Time-related risk of the St. Jude Silzone heart valve

Objective: The St. Jude Medical Silzone heart valve had a silver-impregnated sewing ring designed to reduce the incidence of prosthetic valve endocarditis. Recruitment to the randomized AVERT study comparing Silzone valves with non-Silzone Control valves was stopped because of an increased risk of reoperation for paravalvular leak, but patient follow-up continues. Determining the time-related risk profile of the Silzone valve is important for helping physicians manage the approximately 28,000 patients currently alive with a Silzone valve. Methods: Between 1998 and 2000, 403 Silzone and 404 Control patients were enrolled in AVERT. As of July 2005, there were 1819 Silzone and 1842 Control patient-years of follow-up (mean 4.5, median 5.1 years). Analysis emphasized the use and interpretation of hazard functions, since they are more meaningful than event-free percentages to currently surviving patients. To this end, instead of Cox regression, which estimates the hazard ratio, assuming it is constant over time, we employed primarily Aalen additive regression, which measures the hazard difference, and produces a plot of it over time. We assessed the risks of major paravalvular leak, endocarditis, bleeding and thrombo-embolism. Results: The Silzone valve had a higher initial risk of major paravalvular leak than Control in the mitral (p = 0.02) position, but not in the aortic (p = 0.42) position. Analysis of this risk using additive regression, with all valve positions combined, showed that the initial risk due to Silzone lost statistical significance by 2 years and disappeared by 4 years after implant. In the mitral position, the Silzone valve had a higher initial risk of thrombo-embolism plus bleeding than Control; this risk also lost statistical significance by 2 years and subsided to zero by 4 years. The risks for death and endocarditis were similar for Slizone and Control valves. Conclusions: The additional risks of the Silzone valve, compared to Control, diminish over time and disappear by 4 years after implant. The minimum time after implant of the patients currently alive with Silzone is now well beyond 5 years; thus, these current patients now have a risk profile similar to that of patients with a standard St. Jude valve.