Controversial heart disease prevention guidelines that abandoned specific targets for reducing "bad" LDL cholesterol are under fresh assault after a major study highlighted the benefits of taking LDL to very low levels.
Guidelines issued last year by the American Heart Association and the American College of Cardiology asked doctors to assess individual patients' risk for heart disease over 10 years based on a complex calculation of risks posed by lifestyle, family history and other health conditions. Those deemed at sufficient risk would be prescribed cholesterol-lowering statins.
The recommendation overturned decades of practice in which doctors screened patients for high cholesterol, then sought to reduce LDL to a specific level. Many cardiologists criticized the guidelines, saying they were confusing, and that patients and physicians were comfortable with measurable goals to reduce the risk of heart disease, the world's No. 1 killer.
Those opponents got a boost from data released on Monday showing high-risk patients fared better when their LDL was brought to very low levels by adding Merck & Co's Zetia to treatment with a statin.
Several prominent heart specialists said the guidelines should be changed, with some advocating LDL targets even lower than previous ones. Many have ignored the year-old recommendations.
"I never really bought the new guidelines," said Dr. Andrew Klaus of Mount Carmel Health System in Columbus, Ohio. The Zetia trial “definitely showed that lower is better," he said. "I would predict the guidelines are going to be rewritten very soon."
The so-called Improve-It trial of Merck's Zetia, unveiled at the AHA’s annual meeting in Chicago, studied more than 18,000 high-risk patients. It showed they could further cut heart attacks and strokes by taking LDL cholesterol from about 70 to around 53.
Dr. Steven Nissen, cardiology chief at the Cleveland Clinic, said the result "blows up" the prevention guidelines.
"It matters how low you go (with LDL) ... which is why many of us were so upset about the guidelines," Nissen told Reuters. At a recent meeting of cardiologists and primary care doctors, Nissen asked how many had adopted the guidelines.
"Three out of those 300 raised their hand," he said. "Nobody is using them."
Millions of Americans at risk of heart disease could be affected by the outcome of the debate. Some 83.6 million live with some form or cardiovascular disease or the effects of stroke, according to the AHA.
By some estimates, the new guidelines would boost the use of high-potency statins such as AstraZeneca's Crestor and Pfizer Inc's Lipitor, now available as cheaper generic atorvastatin.
The debate could also affect the future of new medicines from Amgen Inc and Regeneron Pharmaceuticals Inc that reduce LDL even more aggressively.
In interviews with more than a dozen cardiologists attending the AHA meeting, most said they were wrestling with the guidelines.
AHA and ACC officials have heard the complaints and said the guidelines are subject to revision based on new scientific data.
"We don't want guidelines that serve as scientific tomes that nobody finds useful," said Dr. Robert Harrington, an AHA board member. "We need our guidelines to really help guide practice."
When a major trial like Improve-It comes out, "AHA absolutely responds to that," he said.
Dr. Patrick O’Gara, president of the ACC, said the new guidelines were based on the fact that clinical trials of cholesterol-lowering statin drugs were not designed to test the effectiveness of specific cholesterol targets - only the drugs themselves. Doctors following the guidelines tend to test cholesterol levels far less frequently, and that has some in the field worried.
"We're still having this back and forth, which seems to represent a gap between the manner in which trials were designed and the practical implications," O’Gara said. "I hope we will be able to strike the right balance in the process."
CLARIFYING THE MESSAGE
Dr. Lori Mosca of New York-Presbyterian Hospital, who helps train residents, said she is frequently asked how to interpret the guidelines.
"There is sufficient confusion out there that it's worthy of clarifying what the message is," she said.
Dr. Matthew Sorrentino, a preventive cardiologist at University of Chicago Medicine, uses the guidelines. But he said the older targets - an LDL of 70 for high-risk patients - were easier for doctors and patients to grasp.
"Almost everybody knew what the LDL target was," he said. "I can see making the guidelines easier to follow."
Writers of the guidelines, such as Dr. Donald Lloyd-Jones of Northwestern Medicine in Chicago, defended the scientific rigor behind them. He said focusing on a cholesterol goal may have led to undertreatment, perhaps failing to take into account the added risks from diabetes, obesity or smoking.
A new class of drugs, known as PCSK9 inhibitors, that can lower LDL by more than 50 percent may increase the pressure for new, even lower, LDL targets, some doctors said. One from Amgen and another developed by Regeneron and Sanofi
are expected to reach the market next year and initially be used in patients with extremely high cholesterol or those who cannot tolerate statins.
"We can't really get away from paying attention to what the LDL is," said Dr. Daniel Rader, director of the preventive cardiology program at the University of Pennsylvania.