Managed Care - September 2008 - (Page C14)

Table 17 Efficacy of Lovenox in the Prophylaxis of Deep Vein Thrombosis Following Hip Replacement Surgery Dosing Regimen 10 mg q.d. SC 30 mg q12h SC 40 mg q.d. SC Indication n (%) n (%) n (%) All Treated Hip 161 (100) 208 (100) 199 (100) Replacement Patients Treatment Failures Total DVT (%) 40 (25) 22 (11)1 27 (14) Proximal DVT (%) 17 (11) 8 (4)2 9 (5) 1 2 87 years (mean age 68.5 years) with 43.1% men and 56.9% women. Similar to the first study the incidence of DVT during extended prophylaxis was significantly lower for Lovenox compared to placebo, with a statistically significant difference in both total DVT (Lovenox 21 [16%] versus placebo 45 [34%]; p = 0.001) and proximal DVT (Lovenox 8 [6%] versus placebo 28 [21%]; p = <0.001). 14.3 Prophylaxis of Deep Vein Thrombosis (DVT) In Medical Patients with Severely Restricted Mobility During Acute Illness In a double blind multicenter, parallel group study, Lovenox 20 mg or 40 mg once a day SC was compared to placebo in the prophylaxis of DVT in medical patients with severely restricted mobility during acute illness (defined as walking distance of <10 meters for ≤3 days). This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or complicated chronic respiratory insufficiency (not requiring ventilatory support): acute infection (excluding septic shock); or acute rheumatic disorder [acute lumbar or sciatic pain, vertebral compression (due to osteoporosis or tumor), acute arthritic episodes of the lower extremities]. A total of 1102 patients were enrolled in the study, and 1073 patients were treated. Patients ranged in age from 40 to 97 years (mean age 73 years) with equal proportions of men and women. Treatment continued for a maximum of 14 days (median duration 7 days). When given at a dose of 40 mg once a day SC, Lovenox significantly reduced the incidence of DVT as compared to placebo. The efficacy data are provided below [see Table 20]. Table 20 Efficacy of Lovenox in the Prophylaxis of Deep Vein Thrombosis in Medical Patients With Severely Restricted Mobility During Acute Illness Dosing Regimen Lovenox Lovenox Placebo 20 mg q.d. SC 40 mg q.d. SC Indication n (%) n (%) n (%) All Treated Medical 351 (100) 360 (100) 362 (100) Patients During Acute Illness Treatment Failure1 Total VTE2 (%) 43 (12.3) 16 (4.4) 43 (11.9) Total DVT (%) 43 (12.3) 16 (4.4) 41 (11.3) (95% CI3 8.8 (95% CI3 2.3 (95% CI3 8.1 to 15.7) to 6.6 ) to 14.6 ) Proximal DVT (%) 13 (3.7) 5 (1.4) 14 (3.9) 1 Treatment failures during therapy, between Days 1 and 14. 2 VTE = Venous thromboembolic events which included DVT, PE, and death considered to be thromboembolic in origin. 3 CI = Confidence Interval At approximately 3 months following enrollment, the incidence of venous thromboembolism remained significantly lower in the Lovenox 40 mg treatment group versus the placebo treatment group. 14.4 Treatment of Deep Vein Thrombosis (DVT) with or without Pulmonary Embolism (PE) In a multicenter, parallel group study, 900 patients with acute lower extremity DVT with or without PE were randomized to an inpatient (hospital) treatment of either (i) Lovenox 1.5 mg/kg once a day SC, (ii) Lovenox 1 mg/kg every 12 hours SC, or (iii) heparin IV bolus (5000 IU) followed by a continuous infusion (administered to achieve an aPTT of 55 to 85 seconds). A total of 900 patients were randomized in the study and all patients were treated. Patients ranged in age from 18 to 92 years (mean age 60.7 years) with 54.7% men and 45.3% women. All patients also received warfarin sodium (dose adjusted according to PT to achieve an International Normalization Ratio [INR] of 2.0 to 3.0), commencing within 72 hours of initiation of Lovenox or standard heparin therapy, and continuing for 90 days. Lovenox or standard heparin therapy was administered for a minimum of 5 days and until the targeted warfarin sodium INR was achieved. Both Lovenox regimens were equivalent to standard heparin therapy in reducing the risk of recurrent venous thromboembolism (DVT and/or PE). The efficacy data are provided below [see Table 21]. Table 21 Efficacy of Lovenox in Treatment of Deep Vein Thrombosis With or Without Pulmonary Embolism Dosing Regimen1 Lovenox Lovenox Heparin 1.5 mg/kg q.d. SC 1 mg/kg q12h SC aPTT Adjusted I.V. Therapy Indication n (%) n (%) n (%) All Treated DVT 298 (100) 312 (100) 290 (100) Patients with or without PE Patient Outcome Total VTE2 (%) 13 (4.4)3 9 (2.9) 3 12 (4.1) DVT Only (%) 11 (3.7) 7 (2.2) 8 (2.8) Proximal DVT (%) 9 (3.0) 6 (1.9) 7 (2.4) PE (%) 2 (0.7) 2 (0.6) 4 (1.4) 1 All patients were also treated with warfarin sodium commencing within 72 hours of Lovenox or standard heparin therapy. 2 VTE = venous thromboembolic event (DVT and/or PE). 3 The 95% Confidence Intervals for the treatment differences for total VTE were: Lovenox once a day versus heparin (-3.0 to 3.5) Lovenox every 12 hours versus heparin (-4.2 to 1.7). Similarly, in a multicenter, open-label, parallel group study, patients with acute proximal DVT were randomized to Lovenox or heparin. Patients who could not receive outpatient therapy were excluded from entering the study. Outpatient exclusion criteria included the following: inability to receive outpatient heparin therapy because of associated co-morbid conditions or potential for non-compliance and inability to attend follow-up visits as an p value versus Lovenox 10 mg once a day = 0.0008 p value versus Lovenox 10 mg once a day = 0.0168 There was no significant difference between the 30 mg every 12 hours and 40 mg once a day regimens. In a double-blind study, Lovenox 30 mg every 12 hours SC was compared to placebo in patients undergoing knee replacement surgery. A total of 132 patients were randomized in the study and 131 patients were treated, of which 99 had total knee replacement and 32 had either unicompartmental knee replacement or tibial osteotomy. The 99 patients with total knee replacement ranged in age from 42 to 85 years (mean age 70.2 years) with 36.4% men and 63.6% women. After hemostasis was established, treatment was initiated 12 to 24 hours after surgery and was continued up to 15 days after surgery. The incidence of proximal and total DVT after surgery was significantly lower for Lovenox compared to placebo. The efficacy data are provided below [see Table 18]. Table 18 Efficacy of Lovenox in the Prophylaxis of Deep Vein Thrombosis Following Total Knee Replacement Surgery Dosing Regimen Lovenox Placebo 30 mg q12h SC q12h SC Indication n (%) n (%) All Treated Total Knee 47 (100) 52 (100) Replacement Patients Treatment Failures Total DVT (%) 5 (11)1 32 (62) (95% CI2: 1 to 21) (95% CI: 47 to 76) Proximal DVT (%) 0 (0)3 7 (13) (95% Upper CL4: 5) (95% CI: 3 to 24) 1 2 3 4 p value versus placebo = 0.0001 CI = Confidence Interval p value versus placebo = 0.013 CL = Confidence Limit Additionally, in an open-label, parallel group, randomized clinical study, Lovenox 30 mg every 12 hours SC in patients undergoing elective knee replacement surgery was compared to heparin 5000 U every 8 hours SC. A total of 453 patients were randomized in the study and all were treated. Patients ranged in age from 38 to 90 years (mean age 68.5 years) with 43.7% men and 56.3% women. Patients were 92.5% Caucasian, 5.3% Black, and 0.6% others. Treatment was initiated after surgery and continued up to 14 days. The incidence of deep vein thrombosis was significantly lower for Lovenox compared to heparin. Extended Prophylaxis of Deep Vein Thrombosis Following Hip Replacement Surgery: In a study of extended prophylaxis for patients undergoing hip replacement surgery, patients were treated, while hospitalized, with Lovenox 40 mg SC, initiated up to 12 hours prior to surgery for the prophylaxis of post-operative DVT. At the end of the peri-operative period, all patients underwent bilateral venography. In a double-blind design, those patients with no venous thromboembolic disease were randomized to a post-discharge regimen of either Lovenox 40 mg (n = 90) once a day SC or to placebo (n = 89) for 3 weeks. A total of 179 patients were randomized in the double-blind phase of the study and all patients were treated. Patients ranged in age from 47 to 87 years (mean age 69.4 years) with 57% men and 43% women. In this population of patients, the incidence of DVT during extended prophylaxis was significantly lower for Lovenox compared to placebo. The efficacy data are provided below [see Table 19]. Table 19 Efficacy of Lovenox in the Extended Prophylaxis of Deep Vein Thrombosis Following Hip Replacement Surgery Post-Discharge Dosing Regimen Lovenox Placebo Indication 40 mg q.d. SC q.d. SC (Post-Discharge) n (%) n (%) All Treated Extended 90 (100) 89 (100) Prophylaxis Patients Treatment Failures Total DVT (%) 6 (7)1 18 (20) (95% CI2: 3 to 14) (95% CI: 12 to 30) Proximal DVT (%) 5 (6)3 7 (8) (95% CI: 2 to 13) (95% CI: 3 to 16) 1 2 3 p value versus placebo = 0.008 CI= Confidence Interval p value versus placebo = 0.537 In a second study, patients undergoing hip replacement surgery were treated, while hospitalized, with Lovenox 40 mg SC, initiated up to 12 hours prior to surgery. All patients were examined for clinical signs and symptoms of venous thromboembolic (VTE) disease. In a double-blind design, patients without clinical signs and symptoms of VTE disease were randomized to a post-discharge regimen of either Lovenox 40 mg (n = 131) once a day SC or to placebo (n = 131) for 3 weeks. A total of 262 patients were randomized in the study double-blind phase and all patients were treated. Patients ranged in age from 44 to

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Managed Care - September 2008

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