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J Am Coll Cardiol, 2003; 42:2042-2048, doi:10.1016/j.jacc.2003.07.029
© 2003 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: META-ANALYSIS

The optimal intensity of vitamin k antagonists in patients with mechanical heart valves

A meta-analysis

Roel Vink, MD*,*, Roderik A. Kraaijenhagen, MD{dagger}, Barbara A. Hutten, PhD{ddagger}, Renee B. A. van den Brink, MD{dagger}, Bas A. de Mol, MD§, Harry R. Büller, MD* and Marcel Levi, MD*

* Vascular Medicine, Amsterdam, The Netherlands
{dagger} Cardiology, Amsterdam, The Netherlands
{ddagger} Clinical Epidemiology and Biostatistics, Amsterdam, The Netherlands
§ Cardiopulmonary Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Manuscript received February 27, 2003; revised manuscript received July 7, 2003, accepted July 21, 2003.

* Reprint requests and correspondence: Dr. Roel Vink, Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
r.vink{at}amc.uva.nl

OBJECTIVES: The purpose of this study was to compare two different intensities of vitamin K antagonists (VKA) among patients with mechanical heart valves using meta-analytic techniques.

BACKGROUND: Patients with mechanical heart valves are at increased risk for valve thrombosis and systemic embolism, which can be reduced by VKA. The range of optimal intensity of VKA is still a matter of debate.

METHODS: A computerized search in the PubMed database was made for relevant articles. A meta-analysis was performed of all eligible studies with data on the incidences of thromboembolic and bleeding complications in patients with mechanical heart valve prostheses during different intensities of VKA therapy. The studies were classified into low-intensity VKA therapy (mean target international normalized ratio [INR] of 3.0 or lower) or high-intensity VKA therapy (mean target INR above 3.0).

RESULTS: Thirty-five eligible studies were identified, including in total 23,145 patients, who were studied for 108,792 patient-years. For patients with an aortic valve, high intensity resulted in a lower incidence of thromboembolic events (risk ratio [RR] = 0.73, p < 0.0001); however, the incidence of bleeding was increased (RR = 1.23, p < 0.0001). In the mitral valve group, the incidence rate for thromboembolism was lower in the high-intensity group (RR = 0.74, p < 0.0001), without a significantly increased bleeding incidence (RR = 1.08, p = 0.0524). The total number of thromboembolic and bleeding events was decreased in the high-intensity group compared with low-intensity VKA therapy for both aortic and mitral valve prostheses (RR = 0.94 [p = 0.0067] and 0.84 [p < 0.0001]), respectively.

CONCLUSIONS: This meta-analysis shows that both aortic and mitral valves will benefit from a treatment strategy with a target INR higher than 3.0.

Abbreviations and Acronyms
  CI = confidence interval
  INR = international normalized ratio
  RR = risk ratio
  VKA = vitamin K antagonists




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