The majority of symptomatic and fatal venous thromboembolic (VTE) events in hospitalized patients occur in the medical population. It has been shown that therapy with both low dose unfractionated heparin (LDUH; defined as 5000 units subcutaneously BID) and low molecular weight heparin (LMWH) reduce this risk by at least 50%, and that LMWH may be more effective in the highest risk subgroups. Despite the lack of any comparative trials, many practitioners have extrapolated this data to suggest that high dose unfractionated heparin (HDUH; defined as 5000 units subcutaneoulsy TID) is superior to LDUH in moderate to high risk medical patients. Our objective was to use meta-analysis to compare the efficacy of LDUH vs. HDUH in this population.
We searched MEDLINE, EMBASE, Cochrane Clinical Trials Register, clinical trials.gov, CRISP, ACP Journal Club, CDSR, and DARE databases, as well as bibliographies of retrieved articles. Twelve prospective, randomized controlled trials which evaluated either LDUH or HDUH in acutely ill medical patients were included. Two reviewers independently rated study quality using the Chalmer’s and Jadad rating scales. Data were extracted on participants, screening and diagnostic methods, VTE rates, and bleeding rates.
Pooled rates of all major endpoints are shown in table 1. There was no statistical difference between LDUH and HDUH in DVT, PE or combined VTE rates. HDUH was, however, associated with an increased rate of bleeding (major plus minor).
Despite its current clinical and research use, there is no evidence that HDUH is superior to LDUH, and this regimen may even be associated with harm. Our meta-analysis is limited by the fact that the two treatments have never been directly compared. However, over 74,000 patients would have to be enrolled in each arm in order to have the power to detect a 20% relative risk reduction in the rates of VTE.
Until further studies are conducted, HDUH should not be used routinely for VTE prevention in hospitalized medical patients.Patients (N)DVT (95% CI)PE (95% CI)VTE (95% CI)Bleeding (95% CI)LDUH63280.21% (0.085-0.34)0.54% (0.34-0.73)0.82% (0.59-1.04)0.0024 (0.0011-0.0038)HDUH18390.31% (0.00-0.62)0.41% (0.00-0.79)0.95% (0.00-1.45)0.017 (0.0073-0.027)**
Aaron Holley, None.