Look SHARP

(well, maybe not)

Last week, results of the SHARP trialwere released with great fanfare. In this study, investigators randomized over 9000 patients with chronic kidney disease (creatinine ≥ 1.7 mg/dL in men and ≥ 1.5 mg/dL in women) to placebo vs. a combination of ezetimibe and simvastatin, marketed under the brand name Vytorin. Over a median follow-up of 5 years, patients who received the study drug had a 1% lower risk of stroke and a 1.5% lower risk of requiring opening or bypassing a blocked artery in the heart or elsewhere. However, there was no difference in rates of heart attack, death from heart disease, or death from any cause.

What is extraordinary about this trial is not the mixed effect on outcomes, but the fact that it represents yet another wasted opportunity to learn whether ezetimibe actually has any clinical benefit. This drug, launched in the US in 2002, has enjoyed a meteoric rise in sales. By 2006, ezetimibe accounted for 15% of all prescriptions for cholesterol-lowering drugs, and in 2010 over $4 billion was spent on the drug. However, there is practically no data about whether ezetimibe yields any clinical benefit, either when given alone or when used to augment statin therapy.

In a list of clinical trials of ezetimibe, only one completed study to date has evaluated whether ezetimibe on top of a statin drug is better than the statin alone. This study, published in 2008, found that adding ezetimbe had no beneficial effect on a marker of atherosclerosis – and if anything, was slightly worse than the statin alone. Nearly all other completed trials have evaluated the combination of ezetimibe and simvastatin against placebo – which tells us almost nothing about whether adding ezetimibe on top of standard therapy provides any clinical benefit (or harm) above standard therapy alone.

In essence, enormous financial resources are put into trials whose main results clearly have much more value for increasing drug sales than for helping doctors learn the best ways to treat their patients. As a result, many billions of dollars are spent each year on unproven therapies, and millions of patients are exposed to drugs with unclear benefit. We can do better. We must.

P.S. For a succinct and thoughful commentary on the SHARP trial, click here.