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

Background 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. Methods and Results 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 less than or equal to 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 18 001 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). Conclusions In selected patients with mechanical prostheses, moderate anticoagulation prevents thromboembolic events as effectively as conventional anticoagulation and reduces the incidence of hemorrhagic events.