Apixaban versus antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation. A randomised phase II clinical trial.

- Intracerebral haemorrhage, documented with CT or MRI, during treatment with anticoagulation (VKA, any direct thrombin inhibitor, any factor Xa inhibitor, or (low-molecular-weight) heparin at a therapeutic dose).

- The haemorrhage has occurred between 7 and 90 days before randomization.

- Diagnosis of (paroxysmal) non-valvular AF, documented on electrocardiography.

- A CHA2DS2VASc score ≥ 3.

- Score on the modified Rankin scale (mRS) ≤4.

- Equipoise regarding the optimal medical treatment for the prevention of stroke. The clinical equipoise should be self-reported by the attending neurologist after reviewing all relevant information available for the individual patient.

- Age ≥ 18 years.

- Written informed consent by the patient or by a legal representative

- Conditions other than atrial fibrillation for which the patient requires long-term anticoagulation.

- A different clinical indication for the use of an APD, such as clopidogrel for recent coronary stenting.

- Rheumatic mitral valve disease, a prosthetic heart valve, or mitral valve repair.

- Serious bleeding event in the previous 6 months, except for intracerebral haemorrhage.

- High risk of bleeding (e.g., active peptic ulcer disease, a platelet count of <100,000.mL-1 or haemoglobin level of <6.206 mMol.L-1, ischemic stroke in the previous 7 days (patients are eligible thereafter), documented haemorrhagic tendencies, or blood dyscrasias).

- Current alcohol or drug abuse.

- Life expectancy of less than 1 year.

- Severe renal insufficiency (a serum creatinine level of more than 221 μmol per liter or a calculated creatinine clearance of <25 ml per minute).

- Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range or a total bilirubin more than 1.5 times the upper limit of the normal range, unless an benign causative factor, other than moderate or severe liver disease, (e.g. Gilbert’s syndrome) is known or identified.

- Allergy to apixaban.

- Use of strong cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibitors (e.g. systemic azole-antimycotics as ketoconazole or HIV protease inhibitors such as ritonavir).

- Pregnancy or breastfeeding.

- Women of childbearing potential: any woman who has begun menstruation and is not menopausal or otherwise permanently unable to conceive. A post-menopausal woman is defined as a woman who is over the age of 45 and has not had a menstrual period for at least 12 months.