Annual Cardiovascular Conference at Snowmass

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

[email protected]

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

[email protected]

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

[email protected]

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

[email protected]

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

[email protected]

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

[email protected]

SNOWMASS, COLO. – A structured frailty assessment has become an important tool for cardiologists in individualizing decisions regarding referral of elderly patients for heart procedures.

The frailty assessment aids in determining whether the procedure is likely to improve the individual’s long-term outcome, or if instead, multiple converging limitations unrelated to the cardiac condition are pushing the patient toward early functional losses and mortality from noncardiovascular causes.

More than 20 multidimensional frailty scales have been developed in the geriatrics literature during the past decade. For busy cardiologists, two of the simplest, fastest, and least expensive are walking speed and the Dalhousie Clinical Frailty Scale, Dr. Karen P. Alexander said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Walking speed can be assessed by a nonphysician with a stopwatch and two marks on the hallway floor 4-6 meters apart, noted Dr. Alexander, a cardiologist with a special interest in geriatrics at Duke University, Durham, N.C.

The first prospective study of walking speed as a predictor of mortality and major morbidity in elderly patients scheduled for cardiac surgery involved 131 subjects at four university hospitals. Those classified as slow walkers as defined by taking 6 seconds or longer to cover 5 meters in the clinic hallway had a threefold increased rate of the composite endpoint of in-hospital mortality, stroke, renal failure, prolonged infection, deep sternal wound infection, or reoperation. That was true even after adjusting for the widely used Society of Thoracic Surgeons risk score.

Patients with a high STS risk score, of 15% or more, plus a 5-meter walk speed of 6 seconds or longer, had a 43% incidence of mortality or major morbidity. Those with an STS risk score below 15% and a walking speed of less than 6 seconds had an event rate of only 6% (J. Am. Coll. Cardiol. 2010;56:1668-76).

More recently, a pooled analysis of 9 cohort studies totaling nearly 35,000 community-dwelling seniors followed for 6-21 years concluded that gait speed was significantly associated with remaining years of life in both men and women.

Lead investigator Dr. Stephanie Studenski, director of research in the division of geriatric medicine at the University of Pittsburgh, noted that each 0.1-meter/second increment in walking speed was associated with a 12% increase in survival. A walking speed of 0.8 meters/second was associated with the median life expectancy for persons in that age category. She proposed that a walking speed of 0.6 meters/second would be a reasonable threshold for increased risk of early mortality, that a speed faster than 1.0 meters/second suggests better than average life expectancy, and a gait speed above 1.2 meters/second suggests exceptional life expectancy (JAMA 2011;305:50-8).

Dr. Alexander said the Clinical Frailty Scale developed by Dr. Kenneth Rockwood and his coworkers at Dalhousie University in Halifax, Nova Scotia, allows physicians to quickly judge where an individual patient fits on a nine-point frailty scale.

"It gets raters on the same page and improves upon the ‘I know frailty when I see it’ eyeball test," she added.

It appears, however, that cardiologists may be underutilizing frailty assessments. When session moderator Dr. Rick A. Nishimura of the Mayo Clinic, Rochester, Minn., asked for an audience show of hands as to how many routinely make a comment about frailty in elderly patients’ charts, only about 40% responded affirmatively.

Panelist Michael J. Mack, a surgeon who has played a major role in the introduction of transcatheter aortic valve replacement (TAVR) in the United States, said he views frailty assessment as indispensable in deciding whether a patient with aortic stenosis is best served by TAVR, surgical replacement, or no procedure.

"On our heart team we spend a lot of time sorting out this matter of futility, where you can have a successful procedure but the patient dies anyway. We’re trying to sort out the patients who are dying with aortic stenosis from those that are dying from aortic stenosis," explained Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

At the Baylor heart team clinic, patients with aortic stenosis get a complete work-up in 1 day. It includes echocardiography, a CT scan, pulmonary function testing, determination of the STS risk score, and frailty testing. Four frailty tests are done routinely: a 5-meter walk test, grip strength, the Katz Activities of Daily Living, and a serum albumin. Then the surgeon and the cardiologist see the patient together.

"We have a pretty good idea before we ever walk into the room what the patient is a candidate for, on the basis of not only on the echo and CT scan, but also the frailty testing. This used to take a long time, but we see virtually eye to eye now and it requires no consultation outside the patient’s view to decide what we think the best option is," Dr. Mack said. "I see the ceiling coming down. We are denying patients now that 2 or 3 years ago we didn’t, because we realize that although they can get through the procedure successfully, their functional quality outcomes and survival at 1 year are not great."

Dr. Mack reported that he is the recipient of a research grant from Edwards Lifesciences. Dr. Alexander disclosed that she serves as a consultant to Gilead and Pozen.

SNOWMASS, COLO. – A structured frailty assessment has become an important tool for cardiologists in individualizing decisions regarding referral of elderly patients for heart procedures.

The frailty assessment aids in determining whether the procedure is likely to improve the individual’s long-term outcome, or if instead, multiple converging limitations unrelated to the cardiac condition are pushing the patient toward early functional losses and mortality from noncardiovascular causes.

More than 20 multidimensional frailty scales have been developed in the geriatrics literature during the past decade. For busy cardiologists, two of the simplest, fastest, and least expensive are walking speed and the Dalhousie Clinical Frailty Scale, Dr. Karen P. Alexander said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Walking speed can be assessed by a nonphysician with a stopwatch and two marks on the hallway floor 4-6 meters apart, noted Dr. Alexander, a cardiologist with a special interest in geriatrics at Duke University, Durham, N.C.

The first prospective study of walking speed as a predictor of mortality and major morbidity in elderly patients scheduled for cardiac surgery involved 131 subjects at four university hospitals. Those classified as slow walkers as defined by taking 6 seconds or longer to cover 5 meters in the clinic hallway had a threefold increased rate of the composite endpoint of in-hospital mortality, stroke, renal failure, prolonged infection, deep sternal wound infection, or reoperation. That was true even after adjusting for the widely used Society of Thoracic Surgeons risk score.

Patients with a high STS risk score, of 15% or more, plus a 5-meter walk speed of 6 seconds or longer, had a 43% incidence of mortality or major morbidity. Those with an STS risk score below 15% and a walking speed of less than 6 seconds had an event rate of only 6% (J. Am. Coll. Cardiol. 2010;56:1668-76).

More recently, a pooled analysis of 9 cohort studies totaling nearly 35,000 community-dwelling seniors followed for 6-21 years concluded that gait speed was significantly associated with remaining years of life in both men and women.

Lead investigator Dr. Stephanie Studenski, director of research in the division of geriatric medicine at the University of Pittsburgh, noted that each 0.1-meter/second increment in walking speed was associated with a 12% increase in survival. A walking speed of 0.8 meters/second was associated with the median life expectancy for persons in that age category. She proposed that a walking speed of 0.6 meters/second would be a reasonable threshold for increased risk of early mortality, that a speed faster than 1.0 meters/second suggests better than average life expectancy, and a gait speed above 1.2 meters/second suggests exceptional life expectancy (JAMA 2011;305:50-8).

Dr. Alexander said the Clinical Frailty Scale developed by Dr. Kenneth Rockwood and his coworkers at Dalhousie University in Halifax, Nova Scotia, allows physicians to quickly judge where an individual patient fits on a nine-point frailty scale.

"It gets raters on the same page and improves upon the ‘I know frailty when I see it’ eyeball test," she added.

It appears, however, that cardiologists may be underutilizing frailty assessments. When session moderator Dr. Rick A. Nishimura of the Mayo Clinic, Rochester, Minn., asked for an audience show of hands as to how many routinely make a comment about frailty in elderly patients’ charts, only about 40% responded affirmatively.

Panelist Michael J. Mack, a surgeon who has played a major role in the introduction of transcatheter aortic valve replacement (TAVR) in the United States, said he views frailty assessment as indispensable in deciding whether a patient with aortic stenosis is best served by TAVR, surgical replacement, or no procedure.

"On our heart team we spend a lot of time sorting out this matter of futility, where you can have a successful procedure but the patient dies anyway. We’re trying to sort out the patients who are dying with aortic stenosis from those that are dying from aortic stenosis," explained Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

At the Baylor heart team clinic, patients with aortic stenosis get a complete work-up in 1 day. It includes echocardiography, a CT scan, pulmonary function testing, determination of the STS risk score, and frailty testing. Four frailty tests are done routinely: a 5-meter walk test, grip strength, the Katz Activities of Daily Living, and a serum albumin. Then the surgeon and the cardiologist see the patient together.

"We have a pretty good idea before we ever walk into the room what the patient is a candidate for, on the basis of not only on the echo and CT scan, but also the frailty testing. This used to take a long time, but we see virtually eye to eye now and it requires no consultation outside the patient’s view to decide what we think the best option is," Dr. Mack said. "I see the ceiling coming down. We are denying patients now that 2 or 3 years ago we didn’t, because we realize that although they can get through the procedure successfully, their functional quality outcomes and survival at 1 year are not great."

Dr. Mack reported that he is the recipient of a research grant from Edwards Lifesciences. Dr. Alexander disclosed that she serves as a consultant to Gilead and Pozen.

SNOWMASS, COLO. – A structured frailty assessment has become an important tool for cardiologists in individualizing decisions regarding referral of elderly patients for heart procedures.

The frailty assessment aids in determining whether the procedure is likely to improve the individual’s long-term outcome, or if instead, multiple converging limitations unrelated to the cardiac condition are pushing the patient toward early functional losses and mortality from noncardiovascular causes.

More than 20 multidimensional frailty scales have been developed in the geriatrics literature during the past decade. For busy cardiologists, two of the simplest, fastest, and least expensive are walking speed and the Dalhousie Clinical Frailty Scale, Dr. Karen P. Alexander said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Walking speed can be assessed by a nonphysician with a stopwatch and two marks on the hallway floor 4-6 meters apart, noted Dr. Alexander, a cardiologist with a special interest in geriatrics at Duke University, Durham, N.C.

The first prospective study of walking speed as a predictor of mortality and major morbidity in elderly patients scheduled for cardiac surgery involved 131 subjects at four university hospitals. Those classified as slow walkers as defined by taking 6 seconds or longer to cover 5 meters in the clinic hallway had a threefold increased rate of the composite endpoint of in-hospital mortality, stroke, renal failure, prolonged infection, deep sternal wound infection, or reoperation. That was true even after adjusting for the widely used Society of Thoracic Surgeons risk score.

Patients with a high STS risk score, of 15% or more, plus a 5-meter walk speed of 6 seconds or longer, had a 43% incidence of mortality or major morbidity. Those with an STS risk score below 15% and a walking speed of less than 6 seconds had an event rate of only 6% (J. Am. Coll. Cardiol. 2010;56:1668-76).

More recently, a pooled analysis of 9 cohort studies totaling nearly 35,000 community-dwelling seniors followed for 6-21 years concluded that gait speed was significantly associated with remaining years of life in both men and women.

Lead investigator Dr. Stephanie Studenski, director of research in the division of geriatric medicine at the University of Pittsburgh, noted that each 0.1-meter/second increment in walking speed was associated with a 12% increase in survival. A walking speed of 0.8 meters/second was associated with the median life expectancy for persons in that age category. She proposed that a walking speed of 0.6 meters/second would be a reasonable threshold for increased risk of early mortality, that a speed faster than 1.0 meters/second suggests better than average life expectancy, and a gait speed above 1.2 meters/second suggests exceptional life expectancy (JAMA 2011;305:50-8).

Dr. Alexander said the Clinical Frailty Scale developed by Dr. Kenneth Rockwood and his coworkers at Dalhousie University in Halifax, Nova Scotia, allows physicians to quickly judge where an individual patient fits on a nine-point frailty scale.

"It gets raters on the same page and improves upon the ‘I know frailty when I see it’ eyeball test," she added.

It appears, however, that cardiologists may be underutilizing frailty assessments. When session moderator Dr. Rick A. Nishimura of the Mayo Clinic, Rochester, Minn., asked for an audience show of hands as to how many routinely make a comment about frailty in elderly patients’ charts, only about 40% responded affirmatively.

Panelist Michael J. Mack, a surgeon who has played a major role in the introduction of transcatheter aortic valve replacement (TAVR) in the United States, said he views frailty assessment as indispensable in deciding whether a patient with aortic stenosis is best served by TAVR, surgical replacement, or no procedure.

"On our heart team we spend a lot of time sorting out this matter of futility, where you can have a successful procedure but the patient dies anyway. We’re trying to sort out the patients who are dying with aortic stenosis from those that are dying from aortic stenosis," explained Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

At the Baylor heart team clinic, patients with aortic stenosis get a complete work-up in 1 day. It includes echocardiography, a CT scan, pulmonary function testing, determination of the STS risk score, and frailty testing. Four frailty tests are done routinely: a 5-meter walk test, grip strength, the Katz Activities of Daily Living, and a serum albumin. Then the surgeon and the cardiologist see the patient together.

"We have a pretty good idea before we ever walk into the room what the patient is a candidate for, on the basis of not only on the echo and CT scan, but also the frailty testing. This used to take a long time, but we see virtually eye to eye now and it requires no consultation outside the patient’s view to decide what we think the best option is," Dr. Mack said. "I see the ceiling coming down. We are denying patients now that 2 or 3 years ago we didn’t, because we realize that although they can get through the procedure successfully, their functional quality outcomes and survival at 1 year are not great."

Dr. Mack reported that he is the recipient of a research grant from Edwards Lifesciences. Dr. Alexander disclosed that she serves as a consultant to Gilead and Pozen.

SNOWMASS, COLO. – The once highly attractive notion that boosting HDL cholesterol levels will reduce cardiovascular event rates is now dead, or more generously, it remains unsupported by evidence despite expenditure of billions of dollars on negative clinical trials.

"An iconic concept of HDL has not borne good fruit. It really isn’t what we don’t know that hurts us so much as the things that we think are true but just ain’t so – and that’s the story of HDL," Dr. Robert A. Vogel said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Indeed, it now appears that the relationship between HDL and atherosclerosis is far more complicated than lipidologists thought. Evidence now suggests that HDL mass may not be as important as HDL function, which can switch between being anti- and pro-atherogenic in a matter of hours. And HDL may not even be playing an active role in cardiovascular risk; a low HDL may be associated with an increase in cardiovascular events simply because it is a marker for other cardiovascular risk factors, such as obesity, smoking, and insulin resistance.

"This has been a sea change in thinking for me. HDL is something I thought I understood. But I understood it a lot better 10 years ago than I do now," admitted Dr. Vogel of the University of Colorado, Denver.

HDL-raising drugs from multiple classes have now crashed and burned in large randomized trials with clinical endpoints. Thus, the idea that just because a drug does good things to the lipid profile it follows that the agent will also reduce cardiovascular risk "has to die," the cardiologist continued.

Take, for example, niacin.

"Metabolically, niacin does everything right – if you’re a lipidologist. Absolutely everything. It lowers triglycerides, lowers LDL, raises HDL, lowers total cholesterol, lowers C-reactive protein, and increases the beneficial large HDL particles. You would conclude from this that there would be no way niacin would not reduce cardiovascular risk," he explained.

That’s why the negative results of the National Institutes of Health–sponsored 3,414-patient AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglycerides and Impact on Global Health Outcomes) trial came as such a surprise. In AIM-HIGH, randomization to 1.5-2.0 g of extended-release niacin daily in patients on background simvastatin and, if need be, ezetimibe, had no impact on major cardiovascular events (N. Engl. J. Med. 2011;365:2255-67).

The final nail in niacin’s coffin came a few months ago in the form of Merck’s preliminary announcement of a negative result in the massive phase III Health Protection Study-2 THRIVE trial, in which nearly 26,000 subjects with cardiovascular disease and/or diabetes in the United Kingdom, Scandinavia, and China were randomized to 2 g of extended-release niacin plus the antiflushing agent laropiprant daily or placebo on top of background therapy with simvastatin plus or minus ezetimibe. During 3.9 years of prospective follow-up, niacin boosted HDL levels by 17% and reduced LDL by 20%, but it had no impact upon cardiovascular events and was associated with increased risk of serious adverse events.

"I’m going to say it twice: If you have a patient on niacin, take that patient off. Again, if you have a patient on niacin, take that patient off. There is no evidence base at the present time that a patient should be on niacin to reduce cardiovascular risk," Dr. Vogel stressed.

The investigational cholesterol ester transfer protein (CETP) inhibitors produce whopping increases in HDL but to date have proved to be a crushing disappointment in large clinical trials. In the ILLUMINATE trial, the CETP inhibitor torcetrapib raised HDL by 70% and lowered LDL by 30% – and yet it increased all-cause mortality by 60%. Development of torcetrapib has been discontinued.

In the 15,871-patient dal-OUTCOMES trial, the CETP modulator dalcetrapib also produced salutary effects on HDL and LDL, but with absolutely no change in cardiovascular events (N. Engl. J. Med. 2012;367:2089-99).

The only anti-CETP drug that still has a prayer of ever reaching the marketplace is anacetrapib. In the ongoing 1,625-subject DEFINE trial, it has produced a 140% increase in HDL and a 40% drop in LDL. But whether the drug improves clinical outcomes remains to be seen.

As for the fibrates, a meta-analysis of six major randomized trials showed these HDL-raisers had no impact on coronary heart disease (CHD) mortality.

Even the hallowed and robust inverse relation between HDL level and cardiovascular risk described 27 years ago in the Framingham Heart Study (JAMA 1986;256:2835-8) has come under question. This inverse association wasn’t evident in the dal-OUTCOMES trial, and was of only borderline significance in the 10,001-patient Treating to New Targets (TNT) trial (N. Engl. J. Med. 2007;357:1301-10).

"The Framingham data are not quite so right. In these large clinical trials, the inverse relationship between HDL and cardiovascular events was seen only at very low HDL levels – below 30 mg/dL – and not across the broad spectrum," according to the cardiologist.

The most persuasive challenge to the concept that raising HDL will translate into reduced risk of CHD comes from a recent genetic analysis, Dr. Vogel continued. This ambitious project, sponsored by the National Institutes of Health, the Wellcome Trust, the European Union, the British Heart Foundation, and the German government, tracked the prevalence of 14 genetic variants associated with increased HDL in 20 studies totaling more than 100,000 subjects, including nearly 21,000 with a myocardial infarction. The presence of these HDL-raising genes was not associated with reduced risk of MI (Lancet 2012;380:572-80).

What can physicians committed to evidence-based medicine do at this point to prevent cardiovascular events in their patients with low HDL?

Prescribe a statin, regardless of their LDL level, Dr. Vogel said. A consistent finding in the landmark statin trials was that patients with low baseline HDL levels were at higher risk of coronary events, and therefore statin therapy had its biggest benefit. That benefit wasn’t due to the drugs’ small effect on HDL, but rather to their LDL-lowering.

In addition, considerably weaker evidence suggests fibrates may have a limited role in reducing cardiovascular risk in two selected populations. One is in patients with mild to moderate chronic kidney disease, for whom a recent meta-analysis of 10 clinical trials including nearly 17,000 participants showed fibrate therapy reduced the risk of major cardiovascular events by 30% and the risk of cardiovascular mortality by 40% (J. Am. Coll. Cardiol. 2012;60:2061-71). Dr. Vogel rates this evidence worthy of a level IIb recommendation, meaning "you might consider a fibrate in folks with mild to moderate chronic impairment of renal function."

Another group of patients in which fibrate therapy might reasonably be considered are those with a triglyceride level in excess of 200 mg/dL and an HDL level below 35 mg/dL. In subgroup analyses of virtually all of the major fibrate clinical trials, a benefit was shown in that subgroup. Dr. Vogel gives fibrate therapy in such patients a IIb recommendation as well.

As for lifestyle modification as a means of boosting HDL, moderate alcohol consumption, physical exercise, smoking cessation, and weight loss have all been shown to increase HDL. All of these are healthful behaviors, but there is very little hard data to show whether the cardiovascular benefits come from the increase in HDL or some other mechanism.

"If you want to do something in terms of lifestyle modification, tell your patients to run from bar to bar," he quipped.

Dr. Vogel reported having no financial conflicts.

[email protected]

SNOWMASS, COLO. – The once highly attractive notion that boosting HDL cholesterol levels will reduce cardiovascular event rates is now dead, or more generously, it remains unsupported by evidence despite expenditure of billions of dollars on negative clinical trials.

"An iconic concept of HDL has not borne good fruit. It really isn’t what we don’t know that hurts us so much as the things that we think are true but just ain’t so – and that’s the story of HDL," Dr. Robert A. Vogel said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Indeed, it now appears that the relationship between HDL and atherosclerosis is far more complicated than lipidologists thought. Evidence now suggests that HDL mass may not be as important as HDL function, which can switch between being anti- and pro-atherogenic in a matter of hours. And HDL may not even be playing an active role in cardiovascular risk; a low HDL may be associated with an increase in cardiovascular events simply because it is a marker for other cardiovascular risk factors, such as obesity, smoking, and insulin resistance.

"This has been a sea change in thinking for me. HDL is something I thought I understood. But I understood it a lot better 10 years ago than I do now," admitted Dr. Vogel of the University of Colorado, Denver.

HDL-raising drugs from multiple classes have now crashed and burned in large randomized trials with clinical endpoints. Thus, the idea that just because a drug does good things to the lipid profile it follows that the agent will also reduce cardiovascular risk "has to die," the cardiologist continued.

Take, for example, niacin.

"Metabolically, niacin does everything right – if you’re a lipidologist. Absolutely everything. It lowers triglycerides, lowers LDL, raises HDL, lowers total cholesterol, lowers C-reactive protein, and increases the beneficial large HDL particles. You would conclude from this that there would be no way niacin would not reduce cardiovascular risk," he explained.

That’s why the negative results of the National Institutes of Health–sponsored 3,414-patient AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglycerides and Impact on Global Health Outcomes) trial came as such a surprise. In AIM-HIGH, randomization to 1.5-2.0 g of extended-release niacin daily in patients on background simvastatin and, if need be, ezetimibe, had no impact on major cardiovascular events (N. Engl. J. Med. 2011;365:2255-67).

The final nail in niacin’s coffin came a few months ago in the form of Merck’s preliminary announcement of a negative result in the massive phase III Health Protection Study-2 THRIVE trial, in which nearly 26,000 subjects with cardiovascular disease and/or diabetes in the United Kingdom, Scandinavia, and China were randomized to 2 g of extended-release niacin plus the antiflushing agent laropiprant daily or placebo on top of background therapy with simvastatin plus or minus ezetimibe. During 3.9 years of prospective follow-up, niacin boosted HDL levels by 17% and reduced LDL by 20%, but it had no impact upon cardiovascular events and was associated with increased risk of serious adverse events.

"I’m going to say it twice: If you have a patient on niacin, take that patient off. Again, if you have a patient on niacin, take that patient off. There is no evidence base at the present time that a patient should be on niacin to reduce cardiovascular risk," Dr. Vogel stressed.

The investigational cholesterol ester transfer protein (CETP) inhibitors produce whopping increases in HDL but to date have proved to be a crushing disappointment in large clinical trials. In the ILLUMINATE trial, the CETP inhibitor torcetrapib raised HDL by 70% and lowered LDL by 30% – and yet it increased all-cause mortality by 60%. Development of torcetrapib has been discontinued.

In the 15,871-patient dal-OUTCOMES trial, the CETP modulator dalcetrapib also produced salutary effects on HDL and LDL, but with absolutely no change in cardiovascular events (N. Engl. J. Med. 2012;367:2089-99).

The only anti-CETP drug that still has a prayer of ever reaching the marketplace is anacetrapib. In the ongoing 1,625-subject DEFINE trial, it has produced a 140% increase in HDL and a 40% drop in LDL. But whether the drug improves clinical outcomes remains to be seen.

As for the fibrates, a meta-analysis of six major randomized trials showed these HDL-raisers had no impact on coronary heart disease (CHD) mortality.

Even the hallowed and robust inverse relation between HDL level and cardiovascular risk described 27 years ago in the Framingham Heart Study (JAMA 1986;256:2835-8) has come under question. This inverse association wasn’t evident in the dal-OUTCOMES trial, and was of only borderline significance in the 10,001-patient Treating to New Targets (TNT) trial (N. Engl. J. Med. 2007;357:1301-10).

"The Framingham data are not quite so right. In these large clinical trials, the inverse relationship between HDL and cardiovascular events was seen only at very low HDL levels – below 30 mg/dL – and not across the broad spectrum," according to the cardiologist.

The most persuasive challenge to the concept that raising HDL will translate into reduced risk of CHD comes from a recent genetic analysis, Dr. Vogel continued. This ambitious project, sponsored by the National Institutes of Health, the Wellcome Trust, the European Union, the British Heart Foundation, and the German government, tracked the prevalence of 14 genetic variants associated with increased HDL in 20 studies totaling more than 100,000 subjects, including nearly 21,000 with a myocardial infarction. The presence of these HDL-raising genes was not associated with reduced risk of MI (Lancet 2012;380:572-80).

What can physicians committed to evidence-based medicine do at this point to prevent cardiovascular events in their patients with low HDL?

Prescribe a statin, regardless of their LDL level, Dr. Vogel said. A consistent finding in the landmark statin trials was that patients with low baseline HDL levels were at higher risk of coronary events, and therefore statin therapy had its biggest benefit. That benefit wasn’t due to the drugs’ small effect on HDL, but rather to their LDL-lowering.

In addition, considerably weaker evidence suggests fibrates may have a limited role in reducing cardiovascular risk in two selected populations. One is in patients with mild to moderate chronic kidney disease, for whom a recent meta-analysis of 10 clinical trials including nearly 17,000 participants showed fibrate therapy reduced the risk of major cardiovascular events by 30% and the risk of cardiovascular mortality by 40% (J. Am. Coll. Cardiol. 2012;60:2061-71). Dr. Vogel rates this evidence worthy of a level IIb recommendation, meaning "you might consider a fibrate in folks with mild to moderate chronic impairment of renal function."

Another group of patients in which fibrate therapy might reasonably be considered are those with a triglyceride level in excess of 200 mg/dL and an HDL level below 35 mg/dL. In subgroup analyses of virtually all of the major fibrate clinical trials, a benefit was shown in that subgroup. Dr. Vogel gives fibrate therapy in such patients a IIb recommendation as well.

As for lifestyle modification as a means of boosting HDL, moderate alcohol consumption, physical exercise, smoking cessation, and weight loss have all been shown to increase HDL. All of these are healthful behaviors, but there is very little hard data to show whether the cardiovascular benefits come from the increase in HDL or some other mechanism.

"If you want to do something in terms of lifestyle modification, tell your patients to run from bar to bar," he quipped.

Dr. Vogel reported having no financial conflicts.

[email protected]

SNOWMASS, COLO. – The once highly attractive notion that boosting HDL cholesterol levels will reduce cardiovascular event rates is now dead, or more generously, it remains unsupported by evidence despite expenditure of billions of dollars on negative clinical trials.

"An iconic concept of HDL has not borne good fruit. It really isn’t what we don’t know that hurts us so much as the things that we think are true but just ain’t so – and that’s the story of HDL," Dr. Robert A. Vogel said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Indeed, it now appears that the relationship between HDL and atherosclerosis is far more complicated than lipidologists thought. Evidence now suggests that HDL mass may not be as important as HDL function, which can switch between being anti- and pro-atherogenic in a matter of hours. And HDL may not even be playing an active role in cardiovascular risk; a low HDL may be associated with an increase in cardiovascular events simply because it is a marker for other cardiovascular risk factors, such as obesity, smoking, and insulin resistance.

"This has been a sea change in thinking for me. HDL is something I thought I understood. But I understood it a lot better 10 years ago than I do now," admitted Dr. Vogel of the University of Colorado, Denver.

HDL-raising drugs from multiple classes have now crashed and burned in large randomized trials with clinical endpoints. Thus, the idea that just because a drug does good things to the lipid profile it follows that the agent will also reduce cardiovascular risk "has to die," the cardiologist continued.

Take, for example, niacin.

"Metabolically, niacin does everything right – if you’re a lipidologist. Absolutely everything. It lowers triglycerides, lowers LDL, raises HDL, lowers total cholesterol, lowers C-reactive protein, and increases the beneficial large HDL particles. You would conclude from this that there would be no way niacin would not reduce cardiovascular risk," he explained.

That’s why the negative results of the National Institutes of Health–sponsored 3,414-patient AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglycerides and Impact on Global Health Outcomes) trial came as such a surprise. In AIM-HIGH, randomization to 1.5-2.0 g of extended-release niacin daily in patients on background simvastatin and, if need be, ezetimibe, had no impact on major cardiovascular events (N. Engl. J. Med. 2011;365:2255-67).

The final nail in niacin’s coffin came a few months ago in the form of Merck’s preliminary announcement of a negative result in the massive phase III Health Protection Study-2 THRIVE trial, in which nearly 26,000 subjects with cardiovascular disease and/or diabetes in the United Kingdom, Scandinavia, and China were randomized to 2 g of extended-release niacin plus the antiflushing agent laropiprant daily or placebo on top of background therapy with simvastatin plus or minus ezetimibe. During 3.9 years of prospective follow-up, niacin boosted HDL levels by 17% and reduced LDL by 20%, but it had no impact upon cardiovascular events and was associated with increased risk of serious adverse events.

"I’m going to say it twice: If you have a patient on niacin, take that patient off. Again, if you have a patient on niacin, take that patient off. There is no evidence base at the present time that a patient should be on niacin to reduce cardiovascular risk," Dr. Vogel stressed.

The investigational cholesterol ester transfer protein (CETP) inhibitors produce whopping increases in HDL but to date have proved to be a crushing disappointment in large clinical trials. In the ILLUMINATE trial, the CETP inhibitor torcetrapib raised HDL by 70% and lowered LDL by 30% – and yet it increased all-cause mortality by 60%. Development of torcetrapib has been discontinued.

In the 15,871-patient dal-OUTCOMES trial, the CETP modulator dalcetrapib also produced salutary effects on HDL and LDL, but with absolutely no change in cardiovascular events (N. Engl. J. Med. 2012;367:2089-99).

The only anti-CETP drug that still has a prayer of ever reaching the marketplace is anacetrapib. In the ongoing 1,625-subject DEFINE trial, it has produced a 140% increase in HDL and a 40% drop in LDL. But whether the drug improves clinical outcomes remains to be seen.

As for the fibrates, a meta-analysis of six major randomized trials showed these HDL-raisers had no impact on coronary heart disease (CHD) mortality.

Even the hallowed and robust inverse relation between HDL level and cardiovascular risk described 27 years ago in the Framingham Heart Study (JAMA 1986;256:2835-8) has come under question. This inverse association wasn’t evident in the dal-OUTCOMES trial, and was of only borderline significance in the 10,001-patient Treating to New Targets (TNT) trial (N. Engl. J. Med. 2007;357:1301-10).

"The Framingham data are not quite so right. In these large clinical trials, the inverse relationship between HDL and cardiovascular events was seen only at very low HDL levels – below 30 mg/dL – and not across the broad spectrum," according to the cardiologist.

The most persuasive challenge to the concept that raising HDL will translate into reduced risk of CHD comes from a recent genetic analysis, Dr. Vogel continued. This ambitious project, sponsored by the National Institutes of Health, the Wellcome Trust, the European Union, the British Heart Foundation, and the German government, tracked the prevalence of 14 genetic variants associated with increased HDL in 20 studies totaling more than 100,000 subjects, including nearly 21,000 with a myocardial infarction. The presence of these HDL-raising genes was not associated with reduced risk of MI (Lancet 2012;380:572-80).

What can physicians committed to evidence-based medicine do at this point to prevent cardiovascular events in their patients with low HDL?

Prescribe a statin, regardless of their LDL level, Dr. Vogel said. A consistent finding in the landmark statin trials was that patients with low baseline HDL levels were at higher risk of coronary events, and therefore statin therapy had its biggest benefit. That benefit wasn’t due to the drugs’ small effect on HDL, but rather to their LDL-lowering.

In addition, considerably weaker evidence suggests fibrates may have a limited role in reducing cardiovascular risk in two selected populations. One is in patients with mild to moderate chronic kidney disease, for whom a recent meta-analysis of 10 clinical trials including nearly 17,000 participants showed fibrate therapy reduced the risk of major cardiovascular events by 30% and the risk of cardiovascular mortality by 40% (J. Am. Coll. Cardiol. 2012;60:2061-71). Dr. Vogel rates this evidence worthy of a level IIb recommendation, meaning "you might consider a fibrate in folks with mild to moderate chronic impairment of renal function."

Another group of patients in which fibrate therapy might reasonably be considered are those with a triglyceride level in excess of 200 mg/dL and an HDL level below 35 mg/dL. In subgroup analyses of virtually all of the major fibrate clinical trials, a benefit was shown in that subgroup. Dr. Vogel gives fibrate therapy in such patients a IIb recommendation as well.

As for lifestyle modification as a means of boosting HDL, moderate alcohol consumption, physical exercise, smoking cessation, and weight loss have all been shown to increase HDL. All of these are healthful behaviors, but there is very little hard data to show whether the cardiovascular benefits come from the increase in HDL or some other mechanism.

"If you want to do something in terms of lifestyle modification, tell your patients to run from bar to bar," he quipped.

Dr. Vogel reported having no financial conflicts.

[email protected]