Prograf decreases plasma cholesterol in heart transplant recipients with treated but persisting mild dyslipidemia: the canadian multicenter randomized trial of prograf versus neoral

Abstract

Background: Despite optimal use of lipid-lowering agents, most heart transplant recipients (htx) exhibit persisting dyslipidemia not satisfying the current guidelines. We have initiated a prospective study of Neoral maintenance versus (vs) conversion to Prograf immunoprophylaxis in stable htx exhibiting persistent dyslipidemia despite optimal treatment with lipid-lowering agents.Methods: One hundred and twenty-nine stable htx, aged 56.7±10.1 years (mean±SD) and 77.9±42.2 months post-op. were randomized to continue on Neoral (n=64) or switch to Prograf (n=65). Complete lipid profile was measured at baseline (bsl) and after 1, 3 and 6 months (6 mo). Hemostatic parameters (fibrinogen, factor VII, VIII, von Willebrand) and proinflammatory markers (hsCRP, homocysteine, sICAM, sVCAM, MCP-I, TPA, PAI-1) were measured at bsl and at 6 mo.Results: The Prograf-treated group exhibited a significant greater decrease in total cholesterol [5.51±1.16 (bsl) vs 4.88±1.22 mmol/L, (6 mo): Prograf; 5.61±1.36 (bsl) vs 5.38±0.87 mmol/L (6 mo): Neoral, p=0.002]. The Prograf group also yielded a significant decrease in LDL-cholesterol [3.10±0.8 (bsl) vs 2.72±0.88 mmol/L (6 mo); p=0.01], and cholesterol/HDL ratio [4.73±1.48 (bsl) vs 4.15±1.36 (6 mo); p=0.02]. The decrease in cholesterol was maximum at one month post-switch. For patients treated with Prograf, the change in plasma creatinine from baseline to month 6 [-6.97±25.29 μmol/L] was significantly greater than for patients who remained on Neoral [+1.13±19.53 μmol/L] [p=0.01]. Blood glucose remains stable in the Prograf-treated patients [5.96±1.60 vs 6.01±1.87 mmol/L, p=0.5].Conclusions: This large prospective conversion study showed that Prograf provides a significant decrease in total, LDL-cholesterol and cholesterol/HDL ratio as well as an improvement in renal function. These provide a rationale for the use of Prograf in cardiac transplant patients with treated but persisting dyslipidemia.