Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians Clinical Practice Guideline

Ann Intern Med. 2011 Nov 1;155(9):602-15. doi: 10.7326/0003-4819-155-9-201111010-00008.


Background: Venous thromboembolism prophylaxis has been recommended for nonsurgical patients, but its effectiveness remains uncertain.

Purpose: To assess the benefits and harms of prophylaxis in hospitalized adult medical patients and those with acute stroke.

Data sources: MEDLINE and the Cochrane Library from 1950 through April 2011, reference lists, and study authors.

Study selection: English-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 extraction: Two independent investigators extracted data on study characteristics and clinical outcomes up to 120 days after randomization. The primary outcome was total mortality.

Data synthesis: In 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).

Limitation: Non-English-language studies were not included, but these were few and small.

Conclusion: Heparin 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 source: American College of Physicians.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Comparative Effectiveness Research
  • Hemorrhage / chemically induced
  • Heparin / administration & dosage
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Hospital Mortality
  • Hospitalization*
  • Humans
  • Odds Ratio
  • Publication Bias
  • Pulmonary Embolism / mortality
  • Pulmonary Embolism / prevention & control
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Stockings, Compression
  • Stroke / complications*
  • Venous Thromboembolism / prevention & control*


  • Anticoagulants
  • Heparin