Enoxaparin vs. Unfractionated Heparin: Results From the SYNERGY Trial
Enoxaparin vs. Unfractionated Heparin: Results From the SYNERGY Trial
Aims: Elderly patients are at high risk from non-ST-segment elevation acute coronary syndromes (NSTE ACS) as well as from treatment-related complications. Age-associated changes in physiology may alter the risk and benefit expected from therapy. The SYNERGY database was used to study the influence of age on treatment outcomes with enoxaparin vs. unfractionated heparin (UFH) in patients with high-risk NSTE ACS.
Methods and Results: Age was analysed as a continuous and categorical variable (<65, 65-74, and ≥75 years, and <75 and ≥75 years) for descriptive purposes. Logistic regression was used to adjust the outcomes of 30-day death, death or myocardial infarction (MI), and major bleeding for baseline characteristics. Odds ratios compared outcomes by age and by treatment within age groups. Model interaction terms were used to test for statistically different outcomes by treatment and age. Overall, 9977 randomized patients had age information, of whom 25.5% (2540) were ≥75 years of age. Elderly patients (≥75 years) had more cardiovascular risk factors, prior cardiac disease, and higher acuity at presentation. After adjustment, advanced age (per 10 years) was associated with 30-day death or MI [risk odds ratios (ROR): 1.14, P = 0.002], 30-day death (ROR: 1.54, P < 0.0001), and 1-year death (ROR: 1.47, P < 0.0001), as well with TIMI major bleeding (ROR: 1.21, P = 0.001), GUSTO severe bleeding (ROR: 1.20, P = 0.047), and transfusion (ROR: 1.04, P = 0.324). Although there was a higher rate of GUSTO severe bleeding noted with enoxaparin in elderly patients, the overall relationships between treatment (UFH or enoxaparin) and outcomes did not vary significantly as a function of the patient's age.
Conclusion: Although higher rates of adverse events are seen in the oldest subgroup (age ≥75 years) treated with enoxaparin, statistical comparisons confirm similar efficacy and safety of enoxaparin and UFH across age subgroups as was demonstrated overall in SYNERGY.
Antithrombotic therapy plays an important role in the pathophysiology and treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS). This is particularly true for elderly patients (≥75 years of age), who are at higher risk from recurrent thrombotic events and death, and for whom aggressive treatment may yield the greatest benefits. Elderly patients are also at higher risk from bleeding as a complication of antithrombotic therapy.
Clinical guidelines differ on whether low-molecular-weight heparin (LMWH, i.e. enoxaparin) or unfractionated heparin (UFH) is the preferable antithrombotic therapy for patients with NSTE ACS. Owing to the inherent differences between these heparins, the decision focuses on the balance between antithrombotic and bleeding effects. Furthermore, because of the differences in drug metabolism and effect in the elderly, such comparisons are particularly relevant in this subgroup. Therefore, using data from the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) trial, we investigated outcomes in high-risk NSTE ACS patients according to age subgroups (<65, 65-74, and >75 years) assigned to either LMWH or UFH.
Abstract and Introduction
Abstract
Aims: Elderly patients are at high risk from non-ST-segment elevation acute coronary syndromes (NSTE ACS) as well as from treatment-related complications. Age-associated changes in physiology may alter the risk and benefit expected from therapy. The SYNERGY database was used to study the influence of age on treatment outcomes with enoxaparin vs. unfractionated heparin (UFH) in patients with high-risk NSTE ACS.
Methods and Results: Age was analysed as a continuous and categorical variable (<65, 65-74, and ≥75 years, and <75 and ≥75 years) for descriptive purposes. Logistic regression was used to adjust the outcomes of 30-day death, death or myocardial infarction (MI), and major bleeding for baseline characteristics. Odds ratios compared outcomes by age and by treatment within age groups. Model interaction terms were used to test for statistically different outcomes by treatment and age. Overall, 9977 randomized patients had age information, of whom 25.5% (2540) were ≥75 years of age. Elderly patients (≥75 years) had more cardiovascular risk factors, prior cardiac disease, and higher acuity at presentation. After adjustment, advanced age (per 10 years) was associated with 30-day death or MI [risk odds ratios (ROR): 1.14, P = 0.002], 30-day death (ROR: 1.54, P < 0.0001), and 1-year death (ROR: 1.47, P < 0.0001), as well with TIMI major bleeding (ROR: 1.21, P = 0.001), GUSTO severe bleeding (ROR: 1.20, P = 0.047), and transfusion (ROR: 1.04, P = 0.324). Although there was a higher rate of GUSTO severe bleeding noted with enoxaparin in elderly patients, the overall relationships between treatment (UFH or enoxaparin) and outcomes did not vary significantly as a function of the patient's age.
Conclusion: Although higher rates of adverse events are seen in the oldest subgroup (age ≥75 years) treated with enoxaparin, statistical comparisons confirm similar efficacy and safety of enoxaparin and UFH across age subgroups as was demonstrated overall in SYNERGY.
Introduction
Antithrombotic therapy plays an important role in the pathophysiology and treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS). This is particularly true for elderly patients (≥75 years of age), who are at higher risk from recurrent thrombotic events and death, and for whom aggressive treatment may yield the greatest benefits. Elderly patients are also at higher risk from bleeding as a complication of antithrombotic therapy.
Clinical guidelines differ on whether low-molecular-weight heparin (LMWH, i.e. enoxaparin) or unfractionated heparin (UFH) is the preferable antithrombotic therapy for patients with NSTE ACS. Owing to the inherent differences between these heparins, the decision focuses on the balance between antithrombotic and bleeding effects. Furthermore, because of the differences in drug metabolism and effect in the elderly, such comparisons are particularly relevant in this subgroup. Therefore, using data from the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and GlYcoprotein IIb/IIIa inhibitors (SYNERGY) trial, we investigated outcomes in high-risk NSTE ACS patients according to age subgroups (<65, 65-74, and >75 years) assigned to either LMWH or UFH.