Abbreviated Hospitalization for Deep Venous Thrombosis with the Use of Ardeparin

ORIGINAL INVESTIGATION Abbreviated Hospitalization for Deep Venous Thrombosis With the Use of Ardeparin Samuel Z. Goldhaber, MD; Ruth B. Morrison, RN, BSN, CVN; Linda L. Diran, BS; Mark A. Creager, MD; Thomas H. Lee, Jr, MD Background: Ardeparin sodium has recently re- ultrasonography. Evaluation of baseline vs 6-week ceived approval by the Food and Drug Administration venous scans demonstrated that, overall, 31 of the for prophylaxis against venous thromboembolism in 39 ardeparin-treated patients improved, compared patients undergoing elective total knee replacement. with 21 of the 36 patients assigned to receive unfrac- However, this low-molecular-weight heparin has not tionated heparin (P = .05). The 95% confidence in- been previously evaluated in a randomized controlled terval for the difference in improvement was 0.6% trial for treatment of established acute deep venous to 42% in favor of ardeparin. Median charges for arde- thrombosis. parin and unfractionated heparin were $2815 and $6500, respectively (P,.001). There were no differ- Methods: The study included patients with ultrasound- ences in bleeding or patient satisfaction between the 2 documented acute symptomatic deep venous thrombo- groups. sis of the legs. They had to be deemed appropriate for discharge home to receive subcutaneous low-molecular- Conclusions: The results of this small preliminary weight heparin. Patients were randomized to receive ar- trial suggest that ardeparin can be administered effec- deparin with a 2-day hospitalization or unfractionated tively and safely to selected patients with acute deep heparin sodium with a 5-day hospitalization. Both groups venous thrombosis and that, with proper nursing and received warfarin sodium. Follow-up ultrasound exami- home services, it can help decrease the duration of nations were undertaken at 6 weeks. hospitalization. Results: Of the 80 patients enrolled, 75 had follow-up Arch Intern Med. 1998;158:2325-2328 RDEPARIN SODIUM has re- sessed efficacy, safety, hospital charges, and cently received approval patient satisfaction in the 2 treatment by the Food and Drug groups. Administration for prophylaxis against venous RESULTS thromboembolism in patients undergo- A 1-3 ing elective total knee replacement. How- Overall, 80 patients were randomized, 41 ever, this low-molecular-weight heparin to receive ardeparin and 39 to receive has not been previously evaluated in a ran- unfractionated heparin. Baseline charac- domized controlled trial for treatment of teristics were similar in both groups established acute deep venous thrombo- (Table 1). Of the 80 patients, there were sis (DVT). Therefore, in a single-center, no deaths or recurrent DVTs. There was investigator-initiated trial, we tested the 1 symptomatic, hemodynamically stable feasibility of using a shortened hospital stay pulmonary embolism diagnosed by mod- with ardeparin to treat symptomatic pa- erately high-probability lung scan in a patients with acute DVT proved on ultra- tient assigned to receive unfractionated sound. They were randomized to receive heparin. Adverse clinical events are shown either twice-daily subcutaneously in- in Table 2. One patient in each group suf- jected ardeparin with a 2-day hospital- fered a major bleeding complication. The From the Cardiovascular ization or conventional continuous-in- patient assigned to the unfractionated hep- Division, Department of fusion unfractionated heparin sodium arin group had an intraocular hemor- Medicine, Brigham and with a 5-day hospitalization as a bridge to rhage, and the patient who received arde- Women’s Hospital, Harvard oral anticoagulation with warfarin so- parin had undergone thoracic surgery and Medical School, Boston, Mass. dium. In this feasibility study, we as- developed mediastinal bleeding. ARCH INTERN MED/ VOL 158, NOV 23, 1998 2325 ©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 PATIENTS AND METHODS Patients were given a satisfaction questionnaire to return at the time of their 2-week visit. At the 6-week office visit, they underwent venous ultrasonography. Dur- PATIENTS ing the time from hospital discharge to 6 weeks, international normalized ratios were checked at least once The study included patients 18 years of age or older who weekly. At the 6-week visit, the trial ended and manage- had acute (within 14 days) symptomatic DVT of the legs. ment of warfarin dosing was transferred to the primary They had to be deemed appropriate for discharge home to care physician. receive subcutaneous low-molecular-weight heparin, and A sonographic unit (Acuson 128; Acuson, Mountain DVT had to be documented by ultrasound. Our Human View, Calif) was used to perform venous ultrasound ex- Research Committee approved this trial, and each patient aminations of the lower extremities, with the use of 5- and provided written informed consent. 7-MHz transducers (duplex and color pulsed Doppler ca- Principal exclusion criteria were high-risk DVT in- pacity). Studies were obtained at baseline (before treat- volving 3 proximal veins (eg, common femoral, superfi- ment) and were repeated at 6 weeks. cial femoral, and popliteal veins); pelvic vein thrombosis; Examinations were performed by compressing current symptomatic pulmonary embolism; expected the deep veins of the thigh and the calf in a sequential prolonged hospitalization for other reasons; hemoglobin manner in 1- to 2-cm increments along the common fem- level less than 85 g/L or platelet count less than 100 3 109/L; oral, superficial femoral, popliteal, posterior tibial, pero- intracranial or intraocular surgery, stroke, or internal bleed- neal, gastrocnemius, and soleus veins. Lack of venous ing within 3 months; or weight of 120 kg or more. compressibility with the ultrasound transducer held Randomization was accomplished by calling a central transverse to the artery and vein was interpreted as an computerized service based at Wyeth-Ayerst Research, Phila- abnormal study result and was confirmed with color-flow delphia, Pa. The drug assignment was not blinded. and pulsed-wave Doppler analysis.5 Absent or diminished Doppler flow, lack of respiratory variation, and failure to METHODS augment flow with maneuvers (calf compression) were used to confirm the diagnosis of DVT. One of us (M.A.C.) Patients assigned to the ardeparin sodium group received was responsible for adjudicating the comparison of base- 130 anti-Xa U/kg subcutaneously twice daily and were hos- line and 6-week follow-up ultrasound scans. He had no pitalized for 36 to 48 hours. Ardeparin was administered knowledge of the randomization assignment. Improve- (usually by the patient) for 5 to 15 days, while warfarin so- ment, no change, and worsening of DVT were defined by dium, 7.5 to 10 mg, was initiated and titrated to a thera- regression, no change, or extension, respectively, of visu- peutic and stable international normalized ratio of 2.0 to alized thrombus. 3.0. During ardeparin treatment, daily international nor- We previously found that duplex ultrasonography, malized ratios were obtained, and, after discharge, a study when compared with venography, is a reliable technique nurse (R.B.M.) telephoned the patient daily to discuss war- for the detection of suspected infrapopliteal DVT.6 In a se- farin dosing as well as overall progress. Patients assigned ries of 30 symptomatic patients undergoing both contrast to the unfractionated heparin sodium group received a 5000- venography of the calf veins and ultrasonography, 7 had to 7500-unit bolus followed by a continuous intravenous venographically documented isolated calf DVT, and all 7 infusion administered for 5 days or more to achieve a tar- cases were detected by ultrasonography. get partial thromboplastin time of 1.5 to 2.5 times the up- per limit of the control. Titration of unfractionated hepa- STATISTICAL ANALYSIS rin was guided by the Cruickshank et al nomogram4 and was discontinued after 5 days as long as the target inter- Data were entered into TRUE EPISTAT files and analyzed national normalized ratio had been achieved. by means of TRUE EPISTAT software (Epistat Services, Ri- Hospital charges were tracked and computed by the chardson, Tex). Student t test was used to examine differ- Computer Assisted Hospitalization Analysis for the Study ences among continuous variables with normal distribu- of Efficacy at Brigham and Women’s Hospital, Boston, Mass. tions. The Wilcoxon rank sum test was used when These consisted of charges for room, board, laboratory tests, continuous variables failed tests for normality. Differ- medications, and imaging tests. ences among discontinuous variables were analyzed with All patients were discharged home with vascular com- Epi Info software (version 5.01b; Centers for Disease Con- pression stockings and were scheduled to return for 2- trol and Prevention, Epidemiology Program Office, At- week and 6-week office visits. We instructed all patients lanta, Ga) by means of x2 with the Yates correction, ex- about signs and symptoms of recurrent venous thrombo- cept with expected cell values less than 5, in which case embolism. We provided them with 24-hour emergency tele- Fisher exact 2-tailed test was used. Confidence intervals phone numbers. We also suggested to patients in the ar- were calculated with the use of confidence interval analy- deparin group that they not return to their usual activity sis software (Confidence Inverview Analysis, version 1.0; level until ardeparin was discontinued. British Medical Journal, London,

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