Abstract
The platelet P2Y12 antagonists are widely used, usually in combination with aspirin, to prevent atherothrombotic events in patients with acute coronary syndromes, during PCI and after placement of arterial stents.
Inhibition by clopidogrel or prasugrel lasts for the lifetime of the affected platelets and platelet haemostatic function gradually recovers after stopping the drug, as new unaffected platelets are formed.
The optimal durations for dual antiplatelet therapy are prescribed by clinical guidelines. Continuation beyond the recommended duration is associated with an increased mortality, mainly associated with major bleeding.
Fear of a “rebound” of prothrombotic platelet activity on stopping the drug has provoked much discussion and many studies. However, review of the available literature reveals no evidence for production of hyper-reactive platelets after cessation of clopidogrel in stable patients. Any increase in acute coronary and other vascular events after stopping seems most likely therefore to be due to premature discontinuation or disruption of treatment while thrombotic risk is still high. No difference in rebound was found with the newer P2Y12 inhibitors, although ticagrelor and prasugrel are more potent platelet inhibitors than clopidogrel.
Recent RCTs confirm it is safe to stop the thienopyridine and continue with aspirin alone in most patients after the duration of treatment recommended by the guidelines. Decisions on when to stop therapy in individuals, however, remain challenging and there is a growing rationale for platelet testing to assist clinical judgement in certain situations such as patients stopping DAPT before surgery or in individuals at highest bleeding or thrombotic risk.
Inhibition by clopidogrel or prasugrel lasts for the lifetime of the affected platelets and platelet haemostatic function gradually recovers after stopping the drug, as new unaffected platelets are formed.
The optimal durations for dual antiplatelet therapy are prescribed by clinical guidelines. Continuation beyond the recommended duration is associated with an increased mortality, mainly associated with major bleeding.
Fear of a “rebound” of prothrombotic platelet activity on stopping the drug has provoked much discussion and many studies. However, review of the available literature reveals no evidence for production of hyper-reactive platelets after cessation of clopidogrel in stable patients. Any increase in acute coronary and other vascular events after stopping seems most likely therefore to be due to premature discontinuation or disruption of treatment while thrombotic risk is still high. No difference in rebound was found with the newer P2Y12 inhibitors, although ticagrelor and prasugrel are more potent platelet inhibitors than clopidogrel.
Recent RCTs confirm it is safe to stop the thienopyridine and continue with aspirin alone in most patients after the duration of treatment recommended by the guidelines. Decisions on when to stop therapy in individuals, however, remain challenging and there is a growing rationale for platelet testing to assist clinical judgement in certain situations such as patients stopping DAPT before surgery or in individuals at highest bleeding or thrombotic risk.
| Original language | English |
|---|---|
| Pages (from-to) | 141-150 |
| Number of pages | 10 |
| Journal | Therapeutic Advances in Drug Safety |
| Volume | 6 |
| Issue number | 4 |
| Early online date | 1 Jun 2015 |
| DOIs | |
| Publication status | Published - Aug 2015 |
Bibliographical note
FundingIsobel Ford is an employee of the University of Aberdeen. The research for the writing of this review received no specific grant from any funding agency in the public, commercial, or not-forprofit
sectors
Keywords
- antiplatelet therapy
- cessation
- clopidogrel
- P2Y12 inhibitors
- platelet activation
- rebound