ABSTRACT
High on-treatment platelet reactivity is associated with short-term major cardiovascular (CV) events in patients undergoing percutaneous coronary intervention (PCI). Maximum and final aggregation assessed by light transmission aggregometry (LTA) have both been used to predict short-term outcome after PCI, however their long-term prognostic impact remains controversial. There is currently no information regarding the prognostic role of deaggregation and its added value in combination with established aggregation parameters. About 1279 patients with symptomatic coronary artery disease (CAD) undergoing PCI were enrolled in this monocentric study. On-treatment platelet aggregation under clopidogrel maintenance therapy, as well as deaggregation was determined by maximum and final aggregation (5 min after adding of the agonist). Deaggregation was defined as slope of the tangent between Aggmax +0.5 min. Primary endpoints were the composite of myocardial infarction, stroke, and CV death or stent thrombosis according to the ARC criteria. Low deaggregation, defined as values in the lowest tertile (<1.5), was more frequent in patients with acute coronary syndromes (ACS) compared to patients with stable angina pectoris (SAP), ACS: 29.6% vs. SAP: 22.0%, p = 0.001. The combination of high on-treatment platelet reactivity, defined by the upper tertile of Aggmax and low deaggregation, was associated with significantly increased risk for combined long-term CV events. The combination of low deaggregation and high on-treatment platelet reactivity is associated with higher risk for recurrent events in patients with CAD undergoing PCI. Thus, deaggregation might be a more sensitive parameter providing added value in terms of risk prediction for long-term recurrent CV events in relation with established aggregation parameters.
Subject(s)
Blood Platelets/metabolism , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation/drug effects , Postoperative Complications , Ticlopidine/analogs & derivatives , Aged , Aged, 80 and over , Clopidogrel , Coronary Artery Disease/blood , Coronary Artery Disease/mortality , Coronary Artery Disease/therapy , Disease-Free Survival , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/blood , Postoperative Complications/drug therapy , Postoperative Complications/mortality , Predictive Value of Tests , Survival Rate , Ticlopidine/administration & dosageABSTRACT
The antiplatelet therapy with aspirin and the ADP-receptor blocker clopidogrel is currently the standard medication after coronary intervention or after acute coronary syndrome to prevent recurrent ischemic events and reduce mortality. However, high interindividual response variability to antiplatelet treatment is described in up to 44% of treated patients. A poor response to clopidogrel is caused by multifactorial mechanisms. Individual risk assessment including platelet function testing (PFT) can help to identify high risk patients, although recent randomized trials to investigate effects of PFT-guided therapy have failed to detect an impact on prognostic outcome. Poor response to standard antiplatelet agents can be overcome by switching to alternate substances. Elinogrel is a novel competitive, reversible ADP-receptor antagonist available in oral and intravenous formulation. Additional treatment with elinogrel showed advantages over clopidogrel, including more rapid, less variable, and more complete inhibition of platelet function without significantly increased bleeding complications. This review gives an overview over the investigational drug elinogrel for use in a personalized antiplatelet approach.
Subject(s)
Evidence-Based Medicine , Precision Medicine/methods , Quinazolinones/administration & dosage , Quinazolinones/adverse effects , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Thrombosis/drug therapy , Thrombosis/prevention & control , Administration, Oral , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Humans , Injections, Intravenous , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/administration & dosage , Purinergic P2Y Receptor Antagonists/adverse effects , Treatment OutcomeABSTRACT
The antiplatelet therapy with aspirin and the ADP-receptor blocker clopidogrel is currently the standard medication after coronary intervention or after acute coronary syndrome to prevent recurrent ischemic events and reduce mortality. However, high interindividual response variability to antiplatelet treatment is described in up to 44% of treated patients. A poor response to clopidogrel is caused by multifactorial mechanisms. Individual risk assessment including platelet function testing (PFT) can help to identify high risk patients, although recent randomized trials to investigate effects of PFT-guided therapy have failed to detect an impact on prognostic outcome. Poor response to standard antiplatelet agents can be overcome by switching to alternate substances. Elinogrel is a novel competitive, reversible ADP-receptor antagonist available in oral and intravenous formulation. Additional treatment with elinogrel showed advantages over clopidogrel, including more rapid, less variable, and more complete inhibition of platelet function without significantly increased bleeding complications. This review gives an overview over the investigational drug elinogrel for use in a personalized antiplatelet approach.
