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New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis.

Oldgren J, Wallentin L, Alexander JH, James S, Jönelid B, Steg G, Sundström J - Eur. Heart J. (2013)

Bottom Line: We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions.When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09).Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden. jonas.oldgren@ucr.uu.se

ABSTRACT

Background: Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting.

Methods and results: All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.

Conclusion: In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.

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EHT049F1: Flow chart of literature review.

Mentions: The search strategy identified 168 potential articles, of which 13 were read in full text (Figure 1). Among these, seven phase II and III studies with new oral anticoagulants after a recent ACS were identified and included in the analysis. Data from all seven studies (ESTEEM,11 REDEEM,14 RUBY-1,15 APPRAISE-112 and APPRAISE-2,16 ATLAS ACS-TIMI 46,13 and ATLAS ACS 2–TIMI 5117) rendered a study base of 30 866 patients with a recent ACSs, 4135 (13.4%) in the single antiplatelet therapy group and 26 731 (86.6%) in the dual antiplatelet therapy group. Details of these studies are outlined in Table 1 and Supplementary material online, Table S1.Figure 1


New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis.

Oldgren J, Wallentin L, Alexander JH, James S, Jönelid B, Steg G, Sundström J - Eur. Heart J. (2013)

Flow chart of literature review.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675388&req=5

EHT049F1: Flow chart of literature review.
Mentions: The search strategy identified 168 potential articles, of which 13 were read in full text (Figure 1). Among these, seven phase II and III studies with new oral anticoagulants after a recent ACS were identified and included in the analysis. Data from all seven studies (ESTEEM,11 REDEEM,14 RUBY-1,15 APPRAISE-112 and APPRAISE-2,16 ATLAS ACS-TIMI 46,13 and ATLAS ACS 2–TIMI 5117) rendered a study base of 30 866 patients with a recent ACSs, 4135 (13.4%) in the single antiplatelet therapy group and 26 731 (86.6%) in the dual antiplatelet therapy group. Details of these studies are outlined in Table 1 and Supplementary material online, Table S1.Figure 1

Bottom Line: We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions.When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09).Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden. jonas.oldgren@ucr.uu.se

ABSTRACT

Background: Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting.

Methods and results: All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.

Conclusion: In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.

Show MeSH
Related in: MedlinePlus