A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial

Angiolillo, Dominick J.; Badimón, Juan J.; Saucedo, Jorge; Frelinger, Andrew L.; Michelson, Alan D.; Jakubowski, Joseph A.; Zhu, Baojin; Ojeh, Clement K.; Baker, Brian; Effron, Mark B.

doi:10.1093/eurheartj/ehq494

Cited by 180 publications

(151 citation statements)

References 22 publications

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“…Numerous pharmacodynamic studies including unselected patients in terms of their baseline platelet reactivity demonstrated that prasugrel much stronger than clopidogrel, even with high doses of the latter (i.e. a loading dose of 600 mg and a maintenance dose of 150 mg), inhibits ADP-induced platelet aggregation [20,[26][27][28]. This intensified platelet inhibition by prasugrel is believed to account for the reduction of ischemic events when compared with clopidogrel therapy in ACS patients undergoing PCI which was shown in the TRITON-TIMI 38 trial [4].…”

Section: Discussionmentioning

confidence: 99%

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

et al. 2014

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Background: The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI).Methods : A prospective, platelet reactivity-guided, parallel-group, open-label (70.0 [61.3--75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5-46.8 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8 (30.3 [20.4-45.7 (Cardiol J 2014; 21, 5: 547-556) ]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at ]%; p = NS) and then modestly rose at 30 days

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Section: Discussionmentioning

confidence: 99%

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

et al. 2014

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“…Similarly to our findings, in a recently published study by Ford et al [1], where pre-and post-treatment platelet aggregation was assessed, no evidence for rebound of platelet reactivity to above baseline level was found in 171 patients. In other crossover studies of P2Y12 inhibitors for stable CAD patients [1,16] or stable CAD with diabetes [1,17], where also preand post-treatment platelet aggregation were assessed, there were no significant differences compared to baseline seven to ten days after withdrawal. Available clinical studies provided conflicting results when we consider the occurrence of clinical thrombotic events after stopping clopidogrel.…”

Section: Primary Endpointmentioning

confidence: 91%

A single-centre, randomised study on platelet reactivity after abrupt or gradual discontinuation of long-term clopidogrel therapy in patients after percutaneous coronary intervention

et al. 2016

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A b s t r a c tBackground: Clinical studies have suggested increased risk of thrombotic events after planned cessation of clopidogrel therapy, due to increased platelet reactivity (platelet rebound); however, in many studies platelet function was not assessed before introducing clopidogrel. Patients who are scheduled to stop clopidogrel therapy, do it abruptly, so a gradual drug cessation might provide a beneficial treatment strategy. Aim:To determine whether a clopidogrel discontinuation results in platelet rebound hyperaggregability with increased activity compared to pre-treatment values and to assess whether abrupt or tapering clopidogrel cessation may affect platelet reactivity. Methods:Patients with stable coronary artery disease (n = 49), on chronic acetylsalicylic acid treatment, who underwent coronary angiography, and were scheduled for elective percutaneous coronary intervention with stent implantation were enrolled. Patients were randomised to either a tapering clopidogrel discontinuation during a two-week period (tapering group, n = 25) or abrupt drug cessation (abrupt group, n = 24). After 12 months of dual antiplatelet therapy with clopidogrel and acetylsalicylic acid, we performed three follow-up visits with blood sampling. Platelet aggregation was assessed using a multiple electrode aggregometer at inclusion, at cessation day, and seven and 14 days after complete clopidogrel discontinuation. The primary endpoint was the level of adenosine-diphosphate (ADP)-induced platelet aggregation. We also analysed platelet function in the ASPI test and platelet count as secondary endpoints. Results:In 36 patients included in the main analysis, we found significant differences between the two study groups in the levels of ADP-induced platelet aggregation at days seven and 14 after cessation of clopidogrel (p = 0.004 and p = 0.04, respectively). In the abrupt group, platelet aggregation returned to the values similar to baseline at day seven. There were no significant differences between baseline, seven, and 14 days after drug cessation (p = 0.92 and p = 0.37, respectively). However, in the tapering group, ADP values at seven and 14 days after drug cessation were significantly decreased, comparing to baseline (p < 0.0001 and p = 0.009, respectively). For the ASPI test and platelet count we did not find significant differences between the groups. All values returned to levels similar to the baseline. During the follow-up there were no serious cardiovascular events or bleedings.Conclusions: Tapering vs. abrupt discontinuation of clopidogrel treatment results in significantly lower platelet aggregation values after 14 days from complete drug cessation. We found no evidence of a platelet rebound effect.

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“…LTA was performed as previously reported 9. Briefly, blood samples were collected in 3.8% sodium citrate tubes.…”

Section: Methodsmentioning

confidence: 99%

Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2‐Hour Infusion in High‐Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention

Marian

Alli

Solaiman

et al. 2017

JAHA

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BackgroundIn patients with non‐ST‐segment elevation acute coronary syndromes, inhibition of platelet aggregation (IPA) with a potent P2Y12 inhibitor, ticagrelor, was inferior to tirofiban infusion at 2 hours, indicating that glycoprotein IIb/IIIa inhibitors are still needed. Ticagrelor and eptifibatide bolus only may maximally inhibit platelet aggregation and decrease bleeding, but IPA with ticagrelor and eptifibatide bolus versus 2‐hour infusion is unknown.Methods and ResultsA total of 70 P2Y12‐naïve patients, with high‐risk non‐ST‐segment elevation acute coronary syndromes, were randomized to ticagrelor and eptifibatide bolus (group 1) versus ticagrelor and eptifibatide bolus with 2‐hour infusion (group 2). Levels of IPA with ADP, thrombin receptor‐activating peptide, collagen, and high on‐treatment platelet reactivity were measured by light transmission aggregometry at baseline and at 2, 6, and 24 hours after percutaneous coronary intervention in both groups. The primary end point, IPA with ADP 20 μmol/L at 2 hours, was 99.59±0.43% in group 1 versus 99.88±1.0% in group 2 (P<0.001 for noninferiority). High on‐treatment platelet reactivity with ADP was zero at 2, 6, and 24 hours in both groups. IPA levels with ADP, thrombin receptor‐activating peptide, and collagen were significantly higher at 2 and 6 hours than at 24 hours in both groups. Periprocedural myocardial infarction was not significantly different between the groups. Hemoglobin level was significantly less at 24 hours versus baseline in group 2 (13.35±1.8 versus 12.38±1.8 g/dL, respectively; P<0.01).ConclusionsTicagrelor and eptifibatide bolus maximally inhibited platelet aggregation at 2 hours, which was associated with no significant hemoglobin drop after percutaneous coronary intervention. This obviates the need for eptifibatide 2‐hour infusion and might decrease bleeding complications.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01919723.

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A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 Trial

Cited by 180 publications

References 22 publications

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

A single-centre, randomised study on platelet reactivity after abrupt or gradual discontinuation of long-term clopidogrel therapy in patients after percutaneous coronary intervention

Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2‐Hour Infusion in High‐Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention

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