ESC Congress 2013

AMSTERDAM – LUCAS, a mechanical chest compression device, could be as effective as manual chest compressions, based on results from a multicenter, randomized controlled trial of 5,000 cardiac arrest patients.

The LINC (LUCAS in Cardiac Arrest) study showed that the device was no better than manual chest compression at improving the 4-hour survivals of cardiac arrest patients. Patients exposed to the device were not harmed, however, and their 6-month survival rates and neurologic outcomes were similar to those of patients who received manual compressions, said Dr. Sten Rubertsson, the principle investigator of the study and a consultant for the device’s manufacturer, Physio-Control.

One of several mechanical chest compression devices available in the market, LUCAS has a piston and suction cup mechanism that performs chest compressions at guideline recommended rates. The device also permits simultaneous use of a defibrillator.

In a study was conducted between 2008 and 2013, about 2,600 of 5,000 cardiac arrest patients were randomized to either LUCAS or manual compression. The other patients were excluded from the study because they had traumatic cardiac arrest, were pregnant, were defibrillated before LUCAS was on scene, or had a return of spontaneous circulation.

Patients were on average 69 years old and most were men.

The primary endpoint of the study, 4-hour survival, was comparable for both groups at 23.6% for LUCAS and 23.7% for manual compressions.

The study’s secondary endpoint – survival up to 6 months with good neurologic outcome – similarly was comparable at 8.5% for LUCAS and 7.6% for manual compressions.

Conducting a study for several years in a pre-hospital setting is rather difficult, said Dr. Patrick Goldstein of Lille University Hospital France, who commented on the study at the meeting. The results of the trial could be considered neutral, but "I think it is positive for many reasons."

Mechanical chest compressions can be useful in several subgroups, including those patients who need long-term CPR and for those in the non–heart-beating donors programs, for example.

Dr. Rubertsson said that in the future, the device could be used to individualize care, by considering the compressions and EKG, and deciding when to do the interventions.

The LINC study was initiated by Uppsala (Sweden) University and sponsored by Physio-Control/Jolife AB. Dr. Rubertsson has received consultation fee from Physio-Control/Jolife AB. Dr. Goldstein had no relevant conflicts of interest.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – LUCAS, a mechanical chest compression device, could be as effective as manual chest compressions, based on results from a multicenter, randomized controlled trial of 5,000 cardiac arrest patients.

The LINC (LUCAS in Cardiac Arrest) study showed that the device was no better than manual chest compression at improving the 4-hour survivals of cardiac arrest patients. Patients exposed to the device were not harmed, however, and their 6-month survival rates and neurologic outcomes were similar to those of patients who received manual compressions, said Dr. Sten Rubertsson, the principle investigator of the study and a consultant for the device’s manufacturer, Physio-Control.

One of several mechanical chest compression devices available in the market, LUCAS has a piston and suction cup mechanism that performs chest compressions at guideline recommended rates. The device also permits simultaneous use of a defibrillator.

In a study was conducted between 2008 and 2013, about 2,600 of 5,000 cardiac arrest patients were randomized to either LUCAS or manual compression. The other patients were excluded from the study because they had traumatic cardiac arrest, were pregnant, were defibrillated before LUCAS was on scene, or had a return of spontaneous circulation.

Patients were on average 69 years old and most were men.

The primary endpoint of the study, 4-hour survival, was comparable for both groups at 23.6% for LUCAS and 23.7% for manual compressions.

The study’s secondary endpoint – survival up to 6 months with good neurologic outcome – similarly was comparable at 8.5% for LUCAS and 7.6% for manual compressions.

Conducting a study for several years in a pre-hospital setting is rather difficult, said Dr. Patrick Goldstein of Lille University Hospital France, who commented on the study at the meeting. The results of the trial could be considered neutral, but "I think it is positive for many reasons."

Mechanical chest compressions can be useful in several subgroups, including those patients who need long-term CPR and for those in the non–heart-beating donors programs, for example.

Dr. Rubertsson said that in the future, the device could be used to individualize care, by considering the compressions and EKG, and deciding when to do the interventions.

The LINC study was initiated by Uppsala (Sweden) University and sponsored by Physio-Control/Jolife AB. Dr. Rubertsson has received consultation fee from Physio-Control/Jolife AB. Dr. Goldstein had no relevant conflicts of interest.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – LUCAS, a mechanical chest compression device, could be as effective as manual chest compressions, based on results from a multicenter, randomized controlled trial of 5,000 cardiac arrest patients.

The LINC (LUCAS in Cardiac Arrest) study showed that the device was no better than manual chest compression at improving the 4-hour survivals of cardiac arrest patients. Patients exposed to the device were not harmed, however, and their 6-month survival rates and neurologic outcomes were similar to those of patients who received manual compressions, said Dr. Sten Rubertsson, the principle investigator of the study and a consultant for the device’s manufacturer, Physio-Control.

One of several mechanical chest compression devices available in the market, LUCAS has a piston and suction cup mechanism that performs chest compressions at guideline recommended rates. The device also permits simultaneous use of a defibrillator.

In a study was conducted between 2008 and 2013, about 2,600 of 5,000 cardiac arrest patients were randomized to either LUCAS or manual compression. The other patients were excluded from the study because they had traumatic cardiac arrest, were pregnant, were defibrillated before LUCAS was on scene, or had a return of spontaneous circulation.

Patients were on average 69 years old and most were men.

The primary endpoint of the study, 4-hour survival, was comparable for both groups at 23.6% for LUCAS and 23.7% for manual compressions.

The study’s secondary endpoint – survival up to 6 months with good neurologic outcome – similarly was comparable at 8.5% for LUCAS and 7.6% for manual compressions.

Conducting a study for several years in a pre-hospital setting is rather difficult, said Dr. Patrick Goldstein of Lille University Hospital France, who commented on the study at the meeting. The results of the trial could be considered neutral, but "I think it is positive for many reasons."

Mechanical chest compressions can be useful in several subgroups, including those patients who need long-term CPR and for those in the non–heart-beating donors programs, for example.

Dr. Rubertsson said that in the future, the device could be used to individualize care, by considering the compressions and EKG, and deciding when to do the interventions.

The LINC study was initiated by Uppsala (Sweden) University and sponsored by Physio-Control/Jolife AB. Dr. Rubertsson has received consultation fee from Physio-Control/Jolife AB. Dr. Goldstein had no relevant conflicts of interest.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – A study of Japanese patients with hypertension and glucose intolerance showed that as their body mass index increased, their risk of cardiovascular disease decreased, suggesting the existence of the obesity paradox in this particular population of patients.

However, these findings results don’t refute the fact that severe obesity is a risk factor for cardiovascular disease, and that "hypertensive patients with glucose intolerance and a high BMI [body mass index] should lose weight and restore their BMI to normal range," Dr. Takanori Nagahiro said at the annual congress of the European Society of Cardiology.

Furthermore, the results should be interpreted with caution, because the insulin therapy was higher among patients at the lowest BMI category, indicating that the severity of diabetes may have been different in that group, said Dr. Nagahiro of Nagoya (Japan) University.

The study was a subanalysis of the NAGOYA HEART (Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment) study, which compared the effects of an angiotensin II receptor blocker with a calcium channel blocker on cardiovascular outcomes in 1,150 hypertensive patients with type 2 diabetes or impaired glucose tolerance. No significant differences were found between the two classes. The median follow-up was 3.2 years (Hypertension 2012;59:580-6).

For the current analysis, patients were divided into quartiles according to their body mass indices: Patients in quartile 1 (Q1) had BMIs lower than 23.5 kg/m² (283 patients); those in Q2 had a BMI range of 23.5-25 (290); those in Q3 had a range of 25-27.5 (277); and patients in Q4 had BMIs higher than 27.5 (255).

The primary outcome in the subanalysis, as in the main study, was a composite of acute myocardial infarction, stroke, admission for heart failure, coronary revascularization, or sudden cardiac death.

There were no significant differences between the four groups, except for age and insulin therapy, where the lowest BMI group had the highest rate of insulin therapy (11%, compared with 6.2%, 4.7%, and 4.7% in Q2, Q3, and Q4, respectively.)

Forty-two (15%; 4.6/100 person-years) patients reached the primary endpoint in Q1, which was used as reference. In Q2, 24 patients (8.3%; 2.3) reached the primary endpoint; and in Q3, 27 patients (9.7%; 2.8) reached the endpoint, both nonsignificant differences. In Q4, however, 13 patients (5.1%; 1.5) reached the endpoint, a significant difference from Q1.

"I think the picture is quite clear now, that metabolic disorders are more important than obesity per se especially if you measure it by body mass index," said Dr. Heinz Drexel, chairman of the department of medicine and cardiology and of the VIVIT Institute, Academic Teaching Hospital Feldkirch, Austria, who cochaired the session at ESC. "I think that’s the bottom line."

The NAGOYA HEART study was funded by Nagoya University, which has received unrestricted research grants from several companies, including Astellas, Bayer, Pfizer, Sanofi-Aventis, and Takeda. Dr. Drexel had no disclosures.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – A study of Japanese patients with hypertension and glucose intolerance showed that as their body mass index increased, their risk of cardiovascular disease decreased, suggesting the existence of the obesity paradox in this particular population of patients.

However, these findings results don’t refute the fact that severe obesity is a risk factor for cardiovascular disease, and that "hypertensive patients with glucose intolerance and a high BMI [body mass index] should lose weight and restore their BMI to normal range," Dr. Takanori Nagahiro said at the annual congress of the European Society of Cardiology.

Furthermore, the results should be interpreted with caution, because the insulin therapy was higher among patients at the lowest BMI category, indicating that the severity of diabetes may have been different in that group, said Dr. Nagahiro of Nagoya (Japan) University.

The study was a subanalysis of the NAGOYA HEART (Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment) study, which compared the effects of an angiotensin II receptor blocker with a calcium channel blocker on cardiovascular outcomes in 1,150 hypertensive patients with type 2 diabetes or impaired glucose tolerance. No significant differences were found between the two classes. The median follow-up was 3.2 years (Hypertension 2012;59:580-6).

For the current analysis, patients were divided into quartiles according to their body mass indices: Patients in quartile 1 (Q1) had BMIs lower than 23.5 kg/m² (283 patients); those in Q2 had a BMI range of 23.5-25 (290); those in Q3 had a range of 25-27.5 (277); and patients in Q4 had BMIs higher than 27.5 (255).

The primary outcome in the subanalysis, as in the main study, was a composite of acute myocardial infarction, stroke, admission for heart failure, coronary revascularization, or sudden cardiac death.

There were no significant differences between the four groups, except for age and insulin therapy, where the lowest BMI group had the highest rate of insulin therapy (11%, compared with 6.2%, 4.7%, and 4.7% in Q2, Q3, and Q4, respectively.)

Forty-two (15%; 4.6/100 person-years) patients reached the primary endpoint in Q1, which was used as reference. In Q2, 24 patients (8.3%; 2.3) reached the primary endpoint; and in Q3, 27 patients (9.7%; 2.8) reached the endpoint, both nonsignificant differences. In Q4, however, 13 patients (5.1%; 1.5) reached the endpoint, a significant difference from Q1.

"I think the picture is quite clear now, that metabolic disorders are more important than obesity per se especially if you measure it by body mass index," said Dr. Heinz Drexel, chairman of the department of medicine and cardiology and of the VIVIT Institute, Academic Teaching Hospital Feldkirch, Austria, who cochaired the session at ESC. "I think that’s the bottom line."

The NAGOYA HEART study was funded by Nagoya University, which has received unrestricted research grants from several companies, including Astellas, Bayer, Pfizer, Sanofi-Aventis, and Takeda. Dr. Drexel had no disclosures.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – A study of Japanese patients with hypertension and glucose intolerance showed that as their body mass index increased, their risk of cardiovascular disease decreased, suggesting the existence of the obesity paradox in this particular population of patients.

However, these findings results don’t refute the fact that severe obesity is a risk factor for cardiovascular disease, and that "hypertensive patients with glucose intolerance and a high BMI [body mass index] should lose weight and restore their BMI to normal range," Dr. Takanori Nagahiro said at the annual congress of the European Society of Cardiology.

Furthermore, the results should be interpreted with caution, because the insulin therapy was higher among patients at the lowest BMI category, indicating that the severity of diabetes may have been different in that group, said Dr. Nagahiro of Nagoya (Japan) University.

The study was a subanalysis of the NAGOYA HEART (Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment) study, which compared the effects of an angiotensin II receptor blocker with a calcium channel blocker on cardiovascular outcomes in 1,150 hypertensive patients with type 2 diabetes or impaired glucose tolerance. No significant differences were found between the two classes. The median follow-up was 3.2 years (Hypertension 2012;59:580-6).

For the current analysis, patients were divided into quartiles according to their body mass indices: Patients in quartile 1 (Q1) had BMIs lower than 23.5 kg/m² (283 patients); those in Q2 had a BMI range of 23.5-25 (290); those in Q3 had a range of 25-27.5 (277); and patients in Q4 had BMIs higher than 27.5 (255).

The primary outcome in the subanalysis, as in the main study, was a composite of acute myocardial infarction, stroke, admission for heart failure, coronary revascularization, or sudden cardiac death.

There were no significant differences between the four groups, except for age and insulin therapy, where the lowest BMI group had the highest rate of insulin therapy (11%, compared with 6.2%, 4.7%, and 4.7% in Q2, Q3, and Q4, respectively.)

Forty-two (15%; 4.6/100 person-years) patients reached the primary endpoint in Q1, which was used as reference. In Q2, 24 patients (8.3%; 2.3) reached the primary endpoint; and in Q3, 27 patients (9.7%; 2.8) reached the endpoint, both nonsignificant differences. In Q4, however, 13 patients (5.1%; 1.5) reached the endpoint, a significant difference from Q1.

"I think the picture is quite clear now, that metabolic disorders are more important than obesity per se especially if you measure it by body mass index," said Dr. Heinz Drexel, chairman of the department of medicine and cardiology and of the VIVIT Institute, Academic Teaching Hospital Feldkirch, Austria, who cochaired the session at ESC. "I think that’s the bottom line."

The NAGOYA HEART study was funded by Nagoya University, which has received unrestricted research grants from several companies, including Astellas, Bayer, Pfizer, Sanofi-Aventis, and Takeda. Dr. Drexel had no disclosures.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – An early rule-out strategy based upon using two cardiac biomarkers allowed for safe discharge within a couple hours from the emergency department for most low- to intermediate-risk patients who presented with suspected acute coronary syndrome, based on the results of a randomized, multicenter trial conducted in Europe.

Moreover, the 30-day rates of major adverse cardiovascular events in the Biomarkers in Cardiology-8 (BiC-8) study were similarly low in patients discharged from the ED using the early rule-out process and in those who received standard, guideline-recommended care, which includes 6-12 hours of serial ECGs and troponin measurements in the chest pain unit, Dr. Martin Moeckel reported at the annual congress of the European Society of Cardiology.

"This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety," observed Dr. Moeckel of Charité Hospital, Berlin. The copeptin test is approved for use in the European Union but remains investigational in the United States.

Based upon the results of BiC-8, this dual biomarker for early rule-out of myocardial infarction (MI) is now standard clinical practice at Charité, he added.

The rationale for developing the early rule-out strategy tested in BiC-8 lies in the serious overcrowding that is now the norm in many EDs. This overcrowding has been shown to be in and of itself a risk factor for poor outcomes. The quandary is that nearly 12% of all patients who present to the ED do so because of chest pain, yet after an extensive and time-consuming evaluation only 1 in 10 of those patients is found to actually be having an acute MI.

"Rapid rule-out of acute MI is therefore a major clinical need, saving the health care system time and resources, and saving patients unnecessary stress, anxiety, and other risks," he said.

Copeptin is a marker for vasopressin, a hemodynamic stress indicator that shoots up immediately in an acute MI. In earlier studies, a negative result for both troponin and copeptin in an initial blood sample drawn at ED presentation had a 99% negative predictive value for MI.

The BiC-8 trial included 902 low- to intermediate-risk patients who presented with suspected acute coronary syndrome (ACS) to EDs in university medical centers. All had a negative initial cardiac troponin test. They were randomized to standard care in the chest pain unit, including serial troponin testing and ECGs, or to the experimental strategy, in which physicians were informed of the copeptin results from the same initial blood sample as the troponin. If the copeptin test was positive as defined by a level of 10 pmol/L or more, the patient was hospitalized for standard care. If the copeptin result was negative, however, the patient was immediately discharged with a scheduled outpatient visit within 72 hours.

Of the patients in the copeptin group, 66% were discharged directly from the ED, compared with 12% in the standard-care group.

The 30-day incidence of major adverse cardiovascular events (MACE) was 5.5% in the standard-care group and nearly identical at 5.46% in the copeptin group. However, physicians were permitted under the study protocol to overrule negative biomarker test results on the basis of their final clinical assessment, such as if their suspicions were aroused due to recurrent symptoms or new information about the patient’s history. In this per-protocol analysis, the 30-day MACE rate was 5.68% in the standard-care group and 3.18% in the copeptin group.

MACE was defined in BiC-8 as all-cause mortality, MI, rehospitalization for ACS, acute unplanned percutaneous coronary intervention (PCI), coronary artery bypass surgery, life-threatening arrhythmia, or resuscitation from cardiac arrest.

MACE occurred in 14 copeptin-negative patients. However, 12 of the 14 were not discharged early because physicians overruled the negative biomarker results and moved the patients into standard in-hospital management. Two patients, or 0.6% of those discharged from the ED on the basis of a negative copeptin test had adverse events: One was rehospitalized on day 23 and underwent acute unplanned PCI on the next day, and the other was rehospitalized on day 4 and underwent coronary artery bypass graft surgery on day 12.

American Heart Association Immediate Past President Donna K. Arnett, Ph.D., said in an interview that she’d really like to see a second, confirmatory randomized trial before this early rule-out strategy is widely adopted. She considers the lost-to-follow-up rate uncomfortably high: 63 patients in the intention-to-treat analysis, and another 75 not accounted for in the per-protocol analysis, noted Dr. Arnett, professor and chair of the epidemiology department at the University of Alabama, Birmingham.

BiC-8 coinvestigator Dr. Kurt Huber said in an interview that the dual-biomarker early rule-out strategy is now used routinely in the hospital where he practices. Yet like Dr. Arnett, he considers a confirmatory test "extremely important" before concluding that the strategy is ready for prime-time use in every ED.

"The most important message from BiC-8, I think, is that these were patients at low to intermediate risk; they’re not the high-risk patients. And it’s also important that the physician doesn’t rely only on the test result, but also takes a final look at the clinical situation before releasing the patient. There is some overruling when patients are biomarker-negative but have typical risk markers. No test is 100% accurate. Clinical judgment remains extremely important," emphasized Dr. Huber, professor and director of cardiology and emergency medicine at Wilhelminen Hospital, Vienna.

The BiC-8 trial was sponsored by ThermoFisher Scientific and six university medical centers in German-speaking Europe. Dr. Moeckel reported receiving a research grant from ThermoFisher and serving as a consultant to Bayer, AstraZeneca, and The Medicines Company. Dr. Arnett and Dr. Huber had no conflicts of interest to declare.

[email protected]

AMSTERDAM – An early rule-out strategy based upon using two cardiac biomarkers allowed for safe discharge within a couple hours from the emergency department for most low- to intermediate-risk patients who presented with suspected acute coronary syndrome, based on the results of a randomized, multicenter trial conducted in Europe.

Moreover, the 30-day rates of major adverse cardiovascular events in the Biomarkers in Cardiology-8 (BiC-8) study were similarly low in patients discharged from the ED using the early rule-out process and in those who received standard, guideline-recommended care, which includes 6-12 hours of serial ECGs and troponin measurements in the chest pain unit, Dr. Martin Moeckel reported at the annual congress of the European Society of Cardiology.

"This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety," observed Dr. Moeckel of Charité Hospital, Berlin. The copeptin test is approved for use in the European Union but remains investigational in the United States.

Based upon the results of BiC-8, this dual biomarker for early rule-out of myocardial infarction (MI) is now standard clinical practice at Charité, he added.

The rationale for developing the early rule-out strategy tested in BiC-8 lies in the serious overcrowding that is now the norm in many EDs. This overcrowding has been shown to be in and of itself a risk factor for poor outcomes. The quandary is that nearly 12% of all patients who present to the ED do so because of chest pain, yet after an extensive and time-consuming evaluation only 1 in 10 of those patients is found to actually be having an acute MI.

"Rapid rule-out of acute MI is therefore a major clinical need, saving the health care system time and resources, and saving patients unnecessary stress, anxiety, and other risks," he said.

Copeptin is a marker for vasopressin, a hemodynamic stress indicator that shoots up immediately in an acute MI. In earlier studies, a negative result for both troponin and copeptin in an initial blood sample drawn at ED presentation had a 99% negative predictive value for MI.

The BiC-8 trial included 902 low- to intermediate-risk patients who presented with suspected acute coronary syndrome (ACS) to EDs in university medical centers. All had a negative initial cardiac troponin test. They were randomized to standard care in the chest pain unit, including serial troponin testing and ECGs, or to the experimental strategy, in which physicians were informed of the copeptin results from the same initial blood sample as the troponin. If the copeptin test was positive as defined by a level of 10 pmol/L or more, the patient was hospitalized for standard care. If the copeptin result was negative, however, the patient was immediately discharged with a scheduled outpatient visit within 72 hours.

Of the patients in the copeptin group, 66% were discharged directly from the ED, compared with 12% in the standard-care group.

The 30-day incidence of major adverse cardiovascular events (MACE) was 5.5% in the standard-care group and nearly identical at 5.46% in the copeptin group. However, physicians were permitted under the study protocol to overrule negative biomarker test results on the basis of their final clinical assessment, such as if their suspicions were aroused due to recurrent symptoms or new information about the patient’s history. In this per-protocol analysis, the 30-day MACE rate was 5.68% in the standard-care group and 3.18% in the copeptin group.

MACE was defined in BiC-8 as all-cause mortality, MI, rehospitalization for ACS, acute unplanned percutaneous coronary intervention (PCI), coronary artery bypass surgery, life-threatening arrhythmia, or resuscitation from cardiac arrest.

MACE occurred in 14 copeptin-negative patients. However, 12 of the 14 were not discharged early because physicians overruled the negative biomarker results and moved the patients into standard in-hospital management. Two patients, or 0.6% of those discharged from the ED on the basis of a negative copeptin test had adverse events: One was rehospitalized on day 23 and underwent acute unplanned PCI on the next day, and the other was rehospitalized on day 4 and underwent coronary artery bypass graft surgery on day 12.

American Heart Association Immediate Past President Donna K. Arnett, Ph.D., said in an interview that she’d really like to see a second, confirmatory randomized trial before this early rule-out strategy is widely adopted. She considers the lost-to-follow-up rate uncomfortably high: 63 patients in the intention-to-treat analysis, and another 75 not accounted for in the per-protocol analysis, noted Dr. Arnett, professor and chair of the epidemiology department at the University of Alabama, Birmingham.

BiC-8 coinvestigator Dr. Kurt Huber said in an interview that the dual-biomarker early rule-out strategy is now used routinely in the hospital where he practices. Yet like Dr. Arnett, he considers a confirmatory test "extremely important" before concluding that the strategy is ready for prime-time use in every ED.

"The most important message from BiC-8, I think, is that these were patients at low to intermediate risk; they’re not the high-risk patients. And it’s also important that the physician doesn’t rely only on the test result, but also takes a final look at the clinical situation before releasing the patient. There is some overruling when patients are biomarker-negative but have typical risk markers. No test is 100% accurate. Clinical judgment remains extremely important," emphasized Dr. Huber, professor and director of cardiology and emergency medicine at Wilhelminen Hospital, Vienna.

The BiC-8 trial was sponsored by ThermoFisher Scientific and six university medical centers in German-speaking Europe. Dr. Moeckel reported receiving a research grant from ThermoFisher and serving as a consultant to Bayer, AstraZeneca, and The Medicines Company. Dr. Arnett and Dr. Huber had no conflicts of interest to declare.

[email protected]

AMSTERDAM – An early rule-out strategy based upon using two cardiac biomarkers allowed for safe discharge within a couple hours from the emergency department for most low- to intermediate-risk patients who presented with suspected acute coronary syndrome, based on the results of a randomized, multicenter trial conducted in Europe.

Moreover, the 30-day rates of major adverse cardiovascular events in the Biomarkers in Cardiology-8 (BiC-8) study were similarly low in patients discharged from the ED using the early rule-out process and in those who received standard, guideline-recommended care, which includes 6-12 hours of serial ECGs and troponin measurements in the chest pain unit, Dr. Martin Moeckel reported at the annual congress of the European Society of Cardiology.

"This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety," observed Dr. Moeckel of Charité Hospital, Berlin. The copeptin test is approved for use in the European Union but remains investigational in the United States.

Based upon the results of BiC-8, this dual biomarker for early rule-out of myocardial infarction (MI) is now standard clinical practice at Charité, he added.

The rationale for developing the early rule-out strategy tested in BiC-8 lies in the serious overcrowding that is now the norm in many EDs. This overcrowding has been shown to be in and of itself a risk factor for poor outcomes. The quandary is that nearly 12% of all patients who present to the ED do so because of chest pain, yet after an extensive and time-consuming evaluation only 1 in 10 of those patients is found to actually be having an acute MI.

"Rapid rule-out of acute MI is therefore a major clinical need, saving the health care system time and resources, and saving patients unnecessary stress, anxiety, and other risks," he said.

Copeptin is a marker for vasopressin, a hemodynamic stress indicator that shoots up immediately in an acute MI. In earlier studies, a negative result for both troponin and copeptin in an initial blood sample drawn at ED presentation had a 99% negative predictive value for MI.

The BiC-8 trial included 902 low- to intermediate-risk patients who presented with suspected acute coronary syndrome (ACS) to EDs in university medical centers. All had a negative initial cardiac troponin test. They were randomized to standard care in the chest pain unit, including serial troponin testing and ECGs, or to the experimental strategy, in which physicians were informed of the copeptin results from the same initial blood sample as the troponin. If the copeptin test was positive as defined by a level of 10 pmol/L or more, the patient was hospitalized for standard care. If the copeptin result was negative, however, the patient was immediately discharged with a scheduled outpatient visit within 72 hours.

Of the patients in the copeptin group, 66% were discharged directly from the ED, compared with 12% in the standard-care group.

The 30-day incidence of major adverse cardiovascular events (MACE) was 5.5% in the standard-care group and nearly identical at 5.46% in the copeptin group. However, physicians were permitted under the study protocol to overrule negative biomarker test results on the basis of their final clinical assessment, such as if their suspicions were aroused due to recurrent symptoms or new information about the patient’s history. In this per-protocol analysis, the 30-day MACE rate was 5.68% in the standard-care group and 3.18% in the copeptin group.

MACE was defined in BiC-8 as all-cause mortality, MI, rehospitalization for ACS, acute unplanned percutaneous coronary intervention (PCI), coronary artery bypass surgery, life-threatening arrhythmia, or resuscitation from cardiac arrest.

MACE occurred in 14 copeptin-negative patients. However, 12 of the 14 were not discharged early because physicians overruled the negative biomarker results and moved the patients into standard in-hospital management. Two patients, or 0.6% of those discharged from the ED on the basis of a negative copeptin test had adverse events: One was rehospitalized on day 23 and underwent acute unplanned PCI on the next day, and the other was rehospitalized on day 4 and underwent coronary artery bypass graft surgery on day 12.

American Heart Association Immediate Past President Donna K. Arnett, Ph.D., said in an interview that she’d really like to see a second, confirmatory randomized trial before this early rule-out strategy is widely adopted. She considers the lost-to-follow-up rate uncomfortably high: 63 patients in the intention-to-treat analysis, and another 75 not accounted for in the per-protocol analysis, noted Dr. Arnett, professor and chair of the epidemiology department at the University of Alabama, Birmingham.

BiC-8 coinvestigator Dr. Kurt Huber said in an interview that the dual-biomarker early rule-out strategy is now used routinely in the hospital where he practices. Yet like Dr. Arnett, he considers a confirmatory test "extremely important" before concluding that the strategy is ready for prime-time use in every ED.

"The most important message from BiC-8, I think, is that these were patients at low to intermediate risk; they’re not the high-risk patients. And it’s also important that the physician doesn’t rely only on the test result, but also takes a final look at the clinical situation before releasing the patient. There is some overruling when patients are biomarker-negative but have typical risk markers. No test is 100% accurate. Clinical judgment remains extremely important," emphasized Dr. Huber, professor and director of cardiology and emergency medicine at Wilhelminen Hospital, Vienna.

The BiC-8 trial was sponsored by ThermoFisher Scientific and six university medical centers in German-speaking Europe. Dr. Moeckel reported receiving a research grant from ThermoFisher and serving as a consultant to Bayer, AstraZeneca, and The Medicines Company. Dr. Arnett and Dr. Huber had no conflicts of interest to declare.

[email protected]

AMSTERDAM – An implant-based remote monitoring system in patients with advanced heart failure significantly reduced the worsening of their condition, overnight hospitalization, and total mortality, according to a trial conducted by the device-maker.

The IN-TIME study, a multicenter, prospective, randomized, controlled trial, showed that the mortality at 1 year follow-up was 3.4% in the home monitoring group, compared with 8.7% in patients with standard care. This is the first time a home monitoring trial has shown a significant drop in death rate.

"IN-TIME is really a timely study," said Dr. Angelo Auricchio of Lugano, Switzerland, because the study coincides with the most recent ESC guidelines for CRT and pacemakers, which for the very first time contain recommendation for remote monitoring. Dr. Auricchio was one of the guideline’s authors.

Rehospitalization or death resulting from worsening heart failure are often preceded by clinical events or specific trends in clinical parameters. Use of home monitoring can detect some of these events and trends early, "offering the possibility to intervene and prevent hospitalization for worsening heart failure," said Dr. Gerhard Hindricks, the lead investigator of the trial, who presented the results at the annual congress of the European Society of Cardiology.

Findings from other trials, including TRUST and REFORM have hinted at the benefits of remote monitoring, but they didn’t show the significant results seen with IN-TIME.

Patients received Biotronik’s ICD or CRT-D equipped with home monitoring software. The device detects biological signals, such as heart rate, occurrence of arrhythmias, onset of arrhythmia or shocks, and transmits the signals to a small external patient communicator called Cardio Messenger, which in turn sends the signals to a centralized monitoring unit in Heart Center Leipzig, Germany.

"Trained nursing staff took the incoming data, and then activated a chain of action according to prespecified workflows,\" said Dr. Hindricks of University of Leipzig. In some cases, if the physician was not available, the providers would directly contact the patient to advise a follow-up with a general practitioner or appropriate clinic. The physician would also enter the information about the measure taken into the centralized monitoring system.

Researchers randomized 664 patients – 1:1, with no crossover – to either home monitoring (333) or standard of care (331). All patients were receiving optimal medical therapy.

The only significant difference in the use of ACE inhibitors between home monitoring and control groups (92% v. 86%, respectively), said Dr. Hindricks.

Patients were on average 65 years old and the majority was male. On average, 60% had an implanted CRT-D, and 40%, an ICD. Follow-up was 1 year.

The primary endpoint was the modified Packer Score, and 19% of the patients in the home monitoring group suffered from a worsening of their condition, compared with close to 28% in the group who were receiving the current standard of care only (P less than .05).

The secondary endpoint of all-cause mortality, also showed highly significant reduction in the home monitoring group (10 deaths), compared with the control arm (27 deaths) (P = .004). And, while 80% of all deaths were due to cardiovascular causes, there was a significant reduction in the cardiovascular mortality among the home monitoring group (8 deaths vs. 21 deaths in control; P = .012).

The home monitoring transmission rate was 85%, and there were 1,311 home monitoring observations, 66% of which were related to home monitoring issues; for instance, the patient’s device hadn’t transmitted data for 3 consecutive days, triggering an alert. The rest resulted from clinical events, with atrial fibrillation events being the most common (8.5%).

A total of 696 of patient contacts were made as a result of home monitoring alerts. Preliminary analysis of the data showed that 13% were from drug incompliance and 16% triggered additional visit to physician.

Dr. Hindricks said that one of the keys to the success of the program was minimal patient involvement.

Dr. Auricchio said that IN-TIME was a very important study "but we should have a cautionary note about the fact that the technology used is quite proprietary to one company, so the question is if it applies to other providers." He added that the study was done in a very defined patient population, and it’s yet to be seen whether its findings apply to other heart failure patients.

Dr. Hindricks has received honoraria for lectures and has been an adviser/consultant for Biosense, Biotronik, Stereotaxis, and St. Jude Medical. He has also been an adviser/consultant for CyberHeart. Dr. Auricchio has received payments from Biotronik, St. Jude Medical, Medtronic, Abbott, Philips, and several other companies.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – An implant-based remote monitoring system in patients with advanced heart failure significantly reduced the worsening of their condition, overnight hospitalization, and total mortality, according to a trial conducted by the device-maker.

The IN-TIME study, a multicenter, prospective, randomized, controlled trial, showed that the mortality at 1 year follow-up was 3.4% in the home monitoring group, compared with 8.7% in patients with standard care. This is the first time a home monitoring trial has shown a significant drop in death rate.

"IN-TIME is really a timely study," said Dr. Angelo Auricchio of Lugano, Switzerland, because the study coincides with the most recent ESC guidelines for CRT and pacemakers, which for the very first time contain recommendation for remote monitoring. Dr. Auricchio was one of the guideline’s authors.

Rehospitalization or death resulting from worsening heart failure are often preceded by clinical events or specific trends in clinical parameters. Use of home monitoring can detect some of these events and trends early, "offering the possibility to intervene and prevent hospitalization for worsening heart failure," said Dr. Gerhard Hindricks, the lead investigator of the trial, who presented the results at the annual congress of the European Society of Cardiology.

Findings from other trials, including TRUST and REFORM have hinted at the benefits of remote monitoring, but they didn’t show the significant results seen with IN-TIME.

Patients received Biotronik’s ICD or CRT-D equipped with home monitoring software. The device detects biological signals, such as heart rate, occurrence of arrhythmias, onset of arrhythmia or shocks, and transmits the signals to a small external patient communicator called Cardio Messenger, which in turn sends the signals to a centralized monitoring unit in Heart Center Leipzig, Germany.

"Trained nursing staff took the incoming data, and then activated a chain of action according to prespecified workflows,\" said Dr. Hindricks of University of Leipzig. In some cases, if the physician was not available, the providers would directly contact the patient to advise a follow-up with a general practitioner or appropriate clinic. The physician would also enter the information about the measure taken into the centralized monitoring system.

Researchers randomized 664 patients – 1:1, with no crossover – to either home monitoring (333) or standard of care (331). All patients were receiving optimal medical therapy.

The only significant difference in the use of ACE inhibitors between home monitoring and control groups (92% v. 86%, respectively), said Dr. Hindricks.

Patients were on average 65 years old and the majority was male. On average, 60% had an implanted CRT-D, and 40%, an ICD. Follow-up was 1 year.

The primary endpoint was the modified Packer Score, and 19% of the patients in the home monitoring group suffered from a worsening of their condition, compared with close to 28% in the group who were receiving the current standard of care only (P less than .05).

The secondary endpoint of all-cause mortality, also showed highly significant reduction in the home monitoring group (10 deaths), compared with the control arm (27 deaths) (P = .004). And, while 80% of all deaths were due to cardiovascular causes, there was a significant reduction in the cardiovascular mortality among the home monitoring group (8 deaths vs. 21 deaths in control; P = .012).

The home monitoring transmission rate was 85%, and there were 1,311 home monitoring observations, 66% of which were related to home monitoring issues; for instance, the patient’s device hadn’t transmitted data for 3 consecutive days, triggering an alert. The rest resulted from clinical events, with atrial fibrillation events being the most common (8.5%).

A total of 696 of patient contacts were made as a result of home monitoring alerts. Preliminary analysis of the data showed that 13% were from drug incompliance and 16% triggered additional visit to physician.

Dr. Hindricks said that one of the keys to the success of the program was minimal patient involvement.

Dr. Auricchio said that IN-TIME was a very important study "but we should have a cautionary note about the fact that the technology used is quite proprietary to one company, so the question is if it applies to other providers." He added that the study was done in a very defined patient population, and it’s yet to be seen whether its findings apply to other heart failure patients.

Dr. Hindricks has received honoraria for lectures and has been an adviser/consultant for Biosense, Biotronik, Stereotaxis, and St. Jude Medical. He has also been an adviser/consultant for CyberHeart. Dr. Auricchio has received payments from Biotronik, St. Jude Medical, Medtronic, Abbott, Philips, and several other companies.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – An implant-based remote monitoring system in patients with advanced heart failure significantly reduced the worsening of their condition, overnight hospitalization, and total mortality, according to a trial conducted by the device-maker.

The IN-TIME study, a multicenter, prospective, randomized, controlled trial, showed that the mortality at 1 year follow-up was 3.4% in the home monitoring group, compared with 8.7% in patients with standard care. This is the first time a home monitoring trial has shown a significant drop in death rate.

"IN-TIME is really a timely study," said Dr. Angelo Auricchio of Lugano, Switzerland, because the study coincides with the most recent ESC guidelines for CRT and pacemakers, which for the very first time contain recommendation for remote monitoring. Dr. Auricchio was one of the guideline’s authors.

Rehospitalization or death resulting from worsening heart failure are often preceded by clinical events or specific trends in clinical parameters. Use of home monitoring can detect some of these events and trends early, "offering the possibility to intervene and prevent hospitalization for worsening heart failure," said Dr. Gerhard Hindricks, the lead investigator of the trial, who presented the results at the annual congress of the European Society of Cardiology.

Findings from other trials, including TRUST and REFORM have hinted at the benefits of remote monitoring, but they didn’t show the significant results seen with IN-TIME.

Patients received Biotronik’s ICD or CRT-D equipped with home monitoring software. The device detects biological signals, such as heart rate, occurrence of arrhythmias, onset of arrhythmia or shocks, and transmits the signals to a small external patient communicator called Cardio Messenger, which in turn sends the signals to a centralized monitoring unit in Heart Center Leipzig, Germany.

"Trained nursing staff took the incoming data, and then activated a chain of action according to prespecified workflows,\" said Dr. Hindricks of University of Leipzig. In some cases, if the physician was not available, the providers would directly contact the patient to advise a follow-up with a general practitioner or appropriate clinic. The physician would also enter the information about the measure taken into the centralized monitoring system.

Researchers randomized 664 patients – 1:1, with no crossover – to either home monitoring (333) or standard of care (331). All patients were receiving optimal medical therapy.

The only significant difference in the use of ACE inhibitors between home monitoring and control groups (92% v. 86%, respectively), said Dr. Hindricks.

Patients were on average 65 years old and the majority was male. On average, 60% had an implanted CRT-D, and 40%, an ICD. Follow-up was 1 year.

The primary endpoint was the modified Packer Score, and 19% of the patients in the home monitoring group suffered from a worsening of their condition, compared with close to 28% in the group who were receiving the current standard of care only (P less than .05).

The secondary endpoint of all-cause mortality, also showed highly significant reduction in the home monitoring group (10 deaths), compared with the control arm (27 deaths) (P = .004). And, while 80% of all deaths were due to cardiovascular causes, there was a significant reduction in the cardiovascular mortality among the home monitoring group (8 deaths vs. 21 deaths in control; P = .012).

The home monitoring transmission rate was 85%, and there were 1,311 home monitoring observations, 66% of which were related to home monitoring issues; for instance, the patient’s device hadn’t transmitted data for 3 consecutive days, triggering an alert. The rest resulted from clinical events, with atrial fibrillation events being the most common (8.5%).

A total of 696 of patient contacts were made as a result of home monitoring alerts. Preliminary analysis of the data showed that 13% were from drug incompliance and 16% triggered additional visit to physician.

Dr. Hindricks said that one of the keys to the success of the program was minimal patient involvement.

Dr. Auricchio said that IN-TIME was a very important study "but we should have a cautionary note about the fact that the technology used is quite proprietary to one company, so the question is if it applies to other providers." He added that the study was done in a very defined patient population, and it’s yet to be seen whether its findings apply to other heart failure patients.

Dr. Hindricks has received honoraria for lectures and has been an adviser/consultant for Biosense, Biotronik, Stereotaxis, and St. Jude Medical. He has also been an adviser/consultant for CyberHeart. Dr. Auricchio has received payments from Biotronik, St. Jude Medical, Medtronic, Abbott, Philips, and several other companies.

[email protected]

On Twitter @NaseemSMiller

AMSTERDAM – New findings from the landmark Swedish Obese Subjects study "strongly suggest" that bariatric surgery reduces by roughly half the long-term risk of developing heart failure, Dr. Kristjan Karason reported at the annual congress of the European Society of Cardiology.

"This is the first study to look at the effect of bariatric surgery on heart failure risk," observed Dr. Karason of the University of Gothenburg (Sweden). "Our findings support a modulating role of excess body fat in the pathogenesis of heart failure."

The SOS (Swedish Obese Subjects) study has been a major driver of the growing enthusiasm for bariatric surgery, not only as a means of achieving sustained weight loss far beyond what can typically be accomplished medically, but also as a means of reducing obese patients’ elevated risks for a variety of serious chronic comorbid diseases.

For example, the SOS investigators have previously reported that bariatric surgery reduced the long-term risk of developing type 2 diabetes by 87% compared to matched obese controls who didn’t undergo weight-loss surgery (N. Engl. J. Med. 2012;367:695-704), that it reduced the risk of fatal or nonfatal acute MI or stroke by one-third during a median 14.7 years of follow-up (JAMA 2012;307:56-65), and it resulted in a 42% decrease in cancer incidence in women (Lancet Oncol. 2009;10:653-62).

The SOS is a nonrandomized, prospective, observational study involving 2,010 obese subjects who underwent bariatric surgery in 1987-2001, when they were 37-60 years old. A total of 68% of the bariatric surgery recipients had vertical band gastroplasty, 19% underwent gastric banding, and 13% had a Roux en-Y gastric bypass. They were extensively matched by 18 variables to 2,037 obese controls. The SOS study is being conducted at 25 surgical departments and 480 primary care clinics across Sweden. Follow-up is ongoing.

It has been known for more than a decade that increased body mass index is associated with greater risk of developing heart failure. The mechanism involved is not well defined but is probably multifactorial. Obesity imposes a greater hemodynamic load on the heart, both preload and afterload, with resultant left ventricular hypertrophy and diastolic dysfunction. Obesity is also associated with higher levels of cardiovascular risk factors and an increased risk of atrial fibrillation, Dr. Karason noted.

Mean weight loss after a median of 14.7 years of prospective follow-up in the SOS study was 18% in the bariatric surgery group and 1% in controls. During follow-up, 91 bariatric surgery patients and 152 controls were diagnosed with heart failure, for an incidence rate of 3.1 as compared with 5.2 cases per 1,000 person-years in the control subjects.

This translated to a 48% relative risk reduction in new-onset heart failure in a multivariate regression analysis adjusted for age, sex, baseline body mass index, waist circumference, blood glucose, lipids, prior cardiovascular disease, and smoking status.

One audience member asked how to interpret the new SOS findings in light of the heart failure obesity paradox, which is the observation in multiple studies that overweight and obese heart failure patients tends to fare better than leaner ones.

"There have been no studies of weight loss in obese patients with heart failure. There really should be," Dr. Karason replied. "But my feeling is that they would reduce their risk because they will improve several risk factors, and their hemodynamic situation is also improved. So my recommendation would be for those heart failure patients to lose weight. I don’t have any studies to support that."

The SOS study is funded by the Swedish Research Council. Dr. Karason reported having no germane financial interests.

[email protected]

AMSTERDAM – New findings from the landmark Swedish Obese Subjects study "strongly suggest" that bariatric surgery reduces by roughly half the long-term risk of developing heart failure, Dr. Kristjan Karason reported at the annual congress of the European Society of Cardiology.

"This is the first study to look at the effect of bariatric surgery on heart failure risk," observed Dr. Karason of the University of Gothenburg (Sweden). "Our findings support a modulating role of excess body fat in the pathogenesis of heart failure."

The SOS (Swedish Obese Subjects) study has been a major driver of the growing enthusiasm for bariatric surgery, not only as a means of achieving sustained weight loss far beyond what can typically be accomplished medically, but also as a means of reducing obese patients’ elevated risks for a variety of serious chronic comorbid diseases.

For example, the SOS investigators have previously reported that bariatric surgery reduced the long-term risk of developing type 2 diabetes by 87% compared to matched obese controls who didn’t undergo weight-loss surgery (N. Engl. J. Med. 2012;367:695-704), that it reduced the risk of fatal or nonfatal acute MI or stroke by one-third during a median 14.7 years of follow-up (JAMA 2012;307:56-65), and it resulted in a 42% decrease in cancer incidence in women (Lancet Oncol. 2009;10:653-62).

The SOS is a nonrandomized, prospective, observational study involving 2,010 obese subjects who underwent bariatric surgery in 1987-2001, when they were 37-60 years old. A total of 68% of the bariatric surgery recipients had vertical band gastroplasty, 19% underwent gastric banding, and 13% had a Roux en-Y gastric bypass. They were extensively matched by 18 variables to 2,037 obese controls. The SOS study is being conducted at 25 surgical departments and 480 primary care clinics across Sweden. Follow-up is ongoing.

It has been known for more than a decade that increased body mass index is associated with greater risk of developing heart failure. The mechanism involved is not well defined but is probably multifactorial. Obesity imposes a greater hemodynamic load on the heart, both preload and afterload, with resultant left ventricular hypertrophy and diastolic dysfunction. Obesity is also associated with higher levels of cardiovascular risk factors and an increased risk of atrial fibrillation, Dr. Karason noted.

Mean weight loss after a median of 14.7 years of prospective follow-up in the SOS study was 18% in the bariatric surgery group and 1% in controls. During follow-up, 91 bariatric surgery patients and 152 controls were diagnosed with heart failure, for an incidence rate of 3.1 as compared with 5.2 cases per 1,000 person-years in the control subjects.

This translated to a 48% relative risk reduction in new-onset heart failure in a multivariate regression analysis adjusted for age, sex, baseline body mass index, waist circumference, blood glucose, lipids, prior cardiovascular disease, and smoking status.

One audience member asked how to interpret the new SOS findings in light of the heart failure obesity paradox, which is the observation in multiple studies that overweight and obese heart failure patients tends to fare better than leaner ones.

"There have been no studies of weight loss in obese patients with heart failure. There really should be," Dr. Karason replied. "But my feeling is that they would reduce their risk because they will improve several risk factors, and their hemodynamic situation is also improved. So my recommendation would be for those heart failure patients to lose weight. I don’t have any studies to support that."

The SOS study is funded by the Swedish Research Council. Dr. Karason reported having no germane financial interests.

[email protected]

AMSTERDAM – New findings from the landmark Swedish Obese Subjects study "strongly suggest" that bariatric surgery reduces by roughly half the long-term risk of developing heart failure, Dr. Kristjan Karason reported at the annual congress of the European Society of Cardiology.

"This is the first study to look at the effect of bariatric surgery on heart failure risk," observed Dr. Karason of the University of Gothenburg (Sweden). "Our findings support a modulating role of excess body fat in the pathogenesis of heart failure."

The SOS (Swedish Obese Subjects) study has been a major driver of the growing enthusiasm for bariatric surgery, not only as a means of achieving sustained weight loss far beyond what can typically be accomplished medically, but also as a means of reducing obese patients’ elevated risks for a variety of serious chronic comorbid diseases.

For example, the SOS investigators have previously reported that bariatric surgery reduced the long-term risk of developing type 2 diabetes by 87% compared to matched obese controls who didn’t undergo weight-loss surgery (N. Engl. J. Med. 2012;367:695-704), that it reduced the risk of fatal or nonfatal acute MI or stroke by one-third during a median 14.7 years of follow-up (JAMA 2012;307:56-65), and it resulted in a 42% decrease in cancer incidence in women (Lancet Oncol. 2009;10:653-62).

The SOS is a nonrandomized, prospective, observational study involving 2,010 obese subjects who underwent bariatric surgery in 1987-2001, when they were 37-60 years old. A total of 68% of the bariatric surgery recipients had vertical band gastroplasty, 19% underwent gastric banding, and 13% had a Roux en-Y gastric bypass. They were extensively matched by 18 variables to 2,037 obese controls. The SOS study is being conducted at 25 surgical departments and 480 primary care clinics across Sweden. Follow-up is ongoing.

It has been known for more than a decade that increased body mass index is associated with greater risk of developing heart failure. The mechanism involved is not well defined but is probably multifactorial. Obesity imposes a greater hemodynamic load on the heart, both preload and afterload, with resultant left ventricular hypertrophy and diastolic dysfunction. Obesity is also associated with higher levels of cardiovascular risk factors and an increased risk of atrial fibrillation, Dr. Karason noted.

Mean weight loss after a median of 14.7 years of prospective follow-up in the SOS study was 18% in the bariatric surgery group and 1% in controls. During follow-up, 91 bariatric surgery patients and 152 controls were diagnosed with heart failure, for an incidence rate of 3.1 as compared with 5.2 cases per 1,000 person-years in the control subjects.

This translated to a 48% relative risk reduction in new-onset heart failure in a multivariate regression analysis adjusted for age, sex, baseline body mass index, waist circumference, blood glucose, lipids, prior cardiovascular disease, and smoking status.

One audience member asked how to interpret the new SOS findings in light of the heart failure obesity paradox, which is the observation in multiple studies that overweight and obese heart failure patients tends to fare better than leaner ones.

"There have been no studies of weight loss in obese patients with heart failure. There really should be," Dr. Karason replied. "But my feeling is that they would reduce their risk because they will improve several risk factors, and their hemodynamic situation is also improved. So my recommendation would be for those heart failure patients to lose weight. I don’t have any studies to support that."

The SOS study is funded by the Swedish Research Council. Dr. Karason reported having no germane financial interests.

[email protected]

AMSTERDAM – Older men who continued to smoke in their 70s were 50% more likely to die from cancer, cardiovascular disease, and respiratory disease, compared with those who never smoked. They were also less likely to survive to age 85, according to findings from a British survey.

"The real message is that risk remains big for smokers at any age, and the evidence regarding benefits of quitting smoking persists even into old age," said Jonathan Emberson, Ph.D., a senior statistician at the University of Oxford (England), who presented the study at the annual congress of the European Society of Cardiology.

The results were from a prospective study of more than 7,000 surviving men who were initially recruited between 1967 and 1970 in the Whitehall study. The men were surveyed again in 1997-1998, when their mean age was 77 years. Follow-up information was obtained on cause-specific mortality through 2012.

At the resurvey in 1997-1998, 13% were current smokers and smoked a median of 9 cigarettes a day; 58% were former smokers, with median time of 25 years since quitting; and 23% said they never smoked. The remaining 5% said they were never-smokers in the resurvey, but not in the initial survey in 1967-1970, and were handled as a separate category, the researchers noted.

During the median follow-up of 15 years, there were 4,965 deaths, 2,063 of which resulted from cardiovascular disease, 1,167 from cancer, 802 from respiratory disease, and 933 from other causes.

Comparing the 984 smokers with 1,625 never-smokers showed that current smokers had a 50% increase in annual mortality. Their odds of death from vascular causes increased by nearly one-third, and from nonvascular causes by nearly two-thirds.

Meanwhile, a comparison between 4,091 ex-smokers and 1,625 never-smokers showed that ex-smokers had a 15% increase in annual mortality, mainly because of cancer (hazard ratio, 1.24) and respiratory disease (HR, 1.58).

Also, their risk varied considerably depending on the number of years since they had quit smoking. Men who had quit within the past 25 years had a 22% higher mortality than never-smokers, but men who had quit 25 or more years ago had no significant excess risk (HR, 1.05). Men who had quit smoking within the past 10 years had a 44% increase in all-cause mortality, compared with never-smokers. 

Also, current smokers had lower odds of surviving to age 85 (48%) than did never-smokers (65%), losing on average of 3-4 years of life expectancy.

Dr. Emberson said that never-smokers not only lived longer, but had a better quality of life. Nevertheless, "quitting remains beneficial at any age," he said.

Dr. Emberson had no disclosures. The study was funded by the U.K. Medical Research Council, the British Heart Foundation, and Cancer Research UK.

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – Older men who continued to smoke in their 70s were 50% more likely to die from cancer, cardiovascular disease, and respiratory disease, compared with those who never smoked. They were also less likely to survive to age 85, according to findings from a British survey.

"The real message is that risk remains big for smokers at any age, and the evidence regarding benefits of quitting smoking persists even into old age," said Jonathan Emberson, Ph.D., a senior statistician at the University of Oxford (England), who presented the study at the annual congress of the European Society of Cardiology.

The results were from a prospective study of more than 7,000 surviving men who were initially recruited between 1967 and 1970 in the Whitehall study. The men were surveyed again in 1997-1998, when their mean age was 77 years. Follow-up information was obtained on cause-specific mortality through 2012.

At the resurvey in 1997-1998, 13% were current smokers and smoked a median of 9 cigarettes a day; 58% were former smokers, with median time of 25 years since quitting; and 23% said they never smoked. The remaining 5% said they were never-smokers in the resurvey, but not in the initial survey in 1967-1970, and were handled as a separate category, the researchers noted.

During the median follow-up of 15 years, there were 4,965 deaths, 2,063 of which resulted from cardiovascular disease, 1,167 from cancer, 802 from respiratory disease, and 933 from other causes.

Comparing the 984 smokers with 1,625 never-smokers showed that current smokers had a 50% increase in annual mortality. Their odds of death from vascular causes increased by nearly one-third, and from nonvascular causes by nearly two-thirds.

Meanwhile, a comparison between 4,091 ex-smokers and 1,625 never-smokers showed that ex-smokers had a 15% increase in annual mortality, mainly because of cancer (hazard ratio, 1.24) and respiratory disease (HR, 1.58).

Also, their risk varied considerably depending on the number of years since they had quit smoking. Men who had quit within the past 25 years had a 22% higher mortality than never-smokers, but men who had quit 25 or more years ago had no significant excess risk (HR, 1.05). Men who had quit smoking within the past 10 years had a 44% increase in all-cause mortality, compared with never-smokers. 

Also, current smokers had lower odds of surviving to age 85 (48%) than did never-smokers (65%), losing on average of 3-4 years of life expectancy.

Dr. Emberson said that never-smokers not only lived longer, but had a better quality of life. Nevertheless, "quitting remains beneficial at any age," he said.

Dr. Emberson had no disclosures. The study was funded by the U.K. Medical Research Council, the British Heart Foundation, and Cancer Research UK.

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – Older men who continued to smoke in their 70s were 50% more likely to die from cancer, cardiovascular disease, and respiratory disease, compared with those who never smoked. They were also less likely to survive to age 85, according to findings from a British survey.

"The real message is that risk remains big for smokers at any age, and the evidence regarding benefits of quitting smoking persists even into old age," said Jonathan Emberson, Ph.D., a senior statistician at the University of Oxford (England), who presented the study at the annual congress of the European Society of Cardiology.

The results were from a prospective study of more than 7,000 surviving men who were initially recruited between 1967 and 1970 in the Whitehall study. The men were surveyed again in 1997-1998, when their mean age was 77 years. Follow-up information was obtained on cause-specific mortality through 2012.

At the resurvey in 1997-1998, 13% were current smokers and smoked a median of 9 cigarettes a day; 58% were former smokers, with median time of 25 years since quitting; and 23% said they never smoked. The remaining 5% said they were never-smokers in the resurvey, but not in the initial survey in 1967-1970, and were handled as a separate category, the researchers noted.

During the median follow-up of 15 years, there were 4,965 deaths, 2,063 of which resulted from cardiovascular disease, 1,167 from cancer, 802 from respiratory disease, and 933 from other causes.

Comparing the 984 smokers with 1,625 never-smokers showed that current smokers had a 50% increase in annual mortality. Their odds of death from vascular causes increased by nearly one-third, and from nonvascular causes by nearly two-thirds.

Meanwhile, a comparison between 4,091 ex-smokers and 1,625 never-smokers showed that ex-smokers had a 15% increase in annual mortality, mainly because of cancer (hazard ratio, 1.24) and respiratory disease (HR, 1.58).

Also, their risk varied considerably depending on the number of years since they had quit smoking. Men who had quit within the past 25 years had a 22% higher mortality than never-smokers, but men who had quit 25 or more years ago had no significant excess risk (HR, 1.05). Men who had quit smoking within the past 10 years had a 44% increase in all-cause mortality, compared with never-smokers. 

Also, current smokers had lower odds of surviving to age 85 (48%) than did never-smokers (65%), losing on average of 3-4 years of life expectancy.

Dr. Emberson said that never-smokers not only lived longer, but had a better quality of life. Nevertheless, "quitting remains beneficial at any age," he said.

Dr. Emberson had no disclosures. The study was funded by the U.K. Medical Research Council, the British Heart Foundation, and Cancer Research UK.

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – Contrary to concerns that statins may increase cataract risk, statin use was significantly associated with a 19% lower risk of cataracts – and the risk fell to 51% when statins were prescribed to younger people over a longer period, according to a new meta-analysis.

"The bottom line is that statins prevent cataracts," said Dr. John B. Kostis during a presentation at the annual congress of the European Society of Cardiology. "But the bottom line is: Don’t be scared of cataracts when prescribing statins."

The concern about statins’ cataractogenicity arose in the 1980s, when the Food and Drug Administration approved lovastatin with the precaution that patients should be examined with a slit-lamp before and during treatment.

The agency removed that recommendation in 1991, but studies such as the recent Waterloo Eye Study continued to show an association between statin use and an increased risk of cataracts.

Dr. Kostis and his colleagues at Robert Wood Johnson Medical School, New Brunswick, N.J., included 13 studies in their meta-analysis, which included a total of 2.4 million individuals and 25,658 cataract cases.

The average number of patients per study was 171,689 (median study size, 2,746). Dr. Kostis added that two studies were very large and were excluded in the sensitivity analyses. The average patient age was 61 years, and the average duration of statin treatment was 54 months.

Results showed that there was nearly a 20% decrease in the rate of cataracts among patients who were treated with statins, compared with those who were not (odds ratio, 0.81; P = .0009).

The statins’ effect was also significant in studies that examined clinical cataracts (OR, 0.81; P = .0022), although the trend was not significant in studies examining opacities detected by ophthalmologists (OR, 0.81; P = .2106)

There was also a 1.4% absolute risk reduction (P less than .0001), demonstrating that 71 individuals needed to be treated with statins to prevent one case of cataracts, Dr. Kostis said.

Meanwhile, patients who began statin therapy in their 40s had a 51% lower chance of cataracts (OR, 0.49), compared with those who began the treatment in their 70s and probably already had cataracts (OR, 1.03, or no risk reduction), he said.

"It is possible that the two processes (aging and statins) work in parallel or interactively," Dr. Kostis said in a news release.

In addition, there was a 46% reduction in the risk of cataracts when patients were treated with statins for as long as 14 years (OR, 0.54), compared with a 10% risk reduction among those who were treated for only 6 months (OR, 0.90).

Gender did not play a role in the findings.

The meta-analysis had several limitations. Each of the studies had a different design, and the randomized clinical trials didn’t have cataracts as an endpoint. Also, the certainty of exposure to statins in observational studies is imprecise, and there is the possibility of reporting and publication bias, Dr. Kostis noted.

The strength of the meta-analysis was in the consistency of the statins’ effect when it was analyzed from various aspects, he said. In addition, all published reports on the topic were included in the analysis. Moreover, the effect of statins in preventing cataracts was significantly more pronounced for the hard endpoint of cataract extractions.

A large, randomized clinical trial could put the uncertainty to rest, noted Dr. Kim Allan Williams Sr., chair of cardiology at Wayne State University, Detroit. But the findings from this analysis were reassuring, added Dr. Williams, who was not involved in the meta-analysis.

Dr. Kostis had no disclosures. Dr. Williams has received consultant fees/honoraria from Astellas Healthcare.

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – Contrary to concerns that statins may increase cataract risk, statin use was significantly associated with a 19% lower risk of cataracts – and the risk fell to 51% when statins were prescribed to younger people over a longer period, according to a new meta-analysis.

"The bottom line is that statins prevent cataracts," said Dr. John B. Kostis during a presentation at the annual congress of the European Society of Cardiology. "But the bottom line is: Don’t be scared of cataracts when prescribing statins."

The concern about statins’ cataractogenicity arose in the 1980s, when the Food and Drug Administration approved lovastatin with the precaution that patients should be examined with a slit-lamp before and during treatment.

The agency removed that recommendation in 1991, but studies such as the recent Waterloo Eye Study continued to show an association between statin use and an increased risk of cataracts.

Dr. Kostis and his colleagues at Robert Wood Johnson Medical School, New Brunswick, N.J., included 13 studies in their meta-analysis, which included a total of 2.4 million individuals and 25,658 cataract cases.

The average number of patients per study was 171,689 (median study size, 2,746). Dr. Kostis added that two studies were very large and were excluded in the sensitivity analyses. The average patient age was 61 years, and the average duration of statin treatment was 54 months.

Results showed that there was nearly a 20% decrease in the rate of cataracts among patients who were treated with statins, compared with those who were not (odds ratio, 0.81; P = .0009).

The statins’ effect was also significant in studies that examined clinical cataracts (OR, 0.81; P = .0022), although the trend was not significant in studies examining opacities detected by ophthalmologists (OR, 0.81; P = .2106)

There was also a 1.4% absolute risk reduction (P less than .0001), demonstrating that 71 individuals needed to be treated with statins to prevent one case of cataracts, Dr. Kostis said.

Meanwhile, patients who began statin therapy in their 40s had a 51% lower chance of cataracts (OR, 0.49), compared with those who began the treatment in their 70s and probably already had cataracts (OR, 1.03, or no risk reduction), he said.

"It is possible that the two processes (aging and statins) work in parallel or interactively," Dr. Kostis said in a news release.

In addition, there was a 46% reduction in the risk of cataracts when patients were treated with statins for as long as 14 years (OR, 0.54), compared with a 10% risk reduction among those who were treated for only 6 months (OR, 0.90).

Gender did not play a role in the findings.

The meta-analysis had several limitations. Each of the studies had a different design, and the randomized clinical trials didn’t have cataracts as an endpoint. Also, the certainty of exposure to statins in observational studies is imprecise, and there is the possibility of reporting and publication bias, Dr. Kostis noted.

The strength of the meta-analysis was in the consistency of the statins’ effect when it was analyzed from various aspects, he said. In addition, all published reports on the topic were included in the analysis. Moreover, the effect of statins in preventing cataracts was significantly more pronounced for the hard endpoint of cataract extractions.

A large, randomized clinical trial could put the uncertainty to rest, noted Dr. Kim Allan Williams Sr., chair of cardiology at Wayne State University, Detroit. But the findings from this analysis were reassuring, added Dr. Williams, who was not involved in the meta-analysis.

Dr. Kostis had no disclosures. Dr. Williams has received consultant fees/honoraria from Astellas Healthcare.

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – Contrary to concerns that statins may increase cataract risk, statin use was significantly associated with a 19% lower risk of cataracts – and the risk fell to 51% when statins were prescribed to younger people over a longer period, according to a new meta-analysis.

"The bottom line is that statins prevent cataracts," said Dr. John B. Kostis during a presentation at the annual congress of the European Society of Cardiology. "But the bottom line is: Don’t be scared of cataracts when prescribing statins."

The concern about statins’ cataractogenicity arose in the 1980s, when the Food and Drug Administration approved lovastatin with the precaution that patients should be examined with a slit-lamp before and during treatment.

The agency removed that recommendation in 1991, but studies such as the recent Waterloo Eye Study continued to show an association between statin use and an increased risk of cataracts.

Dr. Kostis and his colleagues at Robert Wood Johnson Medical School, New Brunswick, N.J., included 13 studies in their meta-analysis, which included a total of 2.4 million individuals and 25,658 cataract cases.

The average number of patients per study was 171,689 (median study size, 2,746). Dr. Kostis added that two studies were very large and were excluded in the sensitivity analyses. The average patient age was 61 years, and the average duration of statin treatment was 54 months.

Results showed that there was nearly a 20% decrease in the rate of cataracts among patients who were treated with statins, compared with those who were not (odds ratio, 0.81; P = .0009).

The statins’ effect was also significant in studies that examined clinical cataracts (OR, 0.81; P = .0022), although the trend was not significant in studies examining opacities detected by ophthalmologists (OR, 0.81; P = .2106)

There was also a 1.4% absolute risk reduction (P less than .0001), demonstrating that 71 individuals needed to be treated with statins to prevent one case of cataracts, Dr. Kostis said.

Meanwhile, patients who began statin therapy in their 40s had a 51% lower chance of cataracts (OR, 0.49), compared with those who began the treatment in their 70s and probably already had cataracts (OR, 1.03, or no risk reduction), he said.

"It is possible that the two processes (aging and statins) work in parallel or interactively," Dr. Kostis said in a news release.

In addition, there was a 46% reduction in the risk of cataracts when patients were treated with statins for as long as 14 years (OR, 0.54), compared with a 10% risk reduction among those who were treated for only 6 months (OR, 0.90).

Gender did not play a role in the findings.

The meta-analysis had several limitations. Each of the studies had a different design, and the randomized clinical trials didn’t have cataracts as an endpoint. Also, the certainty of exposure to statins in observational studies is imprecise, and there is the possibility of reporting and publication bias, Dr. Kostis noted.

The strength of the meta-analysis was in the consistency of the statins’ effect when it was analyzed from various aspects, he said. In addition, all published reports on the topic were included in the analysis. Moreover, the effect of statins in preventing cataracts was significantly more pronounced for the hard endpoint of cataract extractions.

A large, randomized clinical trial could put the uncertainty to rest, noted Dr. Kim Allan Williams Sr., chair of cardiology at Wayne State University, Detroit. But the findings from this analysis were reassuring, added Dr. Williams, who was not involved in the meta-analysis.

Dr. Kostis had no disclosures. Dr. Williams has received consultant fees/honoraria from Astellas Healthcare.

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – A prospective analysis of CT angiography of more than 13,000 patients bears some good news and some bad news for patients who have quit smoking, and yet another warning for those who continue to smoke. 

Current smokers had nearly a twofold increase in risk of major adverse cardiac events (MACE), compared with those who had quit and those who had never smoked. However, they – along with past smokers – still had a significantly higher prevalence, extent, and severity of coronary artery disease (CAD), compared with individuals who never smoked.

©bilderbox/fotolia.com

The unpublished study, which is from the CONFIRM Registry, was presented by Dr. James K. Min of Weill Cornell Medical College, New York, and New York-Presbyterian Hospital, at the annual congress of the European Society of Cardiology. 

Researchers evaluated the extent and severity of CAD, as well as the risk of MACE, for active smokers, past smokers, and nonsmokers undergoing coronary CT angiography. 

Of the 13,372 patients without known CAD who underwent CT, 21% were current smokers, 24% were past smokers who had quit more than 3 months prior to the CT, and 55% were nonsmokers. 

The average age of the patients was 56 years, and half were men. Patients were followed up for 2 years, and MACE occurred in 279 cases (2.1%). 

Analysis showed that current and past smokers had a 50% or higher risk of obstructive CAD than did nonsmokers. One-vessel disease had a frequency of 11.1% among nonsmokers, compared with 16.6% and 16.2% in current and past smokers, respectively; the frequency of two-vessel disease was 4.8% among nonsmokers vs. 7.3% and 7.8%; and the frequency of three-vessel disease was 2.3% vs. 5.1% and 5%. 

In addition, current smokers had a higher risk of MACE than did nonsmokers (P less than .001), but past smokers did not (P = .29). 

Even after matched-cohort analysis, the relationship remained the same, and current smoking was still significantly associated with MACE risk, but past smoking was not. 

"You’re never too old to quit smoking," said Dr. Freek Verheugt, who moderated the session. 

Dr. Min and Dr. Verheugt had no disclosures. 

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – A prospective analysis of CT angiography of more than 13,000 patients bears some good news and some bad news for patients who have quit smoking, and yet another warning for those who continue to smoke. 

Current smokers had nearly a twofold increase in risk of major adverse cardiac events (MACE), compared with those who had quit and those who had never smoked. However, they – along with past smokers – still had a significantly higher prevalence, extent, and severity of coronary artery disease (CAD), compared with individuals who never smoked.

©bilderbox/fotolia.com

The unpublished study, which is from the CONFIRM Registry, was presented by Dr. James K. Min of Weill Cornell Medical College, New York, and New York-Presbyterian Hospital, at the annual congress of the European Society of Cardiology. 

Researchers evaluated the extent and severity of CAD, as well as the risk of MACE, for active smokers, past smokers, and nonsmokers undergoing coronary CT angiography. 

Of the 13,372 patients without known CAD who underwent CT, 21% were current smokers, 24% were past smokers who had quit more than 3 months prior to the CT, and 55% were nonsmokers. 

The average age of the patients was 56 years, and half were men. Patients were followed up for 2 years, and MACE occurred in 279 cases (2.1%). 

Analysis showed that current and past smokers had a 50% or higher risk of obstructive CAD than did nonsmokers. One-vessel disease had a frequency of 11.1% among nonsmokers, compared with 16.6% and 16.2% in current and past smokers, respectively; the frequency of two-vessel disease was 4.8% among nonsmokers vs. 7.3% and 7.8%; and the frequency of three-vessel disease was 2.3% vs. 5.1% and 5%. 

In addition, current smokers had a higher risk of MACE than did nonsmokers (P less than .001), but past smokers did not (P = .29). 

Even after matched-cohort analysis, the relationship remained the same, and current smoking was still significantly associated with MACE risk, but past smoking was not. 

"You’re never too old to quit smoking," said Dr. Freek Verheugt, who moderated the session. 

Dr. Min and Dr. Verheugt had no disclosures. 

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – A prospective analysis of CT angiography of more than 13,000 patients bears some good news and some bad news for patients who have quit smoking, and yet another warning for those who continue to smoke. 

Current smokers had nearly a twofold increase in risk of major adverse cardiac events (MACE), compared with those who had quit and those who had never smoked. However, they – along with past smokers – still had a significantly higher prevalence, extent, and severity of coronary artery disease (CAD), compared with individuals who never smoked.

©bilderbox/fotolia.com

The unpublished study, which is from the CONFIRM Registry, was presented by Dr. James K. Min of Weill Cornell Medical College, New York, and New York-Presbyterian Hospital, at the annual congress of the European Society of Cardiology. 

Researchers evaluated the extent and severity of CAD, as well as the risk of MACE, for active smokers, past smokers, and nonsmokers undergoing coronary CT angiography. 

Of the 13,372 patients without known CAD who underwent CT, 21% were current smokers, 24% were past smokers who had quit more than 3 months prior to the CT, and 55% were nonsmokers. 

The average age of the patients was 56 years, and half were men. Patients were followed up for 2 years, and MACE occurred in 279 cases (2.1%). 

Analysis showed that current and past smokers had a 50% or higher risk of obstructive CAD than did nonsmokers. One-vessel disease had a frequency of 11.1% among nonsmokers, compared with 16.6% and 16.2% in current and past smokers, respectively; the frequency of two-vessel disease was 4.8% among nonsmokers vs. 7.3% and 7.8%; and the frequency of three-vessel disease was 2.3% vs. 5.1% and 5%. 

In addition, current smokers had a higher risk of MACE than did nonsmokers (P less than .001), but past smokers did not (P = .29). 

Even after matched-cohort analysis, the relationship remained the same, and current smoking was still significantly associated with MACE risk, but past smoking was not. 

"You’re never too old to quit smoking," said Dr. Freek Verheugt, who moderated the session. 

Dr. Min and Dr. Verheugt had no disclosures. 

[email protected]

On Twitter @naseemsmiller

AMSTERDAM – The use of a high-sensitivity cardiac troponin I assay and gender-specific cutoffs to define acute myocardial infarction nearly doubled the diagnosis of MI in women in an early subanalysis from the High-STEACS trial.

High-sensitivity troponin assays have identified gender differences in the normal reference range. This becomes relevant in light of the third universal definition of acute MI, released last year, which defines the biomarker threshold for the diagnosis of MI as a cardiac troponin at the 99th percentile of a healthy reference population (Eur. Heart J. 2012;33:2551-67). The conventional cardiac troponin assays in widespread use today aren’t sufficiently sensitive to detect gender differences in the normal reference range, so they rely upon a single diagnostic threshold that sets the bar so high it appears to lead to underdiagnosis of MI in women. This likely contributes to gender inequalities in treatment and outcome, Dr. Nicholas L. Mills asserted at the annual congress of the European Society of Cardiology.

The high-sensitivity cardiac troponin I assay utilized in the ongoing High-STEACS (High-Sensitivity Troponin in the Evolution of Patients with Acute Coronary Syndrome) trial uses an MI diagnostic threshold of 16 ng/L in women and 34 ng/L in men. These levels were derived by identifying the 99th percentiles in a healthy reference population composed of nearly 4,600 individuals. In contrast, the conventional troponin I assay utilized for purposes of comparison in High-STEACS employs a threshold of 50 ng/L for both men and women, explained Dr. Mills of the University of Edinburgh.

He reported on 1,126 patients with suspected acute coronary syndrome (ACS), 46% of them women, who presented to the Royal Infirmary of Edinburgh, one of the 10 Scottish medical centers participating in High-STEACS. Subjects’ plasma samples were analyzed using both the Abbott conventional sensitive cardiac troponin I assay and Abbott’s newer high-sensitivity assay, but clinicians received only the results of the conventional assay. The aim of this High-STEACS substudy was to evaluate the effect of gender-specific biomarker thresholds. The final diagnosis of acute MI was determined independently by two cardiologists on the basis of all clinical studies and 30-day outcomes.

Using the conventional assay with a requirement of a troponin level of 50 ng/L or more in both men and women, acute MI was diagnosed in 13% of women and 23% of men. Utilization of the high-sensitivity assay with sex-specific thresholds boosted the rate of diagnosis of MI from 13% to 23% in the women while having little effect in men, where the rate inched up from 23% to 24%.

The diagnostic sensitivity of the conventional assay was 77% in men and 47% in women, while the high-sensitivity assay with gender-specific thresholds had a sensitivity of 86% in men and 95% in women, according to Dr. Mills.

Women with an adjudicated diagnosis of MI were less likely than men to undergo coronary angiography, by a margin of 28% compared with 67%, and they were far less likely to undergo coronary revascularization, by a margin of 18% to 58%. That’s largely because 55 women in the study had a high-sensitivity troponin I level of 17-49 ng/L, above the level required for diagnosis of MI using the sex-specific threshold but below the 50 ng/L requirement with the conventional assay that clinicians used in their patient management decisions.

"The critical question is whether reclassification of these patients as having MI would lead to better treatment and change clinical outcomes. At 6 months, one in four of these patients had a recurrent MI or died, compared with less than 2% of women with a high-sensitivity troponin I of 16 ng/L or less. Those outcomes were similar to or worse than those in women with much larger MIs, who were treated based upon the results of the contemporary assay requiring a level of 50 ng/L or more," the cardiologist noted.

In a previous study, Dr. Mills and his coworkers demonstrated that lowering the diagnostic threshold for acute MI using a previous-generation sensitive cardiac troponin assay in patients with suspected ACS led to a 50% reduction in recurrent MI or death (JAMA 2011;305:1210-5). This was accomplished simply by reclassifying patients as having MI provided their peak troponin exceeded the new, lower threshold.

The hypothesis being tested in High-STEACS is that lowering the biomarker diagnostic threshold for MI still further while utilizing gender-specific cutoffs will result in even better clinical outcomes. High-STEACS is an ongoing randomized trial involving a planned 26,000 Scottish patients with suspected ACS who will be followed for 30 months.

"If improved sensitivity does not impinge on specificity in diagnosis, then clinical outcomes will improve through better targeting of therapies for coronary heart disease. But if increased sensitivity leads to poorer specificity, then misdiagnosis and use of inappropriate therapies may lead to detrimental clinical outcomes," Dr. Mills explained.

Discussant Dr. Eva Swahn of Linkoping (Sweden) University commented that if the results of this High-STEACS substudy showing the value of gender-specific biomarker thresholds hold up, the implications regarding diagnosis and management of MI in women could be great. But elevations in cardiac troponins can be caused by other conditions besides acute MI, including stable angina, renal failure, diabetes, and heart failure, and the substudy design leaves her unconvinced that troponin I elevations in the 17- to 49-ng/L range were necessarily due to MI.

"If you don’t have an MI you shouldn’t be treated as though you do. The management will be completely wrong, and maybe the outcome will be worse," she cautioned.

High-STEACS is funded by the British Heart Foundation. Abbott Diagnostics is supplying the cardiac troponin assay materials. Dr. Mills and Dr. Swahn reported having no financial conflicts.

[email protected]

AMSTERDAM – The use of a high-sensitivity cardiac troponin I assay and gender-specific cutoffs to define acute myocardial infarction nearly doubled the diagnosis of MI in women in an early subanalysis from the High-STEACS trial.

High-sensitivity troponin assays have identified gender differences in the normal reference range. This becomes relevant in light of the third universal definition of acute MI, released last year, which defines the biomarker threshold for the diagnosis of MI as a cardiac troponin at the 99th percentile of a healthy reference population (Eur. Heart J. 2012;33:2551-67). The conventional cardiac troponin assays in widespread use today aren’t sufficiently sensitive to detect gender differences in the normal reference range, so they rely upon a single diagnostic threshold that sets the bar so high it appears to lead to underdiagnosis of MI in women. This likely contributes to gender inequalities in treatment and outcome, Dr. Nicholas L. Mills asserted at the annual congress of the European Society of Cardiology.

The high-sensitivity cardiac troponin I assay utilized in the ongoing High-STEACS (High-Sensitivity Troponin in the Evolution of Patients with Acute Coronary Syndrome) trial uses an MI diagnostic threshold of 16 ng/L in women and 34 ng/L in men. These levels were derived by identifying the 99th percentiles in a healthy reference population composed of nearly 4,600 individuals. In contrast, the conventional troponin I assay utilized for purposes of comparison in High-STEACS employs a threshold of 50 ng/L for both men and women, explained Dr. Mills of the University of Edinburgh.

He reported on 1,126 patients with suspected acute coronary syndrome (ACS), 46% of them women, who presented to the Royal Infirmary of Edinburgh, one of the 10 Scottish medical centers participating in High-STEACS. Subjects’ plasma samples were analyzed using both the Abbott conventional sensitive cardiac troponin I assay and Abbott’s newer high-sensitivity assay, but clinicians received only the results of the conventional assay. The aim of this High-STEACS substudy was to evaluate the effect of gender-specific biomarker thresholds. The final diagnosis of acute MI was determined independently by two cardiologists on the basis of all clinical studies and 30-day outcomes.

Using the conventional assay with a requirement of a troponin level of 50 ng/L or more in both men and women, acute MI was diagnosed in 13% of women and 23% of men. Utilization of the high-sensitivity assay with sex-specific thresholds boosted the rate of diagnosis of MI from 13% to 23% in the women while having little effect in men, where the rate inched up from 23% to 24%.

The diagnostic sensitivity of the conventional assay was 77% in men and 47% in women, while the high-sensitivity assay with gender-specific thresholds had a sensitivity of 86% in men and 95% in women, according to Dr. Mills.

Women with an adjudicated diagnosis of MI were less likely than men to undergo coronary angiography, by a margin of 28% compared with 67%, and they were far less likely to undergo coronary revascularization, by a margin of 18% to 58%. That’s largely because 55 women in the study had a high-sensitivity troponin I level of 17-49 ng/L, above the level required for diagnosis of MI using the sex-specific threshold but below the 50 ng/L requirement with the conventional assay that clinicians used in their patient management decisions.

"The critical question is whether reclassification of these patients as having MI would lead to better treatment and change clinical outcomes. At 6 months, one in four of these patients had a recurrent MI or died, compared with less than 2% of women with a high-sensitivity troponin I of 16 ng/L or less. Those outcomes were similar to or worse than those in women with much larger MIs, who were treated based upon the results of the contemporary assay requiring a level of 50 ng/L or more," the cardiologist noted.

In a previous study, Dr. Mills and his coworkers demonstrated that lowering the diagnostic threshold for acute MI using a previous-generation sensitive cardiac troponin assay in patients with suspected ACS led to a 50% reduction in recurrent MI or death (JAMA 2011;305:1210-5). This was accomplished simply by reclassifying patients as having MI provided their peak troponin exceeded the new, lower threshold.

The hypothesis being tested in High-STEACS is that lowering the biomarker diagnostic threshold for MI still further while utilizing gender-specific cutoffs will result in even better clinical outcomes. High-STEACS is an ongoing randomized trial involving a planned 26,000 Scottish patients with suspected ACS who will be followed for 30 months.

"If improved sensitivity does not impinge on specificity in diagnosis, then clinical outcomes will improve through better targeting of therapies for coronary heart disease. But if increased sensitivity leads to poorer specificity, then misdiagnosis and use of inappropriate therapies may lead to detrimental clinical outcomes," Dr. Mills explained.

Discussant Dr. Eva Swahn of Linkoping (Sweden) University commented that if the results of this High-STEACS substudy showing the value of gender-specific biomarker thresholds hold up, the implications regarding diagnosis and management of MI in women could be great. But elevations in cardiac troponins can be caused by other conditions besides acute MI, including stable angina, renal failure, diabetes, and heart failure, and the substudy design leaves her unconvinced that troponin I elevations in the 17- to 49-ng/L range were necessarily due to MI.

"If you don’t have an MI you shouldn’t be treated as though you do. The management will be completely wrong, and maybe the outcome will be worse," she cautioned.

High-STEACS is funded by the British Heart Foundation. Abbott Diagnostics is supplying the cardiac troponin assay materials. Dr. Mills and Dr. Swahn reported having no financial conflicts.

[email protected]

AMSTERDAM – The use of a high-sensitivity cardiac troponin I assay and gender-specific cutoffs to define acute myocardial infarction nearly doubled the diagnosis of MI in women in an early subanalysis from the High-STEACS trial.

High-sensitivity troponin assays have identified gender differences in the normal reference range. This becomes relevant in light of the third universal definition of acute MI, released last year, which defines the biomarker threshold for the diagnosis of MI as a cardiac troponin at the 99th percentile of a healthy reference population (Eur. Heart J. 2012;33:2551-67). The conventional cardiac troponin assays in widespread use today aren’t sufficiently sensitive to detect gender differences in the normal reference range, so they rely upon a single diagnostic threshold that sets the bar so high it appears to lead to underdiagnosis of MI in women. This likely contributes to gender inequalities in treatment and outcome, Dr. Nicholas L. Mills asserted at the annual congress of the European Society of Cardiology.

The high-sensitivity cardiac troponin I assay utilized in the ongoing High-STEACS (High-Sensitivity Troponin in the Evolution of Patients with Acute Coronary Syndrome) trial uses an MI diagnostic threshold of 16 ng/L in women and 34 ng/L in men. These levels were derived by identifying the 99th percentiles in a healthy reference population composed of nearly 4,600 individuals. In contrast, the conventional troponin I assay utilized for purposes of comparison in High-STEACS employs a threshold of 50 ng/L for both men and women, explained Dr. Mills of the University of Edinburgh.

He reported on 1,126 patients with suspected acute coronary syndrome (ACS), 46% of them women, who presented to the Royal Infirmary of Edinburgh, one of the 10 Scottish medical centers participating in High-STEACS. Subjects’ plasma samples were analyzed using both the Abbott conventional sensitive cardiac troponin I assay and Abbott’s newer high-sensitivity assay, but clinicians received only the results of the conventional assay. The aim of this High-STEACS substudy was to evaluate the effect of gender-specific biomarker thresholds. The final diagnosis of acute MI was determined independently by two cardiologists on the basis of all clinical studies and 30-day outcomes.

Using the conventional assay with a requirement of a troponin level of 50 ng/L or more in both men and women, acute MI was diagnosed in 13% of women and 23% of men. Utilization of the high-sensitivity assay with sex-specific thresholds boosted the rate of diagnosis of MI from 13% to 23% in the women while having little effect in men, where the rate inched up from 23% to 24%.

The diagnostic sensitivity of the conventional assay was 77% in men and 47% in women, while the high-sensitivity assay with gender-specific thresholds had a sensitivity of 86% in men and 95% in women, according to Dr. Mills.

Women with an adjudicated diagnosis of MI were less likely than men to undergo coronary angiography, by a margin of 28% compared with 67%, and they were far less likely to undergo coronary revascularization, by a margin of 18% to 58%. That’s largely because 55 women in the study had a high-sensitivity troponin I level of 17-49 ng/L, above the level required for diagnosis of MI using the sex-specific threshold but below the 50 ng/L requirement with the conventional assay that clinicians used in their patient management decisions.

"The critical question is whether reclassification of these patients as having MI would lead to better treatment and change clinical outcomes. At 6 months, one in four of these patients had a recurrent MI or died, compared with less than 2% of women with a high-sensitivity troponin I of 16 ng/L or less. Those outcomes were similar to or worse than those in women with much larger MIs, who were treated based upon the results of the contemporary assay requiring a level of 50 ng/L or more," the cardiologist noted.

In a previous study, Dr. Mills and his coworkers demonstrated that lowering the diagnostic threshold for acute MI using a previous-generation sensitive cardiac troponin assay in patients with suspected ACS led to a 50% reduction in recurrent MI or death (JAMA 2011;305:1210-5). This was accomplished simply by reclassifying patients as having MI provided their peak troponin exceeded the new, lower threshold.

The hypothesis being tested in High-STEACS is that lowering the biomarker diagnostic threshold for MI still further while utilizing gender-specific cutoffs will result in even better clinical outcomes. High-STEACS is an ongoing randomized trial involving a planned 26,000 Scottish patients with suspected ACS who will be followed for 30 months.

"If improved sensitivity does not impinge on specificity in diagnosis, then clinical outcomes will improve through better targeting of therapies for coronary heart disease. But if increased sensitivity leads to poorer specificity, then misdiagnosis and use of inappropriate therapies may lead to detrimental clinical outcomes," Dr. Mills explained.

Discussant Dr. Eva Swahn of Linkoping (Sweden) University commented that if the results of this High-STEACS substudy showing the value of gender-specific biomarker thresholds hold up, the implications regarding diagnosis and management of MI in women could be great. But elevations in cardiac troponins can be caused by other conditions besides acute MI, including stable angina, renal failure, diabetes, and heart failure, and the substudy design leaves her unconvinced that troponin I elevations in the 17- to 49-ng/L range were necessarily due to MI.

"If you don’t have an MI you shouldn’t be treated as though you do. The management will be completely wrong, and maybe the outcome will be worse," she cautioned.

High-STEACS is funded by the British Heart Foundation. Abbott Diagnostics is supplying the cardiac troponin assay materials. Dr. Mills and Dr. Swahn reported having no financial conflicts.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

On Twitter @mitchelzoler