Balancing Clot Prevention and Bleeding Risk in TIA Therapy

June 1, 2005

I prescribed clopidogrel, 75 mg/d, for an 81-year-old man who had had a suspected transient ischemic attack (TIA); he was already taking aspirin (81 mg/d). Shortly after clopidogrel therapy was started, the patient began to bruise easily.

I prescribed clopidogrel, 75 mg/d, for an 81-year-old man who had had a suspected transient ischemic attack (TIA); he was already taking aspirin (81 mg/d). Shortly after clopidogrel therapy was started, the patient began to bruise easily. Should I reduce the dosage of clopidogrel by having him cut the tablets in half or by initiating every-other-day dosing?

---- R. E. Nordling, MD

Hendersonville, NC

The situation you describe is typical and illustrates the difficulties in balancing the benefits of anticoagulant and antiplatelet therapies with their adverse effects. The most recent American College of Chest Physicians (ACCP) symposium on therapy for ischemic stroke offers helpful treatment paradigms for patients who have had either a noncardioembolic stroke or TIA.1 An antiplatelet agent is strongly recommended (grade 1 evidence) as initial therapy. Possible regimens include:

Aspirin, 50 to 325 mg/d.

A combination of aspirin and extended-release dipyridamole, 25 mg/200 mg bid.

Clopidogrel, 75 mg/d.

Slightly less strong (grade 2) evidence supports the superiority of both the aspirin/extended-release dipyridamole combination (25 mg/200 mg bid) and clopidogrel (75 mg/d) to aspirin alone. However, in patients who are at moderate to high risk for bleeding, use low-dosage aspirin (50 to 100 mg/d).

This patient's initial regimen (aspirin, 81 mg/d) was appropriate. When a TIA occurs after aspirin has been initiated, one can infer from the ACCP recommendations that the next therapy to try is either the combination of aspirin and dipyridamole, 25 mg/200 mg bid, or clopidogrel, 75 mg/d. Clopidogrel alone, for example, is about 10% more effective than aspirin in reducing the risk of ischemic stroke, TIA, and vascular death.2

One can also infer from the ACCP recommendations that one of these alternative regimens should be tried alone before adding it to aspirin--to provide increased efficacy with less risk of bleeding. Clopidogrel in combination with aspirin probably confers still greater efficacy; such regimens are being used with increasing frequency in patients with coronary artery disease (eg, after stent placement).3 However, the increase in efficacy is accompanied by an increased risk of bleeding, as shown by your patient's experience.

Thus, I would suggest changing the patient's regimen to aspirin/dipyridamole combination therapy or clopidogrel alone and monitoring him to determine whether this prevents TIA recurrence. If it does not, then a trial of clopidogrel, 75 mg/d, plus aspirin, 100 mg/d, is not unreasonable but can be expected to result in an increased risk of hemorrhage. No data have been published on the safety or efficacy of half doses or alternate-day dosing of clopidogrel.

---- Ronald N. Rubin, MD

Professor of Medicine

Temple University Medical School

Chief of Clinical Hematology, Department of Medicine

Temple University Hospital

Philadelphia

References:

REFERENCES:


1.

Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

Chest.

2004;126(suppl 3):483S-512S.

2.

CAPRIE Steering Committee. A randomized, blinded trial of clopidogrel versus aspirin in patients at risk of ischemic events.

Lancet.

1996;348:1329-1339.

3.

Popma JJ, Berger P, Ohman EM, et al. Antithrombotic therapy during percutaneous coronary intervention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

Chest.

2004;126(suppl 3):576S-599S.

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