Anticoagulation for secondary prevention of stroke

As an internal medicine resident, I often let my neurology colleagues make decisions about patients’ anticoagulation after a stroke. However, in clinic, I recently had a 70-year old man who had immigrated from Taiwan who had a history of vertebrobasiliar infarcts, Parkinsonism, and coronary artery disease who presented to establish care. He was on clopidogrel. His wife reported that his gait was poor and that he fell at least 5-6 times a week, sometimes hitting his head on the stairs or a table. His medication compliance was poor.

This led me to wonder: what agent should be given for anticoagulation for secondary prevention of stroke?

Options include:

  • aspirin
  • clopidogrel
  • dipyridamole
  • DOACs
  • ticlodipine (don’t use ticlodipine)
  • cilostazol (only studied in Asian populations, more expensive in the US)

Should you choose aspirin or clopidogrel? 

It depends greatly on the kind of stroke (was there major stenosis? Lacunar infarct? A minor ischemic stroke or TIA?) as well as the patient (are they elderly? Have diabetes? Atrial fibrillation?). The combination of aspirin + clopidogrel can be used for the first 90 days for ischemic stroke/TIA, but beyond that, this combination is not superior to aspirin or clopidogrel monotherapy, and causes higher rates of bleeding, as you might expect. CAPRIE showed that clopidogrel was more efficacious than aspirin; however, this was only significant for patients with PAD.

If you choose aspirin, 81 mg or 325 mg? 

This review nicely shows that doses of aspirin used in trials vary widely (from 30 mg to 1300 mg) and that for most patients, using 75-81 mg aspirin is probably the sweet spot to provide adequate protection while minimizing risk of bleeding.

I’ve heard about an aspirin-dipyridamole combination…? 

ESPS-1 and ESPRIT showed that the combination of aspirin + dipyridamole resulted in better outcomes than aspirin alone for large vessel disease. The recent PROFESS trial showed this combo is comparable to clopidogrel monotherapy. The caveat is that patients often have side effects from dipyridamole like nausea and fatigue and are not able to tolerate it.

Are there special considerations for patients with atrial fibrillation? 

There is now evidence suggesting warfarin, apixaban, and dabigatran are also ok in patients with AF who previously had strokes. (Class I, grade B recommendation) . Two birds with one stone!

I ended up switching my patient above to 81 mg aspirin. With his CAD, I felt that it was important for him to be on aspirin, and he didn’t have stents or other disease that would necessitate clopidogrel. Furthermore, with his falls and poor medication compliance, I didn’t feel that an irreversible agent or adding on dipyridamole would provide much benefit.


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