Long-term clinical outcome based on aspirin and clopidogrel responsiveness status after elective percutaneous coronary intervention: a 3T/2R (tailoring treatment with tirofiban in patients showing resistance to aspirin and/or resistance to clopidogrel) trial substudy

Objectives The purpose of this study was to investigate the long-term outcome after elective percutaneous coronary intervention in low-risk patients screened for aspirin and/or clopidogrel responsiveness in the 3T/2R (Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel) trial. Background The impact of aspirin and/or clopidogrel poor response on long-term outcome is debated. Methods Aspirin and clopidogrel response was measured with the VerifyNow system aspirin and P2Y12 assays. After percutaneous coronary intervention (PCI), death, stroke, and myocardial infarction were assessed up to 1 year. Results Overall, 1,277 patients were screened, and 826 (65%) were treated with PCI. In all, 124 patients were found to be aspirin poor responders, and there were 179 clopidogrel poor responders (totally, 278 poor responders). The 1-year end point was significantly higher in poor responders as compared to full responders (15.8% vs. 8.6%, p = 0.002), which is principally due to more myocardial infarction occurrence. At multivariable analysis, clopidogrel poor response emerged as an independent predictor (hazard ratio: 1.15, 95% confidence interval: 1.03 to 1.28). Receiver-operator characteristic analysis identifies ≤23 of percentage of platelet inhibition and <208 of P2Y12 reactivity units as optimal cut offs to predict 1-year end point. Excluding periprocedural events, also peri-PCI myocardial infarction, which is strongly related to aspirin/clopidogrel poor response, was an independent predictor (hazard ratio: 1.25, 95% confidence interval: 1.14 to 1.37). Glycoprotein IIb/IIIa inhibitor administration reduces this risk in poor responders (21.2% vs. 34.7%, p = 0.02), but not in full responders (6.3% vs. 6.5%, p = 0.8). Conclusions Poor response to clopidogrel is an independent predictor of periprocedural myocardial infarction and worse 1-year outcome in low-risk patients undergoing PCI, whereas poor response to aspirin failed to predict a worse outcome. Contrary to what was observed in poor responders, glycoprotein IIb/IIa inhibitor therapy failed to provide a benefit in aspirin and/or clopidogrel full responders

Cutting balloon angioplasty in percutaneous carotid interventions.

Purpose: To report a prospective feasibility study of Cutting Balloon angioplasty (CBA) applied in the predilation phase of carotid artery stenting (CAS) in highly calcified lesions. Methods: From January 2003 to February 2007, 178 consecutive patients (109 men; mean age 73.1 ± 7.3 years) with highly calcified carotid lesions underwent CAS with CBA applied as a pre-specified strategy in the predilation phase of the procedure. All steps in the procedure were performed under cerebral filter protection. The cutting balloon ranged in diameter from 3 to 4 mm and was inflated at nominal pressures in the target lesion. Pre-CBA dilation with a low-profile coronary balloon was performed only when the Cutting Balloon was not able to cross the lesion. Selection of the filters and stents was at the operator's discretion. Primary endpoints were the all stroke and death rates at 30 days and 6 months. Secondary endpoints included Cutting Balloon success (positioning and full balloon inflation), CAS technical success (residual angiographic stenosis <30%), CAS procedural success (technical success and no complications), and in-hospital major complications. Results: Cutting Balloon success was achieved in all 178 patients. In 32 (18.0%), pre-CBA dilation was necessary due to inability to cross the lesion with the Cutting Balloon initially. CAS technical success was achieved in all patients. One (0.6%) patient suffered transient neurological intolerance due to flow cessation from massive debris in the distal filter; this event was completely resolved after the filter was removed (CAS procedural success 99.4%). One patient suffered a major stroke at day 15 (0.6% 30-day all stroke and death rate). At the 6-month follow-up, 174 (97.7%) patients were evaluated; 1 patient died from myocardial infarction at day 35, and 2 patients died from non-neurological or cardiac causes at days 103 and 158. The cumulative all stroke and death rate was 2.2%. Conclusion: These data suggest that CBA performed during the predilation phase of CAS in highly calcified lesion is a safe and useful method to prepare this lesion subset for stenting

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