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Antithrombotic Prophylaxis for Patients with CVDs
Abstract & Commentary
By William B. Ershler, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC. Dr. Ershler is on the speaker's bureau for Wyeth, and does research for Ortho Biotech.
This article originally appeared in the April 2007 issue of Clinical Oncology Alert. It was peer reviewed by VR Veerapalli, MD. Dr. Veerapalli is Staff Clinician, INOVA Fairfax Cancer Center. Dr. Veerapalli reports no financial relationships relevant to this field of study.
Synopsis: Current AP schedules do not appear to prevent catheter-related thrombosis. Systemic VTE and mortality, however, appeared lower after prophylaxis.
Source: Fagnani D, et al. Thrombosis-related complications and mortality in cancer patients with central venous devices: An observational study on the effect of antithrombotic prophylaxis. Ann Oncol. 2007;18:551-555.
There have been conflicting studies regarding the advisability of antithrombotic prophylaxis (with low-molecular weight heparin [LMWH], unfractionated heparin, or low-dose warfarin) in patients with cancer for whom indwelling central venous catheters have been employed.1-5 Fagnani and colleagues from the POLONORD Group in northern Italy, report their observational prospective study designed to assess the management of central venous devices (CVDs) in patients treated in community practice, particularly in the context of antithrombotic prophylaxis (AP). Cancer patients from 18 hospital oncology units throughout northern Italy, were enrolled over a 30-month period (through June 2005) if they had a totally implantable CVD (port), an indwelling central venous catheter (CVC), or a peripherally-inserted catheter (PICC). The type of catheter used was at the discretion of the physicians at each hospital, as was the decision of whether or not to prescribe antithrombotic prophylaxis.
Data analyzed included demographic details, type of CVD, position of the catheter tip, type and stage of tumor, history with regard to prior thrombotic events, and past and current cancer treatments (chemotherapy, radiotherapy, hormone therapy and growth factors). One feature that separates this survey from others is the length of follow up. Evaluations on each patient were scheduled every 4 months during the first year, every 6 months during the second and third years, or until removal of the CVD. During follow up, a record was kept of any catheter-related complications (eg, infection, pneumothorax, catheter fracture, etc.), systemic thromboembolic events (eg, pulmonary embolism, DVT other than in the vicinity of the CVD, supraventricular tachycardia, etc.), CVD removal, bleeding episodes (eg, intracranial or retroperitoneal hemorrhage), and the course of the neoplastic disease (progression of disease, death). Furthermore, the type of antithrombotic prophylaxis was recorded as either associated with the procedure (limited to 48 hours at the time of catheter insertion) or continuous, and the type of anti-thrombotic therapy documented. The drugs employed, mini-dose warfarin per the Levine regimen6 (initially 1 mg/day, tapered to maintain INR of 1.3-1.9), LMWH, or unfractionated heparin and duration of treatment were also recorded.
During the 2.5 years of study, 1410 consecutive patients were enrolled and 1390 were seen at least once in the 6- month median follow-up. There was no difference in catheter-related thrombosis in patients given antithrombotic prophylaxis or not (2.8% and 2.2%), and no major bleeding events were recorded. However, systemic (ie, not in the vicinity of the catheter) venous thrombus embolic events, including superficial thromboses and pulmonary embolism, were less frequent with antithrombotic prophylaxis (4% vs 8.2%, P = 0.005), and mortality was lower (25% vs 44%, P = 0.0001). Upon multilogistic regression analysis, only advanced cancer and no antithrombotic prophylaxis were significantly associated with mortality.
This is a very curious finding. Although antithrombotic prophylaxis did not prevent catheter-related thrombosis, it did seem to influence systemic thromboses, including the occurrence of pulmonary emboli and reduction of overall mortality. It's difficult not to be a little bit energized by this finding, albeit derived from an observational, non-randomized study. Reluctantly, we must accept that AP is ineffective at reducing catheter-associated thrombus formation, as the current results confirm what several other studies have indicated previously.2,5 Despite the theoretical appeal of such an approach, there is no evidence that anticoagulation prevents catheter-associated thrombus in cancer patients.
The lack of effect in the current study may be the result of the relatively low incidence of catheter-associated thrombus in either group, those receiving prophylaxis (2.8%) and those not (2.2%). This, in turn, may reflect improved technique, catheter positioning, and the use of less thrombogenic devices. Furthermore, because this was a pattern-of-care type study, participating physicians may have chosen to use antithrombotic prophylaxis for those patients considered at highest risk (advanced disease, history of prior DVT, etc) and, accordingly, the 2.8% incidence might be lower than what would have been observed had this group not been treated.
That antithrombotic prophylaxis influenced non-catheter-associated thrombotic occurrence is remarkable and needs further explanation. The majority of patients who received prophylaxis were given low-dose warfarin, and there have been previous conflicting reports on the value of such treatment in preventing venous thrombosis in cancer patients.6,7 The current study was large, well designed, and of sufficient duration to merit attention. The data would suggest that antithrombotic prophylaxis for patients with advanced cancer with a high risk for venous thrombosis achieve more favorable outcomes (less thromboembolic events and longer overall survival). However, because of the inherent risks associated with anticoagulation, a randomized, prospective study in carefully selected patients is called for.
1. Bern MM, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial. Ann Intern Med. 1990;112:423-428.
2. Couban S, et al. Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer. J Clin Oncol. 2005;23:4063-4069.
3. Karthaus M, et al. Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: Final results of a double-blind, placebo-controlled phase III trial. Ann Oncol. 2006;17:289-296.
4. Monreal M, et al. Upper extremity deep venous thrombosis in cancer patients with venous access devices — prophylaxis with a low molecular weight heparin (Fragmin). Thromb Haemost. 1996;75:251-253.
5. Verso M, et al. Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: A double-blind, placebo-controlled, randomized study in cancer patients. J Clin Oncol. 2005;23:4057-4062.
6. Levine M, et al. Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet. 1994;343:886-889.
7. Cortelezzi A, et al. Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: A prospective multicentre study. Br J Haematol. 2005;129:811-817.