Antithrombotic Therapy in Peripheral Arterial Occlusive Disease: Heparin
Heparin dramatically suppresses neointimal hyperplasia in experimental animals following balloon injury of arteries. The smooth muscle cell antiproliferative effect, coupled with antithrombotic properties, provides a rationale to test long-term administration of low molecular weight heparin (LMWH) in patients undergoing lower-extremity bypass. In a single level II study, LMWH administered for 3 months was compared to aspirin and dipyridamole in patients undergoing femoral-popliteal bypass. Not only was patency significantly better with LMWH heparin treatment, but the effects persisted and became more dramatic with time. This suggested that early treatment with LMWH may have suppressed neointimal hyperplasia in its early stages of development. Although of great interest, confirmatory studies are required before this treatment can be recommended. asthma medications inhalers
The use of LMWH compared with unfractionated heparin (UFH) for intraoperative anticoagulation during infrainguinal bypass surgery has been investigated in two randomized clinical trials. In a multicenter trial of 201 patients (level I), an LMWH, enoxaparin, was compared to UFH. The agent to which the patient was randomized was administered during surgery and for 10 days postoperatively. At the end of the 10 days, graft thrombosis occurred in 8% of patients randomized to LMWH and 22% of those treated with UFH (p = 0.009). No difference in bleeding complications was observed. Conclusions regarding the use of LMWH based upon this study are limited due to the brief follow-up period (10 days) and the inordinately high rate of graft thrombosis in the UFH group. Most series of infrainguinal bypass report acute (within 30 days) thrombosis rates of 2 to 7%. In the other study (level II) of LMWH for intraoperative anticoagulation, 18 patients undergoing infrainguinal bypass were randomized to LMWH (Fragmin) or UFH. Two early graft occlusions occurred in each group and only one bleeding complication occurred in the UFH group. The small number of subjects limits meaningful clinical interpretation. A concern with the use of LMWH during vascular surgery is that it has a longer half-life than UFH and cannot be fully reversed with protamine. The lack of reversibility is probably not a major concern with infrainguinal bypass performed with vein graft, but is of concern for procedures such as aortic revascularization and for bypass procedures performed with prosthetic materials such as PTFE that have a tendency for suture hole bleeding. Most surgeons do not routinely use therapeutic heparin or other anticoagulants beyond the intraoperative period.