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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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Association of effects of adding an oral anticoagulant to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy on rate of MACE with effects on rate of clinically significant bleeding events after an acute coronary syndrome. Random-effects meta-regression, stratified on number of antiplatelet drugs. The area of a circle representing a study arm is proportional to its weight in the random-effects model. Shaded areas are 95% confidence intervals. HR, hazard ratio; MACE, major adverse cardiovascular events; Riv, rivaroxaban; Dab, dabigatran, Api, apixaban; Dar, darexaban; Xim, ximelagatran; b.i.d., twice daily; o.d., once daily; number denotes strength in milligram.
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EHT049F5: Association of effects of adding an oral anticoagulant to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy on rate of MACE with effects on rate of clinically significant bleeding events after an acute coronary syndrome. Random-effects meta-regression, stratified on number of antiplatelet drugs. The area of a circle representing a study arm is proportional to its weight in the random-effects model. Shaded areas are 95% confidence intervals. HR, hazard ratio; MACE, major adverse cardiovascular events; Riv, rivaroxaban; Dab, dabigatran, Api, apixaban; Dar, darexaban; Xim, ximelagatran; b.i.d., twice daily; o.d., once daily; number denotes strength in milligram.

Mentions: There was a non-significant tendency to an inverse association between the effect on MACEs and the effect on clinically significant bleeding when adding an anticoagulant to single antiplatelet therapy, but no association when adding an anticoagulant to dual antiplatelet therapy (Figure 5).Figure 5


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)

Association of effects of adding an oral anticoagulant to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy on rate of MACE with effects on rate of clinically significant bleeding events after an acute coronary syndrome. Random-effects meta-regression, stratified on number of antiplatelet drugs. The area of a circle representing a study arm is proportional to its weight in the random-effects model. Shaded areas are 95% confidence intervals. HR, hazard ratio; MACE, major adverse cardiovascular events; Riv, rivaroxaban; Dab, dabigatran, Api, apixaban; Dar, darexaban; Xim, ximelagatran; b.i.d., twice daily; o.d., once daily; number denotes strength in milligram.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHT049F5: Association of effects of adding an oral anticoagulant to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy on rate of MACE with effects on rate of clinically significant bleeding events after an acute coronary syndrome. Random-effects meta-regression, stratified on number of antiplatelet drugs. The area of a circle representing a study arm is proportional to its weight in the random-effects model. Shaded areas are 95% confidence intervals. HR, hazard ratio; MACE, major adverse cardiovascular events; Riv, rivaroxaban; Dab, dabigatran, Api, apixaban; Dar, darexaban; Xim, ximelagatran; b.i.d., twice daily; o.d., once daily; number denotes strength in milligram.
Mentions: There was a non-significant tendency to an inverse association between the effect on MACEs and the effect on clinically significant bleeding when adding an anticoagulant to single antiplatelet therapy, but no association when adding an anticoagulant to dual antiplatelet therapy (Figure 5).Figure 5

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