Table 2.
RCTs comparing a NOAC vs. warfarin in patients with mechanical prosthetic heart valves
| RCT | Study design | Study cohort | Main findings |
|---|---|---|---|
| RE-ALIGN54 | A Phase II dose-validation RCT comparing dabigatran at initial dose of 150, 220, or 300 mg twice daily (based on kidney function) and then adjusted to obtain a trough plasma level of ≥ 50 ng/mL vs. dose-adjusted warfarin with target INR 2.0–3.0 or 2.5–3.5 | Patients who underwent aortic or mitral valve replacement within the last 7 days (79% of patients) or ≥3 months earlier. n = 252 (terminated prematurely). | Increased rates of thromboembolic and bleeding complications with dabigatran, in comparison to warfarin, thus showing no benefit and an excess risk. Death or TE: HR 1.94 (95% CI, 0.64–5.86). Major bleeding: HR 1.76 (95% CI, 0.37–8.46). |
| PROACT Xa55 | A prospective, randomized, open-label trial with blinded end-point adjudication, comparing apixaban 5 mg twice daily vs. warfarin (target INR 2.0–3.0). The primary efficacy end point was the composite of valve thrombosis or valve-related thromboembolism. The primary safety end point was major bleeding defined as any episode of internal or external bleeding that caused death, hospitalization, or permanent injury or necessitated transfusion, pericardiocentesis, or reoperation. |
Patients with an On-X aortic valve implanted at least 3 months before enrolment. n = 863 (terminated owing to an excess of thromboembolic events in the apixaban group). |
Apixaban was less effective than warfarin and did not reach non-inferiority in the prevention of valve thrombosis or thromboembolism in patients with an On-X mechanical aortic valve. Major bleeding rates were 3.6%/patient-year with apixaban and 4.5%/patient-year with warfarin. |
| RIWA56 | A proof-of-concept, open-label, RCT assessing the incidence of thromboembolic and bleeding events of the rivaroxaban-based strategy (15 mg twice daily) in comparison to dose-adjusted warfarin. |
n = 44 patients with a prosthetic mechanical heart valve. A 90-day follow-up. |
Rivaroxaban 15 mg twice daily had TE and bleeding events similar to warfarin in patients with mechanical heart valves. |
RCT, randomized controlled trial; INR, international normalized ratio; TE, thromboembolic event; HR, hazard ratio; CI, confidence interval; NOAC, non-vitamin K antagonist oral anticoagulant; RIWA, Rivaroxaban vs. Warfarin in Patients With Metallic Prosthesis.