Antiplatelet pearls from Harold P Adams

Adams HP. 10 most commonly askedquestions about which antiplatelet agent to prescribe

1. BMJ 2002 324: 71-86 published a meta-analysis including 100,000 patients with antiplatelet agents for prevention of death, MI and stroke in high risk patients. They showed a benefit of antiplatelet drugs in both men and women, in younger and older patients, diabetics and non-diabetics, patients with TIA or stroke.

2. No benefit of aspirin in primary prevention is proved.

3. Aspirin dosing studies favor low dose 81 mg or 325 mg as equal to or superior to higher doses. This was found in a study of patients undergoing endarterectomy in a study published in 1999(Lancet 353:2179-2184) and also in the meta-analysis cited above in (1).

4. The definition of aspirin "failure" is unclear but Adams favors switching to Plavix, Aggrenox, or Ticlid rather than increasing the dose based on the two studies cited above. Early failure is deemed more significant than if someone has an event after several years of aspirin therapy.

5. The relative benefits of newer antiplatelet agents over aspirin (irrespective of side effects) are: ticlid 12-18 % relative reduction, with most of that in the first year(NEJM 1989; 321:501-507). Clopidogrel had a modest benefit especially in patients with peripheral vascular disease (Caprie trial about 8.7 %). Aggrenox resulted in a risk reduction of approximately thirty percent.

6. Adverse effects of ticlodipine include: epigastric pain, diarrhea, allergic skin reactions. Less commonly, events include cholestatic hepatitis, interstitial pulmonary disease, nephritis, and arthritis. Potentially fatal AE's are neutropenia, aplastic anemia, TTP, and HUS (hemolytic -uremic syndrome). Most hematological AE's occur in the first 4 months and when patients begin therapy, blood monitoring should be done every two weeks. TTP occurs in first month, typically, and if platelet count drops not only should ticlid be stopped but plasma exchange can be considered. Clopidogrel also has caused cases of TTP requiring plasma exchange, as well as HUS.

7. Aggrenox and Plavix have never competed in a trial head to head. (old statement see more recent posts)

More pearls from other sources:
Nonwhites have more risk reduction and less AE's (Gorelick et al.) However, the marginal benefit of ticlid seen in prior pivotal study was not replicated in this somewhat smaller study.

TTP occurs in ticlid users at a rate of 1 in 2000-4000. Clopidogrel has a risk analysis similar "to aspirin."

Withdrawal of antiplatelet drugs for procedures remains a concern, especially in those who are older, have a history of stroke or HTN, hyperlipidemia or family history of stroke



Ticlid and Plavix are "thienopyridine derivatives." The be