A 65-year-old man presents to the emergency department for evaluation of left arm and leg weakness. He was walking in the park about 45 minutes prior to arrival when the patient stumbled and fell. He had sudden weakness in his left leg and was unable to grasp a handrail with his left hand. He currently takes no medications. His temperature is 98.0°F (36.6°C), blood pressure is 128/89 mmHg, pulse is 130/min, and respirations are 18/min. On exam, he has 3/5 strength in the left upper and lower extremities and a left-sided facial droop. A non-contrast CT scan of the head is performed, which suggests parenchymal ischemia in the distribution of the right middle cerebral artery. An ECG is performed, as shown in Figure A. He is given intravenous alteplase with rapid improvement in his strength deficits and facial asymmetry. Which of the following is the most appropriate long-term therapy for secondary stroke prevention for this patient?
Aspirin
Rivaroxaban
Cardiac pacemaker
Atorvastatin
Rivaroxaban
This patient presents with acute onset unilateral left-sided weakness secondary to an ischemic stroke in the right MCA in the setting of an irregularly irregular rhythm without P waves (suggesting that he had an embolic stroke secondary to atrial fibrillation). First-line primary and secondary stroke prevention in patients with atrial fibrillation involves long term anticoagulation with a direct oral anticoagulant (DOAC) such as rivaroxaban.

Atrial fibrillation is caused by uncoordinated atrial contractions, typically due to atrial enlargement, inflammation, or infiltrative disease. Atrial fibrillation can lead to the formation of a thrombus, typically in the left atrial appendage, which can embolize to the brain and lead to an ischemic stroke. For this reason, there is a low threshold to start patients on long term anticoagulation for both primary and secondary stroke prevention (risk stratification is done with the CHA2DS2-VASc score, which considers several cardiovascular risk factors, age, sex, and diabetes). First-line long term anticoagulation is a DOAC medication such as apixaban, dabigatran, rivaroxaban, or edoxaban. Delayed initiation of anticoagulation is recommended at 4-14 days after a stroke, due to the interim risk of hemorrhagic conversion. Further management of atrial fibrillation includes a rate control agent such as a beta blocker or a calcium channel blocker.

JS Alpert reviews the latest American Heart Association/American College of Cardiology guidelines regarding atrial fibrillation. The article reports that for stroke prevention in atrial fibrillation, DOACs are first-line compared to warfarin due to a decreased risk for bleeding with DOACs. In patients with moderate to severe mitral stenosis or a mechanical heart valve, warfarin is the preferred agent.

Figure/Illustration A shows an ECG with an irregularly irregular rhythm (highlighted by the spacing of blue arrows) and no discernable P waves before QRS complexes, which is characteristic of atrial fibrillation.

Incorrect Answers:
Answer A: Aspirin exerts antiplatelet adhesion effects through the inhibition of cyclooxygenase. Patients with atrial fibrillation who are at low risk for stroke (CHA2DS2-VASc score of < 1) can use aspirin monotherapy for stroke prophylaxis. This patient presented after a stroke and will require long term anticoagulation, not anti-platelet monotherapy for stroke prevention.

Answer B: Atorvastatin is an HMG-CoA reductase inhibitor, which works to lower LDL cholesterol and triglycerides, and increase HDL cholesterol. It is most useful in secondary stroke prevention in patients who have suffered a thrombotic or thromboembolic stroke secondary to atherosclerosis. This patient may have atherosclerosis and could benefit from statin therapy; however, anticoagulation for his underlying atrial fibrillation is the highest priority.

Answer C: A cardiac pacemaker is indicated in a large variety of cardiac conditions that primarily involve sinus node dysfunction or high-grade atrioventricular block. Atrial fibrillation does not typically require a pacemaker, as it is typically managed with rate control agents such as beta-blockers, calcium channel blockers, digoxin, or with electrical cardioversion. Rate control will not lower the stroke risk, and thus long-term anticoagulation is required.

Answer E: Warfarin has historically been a mainstay anticoagulant for stroke prevention in atrial fibrillation. DOACs are non-inferior to warfarin, and have a lower risk of bleeding. Note, only the initiation of warfarin requires a heparin bridge to mitigate the transient protein C deficiency that results in a temporary hypercoagulable state (often presenting as warfarin skin necrosis).

Bullet Summary:
For patients who present with an ischemic stroke secondary to a cardiac embolus from atrial fibrillation, first-line long term anticoagulation is a direct oral anticoagulant (apixaban, dabigatran, rivaroxaban, or edoxaban).