• Frank A Lederle, Dylan Zylla, Roderick MacDonald, and Timothy J Wilt.
• Minnesota Evidence-based Practice Center, Minneapolis Veterans Affairs Medical Center, Minnesota, USA. frank.lederle@va.gov
• Ann. Intern. Med. 2011 Nov 1; 155 (9): 602-15.

BackgroundVenous thromboembolism prophylaxis has been recommended for nonsurgical patients, but its effectiveness remains uncertain.PurposeTo assess the benefits and harms of prophylaxis in hospitalized adult medical patients and those with acute stroke.Data SourcesMEDLINE and the Cochrane Library from 1950 through April 2011, reference lists, and study authors.Study SelectionEnglish-language randomized trials were included if they provided clinical outcomes and evaluated therapy with low-dose heparin or related agents or mechanical measures compared with placebo, no treatment, or other active prophylaxis in the target population.Data ExtractionTwo independent investigators extracted data on study characteristics and clinical outcomes up to 120 days after randomization. The primary outcome was total mortality.Data SynthesisIn medical patients, heparin prophylaxis did not reduce total mortality but did result in fewer pulmonary embolisms (PEs) (odds ratio [OR], 0.69 [95% CI, 0.52 to 0.90], but with evidence of publication bias) and an increase in all bleeding events (risk ratio [RR], 1.34 [CI, 1.08 to 1.66]). Heparin prophylaxis had no statistically significant effect on any outcome in patients with acute stroke except for an increase in major bleeding events (OR, 1.66 [CI, 1.20 to 2.28]). When trials of medical patients and those with stroke were considered together (18 studies; 36,122 patients), heparin prophylaxis reduced the incidence of PE (OR, 0.70 [CI, 0.56 to 0.87]; absolute reduction, 3 events per 1000 patients treated [CI, 1 to 5 events]) but increased the incidence of all bleeding (RR, 1.28 [CI, 1.05 to 1.56]) and major bleeding events (OR, 1.61 [CI, 1.23 to 2.10]), with an absolute increase of 9 bleeding events per 1000 patients treated (CI, 2 to 18 events), 4 of which were major (CI, 1 to 7 events). A reduction in total mortality approached statistical significance (RR, 0.93 [CI, 0.86 to 1.00]; P = 0.056; absolute decrease, 6 deaths per 1000 patients treated [CI, 0 to 11 deaths]). No statistically significant differences in clinical outcomes were observed in the 14 trials that compared unfractionated heparin with low-molecular-weight heparin. No improvements in clinical outcomes were seen in the 3 studies of mechanical prophylaxis in patients with stroke, but more patients had lower-extremity skin damage (RR, 4.02 [CI, 2.34 to 6.91])-an increase of 39 events per 1000 patients treated (CI, 17 to 77 events).LimitationNon-English-language studies were not included, but these were few and small.ConclusionHeparin prophylaxis had no significant effect on mortality, may have reduced PE in medical patients and all patients combined, and led to more bleeding and major bleeding events, thus resulting in little or no net benefit. No differences in benefits or harms were found according to type of heparin used. Mechanical prophylaxis provided no benefit and resulted in clinically important harm to patients with stroke.Primary Funding SourceAmerican College of Physicians.

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