Deep vein thrombosis landmark trials in prevention: Difference between revisions
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==Total Knee Replacement== | ==Total Knee Replacement== | ||
===RECORD 3=== | ===RECORD 3 Study<ref name="pmid18582928">{{cite journal |author=Kakkar AK, Brenner B, Dahl OE, ''et al.'' |title=Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial |journal=Lancet |volume=372 |issue=9632 |pages=31–9 |year=2008 |month=July |pmid=18582928 |doi=10.1016/S0140-6736(08)60880-6 |url=}}</ref>=== | ||
'''Background:''' The risk of [[venous thromboembolism]] (VTE) is high after [[total hip arthroplasty]] and could persist after hospital discharge. The researchers sought to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin. | |||
'''Methods:''' 2,509 patients scheduled to undergo elective total hip arthroplasty were randomly assigned, stratified according to center, with a computer-generated randomization code, to receive oral rivaroxaban 10 mg once daily for 31-39 days (with placebo injection for 10-14 days; n=1,252), or enoxaparin 40 mg once daily subcutaneously for 10-14 days (with placebo tablet for 31-39 days; n=1,257). The primary efficacy outcome was the composite of [[deep vein thrombosis]] (DVT) (symptomatic or asymptomatic detected by mandatory, bilateral venography), non-fatal [[pulmonary embolism]] and all-cause mortality up to day 30-42. Analyses were done in the modified intention-to-treat population, which consisted of all patients who had received at least one dose of study medication, had undergone planned surgery, and had adequate assessment of thromboembolism. | |||
'''Findings:''' The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group. The primary outcome occurred in 17 (2%) patients in the rivaroxaban group, compared with 81 (9.3%) in the enoxaparin group (absolute risk reduction 7.3%, 95% CI 5.2-9.4; p<0.0001). The incidence of any on-treatment bleeding was much the same in both groups (81 [6.6%] events in 1228 patients in the rivaroxaban safety population vs. 68 [5.5%] of 1229 patients in the enoxaparin safety population; p=0.25). | |||
'''Interpretation:''' Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of VTE, including symptomatic events, in patients undergoing total hip arthroplasty. | |||
===RECORD 4=== | ===RECORD 4=== | ||
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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Justine Cadet
Overview
Randomized trials have compared the efficacy and safety of antithrombins and anticoagulants in the prevention of deep vein thrombosis in the setting of surgical procedures and in the context of hospitalization for a medical illness.
Total Hip Replacement
RECORD 1 Study[1]
Background: This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty.
Methods: In this randomized, double-blind study, the researchers assigned 4,541 patients to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery, plus a placebo tablet or injection. The primary efficacy outcome was the composite of deep vein thrombosis (DVT) (either symptomatic or detected by bilateral venography if the patient was asymptomatic), nonfatal pulmonary embolism or death from any cause at 36 days (range, 30 to 42). The main secondary efficacy outcome was major venous thromboembolism (proximal deep-vein thrombosis, nonfatal PE or death from venous thromboembolism [VTE]). The primary safety outcome was major bleeding.
Results: A total of 3,153 patients were included in the superiority analysis (after 1,388 exclusions), and 4,433 were included in the safety analysis (after 108 exclusions). The primary efficacy outcome occurred in 18 of 1,595 patients (1.1%) in the rivaroxaban group and in 58 of 1558 patients (3.7%) in the enoxaparin group (absolute risk reduction, 2.6%; 95% confidence interval [CI], 1.5 to 3.7; P<0.001). Major VTE occurred in 4 of 1686 patients (0.2%) in the rivaroxaban group and in 33 of 1678 patients (2%) in the enoxaparin group (absolute risk reduction, 1.7%; 95% CI, 1.0 to 2.5; P<0.001). Major bleeding occurred in six of 2,209 patients (0.3%) in the rivaroxaban group and in two of 2,224 patients (0.1%) in the enoxaparin group (P=0.18).
Conclusions: A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles.
RECORD 2 Study[2]
Background: The researchers investigated the efficacy of rivaroxaban, an orally active direct factor Xa inhibitor, in preventing venous thrombosis after total knee arthroplasty.
Methods: In this randomized, double-blind trial, 2,531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban, 10 mg once daily, beginning six to eight hours after surgery, or subcutaneous enoxaparin, 40 mg once daily, beginning 12 hours before surgery. The primary efficacy outcome was the composite of any deep vein thrombosis, nonfatal pulmonary embolism, or death from any cause within 13 to 17 days after surgery. Secondary efficacy outcomes included major venous thromboembolism (VTE) (i.e., proximal deep vein thrombosis, nonfatal pulmonary embolism or death related to venous thromboembolism) and symptomatic VTE. The primary safety outcome was major bleeding.
Results: The primary efficacy outcome occurred in 79 of 824 patients (9.6%) who received rivaroxaban and in 166 of 878 (18.9%) who received enoxaparin (absolute risk reduction, 9.2%; 95% confidence interval [CI], 5.9 to 12.4; P<0.001). Major VTE occurred in nine of 908 patients (1%) given rivaroxaban and 24 of 925 (2.6%) given enoxaparin (absolute risk reduction, 1.6%; 95% CI, 0.4 to 2.8; P=0.01). Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin (P=0.005). Major bleeding occurred in 0.6% of patients in the rivaroxaban group and 0.5% of patients in the enoxaparin group. The incidence of drug-related adverse events, mainly gastrointestinal, was 12% in the rivaroxaban group and 13% in the enoxaparin group.
Conclusions: Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar rates of bleeding.
Total Knee Replacement
RECORD 3 Study[3]
Background: The risk of venous thromboembolism (VTE) is high after total hip arthroplasty and could persist after hospital discharge. The researchers sought to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin.
Methods: 2,509 patients scheduled to undergo elective total hip arthroplasty were randomly assigned, stratified according to center, with a computer-generated randomization code, to receive oral rivaroxaban 10 mg once daily for 31-39 days (with placebo injection for 10-14 days; n=1,252), or enoxaparin 40 mg once daily subcutaneously for 10-14 days (with placebo tablet for 31-39 days; n=1,257). The primary efficacy outcome was the composite of deep vein thrombosis (DVT) (symptomatic or asymptomatic detected by mandatory, bilateral venography), non-fatal pulmonary embolism and all-cause mortality up to day 30-42. Analyses were done in the modified intention-to-treat population, which consisted of all patients who had received at least one dose of study medication, had undergone planned surgery, and had adequate assessment of thromboembolism.
Findings: The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group. The primary outcome occurred in 17 (2%) patients in the rivaroxaban group, compared with 81 (9.3%) in the enoxaparin group (absolute risk reduction 7.3%, 95% CI 5.2-9.4; p<0.0001). The incidence of any on-treatment bleeding was much the same in both groups (81 [6.6%] events in 1228 patients in the rivaroxaban safety population vs. 68 [5.5%] of 1229 patients in the enoxaparin safety population; p=0.25).
Interpretation: Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of VTE, including symptomatic events, in patients undergoing total hip arthroplasty.
RECORD 4
Medically Ill Patients
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References
- ↑ Eriksson BI, Borris LC, Friedman RJ; et al. (2008). "Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty". N. Engl. J. Med. 358 (26): 2765–75. doi:10.1056/NEJMoa0800374. PMID 18579811. Unknown parameter
|month=ignored (help) - ↑ Lassen MR, Ageno W, Borris LC; et al. (2008). "Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty". N. Engl. J. Med. 358 (26): 2776–86. doi:10.1056/NEJMoa076016. PMID 18579812. Unknown parameter
|month=ignored (help) - ↑ Kakkar AK, Brenner B, Dahl OE; et al. (2008). "Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial". Lancet. 372 (9632): 31–9. doi:10.1016/S0140-6736(08)60880-6. PMID 18582928. Unknown parameter
|month=ignored (help)