CERTIFY: Prophylaxis of venous thromboembolism in patients with severe renal insufficiency

Patients with severe renal insufficiency (SRI) have been suggested to be at an increased risk of bleeding with low-molecular-weight heparins (LMWH). We aimed at assessing the benefits and risks of certoparin in comparison to unfractionated heparin (UFH) in these patients. In this subgroup analysis of the CERTIFY trial, acutely ill, non-surgical patients >= 70 years received certoparin 3,000U aXa o.d. or UFH 5,000 IU t.i.d. One hundred eighty-nine patients had a glomerular filtration rate (GFR) <= 30 ml/min/1.73 m(2), 3,050 patients served as controls. Patients with sRI had a mean age of 85.9 +/- 6.6 years (controls 78.4 +/- 6.0) and were treated for a mean of 9.3 +/- 3.7 days (9.9 4.3). Thromboembolic event rates were comparable (4.55 vs. 4.21%; OR1.08; 95%CI 0.5-2.37) but bleeding was increased in sRI (9.52 vs. 3.54%; OR2.87; 95%CI 1.70-4.83). The incidence of the combined end-point of proximal DVT, symptomatic non-fatal PE and VIE related death was 6.49% with certoparin and 2.60% with UFH (OR2.60; 95%CI0.49-13.85). There was a decrease in total bleeding with certoparin (OR0.33; 95%CI 0.11-0.97), which was non-significant in patients with GFR >30 ml/min/1.73 m(2). In two multivariable regression models certoparin and immobilisation <10 days were associated with less bleeding while a GFR <= 30 ml/min/1.73 m(2) was associated with increased bleeding. A total of 11.3% of certoparin- and 18.5% of UFH-treated patients experienced serious adverse events (14.8 in patients with a GFR <= 30 vs. 5.6% vs. >30 ml/ min/1.73 m(2)). In conclusion, certoparin 3,000U anti Xa o.d. was as efficacious as 5,000 IU UFH t.i.d. in patients with sRI but had a reduced risk of bleeding.