Randomized Comparison of Oral P2Y12-Receptor Inhibitor Loading Strategies for Transitioning From Cangrelor

Hochholzer, Willibald; Kleiner, Pascal; Younas, Iris; Valina, Christian; Löffelhardt, Nikolaus; Amann, Michael; Bömicke, Timo; Ferenc, Mirosław; Hauschke, Dieter; Trenk, Dietmar; Neumann, Franz‐Josef; Stratz, Christian

doi:10.1016/j.jcin.2016.10.004

Cited by 30 publications

(24 citation statements)

References 32 publications

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“…In order to allow enough time for gastric absorption, a necessary 30-min waiting period between administration of the oral medication and termination of the cangrelor infusion was incorporated into the protocol to minimise the potential gap of reduced inhibition during the transition. Recent data suggests that prasugrel could be given even 2 h before discontinuation of cangrelor, whereas clopidogrel-mediated platelet inhibition was significantly impaired under these conditions if tested 2 h after stopping cangrelor infusion [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients

Prüller¹,

Bis

Milke³

et al. 2018

JCM

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Dual antiplatelet therapy is the standard of care for patients with myocardial infarction (MI), who have been resuscitated and treated with therapeutic hypothermia (TH). We compare the antiplatelet effect and bleeding risk of intravenous cangrelor to oral P2Y12-inhibitors in patients with MI receiving TH in a prospective comparison of two matched patient cohorts. Twenty-five patients within the CANGRELOR cohort were compared to 17 patients receiving oral P2Y12-inhibitors. CANGRELOR group (NCT03445546) and the ORAL P2Y12 Group (NCT02914795) were registered at clinicaltrials.gov. Platelet function testing was performed using light-transmittance aggregometry and monitored for 4 days. P2Y12-inhibition was stronger in CANGRELOR compared to ORAL P2Y12 (adenosine diphosphate (ADP) (area under the curve (AUC)) 26.0 (5.9–71.6) vs. 160.9 (47.1–193.7)) at day 1. This difference decreased over the following days as more patients were switched from CANGRELOR to oral P2Y12-inhibitor treatment. There was no difference in the effect of aspirin between the two groups. We did not observe significant differences with respect to thrombolysis in myocardial infarction (TIMI) or Bleeding Academic Research Consortium (BARC) classified bleedings, number of blood transfusions or drop in haemoglobin B (Hb) or hematocrit (Hct) over time. Cangrelor treatment is not only feasible and effective in resuscitated patients, but also inhibited platelet function more effectively than orally administered P2Y12-inhibitors without an increased event rate for bleeding.

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Section: Discussionmentioning

confidence: 99%

Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients

Prüller¹,

Bis

Milke³

et al. 2018

JCM

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“…82 However, the ExcelsiorLOAD2 study (Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate-Advanced Loading Strategies) showed that a 60-mg LD of prasugrel given at the start of a 2-hour infusion of cangrelor was associated with sufficient platelet inhibition after cangrelor, with only rare cases of HPR. 87 These observations may be attributed to the relatively higher concentration and longer half-life of the active metabolite of prasugrel compared with that of clopidogrel. 12 However, whether similar findings would be observed with longer infusions of cangrelor (eg, up to 4 hours) is unknown.…”

Section: Inhibitorsmentioning

confidence: 99%

“…93,94 According to the package insert of the European Medical Agency, but not that of the US Food and Drug Administration, prasugrel may also be administered 30 minutes before the infusion is stopped. 93,94 Although preliminary studies have shown that prasugrel given at the time a 2-hour infusion of cangrelor is started results in sufficient platelet inhibition, 87 this strategy cannot be routinely recommended until more data are available. Although cangrelor is approved for use in patients who have not received an oral P2Y 12 inhibitor before the PCI procedure, for those patients who have been pretreated with a thienopyridine, if the pretreatment was shortly before the initiation of cangrelor or unknown, an LD at the end of the infusion should be considered.…”

Section: Transition From Cangrelor To Oral P2y 12 Inhibitorsmentioning

confidence: 99%

International Expert Consensus on Switching Platelet P2Y ₁₂ Receptor–Inhibiting Therapies

et al. 2017

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Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y 12 inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y 12 inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y 12 inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y 12 inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y 12 inhibitors. Dual antiplatelet therapy with aspirin and a platelet P2Y 12 receptor antagonist (P2Y 12 inhibitor) is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS) and for those undergoing percutaneous coronary intervention (PCI).1,2 Clopidogrel, prasugrel, and ticagrelor are the most commonly used oral platelet P2Y 12 inhibitors; the use of ticlopidine, the first available P2Y 12 inhibitor, has been largely abandoned. 3Clopidogrel is the only oral P2Y 12 inhibitor indicated for the treatment of patients with stable coronary artery disease.1,2 Although all 3 agents have an indication for use in ACS, current guidelines support the preferential use of prasugrel and ticagrelor over clopidogrel because of their superior net clinical benefits.1,2,4-6 Nevertheless, clopidogrel remains widely prescribed. 7,8 The availability of different oral P2Y 12 inhibitors has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. 9 The recent introduction of an intravenous P2Y 12 inhibitor (ie, cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. 6 A variety of factors may contribute to the decision to switch, including the clinical setting, patient characteristics, concomitant therapies, costs, social issues, development of side effects, medication adherence, and patient/physician preference. Therefore, it is not uncommon to change P2Y 12 inhibitor. However, concerns about the safety of switching between these agents have emerged. At present, data from large-scale clinical studie...

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“…For example, ticagrelor also showed higher platelet reactivity inhibition, which is also based on laboratory tests, than prasugrel in a previous meta‐analysis . However, ticagrelor not only reduced platelet reactivity or the rate of periprocedural myonecrosis, but also augmented coronary blood flow velocity as compared with prasugrel . Therefore, several laboratory data for an increased risk of bleeding, or a reduced risk for thrombotic events, may be surrogates for some clinical aspects in ticagrelor.…”

Section: Discussionmentioning

confidence: 92%

“…Through the first electronic literature search, we excluded nine studies due to no clinical endpoints of our interest, six studies due to no RCT, and three studies because of not evaluating patients undergoing PCI in the further review stage. Since no other studies were added through additional web search, 2068 patients in 12 RCTs were included in this meta‐analysis . The characteristics of RCTs and patients are summarized in Table .…”

Section: Resultsmentioning

confidence: 99%

Head‐to‐head comparison of prasugrel versus ticagrelor in patients undergoing percutaneous coronary intervention: A meta‐analysis of randomized controlled trials

Sakurai

Burazor

Bonneau³

et al. 2017

J Interven Cardiology

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Randomized Comparison of Oral P2Y12-Receptor Inhibitor Loading Strategies for Transitioning From Cangrelor

Cited by 30 publications

References 32 publications

Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients

Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients

International Expert Consensus on Switching Platelet P2Y ₁₂ Receptor–Inhibiting Therapies

Head‐to‐head comparison of prasugrel versus ticagrelor in patients undergoing percutaneous coronary intervention: A meta‐analysis of randomized controlled trials

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Randomized Comparison of Oral P2Y12-Receptor Inhibitor Loading Strategies for Transitioning From Cangrelor

Cited by 30 publications

References 32 publications

Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients

Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients

International Expert Consensus on Switching Platelet P2Y 12 Receptor–Inhibiting Therapies

Head‐to‐head comparison of prasugrel versus ticagrelor in patients undergoing percutaneous coronary intervention: A meta‐analysis of randomized controlled trials

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Product

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International Expert Consensus on Switching Platelet P2Y ₁₂ Receptor–Inhibiting Therapies