25 vs. 30%, P = 0.56, respectively). At multivariate analysis, direct stenting (associated with reduced myonecrosis) and postdilatation (associated with increased myonecrosis) predicted cTnT elevation.


CONCLUSIONS
A high-dose bolus of tirofiban in stable diabetic patients undergoing elective PCI, along with double antiplatelet therapy, was associated with a significant further inhibition of platelet aggregation which, however, did not translate in a lower incidence of post-PCI distal embolization.
Talarico
Giovanni Paolo
GP
Institute of Cardiology, Catholic University, Rome, Italy.
Brancati
Marta
M
Burzotta
Francesco
F
Porto
Italo
I
Trani
Carlo
C
De Vita
Maria
M
Todaro
Daniel
D
Giammarinaro
Maura
M
Leone
Antonio Maria
AM
Niccoli
Giampaolo
G
Andreotti
Felicita
F
Mazzari
Mario Attilio
MA
Schiavoni
Giovanni
G
Crea
Filippo
F
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000628:therapy*; D003326:Coronary Circulation / Q000187:drug effects*; D048909:Diabetes Complications / Q000000981:diagnostic imaging / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D015607:Stents; D013997:Time Factors; D000077466:Tirofiban; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D015415:Biomarkers; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D020107:Troponin T; D014443:Tyrosine; D000077466:Tirofiban