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 .
Effects of coadministration of aspirin or clopidogrel on exercise testing in patients with heart failure receiving angiotensin-converting enzyme inhibitors.
Angiotensin-converting enzyme ( ACE ) inhibitors are effective drugs that have been shown to lower morbidity and mortality in patients with heart failure who have left ventricular systolic dysfunction . 1–3 Patients with congestive heart failure ( CHF ) often have indications for using both ACE inhibitors and antiplatelet agents . Various clinical trials have suggested that an adverse interaction exists from the combined use of aspirin and an ACE inhibitor in patients with CHF , but few studies have measured this effect directly . 3–12 The most compelling evidence of a potential adverse interaction between ACE inhibitors and aspirin stems from the Studies Of Left Ventricular Dysfunction ( SOLVD ) 1,10 and Cooperative New Sc and inavian Enalapril Survival Study II ( CONSENSUS II ) 11 trials . In SOLVD , although enalapril and aspirin when used alone were associated with lower mortality rates , retrospective analysis revealed that the addition of enalapril did not reduce mortality in patients already taking aspirin , and conversely , neither did the addition of aspirin in patients receiving enalapril . In a post hoc analysis of CONSENSUS II , aspirin and enalapril , when utilized alone , were associated with lower mortality rates . However , the relative risk of death at the end of the study was 1.23 ( 95 % confi dence interval [ CI ] 0.99 to 1.53 ) for patients taking aspirin and enalapril , and 0.86 ( 95 % CI 0.63 to 1.16 ) for patients taking enalapril without aspirin ( p 0.047 ) . Guazzi et al , 7 in a small prospect i ve study , measured maximal exercise oxygen uptake ( VO2max ) in patients with CHF , and demonstrated an adverse effect when ACE inhibitors were combined with aspirin , but not with ACE inhibitors alone . Therefore , we hypothesized that exercise duration and VO2max would not be attenuated by clopidogrel compared with aspirin in patients with CHF who are taking ACE inhibitors .  This study was approved by the institutional review board and all participants gave written consent before starting the study . We consecutively enrolled 18 patients with chronic stable CHF at our institution . Patient selection was made through chart review and phone interview of those patients who were likely to meet entry criteria . Inclusion criteria included patients between ages 19 and 80 years who were in stable New York Heart Association class II or III CHF due to ischemic or idiopathic dilated cardiomyopathy , with a documented left ventricular ejection fraction of 40 % within the past year . Patients had to be in sinus rhythm and on maintainance moderate-to-high dose ACE inhibitor therapy for 3 months . Exclusion criteria included a history of chronic lung disease , severe valvular heart disease , moderate-to-severe pulmonary hypertension , or a myocardial infa rct ion or cerebrovascular accident within the preceding 3 months . Patients with chronic stable angina or any other vascular , musculoskeletal , or metabolic condition precluding exercise testing were also excluded .  Antiplatelet therapy other than aspirin or clopidogrel within 4 weeks of the study or warfarin anticoagulation was not allowed . Exercise testing was performed using
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 .