, Volume 42, Issue 3, pp 295–306 | Cite as

Efficacy and safety of aspirin combined with warfarin after acute coronary syndrome

A meta-analysis
  • P. Zhang
  • J. Li
  • C. Wu
  • X. Huang
  • L. Li
  • W. Zhang
  • C. Shen
Review articles


A comprehensive meta-analysis was performed to investigate whether the combination of high-/low-dose of aspirin and various intensities of warfarin (W) offer greater benefit than aspirin (ASA) alone. A total of 14 randomized clinical trials (RCTs) having 26,916 patients with acute coronary syndrome (ACS) met inclusion criteria. The efficacy and safety of all outcomes which included myocardial infarction (MI), all-cause death, stroke, and bleeding were calculated. The overall outcomes analysis showed there was no significant difference in the risk of MI (relative ratio [RR] 0.959, 95 % confidence interval [CI] 0.78–1.04, P = 0.308), stroke (RR 0.789, 95 % CI 0.57–1.09, P = 0.145), and all-cause death (RR 1.007, 95 % CI 0.93–1.09, P = 0.87) between the combination group and ASA group. The subgroup analysis suggested that ASA (≤100 mg/day) plus W (mean international normalized ratio [INR] 2.0–3.0) decreased the risk rate of stroke (RR 0.660, 95 % CI 0.50–0.87, P = 0.003). There was a lower risk of MI (RR 0.605, 95 % CI 0.47–0.77, P < 0.0001) as well as stroke (RR 0.594, 95 % CI 0.45–0.79, P < 0.0001) between W (INR 2.0–3.0) combined with ASA (mean dose ≥100 mg/day) and ASA. However, the risk of major bleeding (RR 1.738, 95 % CI 1.45–2.08, P < 0.0001) and minor bleeding (RR 2.767, 95 % CI 2.12–3.61, P < 0.0001) was almost doubled in the combined groups. Compared with ASA, high-dose aspirin with moderate-intensity warfarin (INR 2.0–3.0) may better reduce the risk of MI and stroke but confer an increased risk of bleeding.


Myocardial infarction All-cause death Stroke Bleeding Anticoagulants 

Wirksamkeit und Sicherheit von Aspirin in Kombination mit Warfarin nach akutem Koronarsyndrom

Eine Metaanalyse


Eine umfassende Metaanalyse wurde durchgeführt, um zu untersuchen, ob die Kombination einer hohen/niedrigen Dosis Aspirin und unterschiedlichen Dosen Warfarin (W) einen größeren Nutzen hat als Aspirin alleine (ASA). Insgesamt 14 randomisierte klinische Studien („randomized clinical studies“, RCTs), die 26.916 Patienten mit akutem Koronarsyndrom (AKS) umfassten, erfüllten die Einschlusskriterien. Die Wirksamkeit und Sicherheit aller Outcomes, einschließlich Myokardinfarkt (MI), Tod jeglicher Ursache, Schlaganfall und Blutungen, wurden mit einbezogen. Die Analyse der Gesamt-Outcomes zeigte keine signifikanten Unterschiede für das MI-Risiko (relatives Risiko [RR] 0,959; 95 % Konfidenzintervall [CI] 0,78–1,04; p = 0,308), Schlaganfall (RR 0,789; 95 % CI 0,57–1,09; p = 0,145) und Tod jeglicher Ursache (RR 1,007; 95 % CI 0,93–1,09; p = 0,87) zwischen der Kombinations- und der ASA-Gruppe. Die Subgruppenanalyse zeigte, dass ASA (≤100 mg/Tag) plus W (mittlere internationale normalisierte Ratio [INR] 2,0–3,0) das Risiko für einen Schlaganfall reduzierte (RR 0,660; 95 % CI 0,50–0,87; p = 0,003). Das Risiko für einen MI (RR 0,605; 95 % CI 0,47–0,77; p < 0,0001) sowie für einen Schlaganfall (RR 0,594; 95 % CI 0,45–0,79; p < 0,0001) war bei W (INR 2,0–3,0) in Kombination mit ASA (mittlere Dosis ≥100 mg/Tag) geringer als bei ASA. Das Risiko für schwere Blutungen (RR 1,738; 95 % CI 1,45–2,08; p < 0,0001) und leichte Blutungen (RR 2,767; 95 % CI 2,12–3,61; p < 0,0001) war jedoch in den Kombinationsgruppen doppelt so hoch. Im Vergleich mit ASA könnte eine hohe Dosis Aspirin mit einer mittleren Dosis Warfarin (INR 2,0–3,0) das Risiko für MI und Schlaganfall besser reduzieren, es könnte allerdings ein erhöhtes Risiko für Blutungen bestehen.


Myokardinfarkt Tod jeglicher Ursache Schlaganfall Blutungen Antikoagulanzien 



This study was supported by National Natural Science Fund of China (81173133). This funding did not lead to any conflicts.

Compliance with ethical guidelines

Conflict of interest

P. Zhang, J. Li, C. Wu, X. Huang, L. Li, W. Zhang, and C. Shen state they have no competing interest.

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer Medizin Verlag 2016

Authors and Affiliations

  • P. Zhang
    • 1
    • 2
  • J. Li
    • 3
  • C. Wu
    • 4
  • X. Huang
    • 1
  • L. Li
    • 1
  • W. Zhang
    • 1
  • C. Shen
    • 1
  1. 1.Department of Basic and Clinical Pharmacology, School of PharmacyAnhui Medical UniversityAnhuiChina
  2. 2.Department of PharmacyChenjian Hospital of Hefei CityAnhuiChina
  3. 3.Anhui Provincial Center for Drug Clinical Evaluation, Institute of Clinical Pharmacology and PharmacyYijishan Hospital of Wannan Medical CollegeAnhuiChina
  4. 4.Department of Pharmacology and Institute of Natural MedicineAnhui Medical UniversityAnhuiChina

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