Telemedicine-Guided Very Low-Dose International Normalized Ratio Self-Control in Patients With Mechanical Heart Valve Implants
In patients with mechanical valve replacement, how safe is patient self-management and lower international normalized ratio (INR) targets?
In a group of 1,304 patients undergoing mechanical aortic valve replacement (AVR), 189 patients undergoing mechanical mitral valve replacement (MVR), and 78 patients undergoing double mechanical valve replacement (DVR), patients were randomly assigned to one of three groups: 1) low-intensity INR self-management (target INR 1.8-2.8 for AVR and 2.5-3.5 for MVR and DVR patients), 2) very low-intensity INR self-management once weekly (target INR 1.6-2.1 for AVR and 2.0-2.5 for MVR and DVR patients), or 3) very low-intensity INR self-management twice weekly (same target INR range as group 2). All patients received normal-intensity INR therapy for the first 6 months postoperatively (target INR range 1.8-2.8 for AVR and 2.5-3.5 for MVR and DVR patients). Outcomes assessed included major bleeding and thrombotic events, along with all-cause mortality.
Major bleeding complications were rare in all three groups (3.7% in the low-intensity, 1.4% in the very low-intensity weekly, and 0.9% in the very low-intensity twice-weekly groups, p = 0.008). Thrombotic complications were also rare in all three groups (1.0% in the low-intensity, 0.2% in the very low-intensity weekly, and 1.1% in the very low-intensity twice weekly groups, p = 0.258). The risk for the composite major complications in the per-protocol analysis was lower in the very low-intensity weekly (hazard ratio [HR], 0.307; 95% confidence interval [CI], 0.102-0.926) and very low-intensity twice weekly groups (HR, 0.241; 95% CI, 0.070-0.836) compared to the low-intensity group. Compared to the low-intensity group, 2-year all-cause mortality was similar in the very low-intensity twice weekly group (HR, 1.685; 95% CI, 0.473-5.996), but higher in the very low-intensity weekly group (HR, 4.70; 95% CI, 1.62-13.60). In AVR patients, the time in the therapeutic range (TTR) was 83.9 ± 12.7% for the low-intensity patients, 77.5 ± 15.0% for the very low-intensity weekly patients, and 77.6 ± 13.7% in the very low-intensity twice weekly patients.
The authors concluded that very low-intensity INR self-control is comparable to low-intensity INR management for preventing thrombosis, but provides a lower risk of major bleeding. The authors also concluded that weekly testing is sufficient for the very low-intensity INR group.
Many readers will be surprised to see a study comparing patients with mechanical valves at INR target ranges below 2.0-3.0 for AVR patients and 2.5-3.5 for MVR and DVR patients. However, given the frequency of INR testing with self-management and the lower thrombotic profile of newer heart valves, the authors thought that this strategy was safe for investigation, and their outcomes data support their decision. Additionally, the very high TTR is markedly better than is usually seen in North America, and likely accounts for the very low thrombotic and bleeding event rates. An important limitation of this study is the large number of patients (23%) who did not complete the study protocol and were not included in the per-protocol analysis. In the intention-to-treat analysis, weekly very low-intensity INR management was still shown to be beneficial. This study raises the questions of appropriate INR target ranges for many mechanical valve patients as well as the practicality of patient self-management for long-term anticoagulation with warfarin.
< Back to Listings