Antiplatelet Therapy in the Elderly

Antiplatelet therapy in the elderly: Aspirin, ticlopidine–clopidogrel, and GPIIb/GPIIIa antagonists

Aspirin and Other Cyclooxygenase Inhibitors

Aspirin is widely accepted as a treatment for a variety of disorders and used at three different dosage levels. For example, aspirin can act as an antithrombotic (60- to 325-mg dosage); an analgesic or antipyretic (650-mg dosage), or as an antirheumatic (2- to 6000-mg dosage) agent. This article focuses on the first of these indications, aspirin's antithrombotic role.

Reversible Cyclooxygenase Inhibitors and Dipyridamole

In contrast to aspirin as the example of a nonreversible, covalent modifier of cyclooxygenase, other NSAIDs are competitive, reversible inhibitors of the enzyme and are likely to be less effective and less complete inhibitors of platelet thromboxane A₂ production. These agents have generally been observed to inhibit platelet cyclooxygenase activity by about 75%, which may not be sufficient to affect in vivo platelet aggregation.85, 97 Three NSAIDs (sulfinpyrazone,⁸⁸ indobufen,94, 127 and

Ticlopidine and Clopidogrel

Two thienopyridine drugs with related structures, ticlopidine and clopidogrel, exert antiplatelet effects and have been tested for their antithrombotic activity in clinical settings. Both agents seem to act on the ADP-dependent pathway of platelet activation, and after ingestion, both are apparently modified to active forms that exert a permanent, perhaps covalent, effect on a platelet protein. The effect may be directed toward the ADP receptor itself or a component of the receptor's

Glycoprotein IIb/IIIa Antagonists

Redundant signaling pathways normally function to activate platelets; the effects of aspirin, ticlopidine, and clopidogrel only partially inactivate platelets through thromboxane A₂ and ADP inhibition, respectively. Because the interaction of the platelet surface GPIIb/IIIa receptor (αIIbβ₃ integrin) with fibrinogen leading to platelet aggregation is a major end event in these diverse pathways, much attention has been focused on pharmacologic inhibition of this integrin.

The efficacy and safety

Use of Antiplatelet Agents in the Elderly: Special Considerations

Older age is associated with increased mortality and morbidity after serious vascular events, such as MI and stroke. There are no data suggesting that antiplatelet agents act differently as the patient ages; recommendations derived from large clinical trials with sound methodology are most likely to be applicable to older and younger patients. Analysis of trials in which data are stratified by age serves to confirm this generalization. For example, in the ISIS-2 trial involving 17,187 patients

Summary

Antiplatelet agents including aspirin, dipyridamole, the thienopyridines, and the GPIIb/IIla antagonists have collectively demonstrated their ability to have a significant impact on the incidence of recurrent MIs, strokes, and other vascular ischemic events in the geriatric population. Low-dose aspirin also seems to be effective and safe for the primary prevention of ischemic heart disease in men considered at high risk. There is no evidence that the recommendations from these studies had