Switching patients from clopidogrel to prasugrel in acute coronary syndrome: impact of the clopidogrel loading dose on platelet reactivity.

OBJECTIVES: The present study aimed to assess the pharmacodynamic response of a prasugrel 60-mg loading dose (LD) alone compared with prasugrel 60 mg added to clopidogrel 600 mg. BACKGROUND: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) commonly receive a clopidogrel LD prior to angiography. Switching these patients to prasugrel may be desirable because higher platelet inhibition is expected. METHODS: In this open-label, multicenter, nonrandomized trial, 75 patients were categorized into 2 treatment strategies: Those who received a clopidogrel 600-mg LD and received a reloading dose of prasugrel 60 mg (clopidogrel/prasugrel group) and those who did not receive a clopidogrel LD and received a prasugrel 60-mg LD (prasugrel group). Platelet reactivity was assessed using VerifyNow P2Y12 reaction units (PRU) and Platelet Reactivity Index vasodilator-stimulated phosphoprotein phosphorylation (PRI-VASP) at 3 different times: at the sheath insertion prior to prasugrel LD, 4 hours after prasugrel LD, and at discharge. RESULTS: Four hours after prasugrel LD, platelet reactivity did not differ between the clopidogrel/prasugrel group and the prasugrel group according to the VerifyNow assay (median PRU 23 [5-71] vs. 54 [5-91], respectively; P = 0.18) and the VASP assay (median PRI 8.67 [4.51-16.85] versus 8.03 [4.82-21.72], respectively; P = 1.0). No significant differences in PRU and PRI were observed at discharge. Few bleeding events were reported without any significant differences between the 2 groups. CONCLUSIONS: Platelet reactivity with prasugrel 60 mg added to a clopidogrel 600-mg LD was not significantly different compared with prasugrel 60 mg alone in ACS patients undergoing PCI.

Point-of-care platelet reactivity determination with VerifyNow-P2Y12 following administration of clopidogrel or prasugrel: data from a real-world, clinical care inpatient setting.

OBJECTIVES: To describe VerifyNow-P2Y12 (VN-P2Y12, Accumetrics, San Diego, CA) results from patients treated with either clopidogrel or prasugrel who were seeking care in a hospital setting. BACKGROUND: VN-P2Y12 is a point-of-care device that measures platelet reactivity to adenosine diphosphate. Past assessments of thienopyridine therapy utilizing VN-P2Y12 have largely come from clinical trial settings. There are limited data from real-world settings. METHODS: Electronic medical record data from Huntsville Hospital (Huntsville, AL) for those who underwent VN-P2Y12 testing for clopidogrel or prasugrel between January 1, 2009 and October 31, 2010 were analyzed. The VN-P2Y12 data included P2Y12 reaction units (PRUs) and device-reported percentage of inhibition. Descriptive analyses were conducted with t tests, and a logistic regression model was estimated to assess the association between patient characteristics and the likelihood of platelet nonresponse. RESULTS: In total, 2882 tests (2476 with clopidogrel and 406 with prasugrel) were analyzed. For clopidogrel and prasugrel, respectively, mean PRU standard deviation (SD) was 206 (90) and 107 (93; P < 0.0001) and mean % inhibition (SD) was 31% (26%) and 63% (31%; P < 0.0001). Treatment with clopidogrel alone (odds ratio [OR] = 5.25; P < 0.0001), being non-Caucasian (OR = 1.48; P = 0.0440), obese (OR = 1.49; P = 0.0010), anemic (OR = 3.29; P < 0.0001), diabetic (OR = 1.75; P < 0.0001), and having a history of myocardial infarction (OR = 1.57; P < 0.0001) were significant predictors of having PRU ≥ 235. CONCLUSION: This real-world data analysis shows results that are consistent with clinical trial results, namely that compared with clopidogrel, prasugrel is associated with significantly lower PRU and greater percentage of inhibition, regardless of age, race, gender, diabetes, obesity, or proton pump inhibitor use.

Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation.

The objective of the present study was to assess the safety and effectiveness of vernakalant hydrochloride injection (RSD1235), a novel antiarrhythmic drug, for the conversion of atrial fibrillation (AF) or atrial flutter to sinus rhythm (SR). Patients with either AF or atrial flutter were randomized in a 1:1 ratio to receive vernakalant (n = 138) or placebo (n = 138) and were stratified by an arrhythmia duration of >3 hours to ≤7 days (short duration) and 8 to ≤45 days (long duration). The first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if the arrhythmia had not terminated. A total of 265 patients were randomized and received treatment. The primary end point was conversion of AF to SR for ≥1 minute within 90 minutes of the start of the drug infusion in the short-duration AF group. Of the 86 patients receiving vernakalant in the short-duration AF group, 44 (51.2%) demonstrated conversion to SR compared to 3 (3.6%) of the 84 in the placebo group (p <0.0001). The median interval to conversion of short-duration AF to SR in the responders given vernakalant was 8 minutes. Of the entire AF population (short- and long-duration AF), 47 (39.8%) of the 118 vernakalant patients experienced conversion of AF to SR compared to 4 (3.3%) of the 121 placebo patients (p <0.0001). Transient dysgeusia and sneezing were the most common adverse events in the vernakalant patients. One vernakalant patient who had severe aortic stenosis experienced hypotension and ventricular fibrillation and died. In conclusion, vernakalant demonstrated a rapid and high rate of conversion for short-duration AF and was well tolerated.