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 .
European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke
In 1988 , we undertook a r and omized , placebo-controlled , double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid ( ASA ) , modified-release dipyridamole , and the two agents in combination for secondary prevention of ischemic stroke . Patients with prior stroke or transient ischemic attack ( TIA ) were r and omized to treatment with ASA alone ( 50 mg daily ) , modified-release dipyridamole alone ( 400 mg daily ) , the two agents in a combined formulation , or placebo . Primary endpoints were stroke , death , and stroke or death together . TIA and other vascular events were secondary endpoints . Patients were followed on treatment for two years . Data from 6,602 patients were analysed . Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke ( p < or = 0.001 ) and stroke or death combined ( p < 0.01 ) . In pairwise comparisons , stroke risk in comparison to placebo was reduced by 18 % with ASA alone ( p = 0.013 ) ; 16 % with dipyridamole alone ( p = 0.039 ) ; and 37 % with combination therapy ( p < 0.001 ) . Risk of stroke or death was reduced by 13 % with ASA alone ( p = 0.016 ) ; 15 % with dipyridamole alone ( p = 0.015 ) ; and 24 % with the combination ( p < 0.001 ) . The treatment had no statistically significant effect on the death rate alone . Factorial analysis also demonstrated a highly significant effect of ASA ( p < 0.001 ) and dipyridamole ( p < 0.01 ) for preventing TIA . The risk reduction for the combination was 36 % ( p < 0.001 ) in comparison with placebo .  Headache was the most common adverse event , occurring more frequently in dipyridamole-treated patients . All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole . We conclude that ( 1 ) ASA 25 mg twice daily and dipyridamole , in a modified-release form , at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA ; ( 2 ) when co-prescribed the protective effects are additive , the combination being significantly more effective than either agent prescribed singly ; ( 3 ) low-dose ASA does not eliminate the propensity for induced bleeding
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 .