Bayer Pharma AG

Use of antiplatelet therapy in the secondary prevention of acute coronary syndrome

Use of antiplatelet therapy in the secondary prevention of acute coronary syndrome

Patients are potentially at risk of further ischaemic events for considerable periods after an acute coronary syndrome (ACS) event. Currently, standard of care secondary prevention therapy for patients after ACS is a dual antiplatelet regimen comprising acetylsalicylic acid (ASA) plus clopidogrel, prasugrel or ticagrelor. Although guidelines recommend the indefinite use of ASA after an ACS event, the suggested duration of clopidogrel, prasugrel or ticagrelor therapy varies based on patient characteristics. There are several sets of guidelines for the secondary prevention of ACS, including ACCP 2012, ACC/AHA 2013/2014 and ESC 2011/2012.

Risk of recurrent events in acute coronary syndrome

Improvements in the management of patients with acute coronary syndrome (ACS) and the routine use of antiplatelet therapy have resulted in considerable reductions in recurrence rates and mortality. The risk of a recurrent ACS event remains high, however, and there is a need for therapies that can address the residual rate of recurrent major cardiovascular events, which is estimated at 10% per year after an initial event. The addition of an oral anticoagulant to antiplatelet therapy is an approach that can reduce the risk of recurrent events. Risk stratification schemes can be used to translate patient characteristics into the probability of experiencing a recurrent ACS event. The GRACE risk score is one such tool for assessing the mid-term risk of mortality after an ACS event.

Risk factors for bleeding

The benefits of adding an anticoagulant to antiplatelet therapy in the secondary prevention of acute coronary syndrome (ACS) must be balanced against the associated increased risk of bleeding. Risk stratification schemes that can identify patients at increased risk of bleeding events are, therefore, useful in clinical decision making. Several risk stratification schemes for the evaluation of short-term bleeding risks in patients with ACS have been developed, including the CRUSADE score which predicts the risk of in-hospital major bleeding.

Anticoagulants in combination with antiplatelets in the secondary prevention of acute coronary syndrome

The use of secondary prevention measures, including dual antiplatelet therapy, has reduced the rate of myocardial infarction (MI), stroke and death from cardiovascular causes. However, there is also a rationale for combining antiplatelets and anticoagulants in the secondary prevention of acute coronary syndrome (ACS). Novel oral anticoagulants (OACs) have been studied for secondary prevention of ACS, and of these, a low-dose regimen of rivaroxaban was the only novel OAC to show a positive benefit–risk profile. This has led to the approval of rivaroxaban in Europe (but not in the United States [US]) as an adjunct to standard antiplatelet therapy for prevention of atherothrombotic events in selected patients who have experienced a recent ACS event with elevated cardiac biomarkers and who do not have a history of stroke or transient ischaemic attack. In patients who have experienced an ACS event and have an indication for the use of long-term anticoagulation therapy, US and European guidelines recommend the addition of an OAC to existing antiplatelet therapy for limited time periods owing to the elevated risk of bleeding.

Adjunctive Therapy

Other agents recommended for use in secondary prevention of acute coronary syndrome (ACS) include β­blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers; statins, aldosterone antagonists and vorapaxar. Patients who have experienced an ACS event are also advised to make lifestyle changes to reduce their overall cardiovascular risk, such as smoking cessation, regular physical activity, weight reduction and changes in diet.

Investigational strategies

Other antithrombotics such as atopaxar, dabigatran and TAK-442 have been investigated in phase II trials for the secondary prevention of acute coronary syndrome (ACS), but have not progressed to phase III trials because of disappointing results. Apixaban was investigated in a phase III trial but was associated with high rates of bleeding.