Unstable angina / non ST elevation myocardial infarction complications of bleeding and transfusion prevention


 * ; ; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.

Prevention

 * An optimal NSTEMI/unstable angina management algorithm maximizes the anticoagulant benefit of pharmacological agents, employs coronary intervention when indicated, while simultaneously minimizing bleeding risks.
 * Recent trials (OASIS, ACUTIY etc) have correlated reductions in bleeding events with improvements in outcomes of death, MI and stroke.
 * Reduction of bleeding complications has therefore become a priority in NSTEMI/unstable angina management.

Alternative means of vascular access for coronary intervention
Since the introduction of GP IIb/IIIa inhibitors into practice the risk of transfemoral access site bleeding complications has increased by 10%.
 * Femoral arteriotomy with femoral head fluoroscopy reduces access site complications.
 * Radial artery approach for PCI, is associated with a substantial reduction in bleeding and vascular complications.
 * No benefit has been associated with femoral vascular closure devices.

Judicious dosing of antithrombotic and antiplatelet therapies

 * 15% of major bleeding events in NSTEMI/unstable angina patients are preventable with proper bleeding risk assessment and proper administration of anticoagulative agents.
 * Data from the CRUSADE registry, reported that 42% of 140,000 NSTEMI patients received at least one excess dose of antithrombotic agent during their hospitalization. . The excess dosing of antithrombotic agents were directly associated with increase rate of bleeding and a prolonged length of hospital stay.
 * Risk factors for receiving excessive doses of unfractionated heparin, low-molecular-weight heparin or GP IIb/IIIA inhibitors included:
 * Elderly
 * Female
 * Low body weight
 * Diabetes
 * Heart failure

Synergy of ASA and Plavix

 * The administration of aspirin and clopidogrel to NSTEMI/unstable angina patients is efficacious and supported by published guidelines.
 * The absolute increase in major bleeding is 1% higher with dual antiplatelet therapy compared with aspirin alone.
 * In a post hoc analysis of the CURE trial, Peters et al., described an increased incidence in major bleeding directly associated with aspirin (ASA) dose. (ASA alone: dose 100 mg; 1.9%, 101–199 mg; 2.8%, 200 mg; 3.7%, P=0.0001 ASA+clopidogrel: dose 100 mg; 3.0%, 101–199 mg; 3.4%, 200 mg; 4.9%, P=0.0009).
 * Although the ideal dose of aspirin is unknown, these data do suggest that lower doses of aspirin are safer when combined with thienopyridines.

Newer pharmacological strategies to reduce bleeding

 * Bivalirudin:
 * REPLACE-2 trial assigned 6,010 patients undergoing urgent or elective PCI to receive unfractionated heaparin with planned GP IIb/IIIa inhibitor or bivalirudin with provisional use of a GP IIb/IIIa inhibitor.
 * Composite, 30-day endpoint demonstrated no statistically significant difference in the primary quadruple endpoint of death, MI, target vessel revascularization, or major bleeding between study groups. This was driven by a statistically significant 40% relative risk reduction in major bleeding in patients assigned to bivalirudin.
 * ACUITY trial assigned 13,819 moderate-to-high-risk NSTEMI patients to one of three treatment arms: heparin (unfractionated heparin or enoxaparin) with GP IIb/IIIa inhibitor, bivalirudin with GP IIb/IIIa inhibitor, or bivalirudin alone (with provisional use of a GP IIb/IIIa inhibitor).
 * Primary endpoint was net clinical benefit at 30-days that consisted of death, MI, ischemia-driven revascularization, or non-CABG major bleeding.
 * The bivalirudin-alone strategy was superior to the other two arms (heparin/enoxaparin + GP IIb/IIIa: 11.7%, bivalirudin + GP IIb/IIIa: 11.8%, bivalirudin alone: 10.1%, P < 0.001).
 * There were no significant differences in the rates of death, MI, or revascularization between the three arms, but there was a substantial reduction in ACUITY major bleeding among patients assigned to the bivalirudin alone strategy.


 * Fondaparinux:
 * OASIS-5 trial randomized 20,078 NSTEMI patients to receive fondaparinux or enoxaparin for 6 days.
 * Primary outcome of MI, refractory ischemia, or death at 9 days was not statistically different between study arms (5.8 vs. 5.7%, HR 1.01: 95% CI: 0.90–1.13).
 * There was however, a significant lower rate of major bleeding at 9 days in patients treated with fondaparinux compared with enoxaparin (2.2 vs. 4.1%, HR 0.52: 95% CI: 0.44–0.61).
 * At 30-day follow-up, there was a statistically significant 17% reduction in 30-day mortality among patients treated with fondaparinux versus enoxaparin (2.9 vs. 3.5%, HR 0.83: 95% CI: 0.71–0.97).
 * The incidence of catheter-related thrombus was higher among patients assigned to fondaparinux compared with those assigned to enoxparin (1.3% vs. 0.2%), necessitating a protocol amendment that mandated the addition of unfractionated heparin during PCI in patients treated with fondaparinux undergoing coronary intervention.

Fondaparinux should not be the sole anticoagulant used in patients with ACS undergoing PCI.