Adenosine Diphosphate Test Research Articles

A randomized comparison of platelet reactivity in patients after treatment with various commercial clopidogrel preparations: The CLO-CLO trial

The salt linked to the clopidogrel molecule in generic preparations is suspected to affect its clinical efficacy. There is a lack of information about inhibition of platelet reactivity by generic preparations. To compare the effect of original clopidogrel (clopidogrel bisulphate [Plavix(®)]), generic clopidogrel preparations (clopidogrel hydrochloride [Clopidogrel-Mepha(®)]; clopidogrel besylate [Clopidogrel Sandoz(®)]) and prasugrel (Efient(®)) on platelet reactivity in patients with coronary artery disease. Patients with coronary artery disease treated with stents received, in a random sequence, original clopidogrel bisulphate, clopidogrel hydrochloride and clopidogrel besylate. Platelet function was assessed with the Multiplate analyser after an initial loading dose (600 mg) and at day 10 after each treatment period. Prasugrel was given for another 10 days. An adenosine diphosphate (ADP) test value<46 antiaggregation units (U) was defined as therapeutic platelet inhibition. Sixty patients (mean age 69 ± 10 years; 50 men) were randomized. Original clopidogrel bisulphate, clopidogrel hydrochloride and clopidogrel besylate provided similar inhibition of platelet reactivity with values of 31 ± 25, 33 ± 28 and 28 ± 23 U, respectively (P not significant). Prasugrel provided better inhibition of platelet function (10 ± 11 vs. 31 ± 25 U for clopidogrel bisulphate; P<0.001). An ADP test value>46 U was measured in 11 patients (18%) with clopidogrel bisulphate, 13 (22%) with clopidogrel besylate and 13 (22%) with clopidogrel hydrochloride compared with only one (2%) with prasugrel. Generic clopidogrel preparations provided similar inhibition of platelet reactivity to original clopidogrel bisulphate, although prasugrel was more efficient.

High Residual Platelet Reactivity After Clopidogrel Loading and Long-term Cardiovascular Events Among Patients With Acute Coronary Syndromes Undergoing PCI

High residual platelet reactivity (HRPR) in patients receiving clopidogrel has been associated with high risk of ischemic events after percutaneous coronary intervention (PCI). To test the hypothesis that HRPR after clopidogrel loading is an independent prognostic marker of risk of long-term thrombotic events in patients with acute coronary syndromes (ACS) undergoing an invasive procedure and antithrombotic treatment adjusted according to the results of platelet function tests. Prospective, observational, referral center cohort study of 1789 consecutive patients with ACS undergoing PCI from April 2005 to April 2009 at the Division of Cardiology of Careggi Hospital, Florence, Italy, in whom platelet reactivity was prospectively assessed by light transmittance aggregometry. All patients received 325 mg of aspirin and a loading dose of 600 mg of clopidogrel followed by a maintenance dosage of 325 mg/d of aspirin and 75 mg/d of clopidogrel for at least 6 months. Patients with HRPR as assessed by adenosine diphosphate test (≥70% platelet aggregation) received an increased dose of clopidogrel (150-300 mg/d) or switched to ticlopidine (500-1000 mg/d) under adenosine diphosphate test guidance. The primary end point was a composite of cardiac death, myocardial infarction, any urgent coronary revascularization, and stroke at 2-year follow-up. Secondary end points were stent thrombosis and each component of the primary end point. The primary end point event rate was 14.6% (36/247) in patients with HRPR and 8.7% (132/1525) in patients with low residual platelet reactivity (absolute risk increase, 5.9%; 95% CI, 1.6%-11.1%; P = .003). Stent thrombosis was higher in the HRPR group compared with the low residual platelet reactivity group (6.1% [15/247] vs 2.9% [44/1525]; absolute risk increase, 3.2%; 95% CI, 0.4%-6.7%; P = .01). By multivariable analysis, HRPR was independently associated with the primary end point (hazard ratio, 1.49; 95% CI, 1.08-2.05; P = .02) and with cardiac mortality (hazard ratio, 1.81; 95% CI, 1.18-2.76; P = .006). Among patients receiving platelet reactivity-guided antithrombotic medication after PCI, HRPR status was significantly associated with increased risk of ischemic events at short- and long-term follow-up. clinicaltrials.gov Identifier: NCT01231035.

Comparison of 2 point-of-care platelet function tests, VerifyNow Assay and Multiple Electrode Platelet Aggregometry, for predicting early clinical outcomes in patients undergoing percutaneous coronary intervention

Various platelet function tests are currently used to measure responsiveness to antiplatelet therapy. We sought to compare 2 point-of-care platelet function tests, VerifyNow Assay (Accumetrics, San Diego, CA) and Multiple Electrode Platelet Aggregometry (MEA) (Dynabyte, Munich, Germany), for predicting early clinical outcomes after percutaneous coronary intervention. Platelet reactivity in the arachidonic acid-induced and adenosine diphosphate (ADP)-induced platelet aggregation was measured simultaneously with the VerifyNow Assay and MEA in 222 patients undergoing percutaneous coronary intervention between August and October 2009. We investigated the correlations between the 2 tests and performed receiver operating characteristic curve analysis for major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), stroke, and target vessel revascularization, at 30 days. Major adverse cardiovascular events occurred in 19 patients (8.6%), including 14 patients with periprocedural MI and 5 patients with stroke. Correlations were weak between the 2 tests in the arachidonic acid-induced (Spearman r = 0.189, P = .006) and ADP-induced platelet reactivity (Spearman r = 0.390, P < .001). Although the VerifyNow P2Y12 Assay (Accumetrics) was able to predict periprocedural MI (area under the aggregation curve 0.680, P = .024) and 30-day MACE (area under the aggregation curve 0.649, P = .032), VerifyNow Aspirin Assay (Accumetrics), MEA ASPI test, and MEA ADP test failed to predict such clinical events. Hyporesponsiveness to clopidogrel based on the VerifyNow Assay was associated with about a 6-fold increased risk of MACE at 30 days. Hyporesponsiveness to clopidogrel measured by VerifyNow Assay was able to identify patients with dual antiplatelet therapy who were at higher risk for periprocedural MI and MACE at 30 days. Further randomized studies are required to validate the effectiveness of different platelet function tests for predicting long-term clinical outcomes.

Multiple Electrode Whole-Blood Aggregometry and Bleeding in Cardiac Surgery Patients Receiving Thienopyridines

Preoperative treatment with thienopyridines is associated with increased postoperative bleeding in cardiac surgery patients. Patients under treatment with thienopyridines have different levels of platelet dysfunction and the effects of discontinuation are not totally predictable. The present study aimed to determine if a preoperative assessment of platelet function in these patients could provide clinically relevant information regarding the risks of excessive postoperative bleeding and transfusion requirements. This is a retrospective analysis of prospectively collected data. Patients (n=87) under thienopyridine treatment until at least one week before cardiac surgery were enrolled in the study. Platelet function was assessed preoperatively with multiple electrode aggregometry: the adenosine diphosphate (ADP) test and TRAP (thrombin receptor-associated peptide) test were performed for all patients. Univariate analysis revealed that postoperative bleeding was associated (p<0.1) with preoperative serum creatinine level, platelet count, CPB (cardiopulmonary bypass) duration, and results from the ADP test and the TRAP test. Multivariable linear regression analysis confirmed the CPB duration (p=0.049) and ADP test (p=0.007) as independently associated with postoperative bleeding. The relationship between the ADP test and postoperative bleeding was investigated with polynomial regression analysis, and a logarithmic equation provided the best fit. The accuracy of prediction was good (area under the curve 0.71, p=0.013), with a cutoff value for the ADP test at 31 U (sensitivity 72%, specificity 66%, negative predictive value 92%, and positive predictive value 29%). The multiple electrode aggregometry ADP test in patients under thienopyridine treatment and undergoing cardiac surgery is associated with postoperative bleeding and platelet transfusion and provides an accurate preoperative prediction of postoperative bleeding risk.

The quantitative reduction by heparin of intravenous thrombosis in normal and hypercoagulable animals

The capacity of heparin to inhibit thrombosis in normal rats and rats made hypercoagulable with ellagic acid was assessed quantitatively using 129 animals. The weight of thrombus forming on a 20×0.5 mm platinum wire inserted for one hour in the vena cava was taken as a measure of thrombosis. In normocoagulable animals heparin at low dose (mean 110 i.u. mg/kg/hour) reduced thrombosis by 62%. At high dose (mean 229 i.u./kg/hour) it reduced it by 84%. In hypercoagulable animals the lower dose (114 i.u./kg/hour) also reduced thrombosis by 62%, but the residual clot was still greater than in normal animals. Of the tests used to monitor the effect of heparin, those on native blood were best. The adenosine diphosphate test was more accurate but the kaolin test was more convenient. Activated partial thromboplastin time and thrombin-time were less accurate.

An Investigation of the Effect on Platelet Function of Acetylsalicylic Acid, Dipyridamole and the Two Drugs in Combination in Patients with Transient Attacks of Ischaemia

Twenty patients suffering from transient attacks of ischaemia were studied. Seven received acetylsalicylic acid, six dipyridamole and seven a combination of the two drugs. No significant difference in platelet aggregation was shown in the acute phase between the three treatment groups using an adenosine diphosphate test method. Using Thrombofax platelet substitute, however, a significant difference was seen in all measures. On the seventh day following the ischaemic attack the Thrombofax values returned to normal but, in contrast, Platelet Factor 4 release was increased. Monthly testing of platelet activity during treatment shows that the combination of acetylsalicylic acid with dipyridamole was more effective in bringing about an early inhibition of Platelet Factor 4 release than either agent alone.