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Antiplatelet drugs and Neurosurgery

David Bervini

15 Nov 2012

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Antiplatelet drugs

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1. Aspirin

Gasparyan, A. Y. et al. J Am Coll Cardiol 2008;51:1829-1843

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1.Aspirin (Acetylsalicylic acid)

• Mechanism of action: inhibition of Cyclooxygenase-1 irreversible inhibition of platelet aggregation

• Dosage 75-325 mg once daily• Indications:

– Primary prophylaxis against stroke, TIA, myocardial infarction and thromboembolic disorders (e.g. atrial fibrillation with low CHADS2 score) and in patients with renal failure, HIV,…

– Secondary prophylaxis after stroke, myocardial infarction, in peripheral arterial disease (PAD) and dialysis patients (lifelong)

www.compendium.ch

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1. Aspirin

• Contraindications:

- Allergy

- Hemorragic diathesis (especially platelet count < 50 G/L)

- Severe liver failure

- “Fresh” peptic ulcer

• Maximal plasma concentration 0.3-3h after intake

• The action lasts until new platelets are synthesized: 7-10 days

www.compendium.ch

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2. Thienopyridines

Harvey, R; Champe, P “Lippincott illustrated reviews: Pharmacology”, 4th edition. LWW: 2009.

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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

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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)

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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

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3. Phosphodiesterase inhibitors

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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

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4. GP IIb/IIIa inhibitors

www.integrilin.com

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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

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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-interventional antiplatelet therapy, Thrombosis and Hemostasis, 105.5/2011

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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 in patients with coronary stents undergoing non-cardiac surgery, The Cardiac Society of Australia and NZ, 2009

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Recommendations

Korte et al, GTH recommandations on peri-interventional antiplatelet therapy, Thrombosis and Hemostasis, 105.5/2011

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“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 antiplatelet agents in patients presenting with intracranial hemorrhage: A clinical review, World Neurosurgery, Vol 74, 08/2010, 279-285

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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 antiplatelet agents in patients presenting with intracranial hemorrhage: A clinical review, World Neurosurgery, Vol 74, 08/2010, 279-285

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