Randomized Comparison of Enoxaparin With Unfractionated Heparin for the Prevention of Venous Thromboembolism in Medical Patients With Heart Failure or Severe Respiratory Disease

Background. We compared the efficacy and safety of the low-molecular weight heparin enoxaparin with unfractionated heparin (UFH) for the prevention of venous thromboembolic disease in patients with heart failure or severe respiratory disease. Methods. This was a multicenter, controlled, randomized, open study in which patients received either enoxaparin (40 mg once daily) or UFH (5000 IU three times daily) for 10±2 days in 64 medical departments in Germany. Patients were stratified and enrolled according to their underlying disease: severe respiratory disease or heart failure. The primary efficacy parameter was a thromboembolic event up to 1 day after the treatment period. Results. Of the 665 patients enrolled, 451 patients were able to be evaluated in the primary efficacy analysis. The incidence of thromboembolic events was 8.4% with enoxaparin and 10.4% with UFH. Enoxaparin was at least as effective as UFH, with a 1-sided equivalence region of −4% (90% confidence interval CI, −2.5 to 6.5; p=0.015). Enoxaparin was associated with fewer deaths, less bleeding, and significantly fewer adverse events (45.8% vs. 53.8%; p=0.044). Conclusion. Enoxaparin is at least as effective as UFH in the prevention of thromboembolic events in patients with heart failure or severe respiratory disease. Its beneficial safety profile and once-daily administration is advantageous for inpatient and outpatient use.—Kleber FX, Witt C, Vogel G, et al., for the THE-PRINCE Study Group. Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease. Am Heart J. 2003;145(4):614–621. Comment. Patients who suffer from decompensated congestive heart failure are at increased risk of venous thromboembolic disease for a variety of reasons. The authors of this paper published their data regarding a multicenter, randomized study, which involved the use of low-molecular weight heparin in the form of enoxaparin at a dose of 40 mg once daily, vs. UFH at a dose of 5000 IU given subcutaneously three times daily for a 10-day course. The trial was conducted in 64 separate medical departments in Germany. Patients enrolled in the trial were stratified and enrolled according to the underlying pathology, either severe respiratory disease or heart failure. The end point to determine efficacy was a thromboembolic event occurring up to 1 day after the treatment period. There were 665 patients enrolled in the trial; of these 451 patients were able to be evaluated using this end point. The authors found an incidence of 8.4% of thromboembolic events in those with low-molecular weight heparin vs. 10.4% in those patients who received UFH. Furthermore, there was a lower incidence of death, significant bleeding, and other adverse events noted in the enoxaparin-treated group. Based on the data from the trial, the authors concluded that use of enoxaparin, low-molecular weight heparin, is at least as effective as standard UFH for thromboembolic prophylaxis in patients with heart failure or severe respiratory decompensation. The increased safety benefit was also clearly noted in this regimen. Also of great importance was the fact that enoxaparin can be administered on a once-daily regimen, which would therefore enable its use in outpatient settings as well as inpatient situations much more readily. While the initial cost of using low-molecular weight heparin may be greater, its value to cardiovascular clinicians has clearly been demonstrated in this trial. A look at the pharmacoeconomics of the global picture can help health care policy makers decide on future uses for this very efficacious and safe intervention in order to prevent what can otherwise be disastrous outcomes from thromboembolic venous disease. Further studies in this regard will likely be forthcoming and assist in clinical decision making.