Oral Antiplatelet Therapy in ACS | Ten Points to Remember

Wiviott SD, Steg PG.
Clinical Evidence for Oral Antiplatelet Therapy in Acute Coronary Syndromes. Lancet 2015;Mar 11:[Epub ahead of print].

The following are 10 points to remember about oral antiplatelet therapy in acute coronary syndromes (ACS):

  1. Platelet-mediated thrombosis is a major pathophysiological mechanism for ACS, and antiplatelet therapy is an important component in the treatment and prevention of ACS.
  2. Historically, the first antiplatelet agent to show benefit in acute myocardial infarction was aspirin, which blocks the production of thromboxane A2.
  3. The CURE trial established the benefits of addition of the P2Y12 receptor blocker, clopidogrel, to aspirin in patients with non-ST-segment elevation ACS, showing a 20% reduction in the composite outcome of cardiovascular death, myocardial infarction, and stroke, compared with placebo.
  4. However, clopidogrel has substantial limitations in the management of ACS with a modest inhibition of platelet aggregation and a delayed onset and offset of action.
  5. Prasugrel is a second-generation thienopyridine that, similarly to clopidogrel, needs conversion from an inactive form to an active metabolite by use of cytochromes. Unlike clopidogrel, however, prasugrel is rapidly and more wholly metabolized to its active components.
  6. Ticagrelor is a direct-acting P2Y12 antagonist that does not need metabolic activation and is therefore not dependent on cytochrome P450 enzymes. The drug acts rapidly and has more potent and consistent antiplatelet effects than clopidogrel.
  7. Since both prasugrel and ticagrelor have shown superior outcomes to clopidogrel in pivotal trials, these novel agents are now preferred to clopidogrel as a first-line therapy in conjunction with aspirin, for most patients with ACS, as endorsed by both European and US guidelines. It should be noted that prasugrel is only indicated for patients undergoing percutaneous coronary intervention.
  8. Although the novel P2Y12 blockers are more effective than clopidogrel for most patients, they also have limitations: they increase the risk of bleeding; they do not abolish the residual ischemic risk; their cost is substantially higher than clopidogrel (which is now available as a generic drug); and the rapidity of onset, although quicker than clopidogrel, could be insufficient in some settings such as ST-segment elevation myocardial infarction.
  9. Current data suggest that persistent or longer-duration antiplatelet therapy might be warranted in some patients with ACS who have not had complications in the first year and who are not at high risk of bleeding.
  10. Additional data from trials of novel agents, strategies, combinations of drugs, and for duration of therapy continue to emerge and will help define future recommendations.

Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Lipid Metabolism, Interventions and ACS

Keywords: Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Blood Platelets, Cytochrome P-450 Enzyme System, Cytochromes, Thromboxane A2, Aspirin, Myocardial Infarction, Percutaneous Coronary Intervention, Stroke, Thrombosis, Thiophenes

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