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Summary. Background: In medically ill patients, no contemporary double-blind head-to-head evaluation of low molecular weight heparin vs. unfractionated heparin (UFH) for the prevention of venous thromboembolic events is available. Objectives: To compare the efficacy and safety of certoparin with those of UFH. Patients/Methods: In this double-blind, randomized, controlled trial, acutely ill, non-surgical patients aged ‡ 70 years were randomized to certoparin (3000 U of antifactor Xa once daily) or to UFH (5000 IU t.i.d.). The primary endpoint was the composite of proximal deep vein thrombosis as assessed by bilateral compression ultrasonography, symptomatic non-fatal pulmonary embolism and venous thromboembolism-related death, and was assessed by a blinded central adjudication committee. Non-inferiority margins were set at 1.8 for the odds ratio (OR) and 3.45% for the absolute difference. Results: Three thousand two hundred and thirty-nine patients aged 78.8 ± 6.3 years were treated for 9.1 ± 3.4 days. The incidence of the primary endpoint was 3.94% in the certoparin group and 4.52% in the UFH group, with a difference in proportions of ) 0.59% [95% confidence interval (CI) )2.09 to 0.92; P < 0.0001 for non-inferiority], and an OR of 0.87 (95% CI 0.60-1.26; P = 0.0001 for non-inferiority). Major bleeding occurred in 0.43% of certoparin-treated patients and 0.62% of UFH-treated patients (OR 0.69; 95% CI 0.26-1.83). Any bleeding occurred at 3.20% in certoparin-treated patients vs. 4.58% in UFH-treated patients (OR 0.69; 95% CI 0.48-0.99; P < 0.05), and 5.73% of certoparin-treated patients and 6.63% of UFH-treated patients experienced serious adverse events. All-cause mortality was 1.27% in certoparin-treated patients and 1.36% in UFH-treated patients. Conclusions: In acutely ill, non-surgical elderly patients, thromboprophylaxis with certoparin (3000 U of anti-FXa once daily) was noninferior to 5000 IU of UFH t.i.d., with a favorable safety profile.

Fluvastatin reduces atherogenic dense low-density lipoprotein (dLDL) in patients with type 2 diabetes mellitus (T2DM). dLDLs are associated with platelet-activating factor acetyl hydrolase (PAF-AH), an enzyme involved in inflammation and related to coronary artery disease (CAD). The association of preexisting CAD and PAF-AH and the effect of fluvastatin on enzyme activity is investigated in a placebo-controlled trial in patients with T2DM. A multicenter, double-blind, randomized comparison of fluvastatin XL (80 mg) (n = 42) and placebo (n = 47), each given once-daily for 8 wk, in 89 patients with T2DM, was conducted. At baseline and on treatment, lipoproteins, including lipoprotein (a) [Lp(a)] and LDL subfractions, and the activity of PAF-AH were measured. Increasing PAF-AH activity was significantly associated with a positive history of CAD (+0.7% per IU/liter PAH-AH; P = 0.010), the odds ratio estimate adjusted for age, gender, and body mass index of the highest quartile being 10.6 (P = 0.036). At baseline and at study end, PAF-AH activity was associated with the apolipoprotein B (apoB) content in dLDL (LDL-5 and LDL-6) (r = 0.447; P < 0.001 and r = 0.651; P < 0.001, respectively) and with non-HDL cholesterol at baseline (r = 0.485; P < 0.001). However, after additional adjustment for apoB in dLDL and non-HDL cholesterol at baseline, the odds ratio increment for CAD across PAF-AH quartiles was 2.09 (95% confidence interval, 1.02-4.29; P = 0.043). Fluvastatin treatment decreased the activity of PAF-AH by 22.8% compared with an increase of 0.4% in the placebo group (P < 0.001). This effect was independent of changes of Lp(a) concentrations. In patients with T2DM, PAF-AH activity is associated with a positive history of CAD. Fluvastatin not only decreases atherogenic dLDL but also PAF-AH activity, emphasizing the significance of fluvastatin treatment in T2DM. The antiatherogenic potential of fluvastatin in T2DM may thus be greater than expected from its effects on LDL-C and triglycerides alone.