Updated Nov. 12, 2013 4:36 p.m. ET
The long-standing strategy of reducing heart-attack risk by lowering cholesterol to specific targets is being jettisoned under new clinical guidelines unveiled Tuesday that mark the biggest shift in cardiovascular-disease prevention in nearly three decades.
Gone is the familiar and easy-to-understand guidance to keep LDL, or bad cholesterol, below 100 or below 70 for people at high risk—a mainstay of current prevention policy. Instead, doctors are being told to assess a patient's risk more broadly and prescribe cholesterol-lowering statin drugs to those falling within one of four risk categories.
The aim is to more effectively direct statin treatment to patients with the most to gain, and move away from relatively arbitrary treatment targets that are less reliable in predicting risk than is widely believed.
"We're trying to focus the most appropriate therapy to prevent heart attack and stroke...in a wide range of patients," said Neil J. Stone, professor of medicine at Northwestern University Feinberg School of Medicine and head of the panel that wrote the cholesterol guidelines.
Cardiovascular disease is the Western world's leading killer. In the U.S., heart disease accounts for about 600,000 deaths each year, or about one in four deaths. About 130,000 people in the U.S. die each year of stroke, which is also a major cause of disability.
Numerous studies show that statins, which are among the most prescribed drugs in the world, reduce the risk of heart attack and stroke. But solid data demonstrating the benefit of reaching specific targets are lacking, said Dr. Stone.
While lowering LDL remains a critical goal, the focus is on the risk reduction achieved with statins rather than the effect on LDL, said Donald Lloyd-Jones, chief of preventive medicine at Northwestern and a member of the guidelines panel.
Cardiologists expect the recommendations, jointly developed by the American College of Cardiology and the American Heart Association, to substantially change the conversation between doctors and tens of millions of patients over the best way to lower their risk of a heart attack or stroke.
The risk groups identified in the guidelines include patients who have already had a heart attack, stroke or major symptoms of cardiovascular disease; those with an LDL of 190 or higher, which typically has a genetic cause; people with diabetes; and anyone ages 40 to 79 who faces a 7.5% risk of having a heart attack over the next 10 years, according to a new risk score. That score—with a lower threshold than under current guidelines—takes into account cholesterol level, smoking status, blood pressure and other factors.
All are recommended to take high or moderate statin doses that would results in LDL reductions of about 30% to more than 50%.
If fully implemented, the guidelines could more than double the number of Americans who qualify for statin therapy, to more than 30 million, the authors estimated.
The new approach is likely to have a modest immediate effect on the pharmaceutical industry. All but one of the statins available, including Lipitor, have lost patent protection and are available as inexpensive generics.
AstraZeneca AZN.LN -0.23% Astrazeneca PLC U.K.: London [SUP]GBp[/SUP]3284.50 -7.50 -0.23% Nov. 12, 2013 4:35 pm Volume : 1.94M P/E Ratio 14.01 Market Cap GBp41.26 Billion Dividend Yield N/A Rev. per Employee GBp323,863 11/01/13 Corporate Watch 10/31/13 CFO Moves: AstraZeneca, Moly M... 10/31/13 AstraZeneca Names CFO, Disclos... More quote details and news » AZN.LN in
Your Value Your Change Short position PLC's Crestor, the one remaining branded statin and the most powerful on the market, could get a boost from the recommendations. Merck MRK +1.26% Merck & Co. Inc. U.S.: NYSE [SUP]$[/SUP]47.59 +0.59 +1.26% Nov. 12, 2013 4:00 pm Volume (Delayed 15m) : 13.94M AFTER HOURS [SUP]$[/SUP]47.46 -0.13 -0.27% Nov. 12, 2013 4:42 pm Volume (Delayed 15m): P/E Ratio 31.67 Market Cap $137.33 Billion Dividend Yield 3.61% Rev. per Employee $536,084 11/03/13 Sebelius Gives Drug Makers a S... 10/28/13 Merck Profit Falls 35% Amid We... 10/28/13 Stocks to Watch: Merck, Biogen... More quote details and news » MRK in Your Value Your Change Short position & Co.'s Zetia, a non-statin cholesterol-reducer that is also an ingredient in Vytorin, could take a hit because the guidelines discourage use of agents that haven't been proven to reduce risk of bad events. Zetia hasn't been shown to reduce bad events even though it lowers LDL.
But both supporters and critics of the new guidelines worry they will confuse patients and physicians, and potentially disrupt an easy-to-understand and successful strategy. While statins haven't been the only factor, research shows there has been a significant reduction in heart attacks and death from cardiovascular disease in the past two decades since the drugs were introduced.
"This is a tension between the practical and the scientific," said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. Having targets for LDL "gives doctors and patients something to shoot for" as well as a motivation to try to get there, Dr. Nissen said. "The elimination of target levels is going to be a huge change for physicians and patients."
The authors of the new guidelines say a change was needed because the numerical targets are too blunt a tool. The targets have never been tested in a clinical trial, but a review of the evidence suggested LDL targets could lead to undertreatment of some patients and overtreatment of others, doctors said.
For instance, a high-risk patient with an LDL of 180 who reduces it with a statin to 90 will substantially reduce his heart-attack risk. Yet under current guidelines he may be viewed as failing therapy by not getting to 70. Doctors often prescribe additional non-statin cholesterol agents for patients who weren't reaching targets with a statin alone, but there is no evidence that getting another 20 points lower would lead to a further meaningful reduction in risk.
Similarly, said Dr. Lloyd-Jones, an older patient who had accumulated other risk factors but had an LDL of 99 might be missed under the current strategy, even though statin treatment could offer significant benefit.
Statins "seem to work no matter what your lipids are," said Harlan Krumholz, a Yale University cardiologist, using a term doctors use to refer to blood fats including cholesterol. He wasn't an author of the guidelines, but he has argued in recent medical journal commentaries for moving away from LDL targets as a cornerstone of prevention.
"Knowing your number can be useful in understanding your risk, but not in chasing it as a strategy to improve your outcome," he said.
The new guidelines are expected to significantly increase statin use in part because they add stroke reduction as a goal and thus widen the net to include more women and minorities, who are more prone to suffer strokes than heart attacks. The researchers identified the 7.5% risk threshold as the point where the benefits of statin therapy to prevent first heart attacks or strokes clearly outweighed the risks, which can include muscle pain and a small risk of diabetes.
The cholesterol guideline was issued with three other heart-related recommendations to guide doctors on assessing risk, treating obesity and encouraging healthy diet and exercise habits.
The cholesterol document in particular is expected to generate controversy and will be discussed at a major session next week at the American Heart Association scientific meeting in Dallas.
"There will be a lot of controversy," said Dr. Stone, of Northwestern University. "You can't go anywhere new without creating a lot of questions. The hope is that we can answer those questions in a way that provides better patient care."
Write to Ron Winslow at [email protected]
The long-standing strategy of reducing heart-attack risk by lowering cholesterol to specific targets is being jettisoned under new clinical guidelines unveiled Tuesday that mark the biggest shift in cardiovascular-disease prevention in nearly three decades.
Gone is the familiar and easy-to-understand guidance to keep LDL, or bad cholesterol, below 100 or below 70 for people at high risk—a mainstay of current prevention policy. Instead, doctors are being told to assess a patient's risk more broadly and prescribe cholesterol-lowering statin drugs to those falling within one of four risk categories.
The aim is to more effectively direct statin treatment to patients with the most to gain, and move away from relatively arbitrary treatment targets that are less reliable in predicting risk than is widely believed.
"We're trying to focus the most appropriate therapy to prevent heart attack and stroke...in a wide range of patients," said Neil J. Stone, professor of medicine at Northwestern University Feinberg School of Medicine and head of the panel that wrote the cholesterol guidelines.
Cardiovascular disease is the Western world's leading killer. In the U.S., heart disease accounts for about 600,000 deaths each year, or about one in four deaths. About 130,000 people in the U.S. die each year of stroke, which is also a major cause of disability.
Numerous studies show that statins, which are among the most prescribed drugs in the world, reduce the risk of heart attack and stroke. But solid data demonstrating the benefit of reaching specific targets are lacking, said Dr. Stone.
While lowering LDL remains a critical goal, the focus is on the risk reduction achieved with statins rather than the effect on LDL, said Donald Lloyd-Jones, chief of preventive medicine at Northwestern and a member of the guidelines panel.
Cardiologists expect the recommendations, jointly developed by the American College of Cardiology and the American Heart Association, to substantially change the conversation between doctors and tens of millions of patients over the best way to lower their risk of a heart attack or stroke.
The risk groups identified in the guidelines include patients who have already had a heart attack, stroke or major symptoms of cardiovascular disease; those with an LDL of 190 or higher, which typically has a genetic cause; people with diabetes; and anyone ages 40 to 79 who faces a 7.5% risk of having a heart attack over the next 10 years, according to a new risk score. That score—with a lower threshold than under current guidelines—takes into account cholesterol level, smoking status, blood pressure and other factors.
All are recommended to take high or moderate statin doses that would results in LDL reductions of about 30% to more than 50%.
If fully implemented, the guidelines could more than double the number of Americans who qualify for statin therapy, to more than 30 million, the authors estimated.
The new approach is likely to have a modest immediate effect on the pharmaceutical industry. All but one of the statins available, including Lipitor, have lost patent protection and are available as inexpensive generics.
AstraZeneca AZN.LN -0.23% Astrazeneca PLC U.K.: London [SUP]GBp[/SUP]3284.50 -7.50 -0.23% Nov. 12, 2013 4:35 pm Volume : 1.94M P/E Ratio 14.01 Market Cap GBp41.26 Billion Dividend Yield N/A Rev. per Employee GBp323,863 11/01/13 Corporate Watch 10/31/13 CFO Moves: AstraZeneca, Moly M... 10/31/13 AstraZeneca Names CFO, Disclos... More quote details and news » AZN.LN in
Your Value Your Change Short position PLC's Crestor, the one remaining branded statin and the most powerful on the market, could get a boost from the recommendations. Merck MRK +1.26% Merck & Co. Inc. U.S.: NYSE [SUP]$[/SUP]47.59 +0.59 +1.26% Nov. 12, 2013 4:00 pm Volume (Delayed 15m) : 13.94M AFTER HOURS [SUP]$[/SUP]47.46 -0.13 -0.27% Nov. 12, 2013 4:42 pm Volume (Delayed 15m): P/E Ratio 31.67 Market Cap $137.33 Billion Dividend Yield 3.61% Rev. per Employee $536,084 11/03/13 Sebelius Gives Drug Makers a S... 10/28/13 Merck Profit Falls 35% Amid We... 10/28/13 Stocks to Watch: Merck, Biogen... More quote details and news » MRK in Your Value Your Change Short position & Co.'s Zetia, a non-statin cholesterol-reducer that is also an ingredient in Vytorin, could take a hit because the guidelines discourage use of agents that haven't been proven to reduce risk of bad events. Zetia hasn't been shown to reduce bad events even though it lowers LDL.But both supporters and critics of the new guidelines worry they will confuse patients and physicians, and potentially disrupt an easy-to-understand and successful strategy. While statins haven't been the only factor, research shows there has been a significant reduction in heart attacks and death from cardiovascular disease in the past two decades since the drugs were introduced.
"This is a tension between the practical and the scientific," said Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. Having targets for LDL "gives doctors and patients something to shoot for" as well as a motivation to try to get there, Dr. Nissen said. "The elimination of target levels is going to be a huge change for physicians and patients."
The authors of the new guidelines say a change was needed because the numerical targets are too blunt a tool. The targets have never been tested in a clinical trial, but a review of the evidence suggested LDL targets could lead to undertreatment of some patients and overtreatment of others, doctors said.
For instance, a high-risk patient with an LDL of 180 who reduces it with a statin to 90 will substantially reduce his heart-attack risk. Yet under current guidelines he may be viewed as failing therapy by not getting to 70. Doctors often prescribe additional non-statin cholesterol agents for patients who weren't reaching targets with a statin alone, but there is no evidence that getting another 20 points lower would lead to a further meaningful reduction in risk.
Similarly, said Dr. Lloyd-Jones, an older patient who had accumulated other risk factors but had an LDL of 99 might be missed under the current strategy, even though statin treatment could offer significant benefit.
Statins "seem to work no matter what your lipids are," said Harlan Krumholz, a Yale University cardiologist, using a term doctors use to refer to blood fats including cholesterol. He wasn't an author of the guidelines, but he has argued in recent medical journal commentaries for moving away from LDL targets as a cornerstone of prevention.
"Knowing your number can be useful in understanding your risk, but not in chasing it as a strategy to improve your outcome," he said.
The new guidelines are expected to significantly increase statin use in part because they add stroke reduction as a goal and thus widen the net to include more women and minorities, who are more prone to suffer strokes than heart attacks. The researchers identified the 7.5% risk threshold as the point where the benefits of statin therapy to prevent first heart attacks or strokes clearly outweighed the risks, which can include muscle pain and a small risk of diabetes.
The cholesterol guideline was issued with three other heart-related recommendations to guide doctors on assessing risk, treating obesity and encouraging healthy diet and exercise habits.
The cholesterol document in particular is expected to generate controversy and will be discussed at a major session next week at the American Heart Association scientific meeting in Dallas.
"There will be a lot of controversy," said Dr. Stone, of Northwestern University. "You can't go anywhere new without creating a lot of questions. The hope is that we can answer those questions in a way that provides better patient care."
Write to Ron Winslow at [email protected]