The blockbuster cholesterol-lowering drug Vytorin failed to slow age-related hardening of the heart valve that without surgery can lead to heart attack, stroke or death, doctors said Monday.
Vytorin worked no better than a placebo at blocking aortic stenosis, which leads to 95,000 valve-replacement operations and 25,000 deaths in the USA each year, says lead investigator Terje Pedersen of Ulleval University Hospital in Olso.
"We can conclude it will not affect the course of aortic stenosis," Pedersen says.
The study was designed to determine whether reducing a major risk factor for aortic stenosis, the buildup of plaque in arteries supplying the heart, might prevent valve damage. Within five years of diagnosis, most patients require surgery, develop heart failure or die.
But the study did not answer the most important question: whether Vytorin prevents heart attacks, strokes and deaths in patients who have coronary artery disease. "The jury is still out," says Robert Califf, head of clinical research at Duke University and a lead investigator in an 18,000-patient trial designed to provide an answer but won't produce results until 2012.
Vytorin was approved in 2004 based on its power to lower cholesterol. Researchers raised questions about Vytorin's effectiveness in January when they reported that the drug — a combination of cholesterol-lowering simvastatin and ezetimibe that blocks cholesterol absorption in the kidney — was no better at preventing carotid artery blockages than simvastatin alone.
Their study, called ENHANCE, apparently has slowed sales of Vytorin and Zetia, the trade name for ezetimibe sold alone. On Monday, the drug's makers, Schering-Plough and Merck, announced combined second-quarter sales of $1.2 billion, a 9% drop from the second quarter of 2007.
The new study, called SEAS, involved 1,873 patients and lasted four years. Half got Vytorin; half got a placebo. Vytorin lowered bad cholesterol by an average of 61% in those who took it.
Although Vytorin didn't slow aortic stenosis or reduce its complications, the drug did lower the risk of heart attacks, strokes, bypass surgery and other complications of blocked arteries by 22%, a first tantalizing hint that it might save lives.
But Pederson says the study wasn't designed to provide proof. He says he couldn't rule out the possibility that the combination's effectiveness stemmed solely from simvastatin, a generic statin that already has been shown to reduce the risk of death from coronary artery disease.
Although there were slightly more cancer deaths in patients taking Vytorin, an independent analysis concluded there is "no credible evidence" linking Vytorin with cancer, says Richard Peto of the Clinical Trials Unit at Oxford University.