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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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Related in: MedlinePlus

Effect of adding an oral anticoagulant to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy on rate of major adverse cardiovascular events after an acute coronary syndrome. Effect estimates of individual study arms with horizontal lines representing 95% CI; coloured diamonds, subtotal effects and 95% CI from random effects models for direct thrombin inhibitors and factor Xa inhibitors, respectively, and overall effects in addition to single and dual antiplatelet therapy; Open diamonds, subtotal summary effects and 95% CI from random effects models per trial; HR, hazard ratio; CI, confidence interval; ARR, absolute risk reduction (risk difference); b.i.d., twice daily; o.d., once daily; MACE, major adverse cardiovascular events, i.e. a composite of all-cause mortality, myocardial infarction and stroke.
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EHT049F2: Effect of adding an oral anticoagulant to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy on rate of major adverse cardiovascular events after an acute coronary syndrome. Effect estimates of individual study arms with horizontal lines representing 95% CI; coloured diamonds, subtotal effects and 95% CI from random effects models for direct thrombin inhibitors and factor Xa inhibitors, respectively, and overall effects in addition to single and dual antiplatelet therapy; Open diamonds, subtotal summary effects and 95% CI from random effects models per trial; HR, hazard ratio; CI, confidence interval; ARR, absolute risk reduction (risk difference); b.i.d., twice daily; o.d., once daily; MACE, major adverse cardiovascular events, i.e. a composite of all-cause mortality, myocardial infarction and stroke.

Mentions: In patients receiving single antiplatelet therapy (aspirin), additional treatment with an oral anticoagulant on average decreased the rate of MACEs by 30% (Figure 2), with similar effects for ximelagatran, apixaban, and rivaroxaban (I2= 0%). In those studies, the rate of clinically significant bleeding events increased with 79% (Figure 3). No heterogeneity of effects on bleeding could be discerned (I2 = 0%). In patients on single antiplatelet therapy, 6-month rates of MACEs were ∼15% (149/1000) and 6-month rates of clinically significant bleeding were ∼9% (89/1000). Additional treatment with an oral anticoagulant for 6 months prevented ∼44 MACEs (NNTB 22) and caused ∼70 additional clinically significant bleeding events (NNTH 14) per 1000 patients.Figure 2


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)

Effect of adding an oral anticoagulant to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy on rate of major adverse cardiovascular events after an acute coronary syndrome. Effect estimates of individual study arms with horizontal lines representing 95% CI; coloured diamonds, subtotal effects and 95% CI from random effects models for direct thrombin inhibitors and factor Xa inhibitors, respectively, and overall effects in addition to single and dual antiplatelet therapy; Open diamonds, subtotal summary effects and 95% CI from random effects models per trial; HR, hazard ratio; CI, confidence interval; ARR, absolute risk reduction (risk difference); b.i.d., twice daily; o.d., once daily; MACE, major adverse cardiovascular events, i.e. a composite of all-cause mortality, myocardial infarction and stroke.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHT049F2: Effect of adding an oral anticoagulant to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy on rate of major adverse cardiovascular events after an acute coronary syndrome. Effect estimates of individual study arms with horizontal lines representing 95% CI; coloured diamonds, subtotal effects and 95% CI from random effects models for direct thrombin inhibitors and factor Xa inhibitors, respectively, and overall effects in addition to single and dual antiplatelet therapy; Open diamonds, subtotal summary effects and 95% CI from random effects models per trial; HR, hazard ratio; CI, confidence interval; ARR, absolute risk reduction (risk difference); b.i.d., twice daily; o.d., once daily; MACE, major adverse cardiovascular events, i.e. a composite of all-cause mortality, myocardial infarction and stroke.
Mentions: In patients receiving single antiplatelet therapy (aspirin), additional treatment with an oral anticoagulant on average decreased the rate of MACEs by 30% (Figure 2), with similar effects for ximelagatran, apixaban, and rivaroxaban (I2= 0%). In those studies, the rate of clinically significant bleeding events increased with 79% (Figure 3). No heterogeneity of effects on bleeding could be discerned (I2 = 0%). In patients on single antiplatelet therapy, 6-month rates of MACEs were ∼15% (149/1000) and 6-month rates of clinically significant bleeding were ∼9% (89/1000). Additional treatment with an oral anticoagulant for 6 months prevented ∼44 MACEs (NNTB 22) and caused ∼70 additional clinically significant bleeding events (NNTH 14) per 1000 patients.Figure 2

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