LOVENOX® clinical outcomes summary

Patient Type	Primary Efficacy Outcome	Safety Endpoints	Duration of Treatment/NNS	Study Design
STEMI 18,19	LOVENOX® vs. comparator 17% RRR in death or MI LOVENOX® vs. UFH (9.9% Vs. 12%) 95% Cl; P<.001 N=20,479	LOVENOX® vs. comparator Major hemorrhage; 21% vs. 1.4% P<.001 ICH: .8% vs. .7% P=0.14	8 days or until hospital discharge; whichever came first NNT=48a	ExTRACT TIMI 25 was randomized, double-blind, double- dummy, parallel group, multi-national, active- controlled, clinical trial Comparing LOVENOX® With UFH in acute STEMI patients
UA/NSTEMI 20	16% RRR in death, MI And recurrent angina LOVENOX® vs. UFH (16.6% vs. 19.8%) 95% Cl; P=.019 N=3171	Overall hemorrhage: 18.4% vs. 14.2% P=.001 Major hemorrhage: 6.5% vs. 7% P=NS	48 hours to 8 days; median: 2.6 days NNT= 32a	ESSENCE was a prospective, randomized, double-blind, parallel- group, multi-center, multi-national trial comparing LOVENOX® and UFH in UA/STEMI patients
Acutely ill Medical Patients 11	63% RRR in DVT/PE events LOVENOX® vs. placebo (5.5% vs. 14.9%) 95% Cl; P<.001 N=579	Major hemorrhage: 1.7% vs. 1.1% P=NS Thrombocytopenia: 2.2% vs. 3.6% P=NS	In hospital treatment for 6-14 days median: 7 days NNT=11a	MEDONOX was a multi- center, multi-national, double-blind study of hospitalized acutely ill medical patients Randomized to LOVENOX® or placebo
DVT Outpatient Treatment 16	1.4% ARR in recurrent symptomatic thromboembolism LOVENOX® vs. UFH (5.3% vs. 6.7%) 95% Cl; P=NS N=500	Major hemorrhage: 2.0% vs. 1.2% P=NS	Mean duration of LOVENOX®: 5.8 +- 1.8 days; UFH 5.5 +- 1.2 days	This study was randomized, open-label trial comparing LOVENOX® outpatient treatment of DVT with inpatient IV UFH, each In conjunction with warfarin
Hip- Replacement Surgery 13	LOVENOX® vs. comparator 77% RRR in symptomatic DVT during hospitalization LOVENOX® vs. warfarin (.3% vs. 1.1%) 95% Cl; P=.008 N=3011	LOVENOX® vs. comparator Major hemorrhage: .6% vs. .3% P=NS	Therapy initiated within 24 hours postoperatively; mean duration: 7.3 days NNT=125a	This study was randomized, open-label trial comparing LOVENOX® with warfarin in patients undergoing ip-replacement surgery
Hip- Replacement Surgery (extended prophylaxis) 26	53% RRR in DVT/PE events LOVENOX vs. placebo (17.9% vs. 38.8%) 95% Cl; P<.001 N=233	Injection-site hematoma: 5.2% vs. 1.0% P=NS	In-hospital 7 to 11 days; outpatient 19- 23 days (average 21 days) NNT= 5a	A prospective, randomized, double- blind study conducted at a single center with all patients receiving LOVENOX® during their hospitalization and blinded drug at the end of hospitalization

Knee- Replacement Surgery 14	44% RRR in total VTE documented by venography LOVENOX® vs. warfarin (25.4% vs. 45.5%) 95% Cl; P<.001 N=349	Major hemorrhage: 5.2% vs. 2.3% P=NS	Therapy initiated within 8 hours postoperatively and continued for 4 to 14 days NNT=5a	This study was prospective, randomized, multicenter, open label parallel-group trial comparing LOVENOX® with warfarin in patients undergoing knee-replacement surgery
Abdominal Surgery 15	3.5% ARR in DVT/PE incidence LOVENOX® vs. UFH (14.7% vs. 18.2%) 95% Cl; P=NS N=631	Overall hemorrhage: 18.7% vs. 17.1% P=NS Major hemorrhage: 4.1% vs. 2.9% P=NS	Therapy initiated 2 hours preoperatively and continued for 10 +- 2 days	ENOXACAN was a prospective, double- blind, randomized, multicenter trial comparing LOVENOX® with UFH patients undergoing elective urative surgery for abdominal or pelvic cancer

ARR=absolute risk reduction; DVT=deep vein thrombosis; DVT/PE=deep vein thrombosis/pulmonary embolism; ENOXACAN=Enoxaparin and Cancer; ESSENCE=Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events; ExTRACT–TIMI 25=Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment–Thrombolysis in Myocardial Infarction 25; ICH=intracranial hemorrhage; MEDENOX=Prophylaxis in Medical Patients With Enoxaparin; MI=myocardial infarction; NNT=number needed to treat (as observed difference—the estimated number of patients who need to be treated with LOVENOX® rather than a comparator for 1 additional patient to benefit); NS=not significant; OAD=observed absolute difference (the observed difference between 2 groups [NS]); RRR=relative risk reduction; STEMI=ST-segment elevation MI; UA/NSTEMI=unstable angina/non–ST-segment elevation MI; UFH=unfractionated heparin; VTE=venous thromboembolism=DVT and/or PE.

^a The NNT and the benefit/risk profile were not prespecified analyses in the trials and were calculated using the reported ARR results.¹⁰

^bP value calculated based on Chi-Square test.⁶

^cSafety data reflect prescribing information (PI) data for the treatment of DVT, with or without PE.⁶

^dSafety data reflect PI data from the LOVENOX® vs heparin trial.⁶

^eSafety data reflect PI data from the extended prophylaxis period (does not include a comparator).⁶

Important Safety Information

WARNING: SPINAL/EPIDURAL HEMATOMAS

When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low-molecular-weight heparins or heparinoids for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis.

The risk of these events is increased by the use of indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeated epidural or spinal puncture.

Monitor patients for signs and symptoms of neurological impairment. If neurologic compromise is noted, urgent treatment is necessary.

Consider the potential benefit versus risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis (see Warnings and Precautions [5.1] and Drug Interactions [7]).

LOVENOX® (enoxaparin sodium injection) cannot be used interchangeably with other low-molecular-weight heparins or unfractionated heparin (UFH), as they differ in their manufacturing process, molecular weight distribution, anti-Xa and anti-IIa activities, units, and dosage.

As with other anticoagulants, use with extreme caution in patients with conditions that increase the risk of hemorrhage. Dosage adjustment is recommended in patients with severe renal impairment. Unless otherwise indicated, agents that may affect hemostasis should be discontinued prior to LOVENOX® therapy. Bleeding can occur at any site during LOVENOX® therapy. An unexplained fall in hematocrit (HCT) or blood pressure should lead to a search for a bleeding site. (See WARNINGS and PRECAUTIONS.)

In the ST-segment elevation myocardial infarction (STEMI) pivotal trial, the rates of major hemorrhages (defined as requiring 5 or more units of blood for transfusion, or 15% drop in HCT or clinically overt bleeding, including intracranial hemorrhage [ICH]) at 30 days were 2.1% in the LOVENOX® group and 1.4% in the UFH group. The rates of ICH at 30 days were 0.8% in the LOVENOX® group and 0.7% in the UFH group. The 30-day rate of the composite endpoint of death, myocardial infarction (MI), or ICH (a measure of net clinical benefit) was significantly lower in the LOVENOX® group (10.1%) as compared to the UFH group (12.2%).

Thrombocytopenia can occur with LOVENOX®. In patients with a history of heparin-induced thrombocytopenia (HIT), LOVENOX® should be used with extreme caution. Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm³, LOVENOX® should be discontinued. Cases of HIT have been observed in clinical practice. (See WARNINGS and PRECAUTIONS.)

The use of LOVENOX® has not been adequately studied for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves. (See WARNINGS and PRECAUTIONS.)

LOVENOX® is contraindicated in patients with hypersensitivity to enoxaparin sodium, heparin, or pork products, and in patients with active major bleeding.

For more information, contact your local sanofi-aventis U.S. Representative or call sanofi-aventis U.S. Medical Information Services at 1-800-633-1610.

Please see full Prescribing Information including boxed WARNING.

Prescription LOVENOX® is available in pharmacies.

Home|Terms of Use|About Us|References|Site Map