After
acute coronary syndrome (ACS), long-term dual antiplatelet
therapy with
acetylsalicylic acid and a P2Y(12) platelet receptor antagonist is the standard of care for
secondary prevention. Despite the introduction of more potent P2Y(12) receptor antagonists, the risk of a recurrent vascular event within 12 months remains at approximately 10%, indicating a need for improved
secondary prevention strategies. A recent phase III trial found that addition of a third
antiplatelet agent,
vorapaxar, in patients with
atherosclerosis might benefit those who have previously experienced a
myocardial infarction, although a trial in patients with ACS found this strategy led to increased
bleeding without significant efficacy improvement. Previously, data from patients with ACS given
vitamin K antagonists in addition to
acetylsalicylic acid demonstrated significant reductions in vascular events, but this was associated with an unacceptable
bleeding risk. As expected, phase II trials of newer oral
anticoagulants in addition to dual antiplatelet
therapy also found increased
bleeding risk, with only the
direct factor Xa inhibitors apixaban and
rivaroxaban continuing to phase III. The phase III trial of full-dose
apixaban was stopped early for safety concerns, because the major
bleeding rates were significantly increased with minimal improvement in efficacy. However, the phase III trial of low-dose
rivaroxaban demonstrated a significantly reduced incidence of recurrent vascular events without an increased risk of fatal
bleeding. In conclusion, these trials underline the potential importance of optimal dose selection in phase III studies and suggest that the long-term use of low-dose anticoagulation, together with dual antiplatelet
therapy, might have a role in
secondary prevention after ACS.