By Lilian Anekwe
A new investigational study appears to have shown for the first time that prescribing ezetimibe in addition to a statin does have direct benefits on vascular events in patients with cardiovascular disease.
MSD, the manufacturers of ezetimibe who funded the study, said it was the first prospective randomised controlled trial to demonstrate the benefit of lowering LDL-cholesterol on major vascular events, with a 16% reduction in the incidence of first major vascular events in patients on ezetimibe and simvastatin compared to those on placebo.
The SHARP study involved more than 9,000 patients with either advanced or end-stage CKD who were randomised in a ratio of 4:4:1 to receive either ezetimibe/simvastatin 10/20mg daily, placebo, or simvastatin 20mg alone.
After one year, patients who were initially allocated to simvastatin alone were randomised to either ezetimibe/simvastatin 10/20 mg daily or placebo for the remainder of the study period, which lasted for a median follow-up period of 4.9 years.
In an intention-to-treat analysis that did not include patients initially randomised to simvastatin alone for the first year, ezetimibe/simvastatin reduced first major vascular events by 16.0% compared to placebo.
The analysis of the full study population showed ezetimibe/simvastatin reduced first major vascular events by 15.3% compared to placebo.
The incidence of first major atherosclerotic events was also lower in patients taking ezetimibe and simvastatin, at 11.3%, compared to 13.4% in patients taking placebo.
There was no significant difference between patients in the ezetimibe group and those on to placebo in the incidence of cancer and cancer-related deaths, which were reported in 9.4% and 9.5% of the two groups respectively. Mortality due to cancer was reported in 3.2% and 2.8% respectively.
Ezetimibe is not currently indicated in patients with CKD, but MSD announced it planned to seek regulators approvals for the use of ezetimibe, as an adjunct to simvastatin, in patients with CKD based on these results.
The results were presented at the American Society of Nephrology's annual meeting in Denver last week by researchers from the Oxford University clinical trials service unit.
Lead researcher Professor Colin Baigent said: ‘It was already known that cholesterol-lowering could reduce the risk of heart attacks, strokes and the need for surgery to unblock arteries in people with normal kidney function. But this trial now shows that cholesterol-lowering has similar effects in people with chronic kidney disease.'
Dr Martin Landray, who was also an investigator on the study, said: ‘There was no evidence of any serious adverse effects and, in particular, no support for earlier concerns that ezetimibe might cause cancer.'
Dr Terry McCormack, a cardiology GPSI in Whitby, north Yorkshire who has researched the efficacy of ezetimibe said: ‘SHARP is important for two reasons. Firstly it is the first trial to show benefit from treating cholesterol in renal failure patients. Most of the benefit was seen in the non dialysis patients.
‘The lowering of cholesterol was achieved by combining a low dose of simvastatin 20mg with ezetimibe. We cannot know which drug had the most benefit, or if both did bring about a benefit but the combination did achieve very low LDLs.
‘The second is that there was no significant cancer signal here which reduces fear of harm from ezetimibe as suggested by the SEAS trial.'
Dr Terry McCormack
