AGGRESSIVE LOWERING OF FIBRINOGEN AND CHOLESTEROL IN THE PREVENTION OF GRAFT VESSEL DISEASE AFTER HEART-TRANSPLANTATION

Background A combined treatment of statins and extracorporeal H.E.L.P. -apheresis (Heparin-mediated Extracorporeal LDL/fibrinogen Precipitati on) has already been shown to be beneficial for coronary artery diseas e (CAD). Presumably high levels of LDL cholesterol, Lp(a), and fibrino gen also increase the risk for graft vessel disease (GVD). Therefore, we studied whether this concept can be applied in GVD, based on the hy pothesis that GVD is an accelerated form of CAD.Methods and Results Fo r comparison of statin treatment alone with the combined treatment, tw o matched groups of 10 cardiac transplant recipients were studied duri ng a mean period of 3.6+/-1.0 years. Both groups were comparable in cl inical characteristics, immunosuppressive medication, base line plasma Lp(a), and high fibrinogen levels. Group I had normal LDL-C levels (3 .36+/-0.60 mmol/L). Simvastatin alone was administered in this group t o counteract the LDL-increasing effect of the immunosuppressive medica tion. Group II had marked hypercholesterolemia (LDL-C, 6.07+/-1.89 mmo l/L), which was treated, in addition to simvastatin, with H.E.L.P.-aph eresis weekly. GVD was assessed by coronary angiography. Simvastatin a lone kept LDL-C levels within baseline limits but could not prevent GV D in 7 of 10 patients. In contrast, the combined treatment prevented G VD in 9 of 10 patients (P=.006) by simultaneous and drastic reduction of 48% LDL-C (P=.006), 35% fibrinogen (P=.002), and 47% Lp(a) (P=.006) below baseline. Both treatments were well tolerated and did not affec t prevention of graft rejection and infections. Conclusions A strategy of early, drastic lowering of fibrinogen, LDL-C, and Lp(a) helps to p revent GVD.