June 8th, 2011
SHARP Results Published in Lancet
The main results of SHARP (Study of Heart and Renal Protection) have now been published in the Lancet, following their preliminary presentation last November at the American Society of Nephrology meeting. The results are also posted online on the trial’s website.
In brief, SHARP randomized 9270 patients with chronic kidney disease (CKD) — one-third of whom were on dialysis — to either placebo or the combination of simvastatin and ezetimibe. After a median followup of 4.9 years, the rate of major atherosclerotic events (defined as nonfatal MI or coronary death, nonhemorrhagic stroke, or arterial revascularization excluding dialysis access procedures) was significantly lower in the combination therapy group (11.3%) than in the placebo group (13.4%; RR 0.83, CI 0.74-0.94, p=0.0021).
For the individual components of the endpoint, there were nonsignificant differences in nonfatal MI (3.4% for placebo vs. 2.9% for combination therapy, p=0.12) and CHD death (1.9% vs. 2%, p=0.95). Significant differences were observed between the placebo and combination groups for nonhemorrhagic stroke (3.8% vs. 2.8%; p=0.01) and revascularizations (7.6% vs. 6.1%, p=0.0036).
In their discussion, the SHARP investigators said that the SHARP results are “relevant… to most patients with chronic kidney disease” because “the proportional reduction in major atherosclerotic events produced by a given absolute reduction in LDL cholesterol is broadly similar irrespective of age, sex, diabetes, history of vascular disease, and presenting lipid profile.”
The authors further wrote that because previous trials with statins have found that the reduction in risk “is chiefly determined by the absolute reductions in LDL cholesterol,” and because ezetimibe “reduces LDL cholesterol by the equivalent of around three doublings of the statin dose,” ezetimibe “therefore offers a potentially useful method of increasing benefits in high-risk populations.”
In an accompanying comment, Kathryn Stevens and Alan Jardine offer a “pragmatic interpretation” of SHARP and recommend the use of lipid-lowering therapy in CKD patients, “including those who will progress to end-stage renal disease.” They note, however, that coronary disease plays only a relatively small role in the deaths of patients with advanced CKD, thereby limiting the ultimate effect of lipid lowering therapy in this group of patients.