Does combination therapy with low-dose aspirin and ticlopidine improve antiplatelet effects compared to monotherapy in patients with cerebral ischemia?
Combination therapy with low-dose aspirin and ticlopidine provides comprehensive inhibition of platelet aggregation pathways but is associated with an increased risk of hemorrhagic complications.
Antiplatelet effects by combination therapy with aspirin and ticlopidine were investigated in comparison with single aspirin or ticlopidine therapy in 62 patients with cerebral thrombosis and transient ischemic attack. The 14, 21 and 27 patients were given orally 300mg aspirin, 200mg ticlopidine and 81mg aspirin with 100mg ticlopidine, respectively. Aspirin inhibited platelet aggregation (PA) to ADP and arachidonic acid (AA) but not to PAF, while ticlopidine inhibited PA to ADP and PAF but not to AA. In contrast, aspirin with ticlopidine inhibited PA to all the 3 agonists. Aspirin decreased plasma thromboxane (TX) B2 but not plasma β-thromboglobulin (βTG) or platelet factor (PF) 4, while ticlopidine decreased βTG and PF 4 but not TXB2. In contrast, aspirin with ticlopidine decreased TXB2 as well as βTG and PF 4. Platelet survival and lysis remained unaltered after aspirin or ticlopidine alone, whereas platelet survival was longer and percent platelet lysis was lower in 4 patients treated with both aspirin and ticlopidine than in 3 non-treated patients. Hemorrhagic complications were observed in 2, 3 and 8 patients treated with aspirin, ticlopidine and both, respectively. The results above indicate that combination therapy with aspirin and ticlopidine is a potential antithrombotic strategy, although further investigaton appeared necessary to determine optimal doses for minimizing hemorrhagic complications.
Uchiyama et al. (1988) studied this question.