Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 3—Defining antithrombotic protocols

Abstract

Objectives:To systematically examine the evidence for use of a specific protocol (dose, frequency, route) of selected antithrombotic drugs, in comparisons to no therapy or to other antithrombotic therapies, to reduce the risk of complications or improve outcomes in dogs and cats at risk for thrombosis. Design: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence (LOE) and quality (Good, Fair, or Poor), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice. Settings: Academic and referral veterinary medical centers. Results: Databases searched included Medline via PubMed and CAB abstracts. Eight different antithrombotic drugs were investigated using a standardized Patient, Intervention, Comparison, Outcome (PICO) question format both for dogs and cats, including aspirin, clopidogrel, warfarin, unfractionated heparin (UFH), dalteparin, enoxaparin, fondaparinux, and rivaroxaban, generating a total of 16 worksheets. Most studies identified were experimental controlled laboratory studies in companion animals (LOE 3) with only four randomized controlled clinical trials in companion animals (LOE 1). Conclusions:Overall, evidence-based recommendations concerning specific protocols could not be formulated for most antithrombotic drugs evaluated, either because of the wide range of dosage reported (eg, aspirin in dogs) or the lack of evidence in the current literature. However, clopidogrel administration in dogs and cats at risk of arterial thrombosis, notably in cats at risk of cardiogenic thromboembolism, is supported by the literature, and specific protocols were recommended. Comparably, aspirin should not be used as a sole antithrombotic in cats with cardiomyopathy. Using the available safety profile information contained in the literature, the panel reached consensus on suggested dosage schemes for most antithrombotics. Significant knowledge gaps were highlighted, which will hopefully drive novel research.

Use of Antithrombotic Drugs in Cats and Dogs

“…Femoral arter greft açıklığı çalışmasında, yüksek doz aspirin (13 mg/kg/gün) protez implantasyonundan 24 saat önce başlanıp deneme süresince devam edildiğinde bir haftalık greft açıklığını iyileştirmiştir. 13 Benzer bir çalışmada, ağızdan yüksek doz aspirin (13,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) Aspirinin antitrombotik etkinliğini tromboz riski taşıyan köpeklerde inceleyen çalışmalar da bulunmaktadır. Mellett ve ark., IMHA'lı köpeklerde tromboprofilaktik amaçla aspirin (0,5 mg/kg/gün), klopidogrel ve aspirin+klopidogrel kombinasyonunun etkinliğini karşılaştırmışlardır.…”

“…Hem pıhtılaşma eğilimine eşlik eden diğer hastalıkların bulunması hem de aspirin ile birlikte kullanılan ilaçlar aspirinin güvenlik profilini etkileyebilir. 7 Köpeklerde aspirinin direkt dozunu karşılaştıran sınırlı sayıda çalışma vardır. 8,13,14 Aspirinin bildirilen doz aralığı çok geniştir, ancak günde 0,5 ile 15 mg/kg arasında kullanıldığında etkili olduğu bildirilmektedir.…”

“…38 Bu çalışmalar dikkate alındığında, kedilerde günlük ağızdan 18,75 mg klopidogrelin etkili ve güvenli olduğu, daha düşük bir dozun seçilmesini gerektirecek bir durum olmadığı belirtilebilir. 7 Randomize klinik bir çalışmada, klopidogrelin kedilerde ATE vakasında aspirine tercih edilmesi gerektiği belirlenmiştir. 21 39 2.…”

Safe and effective anticoagulation in small animals – Is that too much to ask? Long‐awaited first steps

“…This special issue of the Journal features perhaps the most ambitious collaboration on the subject of coagulation in companion animals to date; the ACVECC C onsens u s on the R ational use of A n t ithrombotics i n V eterinary Critical Car e (CURATIVE) attempts to stratify the risk of developing thrombosis in various conditions and establish guidelines for the management of small animals with antithrombotics . Five domains were created for this initiative and they were grouped as follows: (i) Defining populations at risk, (ii) Defining rational therapeutic use, (iii) Defining evidence‐based protocols, (iv) Refining and monitoring antithrombotic therapies, and (v) Discontinuing antithrombotic therapies . Such a wide encompassing scope for reaching consensus is uncommon even in human medicine, where it is more likely to encounter a consensus statement for the use of a single agent in relation to a single condition.…”

“…Guidelines for monitoring clopidogrel responses in dogs were not generated, and this will need to be addressed in the next iteration of these guidelines. In regards to warfarin, Domain 3 recommended against the use of warfarin based on lack of evidence of efficacy and the safety profile . However, if warfarin is used, Domain 4 recommended that monitoring should be carried out with PT INR or to a target 1.5 – 2.0 times the baseline PT.…”