The ALERT Trial

The ALERT Trial Assessment of Lescol in Renal Transplantation Reference Holdaas H, Fellstrom B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomized, placebo-controlled trial. Lancet. 2003;361:2024–2031.

Background Premature cardiovascular disease is the leading cause of death in patients with a functioning renal graft. Many transplant recipients have a pre-existing cardiovascular disease at the time of transplantation. Immunosuppressive therapy may aggravate or promote hyperlipidemia in renal transplant patients. Observational studies suggest a putative benefit of statin therapy in these patient groups. Holdass et al. evaluated the effects of fluvastatin on cardiac and renal function in renal transplant patients. This summary presents key excerpts of this trial.

Aim To evaluate the effects of fluvastatin on cardiac and renal functions in renal transplant recipients.

Methods

Key Results • Fluvastatin significantly lowered mean LDL cholesterol by 32% (–33, to –30) as compared to placebo. Fluvastatin produced a mean LDL reduction of 7•9 mmol/L [–10•0 to –5•7]). • Fluvastatin did not differ significantly from a placebo for reductions in the primary endpoint, despite a slightly favorable result for the fluvastatin group (risk ratio: 0•83 [95% CI: 0•64–1•06], P=0•139; Fig. 1). • Fluvastatin reduced the risk of cardiac death by 38% (0•62 [0•40–0•96]) and of definite non-fatal MI by 32% (risk ratio: 0•68 [95% CI: 0•47–1•00]; Fig. 1). • Fluvastatin produced a 35% risk reduction in the combined endpoint of cardiac death or definite non-fatal MI in the fluvastatin group (risk ratio: 0•65 [95% CI: 0•48–0•88]). • Rates of probable non-fatal MI or coronary interventions did not differ significantly between groups. • The rates of cerebrovascular events, non-cardiovascular deaths, all-cause mortality, and the renal composite endpoint of graft loss or doubling of serum creatinine were similar in the two groups. • In comparison to 137 graft losses in the placebo group, fluvastatin group reported 146 graft losses. • In comparison to 165 instances of doubling of serum creatinine in the placebo group, fluvastatin group reported 183 instances serum creatinine doubling.

Conclusion Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Earlier studies have shown that statins are effective in patients with mild renal failure who are at increased cardiovascular risk, some of whom may ultimately require renal transplantation. Results of the ALERT study indicate that the overall effects of fluvastatin were similar to those of statins in other populations. The ALERT study indicates that the overall effects of fluvastatin in patients undergoing renal transplantation were similar to those of statins in other populations.