7. 2. Thienopyridines
• Plavix® (Clopidogrel) 75mg 1/day
• Efient® (Prasugrel) 10mg 1/day
• Brilinta® (Ticagrelor) 90mg 1/day
• Efient® and Brilinta® are “newer”
thienopyridines, indication restricted to acute
myocardial infarction in patients undergoing
PCI (alternative to Plavix)
Australian Medicines Handbook EBS presentation 7
8. 2a. Plavix® (Clopidogrel)
• Indications:
- secondary prophylaxis of myocardial
infarction (mandatory: 3 months after stent
implantation for BMS, 1 year for DES)
- secondary prophylaxis of stroke/TIA
(lifelong)
- secondary prophylaxis in PAD (alone or in
combination with aspirine depending on the
clinical situation)
EBS presentation 8
9. 2a. Plavix®
• Contraindications: same as Aspirin
• CAVE: Clopidogrel is a prodrug (activation in
the liver through CYP450, effect depends on
the CYP2C19 genotype genotypes 2-6
show a decreased metabolism to its active
form and thus a decreased efficacy of the
drug itself)
• Plasma peak levels 45 min after intake
• Effect lasts 7-10 days
www.compendium.ch EBS presentation 9
11. 3. Phosphodiesterase inhibitors
• Asasantine®= Dipyridamole 200mg + Aspirin
50mg
• 1 capsule 2/day
• Indications: secondary prophylaxis after stroke in
patients who were already taking Aspirin
(alternative to Plavix®)
• Inhibits uptake of adenosine in platelets and
endothelial cells
• Duration of effect and contraindications similar to
Aspirin
www.compendium.ch EBS presentation 11
12. 4. GP IIb/IIIa inhibitors
www.integrilin.com EBS presentation 12
13. 4. GP IIb/IIIa inhibitors
• Newer class of molecules
• Only used as infusion before, during and max 72h
after PCI in acute coronary syndrome (mostly STEMI)
• Reopro® (Abciximab)
• Aggrastat® (Tirofiban)
• Integrilin® (Ebtifibatide)
• Platelet function returns to normal 24-48h after the
end of the infusion for Reopro®, a bit faster for
Aggrastat® and Integrilin®
• High risk of bleeding, especially since used
concomitantly to Aspirin and Plavix!
Australian Medicines handbook EBS presentation 13
14. Aspirin, Plavix® and neurosurgery
• We cannot REVERSE their action, since it is
irreversible (but we can administer platelet
transfusions in “emergency” situations)
• When Aspirin is for primary prophylaxis, we
can stop it 5-7 days prior to surgery
• Heparin and LMWH do NOT substitute the
action of antiplatelet drugs
Korte et al, GTH recommandations on peri- EBS presentation 14
interventional antiplatelet therapy, Thrombosis
15. Sometimes it gets complicated…
• Death/MI/stent-thrombosis occurs in 5-30% of patients if
surgery performed within 6 weeks of BMS and at least 5%
of patients if surgery performed within 12 mths after DES,
if dual antiplatelet therapy is ceased
• Whenever possible, defer surgery until dual treatment is
no longer mandatory (i.e. 3 months after PCI for BMS, 1
year for DES)
• If not possible: cease dual antiaggregation in
neurosurgery and contact cardiologist. Patient should be
in a center where PCI is available
• small series have studied a “bridging” therapy with GP
IIb/IIIa antagonists prior to surgery but currently no
evidence
• Recommence antiplatelet therapy ASAP after surgery
Guidelines for the use of antiplatelet therapy EBS presentation 15
in patients with coronary stents undergoing
16. Recommendations
Korte et al, GTH recommandations on peri- EBS presentation 16
interventional antiplatelet therapy, Thrombosis
17. “Reversal” in Intracranial hemorrhage
• Spontaneous ICH: administration of platelets in
patients under Aspirin, Plavix® or dual therapy.
• Traumatic ICH: no current guidelines- no
recommendations based on studies.
• Desmopressin (DDAVP®): increases FVIII and
vWF activity
• rF VIIa (Novoseven®): “reversal” of antiplatelet
drugs in healthy volunteers. CAVE: costs!
Campbell et al, Emergency reversal of EBS presentation 17
antiplatelet agents in patients presenting with
18. Recommendations
• Patients with ICH on Aspirin: give 5 platelet
concentrate units upon admission
• Patients with ICH on Plavix®/dual and small
hemorrhages: give 10 units upon admission
• Patients with severe ICH on Plavix®: 10 units
upon admission in association with 0.3mcg/kg
BW DDAVP® iv initially. Platelet transfusions are
subsequently performed every 12h for 48h.
• CAVE: hyponatremia risk with Desmopressin!
Campbell et al, Emergency reversal of EBS presentation 18
antiplatelet agents in patients presenting with
Here is a summary of the antiplatelets drugs which are available on the market at present; I will shortly describe each class and then focus on the most commonly used agents, which are aspirin and plavix
First of all, Aspirin: the figure shows its mechanism of action. It inhibits COX-1 in an irreversible way, thus preventing the production of TXA2 and the activation of platelets
It is very difficult to list all the precise aspirin indications, but I summarized the most important ones
And here the contraindications, which are quite obvious. It is very important to point out that the action of aspirin lasts until new platelets are produced, i.e. 7-10 days
Now, let’s move to another family of molecules: thienopyridines, which block the binding of ADP to its receptor on the platelet surface, thus inhibiting the activation of the GPIIb/IIIa receptor, necessary to platelet activation, This action is irreversible for Plavix.
Here are some other, newer thienopyridines. They are more expensive and so their indication is restricted to patients after MI undergoing Percutaneous coronary intervention, as an alternative to Plavix.
Since Plavix is still the most commonly used thienopyridine, I will focus on it. First of all, here is a summary of the indications (which, as for aspirin, are complex and numerous)Bms bare metal stent. Des: drug eluting stent
Like Aspirin, the effect of Plavix is irreversible and lasts for 7-10 days, which corresponds to the life span of platelets
Now, let’s move to the phosphodiesterase inhibitors, and the only member of this class is dipyridamole, which is used as Asasantin in combination with aspirin. It inhibits the uptake of adenosin in platelets and endothelial cells
The only indication at present is secondary prophylaxis after stroke in patients who were already taking aspirine. Nevertheless, Plavix is a more commonly used drug for this indication
Just two slides for the last but newer class of antiaggregants, the glycoprotein Iib/IIIa inhibitors, which block the GP Iib/IIIA receptor, thus inhibiting platelet aggregation
Their indication is restricted to the peri-Percutaneous coronary intervention period, and they are used in combination with aspirine and plavix to achieve a higher grade of platelet inactivation. Obviously, the bleeding risk in these patients is extremely high.
Now, I would like to move to how, as neurosurgeons, we can handle patients under antiplatelet drugs… first of all, we must remember that we cannot reverse their action, and that heparin and LMWH are not substitutes. We should stop aspirin or plavix 5-7 days prior to surgery, if their indication is not strict.
Sometimes, though, it is not so easy: in patients after MI and Percutaneous coronary intervention ceasing antiplatelet drugs carries a very high risk of morbidity and mortality. We should defer surgery in patients under dual antiaggregation, whenever possible. Otherwise, we have to stop aspirin and plavix and resume them asap after surgery. Administration of GPIIb/IIIa for bridging until surgery is currently under trial, but at present there is no sufficient evidence. What we can and must do, is contact the cardiologist and transfer the patient in a center with a PCI facility.
And here are the recommendations published in thrombosis and hemostasis 2011. I highlighted in black the part that affects us.
In the emergency setting of ICH, evidence is lacking regarding when and how to “reverse” antiplatelet drugs. Nevertheless, platelets are commonly administered especially in patients on Plavix or dual antiaggregation, who are at higher risk of bleeding, and especially in spontaneous ICH. There are no current guidelines for reversal of antiplatelet drugs in traumatic ICH. Desmopressin is a synthetic derivate of the antidiuretic hormone ADH and it is known to increase FVIII and vWF thus favouring platelet aggregation. Recombinant factor vIIA has not been tested in ICH so far and its cost limits its use.
The only literature review I found recommends giving 5 units platelets to patients with ICH who are on Aspirin, and 10 units to patients on plavix or dual therapy and small ICH. Patients with severe ICH on Plavix should receive 10 units platelets AND desmopressin upon admission, and platelets should be administered every 12h for 48h. We must remember that desmopressin administration carries a high risk of hyponatremia and thus we must monitor the sodium levels strictly. Also, we should contact an hematologist prior to desmopressin administration.
