OBJECTIVE: To determine the safety of dabigatran, rivaroxaban, or apixaban with dual antiplatelet therapy in patients with acute coronary syndromes. DATA SOURCES: A literature search of MEDLINE (1946-January 2013) was conducted, using the search terms dabigatran, rivaroxaban, or apixaban in combination with dual antiplatelet therapy. A search of literature citations was conducted to identify additional references. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials involving the use of one of the new anticoagulants with concomitant dual antiplatelet therapy were included in the review. DATA SYNTHESIS: Five randomized controlled trials were reviewed, including 1 trial of dabigatran, 2 trials of rivaroxaban, and 2 trials of apixaban. These studies were conducted in patients with a recent acute coronary syndrome, so most patients were receiving aspirin and clopidogrel as dual antiplatelet therapy in addition to a therapeutic dose of one of the anticoagulants. The 3 Phase 2 dose-ranging trials (1 each of dabigatran, rivaroxaban, and apixaban) found an increasing risk of major and clinically relevant nonmajor bleeding with increasing doses of the anticoagulants. The Phase 3 trial of apixaban was terminated early due to an excess of bleeding events, and the trial of rivaroxaban also found an increased risk of bleeding. CONCLUSIONS: The emerging use of dabigatran, rivaroxaban, and apixaban into clinical practice has introduced additional management options, but also safety concerns when combined with antiplatelet agents. Due to the increased risk of bleeding when combining an anticoagulant with 2 antiplatelet agents, clinicians should monitor and educate patients on avoiding potential complications. The need for continued triple regimens should be periodically reviewed.
OBJECTIVE: To determine the safety of dabigatran, rivaroxaban, or apixaban with dual antiplatelet therapy in patients with acute coronary syndromes. DATA SOURCES: A literature search of MEDLINE (1946-January 2013) was conducted, using the search terms dabigatran, rivaroxaban, or apixaban in combination with dual antiplatelet therapy. A search of literature citations was conducted to identify additional references. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials involving the use of one of the new anticoagulants with concomitant dual antiplatelet therapy were included in the review. DATA SYNTHESIS: Five randomized controlled trials were reviewed, including 1 trial of dabigatran, 2 trials of rivaroxaban, and 2 trials of apixaban. These studies were conducted in patients with a recent acute coronary syndrome, so most patients were receiving aspirin and clopidogrel as dual antiplatelet therapy in addition to a therapeutic dose of one of the anticoagulants. The 3 Phase 2 dose-ranging trials (1 each of dabigatran, rivaroxaban, and apixaban) found an increasing risk of major and clinically relevant nonmajor bleeding with increasing doses of the anticoagulants. The Phase 3 trial of apixaban was terminated early due to an excess of bleeding events, and the trial of rivaroxaban also found an increased risk of bleeding. CONCLUSIONS: The emerging use of dabigatran, rivaroxaban, and apixaban into clinical practice has introduced additional management options, but also safety concerns when combined with antiplatelet agents. Due to the increased risk of bleeding when combining an anticoagulant with 2 antiplatelet agents, clinicians should monitor and educate patients on avoiding potential complications. The need for continued triple regimens should be periodically reviewed.