Published Online
on December 9, 2002

A more recent version of this article appeared on January 7, 2003

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Submitted on July 16, 2002
Revised on September 27, 2002
Accepted on September 30, 2002

Simvastatin Initiated Early After Heart Transplantation. 8-Year Prospective Experience

Klaus Wenke MD^*, Bruno Meiser MD, Joachim Thiery MD, Dorothea Nagel PhD, Wolfgang von Scheidt MD, Karl Krobot MD, PhD, MPH, Gerhard Steinbeck MD, Dietrich Seidel MD, and Bruno Reichart MD

From the Division of Cardiac Surgery, Munich-Bogenhausen (K.W.); the University Hospital Munich-Grosshadern (B.M., D.N., W.v.S., G.S., D.S., B.R.); the University Hospital Leipzig (J.T.); and MSD Sharp & Dohme GmbH (K.K.), Germany.

^* To whom correspondence should be addressed. E-mail: klaus.wenke{at}extern.lrz-muenchen.de.

Background—Randomized clinical trials have demonstrated that the use of statins in heart transplant patients lowers cholesterol levels and significantly reduces mortality and the development of transplant vasculopathy. The aim of the present study was to test these effects and the safety of statin therapy over an 8-year period.

Methods and Results—In 1991, a prospective, randomized, unmasked study was initiated to compare the efficacy of simvastatin, started on the fourth postoperative day (n=35), with that of dietary therapy alone (n=37). Because of significantly improved survival and a lower incidence of transplant vasculopathy, most patients in both groups received statins as open-label prescriptions after 4 years. After 8 years, the Kaplan-Meier survival rate was 88.6% in the simvastatin group versus 59.5% in the control group (P<0.006 by log rank; hazard ratio, 0.24; 95% CI, 0.08 to 0.71). Deaths in the simvastatin and control groups were due to transplant vasculopathy (1 versus 4; P<0.2), severe transplant rejection (1 versus 5; P<0.1), malignancies (0 versus 3; P<0.1), and other causes (2 versus 3; P<0.7). The incidence of transplant vasculopathy confirmed by angiography was 24.4% in the simvastatin group versus 54.7% in the control group (P<0.02 by log rank). There was no difference in organ function between the 2 groups. No severe adverse effects of the therapy were observed up to the end of the 8-year observation period.

Conclusions—Simvastatin therapy initiated early after heart transplantation leads to significantly better 8-year survival rates and a significantly lower incidence of transplant vasculopathy without impairment of organ function or severe adverse effects.

Key words: cholesterol • transplantation • simvastatin

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