11 research outputs found
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. METHODS AND 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 interventio
Tailoring treatment with tirofiban in aptients showing resistance to aspirin and/or resistance to clopidogrel (3T/2R). Rationale for the study and protocol design
Purpose To assess whether glycoprotein IIb/IIIa inhibition
using tirofiban in low risk patients undergoing percutaneous
coronary intervention (PCI) may reduce the risk of periprocedural
myocardial infarction compared to standard care in
poor responders to aspirin and/or clopidogrel.
Methods We will enroll patients at ten European sites or
more to participate in the Tailoring Treatment with Tirofiban
in patients showing Resistance to aspirin and/or Resistance
to clopidogrel (3T/2R) study with a pre-specified sample size
of 240 patients out of 1,100 or more who will undergo
screening. The primary outcome measure is troponin I or T
elevation ratio at least three times the upper limit of normal
within 48 h after completion of the PCI.
Conclusion The results of 3T/2R study will evaluate
whether tailored intensification of anti-platelet treatment
based on poor individual response to oral anti-platelet
agents may modulate the risk of periprocedural myocardial
infarction during PCI. Our findings attempt at unraveling a
new era of individualized anti-platelet treatment through the
use of point-of-care assessment
Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease
Thioflavin T Promotes Aβ(1−40) Amyloid Fibrils Formation
Fibrillogenesis of the small peptide Aβ(1−40) is considered to be the
hallmark of Alzheimer’s disease. Some evidence indicates small oligomers, rather than mature fibrils, as the key cytotoxic agents. The fluorescent dye Thioflavin T (ThT) is often used to detect amyloid deposits in both in vivo and in vitro experiments, and it is used to study kinetic measurements, under the fundamental hypothesis that this probe does not influence the aggregation processes. We report experimental data showing that ThT may
promote the Aβ(1−40) peptide amyloid aggregation changing solvent−peptide interactions and stabilizing more ordered β-like conformation. This finding has a two-fold importance: It is a fundamental warning in all fibrillation experiments where ThT is used as fluorescent probe, and it suggests that ThT, accelerating fibril formation, could be used to reduce the presence of transient small oligomers, thus interfering with the pathogenic impact of Aβ
peptide