AREVA : Multicenter randomized comparison of low-dose versus standard-dose anticoagulation in patients with mechanical prosthetic heart valves

• Published in: Circulation (New York, N.Y.) N.Y.), 1996-11, Vol.94 (9), p.2107-2112
• Main Authors: ACAR, J, IUNG, B, DE GEVIGNEY, G, VIGUIER, E, SFIHI, A, HANANIA, G, GHANNEM, M, MIRODE, A, NEMOZ, C, BOISSEL, J. P, MEYER SAMAMA, M, MICHEL, P. L, TEPPE, J. P, PONY, J. C, LE BRETON, H, THOMAS, D, ISNARD, R
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Anticoagulants - administration & dosage; Biological and medical sciences; Bleeding Time; Blood. Blood coagulation. Reticuloendothelial system; Dose-Response Relationship, Drug; Female; Heart Valve Prosthesis; Hemorrhage - chemically induced; Hemorrhage - mortality; Humans; Incidence; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Survival Analysis; Thromboembolism - drug therapy; Thromboembolism - mortality; Thromboembolism - prevention & control; Time Factors; Treatment Outcome
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.94.9.2107

Moderate anticoagulation may be proposed to reduce the risk of hemorrhage for certain patients with a mechanical prosthesis, but the consequences for risk of thromboembolism are debated. The purpose of the AREVA trial was to compare moderate oral anticoagulation (international normalized ratio [INR] of 2.0 to 3.0) with the usual regimen (INR of 3.0 to 4.5) after a single-valve replacement with a mechanical prosthesis, either Omnicarbon or St Jude. Patients included were between 18 and 75 years old, in sinus rhythm, and with a left atrial diameter < or = 50 mm on the time-motion echocardiogram. Patients were randomized for INR after surgery. From 1991 to 1994, 433 patients underwent valve replacement (aortic, 414; mitral, 19) with 353 St Jude and 80 Omnicarbon prostheses; 380 patients were randomized for INR: 188 for INR 2.0 to 3.0 and 192 for INR 3.0 to 4.5. Mean follow-up was 2.2 years (1 to 4 years). Analysis of 18001 INR samples showed that the mean of the median of INR was 2.74 +/- 0.35 in the 2.0 to 3.0 group and 3.21 +/- 0.33 in the 3.0 to 4.5 group (P < .0001). Thromboembolic events, as assessed from clinical data and CT brain scans, occurred in 10 patients in the 2.0 to 3.0 INR group and 9 patients in the 3.0 to 4.5 INR group (P = .78). Hemorrhagic events occurred in 34 patients in the 2.0 to 3.0 INR group and 56 patients in the 3.0 to 4.5 INR group (P < .01), with 13 and 19 major hemorrhagic events, respectively (P = .29). In selected patients with mechanical prostheses, moderate anticoagulation prevents thromboembolic events as effectively as conventional anticoagulation and reduces the incidence of hemorrhagic events.