Effect of enoxaparin versus unfractionated heparin in diabetic patients with ST-elevation myocardial infarction in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25) trial.

BACKGROUND: Patients with diabetes mellitus (DM) are at higher risk for complications after ST-elevation myocardial infarction (STEMI) than patients without DM. Potent antithrombotic therapies may offer particular benefit for these high-risk patients and must be balanced against the potential for increased bleeding. METHODS: We performed a prospectively planned analysis of efficacy and safety in patients with DM among 20,479 patients with STEMI treated with fibrinolysis and randomized to a strategy of enoxaparin (up to 8 days) or unfractionated heparin (UFH) (48 hours) in ExTRACT-TIMI 25. RESULTS: Patients with DM (n = 3060) were older and more likely to be women and to present with heart failure (P < .0001 for each) than those without DM. After adjustment for the TIMI Risk Score, sex, and renal function, patients with DM were at 30% higher risk for death or myocardial infarction (MI) by 30 days (OR(adj) 1.29, 95% CI 1.14-1.46). Among patients with DM, the enoxaparin strategy reduced mortality (9.5% vs 11.8%, relative risk [RR] 0.81, 95% CI 0.66-0.99), death/MI (13.6% vs 17.1%, RR 0.80; 95% CI 0.67-0.94), and death/MI/urgent revascularization (16.0% vs 19.7%, RR 0.81, 95% CI 0.70-0.94). The enoxaparin strategy was associated with a trend toward higher major bleeding (2.6% vs 1.6%, RR 1.63, 95% CI 0.99-2.69). Taking efficacy and safety into account, the enoxaparin strategy offered superior net clinical benefit (death/MI/major bleed, 14.8% vs 18.0%, RR 0.83, 95% CI 0.70-0.97) compared with UFH in patients with DM. CONCLUSIONS: In a subgroup analysis, a reperfusion strategy including enoxaparin significantly improved outcomes compared with UFH among high-risk STEMI patients with DM undergoing fibrinolysis.

Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25.

AIMS: To determine the effects of age on outcomes in patients with STEMI treated with a strategy of enoxaparin (ENOX) vs. unfractionated heparin (UFH). METHODS AND RESULTS: In the ExTRACT-TIMI 25 trial, 20,479 patients with STEMI were randomized in a double-blind fashion to UFH or ENOX. A novel reduced dose of ENOX was administered to patients >or=75 years, and a reduced dose in those with an estimated creatinine clearance of < 30 mL/min. Anti-Xa levels were measured in a subset of patients (n = 73). The exposure to anti-Xa over time was lower in the elderly (AUC(0-12 h) P < 0.0001; AUC(steady-state) P = 0.0046). The relative risk reduction (RR) with ENOX on the primary endpoint, i.e. death or non-fatal recurrent myocardial infarction, was greater in patients < 75 years (20%) than > 75 years (6%), but the absolute benefits were similar. When compared with UFH, ENOX was associated with an RR of 1.67 for major bleeding, but the magnitude of the excess risk tended to be lower (RR = 1.15) in patients >or= 75 years assigned to ENOX. CONCLUSION: A dose reduction of ENOX in the elderly appears to be helpful in ameliorating bleeding risk. A strategy of ENOX was superior to UFH in both young and elderly patients with STEMI treated with fibrinolysis.

Ciliary neurotrophic factor (CNTF) genotype and body composition.

Exogenous ciliary neurotrophic factor (CNTF) administration causes significant weight loss in both humans and animal models, but the effects of endogenous CNTF and the CNTF null allele on body composition are not fully understood. A recent study in a European cohort demonstrated a significantly higher body weight and body mass index (BMI) in older males homozygous for the CNTF null allele (A/A genotype). We sought to replicate these findings in three cohorts: the Baltimore Longitudinal Study on Aging (BLSA) consisting of 422 adult men and women (19-90 years); the Study of Osteoporotic Risk in Men (STORM) consisting of 333 older men (50-84 years); and a third sample obtained by combining older males aged 59-73 years from the BLSA and STORM cohorts (n=286). In contrast to the European study, we were unable to detect a significant association between CNTF genotype and body weight in the BLSA (P=0.49), the STORM (P=0.28), or the combined samples (P=0.72). There was also no significant association observed between CNTF genotype and BMI in the BLSA (P=0.59), the STORM (P=0.34) or the combined (P=0.56) samples. In addition, we were unable to detect a significant association between CNTF genotype and total body fat (P=0.95) or fat-free mass (P=0.86) in the BLSA cohort. Our results do not support an effect of the CNTF null allele on body composition, contrary to previous findings.