Compared with aspirin , thienopyridines significantly reduced gastrointestinal adverse effects .
However , thienopyridines increased the odds of skin rash and diarrhoea , ticlopidine more than clopidogrel .
Allocation to ticlopidine , but not clopidogrel , significantly increased the odds of neutropenia .
The thienopyridine derivatives are at least as effective as aspirin in preventing serious vascular events in patients at high risk , and possibly somewhat more so .
However , the size of any additional benefit is uncertain and could be negligible .
Clopidogrel has a more favourable adverse effects profile than ticlopidine and so is the thienopyridine of choice .
BACKGROUND Aspirin is the most widely studied and prescribed antiplatelet agent for preventing serious vascular events , reducing the odds of such events among high vascular risk patients by about a quarter .
Thienopyridine derivatives inhibit platelet activation by a different mechanism and so may be more effective .
OBJECTIVES To determine the effectiveness and safety of thienopyridine derivatives ( ticlopidine and clopidogrel ) versus aspirin for preventing serious vascular events ( stroke , myocardial infa rct ion ( MI ) or vascular death ) in patients at high risk , and specifically in patients with a previous TIA or ischaemic stroke .
Dual Antiplatelet Therapy With Clopidogrel and Aspirin in Symptomatic Carotid Stenosis Evaluated Using Doppler Embolic Signal Detection: The Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) Trial
Background — Evidence for efficacy of dual antiplatelet therapy in stroke is limited . Symptomatic carotid stenosis patients are at high risk of early recurrent stroke . In this group , asymptomatic microembolic signals ( MES ) , detected by transcranial Doppler ultrasound ( TCD ) , are markers of future stroke and transient ischemic attack ( TIA ) risk . They offer a surrogate marker to evaluate antiplatelet therapy , but no multicenter study has evaluated the feasibility of this approach . Methods and Results —Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis ( CARESS ) is a r and omized , double-blind study in subjects with recently symptomatic ≥50 % carotid stenosis . Patients were screened with TCD , and if MES were detected , they were r and omized to clopidogrel and aspirin or aspirin monotherapy . Repeated TCD recordings were made on days 2 and 7 . MES were detected in 110 of 230 patients by online analysis at baseline , of whom 107 were r and omized . Intention-to-treat analysis revealed a significant reduction in the primary end point : 43.8 % of dual-therapy patients were MES positive on day 7 , as compared with 72.7 % of monotherapy patients ( relative risk reduction 39.8 % ; 95 % CI , 13.8 to 58.0 ; P=0.0046 ) . The secondary end point of MES frequency per hour was reduced ( compared with baseline ) by 61.4 % ( 95 % CI , 31.6 to 78.2 ; P=0.0013 ) in the dual-therapy group at day 7 and by 61.6 % ( 95 % CI , 34.9 to 77.4 ; P=0.0005 ) on day 2 . There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis ; 2 additional ipsilateral TIAs occurred before treatment started . MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without ( mean±SD : 24.4±27.7 versus 8.9±11.5 per hour ; P=0.0003 ) . Conclusions —In patients with recently symptomatic carotid stenosis , combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization . Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies
Compared with aspirin , thienopyridines significantly reduced gastrointestinal adverse effects .
However , thienopyridines increased the odds of skin rash and diarrhoea , ticlopidine more than clopidogrel .
Allocation to ticlopidine , but not clopidogrel , significantly increased the odds of neutropenia .
The thienopyridine derivatives are at least as effective as aspirin in preventing serious vascular events in patients at high risk , and possibly somewhat more so .
However , the size of any additional benefit is uncertain and could be negligible .
Clopidogrel has a more favourable adverse effects profile than ticlopidine and so is the thienopyridine of choice .
BACKGROUND Aspirin is the most widely studied and prescribed antiplatelet agent for preventing serious vascular events , reducing the odds of such events among high vascular risk patients by about a quarter .
Thienopyridine derivatives inhibit platelet activation by a different mechanism and so may be more effective .
OBJECTIVES To determine the effectiveness and safety of thienopyridine derivatives ( ticlopidine and clopidogrel ) versus aspirin for preventing serious vascular events ( stroke , myocardial infa rct ion ( MI ) or vascular death ) in patients at high risk , and specifically in patients with a previous TIA or ischaemic stroke .