The optimal intensity of vitamin K antagonists in patients with mechanical heart valves: a meta-analysis.

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.