Impact of an integrated treatment algorithm based on platelet function testing and clinical risk assessment: results of the TRIAGE Patients Undergoing Percutaneous Coronary Interventions To Improve Clinical Outcomes Through Optimal Platelet Inhibition study.

Assessment of platelet reactivity alone for thienopyridine selection with percutaneous coronary intervention (PCI) has not been associated with improved outcomes. In TRIAGE, a prospective multicenter observational pilot study we sought to evaluate the benefit of an integrated algorithm combining clinical risk and platelet function testing to select type of thienopyridine in patients undergoing PCI. Patients on chronic clopidogrel therapy underwent platelet function testing prior to PCI using the VerifyNow assay to determine high on treatment platelet reactivity (HTPR, ≥230 P2Y12 reactivity units or PRU). Based on both PRU and clinical (ischemic and bleeding) risks, patients were switched to prasugrel or continued on clopidogrel per the study algorithm. The primary endpoints were (i) 1-year major adverse cardiovascular events (MACE) composite of death, non-fatal myocardial infarction, or definite or probable stent thrombosis; and (ii) major bleeding, Bleeding Academic Research Consortium type 2, 3 or 5. Out of 318 clopidogrel treated patients with a mean age of 65.9 ± 9.8 years, HTPR was noted in 33.3 %. Ninety (28.0 %) patients overall were switched to prasugrel and 228 (72.0 %) continued clopidogrel. The prasugrel group had fewer smokers and more patients with heart failure. At 1-year MACE occurred in 4.4 % of majority HTPR patients on prasugrel versus 3.5 % of primarily non-HTPR patients on clopidogrel (p = 0.7). Major bleeding (5.6 vs 7.9 %, p = 0.47) was numerically higher with clopidogrel compared with prasugrel. Use of the study clinical risk algorithm for choice and intensity of thienopyridine prescription following PCI resulted in similar ischemic outcomes in HTPR patients receiving prasugrel and primarily non-HTPR patients on clopidogrel without an untoward increase in bleeding with prasugrel. However, the study was prematurely terminated and these findings are therefore hypothesis generating.

Assessment of the efficacy and tolerability of clopidogrel napadisilate in Korean patients with coronary stenting: a multicenter, prospective, open-label, randomized trial.

OBJECTIVE: Clopidogrel is indicated for the treatment and prevention of peripheral vascular, cerebrovascular, and coronary artery diseases. This clinical trial was designed to demonstrate that clopidogrel napadisilate (CN) is not inferior to clopidogrel bisulfate (CB) with respect to its effectiveness in inhibiting platelet aggregation. METHODS: This 4 week multi-center, prospective, open-label, randomized trial was conducted at five clinical centers in South Korea. Patients were randomized into the 75 mg CN group or the 75 mg CB group. Platelet aggregation was assessed by the VerifyNow assay. The primary outcome was the difference of the percentage P2Y12 inhibition and the secondary outcome was the baseline and change in P2Y12 reaction units (PRU). RESULTS: There was no significant difference in the percentage P2Y12 inhibition (CN vs. CB, 34.92 ± 21.33% vs. 30.43 ± 17.90%, p=0.203). The mean difference of the percentage P2Y12 inhibition between groups was 4.49%, their two-sided 95% confidence interval was -2.45% to 11.44%, and the lower bound (-2.45%) was greater than the acceptable non-inferiority margin of -9.0%. The baseline PRU was 96.67 ± 76.76 in the CN group and 216.95 ± 68.86 in the CB group (p=0.121), and the change in the PRU was -3.32 ± 51.71 in the CN group and 10.52 ± 43.31 in the CB group (p=0.106). Four subjects experienced AEs (6.3%, 5 events) in the CN group and 7 subjects (11.11%, 13 events) in the CB group without statistical significance (p=0.364). With respect to serious adverse events, 2 events were reported in 2 subjects, 1 in each group. CONCLUSION: Clopidogrel napadisilate was not inferior to clopidogrel bisulfate in terms of antiplatelet efficacy and tolerability, and there were no clinically significant adverse events.

Assessment of platelet adhesiveness and aggregation in mild acute pancreatitis using the PFA-100 system.

CONTEXT: Acute pancreatitis constitutes a systemic inflammatory process which is often accompanied by thrombosis and bleeding disorders. The role of platelets in the pathophysiology of the disease remains to be elucidated. OBJECTIVE: In the present study, we evaluated the alterations of platelet function in patients suffering from acute edematous pancreatitis using the recently developed platelet function analyzer PFA-100. DESIGN: A cohort study with one end-point (difference between patients with acute edematous pancreatitis and normal controls concerning at least one PFA-100 closure time at the P<0.01 level of statistical significance). MAIN OUTCOME MEASURE: The hemostatic capacity of platelets was tested in citrated blood and standard cartridges containing collagen-ADP or collagen-epinephrine. PATIENTS: We studied 16 patients (6 women and 10 men, mean age 62.1 years) with acute edematous pancreatitis, who had been admitted to our Internal Medicine Department, along with 32 normal controls of similar age and having the same woman-man ratio. RESULTS: The mean closure time using collagen-ADP cartridges was 69.6 s (95% CI: 60.4-78.7 s) in patients and 96.1 s (95% CI: 93.0-99.3 s) in normal controls (t-value: 7.2; P<0.001). The mean closure time using collagen-epinephrine cartridges was 110.7 s (95% CI: 100.1-121.3 s) in patients and 119.7 s (95% CI: 114.6-124.8 s) in normal controls (t-value: 1.8; P=0.078). The hematocrit in all patients was less than the upper reference value. CONCLUSIONS: The PFA-100 represents a simple and easy to use test for investigating primary hemostasis. Although the method has been widely used in hemorrhagic conditions, this is the first time it has been applied in the prethrombotic model of acute pancreatitis, suggesting increased platelet adhesiveness and aggregation.