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 Precipitation) has already been shown to be beneficial for coronary artery disease (CAD). Presumably high levels of LDL cholesterol, Lp(a), and fibrinogen also increase the risk for graft vessel disease (GVD). Therefore, we studied whether this concept can be applied in GVD, based on the hypothesis that GVD is an accelerated form of CAD. METHODS AND RESULTS: For comparison of statin treatment alone with the combined treatment, two matched groups of 10 cardiac transplant recipients were studied during a mean period of 3.6+/-1.0 years. Both groups were comparable in clinical characteristics, immunosuppressive medication, baseline 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 to counteract the LDL-increasing effect of the immunosuppressive medication. Group II had marked hypercholesterolemia (LDL-C, 6.07+/-1.89 mmol/L), which was treated, in addition to simvastatin, with H.E.L.P.-apheresis weekly. GVD was assessed by coronary angiography. Simvastatin alone kept LDL-C levels within baseline limits but could not prevent GVD in 7 of 10 patients. In contrast, the combined treatment prevented GVD 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 affect prevention of graft rejection and infections. CONCLUSIONS: A strategy of early, drastic lowering of fibrinogen, LDL-C, and Lp(a) helps to prevent GVD.