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Current oral antiplatelet agents to prevent atherothrombosis
1Stroke Unit, Royal Perth Hospital, Perth, Australia. gjhankey@cyllene.uwa.edu.au
Insights
Aspirin and ADP receptor antagonists reduce vascular events in high-risk patients. ADP antagonists offer greater efficacy and fewer gastrointestinal bleeds than aspirin, but with some side effects.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Thrombosis Research
Background:
- Aspirin inhibits platelet activation and reduces vascular events in symptomatic atherosclerosis.
- High-risk vascular patients often experience recurrent atherothrombotic events.
Purpose of the Study:
- To compare the efficacy and safety of antiplatelet agents in high-risk vascular patients.
- To evaluate adenosine diphosphate (ADP) receptor antagonists, aspirin, and combination therapies.
Main Methods:
- Systematic review and meta-analysis of antiplatelet therapies.
- Comparison of aspirin, clopidogrel, ticlopidine, dipyridamole, and combination regimens.
Main Results:
- ADP receptor antagonists (clopidogrel, ticlopidine) are more effective than aspirin, reducing vascular events by an additional 10%.
- ADP antagonists significantly reduce gastrointestinal hemorrhage risk by 30% compared to aspirin.
- Ticlopidine has higher rates of rash, diarrhea, and neutropenia; clopidogrel has lower rates of these side effects.
Conclusions:
- ADP receptor antagonists represent a more effective antiplatelet strategy than aspirin for high-risk vascular patients.
- Combination therapy with low-dose aspirin and high-dose dipyridamole shows promise, particularly for stroke prevention.
- Aspirin plus clopidogrel is a safer and effective option for coronary stenting and other high-risk atherothrombotic conditions.
Abstract:
Aspirin inhibits platelet activation by irreversibly inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of serious vascular events (stroke, myocardial infarction or vascular death) by about one quarter in a range of patients with symptomatic atherosclerosis at high risk of a subsequent event. The adenosine diphosphate (ADP) receptor antagonists clopidogrel and ticlopidine are significantly more effective than aspirin in high-risk vascular patients, further reducing the odds of serious vascular events by about 10% (95% CI 2-19%) over the benefit provided by aspirin. The ADP receptor antagonists are also associated with a significant 30% reduction in the odds of gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59-0.86). Ticlopidine increases the odds of skin rash and of diarrhoea by more than twofold compared with aspirin, whereas clopidogrel is associated with a one-third increase in the odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia compared with aspirin. There is no clear evidence as yet for the benefit of dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet agents in atherothrombotic patients. Amongst high vascular risk patients, the combination of low-dose aspirin and high-dose dipyridamole is associated with about a 10% (95% CI 0-20%) reduction in the odds of a serious vascular event. Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of this estimate continues to be investigated in an ongoing study of patients with transient ischaemic attack and stroke. The combined use of aspirin and ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin has been shown to be safer than aspirin and ticlopidine in coronary stenting, and is now under long-term evaluation in unstable angina, and other conditions in which patients are at high risk of atherothrombotic events.