While
clopidogrel represented an important therapeutic advance, variations in platelet response and a relatively slow onset of action compromise outcomes in some patients.
Ticagrelor and
prasugrel are more effective than
clopidogrel, although essentially only one large study supports each
drug. Nevertheless, a detailed examination of the evidence reveals several issues that may influence the decision to prescribe
ticagrelor instead of
prasugrel and vice versa. Arguably,
prasugrel could be the preferred strategy in
STEMI, reflecting the drugs' efficacy in
clopidogrel-naïve patients, the most common group in clinical practice. Conversely,
ticagrelor may be a better option than
clopidogrel in
clopidogrel-pretreated patients showing a mortality benefit irrespective of
clopidogrel pre-treatment. The clinical benefits offered by
prasugrel and
ticagrelor need to be offset against the increased cost and we suggest an algorithm for using these new compounds in the primary
percutaneous coronary intervention (PCI) setting. The risk of
bleeding associated with
prasugrel is similar to that of
clopidogrel and
ticagrelor following exclusion of at-risk patients. Nevertheless,
prasugrel may be especially appropriate for
STEMI patients undergoing PCI who are considered to be at high risk of ischaemia. Conversely,
ticagrelor's short half-life, while potentially a limitation during maintenance
therapy, may reduce
bleeding risk if the patient undergoes CABG during the same hospital admission, although confirmatory studies are needed.
CONCLUSION: Future studies also need to address several other outstanding issues, such as the subsequent approach if patients do not undergo PCI, and to overcome limitations in and differences between the primary studies. In particular, head-to-head comparisons need to compare directly the risks and benefits of
ticagrelor and
prasugrel in
STEMI patients. These caveats notwithstanding,
ticagrelor and
prasugrel markedly improve the prognosis for patients with
STEMI.