Effect of Dalteparin on Healing of Chronic Foot Ulcers in Diabetic Patients With Peripheral Arterial Occlusive Disease
A prospective, randomized, double-blind, placebo-controlled study
- Majid Kalani, MD1,
- Jan Apelqvist, MD, PHD2,
- Margareta Blombäck, MD, PHD3,
- Kerstin Brismar, MD, PHD4,
- Björn Eliasson, MD, PHD5,
- Jan W. Eriksson, MD, PHD6,
- Bengt Fagrell, MD, PHD7,
- Anders Hamsten, MD, PHD, FRCP18,
- Ole Torffvit, MD, PHD9 and
- Gun Jörneskog, MD, PHD4
- 1Department of Cardiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
- 2Department of Endocrinology, University Hospital in Malmö, University of Lund, Malmö, Sweden
- 3Deparment of Surgical Sciences/Coagulation Research, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
- 4Department of Endocrinology and Diabetology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
- 5Diabetes Center, Sahlgrenska University Hospital, Göteborg, Sweden
- 6Department of Medicine, University Hospital in Umeå, Umeå, Sweden
- 7Department of Internal Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
- 8Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
- 9Department of Internal Medicine, University Hospital in Lund, University of Lund, Lund, Sweden
- Address correspondence and reprint requests to Majid Kalani, MD, Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail: majid.kalani{at}ks.se
Abstract
OBJECTIVE—Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers.
RESEARCH DESIGN AND METHODS—A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5,000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1) who healed with intact skin; 2) in whom the study ulcer was improved, unchanged, or impaired; or 3) who were amputated above or below the ankle level, as compared with control subjects.
RESULTS—Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided χ2 test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area ≥50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased ≥50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 ± 8 weeks in the dalteparin group compared with 16 ± 7 weeks in placebo group (NS).
CONCLUSIONS—The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.
- hsCRP, high sensitive C-reactive protein
- LMWH, low–molecular weight heparin
- PAOD, peripheral arterial occlusive disease
- S-AA, serum amyloid A-antigen
- TBP, systolic toe blood pressure
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
See accompanying editorial, p. 2689.
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- Accepted April 25, 2003.
- Received November 11, 2002.
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