Ten-Year Follow-Up of a Randomized Trial of Pravastatin in Heart Transplant Patients

doi:10.1016/j.healun.2005.02.009

The Journal of Heart and Lung Transplantation

Volume 24, Issue 11, November 2005, Pages 1736-1740

https://doi.org/10.1016/j.healun.2005.02.009 Get rights and content

Background

Outcomes from this trial’s first year data demonstrated significant benefit in heart transplant patients treated with pravastatin in cholesterol levels, survival, rejection with hemodynamic compromise, the development of cardiac allograft vasculopathy, and decreased natural killer cell cytotoxicity. Other heart transplant studies have shown similar benefit. We now report the 10-year follow-up of this study.

Methods

Ninety-seven heart transplant recipients were randomized to pravastatin (n = 47) or no pravastatin (n = 50) within 2 weeks after surgery both in combination with cyclosporine and corticosteroids. Ten-year outcomes include survival, cholesterol levels, and development of cardiac allograft vasculopathy documented by coronary angiography.

Results

Forty-two percent of the control patients crossed over to pravastatin treatment during the second year of the study, and 81% of the control patients were eventually placed on statin therapy by the 10-year follow-up. The control group had subsequent low and comparable cholesterol levels in Years 2 to10 of the study compared with the patients originally randomized to pravastatin. Intent-to-treat analysis demonstrated that the pravastatin group compared with control had increased 10-year survival (68% vs 48%, p = 0.026). The 10-year freedom from angiographic cardiac allograft vasculopathy and/or death in the pravastatin group was significantly greater compared with the control group (43% vs 20%, p = 0.009).

Conclusion

The 10-year follow-up of this study suggests that the use of pravastatin in heart transplant patients maintains survival benefit and appears to reduce the development of cardiac allograft vasculopathy.

Section snippets

Selection of Patients

From July 1, 1992, through February 1, 1994, 107 adult patients underwent cardiac transplantation in our program. Eight patients died during the initial hospitalization after transplantation and were not enrolled in this study, and 2 patients declined to participate. The remaining 97 patients were randomly assigned to pravastatin (47 patients) or no pravastatin (50 patients) in addition to their immunosuppressive treatment. The institutional review board approved the study design and informed

Characteristics of the Patients

Pravastatin group and the control group did not differ at baseline except for a higher number of second transplantations in the control group (7 patients vs 3 patients receiving pravastatin) (Table 1). We therefore conducted an additional analysis for all final endpoints of this study excluding second transplant patients.

After transplant the groups did not differ significantly in the number of infectious complications, the degree of renal impairment, or in the use of calcium-channel blockers or

Discussion

The 10-year follow-up of this randomized trial of pravastatin in heart transplant patients suggests that pravastatin has persistent beneficial effects in survival and reduces the development of CAV. These beneficial effects of pravastatin may result from a direct reduction of cholesterol, a cholesterol-independent effect of pravastatin, or another mechanism to be defined.

After our initial publication of this study,¹ other heart transplant investigators published beneficial effects of HMG-CoA

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Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure in pediatric heart transplant recipients (HTRs). Early statin use has been shown to reduce CAV incidence and all-cause mortality in adult HTRs. We sought to evaluate the contemporary prevalence and trends of statin use in pediatric HTRs and the association between statin use with CAV development and graft failure.
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: This study was sponsored in part by an unrestricted educational grant from Bristol Meyer Squibb.

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Clinical heart transplantationTen-Year Follow-Up of a Randomized Trial of Pravastatin in Heart Transplant Patients

Background

Methods

Results

Conclusion

Section snippets

Selection of Patients

Characteristics of the Patients

Discussion

J Heart Lung Transplant

JAMA

JAMA

Cell Immunol

Transpl Proc

J Heart Lung Transplant

Effects of pravastatin on outcomes after cardiac transplantation

N Engl J Med

Simvastatin reduces graft vessel disease and mortality after heart transplantationa four-year randomized trial

Circulation

Lipid treatment and survival after heart transplantation

JAMA

The effect of pravastatin on acute rejection after kidney transplantationa pilot study

Transplantation

Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia

N Engl J Med

Clinical heart transplantation
Ten-Year Follow-Up of a Randomized Trial of Pravastatin in Heart Transplant Patients