Randomised long-term comparison of tinzaparin and dalteparin in haemodialysis

Objective and design: Tinzaparin and dalteparin are low molecular weight heparins (LMWHs) with different pharmacokinetic and pharmacodynamic profiles that may lead to differences in efficacy and safety. In a long-term, multicentre, prospective. randomised trial we compared the efficacy and safety profiles of tinzaparin and dalteparin (starting doses were adjusted to comparable anti-IIa activity). The sample size was calculated to show a relative difference of 50% in unsatisfactory dialyses with a power of 80% (to prove superiority). Patients: 159 patients undergoing chronic intermittent haemodialysis were included in the study, Main outcome measures: Efficacy was assessed by scoring the dialyser (from 1 = good, clear dialyser to 4 = total clotting of the dialyser requiring a change of the extracorporeal circuit) and bubble catcher (from I = no clots to 4 = severe clotting) after each dialysis. Levels of thrombin antithrombin complexes (TAT) were also determined. Safety was assessed by noting all minor and major bleeding. Results: The mean anticoagulant dose for tinzaparin during the maintenance phase was about 10% lower than that of dalteparin: 5024 +/- 2321 (range 70012000) anti-Xa IU and 5546 +/- 2395 (1875-12913) anti-Xa IU, respectively, No difference was found between treatments in clotting for either the dialyser or the bubble catcher (p = 0.59). TAT levels showed no difference between tinzaparin and dalteparin. The number of minor bleeds did not differ between treatments: 1.5% (40/2629 dialyses) for tinzaparin and 1.4% (41/2863 dialyses) for dalteparin, and one major bleed occurred in each treatment arm. Conclusions: Dose calculation of tinzaparin and dalteparin according to anti-IIa activity resulted in equivalent efficacy and safety, although this was achieved with a 10% lower dose of tinzaparin measured in anti-Xa IU. Both LMWHs can be safely administered over a wide dosage range in patients undergoing long-term intermittent haemodialysis.