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The New England Journal of Medicine Jul 2003Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.
METHODS
Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).
RESULTS
During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.
CONCLUSIONS
In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Dalteparin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Secondary Prevention; Survival Analysis; Thromboembolism; Venous Thrombosis; Warfarin
PubMed: 12853587
DOI: 10.1056/NEJMoa025313 -
Medicina (Kaunas, Lithuania) Oct 2023: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs),... (Meta-Analysis)
Meta-Analysis Review
: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. : We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). : It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I 0%). : Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, albeit with no statistical difference. Statistical significance was observed for no major clinically relevant bleeding but not for major bleeding.
Topics: Humans; Dalteparin; Venous Thromboembolism; Anticoagulants; Hemorrhage; Neoplasms
PubMed: 37893585
DOI: 10.3390/medicina59101867 -
Patient Preference and Adherence 2016Weight-based dosing strategy is still challenging due to poor awareness and adherence. It is necessary to let clinicians know of the latest developments in this respect... (Review)
Review
BACKGROUND
Weight-based dosing strategy is still challenging due to poor awareness and adherence. It is necessary to let clinicians know of the latest developments in this respect and the correct circumstances in which weight-based dosing is of clinical relevance.
METHODS
A literature search was conducted using PubMed.
RESULTS
Clinical indications, physiological factors, and types of medication may determine the applicability of weight-based dosing. In some cases, the weight effect may be minimal or the proper dosage can only be determined when weight is combined with other factors. Medications within similar therapeutic or structural class (eg, anticoagulants, antitumor necrosis factor medications, P2Y12-receptor antagonists, and anti-epidermal growth factor receptor antibodies) may exhibit differences in requirements on weight-based dosing. In some cases, weight-based dosing is superior to currently recommended fixed-dose regimen in adult patients (eg, hydrocortisone, vancomycin, linezolid, and aprotinin). On the contrary, fixed dosing is noninferior to or even better than currently recommended weight-based regimen in adult patients in some cases (eg, cyclosporine microemulsion, recombinant activated Factor VII, and epoetin α). Ideal body-weight-based dosing may be superior to the currently recommended total body-weight-based regimen (eg, atracurium and rocuronium). For dosing in pediatrics, whether weight-based dosing is better than body surface-area-based dosing is dependent on the particular medication (eg, methotrexate, prednisone, prednisolone, zidovudine, didanosine, growth hormone, and 13-cis-retinoic acid). Age-based dosing strategy is better than weight-based dosing in some cases (eg, intravenous busulfan and dalteparin). Dosing guided by pharmacogenetic testing did not show pharmacoeconomic advantage over weight-adjusted dosing of 6-mercaptopurine. The common viewpoint (ie, pediatric patients should be dosed on the basis of body weight) is not always correct. Effective weight-based dosing interventions include standardization of weight estimation, documentation and dosing determination, dosing chart, dosing protocol, order set, pharmacist participation, technological information, and educational measures.
CONCLUSION
Although dosing methods are specified in prescribing information for each drug and there are no principal pros and cons to be elaborated, this review of weight-based dosing strategy will enrich the knowledge of medication administration from the perspectives of safety, efficacy, and pharmacoeconomics, and will also provide research opportunities in clinical practice. Clinicians should be familiar with dosage and administration of the medication to be prescribed as well as the latest developments.
PubMed: 27110105
DOI: 10.2147/PPA.S103156 -
RSC Advances Jul 2020Oxytocin (OXT) is a small cyclic peptide that is administered to pregnant women to induce birth in cases where labour is prolonged. It has previously been observed that...
Oxytocin (OXT) is a small cyclic peptide that is administered to pregnant women to induce birth in cases where labour is prolonged. It has previously been observed that patients taking a low molecular weight heparin, dalteparin (DAL), and then prescribed, OXT experienced a swifter labour compared to women given OXT alone. Herein are described the interactions between OXT and a number of heparin-based oligosaccharides; DAL; fondaparinux (FP), which is a synthetic heparin oligosaccharide that represents the predominant antithrombin binding-site, and a family of chemically-derived heparin hexasaccharides. The latter oligosaccharides were chosen as they represent sequences found within the polysaccharide dalteparin. Furthermore, the carbohydrate chemical space was investigated by comparing the interaction between OXT and four chemically derivatived heparin hexasaccharides; I-A (DP6), I-A (DP6-2OH, de-2--sulfated hexasaccharide), I-A (DP6-6OH, de-6--sulfated hexasaccharide) and I-A (DP6-NAc, de--sulfated hexasaccharide). The interactions between the peptide and oligosaccharides were studied using a series of C-H and N-H HSQC NMR experiments, at a range of temperatures. This approach allowed the binding epitopes of the peptide and oligosaccharides to be identified, highlighting that 6-- and -sulfation substituent groups of heparin are important for the interaction between the peptide and carbohydrate. This is an important observation as de--sulfation is a traditional method for decreasing the anticoagulation properties of heparin. Furthermore, low temperature experiments of the OXT : FP complex indicate that hydrogen-bonding is very important for the interaction between the peptide and oligosaccharide.
PubMed: 35519099
DOI: 10.1039/d0ra04204h