MEDLINE Abstracts: Prophylaxis for Thromboembolism After Total Hip Arthroplasty
MEDLINE Abstracts: Prophylaxis for Thromboembolism After Total Hip Arthroplasty
What's the latest in treatment for deep vein thrombosis after total hip arthroplasty? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape.
Turpie AG, Gallus AS, Hoek JA
N Engl J Med. 2001 Mar;344(9):619-25
Background: Venous thromboembolism is a frequent complication of total hip replacement. The pentasaccharide Org31540/SR90107A, a highly selective, indirect inhibitor of activated factor X, is the first of a new class of synthetic antithrombotic agents. To determine the optimal dose for phase 3 studies, we conducted a dose-ranging study in which Org31540/SR90107A was compared with a low-molecular-weight heparin, enoxaparin, in patients undergoing total hip replacement.
Methods: In a double-blind study, patients were randomly assigned to postoperative administration of one of five daily doses of Org31540/SR90107A, given once daily, or to 30 mg of enoxaparin, given every 12 hours. Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days.
Results: Of 933 patients treated, 593 were eligible for the efficacy analysis. With Org31540/SR90107A a dose effect was observed (P=0.002), with rates of venous thromboembolism of 11.8 percent, 6.7 percent, 1.7 percent, 4.4 percent, and 0 percent for the groups assigned to 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg of the drug, respectively, as compared with a rate of 9.4 percent in the enoxaparin group. The reduction in the risk of venous thromboembolism was 82 percent for the 3.0-mg Org31540/SR90107A group (P=0.01) and 29 percent for the 1.5-mg group (P=0.51). Enrollment in the 6.0-mg and 8.0-mg Org31540/SR90107A groups was discontinued because of bleeding complications. Major bleeding occurred 3.5 percent less frequently in the 0.75-mg group (P=0.01) and 3.0 percent less frequently in the 1.5-mg group (P=0.05) than in the enoxaparin group (in which the rate was similar to that in the 3.0-mg group).
Conclusions: A synthetic pentasaccharide, Org31540/SR90107A, has the potential to improve significantly the risk-benefit ratio for the prevention of venous thromboembolism, as compared with low-molecular-weight heparin.
Heit JA, Elliott CG, Trowbridge AA, Morrey BF, Gent M, Hirsh J
Ann Intern Med. 2000 Jun 6;132(11):853-61
Background: The optimal duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain.
Objective: To determine the efficacy and safety of extended out-of-hospital prophylaxis with low-molecular-weight heparin (ardeparin sodium).
Design: Randomized, double-blind, placebo-controlled trial.
Setting: 33 community, university, or university-affiliated hospitals.
Patients: 1195 adults who had elective total hip or knee replacement and completed 4 to 10 days of postoperative ardeparin prophylaxis.
Intervention: Daily subcutaneous ardeparin (100 anti-Xa IU/kg of body weight) or placebo from time of hospital discharge to 6 weeks after surgery.
Measurements: Symptomatic, objectively documented venous thromboembolism or death, along with major bleeding, from time of hospital discharge to 12 weeks after surgery.
Results: Patients who received ardeparin (n = 607) and those who received placebo (n = 588) did not differ significantly in the cumulative incidence of venous thromboembolism or death (9 cases [1.5%] compared with 12 cases [2.0%]; odds ratio, 0.7 [95% CI, 0.3 to 1.7]; P > 0.2; absolute difference, -0.56 percentage points [CI, -2.2 to 1.1 percentage points]) or major bleeding (2 cases [0.3%] compared with 3 cases [0.5%]).
Conclusions: Among patients who had total knee or total hip replacement and received 4 to 10 days of postoperative ardeparin prophylaxis, the cumulative incidence of symptomatic venous thromboembolism or death after hospital discharge was not significantly reduced by extended out-of-hospital ardeparin prophylaxis. Extended ardeparin use could provide a maximum 2.2-percentage point true reduction in such events. The benefit of extended ardeparin use is not clinically important for most patients. Future research should identify high-risk patients who would benefit most from extended prophylaxis.
Wade WE, Hawkins DW
Orthopedics. 2000 Apr;23(4):335-8; discussion 338-9
Guidelines for deep venous thrombosis (DVT) and pulmonary embolism (PE) prophylaxis have been developed for patients undergoing total hip arthroplasty (THA). Studies suggest that risk for developing these complications may exist for as long as 3 months following surgery. Cost-effectiveness analyses were performed on three pharmacoprophylaxis regimens administered over a 30-day period using literature-reported values for incidences of DVT and PE in patients postdischarge following THA. A cost savings of $21,466.89 will occur for each thromboembolic event avoided if low-dose warfarin daily is used routinely compared to enoxaparin 40 mg daily. Additionally, a cost savings of $18,618.10 is experienced if enoxaparin 40 mg daily for 4 days plus low-dose warfarin daily is administered versus enoxaparin 40 mg daily. Clinicians may choose to continue prophylaxis postdischarge with enoxaparin 40 mg daily for 4 days in combination with warfarin for 30 days in these patients until results of more definitive studies become available.
Eikelboom JW, Quinlan DJ, Douketis JD
Lancet. 2001 Jul 7;358(9275):9-15
Background: The optimum duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain. Our primary objective was to establish the efficacy of extended-duration prophylaxis on symptomatic venous thromboembolic events.
Methods: We identified randomised trials comparing extended-duration prophylaxis using heparin or warfarin with placebo or untreated control in patients undergoing elective total hip or knee replacement by searching electronic databases (MEDLINE, EMBASE), references from retrieved articles, and abstracts from conference proceedings, and by contact with pharmaceutical companies and investigators. Two reviewers independently extracted data on study design, symptomatic and symptomless venographic venous thromboembolism, death, and bleeding outcomes from individual trials were combined with the Mantel-Haenszel method.
Findings: Nine studies met our inclusion criteria (3999 patients), eight with low molecular weight heparin, and one with unfractionated heparin. Extended-duration prophylaxis for 30-42 days significantly reduced the frequency of symptomatic venous thromboembolism (1.3% vs 3.3%, OR 0.38; 95% CI 0.24-0.61, numbers needed to treat [NNT]=50), with no statistical evidence of heterogeneity (x(2) test, p=0.69). There was a greater risk reduction in patients undergoing hip replacement (1.4% vs 4.3%, 0.33; 0.19-0.56, 34) compared with knee replacement (1.0% vs 1.4%, 0.74; 0.26-2.15, 250). A significant reduction in symptomless venographic deep vein thrombosis was also observed (9.6% vs 19.6%, 0.48; 0.36-0.63, 10). There was no increase in major bleeding but extended-duration prophylaxis was associated with excess minor bleeding (3.7% vs 2.5%, 1.56; 1.08-2.26, numbers needed to harm [NNH]=83).
Interpretation: Among patients undergoing total hip or knee replacement, extended-duration prophylaxis significantly reduces the frequency of symptomatic venous thromboembolism. The reduction in risk is equivalent to about 20 symptomatic events per 1000 patients treated.
Comp PC, Spiro TE, Friedman RJ, et al
J Bone Joint Surg Am. 2001 Mar;83-A(3):336-45
Background: Patients undergoing hip or knee joint replacement are at risk for venous thromboembolic complications for up to twelve weeks postoperatively. We evaluated the efficacy and safety of a prolonged post-hospital regimen of enoxaparin, a low-molecular-weight heparin, in this patient population.
Methods: Following elective total hip or knee replacement, 968 patients received subcutaneous enoxaparin (30 mg twice daily) for seven to ten days, and 873 were then randomized to receive three weeks of double-blind outpatient treatment with either enoxaparin (40 mg once daily) or a placebo. The primary efficacy end point was the prevalence of objectively confirmed venous thromboembolism or symptomatic pulmonary embolism during the double-blind phase of treatment.
Results: Of the 873 randomized patients, 435 underwent elective total hip replacement and 438 underwent elective total knee replacement. Enoxaparin was superior to the placebo in reducing the prevalence of venous thromboembolism in patients treated with hip replacement: 8.0% (eighteen) of the 224 patients treated with enoxaparin had venous thromboembolism compared with 23.2% (forty-nine) of the 211 patients treated with the placebo (p < 0.001; odds ratio, 3.62; 95% confidence interval, 2.00 to 6.55; relative risk reduction, 65.5%). Enoxaparin had significant benefit in the patients treated with knee replacement: thirty-eight (17.5%) of the 217 patients treated with enoxaparin had venous thromboembolism compared with forty-six (20.8%) of the 221 patients treated with the placebo (p = 0.380; odds ratio, 1.24; 95% confidence interval, 0.76 to 2.02; relative risk reduction, 15.9%). Symptomatic pulmonary embolism developed in three patients, one with a hip replacement and two with a knee replacement; all had received the placebo. There was no significant difference in the prevalence of hemorrhagic episodes or other types of toxicity between the enoxaparin and placebo-treated groups.
Conclusions: Prolonging enoxaparin thromboprophylaxis following hip replacement for a total of four weeks provided therapeutic benefit, by reducing the prevalence of venous thromboembolism, without compromising safety. A similar benefit was not observed in patients treated with knee replacement.
Freedman KB, Brookenthal KR, Fitzgerald RH, Williams S, Lonner JH
J Bone Joint Surg Am. 2000 Jul;82-A(7):929-38
Background: Although several agents have been shown to reduce the risk of thromboembolic disease, there is no clear preference for thromboembolic prophylaxis in elective total hip arthroplasty. The purpose of this study was to define the efficacy and safety of the agents that are currently used for prophylaxis against deep venous thrombosis -- namely, low-molecular-weight heparin, warfarin, aspirin, low-dose heparin, and pneumatic compression.
Methods: A Medline search identified all randomized, controlled trials, published from January 1966 to May 1998, that compared the use of one of the prophylactic agents with the use of any other agent or a placebo in patients undergoing elective total hip arthroplasty. For a study to be included in our analysis, bilateral venography had to have been performed to confirm the presence or absence of deep venous thrombosis. Fifty-two studies, in which 10,929 patients had been enrolled, met the inclusion criteria and were included in the analysis. The rates of distal, proximal, and total (distal and proximal) deep venous thrombosis; symptomatic and fatal pulmonary embolism; minor and major wound-bleeding complications; major non-wound bleeding complications; and total mortality were determined for each agent in each study. The absolute risk of each outcome was determined by dividing the number of events by the number of patients at risk. A general linear model with random effects was used to calculate the 95 percent confidence interval of risk. A crosstabs of study by outcome was performed to test homogeneity (ability to combine studies). The risk of each outcome was compared among agents and between each agent and the placebo.
Results: With prophylaxis, the risk of total (proximal and distal) deep venous thrombosis ranged from 17.7 percent (low-molecular-weight heparin) to 31.1 percent (low-dose heparin); the risk with prophylaxis with any agent was significantly lower than the risk with the placebo (48.5 percent) (p < 0.0001). The risk of proximal deep venous thrombosis was lowest with warfarin (6.3 percent) and low-molecular-weight heparin (7.7 percent), and again the risk with any prophylactic agent was significantly lower than the risk with the placebo (25.8 percent) (p < 0.0001). Compared with the risk with the placebo (1.51 percent), only warfarin (0.16 percent), pneumatic compression (0.26 percent), and low-molecular-weight heparin (0.36 percent) were associated with a significantly lower risk of symptomatic pulmonary embolism. There were no significant differences among agents with regard to the risk of fatal pulmonary embolism or of mortality with any cause. The risk of minor wound-bleeding was significantly higher with low-molecular-weight heparin (8.9 percent) and low-dose heparin (7.6 percent) than it was with the placebo (2.2 percent) (p < 0.05). Compared with the risk with the placebo (0.28 percent), only low-dose heparin was associated with a significantly higher risk of major wound-bleeding (2.56 percent) and total major bleeding (3.46 percent) (p < 0.0001).
Conclusions: The best prophylactic agent in terms of both efficacy and safety was warfarin, followed by pneumatic compression, and the least effective and safe was low-dose heparin. Warfarin provided the lowest risk of both proximal deep venous thrombosis and symptomatic pulmonary embolism. However, there were no identifiable significant differences in the rates of fatal pulmonary embolism or death among the agents. Significant risks of minor and major bleeding complications were observed with greater frequency with certain prophylactic agents, particularly low-molecular-weight heparin (minor bleeding) and low-dose heparin (both major and minor bleeding).
Sarmiento A, Goswami AD
J Bone Joint Surg Am. 1999 Mar;81(3):339-46
Background: Prophylaxis against pulmonary embolism as a complication of total hip arthroplasty remains controversial. Our experience suggests that an inexpensive protocol of prophylaxis that includes aspirin and exercise is effective.
Methods: We investigated the effectiveness of aspirin, a program of intraoperative and postoperative exercises, and graded elastic stockings or intermittent compression devices as prophylaxis against thromboembolic disease in a series of 1267 patients who had had 1492 total hip arthroplasties. All of the operations were done through a posterior approach. For the purpose of this review, the duration of follow-up was limited to a minimum of three months. No patient was lost to follow-up. Any thromboembolic complications that may have occurred after the third postoperative month were not considered to be related to the operation and were not recorded.
Results: A fatal pulmonary embolism occurred after two arthroplasties (0.13 percent), a nonfatal pulmonary embolism was diagnosed after fourteen (0.94 percent), and deep venous thrombosis developed after fifteen (1.01 percent). Regional (epidural) anesthesia was used for 1099 arthroplasties (73.7 percent), and general anesthesia was used for 393 procedures (26.3 percent). A fatal pulmonary embolism occurred after two (0.18 percent) of the 1099 arthroplasties that had been performed with regional anesthesia and after none that had been performed with general anesthesia (chi square = 0.22; p > 0.05). A nonfatal pulmonary embolism occurred after two procedures (0.18 percent) that had been done with regional anesthesia and after twelve (3.05 percent) that had been done with general anesthesia (chi square = 25.3; p < 0.001). Deep venous thrombosis was diagnosed after seven procedures (0.64 percent) that had been performed with regional anesthesia and after eight (2.04 percent) that had been performed with general anesthesia (chi square = 5.45; p < 0.025). We detected a significant difference between men and women with respect to the rate of nonfatal pulmonary embolism (chi square = 4.36; p < 0.05). With the numbers available, we found no significant differences between the 774 arthroplasties (51.9 percent) in patients who had worn graded elastic stockings and the 718 arthroplasties (48.1 percent) in patients who had used intermittent compression devices, between the 774 arthroplasties (51.9 percent) that had been performed in Florida and the 718 (48.1 percent) that had been done in California, or between the 1313 primary arthroplasties (88 percent) and the 179 revision arthroplasties (12 percent), with regard to the prevalence of fatal pulmonary embolism, nonfatal pulmonary embolism, or deep venous thrombosis (p > 0.05 for all comparisons). In summary, we found that the type of compression (graded elastic stockings or intermittent compression devices), the geographic location (California or Florida), and the type of operation (primary or revision) had no significant effect, with the numbers available, on the rate of thromboembolic complications. Compared with general anesthesia, the use of regional anesthesia was associated with a significantly lower rate of nonfatal pulmonary embolism (p < 0.001) and deep venous thrombosis (p < 0.025). Both patients who had a fatal pulmonary embolism had had regional anesthesia (p > 0.05).
Conclusions: This inexpensive method of prophylaxis against thromboembolic disease after total hip arthroplasty, which was based primarily on the use of aspirin as the pharmacological agent and the performance of intraoperative and postoperative exercises, produced good clinical results.
What's the latest in treatment for deep vein thrombosis after total hip arthroplasty? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape.
Turpie AG, Gallus AS, Hoek JA
N Engl J Med. 2001 Mar;344(9):619-25
Background: Venous thromboembolism is a frequent complication of total hip replacement. The pentasaccharide Org31540/SR90107A, a highly selective, indirect inhibitor of activated factor X, is the first of a new class of synthetic antithrombotic agents. To determine the optimal dose for phase 3 studies, we conducted a dose-ranging study in which Org31540/SR90107A was compared with a low-molecular-weight heparin, enoxaparin, in patients undergoing total hip replacement.
Methods: In a double-blind study, patients were randomly assigned to postoperative administration of one of five daily doses of Org31540/SR90107A, given once daily, or to 30 mg of enoxaparin, given every 12 hours. Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days.
Results: Of 933 patients treated, 593 were eligible for the efficacy analysis. With Org31540/SR90107A a dose effect was observed (P=0.002), with rates of venous thromboembolism of 11.8 percent, 6.7 percent, 1.7 percent, 4.4 percent, and 0 percent for the groups assigned to 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg of the drug, respectively, as compared with a rate of 9.4 percent in the enoxaparin group. The reduction in the risk of venous thromboembolism was 82 percent for the 3.0-mg Org31540/SR90107A group (P=0.01) and 29 percent for the 1.5-mg group (P=0.51). Enrollment in the 6.0-mg and 8.0-mg Org31540/SR90107A groups was discontinued because of bleeding complications. Major bleeding occurred 3.5 percent less frequently in the 0.75-mg group (P=0.01) and 3.0 percent less frequently in the 1.5-mg group (P=0.05) than in the enoxaparin group (in which the rate was similar to that in the 3.0-mg group).
Conclusions: A synthetic pentasaccharide, Org31540/SR90107A, has the potential to improve significantly the risk-benefit ratio for the prevention of venous thromboembolism, as compared with low-molecular-weight heparin.
Heit JA, Elliott CG, Trowbridge AA, Morrey BF, Gent M, Hirsh J
Ann Intern Med. 2000 Jun 6;132(11):853-61
Background: The optimal duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain.
Objective: To determine the efficacy and safety of extended out-of-hospital prophylaxis with low-molecular-weight heparin (ardeparin sodium).
Design: Randomized, double-blind, placebo-controlled trial.
Setting: 33 community, university, or university-affiliated hospitals.
Patients: 1195 adults who had elective total hip or knee replacement and completed 4 to 10 days of postoperative ardeparin prophylaxis.
Intervention: Daily subcutaneous ardeparin (100 anti-Xa IU/kg of body weight) or placebo from time of hospital discharge to 6 weeks after surgery.
Measurements: Symptomatic, objectively documented venous thromboembolism or death, along with major bleeding, from time of hospital discharge to 12 weeks after surgery.
Results: Patients who received ardeparin (n = 607) and those who received placebo (n = 588) did not differ significantly in the cumulative incidence of venous thromboembolism or death (9 cases [1.5%] compared with 12 cases [2.0%]; odds ratio, 0.7 [95% CI, 0.3 to 1.7]; P > 0.2; absolute difference, -0.56 percentage points [CI, -2.2 to 1.1 percentage points]) or major bleeding (2 cases [0.3%] compared with 3 cases [0.5%]).
Conclusions: Among patients who had total knee or total hip replacement and received 4 to 10 days of postoperative ardeparin prophylaxis, the cumulative incidence of symptomatic venous thromboembolism or death after hospital discharge was not significantly reduced by extended out-of-hospital ardeparin prophylaxis. Extended ardeparin use could provide a maximum 2.2-percentage point true reduction in such events. The benefit of extended ardeparin use is not clinically important for most patients. Future research should identify high-risk patients who would benefit most from extended prophylaxis.
Wade WE, Hawkins DW
Orthopedics. 2000 Apr;23(4):335-8; discussion 338-9
Guidelines for deep venous thrombosis (DVT) and pulmonary embolism (PE) prophylaxis have been developed for patients undergoing total hip arthroplasty (THA). Studies suggest that risk for developing these complications may exist for as long as 3 months following surgery. Cost-effectiveness analyses were performed on three pharmacoprophylaxis regimens administered over a 30-day period using literature-reported values for incidences of DVT and PE in patients postdischarge following THA. A cost savings of $21,466.89 will occur for each thromboembolic event avoided if low-dose warfarin daily is used routinely compared to enoxaparin 40 mg daily. Additionally, a cost savings of $18,618.10 is experienced if enoxaparin 40 mg daily for 4 days plus low-dose warfarin daily is administered versus enoxaparin 40 mg daily. Clinicians may choose to continue prophylaxis postdischarge with enoxaparin 40 mg daily for 4 days in combination with warfarin for 30 days in these patients until results of more definitive studies become available.
Eikelboom JW, Quinlan DJ, Douketis JD
Lancet. 2001 Jul 7;358(9275):9-15
Background: The optimum duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain. Our primary objective was to establish the efficacy of extended-duration prophylaxis on symptomatic venous thromboembolic events.
Methods: We identified randomised trials comparing extended-duration prophylaxis using heparin or warfarin with placebo or untreated control in patients undergoing elective total hip or knee replacement by searching electronic databases (MEDLINE, EMBASE), references from retrieved articles, and abstracts from conference proceedings, and by contact with pharmaceutical companies and investigators. Two reviewers independently extracted data on study design, symptomatic and symptomless venographic venous thromboembolism, death, and bleeding outcomes from individual trials were combined with the Mantel-Haenszel method.
Findings: Nine studies met our inclusion criteria (3999 patients), eight with low molecular weight heparin, and one with unfractionated heparin. Extended-duration prophylaxis for 30-42 days significantly reduced the frequency of symptomatic venous thromboembolism (1.3% vs 3.3%, OR 0.38; 95% CI 0.24-0.61, numbers needed to treat [NNT]=50), with no statistical evidence of heterogeneity (x(2) test, p=0.69). There was a greater risk reduction in patients undergoing hip replacement (1.4% vs 4.3%, 0.33; 0.19-0.56, 34) compared with knee replacement (1.0% vs 1.4%, 0.74; 0.26-2.15, 250). A significant reduction in symptomless venographic deep vein thrombosis was also observed (9.6% vs 19.6%, 0.48; 0.36-0.63, 10). There was no increase in major bleeding but extended-duration prophylaxis was associated with excess minor bleeding (3.7% vs 2.5%, 1.56; 1.08-2.26, numbers needed to harm [NNH]=83).
Interpretation: Among patients undergoing total hip or knee replacement, extended-duration prophylaxis significantly reduces the frequency of symptomatic venous thromboembolism. The reduction in risk is equivalent to about 20 symptomatic events per 1000 patients treated.
Comp PC, Spiro TE, Friedman RJ, et al
J Bone Joint Surg Am. 2001 Mar;83-A(3):336-45
Background: Patients undergoing hip or knee joint replacement are at risk for venous thromboembolic complications for up to twelve weeks postoperatively. We evaluated the efficacy and safety of a prolonged post-hospital regimen of enoxaparin, a low-molecular-weight heparin, in this patient population.
Methods: Following elective total hip or knee replacement, 968 patients received subcutaneous enoxaparin (30 mg twice daily) for seven to ten days, and 873 were then randomized to receive three weeks of double-blind outpatient treatment with either enoxaparin (40 mg once daily) or a placebo. The primary efficacy end point was the prevalence of objectively confirmed venous thromboembolism or symptomatic pulmonary embolism during the double-blind phase of treatment.
Results: Of the 873 randomized patients, 435 underwent elective total hip replacement and 438 underwent elective total knee replacement. Enoxaparin was superior to the placebo in reducing the prevalence of venous thromboembolism in patients treated with hip replacement: 8.0% (eighteen) of the 224 patients treated with enoxaparin had venous thromboembolism compared with 23.2% (forty-nine) of the 211 patients treated with the placebo (p < 0.001; odds ratio, 3.62; 95% confidence interval, 2.00 to 6.55; relative risk reduction, 65.5%). Enoxaparin had significant benefit in the patients treated with knee replacement: thirty-eight (17.5%) of the 217 patients treated with enoxaparin had venous thromboembolism compared with forty-six (20.8%) of the 221 patients treated with the placebo (p = 0.380; odds ratio, 1.24; 95% confidence interval, 0.76 to 2.02; relative risk reduction, 15.9%). Symptomatic pulmonary embolism developed in three patients, one with a hip replacement and two with a knee replacement; all had received the placebo. There was no significant difference in the prevalence of hemorrhagic episodes or other types of toxicity between the enoxaparin and placebo-treated groups.
Conclusions: Prolonging enoxaparin thromboprophylaxis following hip replacement for a total of four weeks provided therapeutic benefit, by reducing the prevalence of venous thromboembolism, without compromising safety. A similar benefit was not observed in patients treated with knee replacement.
Freedman KB, Brookenthal KR, Fitzgerald RH, Williams S, Lonner JH
J Bone Joint Surg Am. 2000 Jul;82-A(7):929-38
Background: Although several agents have been shown to reduce the risk of thromboembolic disease, there is no clear preference for thromboembolic prophylaxis in elective total hip arthroplasty. The purpose of this study was to define the efficacy and safety of the agents that are currently used for prophylaxis against deep venous thrombosis -- namely, low-molecular-weight heparin, warfarin, aspirin, low-dose heparin, and pneumatic compression.
Methods: A Medline search identified all randomized, controlled trials, published from January 1966 to May 1998, that compared the use of one of the prophylactic agents with the use of any other agent or a placebo in patients undergoing elective total hip arthroplasty. For a study to be included in our analysis, bilateral venography had to have been performed to confirm the presence or absence of deep venous thrombosis. Fifty-two studies, in which 10,929 patients had been enrolled, met the inclusion criteria and were included in the analysis. The rates of distal, proximal, and total (distal and proximal) deep venous thrombosis; symptomatic and fatal pulmonary embolism; minor and major wound-bleeding complications; major non-wound bleeding complications; and total mortality were determined for each agent in each study. The absolute risk of each outcome was determined by dividing the number of events by the number of patients at risk. A general linear model with random effects was used to calculate the 95 percent confidence interval of risk. A crosstabs of study by outcome was performed to test homogeneity (ability to combine studies). The risk of each outcome was compared among agents and between each agent and the placebo.
Results: With prophylaxis, the risk of total (proximal and distal) deep venous thrombosis ranged from 17.7 percent (low-molecular-weight heparin) to 31.1 percent (low-dose heparin); the risk with prophylaxis with any agent was significantly lower than the risk with the placebo (48.5 percent) (p < 0.0001). The risk of proximal deep venous thrombosis was lowest with warfarin (6.3 percent) and low-molecular-weight heparin (7.7 percent), and again the risk with any prophylactic agent was significantly lower than the risk with the placebo (25.8 percent) (p < 0.0001). Compared with the risk with the placebo (1.51 percent), only warfarin (0.16 percent), pneumatic compression (0.26 percent), and low-molecular-weight heparin (0.36 percent) were associated with a significantly lower risk of symptomatic pulmonary embolism. There were no significant differences among agents with regard to the risk of fatal pulmonary embolism or of mortality with any cause. The risk of minor wound-bleeding was significantly higher with low-molecular-weight heparin (8.9 percent) and low-dose heparin (7.6 percent) than it was with the placebo (2.2 percent) (p < 0.05). Compared with the risk with the placebo (0.28 percent), only low-dose heparin was associated with a significantly higher risk of major wound-bleeding (2.56 percent) and total major bleeding (3.46 percent) (p < 0.0001).
Conclusions: The best prophylactic agent in terms of both efficacy and safety was warfarin, followed by pneumatic compression, and the least effective and safe was low-dose heparin. Warfarin provided the lowest risk of both proximal deep venous thrombosis and symptomatic pulmonary embolism. However, there were no identifiable significant differences in the rates of fatal pulmonary embolism or death among the agents. Significant risks of minor and major bleeding complications were observed with greater frequency with certain prophylactic agents, particularly low-molecular-weight heparin (minor bleeding) and low-dose heparin (both major and minor bleeding).
Sarmiento A, Goswami AD
J Bone Joint Surg Am. 1999 Mar;81(3):339-46
Background: Prophylaxis against pulmonary embolism as a complication of total hip arthroplasty remains controversial. Our experience suggests that an inexpensive protocol of prophylaxis that includes aspirin and exercise is effective.
Methods: We investigated the effectiveness of aspirin, a program of intraoperative and postoperative exercises, and graded elastic stockings or intermittent compression devices as prophylaxis against thromboembolic disease in a series of 1267 patients who had had 1492 total hip arthroplasties. All of the operations were done through a posterior approach. For the purpose of this review, the duration of follow-up was limited to a minimum of three months. No patient was lost to follow-up. Any thromboembolic complications that may have occurred after the third postoperative month were not considered to be related to the operation and were not recorded.
Results: A fatal pulmonary embolism occurred after two arthroplasties (0.13 percent), a nonfatal pulmonary embolism was diagnosed after fourteen (0.94 percent), and deep venous thrombosis developed after fifteen (1.01 percent). Regional (epidural) anesthesia was used for 1099 arthroplasties (73.7 percent), and general anesthesia was used for 393 procedures (26.3 percent). A fatal pulmonary embolism occurred after two (0.18 percent) of the 1099 arthroplasties that had been performed with regional anesthesia and after none that had been performed with general anesthesia (chi square = 0.22; p > 0.05). A nonfatal pulmonary embolism occurred after two procedures (0.18 percent) that had been done with regional anesthesia and after twelve (3.05 percent) that had been done with general anesthesia (chi square = 25.3; p < 0.001). Deep venous thrombosis was diagnosed after seven procedures (0.64 percent) that had been performed with regional anesthesia and after eight (2.04 percent) that had been performed with general anesthesia (chi square = 5.45; p < 0.025). We detected a significant difference between men and women with respect to the rate of nonfatal pulmonary embolism (chi square = 4.36; p < 0.05). With the numbers available, we found no significant differences between the 774 arthroplasties (51.9 percent) in patients who had worn graded elastic stockings and the 718 arthroplasties (48.1 percent) in patients who had used intermittent compression devices, between the 774 arthroplasties (51.9 percent) that had been performed in Florida and the 718 (48.1 percent) that had been done in California, or between the 1313 primary arthroplasties (88 percent) and the 179 revision arthroplasties (12 percent), with regard to the prevalence of fatal pulmonary embolism, nonfatal pulmonary embolism, or deep venous thrombosis (p > 0.05 for all comparisons). In summary, we found that the type of compression (graded elastic stockings or intermittent compression devices), the geographic location (California or Florida), and the type of operation (primary or revision) had no significant effect, with the numbers available, on the rate of thromboembolic complications. Compared with general anesthesia, the use of regional anesthesia was associated with a significantly lower rate of nonfatal pulmonary embolism (p < 0.001) and deep venous thrombosis (p < 0.025). Both patients who had a fatal pulmonary embolism had had regional anesthesia (p > 0.05).
Conclusions: This inexpensive method of prophylaxis against thromboembolic disease after total hip arthroplasty, which was based primarily on the use of aspirin as the pharmacological agent and the performance of intraoperative and postoperative exercises, produced good clinical results.