Certoparin versus UFH to prevent venous thromboembolic events in the very elderly patient: an analysis of the CERTIFY study.

INTRODUCTION: There is an exponential rise of thromboembolic risk with age because of co-morbidities, immobility and pharmacotherapy. We aimed to investigate the benefits and risks of heparin prophylaxis in very elderly patients ≥80 years and the type of heparin used in a subgroup analysis of the CERTIFY trial. PATIENTS/METHODS: 3,239 patients were randomized to 3,000 U aXa o.d. certoparin or 5,000 IU t.i.d. unfractionated heparin (UFH) for 8-20 days. RESULTS: Patients ≥80 years (n=1,365) were more likely to be female, had a lower mean bodyweight, were more frequently using antiplatelets and had a GFR below 30 ml/min/1.73 m(2) more often than patients <80 years (n=1,875). The combined endpoint of proximal DVT, symptomatic non-fatal PE and VTE related death was experience by 5.26% of patients ≥80 years versus 3.51% in younger patients (OR 1.53; 95%CI 1.05-2.21; p=0.03). There were no significant differences in both minor (OR 1.11; 95%CI 0.75-1.62) and major (OR 2.53; 95%CI 0.93-6.86) bleeding risks. Certoparin and UFH were equally effective in reducing thromboembolic risk in either age group. The risk of any (OR 0.45; 95%CI 0.26-0.79) and minor bleeding (OR 0.42; 95%CI 0.23-0.78) was reduced with certoparin in the very elderly only. There were more adverse events in elderly patients (OR 1.26; 95%CI 1.1-1.46), but rates were otherwise comparable. CONCLUSIONS: The analysis confirmed the increased thromboembolic risk in very elderly patients, but demonstrated no increased bleeding risk. Certoparin and UFH were equally effective and safe with a reduced risk of minor bleeding complications with certoparin in the very elderly.

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 m2, 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 VTE related death was 6.49% with certoparin and 2.60% with UFH (OR2.60; 95%CI 0.49-13.85). 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 m2. In two multivariable regression models certoparin and immobilisation <10 days were associated with less bleeding while a GFR ≤30 ml/min/1.73 m2 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 m2). 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.

A randomized, double-blind study of certoparin vs. unfractionated heparin to prevent venous thromboembolic events in acutely ill, non-surgical patients: CERTIFY Study.

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 > or = 70 years were randomized to certoparin (3000 U of anti-factor 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 + or - 6.3 years were treated for 9.1 + or - 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 non-inferior to 5000 IU of UFH t.i.d., with a favorable safety profile.

Implementation of outpatient treatment of deep-vein thrombosis in private practices in Germany.

OBJECTIVE: Implementation of outpatient treatment (OT) of deep-vein thrombosis (DVT) is slow despite clear evidence that it is effective, safe and cost-efficient. DESIGN AND METHOD: An initiative was launched with the help of the Professional Association of Phlebologists of Germany and the industry to familiarize physicians in private practice who had no prior experience with OT of DVT. Data on quality of treatment with the low-molecular-weight heparin tinzaparin and phenprocoumon, compliance, clinical outcome, venous ultrasound, patients' satisfaction and quality of life were collected in a registry, which was open from July 1999 to December 2000. The results were published and their impact on further management of patients was assessed in second survey reported here. Patients of both series were followed-up clinically and with ultrasound over the 1st month of treatment. RESULTS: Of 67 physicians entering 827 patients into the registry 26 answered a questionnaire on how they treated further patients. Their case load had increased by 450% and data were provided on 540 consecutive patients managed between January and June 2002. OT increased overall from 76 to 92%, that of popliteo-femoral DVT from 71 to 92%, and that of pelvic DVT from 38 to 65%. Medical reasons to decide against OT decreased from 89 to 56% (p<.01). Immediate leg compression was changed from bandaging to medical compression stockings in 20 of the 26 centres (p<.05). In total, data were gathered from OT of 1124 patients. No secondary hospitalisations were required and only one patient had a documented progression of the DVT. CONCLUSIONS: OT was successfully implemented in private practices through the initiative of individual physicians with support of the professional association and sponsoring by the industry-to the benefit of the providers but as much of the patients and their cost bearers.