Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study.
BACKGROUND
Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown.


RESULTS
We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups.


CONCLUSIONS
In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention.
Valgimigli
Marco
M
Cardiovascular Institute, University of Ferrara, S. Anna Hospital, Corso Giovecca 203, Ferrara, Italy. vlgmrc@unife.it
Campo
Gianluca
G
de Cesare
Nicoletta
N
Meliga
Emanuele
E
Vranckx
Pascal
P
Furgieri
Alessandro
A
Angiolillo
Dominick J
DJ
Sabatè
Manel
M
Hamon
Martial
M
Repetto
Alessandra
A
Colangelo
Salvatore
S
Brugaletta
Salvatore
S
Parrinello
Giovanni
G
Percoco
Gianfranco
G
Ferrari
Roberto
R
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000453:epidemiology; D003328:Coronary Thrombosis / Q000453:epidemiology / Q000517:prevention & control*; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D000077144:Clopidogrel; D000077466:Tirofiban; D013988:Ticlopidine; D001241:Aspirin