cangrelor and Postoperative-Complications

Topics: Adenosine Monophosphate; Coronary Artery Disease; Humans; Injections, Intravenous; Percutaneous Coronary Intervention; Postoperative Complications; Purinergic P2Y Receptor Antagonists

Cangrelor is a new parenteral adenosine diphosphate P2Y12 receptor inhibitor with rapid, profound and reversible inhibition of platelet activity. The aim of this meta-analysis was to evaluate efficacy and safety of this new agent in patients undergoing percutaneous coronary intervention (PCI). We searched PubMed, Cochrane Library, EMBASE, Web of Science and CINAHL databases from the inception through April 2013. Randomized controlled trials (RCTs) comparing cangrelor with control (clopidogrel/placebo) were selected. We used the random-effects models to calculate the risk ratio. The primary efficacy outcome was risk of myocardial infarction, and the primary safety outcome was TIMI major bleeding at 48 h. Three RCTs included a total of 25,107 participants. Effects of Cangrelor were not different against comparators for myocardial infarction (MI) (Risk ratio [RR] 0.94, 95% confidence interval [CI] 0.78-1.13) and all-cause mortality (RR 0.72, 95% CI 0.36-1.43). However, cangrelor significantly reduced the risk of ischemia-driven revascularization (RR 0.72, 95% CI 0.52-0.98), stent thrombosis (RR 0.60, 95% CI 0.44-0.82) and Q wave MI (RR 0.53, 95% CI 0.30-0.92) without causing extra major bleeding (Thrombolysis in Myocardial infarction criteria) and severe or life-threatening bleeding (Global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries criteria). Separate analysis against only clopidogrel also showed similar findings except Q wave MI outcome. Use of cangrelor during PCI might reduce the risk of ischemia-driven revascularization and stent thrombosis, without causing extra major bleeding.

Topics: Adenosine Monophosphate; Female; Hemorrhage; Humans; Male; Models, Biological; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Complications; PubMed; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Thrombosis

In the CHAMPION PHOENIX trial, the potent, rapidly acting, intravenous platelet adenosine diphosphate receptor antagonist cangrelor reduced the 48-h incidence of major adverse cardiac events (MACE; death, myocardial infarction, stent thrombosis, or ischaemia-driven revascularization) compared with a loading dose of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We sought to determine whether the efficacy of cangrelor during PCI varies in patients with simple vs. complex target lesion coronary anatomy.. Blinded angiographic core laboratory analysis was completed in 10 854 of 10 942 (99.2%) randomized patients in CHAMPION PHOENIX (13 418 target lesions). Outcomes were analysed according to the number of angiographic PCI target lesion high-risk features (HRF) present (bifurcation, left main, thrombus, angulated, tortuous, eccentric, calcified, long, or multi-lesion treatment). The number of patients with 0, 1, 2, and ≥3 HRFs was 1817 (16.7%), 3442 (31.7%), 2901 (26.7%), and 2694 (24.8%), respectively. The 48-h MACE rate in clopidogrel-treated patients increased progressively with lesion complexity (from 3.3% to 4.4% to 6.9% to 8.7%, respectively, P < 0.0001). Cangrelor reduced the 48-h rate of MACE by 21% {4.7% vs. 5.9%, odds ratio (OR) [95% confidence interval (95% CI)] 0.79 (0.67, 0.93), P = 0.006} compared with clopidogrel, an effect which was consistent regardless of PCI lesion complexity (Pinteraction = 0.66) and presentation with stable ischaemic heart disease (SIHD) or an acute coronary syndrome (ACS). By multivariable analysis, the number of high-risk PCI characteristics [OR (95% CI) 1.68 (1.20, 2.36), 2.78 (2.00, 3.87), and 3.23 (2.33, 4.48) for 1, 2, and 3 HRFs compared with 0 HRFs, all P < 0.0001] and treatment with cangrelor vs. clopidogrel [OR (95% CI) 0.78 (0.66, 0.92), P = 0.004] were independent predictors of the primary 48-h MACE endpoint. Major bleeding rates were unrelated to lesion complexity and were not increased by cangrelor.. Peri-procedural MACE after PCI is strongly dependent on the number of treated high-risk target lesion features. Compared with a loading dose of clopidogrel, cangrelor reduced MACE occurring within 48 h after PCI in patients with SIHD and ACS regardless of baseline lesion complexity. The absolute benefit:risk profile for cangrelor will therefore be greatest during PCI in patients with complex coronary anatomy.. NCT01156571.

Topics: Adenosine Monophosphate; Aged; Clopidogrel; Coronary Angiography; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Incidence; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Perioperative Care; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Risk Factors; Survival Rate; Treatment Outcome; United States

To examine the safety and efficacy of cangrelor in patients with single-vessel disease (SVD) and multi-vessel disease (MVD).. Cangrelor, an intravenous, rapidly acting P2Y. We studied a modified intention to treat population of patients with SVD and MVD from the CHAMPION PHOENIX trial. The primary efficacy outcome was the composite of death, myocardial infarction (MI), ischemia-driven revascularization (IDR), and stent thrombosis (ST) at 48hours. The key safety outcome was non-coronary artery bypass grafting GUSTO severe bleeding at 48hours.. Among 10,921 patients, 5,220 (48%) had SVD and 5,701 (52%) had MVD. MVD patients were older and more often had diabetes, hyperlipidemia, hypertension, prior stroke, and prior MI. After adjustment, MVD patients had similar rates of 48-hour death/MI/IDR/ST (6.3% vs 4.2%, adjusted odds ratio [OR] 1.6 [95% CI 0.42-6.06]) and GUSTO severe bleeding (0.1% vs 0.2%, P=.67) compared with SVD patients. Consistent with overall trial findings, cangrelor use reduced ischemic complications in patients with both SVD (3.9% vs 4.5%; OR 0.86, 95% CI 0.65-1.12) and MVD (5.5% vs 7.2%; OR 0.74, 95% CI 0.6-0.92, P-interaction=.43). GUSTO severe bleeding outcomes were not significantly increased with cangrelor or clopidogrel in either SVD or MVD patients.. In the CHAMPION PHOENIX trial, MVD and SVD patients had similar ischemic outcomes at 48hours and 30days. Cangrelor consistently reduced ischemic complications in both SVD and MVD patients without a significant increase in GUSTO severe bleeding. CLINICAL PERSPECTIVES.

Topics: Adenosine Monophosphate; Administration, Oral; Aged; Cause of Death; Clopidogrel; Coronary Angiography; Coronary Artery Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Global Health; Humans; Incidence; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Survival Rate; Ticlopidine; Time Factors

Cangrelor is approved for use during percutaneous coronary intervention (PCI) and is administered with different parenteral anticoagulants. We examined the efficacy and safety of cangrelor in the subgroup of patients who received unfractionated heparin (UFH) during PCI in the modified intention-to-treat population of the randomized CHAMPION PHOENIX trial (cangrelor vs clopidogrel; n = 10,939). The primary efficacy end point was the composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis (ST) at 48 hours. The key secondary efficacy end point was ST. UFH was used in 69.2% (7,569/10,939) of patients. In the UFH subgroup, cangrelor reduced the primary composite efficacy end point at 48 hours compared with clopidogrel (4.8% vs 5.9%; odds ratio [OR] 0.80 [0.65 to 0.98]; p = 0.03). Cangrelor consistently reduced ST at 2 hours (0.7% vs 1.3%; OR 0.56 [0.35 to 0.90]; p = 0.01) and 48 hours (0.9% vs 1.4%; OR 0.70 [0.45 to 1.07]; p = 0.10). There was no difference in GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries)-defined severe or life-threatening bleeding (0.1% vs 0.1%; OR 1.24 [0.33 to 4.61]; p = 0.75) or blood transfusion requirement at 48 hours (0.4% vs 0.2%; OR 1.87 [0.83 to 4.21]; p = 0.12). In conclusion, cangrelor reduces early ischemic periprocedural complications without increasing severe bleeding compared with clopidogrel in patients undergoing PCI with UFH.

Topics: Adenosine Monophosphate; Aged; Anticoagulants; Clopidogrel; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Humans; Intraoperative Period; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Retrospective Studies; Ticlopidine; Treatment Outcome

There is a clinical need for an intravenous P2Y(12) inhibitor in patients with acute coronary syndromes (ACS) for patients who are unable to take oral medications or might benefit from a rapidly reversible compound. As the time from admission to percutaneous coronary intervention (PCI) shortens, establishing the benefit of novel therapies impacting ischemic events is increasingly challenging. Cangrelor, an intravenous potent rapidly acting P2Y(12) inhibitor, bolus 30 μg/Kg plus infusion of 4 μg/Kg/min, was compared to a 600-mg loading dose of clopidogrel either before or early after PCI in patients with ACS undergoing PCI in The CHAMPION (Cangrelor versus standard tHerapy to Achieve optimal Management of Platelet InhibitiON) PLATFORM and PCI studies.. As both CHAMPION studies used similar inclusion/exclusion criteria and death, myocardial infarction, or ischemia-driven revascularization (including stent thrombosis) at 48 hours as their primary end points, the studies were pooled. The clinical events committee adjudicated myocardial infarction. The universal definition was used to define myocardial infarction.. A total of 13 049 patients were included. Cangrelor had no effect on the primary end point with the original MI definition (P = .646). With the use of the universal definition, the primary end point was decreased with cangrelor (odds ratio 0.82, 95% confidence interval 0.68-0.99, P = .037). Stent thrombosis was reduced from 0.4% to 0.2% (odds ratio 0.44, 95% confidence interval 0.22-0.87, P = .018). Thrombolysis in Myocardial Infarction major bleeding and transfusions were not increased with cangrelor.. With the use of the universal definition of myocardial infarction, cangrelor was associated with a significant reduction in early ischemic events when compared with clopidogrel in patients with non-ST-elevation ACS undergoing PCI.

Topics: Adenosine Monophosphate; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Survival Rate; Treatment Outcome

A 66-YEAR-OLD female requiring cardiac surgery had persisting anti-platelet factor 4 (PF4)/heparin antibodies (HIT-abs) 8 years after heparin-induced thrombocytopenia (HIT). In 2010, she developed thrombotic thrombocytopenic purpura (TTP) (ADAMTS-13 <5%, inhibitor at 1.0 BU/mL), which was treated successfully with corticotherapy, plasmapheresis, and intravenous heparin. While taking heparin, she developed HIT, as evidenced by a positive functional test. Her platelet count fully resolved without thrombotic complications with danaparoid treatment. In 2018, the preoperative titer of HIT-abs was still 0.38 U/mL by chemoluminescent immunoassay (CLIA), and positive by particle-gel agglutination immunoassay (PaGIA) with a titer of 2 and was strongly positive on an enzyme-linked immunosorbent assay (ELISA). The authors of the case report chose to use cangrelor combined with heparin during cardiopulmonary bypass (CPB). Cangrelor was used without increased postoperative bleeding or thrombotic complications. Postoperatively she exhibited a huge rise in HIT-abs (14.22 U/mL on postoperative day 11) with a positive functional assay. There was no recurrence of HIT, however. This case illustrates the importance of excluding the presence of persisting HIT-abs before CPB and ensuring close medical follow-up after even a single exposure to heparin.

Topics: Adenosine Monophosphate; Anticoagulants; Cardiac Surgical Procedures; Female; Follow-Up Studies; Forecasting; Heparin; Humans; Middle Aged; Platelet Aggregation Inhibitors; Platelet Factor 4; Postoperative Complications; Thrombocytopenia

Cangrelor is an intravenous P2Y. To describe the dosing, laboratory monitoring, and clinical outcomes of a series of patients who received cangrelor as a "bridging" antiplatelet agent.. This study is a retrospective analysis of all patients within the study center with coronary stents who received cangrelor as a bridge to surgical procedure and had VerifyNow monitoring during treatment.

Topics: Adenosine Monophosphate; Administration, Oral; Aged; Aged, 80 and over; Coronary Thrombosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Substitution; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Postoperative Care; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Stents; Treatment Outcome

Dual antiplatelet therapy consisting of aspirin and a P2Y12-receptor antagonist is important for preventing major adverse cardiovascular events in patients managed with percutaneous coronary intervention (PCI). The current P2Y12-receptor antagonists are only available for oral administration and exhibit a delayed onset of action. Furthermore, several days are required for platelet function to return to normal following cessation of therapy. Cangrelor is an intravenous ATP analog that directly, selectively and reversibly inhibits P2Y12 receptors on platelets. A 30-μg/kg bolus dose followed by a 4-μg/kg per minute continuous infusion of cangrelor achieves peak concentration and maximal platelet inhibition within minutes of administration. Cangrelor also demonstrates a fast offset as normal platelet function is restored 1-2 h after cessation of the infusion. Three large, double-blind, randomized trials - CHAMPION PLATFORM, CHAMPION PCI and CHAMPION PHOENIX - assessed the efficacy and safety of cangrelor compared with clopidogrel (during or immediately after PCI) or placebo in the setting of PCI. In the most recent CHAMPION PHOENIX trial, cangrelor was superior to clopidogrel for preventing adverse cardiovascular events with no significant increase in major bleeding. Based on the clinical trial results combined with unique properties such as intravenous administration and fast onset and offset, cangrelor may provide benefit in certain patients undergoing PCI.

Topics: Acute Coronary Syndrome; Adenosine Monophosphate; Aspirin; Clinical Trials as Topic; Coronary Thrombosis; Drug Interactions; Drug Therapy, Combination; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Stents