Mitchel L. Zoler, PhD

AMSTERDAM – When the European Society of Cardiology in June reset its target systolic blood pressure for patients with diabetes, chronic kidney disease, or a history of cardiovascular disease to less than 140 mm Hg, it joined a small but growing cadre of medical societies that have looked at recent evidence and concluded that nothing currently justifies treating to a target systolic blood pressure below 130 mm Hg or to a diastolic pressure below 80 mm Hg.

The European Society of Cardiology’s new edition of hypertension management guidelines, produced in collaboration with the European Society of Hypertension, contrasts with the conspicuous void in U.S. practice that’s been widely acknowledged for a few years now: the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), the prevailing version of U.S. hypertension-management guidelines, is a decade old and outdated.

The delay-plagued process to come out with the eighth JNC edition (JNC 8) took an unexpected turn last June, when the National Heart, Lung, and Blood Institute, the agency that shepherded the first seven editions of U.S. hypertension guidelines going back to 1976, announced that it was immediately turning responsibility for getting JNC 8 finalized and out to the public over to "partner organizations" such as the American College of Cardiology and American Heart Association.

With this new wrinkle, even with the ACC and AHA scrambling to deal with their new responsibility, it seems like JNC 8 – or whatever name it will have when it finally emerges – will not come out until 2014 at the soonest, making the ESC guidelines the only up-to-date hypertension recommendations from a cardiology-oriented medical group for at least several more months.

A U.S. view of the Euro guidelines

"U.S. physicians need to be aware of the evidence as it evolves," said Dr. Sidney C. Smith Jr., professor of medicine at the University of North Carolina in Chapel Hill, and a member of the panel that’s been writing JNC 8.

"The American Diabetes Association came out with a similar recommendation" on the systolic blood pressure target for patients with diabetes. U.S. physicians should "see what the ADA says, see what the ESC says, and then decide what they should do. They need to read the recommendations and supporting evidence and see if it applies to their patients," Dr. Smith advised in an interview. "I think that patients and physicians will look at the current evidence and respond. You’ve got to go with what the evidence says and what seems best for the patient. No law says that you shall only do what is in the" JNC 7 guidelines.

A trickier situation may be settings in which physicians are assessed based on how many of their patients with diabetes reach a blood pressure target of less than 130/80, he said. "How do health care systems respond to evidence as it evolves? At what point should performance measures get changed?" Dr. Smith asked.

But because of its orientation to European populations, the new ESC hypertension guidelines can’t completely fill the U.S. vacuum.

"I’m sure JNC 8 will be nuanced differently than the European guidelines because we have a different population in the U.S., particularly African Americans and more patients with renal failure," said Dr. Kim Allan Williams Sr. of Wayne State University, Detroit. Dr. Williams will take the position of professor of medicine and chief of cardiovascular services at Rush University Medical Center in Chicago on Nov. 1. "As a practitioner, I would worry about using 140/90 mm Hg as the only target for the African American population that I deal with all the time. The stroke and renal failure rates are much higher in these patients" than in other patients with hypertension, he said in an interview. "The new European guidelines don’t deal with patients with African ancestry. JNC 7 had a section on blood pressure management in minority groups, which was very helpful."

Resetting the target for diabetics

The dialing up of the target systolic blood pressure for patients with diabetes or other high-risk factors, and the resulting damping down of antihypertensive treatment intensity, is the biggest change in the 2013 ESC hypertension recommendations, said Dr. Giuseppe Mancia, who chaired the task force that wrote the recommendations.

"We need to base the recommendations on the evidence. It’s been a consistent finding, in ONTARGET, ACCORD, and in other studies, that pushing the blood pressure of patients with diabetes below 130 mm Hg provided no additional benefit but was linked with more adverse events. If you set a lower target you need to be absolutely sure there is no harm associated with it, and at the moment we cannot say that.

"Adverse events [leads to] more discontinuation of treatment, and there is now evidence that discontinuation is closely related to an increase in events," said Dr. Mancia, professor of medicine at the University of Milan and cochair of the ESC hypertension task force. "There is a remarkable relationship between longer time taking antihypertensive drugs and cardiovascular protection."

"We were probably too radical in the previous guidelines" in setting a target systolic pressure at less than 130 mm Hg, said Dr. Renata Cífková, professor and head of preventive cardiology at Thomayer Teaching Hospital in Prague and a member of the ESC hypertension panel. "We saw that this was not evidence based. When we reviewed the same studies and also included the newer studies, like ACCORD, it basically confirmed our new blood pressure targets." Another advantage is that patients and physicians "will feel more comfortable with these goals," both in their achievability and by producing fewer adverse events," she said in an interview.

"This is the first major change in the hypertension guidelines for a number of years," the first full update since 2007, said Dr. Bryan Williams, professor and chairman of medicine at University College, London. "The data presented showed that, while there is indisputable evidence to lower pressures below 150/90 mm Hg, and strong evidence to lower below 140/90 mm Hg, there is limited or no evidence to recommend lowering pressures to below 130/80 mm Hg, and in some situations there is evidence for a signal of harm," said Dr. Williams. "The new guidelines simplify the target, a blood pressure of less than 140 mm Hg for everyone, regardless of their level of risk."

"The change in target means that ‘the lower the better’ is no longer true. This will reduce the number of drugs that patients receive and will avoid some adverse effects," said Dr. Nikolaus Marx, professor and director of medicine at Aachen (Germany) University Hospital.

Other groups came first

As Dr. Smith noted, the ESC is not the first medical group to scale back aggressive blood pressure targets for patients with diabetes or chronic kidney disease, but it may be the first major cardiology society to do so. Last year, the Kidney Disease Improving Global Outcomes foundation issued guidelines for hypertension management in patients with chronic kidney disease (Kidney International Supplement 2012;2:340-414). The expert panel recommended a target pressure of 140/90 mm Hg or below for patients with chronic kidney disease with or without diabetes as long as their daily urine albumin remained below 30 mg. For patients with more severe albuminuria, the panel recommended a target of 130/80 mm Hg or less for all chronic kidney disease patients regardless of their diabetes status.

Earlier this year, the American Diabetes Association published its Standards of Medical Care in Diabetes–2013, which set a target blood pressure for patients with diabetes at less than 140/80 mm Hg (the ESC set a diastolic pressure target of less than 85 mm Hg) (Diabetes Care 2013;36:S11-S66).

Other changes in the ESC guidelines

The ESC guidelines include some other notable changes (Euro. Heart J. 2013;34:2159-219):

• The basic systolic blood pressure goal for elderly patients, defined as 65 years or older, was set as less than 150 mm Hg. The goal can lower to less than 140 mm Hg for "fit elderly patients" younger than 80 years old if treatment is well tolerated.

• The guidelines place new emphasis on using some method for out-of-office blood pressure measurement – either ambulatory or home-based blood pressure measurement – for patients suspected of having either false-positive office-based blood pressure measurements (white coat hypertension) or false-negative office blood pressure levels (masked hypertension).

• The universe of first-line antihypertensive medications was whittled down to four: thiazide diuretics, calcium channel blockers, ACE inhibitors, and angiotensin-receptor blockers. Although the new guidelines call beta-blockers a "cornerstone" of treatment for patients with coronary heart disease and tachyarrhythmias, including atrial fibrillation, they are no longer seen as first-line agents for patients without these coexisting cardiac diseases or for young patients.

• A section on treating hypertension in young adults encourages applying the below 140/90 mm Hg target to these patients as well after a reasonable attempt at lifestyle intervention only.

• An updated approach to managing gestational hypertension and preventing preeclampsia includes use of prophylactic aspirin by women at moderate or high risk of preeclampsia, and treating pregnant women to a blood pressure of less than 150/95 mm Hg if pressure this high is persistent, or to a target of less than 140/90 mm Hg in women with gestational hypertension, symptoms, or subclinical organ damage.

Dr. Smith and Dr. Williams said that they had no relevant disclosures. Dr. Mancia said that he has been a consultant to 14 drug and device companies. Dr. Renata Cífková said that she had been a consultant to Daiichi Sankyo, Teva, Zentiva, Merck Sharpe and Dohme, Actavis, Berlin Chemie, Boehringer Ingelheim, and Bayer. Dr. Marx said that he has been a consultant to 13 drug and device companies. Dr. Williams said that he has been a consultant to Pfizer, Merck, Sanofi-BMS, and Novartis.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

AMSTERDAM – When the European Society of Cardiology in June reset its target systolic blood pressure for patients with diabetes, chronic kidney disease, or a history of cardiovascular disease to less than 140 mm Hg, it joined a small but growing cadre of medical societies that have looked at recent evidence and concluded that nothing currently justifies treating to a target systolic blood pressure below 130 mm Hg or to a diastolic pressure below 80 mm Hg.

The European Society of Cardiology’s new edition of hypertension management guidelines, produced in collaboration with the European Society of Hypertension, contrasts with the conspicuous void in U.S. practice that’s been widely acknowledged for a few years now: the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), the prevailing version of U.S. hypertension-management guidelines, is a decade old and outdated.

The delay-plagued process to come out with the eighth JNC edition (JNC 8) took an unexpected turn last June, when the National Heart, Lung, and Blood Institute, the agency that shepherded the first seven editions of U.S. hypertension guidelines going back to 1976, announced that it was immediately turning responsibility for getting JNC 8 finalized and out to the public over to "partner organizations" such as the American College of Cardiology and American Heart Association.

With this new wrinkle, even with the ACC and AHA scrambling to deal with their new responsibility, it seems like JNC 8 – or whatever name it will have when it finally emerges – will not come out until 2014 at the soonest, making the ESC guidelines the only up-to-date hypertension recommendations from a cardiology-oriented medical group for at least several more months.

A U.S. view of the Euro guidelines

"U.S. physicians need to be aware of the evidence as it evolves," said Dr. Sidney C. Smith Jr., professor of medicine at the University of North Carolina in Chapel Hill, and a member of the panel that’s been writing JNC 8.

"The American Diabetes Association came out with a similar recommendation" on the systolic blood pressure target for patients with diabetes. U.S. physicians should "see what the ADA says, see what the ESC says, and then decide what they should do. They need to read the recommendations and supporting evidence and see if it applies to their patients," Dr. Smith advised in an interview. "I think that patients and physicians will look at the current evidence and respond. You’ve got to go with what the evidence says and what seems best for the patient. No law says that you shall only do what is in the" JNC 7 guidelines.

A trickier situation may be settings in which physicians are assessed based on how many of their patients with diabetes reach a blood pressure target of less than 130/80, he said. "How do health care systems respond to evidence as it evolves? At what point should performance measures get changed?" Dr. Smith asked.

But because of its orientation to European populations, the new ESC hypertension guidelines can’t completely fill the U.S. vacuum.

"I’m sure JNC 8 will be nuanced differently than the European guidelines because we have a different population in the U.S., particularly African Americans and more patients with renal failure," said Dr. Kim Allan Williams Sr. of Wayne State University, Detroit. Dr. Williams will take the position of professor of medicine and chief of cardiovascular services at Rush University Medical Center in Chicago on Nov. 1. "As a practitioner, I would worry about using 140/90 mm Hg as the only target for the African American population that I deal with all the time. The stroke and renal failure rates are much higher in these patients" than in other patients with hypertension, he said in an interview. "The new European guidelines don’t deal with patients with African ancestry. JNC 7 had a section on blood pressure management in minority groups, which was very helpful."

Resetting the target for diabetics

The dialing up of the target systolic blood pressure for patients with diabetes or other high-risk factors, and the resulting damping down of antihypertensive treatment intensity, is the biggest change in the 2013 ESC hypertension recommendations, said Dr. Giuseppe Mancia, who chaired the task force that wrote the recommendations.

"We need to base the recommendations on the evidence. It’s been a consistent finding, in ONTARGET, ACCORD, and in other studies, that pushing the blood pressure of patients with diabetes below 130 mm Hg provided no additional benefit but was linked with more adverse events. If you set a lower target you need to be absolutely sure there is no harm associated with it, and at the moment we cannot say that.

"Adverse events [leads to] more discontinuation of treatment, and there is now evidence that discontinuation is closely related to an increase in events," said Dr. Mancia, professor of medicine at the University of Milan and cochair of the ESC hypertension task force. "There is a remarkable relationship between longer time taking antihypertensive drugs and cardiovascular protection."

"We were probably too radical in the previous guidelines" in setting a target systolic pressure at less than 130 mm Hg, said Dr. Renata Cífková, professor and head of preventive cardiology at Thomayer Teaching Hospital in Prague and a member of the ESC hypertension panel. "We saw that this was not evidence based. When we reviewed the same studies and also included the newer studies, like ACCORD, it basically confirmed our new blood pressure targets." Another advantage is that patients and physicians "will feel more comfortable with these goals," both in their achievability and by producing fewer adverse events," she said in an interview.

"This is the first major change in the hypertension guidelines for a number of years," the first full update since 2007, said Dr. Bryan Williams, professor and chairman of medicine at University College, London. "The data presented showed that, while there is indisputable evidence to lower pressures below 150/90 mm Hg, and strong evidence to lower below 140/90 mm Hg, there is limited or no evidence to recommend lowering pressures to below 130/80 mm Hg, and in some situations there is evidence for a signal of harm," said Dr. Williams. "The new guidelines simplify the target, a blood pressure of less than 140 mm Hg for everyone, regardless of their level of risk."

"The change in target means that ‘the lower the better’ is no longer true. This will reduce the number of drugs that patients receive and will avoid some adverse effects," said Dr. Nikolaus Marx, professor and director of medicine at Aachen (Germany) University Hospital.

Other groups came first

As Dr. Smith noted, the ESC is not the first medical group to scale back aggressive blood pressure targets for patients with diabetes or chronic kidney disease, but it may be the first major cardiology society to do so. Last year, the Kidney Disease Improving Global Outcomes foundation issued guidelines for hypertension management in patients with chronic kidney disease (Kidney International Supplement 2012;2:340-414). The expert panel recommended a target pressure of 140/90 mm Hg or below for patients with chronic kidney disease with or without diabetes as long as their daily urine albumin remained below 30 mg. For patients with more severe albuminuria, the panel recommended a target of 130/80 mm Hg or less for all chronic kidney disease patients regardless of their diabetes status.

Earlier this year, the American Diabetes Association published its Standards of Medical Care in Diabetes–2013, which set a target blood pressure for patients with diabetes at less than 140/80 mm Hg (the ESC set a diastolic pressure target of less than 85 mm Hg) (Diabetes Care 2013;36:S11-S66).

Other changes in the ESC guidelines

The ESC guidelines include some other notable changes (Euro. Heart J. 2013;34:2159-219):

• The basic systolic blood pressure goal for elderly patients, defined as 65 years or older, was set as less than 150 mm Hg. The goal can lower to less than 140 mm Hg for "fit elderly patients" younger than 80 years old if treatment is well tolerated.

• The guidelines place new emphasis on using some method for out-of-office blood pressure measurement – either ambulatory or home-based blood pressure measurement – for patients suspected of having either false-positive office-based blood pressure measurements (white coat hypertension) or false-negative office blood pressure levels (masked hypertension).

• The universe of first-line antihypertensive medications was whittled down to four: thiazide diuretics, calcium channel blockers, ACE inhibitors, and angiotensin-receptor blockers. Although the new guidelines call beta-blockers a "cornerstone" of treatment for patients with coronary heart disease and tachyarrhythmias, including atrial fibrillation, they are no longer seen as first-line agents for patients without these coexisting cardiac diseases or for young patients.

• A section on treating hypertension in young adults encourages applying the below 140/90 mm Hg target to these patients as well after a reasonable attempt at lifestyle intervention only.

• An updated approach to managing gestational hypertension and preventing preeclampsia includes use of prophylactic aspirin by women at moderate or high risk of preeclampsia, and treating pregnant women to a blood pressure of less than 150/95 mm Hg if pressure this high is persistent, or to a target of less than 140/90 mm Hg in women with gestational hypertension, symptoms, or subclinical organ damage.

Dr. Smith and Dr. Williams said that they had no relevant disclosures. Dr. Mancia said that he has been a consultant to 14 drug and device companies. Dr. Renata Cífková said that she had been a consultant to Daiichi Sankyo, Teva, Zentiva, Merck Sharpe and Dohme, Actavis, Berlin Chemie, Boehringer Ingelheim, and Bayer. Dr. Marx said that he has been a consultant to 13 drug and device companies. Dr. Williams said that he has been a consultant to Pfizer, Merck, Sanofi-BMS, and Novartis.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

AMSTERDAM – When the European Society of Cardiology in June reset its target systolic blood pressure for patients with diabetes, chronic kidney disease, or a history of cardiovascular disease to less than 140 mm Hg, it joined a small but growing cadre of medical societies that have looked at recent evidence and concluded that nothing currently justifies treating to a target systolic blood pressure below 130 mm Hg or to a diastolic pressure below 80 mm Hg.

The European Society of Cardiology’s new edition of hypertension management guidelines, produced in collaboration with the European Society of Hypertension, contrasts with the conspicuous void in U.S. practice that’s been widely acknowledged for a few years now: the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), the prevailing version of U.S. hypertension-management guidelines, is a decade old and outdated.

The delay-plagued process to come out with the eighth JNC edition (JNC 8) took an unexpected turn last June, when the National Heart, Lung, and Blood Institute, the agency that shepherded the first seven editions of U.S. hypertension guidelines going back to 1976, announced that it was immediately turning responsibility for getting JNC 8 finalized and out to the public over to "partner organizations" such as the American College of Cardiology and American Heart Association.

With this new wrinkle, even with the ACC and AHA scrambling to deal with their new responsibility, it seems like JNC 8 – or whatever name it will have when it finally emerges – will not come out until 2014 at the soonest, making the ESC guidelines the only up-to-date hypertension recommendations from a cardiology-oriented medical group for at least several more months.

A U.S. view of the Euro guidelines

"U.S. physicians need to be aware of the evidence as it evolves," said Dr. Sidney C. Smith Jr., professor of medicine at the University of North Carolina in Chapel Hill, and a member of the panel that’s been writing JNC 8.

"The American Diabetes Association came out with a similar recommendation" on the systolic blood pressure target for patients with diabetes. U.S. physicians should "see what the ADA says, see what the ESC says, and then decide what they should do. They need to read the recommendations and supporting evidence and see if it applies to their patients," Dr. Smith advised in an interview. "I think that patients and physicians will look at the current evidence and respond. You’ve got to go with what the evidence says and what seems best for the patient. No law says that you shall only do what is in the" JNC 7 guidelines.

A trickier situation may be settings in which physicians are assessed based on how many of their patients with diabetes reach a blood pressure target of less than 130/80, he said. "How do health care systems respond to evidence as it evolves? At what point should performance measures get changed?" Dr. Smith asked.

But because of its orientation to European populations, the new ESC hypertension guidelines can’t completely fill the U.S. vacuum.

"I’m sure JNC 8 will be nuanced differently than the European guidelines because we have a different population in the U.S., particularly African Americans and more patients with renal failure," said Dr. Kim Allan Williams Sr. of Wayne State University, Detroit. Dr. Williams will take the position of professor of medicine and chief of cardiovascular services at Rush University Medical Center in Chicago on Nov. 1. "As a practitioner, I would worry about using 140/90 mm Hg as the only target for the African American population that I deal with all the time. The stroke and renal failure rates are much higher in these patients" than in other patients with hypertension, he said in an interview. "The new European guidelines don’t deal with patients with African ancestry. JNC 7 had a section on blood pressure management in minority groups, which was very helpful."

Resetting the target for diabetics

The dialing up of the target systolic blood pressure for patients with diabetes or other high-risk factors, and the resulting damping down of antihypertensive treatment intensity, is the biggest change in the 2013 ESC hypertension recommendations, said Dr. Giuseppe Mancia, who chaired the task force that wrote the recommendations.

"We need to base the recommendations on the evidence. It’s been a consistent finding, in ONTARGET, ACCORD, and in other studies, that pushing the blood pressure of patients with diabetes below 130 mm Hg provided no additional benefit but was linked with more adverse events. If you set a lower target you need to be absolutely sure there is no harm associated with it, and at the moment we cannot say that.

"Adverse events [leads to] more discontinuation of treatment, and there is now evidence that discontinuation is closely related to an increase in events," said Dr. Mancia, professor of medicine at the University of Milan and cochair of the ESC hypertension task force. "There is a remarkable relationship between longer time taking antihypertensive drugs and cardiovascular protection."

"We were probably too radical in the previous guidelines" in setting a target systolic pressure at less than 130 mm Hg, said Dr. Renata Cífková, professor and head of preventive cardiology at Thomayer Teaching Hospital in Prague and a member of the ESC hypertension panel. "We saw that this was not evidence based. When we reviewed the same studies and also included the newer studies, like ACCORD, it basically confirmed our new blood pressure targets." Another advantage is that patients and physicians "will feel more comfortable with these goals," both in their achievability and by producing fewer adverse events," she said in an interview.

"This is the first major change in the hypertension guidelines for a number of years," the first full update since 2007, said Dr. Bryan Williams, professor and chairman of medicine at University College, London. "The data presented showed that, while there is indisputable evidence to lower pressures below 150/90 mm Hg, and strong evidence to lower below 140/90 mm Hg, there is limited or no evidence to recommend lowering pressures to below 130/80 mm Hg, and in some situations there is evidence for a signal of harm," said Dr. Williams. "The new guidelines simplify the target, a blood pressure of less than 140 mm Hg for everyone, regardless of their level of risk."

"The change in target means that ‘the lower the better’ is no longer true. This will reduce the number of drugs that patients receive and will avoid some adverse effects," said Dr. Nikolaus Marx, professor and director of medicine at Aachen (Germany) University Hospital.

Other groups came first

As Dr. Smith noted, the ESC is not the first medical group to scale back aggressive blood pressure targets for patients with diabetes or chronic kidney disease, but it may be the first major cardiology society to do so. Last year, the Kidney Disease Improving Global Outcomes foundation issued guidelines for hypertension management in patients with chronic kidney disease (Kidney International Supplement 2012;2:340-414). The expert panel recommended a target pressure of 140/90 mm Hg or below for patients with chronic kidney disease with or without diabetes as long as their daily urine albumin remained below 30 mg. For patients with more severe albuminuria, the panel recommended a target of 130/80 mm Hg or less for all chronic kidney disease patients regardless of their diabetes status.

Earlier this year, the American Diabetes Association published its Standards of Medical Care in Diabetes–2013, which set a target blood pressure for patients with diabetes at less than 140/80 mm Hg (the ESC set a diastolic pressure target of less than 85 mm Hg) (Diabetes Care 2013;36:S11-S66).

Other changes in the ESC guidelines

The ESC guidelines include some other notable changes (Euro. Heart J. 2013;34:2159-219):

• The basic systolic blood pressure goal for elderly patients, defined as 65 years or older, was set as less than 150 mm Hg. The goal can lower to less than 140 mm Hg for "fit elderly patients" younger than 80 years old if treatment is well tolerated.

• The guidelines place new emphasis on using some method for out-of-office blood pressure measurement – either ambulatory or home-based blood pressure measurement – for patients suspected of having either false-positive office-based blood pressure measurements (white coat hypertension) or false-negative office blood pressure levels (masked hypertension).

• The universe of first-line antihypertensive medications was whittled down to four: thiazide diuretics, calcium channel blockers, ACE inhibitors, and angiotensin-receptor blockers. Although the new guidelines call beta-blockers a "cornerstone" of treatment for patients with coronary heart disease and tachyarrhythmias, including atrial fibrillation, they are no longer seen as first-line agents for patients without these coexisting cardiac diseases or for young patients.

• A section on treating hypertension in young adults encourages applying the below 140/90 mm Hg target to these patients as well after a reasonable attempt at lifestyle intervention only.

• An updated approach to managing gestational hypertension and preventing preeclampsia includes use of prophylactic aspirin by women at moderate or high risk of preeclampsia, and treating pregnant women to a blood pressure of less than 150/95 mm Hg if pressure this high is persistent, or to a target of less than 140/90 mm Hg in women with gestational hypertension, symptoms, or subclinical organ damage.

Dr. Smith and Dr. Williams said that they had no relevant disclosures. Dr. Mancia said that he has been a consultant to 14 drug and device companies. Dr. Renata Cífková said that she had been a consultant to Daiichi Sankyo, Teva, Zentiva, Merck Sharpe and Dohme, Actavis, Berlin Chemie, Boehringer Ingelheim, and Bayer. Dr. Marx said that he has been a consultant to 13 drug and device companies. Dr. Williams said that he has been a consultant to Pfizer, Merck, Sanofi-BMS, and Novartis.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

AMSTERDAM – When the European Society of Cardiology in June reset its target systolic blood pressure for patients with diabetes, chronic kidney disease, or a history of cardiovascular disease to less than 140 mm Hg, it joined a small but growing cadre of medical societies that have looked at recent evidence and concluded that nothing currently justifies treating to a target systolic blood pressure below 130 mm Hg or to a diastolic pressure below 80 mm Hg.

The European Society of Cardiology’s new edition of hypertension management guidelines, produced in collaboration with the European Society of Hypertension, contrasts with the conspicuous void in U.S. practice that’s been widely acknowledged for a few years now: the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), the prevailing version of U.S. hypertension-management guidelines, is a decade old and outdated.

The delay-plagued process to come out with the eighth JNC edition (JNC 8) took an unexpected turn last June, when the National Heart, Lung, and Blood Institute, the agency that shepherded the first seven editions of U.S. hypertension guidelines going back to 1976, announced that it was immediately turning responsibility for getting JNC 8 finalized and out to the public over to "partner organizations" such as the American College of Cardiology and American Heart Association.

With this new wrinkle, even with the ACC and AHA scrambling to deal with their new responsibility, it seems like JNC 8 – or whatever name it will have when it finally emerges – will not come out until 2014 at the soonest, making the ESC guidelines the only up-to-date hypertension recommendations from a cardiology-oriented medical group for at least several more months.

A U.S. view of the Euro guidelines

"U.S. physicians need to be aware of the evidence as it evolves," said Dr. Sidney C. Smith Jr., professor of medicine at the University of North Carolina in Chapel Hill, and a member of the panel that’s been writing JNC 8.

"The American Diabetes Association came out with a similar recommendation" on the systolic blood pressure target for patients with diabetes. U.S. physicians should "see what the ADA says, see what the ESC says, and then decide what they should do. They need to read the recommendations and supporting evidence and see if it applies to their patients," Dr. Smith advised in an interview. "I think that patients and physicians will look at the current evidence and respond. You’ve got to go with what the evidence says and what seems best for the patient. No law says that you shall only do what is in the" JNC 7 guidelines.

A trickier situation may be settings in which physicians are assessed based on how many of their patients with diabetes reach a blood pressure target of less than 130/80, he said. "How do health care systems respond to evidence as it evolves? At what point should performance measures get changed?" Dr. Smith asked.

But because of its orientation to European populations, the new ESC hypertension guidelines can’t completely fill the U.S. vacuum.

"I’m sure JNC 8 will be nuanced differently than the European guidelines because we have a different population in the U.S., particularly African Americans and more patients with renal failure," said Dr. Kim Allan Williams Sr. of Wayne State University, Detroit. Dr. Williams will take the position of professor of medicine and chief of cardiovascular services at Rush University Medical Center in Chicago on Nov. 1. "As a practitioner, I would worry about using 140/90 mm Hg as the only target for the African American population that I deal with all the time. The stroke and renal failure rates are much higher in these patients" than in other patients with hypertension, he said in an interview. "The new European guidelines don’t deal with patients with African ancestry. JNC 7 had a section on blood pressure management in minority groups, which was very helpful."

Resetting the target for diabetics

The dialing up of the target systolic blood pressure for patients with diabetes or other high-risk factors, and the resulting damping down of antihypertensive treatment intensity, is the biggest change in the 2013 ESC hypertension recommendations, said Dr. Giuseppe Mancia, who chaired the task force that wrote the recommendations.

"We need to base the recommendations on the evidence. It’s been a consistent finding, in ONTARGET, ACCORD, and in other studies, that pushing the blood pressure of patients with diabetes below 130 mm Hg provided no additional benefit but was linked with more adverse events. If you set a lower target you need to be absolutely sure there is no harm associated with it, and at the moment we cannot say that.

"Adverse events [leads to] more discontinuation of treatment, and there is now evidence that discontinuation is closely related to an increase in events," said Dr. Mancia, professor of medicine at the University of Milan and cochair of the ESC hypertension task force. "There is a remarkable relationship between longer time taking antihypertensive drugs and cardiovascular protection."

"We were probably too radical in the previous guidelines" in setting a target systolic pressure at less than 130 mm Hg, said Dr. Renata Cífková, professor and head of preventive cardiology at Thomayer Teaching Hospital in Prague and a member of the ESC hypertension panel. "We saw that this was not evidence based. When we reviewed the same studies and also included the newer studies, like ACCORD, it basically confirmed our new blood pressure targets." Another advantage is that patients and physicians "will feel more comfortable with these goals," both in their achievability and by producing fewer adverse events," she said in an interview.

"This is the first major change in the hypertension guidelines for a number of years," the first full update since 2007, said Dr. Bryan Williams, professor and chairman of medicine at University College, London. "The data presented showed that, while there is indisputable evidence to lower pressures below 150/90 mm Hg, and strong evidence to lower below 140/90 mm Hg, there is limited or no evidence to recommend lowering pressures to below 130/80 mm Hg, and in some situations there is evidence for a signal of harm," said Dr. Williams. "The new guidelines simplify the target, a blood pressure of less than 140 mm Hg for everyone, regardless of their level of risk."

"The change in target means that ‘the lower the better’ is no longer true. This will reduce the number of drugs that patients receive and will avoid some adverse effects," said Dr. Nikolaus Marx, professor and director of medicine at Aachen (Germany) University Hospital.

Other groups came first

As Dr. Smith noted, the ESC is not the first medical group to scale back aggressive blood pressure targets for patients with diabetes or chronic kidney disease, but it may be the first major cardiology society to do so. Last year, the Kidney Disease Improving Global Outcomes foundation issued guidelines for hypertension management in patients with chronic kidney disease (Kidney International Supplement 2012;2:340-414). The expert panel recommended a target pressure of 140/90 mm Hg or below for patients with chronic kidney disease with or without diabetes as long as their daily urine albumin remained below 30 mg. For patients with more severe albuminuria, the panel recommended a target of 130/80 mm Hg or less for all chronic kidney disease patients regardless of their diabetes status.

Earlier this year, the American Diabetes Association published its Standards of Medical Care in Diabetes–2013, which set a target blood pressure for patients with diabetes at less than 140/80 mm Hg (the ESC set a diastolic pressure target of less than 85 mm Hg) (Diabetes Care 2013;36:S11-S66).

Other changes in the ESC guidelines

The ESC guidelines include some other notable changes (Euro. Heart J. 2013;34:2159-219):

• The basic systolic blood pressure goal for elderly patients, defined as 65 years or older, was set as less than 150 mm Hg. The goal can lower to less than 140 mm Hg for "fit elderly patients" younger than 80 years old if treatment is well tolerated.

• The guidelines place new emphasis on using some method for out-of-office blood pressure measurement – either ambulatory or home-based blood pressure measurement – for patients suspected of having either false-positive office-based blood pressure measurements (white coat hypertension) or false-negative office blood pressure levels (masked hypertension).

• The universe of first-line antihypertensive medications was whittled down to four: thiazide diuretics, calcium channel blockers, ACE inhibitors, and angiotensin-receptor blockers. Although the new guidelines call beta-blockers a "cornerstone" of treatment for patients with coronary heart disease and tachyarrhythmias, including atrial fibrillation, they are no longer seen as first-line agents for patients without these coexisting cardiac diseases or for young patients.

• A section on treating hypertension in young adults encourages applying the below 140/90 mm Hg target to these patients as well after a reasonable attempt at lifestyle intervention only.

• An updated approach to managing gestational hypertension and preventing preeclampsia includes use of prophylactic aspirin by women at moderate or high risk of preeclampsia, and treating pregnant women to a blood pressure of less than 150/95 mm Hg if pressure this high is persistent, or to a target of less than 140/90 mm Hg in women with gestational hypertension, symptoms, or subclinical organ damage.

Dr. Smith and Dr. Williams said that they had no relevant disclosures. Dr. Mancia said that he has been a consultant to 14 drug and device companies. Dr. Renata Cífková said that she had been a consultant to Daiichi Sankyo, Teva, Zentiva, Merck Sharpe and Dohme, Actavis, Berlin Chemie, Boehringer Ingelheim, and Bayer. Dr. Marx said that he has been a consultant to 13 drug and device companies. Dr. Williams said that he has been a consultant to Pfizer, Merck, Sanofi-BMS, and Novartis.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

AMSTERDAM – When the European Society of Cardiology in June reset its target systolic blood pressure for patients with diabetes, chronic kidney disease, or a history of cardiovascular disease to less than 140 mm Hg, it joined a small but growing cadre of medical societies that have looked at recent evidence and concluded that nothing currently justifies treating to a target systolic blood pressure below 130 mm Hg or to a diastolic pressure below 80 mm Hg.

The European Society of Cardiology’s new edition of hypertension management guidelines, produced in collaboration with the European Society of Hypertension, contrasts with the conspicuous void in U.S. practice that’s been widely acknowledged for a few years now: the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), the prevailing version of U.S. hypertension-management guidelines, is a decade old and outdated.

The delay-plagued process to come out with the eighth JNC edition (JNC 8) took an unexpected turn last June, when the National Heart, Lung, and Blood Institute, the agency that shepherded the first seven editions of U.S. hypertension guidelines going back to 1976, announced that it was immediately turning responsibility for getting JNC 8 finalized and out to the public over to "partner organizations" such as the American College of Cardiology and American Heart Association.

With this new wrinkle, even with the ACC and AHA scrambling to deal with their new responsibility, it seems like JNC 8 – or whatever name it will have when it finally emerges – will not come out until 2014 at the soonest, making the ESC guidelines the only up-to-date hypertension recommendations from a cardiology-oriented medical group for at least several more months.

A U.S. view of the Euro guidelines

"U.S. physicians need to be aware of the evidence as it evolves," said Dr. Sidney C. Smith Jr., professor of medicine at the University of North Carolina in Chapel Hill, and a member of the panel that’s been writing JNC 8.

"The American Diabetes Association came out with a similar recommendation" on the systolic blood pressure target for patients with diabetes. U.S. physicians should "see what the ADA says, see what the ESC says, and then decide what they should do. They need to read the recommendations and supporting evidence and see if it applies to their patients," Dr. Smith advised in an interview. "I think that patients and physicians will look at the current evidence and respond. You’ve got to go with what the evidence says and what seems best for the patient. No law says that you shall only do what is in the" JNC 7 guidelines.

A trickier situation may be settings in which physicians are assessed based on how many of their patients with diabetes reach a blood pressure target of less than 130/80, he said. "How do health care systems respond to evidence as it evolves? At what point should performance measures get changed?" Dr. Smith asked.

But because of its orientation to European populations, the new ESC hypertension guidelines can’t completely fill the U.S. vacuum.

"I’m sure JNC 8 will be nuanced differently than the European guidelines because we have a different population in the U.S., particularly African Americans and more patients with renal failure," said Dr. Kim Allan Williams Sr. of Wayne State University, Detroit. Dr. Williams will take the position of professor of medicine and chief of cardiovascular services at Rush University Medical Center in Chicago on Nov. 1. "As a practitioner, I would worry about using 140/90 mm Hg as the only target for the African American population that I deal with all the time. The stroke and renal failure rates are much higher in these patients" than in other patients with hypertension, he said in an interview. "The new European guidelines don’t deal with patients with African ancestry. JNC 7 had a section on blood pressure management in minority groups, which was very helpful."

Resetting the target for diabetics

The dialing up of the target systolic blood pressure for patients with diabetes or other high-risk factors, and the resulting damping down of antihypertensive treatment intensity, is the biggest change in the 2013 ESC hypertension recommendations, said Dr. Giuseppe Mancia, who chaired the task force that wrote the recommendations.

"We need to base the recommendations on the evidence. It’s been a consistent finding, in ONTARGET, ACCORD, and in other studies, that pushing the blood pressure of patients with diabetes below 130 mm Hg provided no additional benefit but was linked with more adverse events. If you set a lower target you need to be absolutely sure there is no harm associated with it, and at the moment we cannot say that.

"Adverse events [leads to] more discontinuation of treatment, and there is now evidence that discontinuation is closely related to an increase in events," said Dr. Mancia, professor of medicine at the University of Milan and cochair of the ESC hypertension task force. "There is a remarkable relationship between longer time taking antihypertensive drugs and cardiovascular protection."

"We were probably too radical in the previous guidelines" in setting a target systolic pressure at less than 130 mm Hg, said Dr. Renata Cífková, professor and head of preventive cardiology at Thomayer Teaching Hospital in Prague and a member of the ESC hypertension panel. "We saw that this was not evidence based. When we reviewed the same studies and also included the newer studies, like ACCORD, it basically confirmed our new blood pressure targets." Another advantage is that patients and physicians "will feel more comfortable with these goals," both in their achievability and by producing fewer adverse events," she said in an interview.

"This is the first major change in the hypertension guidelines for a number of years," the first full update since 2007, said Dr. Bryan Williams, professor and chairman of medicine at University College, London. "The data presented showed that, while there is indisputable evidence to lower pressures below 150/90 mm Hg, and strong evidence to lower below 140/90 mm Hg, there is limited or no evidence to recommend lowering pressures to below 130/80 mm Hg, and in some situations there is evidence for a signal of harm," said Dr. Williams. "The new guidelines simplify the target, a blood pressure of less than 140 mm Hg for everyone, regardless of their level of risk."

"The change in target means that ‘the lower the better’ is no longer true. This will reduce the number of drugs that patients receive and will avoid some adverse effects," said Dr. Nikolaus Marx, professor and director of medicine at Aachen (Germany) University Hospital.

Other groups came first

As Dr. Smith noted, the ESC is not the first medical group to scale back aggressive blood pressure targets for patients with diabetes or chronic kidney disease, but it may be the first major cardiology society to do so. Last year, the Kidney Disease Improving Global Outcomes foundation issued guidelines for hypertension management in patients with chronic kidney disease (Kidney International Supplement 2012;2:340-414). The expert panel recommended a target pressure of 140/90 mm Hg or below for patients with chronic kidney disease with or without diabetes as long as their daily urine albumin remained below 30 mg. For patients with more severe albuminuria, the panel recommended a target of 130/80 mm Hg or less for all chronic kidney disease patients regardless of their diabetes status.

Earlier this year, the American Diabetes Association published its Standards of Medical Care in Diabetes–2013, which set a target blood pressure for patients with diabetes at less than 140/80 mm Hg (the ESC set a diastolic pressure target of less than 85 mm Hg) (Diabetes Care 2013;36:S11-S66).

Other changes in the ESC guidelines

The ESC guidelines include some other notable changes (Euro. Heart J. 2013;34:2159-219):

• The basic systolic blood pressure goal for elderly patients, defined as 65 years or older, was set as less than 150 mm Hg. The goal can lower to less than 140 mm Hg for "fit elderly patients" younger than 80 years old if treatment is well tolerated.

• The guidelines place new emphasis on using some method for out-of-office blood pressure measurement – either ambulatory or home-based blood pressure measurement – for patients suspected of having either false-positive office-based blood pressure measurements (white coat hypertension) or false-negative office blood pressure levels (masked hypertension).

• The universe of first-line antihypertensive medications was whittled down to four: thiazide diuretics, calcium channel blockers, ACE inhibitors, and angiotensin-receptor blockers. Although the new guidelines call beta-blockers a "cornerstone" of treatment for patients with coronary heart disease and tachyarrhythmias, including atrial fibrillation, they are no longer seen as first-line agents for patients without these coexisting cardiac diseases or for young patients.

• A section on treating hypertension in young adults encourages applying the below 140/90 mm Hg target to these patients as well after a reasonable attempt at lifestyle intervention only.

• An updated approach to managing gestational hypertension and preventing preeclampsia includes use of prophylactic aspirin by women at moderate or high risk of preeclampsia, and treating pregnant women to a blood pressure of less than 150/95 mm Hg if pressure this high is persistent, or to a target of less than 140/90 mm Hg in women with gestational hypertension, symptoms, or subclinical organ damage.

Dr. Smith and Dr. Williams said that they had no relevant disclosures. Dr. Mancia said that he has been a consultant to 14 drug and device companies. Dr. Renata Cífková said that she had been a consultant to Daiichi Sankyo, Teva, Zentiva, Merck Sharpe and Dohme, Actavis, Berlin Chemie, Boehringer Ingelheim, and Bayer. Dr. Marx said that he has been a consultant to 13 drug and device companies. Dr. Williams said that he has been a consultant to Pfizer, Merck, Sanofi-BMS, and Novartis.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

AMSTERDAM – When the European Society of Cardiology in June reset its target systolic blood pressure for patients with diabetes, chronic kidney disease, or a history of cardiovascular disease to less than 140 mm Hg, it joined a small but growing cadre of medical societies that have looked at recent evidence and concluded that nothing currently justifies treating to a target systolic blood pressure below 130 mm Hg or to a diastolic pressure below 80 mm Hg.

The European Society of Cardiology’s new edition of hypertension management guidelines, produced in collaboration with the European Society of Hypertension, contrasts with the conspicuous void in U.S. practice that’s been widely acknowledged for a few years now: the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), the prevailing version of U.S. hypertension-management guidelines, is a decade old and outdated.

The delay-plagued process to come out with the eighth JNC edition (JNC 8) took an unexpected turn last June, when the National Heart, Lung, and Blood Institute, the agency that shepherded the first seven editions of U.S. hypertension guidelines going back to 1976, announced that it was immediately turning responsibility for getting JNC 8 finalized and out to the public over to "partner organizations" such as the American College of Cardiology and American Heart Association.

With this new wrinkle, even with the ACC and AHA scrambling to deal with their new responsibility, it seems like JNC 8 – or whatever name it will have when it finally emerges – will not come out until 2014 at the soonest, making the ESC guidelines the only up-to-date hypertension recommendations from a cardiology-oriented medical group for at least several more months.

A U.S. view of the Euro guidelines

"U.S. physicians need to be aware of the evidence as it evolves," said Dr. Sidney C. Smith Jr., professor of medicine at the University of North Carolina in Chapel Hill, and a member of the panel that’s been writing JNC 8.

"The American Diabetes Association came out with a similar recommendation" on the systolic blood pressure target for patients with diabetes. U.S. physicians should "see what the ADA says, see what the ESC says, and then decide what they should do. They need to read the recommendations and supporting evidence and see if it applies to their patients," Dr. Smith advised in an interview. "I think that patients and physicians will look at the current evidence and respond. You’ve got to go with what the evidence says and what seems best for the patient. No law says that you shall only do what is in the" JNC 7 guidelines.

A trickier situation may be settings in which physicians are assessed based on how many of their patients with diabetes reach a blood pressure target of less than 130/80, he said. "How do health care systems respond to evidence as it evolves? At what point should performance measures get changed?" Dr. Smith asked.

But because of its orientation to European populations, the new ESC hypertension guidelines can’t completely fill the U.S. vacuum.

"I’m sure JNC 8 will be nuanced differently than the European guidelines because we have a different population in the U.S., particularly African Americans and more patients with renal failure," said Dr. Kim Allan Williams Sr. of Wayne State University, Detroit. Dr. Williams will take the position of professor of medicine and chief of cardiovascular services at Rush University Medical Center in Chicago on Nov. 1. "As a practitioner, I would worry about using 140/90 mm Hg as the only target for the African American population that I deal with all the time. The stroke and renal failure rates are much higher in these patients" than in other patients with hypertension, he said in an interview. "The new European guidelines don’t deal with patients with African ancestry. JNC 7 had a section on blood pressure management in minority groups, which was very helpful."

Resetting the target for diabetics

The dialing up of the target systolic blood pressure for patients with diabetes or other high-risk factors, and the resulting damping down of antihypertensive treatment intensity, is the biggest change in the 2013 ESC hypertension recommendations, said Dr. Giuseppe Mancia, who chaired the task force that wrote the recommendations.

"We need to base the recommendations on the evidence. It’s been a consistent finding, in ONTARGET, ACCORD, and in other studies, that pushing the blood pressure of patients with diabetes below 130 mm Hg provided no additional benefit but was linked with more adverse events. If you set a lower target you need to be absolutely sure there is no harm associated with it, and at the moment we cannot say that.

"Adverse events [leads to] more discontinuation of treatment, and there is now evidence that discontinuation is closely related to an increase in events," said Dr. Mancia, professor of medicine at the University of Milan and cochair of the ESC hypertension task force. "There is a remarkable relationship between longer time taking antihypertensive drugs and cardiovascular protection."

"We were probably too radical in the previous guidelines" in setting a target systolic pressure at less than 130 mm Hg, said Dr. Renata Cífková, professor and head of preventive cardiology at Thomayer Teaching Hospital in Prague and a member of the ESC hypertension panel. "We saw that this was not evidence based. When we reviewed the same studies and also included the newer studies, like ACCORD, it basically confirmed our new blood pressure targets." Another advantage is that patients and physicians "will feel more comfortable with these goals," both in their achievability and by producing fewer adverse events," she said in an interview.

"This is the first major change in the hypertension guidelines for a number of years," the first full update since 2007, said Dr. Bryan Williams, professor and chairman of medicine at University College, London. "The data presented showed that, while there is indisputable evidence to lower pressures below 150/90 mm Hg, and strong evidence to lower below 140/90 mm Hg, there is limited or no evidence to recommend lowering pressures to below 130/80 mm Hg, and in some situations there is evidence for a signal of harm," said Dr. Williams. "The new guidelines simplify the target, a blood pressure of less than 140 mm Hg for everyone, regardless of their level of risk."

"The change in target means that ‘the lower the better’ is no longer true. This will reduce the number of drugs that patients receive and will avoid some adverse effects," said Dr. Nikolaus Marx, professor and director of medicine at Aachen (Germany) University Hospital.

Other groups came first

As Dr. Smith noted, the ESC is not the first medical group to scale back aggressive blood pressure targets for patients with diabetes or chronic kidney disease, but it may be the first major cardiology society to do so. Last year, the Kidney Disease Improving Global Outcomes foundation issued guidelines for hypertension management in patients with chronic kidney disease (Kidney International Supplement 2012;2:340-414). The expert panel recommended a target pressure of 140/90 mm Hg or below for patients with chronic kidney disease with or without diabetes as long as their daily urine albumin remained below 30 mg. For patients with more severe albuminuria, the panel recommended a target of 130/80 mm Hg or less for all chronic kidney disease patients regardless of their diabetes status.

Earlier this year, the American Diabetes Association published its Standards of Medical Care in Diabetes–2013, which set a target blood pressure for patients with diabetes at less than 140/80 mm Hg (the ESC set a diastolic pressure target of less than 85 mm Hg) (Diabetes Care 2013;36:S11-S66).

Other changes in the ESC guidelines

The ESC guidelines include some other notable changes (Euro. Heart J. 2013;34:2159-219):

• The basic systolic blood pressure goal for elderly patients, defined as 65 years or older, was set as less than 150 mm Hg. The goal can lower to less than 140 mm Hg for "fit elderly patients" younger than 80 years old if treatment is well tolerated.

• The guidelines place new emphasis on using some method for out-of-office blood pressure measurement – either ambulatory or home-based blood pressure measurement – for patients suspected of having either false-positive office-based blood pressure measurements (white coat hypertension) or false-negative office blood pressure levels (masked hypertension).

• The universe of first-line antihypertensive medications was whittled down to four: thiazide diuretics, calcium channel blockers, ACE inhibitors, and angiotensin-receptor blockers. Although the new guidelines call beta-blockers a "cornerstone" of treatment for patients with coronary heart disease and tachyarrhythmias, including atrial fibrillation, they are no longer seen as first-line agents for patients without these coexisting cardiac diseases or for young patients.

• A section on treating hypertension in young adults encourages applying the below 140/90 mm Hg target to these patients as well after a reasonable attempt at lifestyle intervention only.

• An updated approach to managing gestational hypertension and preventing preeclampsia includes use of prophylactic aspirin by women at moderate or high risk of preeclampsia, and treating pregnant women to a blood pressure of less than 150/95 mm Hg if pressure this high is persistent, or to a target of less than 140/90 mm Hg in women with gestational hypertension, symptoms, or subclinical organ damage.

Dr. Smith and Dr. Williams said that they had no relevant disclosures. Dr. Mancia said that he has been a consultant to 14 drug and device companies. Dr. Renata Cífková said that she had been a consultant to Daiichi Sankyo, Teva, Zentiva, Merck Sharpe and Dohme, Actavis, Berlin Chemie, Boehringer Ingelheim, and Bayer. Dr. Marx said that he has been a consultant to 13 drug and device companies. Dr. Williams said that he has been a consultant to Pfizer, Merck, Sanofi-BMS, and Novartis.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

AMSTERDAM – People with congenitally reduced triglyceride levels had about a 20% reduced risk of all-cause death compared with people without inherently low triglyceride levels during more than 30-years follow-up of nearly 14,000 people enrolled in the Copenhagen City Heart Study.

Data from the study also showed that people with higher triglyceride (TG) levels at the time they entered the study had significantly higher all-cause mortality during more than 30 years of follow-up than did people who entered with lower TG levels, Dr. Børge G. Nordestgaard said at the European Society of Cardiology annual congress.

But the result from the genetic analysis provided even more persuasive evidence that it is time to run a large, prospective intervention trial aimed at testing the preventive efficacy of TG lowering in patients selected based on elevated TGs, he said.

The genetic analysis "took advantage of nature’s randomized trial," said Dr. Nordestgaard, professor and chief of clinical biochemistry at Copenhagen University Hospital. The genetic analysis looked at long-term survival relative to the number of TG-lowering alleles each person had in their lipoprotein lipase genes. "These data suggest a causal relationship between low TGs and improved survival. Lots of drugs are available to lower triglycerides, such as atorvastatin and rosuvastatin, but so far all the trials only focused on high LDL or low HDL cholesterol. No trial enrolled patients on the basis of high triglycerides.

"A lot of people have normal LDL levels and high TGs, and right now they are ignored," he said. "Before statins, everyone talked about high LDL and high TGs as being equal risk factors, but now TGs are completely forgotten. A big mistake has been interpreting results from the statin trials, because the participants in those studies did not enter the trials because of their TG levels."

Dr. Nordestgaard and his associates performed an analysis of the hazard ratio for all-cause death among 13,957 people enrolled in the Copenhagen study. Compared with people who entered the study with a nonfasting serum triglyceride level of 266-442 mg/dL, 8% of everyone enrolled, those with a level of 177-265 mg/dL, 17% of enrollees, had an all-cause mortality rate that was relatively reduced by 10%, a statistically significant difference. People who entered with a TG level of 89-176 mg/dL, about half of the enrollees, had their relative mortality rate cut by 25% compared with the reference group, and those who entered with a level of less than 89 mg/dL, 22% of the enrollees, had a mortality rate that ran half that of the reference group, also statistically significant differences.

To better document an effect from reduced TG levels, the investigators used data that had been collected on six different genetic alleles in the gene coding for lipoprotein lipase linked to reduced TG levels. Data on allele numbers were available for 10,208 of the study participants, and those with 0-3 of the alleles were used as the reference group. People with four, five, or six of these alleles showed progressively larger drops in TG level; those with 4 of the alleles had a level about 10% below the reference group, those with five alleles were about 20% below, and those with six alleles had a TG level that averaged 30% below the reference group.

Mortality during follow-up tracked with TG levels at baseline and the number of TG-lowering alleles. People with 4 alleles had a mortality rate 15% below the rate among those with 0-3 alleles. People with five TG-lowering alleles had a 20% cut in mortality, and those with six alleles had a 22% reduction.

Dr. Nordestgaard said that he has been a consultant to 11 drug companies, including AstraZeneca, Merck, and Pfizer.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

AMSTERDAM – People with congenitally reduced triglyceride levels had about a 20% reduced risk of all-cause death compared with people without inherently low triglyceride levels during more than 30-years follow-up of nearly 14,000 people enrolled in the Copenhagen City Heart Study.

Data from the study also showed that people with higher triglyceride (TG) levels at the time they entered the study had significantly higher all-cause mortality during more than 30 years of follow-up than did people who entered with lower TG levels, Dr. Børge G. Nordestgaard said at the European Society of Cardiology annual congress.

But the result from the genetic analysis provided even more persuasive evidence that it is time to run a large, prospective intervention trial aimed at testing the preventive efficacy of TG lowering in patients selected based on elevated TGs, he said.

The genetic analysis "took advantage of nature’s randomized trial," said Dr. Nordestgaard, professor and chief of clinical biochemistry at Copenhagen University Hospital. The genetic analysis looked at long-term survival relative to the number of TG-lowering alleles each person had in their lipoprotein lipase genes. "These data suggest a causal relationship between low TGs and improved survival. Lots of drugs are available to lower triglycerides, such as atorvastatin and rosuvastatin, but so far all the trials only focused on high LDL or low HDL cholesterol. No trial enrolled patients on the basis of high triglycerides.

"A lot of people have normal LDL levels and high TGs, and right now they are ignored," he said. "Before statins, everyone talked about high LDL and high TGs as being equal risk factors, but now TGs are completely forgotten. A big mistake has been interpreting results from the statin trials, because the participants in those studies did not enter the trials because of their TG levels."

Dr. Nordestgaard and his associates performed an analysis of the hazard ratio for all-cause death among 13,957 people enrolled in the Copenhagen study. Compared with people who entered the study with a nonfasting serum triglyceride level of 266-442 mg/dL, 8% of everyone enrolled, those with a level of 177-265 mg/dL, 17% of enrollees, had an all-cause mortality rate that was relatively reduced by 10%, a statistically significant difference. People who entered with a TG level of 89-176 mg/dL, about half of the enrollees, had their relative mortality rate cut by 25% compared with the reference group, and those who entered with a level of less than 89 mg/dL, 22% of the enrollees, had a mortality rate that ran half that of the reference group, also statistically significant differences.

To better document an effect from reduced TG levels, the investigators used data that had been collected on six different genetic alleles in the gene coding for lipoprotein lipase linked to reduced TG levels. Data on allele numbers were available for 10,208 of the study participants, and those with 0-3 of the alleles were used as the reference group. People with four, five, or six of these alleles showed progressively larger drops in TG level; those with 4 of the alleles had a level about 10% below the reference group, those with five alleles were about 20% below, and those with six alleles had a TG level that averaged 30% below the reference group.

Mortality during follow-up tracked with TG levels at baseline and the number of TG-lowering alleles. People with 4 alleles had a mortality rate 15% below the rate among those with 0-3 alleles. People with five TG-lowering alleles had a 20% cut in mortality, and those with six alleles had a 22% reduction.

Dr. Nordestgaard said that he has been a consultant to 11 drug companies, including AstraZeneca, Merck, and Pfizer.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

AMSTERDAM – People with congenitally reduced triglyceride levels had about a 20% reduced risk of all-cause death compared with people without inherently low triglyceride levels during more than 30-years follow-up of nearly 14,000 people enrolled in the Copenhagen City Heart Study.

Data from the study also showed that people with higher triglyceride (TG) levels at the time they entered the study had significantly higher all-cause mortality during more than 30 years of follow-up than did people who entered with lower TG levels, Dr. Børge G. Nordestgaard said at the European Society of Cardiology annual congress.

But the result from the genetic analysis provided even more persuasive evidence that it is time to run a large, prospective intervention trial aimed at testing the preventive efficacy of TG lowering in patients selected based on elevated TGs, he said.

The genetic analysis "took advantage of nature’s randomized trial," said Dr. Nordestgaard, professor and chief of clinical biochemistry at Copenhagen University Hospital. The genetic analysis looked at long-term survival relative to the number of TG-lowering alleles each person had in their lipoprotein lipase genes. "These data suggest a causal relationship between low TGs and improved survival. Lots of drugs are available to lower triglycerides, such as atorvastatin and rosuvastatin, but so far all the trials only focused on high LDL or low HDL cholesterol. No trial enrolled patients on the basis of high triglycerides.

"A lot of people have normal LDL levels and high TGs, and right now they are ignored," he said. "Before statins, everyone talked about high LDL and high TGs as being equal risk factors, but now TGs are completely forgotten. A big mistake has been interpreting results from the statin trials, because the participants in those studies did not enter the trials because of their TG levels."

Dr. Nordestgaard and his associates performed an analysis of the hazard ratio for all-cause death among 13,957 people enrolled in the Copenhagen study. Compared with people who entered the study with a nonfasting serum triglyceride level of 266-442 mg/dL, 8% of everyone enrolled, those with a level of 177-265 mg/dL, 17% of enrollees, had an all-cause mortality rate that was relatively reduced by 10%, a statistically significant difference. People who entered with a TG level of 89-176 mg/dL, about half of the enrollees, had their relative mortality rate cut by 25% compared with the reference group, and those who entered with a level of less than 89 mg/dL, 22% of the enrollees, had a mortality rate that ran half that of the reference group, also statistically significant differences.

To better document an effect from reduced TG levels, the investigators used data that had been collected on six different genetic alleles in the gene coding for lipoprotein lipase linked to reduced TG levels. Data on allele numbers were available for 10,208 of the study participants, and those with 0-3 of the alleles were used as the reference group. People with four, five, or six of these alleles showed progressively larger drops in TG level; those with 4 of the alleles had a level about 10% below the reference group, those with five alleles were about 20% below, and those with six alleles had a TG level that averaged 30% below the reference group.

Mortality during follow-up tracked with TG levels at baseline and the number of TG-lowering alleles. People with 4 alleles had a mortality rate 15% below the rate among those with 0-3 alleles. People with five TG-lowering alleles had a 20% cut in mortality, and those with six alleles had a 22% reduction.

Dr. Nordestgaard said that he has been a consultant to 11 drug companies, including AstraZeneca, Merck, and Pfizer.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Assessment of deep brain stimulation for patients with treatment-resistant depression has inched forward over the past decade with promising results but remains in its early days with a total worldwide experience of roughly 60 patients.

That total includes patients who have received deep brain stimulation (DBS) leads placed in six different brain regions. However, the results suggest that one of the better target locations for DBS in patients with treatment-resistant depression (TRD) is in the nucleus accumbens, Dr. Bruno Millet said at the annual congress of the European College of Neuropsychopharmacology.

"The nucleus accumbens is a very good target that we will continue to study. It is very safe, and the surgery is easy and rapid. The nucleus accumbens has a good benefit-to-risk ratio," said Dr. Millet, professor of psychiatry at the University of Rennes (France). "This is a strength of this target."

The nucleus accumbens became a target because it is "at the center of a circuit involved in major depressive disorder," and plays a "central role in reward circuitry and its dysfunctions," he added.

All patients who have received DBS had stage 5 TRD, which meant that their depression was unresponsive to all possible drug classes, including monamine oxidase inhibitors. These patients also failed to adequately respond to electroconvulsive therapy.

Dr. Millet and his associates at nine other French centers ran a pilot study with four patients who received DBS in the nuclear accumbens starting in 2009. Patients received stimulation at a level of 1.5-4 V. All four patients showed gradual improvement in their depression during the first 6 months after treatment. After 1 year of follow-up, all patients had responded, with response defined as at least a 50% decline from the baseline Hamilton Rating Scale for Depression (HRSD) score. One patient went into remission, defined as an HRSD score of less than 10. None of the patients had somatic adverse effects during 15 months of follow-up, but one patient had worsening mood and anxiety and made a suicide attempt; one patient had worsening mood and sleep and increased food intake; and one patient developed paresthesia.

The largest patient series and the longest follow-up of patients who received DBS in their nucleus accumbens for TRD involved 11 patients treated in Germany. The patients had minimal adverse effects, and 5 of the 11 responded, with the response remaining stable during 4 years of follow-up (Neuropsychopharmacology 2012;37:1975-85).

Another target that produced notable results is the medial forebrain bundle, which led to good DBS results in seven patients treated by the same German team. Earlier this year, the investigators reported that six of the seven patients had responded and four patients had reached remission of their depression after 3-7 months of follow-up (Biol. Psychiatry 2013;73:1204-12). Two other brain targets that have been used by other groups with success are the subgenual cingulate gyrus, and the ventral capsule and ventral striatum (World Neurosurg. 2013;80:S27.e17-24).

But "one of the striking things in DBS for the moment is the lack of any randomized controlled trials," Dr. Millet said. He and his French associates have expanded their network to 12 centers, including one in Geneva, and they have designed and are now starting a trial that will place DBS leads in all patients but will withhold active stimulation in half the patients for the first 7 months after lead placement. This trial is sponsored by Medtronic, a company that markets the DBS device Reclaim.

Medtronic primarily markets its DBS device for the treatment of Parkinson’s disease, essential tremor, and dystonia, but in 2009, the Food and Drug Administration also approved its use to treat obsessive-compulsive disorder under a humanitarian device exemption. Some medical ethicists, psychiatrists, and neurosurgeons have questioned the growing use of DBS for obsessive-compulsive disorder in the absence of evidence for its efficacy in a randomized controlled trial, calling this practice "misuse" of the device (Health Aff. 2011;30:302-11). One of these critics, Dr. Thomas E. Schlaepfer of Bonn, Germany, also is head of the group with perhaps the largest experience in using DBS to treat patients with depression.

Dr. Millet said he has received grant support from Medtronic, marketer of the Reclaim DBS therapy device. He also said he has been a consultant to, has been a speaker for, or has received research funding from nine other drug or device companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Assessment of deep brain stimulation for patients with treatment-resistant depression has inched forward over the past decade with promising results but remains in its early days with a total worldwide experience of roughly 60 patients.

That total includes patients who have received deep brain stimulation (DBS) leads placed in six different brain regions. However, the results suggest that one of the better target locations for DBS in patients with treatment-resistant depression (TRD) is in the nucleus accumbens, Dr. Bruno Millet said at the annual congress of the European College of Neuropsychopharmacology.

"The nucleus accumbens is a very good target that we will continue to study. It is very safe, and the surgery is easy and rapid. The nucleus accumbens has a good benefit-to-risk ratio," said Dr. Millet, professor of psychiatry at the University of Rennes (France). "This is a strength of this target."

The nucleus accumbens became a target because it is "at the center of a circuit involved in major depressive disorder," and plays a "central role in reward circuitry and its dysfunctions," he added.

All patients who have received DBS had stage 5 TRD, which meant that their depression was unresponsive to all possible drug classes, including monamine oxidase inhibitors. These patients also failed to adequately respond to electroconvulsive therapy.

Dr. Millet and his associates at nine other French centers ran a pilot study with four patients who received DBS in the nuclear accumbens starting in 2009. Patients received stimulation at a level of 1.5-4 V. All four patients showed gradual improvement in their depression during the first 6 months after treatment. After 1 year of follow-up, all patients had responded, with response defined as at least a 50% decline from the baseline Hamilton Rating Scale for Depression (HRSD) score. One patient went into remission, defined as an HRSD score of less than 10. None of the patients had somatic adverse effects during 15 months of follow-up, but one patient had worsening mood and anxiety and made a suicide attempt; one patient had worsening mood and sleep and increased food intake; and one patient developed paresthesia.

The largest patient series and the longest follow-up of patients who received DBS in their nucleus accumbens for TRD involved 11 patients treated in Germany. The patients had minimal adverse effects, and 5 of the 11 responded, with the response remaining stable during 4 years of follow-up (Neuropsychopharmacology 2012;37:1975-85).

Another target that produced notable results is the medial forebrain bundle, which led to good DBS results in seven patients treated by the same German team. Earlier this year, the investigators reported that six of the seven patients had responded and four patients had reached remission of their depression after 3-7 months of follow-up (Biol. Psychiatry 2013;73:1204-12). Two other brain targets that have been used by other groups with success are the subgenual cingulate gyrus, and the ventral capsule and ventral striatum (World Neurosurg. 2013;80:S27.e17-24).

But "one of the striking things in DBS for the moment is the lack of any randomized controlled trials," Dr. Millet said. He and his French associates have expanded their network to 12 centers, including one in Geneva, and they have designed and are now starting a trial that will place DBS leads in all patients but will withhold active stimulation in half the patients for the first 7 months after lead placement. This trial is sponsored by Medtronic, a company that markets the DBS device Reclaim.

Medtronic primarily markets its DBS device for the treatment of Parkinson’s disease, essential tremor, and dystonia, but in 2009, the Food and Drug Administration also approved its use to treat obsessive-compulsive disorder under a humanitarian device exemption. Some medical ethicists, psychiatrists, and neurosurgeons have questioned the growing use of DBS for obsessive-compulsive disorder in the absence of evidence for its efficacy in a randomized controlled trial, calling this practice "misuse" of the device (Health Aff. 2011;30:302-11). One of these critics, Dr. Thomas E. Schlaepfer of Bonn, Germany, also is head of the group with perhaps the largest experience in using DBS to treat patients with depression.

Dr. Millet said he has received grant support from Medtronic, marketer of the Reclaim DBS therapy device. He also said he has been a consultant to, has been a speaker for, or has received research funding from nine other drug or device companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Assessment of deep brain stimulation for patients with treatment-resistant depression has inched forward over the past decade with promising results but remains in its early days with a total worldwide experience of roughly 60 patients.

That total includes patients who have received deep brain stimulation (DBS) leads placed in six different brain regions. However, the results suggest that one of the better target locations for DBS in patients with treatment-resistant depression (TRD) is in the nucleus accumbens, Dr. Bruno Millet said at the annual congress of the European College of Neuropsychopharmacology.

"The nucleus accumbens is a very good target that we will continue to study. It is very safe, and the surgery is easy and rapid. The nucleus accumbens has a good benefit-to-risk ratio," said Dr. Millet, professor of psychiatry at the University of Rennes (France). "This is a strength of this target."

The nucleus accumbens became a target because it is "at the center of a circuit involved in major depressive disorder," and plays a "central role in reward circuitry and its dysfunctions," he added.

All patients who have received DBS had stage 5 TRD, which meant that their depression was unresponsive to all possible drug classes, including monamine oxidase inhibitors. These patients also failed to adequately respond to electroconvulsive therapy.

Dr. Millet and his associates at nine other French centers ran a pilot study with four patients who received DBS in the nuclear accumbens starting in 2009. Patients received stimulation at a level of 1.5-4 V. All four patients showed gradual improvement in their depression during the first 6 months after treatment. After 1 year of follow-up, all patients had responded, with response defined as at least a 50% decline from the baseline Hamilton Rating Scale for Depression (HRSD) score. One patient went into remission, defined as an HRSD score of less than 10. None of the patients had somatic adverse effects during 15 months of follow-up, but one patient had worsening mood and anxiety and made a suicide attempt; one patient had worsening mood and sleep and increased food intake; and one patient developed paresthesia.

The largest patient series and the longest follow-up of patients who received DBS in their nucleus accumbens for TRD involved 11 patients treated in Germany. The patients had minimal adverse effects, and 5 of the 11 responded, with the response remaining stable during 4 years of follow-up (Neuropsychopharmacology 2012;37:1975-85).

Another target that produced notable results is the medial forebrain bundle, which led to good DBS results in seven patients treated by the same German team. Earlier this year, the investigators reported that six of the seven patients had responded and four patients had reached remission of their depression after 3-7 months of follow-up (Biol. Psychiatry 2013;73:1204-12). Two other brain targets that have been used by other groups with success are the subgenual cingulate gyrus, and the ventral capsule and ventral striatum (World Neurosurg. 2013;80:S27.e17-24).

But "one of the striking things in DBS for the moment is the lack of any randomized controlled trials," Dr. Millet said. He and his French associates have expanded their network to 12 centers, including one in Geneva, and they have designed and are now starting a trial that will place DBS leads in all patients but will withhold active stimulation in half the patients for the first 7 months after lead placement. This trial is sponsored by Medtronic, a company that markets the DBS device Reclaim.

Medtronic primarily markets its DBS device for the treatment of Parkinson’s disease, essential tremor, and dystonia, but in 2009, the Food and Drug Administration also approved its use to treat obsessive-compulsive disorder under a humanitarian device exemption. Some medical ethicists, psychiatrists, and neurosurgeons have questioned the growing use of DBS for obsessive-compulsive disorder in the absence of evidence for its efficacy in a randomized controlled trial, calling this practice "misuse" of the device (Health Aff. 2011;30:302-11). One of these critics, Dr. Thomas E. Schlaepfer of Bonn, Germany, also is head of the group with perhaps the largest experience in using DBS to treat patients with depression.

Dr. Millet said he has received grant support from Medtronic, marketer of the Reclaim DBS therapy device. He also said he has been a consultant to, has been a speaker for, or has received research funding from nine other drug or device companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Patients with type 2 diabetes who undergo bariatric surgery benefit from an increasingly reduced incidence of macro- and microvascular complications over the ensuing 20 years compared with matched controls, based on 20-year follow-up of more than 600 patients treated in Sweden.

The rate of complications that were prevented accelerated during 20 years of follow-up even though the prevalence of patients in remission from type 2 diabetes following bariatric surgery fell over time, with a nadir in remission reached at 20 years, Dr. Lars Sjötröm reported at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

Dr. Sjötröm and his associates previously reported results from the Swedish Obese Subjects (SOS) study showing that among the subgroup of patients who entered the study with diabetes, 72% were in remission from diabetes 2 years after bariatric surgery, and 36% were still in remission 10 years after surgery (N. Engl. J. Med. 2004;351:2683-93). Longer follow-up data he reported at the meeting show that after 15 years the remission rate dropped further to 30%, and after 20 years just 18% of the starting population remained in remission of their diabetes. After 20 years, roughly three-quarters of the patients who initially went into remission of their diabetes had relapsed back into active diabetes.

Despite this, the incidence of macro- and microvascular complications continued to fall compared with the control patients, reported Dr. Sjötröm, professor of medicine at the University of Gothenburg, Sweden, and lead investigator of SOS. The rate of complications of the eyes, kidneys, peripheral nerves, or peripheral circulation that required hospitalization was about 8% in the surgery patients and 12% in the controls after 10 years, and after 20 years the rates were about 20% in the surgery patients and 45% in the controls, a 54% relative risk reduction in favor of surgery that appeared greater than after 10 years. His group previously reported a similar finding for the incidence of myocardial infarctions (Diabetes Care 2012;35:2613-7).

"I think you should operate on patients with diabetes; we saw a drop in their complications," he said. "Even when patients relapse, their cardiovascular risk factors are still improved. This may be why we see an effect on complications despite the patients relapsing. Even with all the relapses, the effect of surgery on diabetic complications remains strong after 20 years." Gastric bypass surgery appeared to offer a feasible operation that also resulted in good diabetes control, he added.

The SOS enrolled 607 patients with diabetes out of the 4,047 total patients in the study. The diabetes subgroup comprised 345 who underwent some form of bariatric surgery, and 262 matched controls who did not receive surgery. Their average age was 50 years, their average body mass index was 40 kg/m², and they had diabetes for an average of 3 years.

In addition to producing diabetes remission and preventing complications, surgery also blunted the incidence of new-onset diabetes. A prior report from SOS showed prevention of new-onset diabetes in the surgery group through the first 15 years of follow-up, (N. Engl. J. Med. 2012;367:695-704), and after 20 years this effect "remained quite strong," with a 77% relative risk reduction in incident diabetes during 20 years of follow-up compared with the controls, Dr. Sjötröm reported.

He also called for scaling back body mass index criteria for performing bariatric surgery because the benefits following surgery appeared similar in patients with relatively low BMIs. He cited a recent analysis his group ran on the 233 patients from SOS who did not meet current criteria for bariatric surgery because their BMI was too low. The average BMI in this subgroup was 36 kg/m², and 104 of these patients underwent bariatric surgery (Diabetes Care 2013;36:1335-40). This exploratory analysis of SOS results showed that the benefits from bariatric surgery were similar in patients with lower BMIs and in patients with higher BMIs who meet the standard surgical criteria.

"Current BMI-based eligibility criteria [for bariatric surgery] are not valid," Dr. Sjötröm declared. "Baseline BMI does not predict any treatment effect examined so far. We should give more importance to metabolic variables to select the patients who would benefit the most from bariatric surgery."

SOS has been supported by grants from Astra Zeneca, Cederroth, Hoffman-La Roche, Johnson & Johnson, and Sanofi-Aventis. Dr. Sjötröm has been a speaker for Astra Zeneca and Johnson & Johnson, and he serves on the board of Lenimen.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Patients with type 2 diabetes who undergo bariatric surgery benefit from an increasingly reduced incidence of macro- and microvascular complications over the ensuing 20 years compared with matched controls, based on 20-year follow-up of more than 600 patients treated in Sweden.

The rate of complications that were prevented accelerated during 20 years of follow-up even though the prevalence of patients in remission from type 2 diabetes following bariatric surgery fell over time, with a nadir in remission reached at 20 years, Dr. Lars Sjötröm reported at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

Dr. Sjötröm and his associates previously reported results from the Swedish Obese Subjects (SOS) study showing that among the subgroup of patients who entered the study with diabetes, 72% were in remission from diabetes 2 years after bariatric surgery, and 36% were still in remission 10 years after surgery (N. Engl. J. Med. 2004;351:2683-93). Longer follow-up data he reported at the meeting show that after 15 years the remission rate dropped further to 30%, and after 20 years just 18% of the starting population remained in remission of their diabetes. After 20 years, roughly three-quarters of the patients who initially went into remission of their diabetes had relapsed back into active diabetes.

Despite this, the incidence of macro- and microvascular complications continued to fall compared with the control patients, reported Dr. Sjötröm, professor of medicine at the University of Gothenburg, Sweden, and lead investigator of SOS. The rate of complications of the eyes, kidneys, peripheral nerves, or peripheral circulation that required hospitalization was about 8% in the surgery patients and 12% in the controls after 10 years, and after 20 years the rates were about 20% in the surgery patients and 45% in the controls, a 54% relative risk reduction in favor of surgery that appeared greater than after 10 years. His group previously reported a similar finding for the incidence of myocardial infarctions (Diabetes Care 2012;35:2613-7).

"I think you should operate on patients with diabetes; we saw a drop in their complications," he said. "Even when patients relapse, their cardiovascular risk factors are still improved. This may be why we see an effect on complications despite the patients relapsing. Even with all the relapses, the effect of surgery on diabetic complications remains strong after 20 years." Gastric bypass surgery appeared to offer a feasible operation that also resulted in good diabetes control, he added.

The SOS enrolled 607 patients with diabetes out of the 4,047 total patients in the study. The diabetes subgroup comprised 345 who underwent some form of bariatric surgery, and 262 matched controls who did not receive surgery. Their average age was 50 years, their average body mass index was 40 kg/m², and they had diabetes for an average of 3 years.

In addition to producing diabetes remission and preventing complications, surgery also blunted the incidence of new-onset diabetes. A prior report from SOS showed prevention of new-onset diabetes in the surgery group through the first 15 years of follow-up, (N. Engl. J. Med. 2012;367:695-704), and after 20 years this effect "remained quite strong," with a 77% relative risk reduction in incident diabetes during 20 years of follow-up compared with the controls, Dr. Sjötröm reported.

He also called for scaling back body mass index criteria for performing bariatric surgery because the benefits following surgery appeared similar in patients with relatively low BMIs. He cited a recent analysis his group ran on the 233 patients from SOS who did not meet current criteria for bariatric surgery because their BMI was too low. The average BMI in this subgroup was 36 kg/m², and 104 of these patients underwent bariatric surgery (Diabetes Care 2013;36:1335-40). This exploratory analysis of SOS results showed that the benefits from bariatric surgery were similar in patients with lower BMIs and in patients with higher BMIs who meet the standard surgical criteria.

"Current BMI-based eligibility criteria [for bariatric surgery] are not valid," Dr. Sjötröm declared. "Baseline BMI does not predict any treatment effect examined so far. We should give more importance to metabolic variables to select the patients who would benefit the most from bariatric surgery."

SOS has been supported by grants from Astra Zeneca, Cederroth, Hoffman-La Roche, Johnson & Johnson, and Sanofi-Aventis. Dr. Sjötröm has been a speaker for Astra Zeneca and Johnson & Johnson, and he serves on the board of Lenimen.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Patients with type 2 diabetes who undergo bariatric surgery benefit from an increasingly reduced incidence of macro- and microvascular complications over the ensuing 20 years compared with matched controls, based on 20-year follow-up of more than 600 patients treated in Sweden.

The rate of complications that were prevented accelerated during 20 years of follow-up even though the prevalence of patients in remission from type 2 diabetes following bariatric surgery fell over time, with a nadir in remission reached at 20 years, Dr. Lars Sjötröm reported at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

Dr. Sjötröm and his associates previously reported results from the Swedish Obese Subjects (SOS) study showing that among the subgroup of patients who entered the study with diabetes, 72% were in remission from diabetes 2 years after bariatric surgery, and 36% were still in remission 10 years after surgery (N. Engl. J. Med. 2004;351:2683-93). Longer follow-up data he reported at the meeting show that after 15 years the remission rate dropped further to 30%, and after 20 years just 18% of the starting population remained in remission of their diabetes. After 20 years, roughly three-quarters of the patients who initially went into remission of their diabetes had relapsed back into active diabetes.

Despite this, the incidence of macro- and microvascular complications continued to fall compared with the control patients, reported Dr. Sjötröm, professor of medicine at the University of Gothenburg, Sweden, and lead investigator of SOS. The rate of complications of the eyes, kidneys, peripheral nerves, or peripheral circulation that required hospitalization was about 8% in the surgery patients and 12% in the controls after 10 years, and after 20 years the rates were about 20% in the surgery patients and 45% in the controls, a 54% relative risk reduction in favor of surgery that appeared greater than after 10 years. His group previously reported a similar finding for the incidence of myocardial infarctions (Diabetes Care 2012;35:2613-7).

"I think you should operate on patients with diabetes; we saw a drop in their complications," he said. "Even when patients relapse, their cardiovascular risk factors are still improved. This may be why we see an effect on complications despite the patients relapsing. Even with all the relapses, the effect of surgery on diabetic complications remains strong after 20 years." Gastric bypass surgery appeared to offer a feasible operation that also resulted in good diabetes control, he added.

The SOS enrolled 607 patients with diabetes out of the 4,047 total patients in the study. The diabetes subgroup comprised 345 who underwent some form of bariatric surgery, and 262 matched controls who did not receive surgery. Their average age was 50 years, their average body mass index was 40 kg/m², and they had diabetes for an average of 3 years.

In addition to producing diabetes remission and preventing complications, surgery also blunted the incidence of new-onset diabetes. A prior report from SOS showed prevention of new-onset diabetes in the surgery group through the first 15 years of follow-up, (N. Engl. J. Med. 2012;367:695-704), and after 20 years this effect "remained quite strong," with a 77% relative risk reduction in incident diabetes during 20 years of follow-up compared with the controls, Dr. Sjötröm reported.

He also called for scaling back body mass index criteria for performing bariatric surgery because the benefits following surgery appeared similar in patients with relatively low BMIs. He cited a recent analysis his group ran on the 233 patients from SOS who did not meet current criteria for bariatric surgery because their BMI was too low. The average BMI in this subgroup was 36 kg/m², and 104 of these patients underwent bariatric surgery (Diabetes Care 2013;36:1335-40). This exploratory analysis of SOS results showed that the benefits from bariatric surgery were similar in patients with lower BMIs and in patients with higher BMIs who meet the standard surgical criteria.

"Current BMI-based eligibility criteria [for bariatric surgery] are not valid," Dr. Sjötröm declared. "Baseline BMI does not predict any treatment effect examined so far. We should give more importance to metabolic variables to select the patients who would benefit the most from bariatric surgery."

SOS has been supported by grants from Astra Zeneca, Cederroth, Hoffman-La Roche, Johnson & Johnson, and Sanofi-Aventis. Dr. Sjötröm has been a speaker for Astra Zeneca and Johnson & Johnson, and he serves on the board of Lenimen.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – More than a third of treatment-naive patients with newly diagnosed schizophrenia had hyperprolactinemia, in an analysis of data from 73 such patients enrolled in a multicenter, international study.

"Hyperprolactinemia can be found independent of antipsychotic treatment in drug-naive, first-episode schizophrenia patients," Dr. Anita Riecher-Rössler said at the annual congress of the European College of Neuropsychopharmacology The frequent occurrence of hyperprolactinemia in these patients has clinical implications, she added.

Mitchel Zoler/IMNG Medical Media

First, physicians should measure prolactin levels in newly diagnosed schizophrenia patients to both check for hyperprolactinemia and to establish the patient’s baseline level before starting antipsychotic treatment. Patients should also get assessed for signs and symptoms of hyperprolactinemia, such as menstrual irregularities, loss of libido, and infertility, Dr. Riecher-Rössler said. Patients found to have hyperprolactinemia should undergo a thorough work-up to see if it has a somatic cause that requires treatment. Physicians should also avoid prescribing antipsychotic drugs that can raise prolactin levels to patients who already have an elevated level of the hormone. First-generation antipsychotic drugs, as well as certain second-generation agents such as amisulpride and risperidone are known inducers of hyperprolactinemia (Pharmacotherapy 2009;29:64-73).

"In patients with hyperprolactinemia, consider using a prolactin-sparing antipsychotic, or treat women with estradiol to normalize their prolactin level," said Dr. Riecher-Rössler, a professor of psychiatry and head of the Center for Gender Research and Early Detection at the University of Basel, Switzerland. Hyperprolactinemia poses a threat to young women of triggering early menopause with the resulting complications of loss of fertility and early-onset osteoporosis, she noted. But it also poses a threat to men, causing suppression of the testes and reduced sexuality. "Hyperprolactinemia is a reason to avoid using antipsychotic drugs that can cause it, especially in young women because of the risk of causing early menopause," she said, although drug-induced hyperprolactinemia is less of a threat in patients who start treatment with normal prolactin levels.

The finding also raises the possibility that hyperprolactinemia might play a role in causing schizophrenia, or that emerging schizophrenia or other stresses on the patient cause elevated prolactin levels,

If the patient has no other apparent cause of hyperprolactinemia "the idea is that it is stress induced, and stress is part of an emerging psychosis," she said in an interview. "If you treat the psychosis, you may also lower the prolactin."

Because elevated prolactin levels trigger release of prolactin-inhibiting factor, which is dopamine, another possibility is that high dopamine levels triggered by hyperprolactinemia might affect the brain and play a role in the pathogenesis of schizophrenia. These hypotheses need further study, Dr. Riecher-Rössler said.

The data she and her associates used came from the European First Episode of Schizophrenia Trial (EUFEST), which enrolled 498 patients with newly diagnosed schizophrenia at 50 centers in Europe and Israel (Lancet 2008;371:1085-97). From this group, 249 patients had reliable records on their medical treatment before entering the study and had blood samples available that had been drawn prior to the start of their treatment. The researchers identified 73 of these patients who had been completely free of any antipsychotic or other drug treatment that could have possibly caused elevated prolactin levels prior to their initial blood draw.

Analysis of the blood specimens showed that 19 of the 51 men (37%) and 11 of the 22 women (50%) had hyperprolactinemia, defined as a blood prolactin level greater than 38 U/L in men and greater than 53 U/L in women. The overall prevalence in all 73 patients was 41%.

All antipsychotics have adverse effects, and the risk that some might trigger hyperprolactinemia has to be taken into account along with all the other possible adverse effects when choosing drugs to prescribe to patients, she said.

"Do you prescribe olanzapine or quetiapine, which cause weight gain, or do you use amisulpride or risperidone, which raise prolactin?" Dr. Riecher-Rössler asked. "Which side effect is the patient prepared to cope with? I try to avoid using amisulpride in women who are young and still want to become pregnant or in young men so I don’t suppress their sexuality."

She and her associates reported the results in an article published earlier this year (Psychol Med. 2013 [doi:10.1017/S0033291713000226]).

EUFEST received support from Astra Zeneca, Pfizer, and Sanofi. Dr. Riecher-Rössler said she had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – More than a third of treatment-naive patients with newly diagnosed schizophrenia had hyperprolactinemia, in an analysis of data from 73 such patients enrolled in a multicenter, international study.

"Hyperprolactinemia can be found independent of antipsychotic treatment in drug-naive, first-episode schizophrenia patients," Dr. Anita Riecher-Rössler said at the annual congress of the European College of Neuropsychopharmacology The frequent occurrence of hyperprolactinemia in these patients has clinical implications, she added.

Mitchel Zoler/IMNG Medical Media

First, physicians should measure prolactin levels in newly diagnosed schizophrenia patients to both check for hyperprolactinemia and to establish the patient’s baseline level before starting antipsychotic treatment. Patients should also get assessed for signs and symptoms of hyperprolactinemia, such as menstrual irregularities, loss of libido, and infertility, Dr. Riecher-Rössler said. Patients found to have hyperprolactinemia should undergo a thorough work-up to see if it has a somatic cause that requires treatment. Physicians should also avoid prescribing antipsychotic drugs that can raise prolactin levels to patients who already have an elevated level of the hormone. First-generation antipsychotic drugs, as well as certain second-generation agents such as amisulpride and risperidone are known inducers of hyperprolactinemia (Pharmacotherapy 2009;29:64-73).

"In patients with hyperprolactinemia, consider using a prolactin-sparing antipsychotic, or treat women with estradiol to normalize their prolactin level," said Dr. Riecher-Rössler, a professor of psychiatry and head of the Center for Gender Research and Early Detection at the University of Basel, Switzerland. Hyperprolactinemia poses a threat to young women of triggering early menopause with the resulting complications of loss of fertility and early-onset osteoporosis, she noted. But it also poses a threat to men, causing suppression of the testes and reduced sexuality. "Hyperprolactinemia is a reason to avoid using antipsychotic drugs that can cause it, especially in young women because of the risk of causing early menopause," she said, although drug-induced hyperprolactinemia is less of a threat in patients who start treatment with normal prolactin levels.

The finding also raises the possibility that hyperprolactinemia might play a role in causing schizophrenia, or that emerging schizophrenia or other stresses on the patient cause elevated prolactin levels,

If the patient has no other apparent cause of hyperprolactinemia "the idea is that it is stress induced, and stress is part of an emerging psychosis," she said in an interview. "If you treat the psychosis, you may also lower the prolactin."

Because elevated prolactin levels trigger release of prolactin-inhibiting factor, which is dopamine, another possibility is that high dopamine levels triggered by hyperprolactinemia might affect the brain and play a role in the pathogenesis of schizophrenia. These hypotheses need further study, Dr. Riecher-Rössler said.

The data she and her associates used came from the European First Episode of Schizophrenia Trial (EUFEST), which enrolled 498 patients with newly diagnosed schizophrenia at 50 centers in Europe and Israel (Lancet 2008;371:1085-97). From this group, 249 patients had reliable records on their medical treatment before entering the study and had blood samples available that had been drawn prior to the start of their treatment. The researchers identified 73 of these patients who had been completely free of any antipsychotic or other drug treatment that could have possibly caused elevated prolactin levels prior to their initial blood draw.

Analysis of the blood specimens showed that 19 of the 51 men (37%) and 11 of the 22 women (50%) had hyperprolactinemia, defined as a blood prolactin level greater than 38 U/L in men and greater than 53 U/L in women. The overall prevalence in all 73 patients was 41%.

All antipsychotics have adverse effects, and the risk that some might trigger hyperprolactinemia has to be taken into account along with all the other possible adverse effects when choosing drugs to prescribe to patients, she said.

"Do you prescribe olanzapine or quetiapine, which cause weight gain, or do you use amisulpride or risperidone, which raise prolactin?" Dr. Riecher-Rössler asked. "Which side effect is the patient prepared to cope with? I try to avoid using amisulpride in women who are young and still want to become pregnant or in young men so I don’t suppress their sexuality."

She and her associates reported the results in an article published earlier this year (Psychol Med. 2013 [doi:10.1017/S0033291713000226]).

EUFEST received support from Astra Zeneca, Pfizer, and Sanofi. Dr. Riecher-Rössler said she had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – More than a third of treatment-naive patients with newly diagnosed schizophrenia had hyperprolactinemia, in an analysis of data from 73 such patients enrolled in a multicenter, international study.

"Hyperprolactinemia can be found independent of antipsychotic treatment in drug-naive, first-episode schizophrenia patients," Dr. Anita Riecher-Rössler said at the annual congress of the European College of Neuropsychopharmacology The frequent occurrence of hyperprolactinemia in these patients has clinical implications, she added.

Mitchel Zoler/IMNG Medical Media

First, physicians should measure prolactin levels in newly diagnosed schizophrenia patients to both check for hyperprolactinemia and to establish the patient’s baseline level before starting antipsychotic treatment. Patients should also get assessed for signs and symptoms of hyperprolactinemia, such as menstrual irregularities, loss of libido, and infertility, Dr. Riecher-Rössler said. Patients found to have hyperprolactinemia should undergo a thorough work-up to see if it has a somatic cause that requires treatment. Physicians should also avoid prescribing antipsychotic drugs that can raise prolactin levels to patients who already have an elevated level of the hormone. First-generation antipsychotic drugs, as well as certain second-generation agents such as amisulpride and risperidone are known inducers of hyperprolactinemia (Pharmacotherapy 2009;29:64-73).

"In patients with hyperprolactinemia, consider using a prolactin-sparing antipsychotic, or treat women with estradiol to normalize their prolactin level," said Dr. Riecher-Rössler, a professor of psychiatry and head of the Center for Gender Research and Early Detection at the University of Basel, Switzerland. Hyperprolactinemia poses a threat to young women of triggering early menopause with the resulting complications of loss of fertility and early-onset osteoporosis, she noted. But it also poses a threat to men, causing suppression of the testes and reduced sexuality. "Hyperprolactinemia is a reason to avoid using antipsychotic drugs that can cause it, especially in young women because of the risk of causing early menopause," she said, although drug-induced hyperprolactinemia is less of a threat in patients who start treatment with normal prolactin levels.

The finding also raises the possibility that hyperprolactinemia might play a role in causing schizophrenia, or that emerging schizophrenia or other stresses on the patient cause elevated prolactin levels,

If the patient has no other apparent cause of hyperprolactinemia "the idea is that it is stress induced, and stress is part of an emerging psychosis," she said in an interview. "If you treat the psychosis, you may also lower the prolactin."

Because elevated prolactin levels trigger release of prolactin-inhibiting factor, which is dopamine, another possibility is that high dopamine levels triggered by hyperprolactinemia might affect the brain and play a role in the pathogenesis of schizophrenia. These hypotheses need further study, Dr. Riecher-Rössler said.

The data she and her associates used came from the European First Episode of Schizophrenia Trial (EUFEST), which enrolled 498 patients with newly diagnosed schizophrenia at 50 centers in Europe and Israel (Lancet 2008;371:1085-97). From this group, 249 patients had reliable records on their medical treatment before entering the study and had blood samples available that had been drawn prior to the start of their treatment. The researchers identified 73 of these patients who had been completely free of any antipsychotic or other drug treatment that could have possibly caused elevated prolactin levels prior to their initial blood draw.

Analysis of the blood specimens showed that 19 of the 51 men (37%) and 11 of the 22 women (50%) had hyperprolactinemia, defined as a blood prolactin level greater than 38 U/L in men and greater than 53 U/L in women. The overall prevalence in all 73 patients was 41%.

All antipsychotics have adverse effects, and the risk that some might trigger hyperprolactinemia has to be taken into account along with all the other possible adverse effects when choosing drugs to prescribe to patients, she said.

"Do you prescribe olanzapine or quetiapine, which cause weight gain, or do you use amisulpride or risperidone, which raise prolactin?" Dr. Riecher-Rössler asked. "Which side effect is the patient prepared to cope with? I try to avoid using amisulpride in women who are young and still want to become pregnant or in young men so I don’t suppress their sexuality."

She and her associates reported the results in an article published earlier this year (Psychol Med. 2013 [doi:10.1017/S0033291713000226]).

EUFEST received support from Astra Zeneca, Pfizer, and Sanofi. Dr. Riecher-Rössler said she had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Lurasidone, an atypical antipsychotic approved by the Food and Drug Administration last June for the treatment of depression in patients with bipolar I disorder, has the potential to become a first-line treatment for these patients as physicians grow more familiar and comfortable with the drug, Dr. Joseph R. Calabrese said at the annual Congress of the European College of Neuropsychopharmacology.

In addition to showing significant efficacy for reducing depression in bipolar I patients when used as either monotherapy or as adjunctive therapy in a pair of phase III trials, lurasidone (Latuda) "does not have the metabolic burden caused by some other drugs" used in these patients, and also showed no statistically significant increase in dropout rates compared with placebo. The discontinuation rate because of adverse effects was especially low when the drug was administered at a dosage of 20-60 mg/day. This safety finding is "remarkable," said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland.

Mitchel L. Zoler/IMNG Medical Media

The results from the two phase III trials provide "unequivocal evidence that the drug has short-term efficacy for patients with depressive episodes in bipolar I disorder. I think the evidence is very persuasive," Dr. Calabrese said in an interview. "I think this drug will be used adjunctively at first, but with more familiarity, physicians will start using it up front. The No. 1 attraction for first-line therapy is no metabolic burden; that’s a huge issue. And sedation is minimal." Dr. Calabrese stressed that the trial results showed no dropouts because of sedation, and 10%-15% of patients reported a sedation effect, compared with the 40% rate typically seen with lamotrigine (Lamictal).

One of the trials assessed lurasidone as an adjunctive treatment in 340 patients already on treatment with lithium or valproate. After 6 weeks, patients on lurasidone plus one of the other drugs had an average drop from baseline in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 17.1 points, compared with an average 13.5-point drop in the control patients who were on lithium or valproate plus placebo, a statistically significant difference. Fifty-seven percent of the 179 patients receiving lurasidone had at least a 50% drop in their MADRS score, compared with 42% of 161 patients in the control arm. Remission – achievement of a MADRS score of 12 or less – occurred in half the lurasidone patients and 35% of the controls.

Also notable was the impact the drug had on the 10 individual components of the MADRS score. Six of these 10 items showed statistically significant reductions with lurasidone treatment, including the two core measures of depression, apparent sadness and reported sadness.

The second trial tested lurasidone as monotherapy, at two different dosages, either 20-60 mg/day or 80-120 mg/day, and both were compared with placebo during 6 weeks of treatment, with a total of 485 patients randomized and completing 6 weeks on treatment. Lurasidone resulted in a similar pattern of efficacy, with 42% (lower dosage) and 40% of patients having their MADRS score drop to 12 points or less, compared with a 25% remission rate in the placebo group. Both dosages of lurasidone led to statistically significant reductions in 7 of the 10 MADRS component measures compared with the control arm.

The monotherapy study also showed that while the lower lurasidone dosage was just as effective as the higher dosage, it was more tolerable, with lower rates of akathisia and extrapyramidal symptoms. Lurasidone appears to produce low rates of sedation, appetite stimulation, and weight gain because of its negligible binding to the histamine₁ receptor, Dr. Calabrese said. In the adjunctive study, lurasidone treatment resulted in virtually no change in weight or body mass index, and very small changes in cholesterol, triglycerides, and fasting glucose.

The two trials were sponsored by Sunovion, the company that markets lurasidone. Dr. Calabrese said he has been a consultant to and has received research support from Sunovion as well as from more than a dozen other drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Lurasidone, an atypical antipsychotic approved by the Food and Drug Administration last June for the treatment of depression in patients with bipolar I disorder, has the potential to become a first-line treatment for these patients as physicians grow more familiar and comfortable with the drug, Dr. Joseph R. Calabrese said at the annual Congress of the European College of Neuropsychopharmacology.

In addition to showing significant efficacy for reducing depression in bipolar I patients when used as either monotherapy or as adjunctive therapy in a pair of phase III trials, lurasidone (Latuda) "does not have the metabolic burden caused by some other drugs" used in these patients, and also showed no statistically significant increase in dropout rates compared with placebo. The discontinuation rate because of adverse effects was especially low when the drug was administered at a dosage of 20-60 mg/day. This safety finding is "remarkable," said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland.

Mitchel L. Zoler/IMNG Medical Media

The results from the two phase III trials provide "unequivocal evidence that the drug has short-term efficacy for patients with depressive episodes in bipolar I disorder. I think the evidence is very persuasive," Dr. Calabrese said in an interview. "I think this drug will be used adjunctively at first, but with more familiarity, physicians will start using it up front. The No. 1 attraction for first-line therapy is no metabolic burden; that’s a huge issue. And sedation is minimal." Dr. Calabrese stressed that the trial results showed no dropouts because of sedation, and 10%-15% of patients reported a sedation effect, compared with the 40% rate typically seen with lamotrigine (Lamictal).

One of the trials assessed lurasidone as an adjunctive treatment in 340 patients already on treatment with lithium or valproate. After 6 weeks, patients on lurasidone plus one of the other drugs had an average drop from baseline in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 17.1 points, compared with an average 13.5-point drop in the control patients who were on lithium or valproate plus placebo, a statistically significant difference. Fifty-seven percent of the 179 patients receiving lurasidone had at least a 50% drop in their MADRS score, compared with 42% of 161 patients in the control arm. Remission – achievement of a MADRS score of 12 or less – occurred in half the lurasidone patients and 35% of the controls.

Also notable was the impact the drug had on the 10 individual components of the MADRS score. Six of these 10 items showed statistically significant reductions with lurasidone treatment, including the two core measures of depression, apparent sadness and reported sadness.

The second trial tested lurasidone as monotherapy, at two different dosages, either 20-60 mg/day or 80-120 mg/day, and both were compared with placebo during 6 weeks of treatment, with a total of 485 patients randomized and completing 6 weeks on treatment. Lurasidone resulted in a similar pattern of efficacy, with 42% (lower dosage) and 40% of patients having their MADRS score drop to 12 points or less, compared with a 25% remission rate in the placebo group. Both dosages of lurasidone led to statistically significant reductions in 7 of the 10 MADRS component measures compared with the control arm.

The monotherapy study also showed that while the lower lurasidone dosage was just as effective as the higher dosage, it was more tolerable, with lower rates of akathisia and extrapyramidal symptoms. Lurasidone appears to produce low rates of sedation, appetite stimulation, and weight gain because of its negligible binding to the histamine₁ receptor, Dr. Calabrese said. In the adjunctive study, lurasidone treatment resulted in virtually no change in weight or body mass index, and very small changes in cholesterol, triglycerides, and fasting glucose.

The two trials were sponsored by Sunovion, the company that markets lurasidone. Dr. Calabrese said he has been a consultant to and has received research support from Sunovion as well as from more than a dozen other drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Lurasidone, an atypical antipsychotic approved by the Food and Drug Administration last June for the treatment of depression in patients with bipolar I disorder, has the potential to become a first-line treatment for these patients as physicians grow more familiar and comfortable with the drug, Dr. Joseph R. Calabrese said at the annual Congress of the European College of Neuropsychopharmacology.

In addition to showing significant efficacy for reducing depression in bipolar I patients when used as either monotherapy or as adjunctive therapy in a pair of phase III trials, lurasidone (Latuda) "does not have the metabolic burden caused by some other drugs" used in these patients, and also showed no statistically significant increase in dropout rates compared with placebo. The discontinuation rate because of adverse effects was especially low when the drug was administered at a dosage of 20-60 mg/day. This safety finding is "remarkable," said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland.

Mitchel L. Zoler/IMNG Medical Media

The results from the two phase III trials provide "unequivocal evidence that the drug has short-term efficacy for patients with depressive episodes in bipolar I disorder. I think the evidence is very persuasive," Dr. Calabrese said in an interview. "I think this drug will be used adjunctively at first, but with more familiarity, physicians will start using it up front. The No. 1 attraction for first-line therapy is no metabolic burden; that’s a huge issue. And sedation is minimal." Dr. Calabrese stressed that the trial results showed no dropouts because of sedation, and 10%-15% of patients reported a sedation effect, compared with the 40% rate typically seen with lamotrigine (Lamictal).

One of the trials assessed lurasidone as an adjunctive treatment in 340 patients already on treatment with lithium or valproate. After 6 weeks, patients on lurasidone plus one of the other drugs had an average drop from baseline in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 17.1 points, compared with an average 13.5-point drop in the control patients who were on lithium or valproate plus placebo, a statistically significant difference. Fifty-seven percent of the 179 patients receiving lurasidone had at least a 50% drop in their MADRS score, compared with 42% of 161 patients in the control arm. Remission – achievement of a MADRS score of 12 or less – occurred in half the lurasidone patients and 35% of the controls.

Also notable was the impact the drug had on the 10 individual components of the MADRS score. Six of these 10 items showed statistically significant reductions with lurasidone treatment, including the two core measures of depression, apparent sadness and reported sadness.

The second trial tested lurasidone as monotherapy, at two different dosages, either 20-60 mg/day or 80-120 mg/day, and both were compared with placebo during 6 weeks of treatment, with a total of 485 patients randomized and completing 6 weeks on treatment. Lurasidone resulted in a similar pattern of efficacy, with 42% (lower dosage) and 40% of patients having their MADRS score drop to 12 points or less, compared with a 25% remission rate in the placebo group. Both dosages of lurasidone led to statistically significant reductions in 7 of the 10 MADRS component measures compared with the control arm.

The monotherapy study also showed that while the lower lurasidone dosage was just as effective as the higher dosage, it was more tolerable, with lower rates of akathisia and extrapyramidal symptoms. Lurasidone appears to produce low rates of sedation, appetite stimulation, and weight gain because of its negligible binding to the histamine₁ receptor, Dr. Calabrese said. In the adjunctive study, lurasidone treatment resulted in virtually no change in weight or body mass index, and very small changes in cholesterol, triglycerides, and fasting glucose.

The two trials were sponsored by Sunovion, the company that markets lurasidone. Dr. Calabrese said he has been a consultant to and has received research support from Sunovion as well as from more than a dozen other drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Not all type 2 diabetes is the same, and pathophysiologic differences among diabetes subtypes mean that different type 2 patients need different treatment.

"Several specific causes of hyperglycemia are hidden behind the clinical diagnosis of type 2 diabetes," Dr. Henning Beck-Nielsen said at the annual meeting of the European Association for the Study of Diabetes.

"Patients with type 2 diabetes can be divided into three basic pathophysiologic phenotypes: classic type 2 diabetes, insulinopenic type 2 diabetes, and hyperinsulinemic type 2 diabetes." He and his associates identified these and other, less common subtypes by systematically studying more than 1,000 Danish patients newly diagnosed with type 2 diabetes who were entered into a national registry that now totals 40,000 patients.

"We recommend that clinicians measure both GAD [glutamic acid decarboxylase] antibodies and fasting C-peptide in newly diagnosed patients with type 2 diabetes to properly classify the phenotypes," said Dr. Beck-Nielsen, professor and head of the endocrinology research unit at Odense (Denmark) University Hospital. "Measuring C-peptide gives a lot of information."

Patients with the insulinopenic form of type 2 diabetes should receive insulin treatment, those with the hyperinsulinemic form should ideally be treated with a sensitizer drug, while patients with a combination of both defects – classic type 2 diabetes – should be treated according to current recommendations (Diabetes Care 2012;35:1364-79), he said in an interview.

Dr. Beck-Nielsen and his associates studied the first 1,048 Danish patients newly diagnosed with type 2 diabetes by a general practitioner or in an outpatient clinic and enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study. The patients averaged 61 years old, and slightly more than half were men.

Initial analysis identified 918 (87%) of the patients with true type 2 diabetes. Another 6% had steroid-associated diabetes; 4% had diabetes secondary to pancreatitis; 3% were positive for GAD antibodies showing they had latent autoimmune diabetes of adulthood (LADA); and a small number of patients had rare disorders.

Among the 918 with true type 2 diabetes, the Odense researchers used data collected on fasting levels of C-peptide and plasma glucose to make a homeostasis model assessment (HOMA2) and derive from it information on insulin sensitivity and beta-cell activity.

Roughly half the patients had classic type 2 diabetes, about a third had the hyperinsulinemic form, and fewer than a quarter had the insulinopenic form (but not type 1 diabetes or LADA). These clusterings appeared independent of age and sex, but patients with classic type 2 diabetes or the hyperinsulinemic form had a greater prevalence of metabolic syndrome and increased waist circumference.

Patients with insulinopenic type 2 diabetes had an average body mass index of 26.9 kg/m², were sensitive to insulin, and had a relatively low prevalence of cardiovascular disease, compared with the other two types. Cardiovascular disease prevalence was highest among the hyperinsulinemic patients, who were generally obese and had a 25% cardiovascular disease prevalence compared with a 13% rate in those with insulinopenic diabetes, and an 18% rate in those with classic type 2 diabetes.

Dr. Beck-Nielsen said that he has received research support from Novo Nordisk.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Not all type 2 diabetes is the same, and pathophysiologic differences among diabetes subtypes mean that different type 2 patients need different treatment.

"Several specific causes of hyperglycemia are hidden behind the clinical diagnosis of type 2 diabetes," Dr. Henning Beck-Nielsen said at the annual meeting of the European Association for the Study of Diabetes.

"Patients with type 2 diabetes can be divided into three basic pathophysiologic phenotypes: classic type 2 diabetes, insulinopenic type 2 diabetes, and hyperinsulinemic type 2 diabetes." He and his associates identified these and other, less common subtypes by systematically studying more than 1,000 Danish patients newly diagnosed with type 2 diabetes who were entered into a national registry that now totals 40,000 patients.

"We recommend that clinicians measure both GAD [glutamic acid decarboxylase] antibodies and fasting C-peptide in newly diagnosed patients with type 2 diabetes to properly classify the phenotypes," said Dr. Beck-Nielsen, professor and head of the endocrinology research unit at Odense (Denmark) University Hospital. "Measuring C-peptide gives a lot of information."

Patients with the insulinopenic form of type 2 diabetes should receive insulin treatment, those with the hyperinsulinemic form should ideally be treated with a sensitizer drug, while patients with a combination of both defects – classic type 2 diabetes – should be treated according to current recommendations (Diabetes Care 2012;35:1364-79), he said in an interview.

Dr. Beck-Nielsen and his associates studied the first 1,048 Danish patients newly diagnosed with type 2 diabetes by a general practitioner or in an outpatient clinic and enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study. The patients averaged 61 years old, and slightly more than half were men.

Initial analysis identified 918 (87%) of the patients with true type 2 diabetes. Another 6% had steroid-associated diabetes; 4% had diabetes secondary to pancreatitis; 3% were positive for GAD antibodies showing they had latent autoimmune diabetes of adulthood (LADA); and a small number of patients had rare disorders.

Among the 918 with true type 2 diabetes, the Odense researchers used data collected on fasting levels of C-peptide and plasma glucose to make a homeostasis model assessment (HOMA2) and derive from it information on insulin sensitivity and beta-cell activity.

Roughly half the patients had classic type 2 diabetes, about a third had the hyperinsulinemic form, and fewer than a quarter had the insulinopenic form (but not type 1 diabetes or LADA). These clusterings appeared independent of age and sex, but patients with classic type 2 diabetes or the hyperinsulinemic form had a greater prevalence of metabolic syndrome and increased waist circumference.

Patients with insulinopenic type 2 diabetes had an average body mass index of 26.9 kg/m², were sensitive to insulin, and had a relatively low prevalence of cardiovascular disease, compared with the other two types. Cardiovascular disease prevalence was highest among the hyperinsulinemic patients, who were generally obese and had a 25% cardiovascular disease prevalence compared with a 13% rate in those with insulinopenic diabetes, and an 18% rate in those with classic type 2 diabetes.

Dr. Beck-Nielsen said that he has received research support from Novo Nordisk.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Not all type 2 diabetes is the same, and pathophysiologic differences among diabetes subtypes mean that different type 2 patients need different treatment.

"Several specific causes of hyperglycemia are hidden behind the clinical diagnosis of type 2 diabetes," Dr. Henning Beck-Nielsen said at the annual meeting of the European Association for the Study of Diabetes.

"Patients with type 2 diabetes can be divided into three basic pathophysiologic phenotypes: classic type 2 diabetes, insulinopenic type 2 diabetes, and hyperinsulinemic type 2 diabetes." He and his associates identified these and other, less common subtypes by systematically studying more than 1,000 Danish patients newly diagnosed with type 2 diabetes who were entered into a national registry that now totals 40,000 patients.

"We recommend that clinicians measure both GAD [glutamic acid decarboxylase] antibodies and fasting C-peptide in newly diagnosed patients with type 2 diabetes to properly classify the phenotypes," said Dr. Beck-Nielsen, professor and head of the endocrinology research unit at Odense (Denmark) University Hospital. "Measuring C-peptide gives a lot of information."

Patients with the insulinopenic form of type 2 diabetes should receive insulin treatment, those with the hyperinsulinemic form should ideally be treated with a sensitizer drug, while patients with a combination of both defects – classic type 2 diabetes – should be treated according to current recommendations (Diabetes Care 2012;35:1364-79), he said in an interview.

Dr. Beck-Nielsen and his associates studied the first 1,048 Danish patients newly diagnosed with type 2 diabetes by a general practitioner or in an outpatient clinic and enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study. The patients averaged 61 years old, and slightly more than half were men.

Initial analysis identified 918 (87%) of the patients with true type 2 diabetes. Another 6% had steroid-associated diabetes; 4% had diabetes secondary to pancreatitis; 3% were positive for GAD antibodies showing they had latent autoimmune diabetes of adulthood (LADA); and a small number of patients had rare disorders.

Among the 918 with true type 2 diabetes, the Odense researchers used data collected on fasting levels of C-peptide and plasma glucose to make a homeostasis model assessment (HOMA2) and derive from it information on insulin sensitivity and beta-cell activity.

Roughly half the patients had classic type 2 diabetes, about a third had the hyperinsulinemic form, and fewer than a quarter had the insulinopenic form (but not type 1 diabetes or LADA). These clusterings appeared independent of age and sex, but patients with classic type 2 diabetes or the hyperinsulinemic form had a greater prevalence of metabolic syndrome and increased waist circumference.

Patients with insulinopenic type 2 diabetes had an average body mass index of 26.9 kg/m², were sensitive to insulin, and had a relatively low prevalence of cardiovascular disease, compared with the other two types. Cardiovascular disease prevalence was highest among the hyperinsulinemic patients, who were generally obese and had a 25% cardiovascular disease prevalence compared with a 13% rate in those with insulinopenic diabetes, and an 18% rate in those with classic type 2 diabetes.

Dr. Beck-Nielsen said that he has received research support from Novo Nordisk.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Not all type 2 diabetes is the same, and pathophysiologic differences among diabetes subtypes mean that different type 2 patients need different treatment.

"Several specific causes of hyperglycemia are hidden behind the clinical diagnosis of type 2 diabetes," Dr. Henning Beck-Nielsen said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

"Patients with type 2 diabetes can be divided into three basic pathophysiologic phenotypes: classic type 2 diabetes, insulinopenic type 2 diabetes, and hyperinsulinemic type 2 diabetes." He and his associates identified these and other, less common subtypes by systematically studying more than 1,000 Danish patients newly diagnosed with type 2 diabetes who were entered into a national registry that now totals 40,000 patients.

"We recommend that clinicians measure both GAD [glutamic acid decarboxylase] antibodies and fasting C-peptide in newly diagnosed patients with type 2 diabetes to properly classify the phenotypes," said Dr. Beck-Nielsen, professor and head of the endocrinology research unit at Odense (Denmark) University Hospital. "Measuring C-peptide gives a lot of information."

Patients with the insulinopenic form of type 2 diabetes should receive insulin treatment, those with the hyperinsulinemic form should ideally be treated with a sensitizer drug, while patients with a combination of both defects – classic type 2 diabetes – should be treated according to current recommendations (Diabetes Care 2012;35:1364-79), he said in an interview.

Dr. Beck-Nielsen and his associates studied the first 1,048 Danish patients newly diagnosed with type 2 diabetes by a general practitioner or in an outpatient clinic and enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study. The patients averaged 61 years old, and slightly more than half were men.

Initial analysis identified 918 (87%) of the patients with true type 2 diabetes. Another 6% had steroid-associated diabetes; 4% had diabetes secondary to pancreatitis; 3% were positive for GAD antibodies showing they had latent autoimmune diabetes of adulthood (LADA); and a small number of patients had rare disorders.

Among the 918 with true type 2 diabetes, the Odense researchers used data collected on fasting levels of C-peptide and plasma glucose to make a homeostasis model assessment (HOMA2) and derive from it information on insulin sensitivity and beta-cell activity.

Roughly half the patients had classic type 2 diabetes, about a third had the hyperinsulinemic form, and fewer than a quarter had the insulinopenic form (but not type 1 diabetes or LADA). These clusterings appeared independent of age and sex, but patients with classic type 2 diabetes or the hyperinsulinemic form had a greater prevalence of metabolic syndrome and increased waist circumference.

Patients with insulinopenic type 2 diabetes had an average body mass index of 26.9 kg/m², were sensitive to insulin, and had a relatively low prevalence of cardiovascular disease, compared with the other two types. Cardiovascular disease prevalence was highest among the hyperinsulinemic patients, who were generally obese and had a 25% cardiovascular disease prevalence compared with a 13% rate in those with insulinopenic diabetes, and an 18% rate in those with classic type 2 diabetes.

Dr. Beck-Nielsen said that he has received research support from Novo Nordisk.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Not all type 2 diabetes is the same, and pathophysiologic differences among diabetes subtypes mean that different type 2 patients need different treatment.

"Several specific causes of hyperglycemia are hidden behind the clinical diagnosis of type 2 diabetes," Dr. Henning Beck-Nielsen said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

"Patients with type 2 diabetes can be divided into three basic pathophysiologic phenotypes: classic type 2 diabetes, insulinopenic type 2 diabetes, and hyperinsulinemic type 2 diabetes." He and his associates identified these and other, less common subtypes by systematically studying more than 1,000 Danish patients newly diagnosed with type 2 diabetes who were entered into a national registry that now totals 40,000 patients.

"We recommend that clinicians measure both GAD [glutamic acid decarboxylase] antibodies and fasting C-peptide in newly diagnosed patients with type 2 diabetes to properly classify the phenotypes," said Dr. Beck-Nielsen, professor and head of the endocrinology research unit at Odense (Denmark) University Hospital. "Measuring C-peptide gives a lot of information."

Patients with the insulinopenic form of type 2 diabetes should receive insulin treatment, those with the hyperinsulinemic form should ideally be treated with a sensitizer drug, while patients with a combination of both defects – classic type 2 diabetes – should be treated according to current recommendations (Diabetes Care 2012;35:1364-79), he said in an interview.

Dr. Beck-Nielsen and his associates studied the first 1,048 Danish patients newly diagnosed with type 2 diabetes by a general practitioner or in an outpatient clinic and enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study. The patients averaged 61 years old, and slightly more than half were men.

Initial analysis identified 918 (87%) of the patients with true type 2 diabetes. Another 6% had steroid-associated diabetes; 4% had diabetes secondary to pancreatitis; 3% were positive for GAD antibodies showing they had latent autoimmune diabetes of adulthood (LADA); and a small number of patients had rare disorders.

Among the 918 with true type 2 diabetes, the Odense researchers used data collected on fasting levels of C-peptide and plasma glucose to make a homeostasis model assessment (HOMA2) and derive from it information on insulin sensitivity and beta-cell activity.

Roughly half the patients had classic type 2 diabetes, about a third had the hyperinsulinemic form, and fewer than a quarter had the insulinopenic form (but not type 1 diabetes or LADA). These clusterings appeared independent of age and sex, but patients with classic type 2 diabetes or the hyperinsulinemic form had a greater prevalence of metabolic syndrome and increased waist circumference.

Patients with insulinopenic type 2 diabetes had an average body mass index of 26.9 kg/m², were sensitive to insulin, and had a relatively low prevalence of cardiovascular disease, compared with the other two types. Cardiovascular disease prevalence was highest among the hyperinsulinemic patients, who were generally obese and had a 25% cardiovascular disease prevalence compared with a 13% rate in those with insulinopenic diabetes, and an 18% rate in those with classic type 2 diabetes.

Dr. Beck-Nielsen said that he has received research support from Novo Nordisk.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BARCELONA – Not all type 2 diabetes is the same, and pathophysiologic differences among diabetes subtypes mean that different type 2 patients need different treatment.

"Several specific causes of hyperglycemia are hidden behind the clinical diagnosis of type 2 diabetes," Dr. Henning Beck-Nielsen said at the annual meeting of the European Association for the Study of Diabetes.

Mitchel L. Zoler/IMNG Medical Media

"Patients with type 2 diabetes can be divided into three basic pathophysiologic phenotypes: classic type 2 diabetes, insulinopenic type 2 diabetes, and hyperinsulinemic type 2 diabetes." He and his associates identified these and other, less common subtypes by systematically studying more than 1,000 Danish patients newly diagnosed with type 2 diabetes who were entered into a national registry that now totals 40,000 patients.

"We recommend that clinicians measure both GAD [glutamic acid decarboxylase] antibodies and fasting C-peptide in newly diagnosed patients with type 2 diabetes to properly classify the phenotypes," said Dr. Beck-Nielsen, professor and head of the endocrinology research unit at Odense (Denmark) University Hospital. "Measuring C-peptide gives a lot of information."

Patients with the insulinopenic form of type 2 diabetes should receive insulin treatment, those with the hyperinsulinemic form should ideally be treated with a sensitizer drug, while patients with a combination of both defects – classic type 2 diabetes – should be treated according to current recommendations (Diabetes Care 2012;35:1364-79), he said in an interview.

Dr. Beck-Nielsen and his associates studied the first 1,048 Danish patients newly diagnosed with type 2 diabetes by a general practitioner or in an outpatient clinic and enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study. The patients averaged 61 years old, and slightly more than half were men.

Initial analysis identified 918 (87%) of the patients with true type 2 diabetes. Another 6% had steroid-associated diabetes; 4% had diabetes secondary to pancreatitis; 3% were positive for GAD antibodies showing they had latent autoimmune diabetes of adulthood (LADA); and a small number of patients had rare disorders.

Among the 918 with true type 2 diabetes, the Odense researchers used data collected on fasting levels of C-peptide and plasma glucose to make a homeostasis model assessment (HOMA2) and derive from it information on insulin sensitivity and beta-cell activity.

Roughly half the patients had classic type 2 diabetes, about a third had the hyperinsulinemic form, and fewer than a quarter had the insulinopenic form (but not type 1 diabetes or LADA). These clusterings appeared independent of age and sex, but patients with classic type 2 diabetes or the hyperinsulinemic form had a greater prevalence of metabolic syndrome and increased waist circumference.

Patients with insulinopenic type 2 diabetes had an average body mass index of 26.9 kg/m², were sensitive to insulin, and had a relatively low prevalence of cardiovascular disease, compared with the other two types. Cardiovascular disease prevalence was highest among the hyperinsulinemic patients, who were generally obese and had a 25% cardiovascular disease prevalence compared with a 13% rate in those with insulinopenic diabetes, and an 18% rate in those with classic type 2 diabetes.

Dr. Beck-Nielsen said that he has received research support from Novo Nordisk.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler