Antithrombotic Therapy In Acute Coronary Syndromes Research Articles

De-escalation of antiplatelet therapy in acute coronary syndromes: Why, how and when?

The synergistic blockade of the key platelet signaling pathways of cyclooxygenase-1 blockade and P2Y12 signaling by combining aspirin plus a potent P2Y12 inhibitor (prasugrel or ticagrelor), the so called dual antiplatelet treatment (DAPT), has represented the antithrombotic regimen of choice in patients with acute coronary syndrome (ACS) for nearly a decade. Nevertheless, the use of such antiplatelet treatment regimen, while reduced the risk of thrombotic complications, it is inevitably associated with increased bleeding and this risk may outweigh the benefit of a reduction of ischemic events in specific subgroup of patients. In light of the adverse prognostic implications of a bleeding complication, there has been a great interest in the development of antiplatelet regimens aimed at reducing bleeding without any trade-off in ischemic events. The fact that the ischemic risk is highest in the early phase after an ACS while the risk of bleeding remains relatively stable over time has represented the rationale for the implementation of a more intense antithrombotic regimen early after an ACS, followed by a less intense antithrombotic regimen thereafter. This practice, known as a “de-escalation” strategy, represents one of the more promising approaches for personalization of antithrombotic therapy in ACS. In this review we discuss the rationale, appraise the evidence and provide practical recommendations on the use of a de-escalation strategy of antiplatelet therapy in patients with an ACS.

Antithrombotic Therapy for ACS in Elderly Patients.

Patients over 75 account for more than one third of those presenting with myocardial infarction and more than 50% of intrahospital mortality. There are no specific guidelines for the management of acute coronary syndromes (ACS) in the elderly. Although antithrombotic therapy seems to be effective and safe in such patients, it requires specific precautions and treatment adjustments because of the higher bleeding risk due to comorbidities such as renal function impairment and malnutrition. Scientific evidence concerning elderly patients is scarce as they are either excluded or underrepresented in most randomized trials. Overall, the antithrombotic therapy needs to be adapted to avoid complications, mainly bleeding complications, without compromising the effectiveness of the treatment in this high-risk population. In the present paper, we review the current treatment strategies in ACS while focusing on data concerning the elderly, according to available data in pivotal trials and in both AHA/ACC and ESC guidelines.

Bleeding associated with the management of acute coronary syndromes

### Learning objectives Rupture or erosion of a coronary artery atheroma exposes flowing blood to the prothrombotic contents of the plaque, resulting in platelet activation and subsequent thrombus formation. If...

Abstract 5764: Discharge Without Antiplatelet Therapy After Inhospital Bleeding is an Independent Predictor of 6-Month Mortality Among Patients With Acute Coronary Syndrome: A Pooled Analysis From PURSUIT, PARAGON-A, PARAGON-B and SYNERGY

Bleeding is an important complication of the management of acute coronary syndrome (ACS). Patients (pts) with bleeding are more likely to be discharged without antiplatelet therapy (AT); however, there are limited data on the impact of discharge without AT on longitudinal outcomes in this population. Methods: We examined discharge AT (aspirin and/or thienopyridine) use among 8582 pts who experienced inhospital bleeding in 4 large trials of antithrombotic therapy in ACS. After adjusting for the propensity to receive AT, we compared 6-month outcomes among pts discharged with at least one antiplatelet drug vs. those discharged without AT. Results: Almost 1 in 10 pts with bleeding were discharged without AT (n=826). These pts had more baseline comorbidities and were more likely to experience other inhospital non-fatal adverse events compared to patients discharged with AT. Adjusted outcomes associated with no AT vs. AT are shown in the Table . In an interaction analysis, the effect of discharge without AT was worst among pts with more severe bleeding and those treated with PCI. In a treatment effect by treatment intensity analysis, the adjusted hazard ratio for death or myocardial infarction was 1.45 (95% Confidence interval(CI) 1.08–1.94) for pts receiving monotherapy and 1.90 (95% CI 1.27–2.84) for patients receiving no AT, compared to patients receiving dual AT. Conclusions: Among patients with bleeding during ACS, discharge without antiplatelet therapy was associated with worse 6-month adverse outcomes. This effect was more pronounced among patients with more severe bleeding and among patients undergoing PCI. A gradient of better outcomes with greater AT intensity was observed. Thus, more research is required to determine the optimal approach to reinitiating AT among patients who bleed yet remain at high risk of recurrent ischemic events after discharge. Table. Six-month Outcomes Among Patients Discharged Without Vs. With Antiplatelet Therapy

The Challenge of Defining Bleeding Among Patients with Acute Coronary Syndromes

Advances in the management of patients with acute coronary syndromes (ACS), specifically, the use of combined pharmacotherapy with antithrombotic and antiplatelet therapies and routine percutaneous coronary intervention (PCI), have greatly reduced rates of thrombotic outcomes and mortality in these patients. However, these same therapies also can increase the risk of bleeding and transfusion use, which are predictive of poor outcomes in patients with ACS. Accurate assessment of the risk-to-benefit ratio for any therapy depends on the use of clinically relevant, preferably standardized, definitions of endpoint events. Unfortunately, clinical trials of antithrombotic therapies have used various definitions for bleeding, most of which were originally developed for trials of fibrinolytic therapy in acute myocardial infarction (MI). These variations in bleeding definitions have complicated cross-study comparisons and assessments of drug class effects. Further, it is unclear whether these definitions remain clinically relevant in the era of routine PCI and aggressive antithrombotic therapy for ACS. Although an argument can be made for development of a standardized bleeding definition, a more prudent approach may be to develop standardized data elements, which can then be used to tailor bleeding definitions according to the goals of future clinical investigations.

The evolving role of platelet glycoprotein IIb/IIIa inhibitors in the management of acute coronary syndromes.

To briefly discuss the pathophysiology of acute coronary syndromes (ACS) and to present the clinical data currently available regarding the use of platelet glycoprotein (GP) IIb/IIIa inhibitors in the management of ACS. Literature on antithrombotic therapy in ACS was identified using a MEDLINE search (January 1988-September 1998), along with the Agency on Health Care Policy and Research guidelines for the management of unstable angina. Abstracts from recent scientific meetings were also reviewed. Review articles from the cardiology literature (pathophysiology) and randomized, controlled clinical trials of currently approved platelet GP IIb/IIIa inhibitors in ACS were evaluated. Ex vivo platelet aggregation studies and pharmacology literature were also included. Abstract data were included to illustrate specific points when published literature was not available. Study data were evaluated based on study design, outcome parameters, and adverse drug reactions. Clinical information from review articles was evaluated based on applicability to the treatment of ACS. Platelet adhesion and aggregation are pivotal events in the pathophysiology of ACS. The GP IIb/IIIa inhibitors represent a new and unique class of drugs that block fibrinogen and von Willebrand factor-mediated platelet aggregation, the common end point of all biologic pathways of platelet aggregation. Three agents are currently approved by the Food and Drug Administration: abciximab, a monoclonal antibody; eptifibatide, a synthetic peptide; and tirofiban, a synthetic nonpeptide. Clinical trial data demonstrate efficacy of all three GP IIb/IIIa inhibitors in reducing the combined end point of morbidity and mortality in patients undergoing angioplasty. Eptifibatide and tirofiban also reduce the combined end point of morbidity and mortality in patients with unstable angina. These data expand the present role of platelet GP IIb/IIIa inhibitors by providing evidence for their effectiveness in the medical treatment of ACS. However, the specific role that these agents will have in the management of ACS is yet to be fully defined.

Bleeding Complications and INR Control of Combined Warfarin and Low-Dose Aspirin Therapy in Patients with Unstable Angina and Non-Q-Wave Myocardial Infarction.

The purpose of this study was to compare bleeding complications in patients with non-Q-wave myocardial infarction and unstable angina receiving combination therapy with aspirin plus warfarin versus aspirin alone. A post-hoc analysis was performed on patients enrolled in the Antithrombotic Therapy in Acute Coronary Syndrome (ACTACS) study, which was a prospective, randomized, multicenter trial of antithrombotic therapy in unstable angina or non-Q-wave myocardial infarction. A total of 358 patients admitted within 48 hours of chest pain were randomized to antithrombotic therapy with either (1) aspirin alone or (2) aspirin (162.5 mg) plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Major and minor bleeding episodes, hemoglobin levels, and prothrombin times or INR levels were prospectively recorded. Major bleeding episodes were subclassified as relating to CABG/PTCA or not. The rate of major bleeding complications not associated with CABG or PTCA was 2.0%, and did not differ between therapy assignments. Among 55 patients undergoing CABG, 29 (53%) required transfusion of two or more units of blood. Minor bleeding was also infrequent (2.8%). All patients with minor bleeding had a full clinical recovery, and only one patient with a major bleed resulted in minor disability. Warfarin was well managed, with 50% of INRs falling between 1.9 and 2.7. Combination therapy with low-dose aspirin and warfarin (INR mean 2.5) produces an insignificant rise in the incidence of major and minor bleeding. These events are infrequent and do not usually result in major disability. The effect of longer duration combination therapy remains to be determined.