prasugrel-hydrochloride and Blood-Loss--Surgical

Since the publication of the 2009 Canadian Cardiovascular Society position paper on antiplatelet therapy and cardiac surgery, new antiplatelet strategies with either double-dose clopidogrel or with new and more potent agents (prasugrel and ticagrelor) have become accepted practice. For the patient requiring coronary artery bypass surgery who has recently received either double-dose clopidogrel or one of the new P2Y12 platelet inhibitors, increased perioperative bleeding can be anticipated. For patients who are stable and can wait, surgery should be delayed for 5 days after the last dose of clopidogrel (standard or double-dose), and for 7 days after the last dose of prasugrel. Patients who have received ticagrelor should wait 5 days after the last dose before surgery, although it is likely that surgery can be safely performed 3 days after discontinuing ticagrelor. For patients who require emergency surgery despite recently receiving double-dose clopidogrel, prasugrel, or ticagrelor, the measures to limit perioperative bleeding discussed in the 2009 Canadian Cardiovascular Society position paper remain applicable, but have not yet been rigourously tested. Recent studies have suggested the value of preoperative in vitro platelet aggregometry to determine perioperative bleeding risk.

Topics: Adenosine; Blood Loss, Surgical; Clopidogrel; Combined Modality Therapy; Coronary Artery Bypass; Drug Therapy, Combination; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine

The management of patients scheduled for surgery with a coronary stent, and receiving 1 or more antiplatelet drugs, has many controversies. The premature discontinuation of antiplatelet drugs substantially increases the risk of stent thrombosis (ST), myocardial infarction, and cardiac death, and surgery under an altered platelet function could also lead to an increased risk of bleeding in the perioperative period. Because of the conflict in the recommendations, this article reviews the current antiplatelet protocols after positioning a coronary stent, the evidence of increased risk of ST associated with the withdrawal of antiplatelet drugs and increased bleeding risk associated with its maintenance, the different perioperative antiplatelet protocols when patients are scheduled for surgery or need an urgent operation, and the therapeutic options if excessive bleeding occurs.

Topics: Aspirin; Blood Loss, Surgical; Clopidogrel; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Humans; Myocardial Revascularization; Perioperative Care; Perioperative Period; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticlopidine

Prasugrel (Efient) is a potent, selective and irreversible inhibitor of adenosine diphosphate (ADP)-mediated platelet aggregation that is indicated for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS) [comprising unstable angina pectoris/non-ST-segment-elevation myocardial infarction (unstable angina/NSTEMI) and ST-segment-elevation myocardial infarction (STEMI)] undergoing percutaneous coronary intervention (PCI). Oral prasugrel provides rapid, potent inhibition of platelet aggregation and is an effective antiplatelet agent for the management of patients with ACS who are undergoing PCI. In these patients, prasugrel was associated with a significantly lower incidence of ischaemic events than clopidogrel, and was particularly effective in specific subgroups of patients, such as those with diabetes mellitus. However, the efficacy of prasugrel was offset by a higher risk of bleeding than clopidogrel, with patients aged > or =75 years, those weighing <60 kg and those with a history of stroke or transient ischaemic attack at the greatest risk. A lower dose of prasugrel in patients aged > or =75 years and those weighing <60 kg may help to minimize the bleeding risk, although more data are needed to establish this; prasugrel is contraindicated in patients with a history of stroke or transient ischaemic attack. Thus, prasugrel provides a new option for the management of patients with ACS who are undergoing PCI; the risk-benefit ratio should be carefully assessed before intensive antiplatelet therapy with prasugrel is initiated.

Topics: Acute Coronary Syndrome; Adult; Aged; Angioplasty, Balloon, Coronary; Blood Loss, Surgical; Clopidogrel; Female; Humans; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Ticlopidine; Tissue Distribution; Young Adult

The objective of this study was to characterize the bleeding, transfusion, and other outcomes of patients related to the timing of prasugrel or clopidogrel withdrawal before coronary artery bypass grafting (CABG).. There is little evidence to guide clinical decision making regarding the use of prasugrel in patients who may need urgent or emergency CABG. Experience with performing CABG in the presence of clopidogrel has raised concern about perioperative bleeding complications that are unresolved.. A subset of the TRITON-TIMI 38 study (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38), in which patients with acute coronary syndrome were randomized to treatment with aspirin and either clopidogrel or prasugrel, underwent isolated CABG (N = 346). A supplemental case report form was designed and administered, and the data combined with the existing TRITON-TIMI 38 database. Baseline imbalances were corrected for using elements of the European System for Cardiac Operative Risk Evaluation and The Society of Thoracic Surgeons predictive algorithm.. A significantly higher mean 12-h chest tube blood loss (655 ± 580 ml vs. 503 ± 378 ml; p = 0.050) was observed with prasugrel compared with clopidogrel, without significant differences in red blood cell transfusion (2.1 U vs. 1.7 U; p = 0.442) or the total donor exposure (4.4 U vs. 3.0 U; p = 0.463). All-cause mortality was significantly reduced with prasugrel (2.31%) compared with 8.67% with clopidogrel (adjusted odds ratio: 0.26; p = 0.025).. Despite an increase in observed bleeding, platelet transfusion, and surgical re-exploration for bleeding, prasugrel was associated with a lower rate of death after CABG compared with clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Aspirin; Blood Loss, Surgical; Cause of Death; Chest Tubes; Clopidogrel; Cohort Studies; Combined Modality Therapy; Coronary Artery Bypass; Drug Administration Schedule; Drug Therapy, Combination; Erythrocyte Transfusion; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recurrence; Retrospective Studies; Risk Adjustment; Thiophenes; Ticlopidine

The goal of this study was to assess the offset of the antiplatelet effects of prasugrel and clopidogrel.. Guidelines recommend discontinuing clopidogrel at least 5 days and prasugrel at least 7 days before surgery. The pharmacodynamic basis for these recommendations is limited.. Aspirin-treated patients with coronary artery disease were randomly assigned to either prasugrel 10 mg or clopidogrel 75 mg daily for 7 days. Platelet reactivity was measured before study drug administration and for up to 12 days during washout. The primary endpoint was the cumulative proportion of patients returning to baseline reactivity after study drug discontinuation.. A total of 56 patients were randomized; 54 were eligible for analysis. Platelet reactivity was lower 24 h after the last dose of prasugrel compared with clopidogrel. After prasugrel, ≥75% of patients returned to baseline reactivity by washout day 7 compared with day 5 after clopidogrel. Recovery time was dependent on the level of platelet reactivity before study drug exposure and the initial degree of platelet inhibition after study drug discontinuation but not on treatment assignment.. Recovery time after thienopyridine discontinuation depends on the magnitude of on-treatment platelet inhibition, resulting, on average, in a more delayed recovery with prasugrel compared with clopidogrel. The offset of prasugrel was consistent with current guidelines regarding the recommended waiting period for surgery after discontinuation. (Prasugrel/Clopidogrel Maintenance Dose Washout Study; NCT01014624).

Topics: Adult; Aged; Aspirin; Blood Loss, Surgical; Blood Platelets; Clopidogrel; Confounding Factors, Epidemiologic; Coronary Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Thiophenes; Ticlopidine

Patients with acute myocardial infarction pretreated with prasugrel or ticagrelor may require urgent coronary artery bypass grafting (CABG). However, prasugrel and ticagrelor withdrawal period is recommended for 5-7 days before planned CABG to enable full platelet recovery. We hypothesized that monitoring sequential platelet reactivity (PR) could identify patients with early platelet recovery who may benefit from earlier surgery before the guideline-recommended 5-7 day delay.. We performed preoperative PR assays in 35 patients with acute myocardial infarction who received prasugrel (60%) or ticagrelor (40%) and required an urgent CABG. When platelet inhibition levels were favorable, on the basis of the VerifyNow assay, surgery was endorsed. CABG-related bleeding parameters were collected and compared with two matched control groups composed of patients who received fewer potent antiplatelet regimens.. On the basis of platelet function monitoring, we identified 21 (56.7%) patients with a relatively earlier platelet recovery who underwent CABG before the end of the conventional washout period (5-7 days). For these patients, the washout periods were shortened to an average time of 2.6±1.0 days for ticagrelor and 3.8±1.5 days for prasugrel. CABG-related bleeding parameters were comparable with the two matched control groups.. A strategy of performing preoperative PR assays can identify patients who recover platelet function in less than 5-7 days after ticagrelor or prasugrel discontinuation. This strategy may provide the basis for performing urgent CABGs earlier than the currently recommended delay. Future, larger studies are required to establish these preliminary findings.

Topics: Adenosine; Aged; Blood Loss, Surgical; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Myocardial Infarction; Pilot Projects; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Point-of-Care Testing; Postoperative Hemorrhage; Prasugrel Hydrochloride; Predictive Value of Tests; Preoperative Period; Risk Factors; Ticagrelor; Time Factors; Time-to-Treatment; Treatment Outcome