Anticoagulation Therapy in Patients with Parkinson's Disease

Introduction to DOACs and Parkinson's Disease

The American College of Cardiology recommends that DOACs are preferred over warfarin in patients with atrial fibrillation and Parkinson's disease, except in cases of moderate to severe mitral stenosis or mechanical heart valves 4
The European Heart Journal suggests that apixaban has shown superiority over warfarin in reducing thromboembolic events (1.27% vs 1.60%) and bleeding (2.13% vs 3.09%) 6

The DOACs are primarily influenced by drugs that strongly modulate P-glycoprotein (P-gp) and, to a lesser extent, by strong inhibitors/inducers of CYP3A4, according to the American Heart Association 1, 2
Dabigatran and edoxaban are primarily influenced by P-gp modulation, as stated by the American Heart Association 1, 3
Apixaban and rivaroxaban require avoidance of simultaneous strong inhibitors of CYP3A4 and P-gp, as recommended by the American Heart Association 1, 2

The standard dosages recommended for each DOAC should be used without modification due to antiparkinsonian therapy, as suggested by the American Heart Association 1
Apixaban: 5 mg twice daily (2.5 mg twice daily if two of the following criteria: age ≥80 years, weight ≤60 kg, creatinine ≥1.5 mg/dL), according to the American College of Cardiology 7
Rivaroxaban: 20 mg once daily with the evening meal (15 mg if creatinine clearance 15-49 mL/min), as recommended by the American College of Cardiology 7

Patients with Parkinson's disease have an increased risk of falls, which could theoretically increase the risk of bleeding with any anticoagulant, but the thromboembolic risk generally outweighs the bleeding risk, and anticoagulation remains indicated according to the CHA2DS2-VASc score, as stated by the American College of Cardiology 4, 6
Strategies to reduce the risk of falls (physical therapy, optimization of antiparkinsonian therapy) should be considered rather than avoiding anticoagulation, as suggested by the American College of Cardiology 4

The use of strong inducers of CYP3A4 or P-gp (rifampicin, carbamazepine, phenytoin, St. John's wort) with all DOACs should be avoided, as recommended by the American Heart Association 1, 2, 3
Simultaneous strong inhibitors of CYP3A4 and P-gp (ketoconazole, itraconazole, ritonavir) with apixaban and rivaroxaban should be avoided, or the dose of apixaban should be reduced by 50% if unavoidable, as suggested by the American Heart Association 2, 3

Renal function should be monitored at least annually (more frequently if creatinine clearance <60 mL/min), as all DOACs have renal elimination to some extent, according to the American Heart Association 3
Dabigatran has the highest renal elimination (~80%) and requires particular attention in patients with renal insufficiency, as stated by the American Heart Association 3