Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome

Systematic review and meta-analysis of randomized controlled trials

A. Komócsi, Andraś Vorobcsuk, Dańiel Kehl, D. Aradi

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Background: Despite receipt of dual antiplatelet therapy, patients after an acute coronary syndrome (ACS) remain at significant risk for thrombotic events. The role of orally activated Xa antagonist (anti-Xa) and direct thrombin inhibitors is debated in this setting. Our study objective was to evaluate the efficacy and safety of newgeneration oral anticoagulant agents compared with placebo in patients receiving antiplatelet therapy after an ACS. Methods: Electronic databases were searched to identify prospective randomized placebo-controlled clinical trials that evaluated the effects of anti-Xa or direct thrombin inhibitors in patients receiving antiplatelet therapy after an ACS. Efficacy measures included stent thrombosis, overall mortality, and a composite end point of major ischemic events, while thrombolysis in myocardial infarction- defined major bleeding events were used as a safety end point. The net clinical benefit was calculated as the sum of composite ischemic events and major bleeding events. Results: For the period January 1, 2000, through December 31, 2011, we identified 7 prospective randomized placebo-controlled clinical trials that met the study criteria, involving 31 286 patients. Based on the pooled results, the use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an ACS was associated with a dramatic increase in major bleeding events (odds ratio, 3.03; 95% CI, 2.20-4.16; P <.001). Significant but moderate reductions in the risk for stent thrombosis or composite ischemic events were observed, without a significant effect on overall mortality. For the net clinical benefit, treatment with newgeneration oral anticoagulant agents provided no advantage over placebo (odds ratio, 0.98; 95% CI, 0.90-1.06; P =.57). Conclusion: The use of anti-Xa or direct thrombin inhibitors is associated with a dramatic increase in major bleeding events, which might offset all ischemic benefits in patients receiving antiplatelet therapy after an ACS.

Original languageEnglish
Pages (from-to)1537-1545
Number of pages9
JournalArchives of Internal Medicine
Volume172
Issue number20
DOIs
Publication statusPublished - Nov 12 2012

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Acute Coronary Syndrome
Anticoagulants
Meta-Analysis
Randomized Controlled Trials
Antithrombins
Placebos
Hemorrhage
Stents
Thrombosis
Therapeutics
Odds Ratio
Safety
Mortality
Risk Reduction Behavior
Myocardial Infarction
Databases

ASJC Scopus subject areas

  • Internal Medicine

Cite this

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title = "Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: Systematic review and meta-analysis of randomized controlled trials",
abstract = "Background: Despite receipt of dual antiplatelet therapy, patients after an acute coronary syndrome (ACS) remain at significant risk for thrombotic events. The role of orally activated Xa antagonist (anti-Xa) and direct thrombin inhibitors is debated in this setting. Our study objective was to evaluate the efficacy and safety of newgeneration oral anticoagulant agents compared with placebo in patients receiving antiplatelet therapy after an ACS. Methods: Electronic databases were searched to identify prospective randomized placebo-controlled clinical trials that evaluated the effects of anti-Xa or direct thrombin inhibitors in patients receiving antiplatelet therapy after an ACS. Efficacy measures included stent thrombosis, overall mortality, and a composite end point of major ischemic events, while thrombolysis in myocardial infarction- defined major bleeding events were used as a safety end point. The net clinical benefit was calculated as the sum of composite ischemic events and major bleeding events. Results: For the period January 1, 2000, through December 31, 2011, we identified 7 prospective randomized placebo-controlled clinical trials that met the study criteria, involving 31 286 patients. Based on the pooled results, the use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an ACS was associated with a dramatic increase in major bleeding events (odds ratio, 3.03; 95{\%} CI, 2.20-4.16; P <.001). Significant but moderate reductions in the risk for stent thrombosis or composite ischemic events were observed, without a significant effect on overall mortality. For the net clinical benefit, treatment with newgeneration oral anticoagulant agents provided no advantage over placebo (odds ratio, 0.98; 95{\%} CI, 0.90-1.06; P =.57). Conclusion: The use of anti-Xa or direct thrombin inhibitors is associated with a dramatic increase in major bleeding events, which might offset all ischemic benefits in patients receiving antiplatelet therapy after an ACS.",
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T1 - Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome

T2 - Systematic review and meta-analysis of randomized controlled trials

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AU - Vorobcsuk, Andraś

AU - Kehl, Dańiel

AU - Aradi, D.

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N2 - Background: Despite receipt of dual antiplatelet therapy, patients after an acute coronary syndrome (ACS) remain at significant risk for thrombotic events. The role of orally activated Xa antagonist (anti-Xa) and direct thrombin inhibitors is debated in this setting. Our study objective was to evaluate the efficacy and safety of newgeneration oral anticoagulant agents compared with placebo in patients receiving antiplatelet therapy after an ACS. Methods: Electronic databases were searched to identify prospective randomized placebo-controlled clinical trials that evaluated the effects of anti-Xa or direct thrombin inhibitors in patients receiving antiplatelet therapy after an ACS. Efficacy measures included stent thrombosis, overall mortality, and a composite end point of major ischemic events, while thrombolysis in myocardial infarction- defined major bleeding events were used as a safety end point. The net clinical benefit was calculated as the sum of composite ischemic events and major bleeding events. Results: For the period January 1, 2000, through December 31, 2011, we identified 7 prospective randomized placebo-controlled clinical trials that met the study criteria, involving 31 286 patients. Based on the pooled results, the use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an ACS was associated with a dramatic increase in major bleeding events (odds ratio, 3.03; 95% CI, 2.20-4.16; P <.001). Significant but moderate reductions in the risk for stent thrombosis or composite ischemic events were observed, without a significant effect on overall mortality. For the net clinical benefit, treatment with newgeneration oral anticoagulant agents provided no advantage over placebo (odds ratio, 0.98; 95% CI, 0.90-1.06; P =.57). Conclusion: The use of anti-Xa or direct thrombin inhibitors is associated with a dramatic increase in major bleeding events, which might offset all ischemic benefits in patients receiving antiplatelet therapy after an ACS.

AB - Background: Despite receipt of dual antiplatelet therapy, patients after an acute coronary syndrome (ACS) remain at significant risk for thrombotic events. The role of orally activated Xa antagonist (anti-Xa) and direct thrombin inhibitors is debated in this setting. Our study objective was to evaluate the efficacy and safety of newgeneration oral anticoagulant agents compared with placebo in patients receiving antiplatelet therapy after an ACS. Methods: Electronic databases were searched to identify prospective randomized placebo-controlled clinical trials that evaluated the effects of anti-Xa or direct thrombin inhibitors in patients receiving antiplatelet therapy after an ACS. Efficacy measures included stent thrombosis, overall mortality, and a composite end point of major ischemic events, while thrombolysis in myocardial infarction- defined major bleeding events were used as a safety end point. The net clinical benefit was calculated as the sum of composite ischemic events and major bleeding events. Results: For the period January 1, 2000, through December 31, 2011, we identified 7 prospective randomized placebo-controlled clinical trials that met the study criteria, involving 31 286 patients. Based on the pooled results, the use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an ACS was associated with a dramatic increase in major bleeding events (odds ratio, 3.03; 95% CI, 2.20-4.16; P <.001). Significant but moderate reductions in the risk for stent thrombosis or composite ischemic events were observed, without a significant effect on overall mortality. For the net clinical benefit, treatment with newgeneration oral anticoagulant agents provided no advantage over placebo (odds ratio, 0.98; 95% CI, 0.90-1.06; P =.57). Conclusion: The use of anti-Xa or direct thrombin inhibitors is associated with a dramatic increase in major bleeding events, which might offset all ischemic benefits in patients receiving antiplatelet therapy after an ACS.

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