Effect of warfarin on calcification of spontaneously degenerated porcine bioprosthetic valves

Synthesis of a calcium-binding amino acid, gamma-carboxyglutamic acid, is a vitamin K-dependent enzymatic process. Warfarin inhibits gamma-carboxyglutamic acid synthesis and, therefore, might diminish the calcification of porcine bioprosthetic valves. To evaluate this, we studied 40 porcine bioprosthetic valves removed because of spontaneous degeneration; 17 patients were treated with warfarin (prothrombin time greater than or equal to 1.5 control) and 23 were untreated. Gross visualization of calcification corresponded closely to x-ray visualization of calcification in explanted valves. No grossly visible calcification or only a single localized nodule was shown in 11 of 17 valves (65%) in treated patients and in only five of 23 valves (22%) in untreated patients (p less than 0.02). Histologic examination showed no calcium or only fine specks of calcium in nine of 13 valves (69%) among warfarin-treated patients and three of 19 valves (16%) from untreated patients. Warfarin, therefore, administered in usual clinical doses, appeared to diminish calcification in spontaneously degenerated porcine bioprosthetic valves.