Nikolaos Koutsogiannis

Randomized Assessment of Ticagrelor Versus Prasugrel Antiplatelet Effects in Patients with ST-Segment–Elevation Myocardial Infarction

Background—Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel. Direct pharmacodynamic comparison between them has not yet been reported in ST-segment–elevation myocardial infarction patients. Methods and Results—In a prospective, single-center, single-blind study, 55 out of 117 (47%) screened consecutive ST-segment–elevation myocardial infarction patients undergoing primary percutaneous coronary intervention were randomized to either ticagrelor 180 mg loading followed by 90 mg bid, or prasugrel 60 mg loading followed by 10 mg od for 5 days. Platelet reactivity (PR) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0, 1, 2, 6, 24 hours, and 5 days postrandomization. The primary end point, PR with VerifyNow at hour 1, did not differ significantly between patients randomized to ticagrelor versus prasugrel (257.3 P2Y12 reaction unit [PRU], 95% CI 230.8–283.8 versus 231.3 PRU, 95% CI 205.3–257.4; P=0.2). PR did not differ at 2, 6, and 24 hours, although at day 5 it was lower with ticagrelor than prasugrel (25.6 PRU, 95% CI 12.3–38.9 versus 50.3 PRU, 95% CI 36.4–64.1; P=0.01). At hour 2, high on-treatment PR rates (cutoff 208 PRU) were 46.2% and 34.6% for ticagrelor and prasugrel, respectively, decreased significantly thereafter, whereas did not differ significantly between the 2 agents at all the time points of the study. Conclusions—In patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action. Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment–elevation myocardial infarction. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463163.

Preferred QT correction formula for the assessment of drug-induced QT interval prolongation.

Drug‐Induced QTc Interval Assessment. Introduction: There is debate on the optimal QT correction method to determine the degree of the drug‐induced QT interval prolongation in relation to heart rate (ΔQTc).

Double Versus Standard Loading Dose of Ticagrelor : Onset of Antiplatelet Action in Patients With STEMI Undergoing Primary PCI

To the Editor: Early and strong platelet inhibition is highly desirable in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Ticagrelor, which has direct action on the P2Y12 receptor and no need for previous metabolic

Differential Effect of Ticagrelor Versus Prasugrel on Coronary Blood Flow Velocity in Patients With Non–ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: An Exploratory Study

Background—Prasugrel and ticagrelor provide a superior anti-ischemic action than clopidogrel, with some of ticagrelor’s benefits possibly attributed to adenosine-mediated mechanisms. We aimed to compare the effect of maintenance dose of ticagrelor versus prasugrel on coronary blood flow velocity (CBFV) during increasing doses of intravenously administered adenosine. Methods and Results—In a prospective, single-center, single-blind, crossover study, 56 patients with non–ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention were randomized to receive either ticagrelor 90 mg BID or prasugrel 10 mg OD with a 15-day treatment period. At the end of each treatment period, CBFV by transthoracic Doppler echocardiography was assessed at baseline and under incremental doses (50 &mgr;g/kg per minute, 80 &mgr;g/kg per minute, 110 &mgr;g/kg per minute, and 140 &mgr;g/kg per minute) of adenosine infusion. Maximal CBFV area under the curve was higher for ticagrelor-treated than for prasugrel-treated patients, with a least squares mean difference of 7.16 (95% confidence interval, 2.61–11.7; P=0.003). Maximal CBFV/baseline CBFV ratio was higher with ticagrelor than prasugrel at 50, 80, and 110 &mgr;g/kg per minute but not at 140 &mgr;g/kg per minute adenosine infusion rate, with mean difference (95% confidence interval) of 0.17 (0.08–0.26; P<0.001), 0.21 (0.02–0.41; P=0.03), 0.24 (0.01–0.47; P=0.04), and 0.14 (−0.12 to 0.4; P=0.3), respectively. Conclusions—In patients with non–ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention, ticagrelor augments CBFV to a greater extent than prasugrel when incremental doses of adenosine are administered. Although exploratory, these results may represent a pleiotropic action of ticagrelor, possibly contributing to its beneficial effects in such patients. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01642966

Heart rate-dependence of QTc intervals assessed by different correction methods in patients with normal or prolonged repolarization.

Background: There is a continuing debate about the optimal method for QT interval adjustment to heart rate changes. We evaluated the heart rate dependence of QTc intervals derived from five different QT correction methods.

CorrespondenceResearch CorrespondenceDouble Versus Standard Loading Dose of Ticagrelor: Onset of Antiplatelet Action in Patients With STEMI Undergoing Primary PCI

To the Editor: Early and strong platelet inhibition is highly desirable in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Ticagrelor, which has direct action on the P2Y12 receptor and no need for previous metabolic

Onset of Antiplatelet Action With High (100 mg) Versus Standard (60 mg) Loading Dose of Prasugrel in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention Pharmacodynamic Study

Background—In patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, a suboptimal degree of platelet inhibition for the first 2 hours after the standard 60 mg loading dose of prasugrel has been described. Methods and Results—In a prospective, 3-center, nonrandomized, controlled study, 2 sequential groups of P2Y12 inhibitor-naive consecutive patients were loaded with either 100 mg (n=47) or 60 mg (n=35) of prasugrel. Platelet reactivity was assessed by VerifyNow at hours 0, 0.5, 1, 2, and 4. At hour 2, there was a strong trend for the primary end point of platelet reactivity (in P2Y12 reaction units) to be lower (least squares estimates of the mean difference [95% confidence interval], −45.5 [−91.2 to 0.3]; P=0.051), whereas platelet reactivity percentage inhibition (median, first to third quartile) was higher (75.5% [24%–91.8%] versus 23.5% [0%–78.3%]; P=0.02) in the 100-mg compared with 60-mg loading dose group. At hour 2, prasugrel 100 mg over 60 mg loading dose significantly reduced high platelet reactivity rates from 28.6% to 8.5% (≥230 P2Y12 reaction units threshold; P=0.036) and from 31.4% to 10.6% (≥208 P2Y12 reaction units threshold; P=0.024), whereas resulted in lower rate of ⩽20% platelet inhibition (23.4% versus 51.4%; P=0.009). Conclusions—In patients with ST-segment–elevation myocardial infarction treated with primary percutaneous coronary intervention, a higher (100 mg) than the standard loading dose of prasugrel results in greater and more consistent platelet inhibition, yet this will need to be further validated in additional studies. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01835353.

Predicting torsade de pointes in acquired long QT syndrome: optimal identification of critical QT interval prolongation.

Objectives: To determine the optimal method of ventricular repolarization assessment in predicting torsade de pointes (Tdp) in acquired long QT syndrome (LQTS) within the context of the recommended cutoff levels of concern for QT/corrected QT (QTc) interval prolongation. Methods: Twenty-nine patients with LQTS and Tdp (age 66 ± 11 years) and matched controls were studied. Standard 12-lead electrocardiograms were utilized to evaluate ventricular repolarization by using six different QT/JT heart rate correction methods. We compared the distribution of QT/QTc and JT/corrected JT intervals of patients who experienced Tdp with (1) the corresponding intervals in the matched controls and (2) the recommended cutoff levels for QT/JT interval prolongation. Results: Patients with Tdp (23 with narrow QRS, 6 with wide QRS) had longer ventricular repolarization intervals than controls (p < 0.001). For patients with narrow QRS, the QTc interval as determined firstly by the method of Hodges (t = 7.56, c = 0.933, p < 0.001), followed by the Nomogram and Fridericia methods, best discriminated Tdp patients from controls and provided the optimal balance between sensitivity and specificity at all three cutoff levels. For patients with wide QRS, the JT interval or, alternatively, the Hodges method seemed most useful. Conclusions: Assessment of ventricular repolarization by the Hodges, Nomogram and Fridericia methods performs best in identifying subsequent Tdp.

Optimal QT/JT interval assessment in patients with complete bundle branch block.

Background: Prolonged ventricular repolarization duration confers increased risk for malignant ventricular arrhythmias. We sought to clarify the optimal method of QT/JT interval assessment in patients with complete bundle branch block (BBB).

Diagnostic accuracy of electrocardiographic ST-segment depression in patients with rapid atrial fibrillation for the prediction of coronary artery disease.

BACKGROUND We aimed to examine the diagnostic value of ST-segment depression in patients with rapid atrial fibrillation (AF) for the prediction of coronary artery disease (CAD). METHODS Hemodynamically stable patients with AF, and a heart rate > 80% of their maximum predicted according to their age, were allocated to 2 groups according to their electrocardiographic findings on admission: group A included patients without any ST-segment abnormalities and group B, patients with downward or horizontal ST-segment depression ≥ 1 mm in 2 or more contiguous leads. Group A patients were subjected to a dobutamine stress echo or Tl-201 myocardial single-photon emission computed tomography, followed by coronary angiography in case of abnormal results and Group B patients to coronary angiography. CAD was defined angiographically as stenosis of ≥ 50% in any major epicardial coronary vessel. RESULTS Out of 115 consecutive patients, with a mean age of 65.9 ± 10.2 years, 42.6% were male, 18.3% smokers, 68.7% hypertensive, 21.7% had diabetes, and 40% had hyperlipidemia. We enrolled 71 and 44 patients in group A and B, respectively. Prevalence of significant CAD among studied patients was 21.7%, 3/71 (4.2%) and 22/44 (50.0%) in group A and B, respectively. Overall ST-segment depression during rapid AF had 88.0% sensitivity (95% confidence interval [CI], 67.7%-96.8%) and 75.6% specificity (95% CI, 65.2%-83.7%) in predicting presence of CAD, and positive and negative predictive value was 50.0% (95% CI, 34.8%-65.2%) and 95.8% (95% CI, 87.3%-98.7%), respectively. CONCLUSIONS In consecutive patients with rapid AF, the absence of ST-segment depression might indicate absence of CAD.