Bridging Anticoagulant Therapy for Mechanical Valve Patients
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer. This article originally appeared in the December 2008 issue of Clinical Cardiology Alert. It was peer reviewed by Rakesh Mishra, MD. Dr. Mishra is Assistant Professor of Medicine; Weill Medical College, Cornell University; Assistant Attending Physician, NewYork-Presbyterian Hospital. Dr. Mishra reports no financial relationships relevant to this field of study.
Source: Spyropoulos AC, et al. Perioperative bridging therapy with unfractionated heparin or low-molecular-weight heparin in patients with mechanical prosthetic heart valves on long-term oral anticoagulants (from the REGIMEN Registry). Am J Cardiol. 2008;102:883-889.
Unfractionated heparin (UFH) is the standard bridging therapy for patients with mechanical heart valves who need to temporarily stop oral anticoagulants. Small case series have suggested that low molecular weight heparin (LMWH) may be useful for this purpose. Accordingly, a multicentered registry of patients undergoing bridging therapy was interrogated to assess outcomes in those with mechanical valves put on UFH vs LMWH. Patients were involved in the trial if they needed bridging for elective surgical procedures. Adverse outcomes over 30 days after the procedure were noted. This was an observational study, and no set protocol for bridging was followed.
Results: Of the 1,077 patients requiring bridging, 245 were on oral anticoagulants for mechanical heart valves; UFH was used in 73 and LMWH in 172. The groups were fairly comparable, although there were more men and more bileaflet valves in the LMWH group. About one-quarter of both groups were also on antiplatelet drugs. About 40% of both groups had major surgery. Duration of bridging therapy was similar in both groups, but the LMWH patients were discharged earlier on average. There were no significant differences in adverse events between treatment groups, but the rate of major bleeding was higher in the UFH group (8.8 vs 4.2%). Spyropoulos et al concluded that in patients with mechanical valves, bridging therapy with LMWH is feasible and safe and allows for earlier discharge.
Mechanical prosthetic valve patients are high-risk patients for anticoagulation cessation, as valve thrombosis may occur after 48 hours of subtherapeutic INR values. Therefore, they often undergo bridging therapy with heparin for surgical procedures. In this registry study of bridging therapy, 25% had mechanical valves. There has been interest in using LMWH because it can be given as an outpatient therapy and does not require blood test monitoring of anticoagulation levels. However, up until 2002, there was a black box warning in the package inserts of LMWHs not to use them with mechanical valves because of a lack of data suggesting their effectiveness in this situation. Several small studies have shown equivalent efficacy to UFH, so this warning has been modified, but lack of strong data has dampened enthusiasm for the use of LMWH for this purpose.
This registry study is the largest experience reported with LMWH for prosthetic valves. The study group was a high-risk one: 50% had mechanical mitral valves; two-thirds had hypertension; half had atrial fibrillation; and one-quarter had heart failure. Also, 40% had major surgery and one-quarter were also on antiplatelet drugs. The composite endpoint of major adverse events, including death, thromboembolism, and major bleeding favored LMWH (5.5 vs 10.3%), but the difference was not statistically significant. The thromboembolism risk on LMWH was < 1%. Importantly, about 70% of the patients treated with LMWH were either outpatient or were in the hospital < 24 hrs. Most of the patients received enoxaparin at full therapeutic doses twice a day.
One reason for the lower bleeding rates for LMWH was that patients undergoing surgery with a high risk of bleeding, such as cardiothoracic surgery, were more often put on UFH because it can be reversed more easily. Other limitations include the observational nature of the study without a randomized treatment protocol. Also, the power to detect some endpoints was limited because of a lack of events. For example, only one patient in each group experienced a thromboembolic event. However, this study confirms the results of smaller studies and supports the conclusion that LMWH for bridging patients on oral anticoagulants with mechanical valves who need surgery is safe and efficacious and may reduce costs by permitting earlier discharge from the hospital.