A retrospective review showed no mortality benefit, but more bleeding.
Background: The 2014 AHA guidelines for the management of NSTEMI, recommend unfractionated heparin with an initial loading dose of 60IU/KG (maximum 4,000 IU) with an initial infusion of 12 IU/kg/hr (maximum 1,000 IU/hr) adjusted per active partial thromboplastin time to maintain therapeutic anticoagulation according to the specific hospital protocol, continued for 48 hours or until PCI is performed (Level of Evidence B).
With even a higher level of evidence the 2014 AHA guidelines for the management of NSTEMI, also recommend enoxaparin 1mg/kg subcutaneously every 12 hours with reduced dosing to 1mg/kg subcutaneously in patients with a creatinine clearance <30mL/min) (Level of Evidence A). The studies supporting this therapy were performed primarily on patients with a diagnosis of unstable angina and in the era before dual anti platelet therapy and early catheterization/revascularization. Therefore, the authors of this paper looked to evaluate the clinical outcomes associated with parenteral anticoagulation therapy in the era of dual antiplatelet therapy in patients with NSTEMI.
In performing a retrospective, cohort study of adult patients, the authors of the paper looked to evaluate the association between parenteral anticoagulation therapy and clinical outcomes in patients with non-ST-segment elevation undergoing percutaneous coronary interventions at five medical centers in China. Parenteral anticoagulation therapy was defined as anticoagulation prior to PCI with unfractionated heparin, while no parenteral anticoagulation therapy was defined as only receiving anticoagulation during PCI with low molecular weight heparin or fondaparinux.
Discoveries: The primary outcomes evaluated were all-cause in-hospital mortality and in-hospital major bleeding. Other secondary outcomes of note included myocardial infarction, and composite outcomes of death, myocardial infarction, or major bleeding while in-hospital.
Of 8,197 patients undergoing PCI, 6,804 patients met the final criteria for inclusion in the study (3,901 patients with confirmed NSTEMI and 2,903 patients with unstable angina). The majority of patients were given dual antiplatelet therapy (96.9%). The key results were no difference in in-hospital mortality (0.3% vs. 0.1%) or myocardial infarction (0.3% vs 0.3%), while there was a statistically significant increase in major bleeding (2.5% vs. 1.0%).
Although, this is a retrospective study, it is the first study to evaluate the association between parenteral anticoagulation therapy and clinical outcomes in patients undergoing PCI for NSTEMI in the era of dual antiplatelet therapy. Also now that PCI is more widely used to prevent ischemic events, the protective effect of parenteral anticoagulation therapy may be less significant than before.
Clinical Take Home Point: Parenteral anticoagulation therapy did not decrease mortality in patients with NSTEMI undergoing PCI, but did have more bleeding events compared to non-parenteral anticoagulation therapy. As this is a retrospective review, which has methodological limitations, the findings of this study should be considered hypothesis generating, urging the need for RCTs.
At this point in time, with no mortality benefit and increased bleeding risk, I would recommend holding off on parenteral anticoagulation therapy in UA/NSTEMI until I have had a discussion with my consultant cardiologist about their preference of anticoagulation prior to PCI.
References:
- Chen, JY et al. Association of Parenteral Anticoagulation Therapy With Outcomes in Chinese Patients Undergoing Percutaneous Coronary Intervention for Non-ST-Segment Elevation Acute Coronary Syndrome. JAMA Intern Med 2018. PMID: 30592483
- Amsterdam EA et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. JACC 2014. PMID: 25260718
