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Enoxaparin for the Prevention of VT in Acutely Ill Patients
CLINICAL QUESTION: Is enoxaparin safe and effective for preventing venous thromboembolism (VT) and pulmonary embolism (PE) in hospitalized moderately ill nonsurgical patients?
BACKGROUND: Patients hospitalized for congestive heart failure, respiratory distress, or infection are at increased risk for venous thromboembolism (VT). Enoxaparin is effective as prophylaxis for VT in certain groups of surgical, cardiac, and stroke patients.1 The authors of this study compared this drug in 2 different doses with placebo for the prophylaxis of VT in hospitalized medical patients.
POPULATION STUDIED: A total of 1102 patients older than 40 years from 60 centers in 9 countries were enrolled. The patients were expected to be hospitalized for at least 6 days but immobilized for not more than 3 days. Most patients were considered moderately ill and were hospitalized for congestive heart failure, respiratory failure without intubation, or infection without sepsis. Patients were excluded if they had indications for anticoagulation or if they had contraindications to anticoagulation or venography.
STUDY DESIGN AND VALIDITY: This is a randomized double-blind trial comparing placebo with 20 mg and 40 mg of enoxaparin given subcutaneously once daily. All patients were screened for deep venous thromboembolism (DVT) between days 6 and 14 with a venogram or venous ultrasound study. Patients were screened earlier if they were symptomatic for DVT or PE. Images were independently reviewed by a group of radiologists unaware of treatment assignments. Risk factors for VT or PE, the degree of illness, and the duration of hospitalization were not analyzed to determine if placebo and enoxaparin groups were statistically similar. In addition, the actual number of days of prophylaxis and the incidence of chronic anticoagulation treatment were not reported.
OUTCOMES MEASURED: The primary outcomes were the rates of DVT (symptomatic and asymptomatic) and PE (fatal and nonfatal) by day 14 as confirmed by imaging or venography. Secondary outcomes included the same results by day 110 as determined by phone follow-up (60% of patients) or visit. The rates of adverse events, such as hemorrhage and thrombocytopenia, were also reported.
RESULTS: There were 6 symptomatic DVTs, 94 asymptomatic DVTs, and 4 nonfatal PEs in the study population by day 14. The 40-mg enoxaparin group had a significantly lower overall rate of VT than the placebo group (5.5% vs 14.9%; relative risk [RR] = 0.37; 95% confidence interval [CI], 0.22-0.63; number needed to treat [NNT] = 11) as well as a lower incidence of proximal DVT (1.7% vs 4.9%, P= .04; NNT = 33). However, there was no significant decrease in the rate of symptomatic DVT (0.3%, 0.7%) or PE (0%, 1.0%). Results were similar at day 110 with a significantly lower overall rate of VT (7% vs 17.1%; RR = 0.41; 95% CI, 0.25-0.68) and a decrease in the rate of proximal DVT (2.2% vs 6.5%, P = .02). There was no significant decrease in the rates of symptomatic DVT (1.1% vs 1.5%) or PE (0% vs 1.2%). There was also no statistically significant difference between the 20-mg enoxaparin and placebo groups for any outcome at days 14 or 110 of follow-up. Of the 4 fatal PEs, 2 occurred in the 40-mg enoxaparin group 2 months after the end of treatment. By day 110, there was no significant difference between the 40-mg enoxaparin and placebo groups for the rate of death from any cause, and the rate of major hemorrhage and thrombocytopenia.
This study reminds us that nonsurgical moderately ill hospitalized patients are at increased risk for VT and may benefit from prophylaxis. Enoxaparin 40 mg daily reduced asymptomatic VT without a statistically significant reduction in symptomatic lower extremity VT, PE, or mortality at 2 weeks and 3 months. Enoxaparin 20 mg daily was no different from placebo. Although enoxaparin 40 mg daily appears to be safe, its benefit as a VT prophylaxis depends on the undetermined clinical significance of preventing asymptomatic lower extremity VT. The fact that fatal PEs occurred after termination of the study treatment indiactes a need to establish an appropriate duration of VT prophylaxis.
CLINICAL QUESTION: Is enoxaparin safe and effective for preventing venous thromboembolism (VT) and pulmonary embolism (PE) in hospitalized moderately ill nonsurgical patients?
BACKGROUND: Patients hospitalized for congestive heart failure, respiratory distress, or infection are at increased risk for venous thromboembolism (VT). Enoxaparin is effective as prophylaxis for VT in certain groups of surgical, cardiac, and stroke patients.1 The authors of this study compared this drug in 2 different doses with placebo for the prophylaxis of VT in hospitalized medical patients.
POPULATION STUDIED: A total of 1102 patients older than 40 years from 60 centers in 9 countries were enrolled. The patients were expected to be hospitalized for at least 6 days but immobilized for not more than 3 days. Most patients were considered moderately ill and were hospitalized for congestive heart failure, respiratory failure without intubation, or infection without sepsis. Patients were excluded if they had indications for anticoagulation or if they had contraindications to anticoagulation or venography.
STUDY DESIGN AND VALIDITY: This is a randomized double-blind trial comparing placebo with 20 mg and 40 mg of enoxaparin given subcutaneously once daily. All patients were screened for deep venous thromboembolism (DVT) between days 6 and 14 with a venogram or venous ultrasound study. Patients were screened earlier if they were symptomatic for DVT or PE. Images were independently reviewed by a group of radiologists unaware of treatment assignments. Risk factors for VT or PE, the degree of illness, and the duration of hospitalization were not analyzed to determine if placebo and enoxaparin groups were statistically similar. In addition, the actual number of days of prophylaxis and the incidence of chronic anticoagulation treatment were not reported.
OUTCOMES MEASURED: The primary outcomes were the rates of DVT (symptomatic and asymptomatic) and PE (fatal and nonfatal) by day 14 as confirmed by imaging or venography. Secondary outcomes included the same results by day 110 as determined by phone follow-up (60% of patients) or visit. The rates of adverse events, such as hemorrhage and thrombocytopenia, were also reported.
RESULTS: There were 6 symptomatic DVTs, 94 asymptomatic DVTs, and 4 nonfatal PEs in the study population by day 14. The 40-mg enoxaparin group had a significantly lower overall rate of VT than the placebo group (5.5% vs 14.9%; relative risk [RR] = 0.37; 95% confidence interval [CI], 0.22-0.63; number needed to treat [NNT] = 11) as well as a lower incidence of proximal DVT (1.7% vs 4.9%, P= .04; NNT = 33). However, there was no significant decrease in the rate of symptomatic DVT (0.3%, 0.7%) or PE (0%, 1.0%). Results were similar at day 110 with a significantly lower overall rate of VT (7% vs 17.1%; RR = 0.41; 95% CI, 0.25-0.68) and a decrease in the rate of proximal DVT (2.2% vs 6.5%, P = .02). There was no significant decrease in the rates of symptomatic DVT (1.1% vs 1.5%) or PE (0% vs 1.2%). There was also no statistically significant difference between the 20-mg enoxaparin and placebo groups for any outcome at days 14 or 110 of follow-up. Of the 4 fatal PEs, 2 occurred in the 40-mg enoxaparin group 2 months after the end of treatment. By day 110, there was no significant difference between the 40-mg enoxaparin and placebo groups for the rate of death from any cause, and the rate of major hemorrhage and thrombocytopenia.
This study reminds us that nonsurgical moderately ill hospitalized patients are at increased risk for VT and may benefit from prophylaxis. Enoxaparin 40 mg daily reduced asymptomatic VT without a statistically significant reduction in symptomatic lower extremity VT, PE, or mortality at 2 weeks and 3 months. Enoxaparin 20 mg daily was no different from placebo. Although enoxaparin 40 mg daily appears to be safe, its benefit as a VT prophylaxis depends on the undetermined clinical significance of preventing asymptomatic lower extremity VT. The fact that fatal PEs occurred after termination of the study treatment indiactes a need to establish an appropriate duration of VT prophylaxis.
CLINICAL QUESTION: Is enoxaparin safe and effective for preventing venous thromboembolism (VT) and pulmonary embolism (PE) in hospitalized moderately ill nonsurgical patients?
BACKGROUND: Patients hospitalized for congestive heart failure, respiratory distress, or infection are at increased risk for venous thromboembolism (VT). Enoxaparin is effective as prophylaxis for VT in certain groups of surgical, cardiac, and stroke patients.1 The authors of this study compared this drug in 2 different doses with placebo for the prophylaxis of VT in hospitalized medical patients.
POPULATION STUDIED: A total of 1102 patients older than 40 years from 60 centers in 9 countries were enrolled. The patients were expected to be hospitalized for at least 6 days but immobilized for not more than 3 days. Most patients were considered moderately ill and were hospitalized for congestive heart failure, respiratory failure without intubation, or infection without sepsis. Patients were excluded if they had indications for anticoagulation or if they had contraindications to anticoagulation or venography.
STUDY DESIGN AND VALIDITY: This is a randomized double-blind trial comparing placebo with 20 mg and 40 mg of enoxaparin given subcutaneously once daily. All patients were screened for deep venous thromboembolism (DVT) between days 6 and 14 with a venogram or venous ultrasound study. Patients were screened earlier if they were symptomatic for DVT or PE. Images were independently reviewed by a group of radiologists unaware of treatment assignments. Risk factors for VT or PE, the degree of illness, and the duration of hospitalization were not analyzed to determine if placebo and enoxaparin groups were statistically similar. In addition, the actual number of days of prophylaxis and the incidence of chronic anticoagulation treatment were not reported.
OUTCOMES MEASURED: The primary outcomes were the rates of DVT (symptomatic and asymptomatic) and PE (fatal and nonfatal) by day 14 as confirmed by imaging or venography. Secondary outcomes included the same results by day 110 as determined by phone follow-up (60% of patients) or visit. The rates of adverse events, such as hemorrhage and thrombocytopenia, were also reported.
RESULTS: There were 6 symptomatic DVTs, 94 asymptomatic DVTs, and 4 nonfatal PEs in the study population by day 14. The 40-mg enoxaparin group had a significantly lower overall rate of VT than the placebo group (5.5% vs 14.9%; relative risk [RR] = 0.37; 95% confidence interval [CI], 0.22-0.63; number needed to treat [NNT] = 11) as well as a lower incidence of proximal DVT (1.7% vs 4.9%, P= .04; NNT = 33). However, there was no significant decrease in the rate of symptomatic DVT (0.3%, 0.7%) or PE (0%, 1.0%). Results were similar at day 110 with a significantly lower overall rate of VT (7% vs 17.1%; RR = 0.41; 95% CI, 0.25-0.68) and a decrease in the rate of proximal DVT (2.2% vs 6.5%, P = .02). There was no significant decrease in the rates of symptomatic DVT (1.1% vs 1.5%) or PE (0% vs 1.2%). There was also no statistically significant difference between the 20-mg enoxaparin and placebo groups for any outcome at days 14 or 110 of follow-up. Of the 4 fatal PEs, 2 occurred in the 40-mg enoxaparin group 2 months after the end of treatment. By day 110, there was no significant difference between the 40-mg enoxaparin and placebo groups for the rate of death from any cause, and the rate of major hemorrhage and thrombocytopenia.
This study reminds us that nonsurgical moderately ill hospitalized patients are at increased risk for VT and may benefit from prophylaxis. Enoxaparin 40 mg daily reduced asymptomatic VT without a statistically significant reduction in symptomatic lower extremity VT, PE, or mortality at 2 weeks and 3 months. Enoxaparin 20 mg daily was no different from placebo. Although enoxaparin 40 mg daily appears to be safe, its benefit as a VT prophylaxis depends on the undetermined clinical significance of preventing asymptomatic lower extremity VT. The fact that fatal PEs occurred after termination of the study treatment indiactes a need to establish an appropriate duration of VT prophylaxis.