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evident
Original paper
1999NEJMHospital Medicine/General Medicine

MEDENOX

A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group

RCTVTE prophylaxis

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Overview

In hospitalized medical patients older than 40, enoxaparin 40 mg daily reduced VTE versus placebo; the 20 mg dose did not.

Clinical takeaway

Use the 40 mg daily dose if the goal is the VTE reduction MEDENOX showed. Twenty milligrams did not differ from placebo, and deaths by day 110 were not significantly different.

Key result

Among 866 patients in whom the primary outcome could be assessed, VTE occurred in 5.5% (16 of 291) with enoxaparin 40 mg vs 14.9% (43 of 288) with placebo (RR 0.37, 97.6% CI 0.22-0.63; P<0.001). The 20 mg dose was 15.0% (43 of 287).

Practice impact

For VTE prophylaxis in acutely ill medical inpatients older than 40, enoxaparin 40 mg daily reduced VTE; 20 mg did not.

Evidence

Study design

Double-blind randomized trial of two enoxaparin doses versus placebo.

Enrollment

1,102

Follow-up

Three months; the primary venous thromboembolism outcome was assessed between days 1 and 14.

Geography

Not listed

Clinical question

Does prophylactic enoxaparin reduce venous thromboembolism compared with placebo in hospitalized patients with acute medical illness?

Population

  • Hospitalized patients older than 40 years with acute medical illnesses; most were not in an intensive care unit.

Intervention

Enoxaparin 40 mg or 20 mg subcutaneously once daily for 6 to 14 days.

Comparator

Placebo subcutaneously once daily for 6 to 14 days.

Primary outcome

Venous thromboembolism between days 1 and 14, defined as deep-vein thrombosis detected by bilateral venography (or duplex ultrasonography) between days 6 and 14 (or earlier if clinically indicated) or documented pulmonary embolism.

Enoxaparin 40 mg daily reduced VTE versus placebo. The 20 mg dose did not, and deaths were not significantly different.

Relative risk (enoxaparin 40 mg vs placebo) / 0.37 / 97.6% CI 0.22-0.63 / p<0.001

Key results

  • Of 1102 randomized patients, the primary outcome could be assessed in 866.
  • VTE between days 1 and 14 was 5.5% (16 of 291) with enoxaparin 40 mg vs 14.9% (43 of 288) with placebo; relative risk 0.37 (97.6% CI 0.22-0.63; P<0.001). That benefit was maintained at three months.
  • There was no significant difference between enoxaparin 20 mg (43 of 287; 15.0%) and placebo.
  • By day 110, deaths were 50 (13.9%) with placebo, 51 (14.7%) with 20 mg, and 41 (11.4%) with 40 mg; the differences were not significant.

Harms

  • The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group.
  • Deaths by day 110 were not significantly different across the three groups.

Clinical Use

Practice impact

  • For acutely ill medical inpatients older than 40, enoxaparin 40 mg subcutaneously once daily reduced VTE in the assessable cohort.
  • Do not expect the 20 mg dose to provide that VTE reduction, and do not cite MEDENOX as a mortality trial.

Applicability

  • Most applicable to hospitalized patients older than 40 years with acute medical illness, mostly outside an ICU, treated for 6 to 14 days.

Limitations

  • The primary outcome could be assessed in 866 of 1102 randomized patients, reflecting venographic or duplex surveillance rather than only symptomatic events.
  • The confidence interval around the 40 mg effect is a 97.6% interval, not a 95% interval.
  • Deaths by day 110 did not differ significantly.

Common misinterpretations

  • A positive 40 mg result is not a license for 20 mg prophylaxis; 20 mg looked like placebo.
  • The primary VTE rate is among patients who could be assessed, not among all 1102 randomized patients.

Citation

Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med. 1999;341(11):793-800. doi:10.1056/NEJM199909093411103

Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses.