Ibrutinib- concurrent antiplatelets and anticoagulants

Antiplatelet management with ibrutinib

 1. Patients should be cautioned against the use of NSAIDs, fish oils, vitamin E, and inadvertent use of aspirin-containing products. 

2. Consider stopping aspirin in patients on ibrutinib who have low or moderate cardiovascular risk. 

3. For patients at high cardiovascular risk that may compromise their survival, including those with recent myocardial infarction (MI) or stroke, consider ibrutinib plus 81 mg of aspirin. We recommend against higher doses of aspirin in light of data suggesting increased bleeding with no benefit [50]. 

4. For patients with recent bare metal cardiac stent placement, consider delaying or withholding ibrutinib while on DAPT. After the required DAPT period, consider ibrutinib plus 81 mg of aspirin. 

5. For patients with recent drug-eluting stent placement, consider replacing ibrutinib with an alternative treatment strategy given the extended duration of recommended DAPT. 

6. Some authors initially trial ibrutinib at a lower dose (280 mg day
1 ) in patients on other antiplatelet agents or anticoagulants and slowly increase to treatment dose if bleeding does not occur. This dose-escalation strategy is based on in vitro data suggesting that the antiplatelet effects of ibrutinib are dose-dependent [18,19]. It is important to note, however, that there are no clinical data to endorse this practical strategy, and that studies have shown significant bleeding rates at both lower (420 mg day
1 ) [7,10–12] and higher (560 mg day
1 ) [8,9] doses of ibrutinib.

For patients potentially requiring ibrutinib concurrent with anticoagulation we propose the following:

1. For patients who require short courses of anticoagulation for a provoked VTE, consider postponing ibrutinib therapy if feasible and using an alternative agent in the interim. If overlapping with ibrutinib, we recommend using a DOAC such as apixaban given the smaller bleeding rates as compared with warfarin [55]. Avoid concurrent antiplatelet therapy unless there is a strong indication. 

2. For patients requiring extended anticoagulation for unprovoked VTE, consider using another agent or using a DOAC such as apixaban, again avoiding other antiplatelet agents unless strongly indicated. Half-dose apixaban can be safely used after 6 months of therapy and is likely to decrease bleeding risk [56]. 

3. Patients should be cautioned against the use of NSAIDs, fish oils and vitamin E, and inadvertent use of aspirin-containing products. 

4. Some authors initially trial ibrutinib at a lower dose (280 mg day
1 ) in patients on other antiplatelet or anticoagulants and slowly increase to treatment dose if bleeding does not occur. 

Management of elective and unplanned procedures 

Ibrutinib should be withheld for 7 days prior to major procedures as the antiplatelet effects of ibrutinib have been shown to be fully reversed after a week off therapy [19,20]. Ibrutinib can be restarted 1–3 days postoperatively [11,13]. The risk of bleeding during urgent, unplanned procedures can be mitigated with platelet transfusion to achieve 50% fresh platelets.

Patients on ibrutinib who develop atrial fibrillation.

 1. If patents have a high bleeding risk, including mandated use of DAPT, or a history of significant bleeding, consider using an alternative agent to ibrutinib and managing their atrial fibrillation per conventional guidelines.

 2. In patients who are to continue ibrutinib and have a sufficiently elevated stroke risk per standard models (CHA2DS2VASc score of 2 or greater), we recommend a DOAC be used as opposed to a vitamin K antagonist, without additional antiplatelet agents. We at our institution, as well as our colleagues across the USA, have successfully combined ibrutinib with DOACs in patients who develop atrial fibrillation. As discussed above, in this setting we use a dose-escalation strategy for ibrutinib (often starting at 280 mg/day), slowly increasing to standard treatment doses if bleeding does not occur. 

3. For patients at low risk of cardioembolic stroke (CHA2DS2VASc score of zero), we recommend continuing ibrutinib alone without the addition of anticoagulation or alternative antiplatelet agents.

 4. For patients at intermediate risk of cardioembolic stroke (CHA2DS2VASc score of 1), we recommend continuing ibrutinib alone or ibrutinib plus aspirin, based on patient and physician preferences and consideration of individualized risks. 

5. In patients requiring DAPT (e.g. those with recent coronary artery stenting) who develop atrial fibrillation and have a high risk of stroke, we recommend discontinuing ibrutinib because of the significant risk of bleeding and switching to alternative therapy for lymphoproliferative disorders. 

6. In patients with an indication for aspirin for cardioprotective benefit who develop atrial fibrillation with elevated stroke risk (CHA2DS2VASc score of 2 or greater), we recommend treating with a DOAC plus ibrutinib alone and stopping other antiplatelet agents. This is based on prospective data showing that single antiplatelet therapy with anticoagulation had equal efficacy and superior safety to dual antiplatelet therapy with anticoagulation.

Pain meds on ibrutinib

Acceptable analgesics with no major adverse platelet effects include acetaminophen and opioids, as well as anti-epileptic drugs such as gabapentin, pregabalin and tricyclic antidepressants. COX2 inhibitors ok

Reference: Ibrutinib associated bleeding