Clinical Efficacy
Only one study evaluating the efficacy and safety of tinzaparin for the treatment of DVT has been published. In a multicenter, randomized, double-blind trial by the American- Canadian Thrombosis Study Group, tinzaparin administered at 175 IU/kg s.c. every 24 hours was compared with a continuous i.v. infusion of UFH for the treatment of DVT.[12] A total of 432 patients 18 years of age or older with proximal DVT documented by venography were included. Two-hundred nineteen patients received UFH and 213 received tinzaparin. A 5,000-unit i.v. bolus dose of UFH was administered, followed by a starting infusion rate of 29,760 units per 24 hours for patients with at least one risk factor for bleeding or 40,320 units per 24 hours for patients who did not have risk factors for bleeding. The infusion was subsequently adjusted to achieve an aPTT of 45-75 seconds. Blinding was achieved by giving the tinzaparin recipients a continuous infusion of placebo solution and the UFH recipients subcutaneous injections of placebo. Tinzaparin or UFH was started as soon as possible after the diagnosis was confirmed; warfarin was initiated on day 2 of therapy at a dosage of 10 mg/day. The dosage was adjusted as needed to achieve an International Normalized Ratio (INR) of 2-3, and warfarin was continued for a minimum of three months. Treatment with tinzaparin or UFH was discontinued on hospital day 6 or when the targeted INR (≥2) was reached, whichever occurred later.
At three months, new VTE occurred in 6 patients (2.8%) in the tinzaparin group and 15 patients (6.9%) in the UFH group. VTE was defined as DVT documented by venography or impedence plethysmography and PE documented by a high-probability ventilation/perfusion (V/Q) scan, pulmonary angiography, or autopsy. The statistical significance of the results was unclear: The p value for the difference was 0.07 by Fisher's exact test (95% confidence interval [CI], 0.02-8.1), but analysis by the log-rank test, which accounts for the time to an event, yielded a p value of 0.049. To put these conflicting results into a clinical perspective, the absolute risk reduction was 4.1%, indicating that approximately 25 patients needed to be treated with tinzaparin rather than UFH to prevent one recurrent VTE event. Three events in the tinzaparin group (1.4%) and 6 in the UFH group (2.7%) were PE (absolute risk reduction, 1.3%; number needed to treat, 77). Fifty-three patients in the UFH group had at least one risk factor for bleeding, as did 56 tinzaparin recipients. Fewer major bleeding complications were observed during initial therapy in the tinzaparin group; major bleeding was observed in 1 patient (0.5%) receiving tinzaparin and 11 patients (5%) treated with UFH (p = 0.006). Five patients in the UFH group had PT or aPTT values above the targeted range when the bleeding occurred. No difference in minor bleeding was noted. During long-term follow-up (three months), more tinzaparin recipients had major bleeding than UFH recipients (2.3% versus 0%) (p = 0.028); however, the INR was above the targeted range in 80% of these patients, so this increased risk of bleeding probably was not attributable to tinzaparin. Ten tinzaparintreated patients (4.7%) and 21 UFH recipients (9.6%) died during the study (p = 0.062, Fisher's exact test; p = 0.049, uncorrected chi-square test). One death in the tinzaparin group (0.5%) was possibly related to PE, while 4 deaths in the UFH group (1.8%) were probably or possibly related to PE. The results indicate that tinzaparin is at least as effective as UFH in the treatment of DVT but causes fewer bleeding events during the initial treatment period.
Few data on the use of tinzaparin for the outpatient treatment of DVT are available. One prospective cohort study was performed in two Canadian thromboembolism clinics.[13] The investigators prescribed either dalteparin 100 IU/kg s.c. twice daily or tinzaparin 175 IU/kg s.c. once daily. LMWH treatment was continued for at least five days or until the patient reached a targeted INR (2-3) for two consecutive days while receiving warfarin. Warfarin therapy was continued for three months. Efficacy and safety outcomes, as well as patient satisfaction with home treatment, were evaluated at the end of warfarin therapy. Only 25 of 89 patients were treated with tinzaparin; outcomes for these patients were not analyzed separately from those of patients given dalteparin. The authors did not report whether recurrent VTE episodes and bleeding events occurred during or after LMWH therapy, nor was the INR at the time of these events reported. For these reasons, little can be concluded from this study regarding the safety and efficacy of tinzaparin for the outpatient treatment of DVT.
Simonneau et al.[14] evaluated the safety and efficacy of tinzaparin versus UFH in 612 patients with symptomatic PE. The presence of PE was confirmed by objective measures (pulmonary angiography, high-probability V/Q scanning, or indeterminate V/Q scanning with DVT documented by venography or compression ultrasonography). Although patients requiring thrombolytic therapy or pulmonary embolectomy were excluded, 89 of 304 patients in the tinzaparin group and 82 of 308 patients in the UFH group had symptoms suggestive of severe PE (acute right ventricular failure, cyanosis, syncope, or cardiovascular collapse). The study was unblinded, and patients were randomly assigned to receive tinzaparin 175 IU/kg s.c. daily or a 50-unit/kg initial i.v. bolus dose of UFH followed by a continuous i.v. infusion at a rate of 500 units/kg/day. The infusion rate was then adjusted to achieve a targeted aPTT that was two to three times each participating institution's control value for healthy subjects. Seventy-three percent of patients in the tinzaparin group and 65% of those in the UFH group received therapeutic doses of UFH for a mean of 18 hours before they could be randomized. Presumably, the remaining patients did not receive anticoagulation therapy before randomization. Warfarin therapy was begun between days 1 and 3, and the dosage was adjusted to achieve an INR of 2-3. Therapy was continued for a minimum of three months. Tinzaparin and UFH were discontinued after five days or when a targeted INR was reached and maintained for two consecutive days, whichever occurred later. On days 8 and 90, there were no significant differences between the two groups with respect to the frequency of the combined endpoint, which included symptomatic recurrent VTE, major bleeding, and death (absolute difference of 1.2 percentage points, 95% CI, -2.7 to 5.1) (p = 0.55). When individual outcomes were evaluated, no differences between the treatment groups were observed (absolute difference of 0.3 percentage points, 95% CI for recurrent VTE, -1.8 to 2.4; absolute difference of 0.6 percentage points, 95% CI for major bleeding, -1.8 to 3.0; and absolute difference of 0.6 percentage points, 95% CI for death, -2.6 to 3.8).
In a substudy performed by the American-Canadian Thrombosis Study Group, investigators compared tinzaparin 175 IU/kg s.c. once daily with i.v. heparin for the treatment of patients with documented PE.[15] UFH was administered as a 5,000-unit i.v. bolus dose, followed by a continuous i.v. infusion of 29,760 units per 24 hours for patients with at least one risk factor for bleeding or 40,320 units per 24 hours for patients without risk factors for bleeding. The infusion was subsequently adjusted to achieve a targeted aPTT of 45-75 seconds. Eligible patients had proximal DVT documented by venography and had no contraindications to the study medications. Four-hundred nineteen of the 432 patients enrolled underwent perfusion lung scanning within 48 hours of study entry; in 200 of these patients (103 of 219 patients in the UFH group and 97 of 213 patients in the tinzaparin group), the results showed a high probability of PE; in 183, the results were nondiagnostic; and in 36, the results were normal. Only 28 patients actually had symptoms associated with PE. Patients were started on warfarin 10 mg p.o. daily on the second day of therapy, and treatment was continued for a minimum of three months with a goal INR of 2-3. Tinzaparin and UFH were discontinued on day 6 if a targeted INR of ≥2 was achieved. None of the 97 patients receiving tinzaparin who had scan results showing a high probability of PE had recurrent VTE. During three months of follow-up, 7 of the 103 patients receiving UFH did have recurrent VTE (95% CI for the 6.8% difference, 1.94-11.7) (p = 0.01). PE occurred in 4 of these 7 patients; 2 of the 7 had an INR below the targeted range before or at the time of recurrence. No significant differences were noted between the tinzaparin and UFH groups in major or minor bleeding complications, deaths, or the combined endpoint of death and recurrent VTE.
The available study data indicate that tinzaparin can be used safely for the treatment of PE in hospitalized patients who can be closely monitored. Until more data are available, however, the use of tinzaparin for this indication should be limited to patients who are hemodynamically stable and who are not at high risk of respiratory decompensation. Tinzaparin should not be administered to patients who require fibrinolytic therapy.
The prophylactic efficacy of tinzaparin in patients undergoing total hip replacement surgery was investigated in a preliminary dose-ranging study[16]; subsequently, tinzaparin doses of 35-75 anti-factor Xa IU/kg were compared with placebo, intravenous dextran 70, enoxaparin, and oral warfarin.[17,18,19,20,21]
In the dose-ranging study, Matsch et al.[16] evaluated the rate of confirmed PE or DVT after tinzaparin prophylaxis in 29 patients. The patients were divided into three groups and received a weight-based regimen of 35 or 50 anti-factor Xa IU/kg or a fixed-dose regimen of 3500 anti-factor Xa IU. The patients were between 58 and 75 years of age and weighed an average of 73 kg. A patient was excluded if he or she demonstrated iodine hypersensitivity, impaired renal function, stroke, or hemorrhagic diathesis or was already being treated with anticoagulants. There were no significant differences among treatment groups with respect to hemorrhagic complications or thromboembolic events, and the overall frequency of thromboembolic events was relatively low at 13.8%. The patient groups were too small (approximately 10 patients per group), however, for any firm conclusions to be drawn.
The prophylactic safety and efficacy of tinzaparin were assessed in a randomized, double-blind, placebo-controlled study in two Danish hospitals.[17] The patients were 40 years of age or older and were scheduled for elective hip replacement surgery. Injections of tinzaparin 50 anti-factor Xa IU/kg were given subcutaneously into the abdominal wall beginning two hours postoperatively and continued once daily for seven days. DVT was diagnosed by bilateral ascending phlebography between postoperative days 8 and 10. DVT occurred in 31% of the tinzaparintreated patients (n = 93), compared with 45% of the placebo recipients (n = 97), while PE occurred in 1% of both groups. When combined with early mobilization (day 4 after surgery), tinzaparin was significantly more effective than placebo in preventing DVT (p = 0.003). The authors concluded that thromboprophylaxis with an LMWH once daily is safe and is more effective than placebo in patients undergoing total hip replacement.
Two prospective randomized studies determined that weight-based tinzaparin (35 or 50 anti-factor Xa IU/kg) was more efficacious than dextran 70 in patients undergoing hip surgery, with the larger tinzaparin dose resulting in a DVT frequency of 17.1%, versus 28.7% for dextran 70 (p = 0.04). Hemorrhagic risk did not increase with the higher dose of tinzaparin. Only minor differences in blood loss and in transfusion requirements were observed between the two groups.[18,19]
A fixed dose of tinzaparin 4500 anti-factor Xa IU s.c. daily was compared with a fixed dose of enoxaparin of 40 mg s.c. daily for the prevention of VTE in 440 patients weighing 50-90 kg who underwent total hip replacement surgery.[20] The first dose of each LMWH was given 12 hours preoperatively, and the second dose was given 12 hours postoperatively. Subsequent doses were then given daily. Bilateral venography was performed 12-14 days after surgery unless there were overt signs or symptoms of VTE that necessitated an earlier imaging study. The overall rate of DVT was 21.7% (48 of 221 patients) in the tinzaparin group and 20.1% (44 of 219 patients) in the enoxaparin group (95% CI for the 1.6% difference, -6.0 to 9.2%). Proximal DVT occurred in 9.5% and 10.5% of the tinzaparin and enoxaparin recipients, respectively (the difference was not significant). One nonfatal PE was documented in each group. One enoxaparin recipient developed severe thrombocytopenia and died. No differences in major or minor bleeding were observed. The authors concluded that tinzaparin appeared to be as safe and effective as enoxaparin for the prophylaxis of VTE after total hip replacement.
A multicenter, randomized, double-blind clinical trial by Hull et al.[21] compared the safety and efficacy of tinzaparin with warfarin sodium for the prevention of VTE in patients undergoing hip or knee implantation. A total of 1436 patients were enrolled; of these, 641 underwent elective knee surgery and 795 had hip surgery. The primary endpoint was DVT detected by contrast venography performed a mean of 9.4 days after surgery. Tinzaparin was given subcutaneously at a dosage of 75 anti-factor Xa IU per kilogram of body weight once daily beginning 18-24 hours after surgery if there was no clinical evidence of bleeding or excessive drainage from the wound. If excessive blood loss was detected, the first injection was deferred until the bleeding stopped. The dosage of tinzaparin was larger than in other studies. The researchers noted that the dosage used for prophylaxis in this study was moderate compared with the dosage used for treatment of DVT (175 anti-factor Xa IU/kg). Patients receiving warfarin were given an initial 10-mg dose on the first postoperative evening. Subsequent warfarin doses were adjusted by a standardized protocol based on the patients' PTs and according to a predefined warfarin nomogram. PTs were standardized among participating hospitals by converting them to INRs, with the goal INR being 2-3. Prophylaxis in both treatment groups was discontinued on postoperative day 14 or upon discharge from the hospital, whichever occurred first.
The final analysis included 617 warfarin-treated patients and 590 tinzaparin-treated patients with interpretable venograms. There was a significant difference in the rates of DVT, major bleeding, and wound hematomas between tinzaparin and warfarin. The overall rate of DVT was 37.4% in the warfarin group and 31.4% in the tinzaparin group (p = 0.03). Although the difference was not significant, proximal DVT occurred in 7.6% of the warfarin recipients and 6.1% of the tinzaparin recipients. The overall rate of major bleeding was 1.2% and 2.8% in the warfarin and tinzaparin groups, respectively (p = 0.04). For wound hematomas, the overall rate was 4.0% in the warfarin group and 7.1% in the tinzaparin group (p = 0.01).
Separate analysis of the hip and knee surgery groups revealed a significant difference in the rate of DVT. For patients undergoing knee surgery, 54.9% in the warfarin group had documented DVT, compared with 45% in the tinzaparin group (p = 0.02). In the hip surgery group, 23.2% and 20.8% of warfarin recipients and tinzaparin recipients, respectively, had DVT (no p value reported). While the difference in DVT rates was significant for knee surgery patients, it was not for those undergoing hip surgery.
Overall, the researchers concluded that tinzaparin is at least as effective as warfarin for protecting against venous thrombosis in patients undergoing knee or hip implantation. There were significantly higher frequencies of bleeding and wound hematomas in the tinzaparin group, however, so the benefit of a reduced risk of venous thrombosis may be offset by an increased risk of bleeding.[22]
Fifty-one patients undergoing major elective abdominal surgery were evaluated in a dose-finding study of the efficacy of three tinzaparin dosages for the prevention of DVT.[23] The patients were given a fixed dosage of 2500 IU s.c. daily, a weight-based dosage of 50 IU/kg s.c. daily, or a fixed dosage of 3500 IU s.c. daily. Patients 40 years of age or older who were expected to be hospitalized for at least seven days postoperatively were included. The first dose of tinzaparin was given two hours preoperatively, and therapy was continued for seven days or until discharge. An FUT was performed preoperatively, postoperatively, and on postoperative days 1, 3, 5, and 7. FUT consists of blocking the thyroid gland with sodium iodide and then injecting 125I-labeled fibrinogen one hour after the sodium iodide is administered. A hand-held detector is then used to count the number of sodium iodide crystals at various points on the legs after they have been elevated to empty the veins of blood.[24] Labeled fibrinogen is concentrated in the area of a clot, and higher radioactivity counts are expected for such areas. The test is not considered highly sensitive or specific, however.[2] When the results of FUT in the study were abnormal (a 15% higher count of labeled fibrinogen at three adjacent measuring points compared with the corresponding points on the healthy leg[24]) or clinical signs of DVT were present, ascending phlebography was performed.
Two of 16 patients receiving 2500 IU developed DVT, while no patients in the 50-IU/kg and 3500-IU groups developed a thrombus. No patients developed clinical signs suggestive of PE. One patient died, but an autopsy did not implicate VTE as a contributing factor. There were no significant differences between the groups in operative blood loss, transfusion requirements, or bleeding complications. One major hemorrhage did occur in a patient receiving tinzaparin 3500 IU daily. No significant differences were detected in the rates of nonhemorrhagic adverse effects. A limitation was that 11 of the 51 patients were observed for less than seven days.
Liezorovicz et al.[25] compared two doses of tinzaparin (2500 and 3500 IU s.c. daily) with UFH (5000 units s.c. twice daily) for the prevention of DVT in 1290 patients undergoing abdominal, gynecologic, urologic, or noncardiac thoracic surgery. The patients were age 40 years or older, had an expected anesthesia time of greater than 30 minutes, and had at least one risk factor for thromboembolic disease. Treatment was begun two hours before surgery and was continued for 7-10 days. If prophylaxis was required for more than 10 days, UFH was used to complete the course of therapy. Patients receiving tinzaparin also received one placebo injection per day to blind them and the investigators to the treatment regimen. An FUT was performed daily on days 2 through 7 or 8 except on Sundays and holidays, when the test was performed only if the result had been positive on the previous day. A result was considered positive when a 20% relative increase in the labeled fibrinogen count was detected at one measuring point on the leg compared with the highest adjacent point or the contralateral point and persisted on the following day. An angiogram was performed within 36 hours of a positive FUT result. Once the patient was discharged, a follow-up angiogram was performed one month later to determine if DVT had developed within that time frame. Data were evaluated on an intention-to-treat basis.
At the one-month follow-up, a multivariate analysis showed no significant difference in the development of DVT between the UFH group and the tinzaparin 3500-IU/ day group (p = 0.52). However, significantly more patients in the tinzaparin 2500-IU group had DVT than patients in the UFH group (p = 0.01), suggesting that a dosage of ≤2500 IU/ day is less effective than UFH. No differences were seen in PE, bleeding complications, or death. The rate of positive FUTs was lower in the UFH group than during previous studies. This could indicate that the sample was at a lower risk than expected; one should question whether these same outcomes could be achieved in higher-risk patients.
Tinzaparin 3500 IU/kg s.c. daily was compared with placebo in a multicenter, randomized, double-blind trial evaluating the drug's effectiveness for the prophylaxis of VTE in patients undergoing emergency abdominal surgery.[26] Eighty patients who were 40 years of age or older, had undergone emergency surgery within 48 hours of admission, had had an operation time of more than 30 minutes, and had an estimated hospital stay of five days or more were included. Patients requiring emergency reoperation were excluded. Prophylaxis was started within 24 hours after surgery and continued for five days or until an endpoint was reached, an adverse effect occurred, or the patient was discharged from the hospital. The patients were screened for VTE with a daily FUT and underwent phlebography if the result was positive. Follow-up evaluations were performed on postoperative day 30 either during outpatient visits or by telephone. VTE developed in 7.7% of patients who were assigned to receive tinzaparin and 22% of those assigned to receive placebo. The difference was not significant, but the study was lacking in power; it was stopped early when delivery of labeled fibrinogen was ceased by the supplier.
In an open-label study by Lausen et al.,[27] patients undergoing major elective abdominal or noncardiac thoracic surgery received DVT prophylaxis with tinzaparin 3500 IU s.c. daily beginning two hours preoperatively and with the wearing of graded compression stockings. Prophylaxis was continued for seven days. The patients were then randomized to continue tinzaparin for an additional three weeks or to receive no further prophylaxis. If reoperation was necessary during the study, the day of reoperation was considered day 0, and tinzaparin 3500 IU s.c. daily was restarted and continued for seven days. The patients then resumed treatment according to their original treatment allocation. If DVT was suspected at any point during the study, ascending venography was performed immediately. If no DVT was diagnosed, bilateral venography was performed on day 28 of the study. All venograms were evaluated by two radiologists who were blinded to the patients' treatment regimens. Ten percent of the patients in the 7-day group (6 of 60 patients) and 5.2% of those in the 28-day group (3 of 58 patients) had a confirmed DVT (difference not significant). None of the detected thromboses were located in the proximal leg veins. PE was suspected in two patients but not confirmed. No difference between the groups was seen in postoperative or hemorrhagic complications. This study had less than a 20% power to detect a clinically significant difference in the rate of DVT.
Because of the small number of patients in most of the studies, the design flaws, and the failure to demonstrate superiority of tinzaparin over UFH, tinzaparin cannot be recommended over low-dose subcutaneous UFH for the prevention of VTE after general and abdominal surgery.
Tinzaparin was evaluated for use in the treatment of unstable angina in a pilot study involving 40 patients.[28] This single-blind trial included patients with an episode of recent-onset angina, crescendo angina, or rest angina occurring within 24 hours of randomization. Evidence of coronary artery disease, including electrocardiographic evidence of ischemia, previously documented myocardial infarction, previous evidence of 70% narrowing of a major coronary artery, or a previous positive stress test result, was required as well. Twenty patients received a 5000-unit i.v. bolus of UFH followed by a continuous i.v. infusion of 1000 units/hr adjusted to achieve an aPTT approximately twice the patient's normal value. An additional 20 patients received tinzaparin 3500 IU s.c. twice daily. Both treatments were continued for five days, all patients received aspirin 160 mg p.o. daily and intravenous nitroglycerin, and use of ß-blockers and calcium-channel antagonists was left to the discretion of the treating physician.
The clinical endpoints of the study were recurrent symptomatic angina, acute myocardial infarction, urgent need for revascularization, and bleeding during the five-day study. Nine patients (45%) in the UFH group and 5 (25%) in the tinzaparin group had one of the clinical endpoints (significance not reported). Five of six patients in the UFH group who experienced recurrent angina had an aPTT below the targeted range at the time the pain occurred. No major bleeding occurred in either study group. This preliminary study provides support for larger studies of tinzaparin for the treatment of unstable angina, but tinzaparin cannot yet be recommended for this indication.
The Tinzaparin in Acute Ischemic Stroke Trial (TAIST) was a double-blind, double-dummy, multicenter trial that randomized 1486 patients within 48 hours of an acute ischemic stroke to receive tinzaparin 175 IU/kg s.c. once daily, tinzaparin 100 IU/kg s.c. once daily, or aspirin 300 mg orally once daily.[29] Treatment was then continued for up to 10 days. All patients were between 18 and 90 years of age and had hemorrhage ruled out as a cause of stroke by computed tomography before randomization. The use of nonstudy antiplatelet agents, anticoagulants, and thrombolytics was prohibited. Leg compression stockings were recommended for immobile patients to help prevent VTE, and antiplatelet agents or anticoagulants were recommended after completion of the 10-day study for secondary prevention of stroke.
The primary outcome measure was independence at a six-month follow-up visit, defined as a score of 0, 1, or 2 on the Modified Rankin Scale. Analysis was performed for prespecified subgroups on the basis of sex, age less than 80 years, age 80- 90 years, stroke severity (Scandinavian Neurological Stroke Scale [SNSS] score, <30, 30-40, and >40), time to treatment (<24 and >24 hours), and presumed stroke cause. Secondary six-month outcome measures included proportion of patients achieving a Barthel Index of >90, death, and quality of life as measured by the Medical Outcomes Study 36-Item Short-Form General Health Survey. The percentage of patients achieving independence at three months was another secondary outcome measure. Outcomes assessed at the end of treatment included neurologic deterioration, recurrent stroke, VTE, and death. All patients underwent a second computed-tomography scan on days 8-12 to rule out hemorrhage, unless earlier assessment was clinically indicated. Assessment of safety included occurrence of VTE or hemorrhagic stroke during treatment or within five days after the study.
An intention-to-treat analysis was performed for 1484 participants, while a per protocol analysis included 1150 patients who met all inclusion criteria and received treatment for at least seven days. Six-month follow-up data were available for 1436 patients. Because a disproportionate number of patients with mild stroke were being enrolled, the protocol was amended after approximately 800 patients had been entered to limit recruitment to patients with moderate or severe stroke (SNSS score, <40). No significant differences in characteristics existed between the two groups at baseline. The percentage of patients achieving independence at month 6 in the intention-to-treat analysis was 41.5%, 42.4%, and 42.5% for the tinzaparin 175-IU/kg group, the tinzaparin 100-IU/kg group, and the aspirin group, respectively. There was no significant difference between either tinzaparin group and the aspirin group (odds ratio, 0.96; 95% CI, 0.74-1.24 for tinzaparin 175 IU/kg versus aspirin and odds ratio, 0.99; 95% CI, 0.77-1.28 for tinzaparin 100 IU/kg versus aspirin). The per protocol analysis also failed to show any difference between the tinzaparin groups and the aspirin group. There were no differences in efficacy between tinzaparin and aspirin in the prespecified subgroups. Patients receiving tinzaparin 175 IU/kg had fewer episodes of VTE than those receiving aspirin (0.4% versus 2.6%) (odds ratio, 0.15; 95% CI, 0.03-0.68). However, there was a higher rate of symptomatic intracranial hemorrhage in the tinzaparin 175-IU/kg group than in the aspirin group (1.4% versus 0.2%) (odds ratio, 7.15; 95% CI, 1.10-163). Analysis of a Kaplan-Meier survival plot showed no survival benefit for any one treatment over the others at any time during the six months after treatment. The findings of this study support the current recommendation of the American College of Chest Physicians to avoid full-dose anticoagulation therapy in unselected patients with ischemic stroke.[30]
Several small dose-finding studies have evaluated tinzaparin for the prevention of clots within the extracorporeal circuit during hemodialysis.[31,32,33,34] Typically, tinzaparin was administered as a bolus into the arterial side of the dialyzer at the beginning of the dialysis session,[31,32,33] but one study evaluated the administration of tinzaparin into the venous needle of the patient's fistula.[34] The amount of tinzaparin required to prevent clot formation ranged from 2100 to 5000 IU for most patients and was dependent on the type of dialyzer, the length of the dialysis session, the rate of blood flow, and the patient's weight. The mean one-hour plasma anti-factor Xa activity associated with clinical efficacy was 0.4 unit/mL.[31] The authors of one study noted that the half-life of tinzaparin appeared to increase with increasing doses.[34] This information should be interpreted cautiously, because a detailed pharmacokinetic analysis was not performed.
Am J Health Syst Pharm. 2002;59(15) © 2002 American Society of Health-System Pharmacists
Cite this: Tinzaparin Sodium: A Low-Molecular-Weight Heparin - Medscape - Aug 01, 2002.
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