CURATIVE Domaine 2: defining rational therapeutic use Flashcards
Domain 2 sought to establish what drug or drug combination should be administered in venous and arterial thromboembolic disease settings, to define rational therapeutic usage
conclusion
2 strong recommendations, 19 weak recommendations (formulated as suggestions), 9 situations where the evidence was insufficient to make strong recommendations, and 8 situations where no relevant evidence was retrieved to aid guideline generation
MoA and diseases associated with venous thromboembolism (VTE):
MoA and diseases associated with arterial thrombotic complications (ATE):
It is this pathophysiologic rationale that underpins the convention of administration of:
protein‐losing nephropathy
IMHA
thrombi form under low‐shear conditions
- typically fibrin rich
- formation is less dependent on plt
feline cardiomyopathies
thrombi form under high‐shear conditions
- typically platelet rich
- drugs that limit the ability of platelets to activate, aggregate, or adhere may be most effective
anticoagulant drugs in venous thrombosis
antiplatelet agents in arterial thrombosis
however, cell‐based model of hemostasis posits that platelets are integral to hemostasis in vivo, and there is thus a rationale for the use of antiplatelet drugs in venous thrombosis. Experimental data support
this proposition, and antiplatelet drugs reduce the risk of venous thrombosis in people
and visa-verse ATE may benefit from anticoag. (acute coronary syndrome)
- 1 Antiplatelet agents vs anticoagulants for VTE (dogs)
2. 2 Antiplatelet agents vs anticoagulants for VTE (cats)
we suggest that anticoagulants
more effective than antiplatelet agents for VTE
-especially in dirofilariasis
(LOE 3, Good) evaluated thrombus formation in the low‐shear setting of the pulmonary arterial system in dogs with experimentally induced dirofilariasis and demonstrated that neither aspirin or aspirin and dipyridamole protect against PTE in dirofilariasis
no evidence‐based recommendations can be made
we suggest that anticoagulants rather than antiplatelet agents be used for the prevention of VTE in cats.
aspirin has limited, if any, efficacy for prevention of pulmonary thromboembolism due to dirofilariasis in cats
- 3 Antiplatelet agents vs anticoagulants for ATE (dogs)
2. 4 Antiplatelet agents vs anticoagulants for ATE (cats)
EITHER antiplt > anticoag
We suggest that antiplatelet agents
-may be more effective than anticoagulants for the prevention of ATE in dogs
-But we suggest that anticoagulants may also be effective for prevention of ATE in dogs
3 studies (all LOE 3, Good) suggested that anticoagulants were inferior to antiplatelet agents in the setting of provoked arterial thrombosis -multiple studies (19 LOE 3, Good; 1 LOE 3, Fair) also suggest efficacy of anticoagulants for ATE in dogs hw
we recommend that antiplatelet agents be used for the prevention of ATE in cats.
No evidence‐based recommendations can be made regarding the use of anticoagulants for ATE in cats.
- 5 Clopidogrel versus aspirin (dogs)
- 6 Clopidogrel versus aspirin (cats)
Hogan DF, Jacob K, et al. Secondary prevention of cardiogenic ATE in the cat: The double‐blind, randomized, positive‐controlled feline arterial thromboembolism; clopidogrel vs. aspirin trial (FAT CAT). J Vet Cardiol. 2015
insufficient evidence to make strong recommendations
we suggest that clopidogrel may be more effective than aspirin in dogs at risk for ATE.
one experimental study (LOE 3, Fair) suggests clopidogrel is superior to aspirin in a model of coronary artery thrombosis
recommend that clopidogrel be used instead of aspirin in cats at risk for ATE
prospective study in cats (LOE 1, Good) provides evidence that clopidogrel is superior to aspirin for thromboprophylaxis in cats with previous aortic thromboembolic events
no evidence on which to base recommendations regarding the use of aspirin or clopidogrel in cats at risk for VTE
2.7 New antiplatelet agents vs clopid or aspirin (dogs)
MoA: abciximab, lotrafiban MoA: ticagrelor MoA: GPG‐290 MoA: terutroban all been demonstrated to have efficacy against canine platelets
2.8 New antiplatelet drugs vs clopid or aspirin (cats)
insufficient evidence to make recommendations
suggest that both abciximab and ticagrelor appear safe and may be efficacious antiplatelet agents in dogs
agents that antagonize platelet receptors for fibrinogen reversible P2Y12 drug
antagonize collagen-vWF
antagonize thromboxane
insufficient evidence to make recommendations
we suggest that abciximab (antagonise fibrinogen) appears safe and may be efficacious
- 9 UFH versus LMWH (dogs)
2. 10 UFH versus LMWH (cats)
insufficient evidence
suggest that LMWH may be used in preference to UFH because of the positive safety profile of LMWH and more reliable bioavailability
no evidence‐based recommendations can be made suggest that LMWH may be used in preference to UFH because of the documented efficacy of LMWH and the positive safety profile of LMWH
2.11 Direct Xa inhibitors versus UFH (dogs)
There is insufficient evidence to make strong recommendations regarding the use of the direct Xa inhibitors versus UFH in dogs.
2.12 Direct Xa inhibitors versus UFH (cats)
insufficient evidence to make strong recommendations -suggest the direct Xa inhibitors may be used in preference to UFH based on evidence of equivalent efficacy, combined with reliable PK & the ease of oral dosing
studies suggest rivaroxaban is safe and may be efficacious in dogs but evidence comparing the direct Xa inhibitors with UFH in dogs with spontaneous disease is lacking
no evidence‐based recommendations can be made
-suggest that the direct Xa inhibitors can be considered in cats based on reliable PK and a favorable preliminary safety profile
2 pharmacokinetic–pharmacodynamic (PK–PD) studies (LOE 3, Good) suggest that rivaroxaban and apixaban are well tolerated in cats and have reproducible PK–PD parameters
- 13 Direct Xa inhibitors versus LMWH (dogs)
2. 14 Direct Xa inhibitors versus LMWH (cats)
insufficient evidence to make strong recommendations
EITHER suggest that use of either the direct Xa inhibitors or LMWH in dogs is reasonable
1 experimental study (LOE 3, Good) demonstrated that a direct Xa inhibitor had equivalent efficacy to enoxaparin for prevention of arterial and venous thrombosis 7 studies (all LOE 3, Good–Fair) of direct Xa inhibitors suggest these drugs are safe, orally active, and have reliable and reproducible PK–PD parameters
no evidence‐based recommendations can be made –suggest that use of either the direct Xa inhibitors or LMWH in cats is reasonable
- 15 UFH vs warfarin & LMWH vs warfarin (dogs and cats)
2. 16 Direct Xa inhibitors versus warfarin (dogs and cats)
insufficient evidence to make strong recommendations suggest that UFH or LMWH be used in preference
no evidence‐based recommendation
we suggest direct Xa inhibitors be used in preference
direct Xa inhibitors are at least as effective as warfarin and are associated with better safety profiles
- 17 Combination anticoagulant &; antiplatelet therapy for VTE (dogs)
- 18 Combination anticoagulant & antiplatelet therapy for VTE (cats)
we suggest admin of aspirin or clopidogrel in addition to LMWH or UFH therapy may be considered in dogs at high risk of VTE, where the risk of clot formation is felt to outweigh the increased risk of bleeding resulting from combination therapy.
insufficient evidence to make strong recommendations
-suggest that combination therapy may be considered where there is a high risk of thrombosis and the risk of clot formation is felt to outweigh the increased risk of bleeding resulting from combination therapy
- 19 Combination antiplatelet & anticoagulant therapy for ATE (dogs)
- 20 Combination antiplatelet and anticoagulant therapy for ATE (cats)
insufficient evidence to make strong recommendations we suggest that administration of clopidogrel or aspirin with LMWH may be considered in dogs at risk for ATE.
meta‐analysis of 6 trials comprising 29,667 people with acute coronary syndromes suggests use of direct oral anticoagulants in addition to antiplatelet therapy reduced ischemic events
No evidence‐based recommendations
we suggest that administration of clopidogrel in combination with LMWH may be considered in cats at risk for ATE
multimodal therapy compared to antiplatelet therapy alone may decrease recurrence of feline ATE
clopidogrel and for LMWH in cats- first choice of the panel if combination therapy is selected for an individual patient
