ESC Congress 2012

MUNICH – Results from the largest study to ever assess treatment with spironolactone in patients with diastolic heart failure showed clear indications that the drug exerted beneficial structural, hemodynamic, and physiologic effects with a generally reasonable safety profile.

But the mottled results also showed a puzzling lack of efficacy for other end points, and when coupled with some worrisome signs of harm, most physicians will probably reserve judgment on using spironolactone on patients with heart failure and preserved left ventricular ejection fraction until results from an even larger, clinical end point trial are available next year.

Mitchel L. Zoler/IMNG Medical Media

Based on the results, "spironolactone can be considered in patients with diastolic heart failure for improving cardiac function and blood pressure control," Dr. Burkert M. Pieske said at the annual congress of the European Society of Cardiology.

Moreover, spironolactone’s performance in the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial with 422 patients randomized to treatment with spironolactone or placebo gives the drug a unique position in the world of diastolic heart failure: Spironolactone is now the only drug with any sort of positive track record in a prospective controlled trial.

"I can’t give a general recommendation to use it because patients [on spironolactone in the trial] did not feel better" after a year on treatment, Dr. Pieske acknowledged in an interview. "But if I had a [diastolic heart failure] patient on dual or triple antihypertensive therapy who still had high blood pressure, I would not hesitate to put the patient on spironolactone if their renal function and potassium level allowed it. This treatment will reduce blood pressure and improve cardiac structure and function," said Dr. Pieske, professor and head of the department of cardiology at the Medical University of Graz, Austria.

But other experts who heard the results had doubts.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Dr. Anker advised waiting for results that are expected to come out next year from TOPCAT, a U.S. study of spironolactone in more than 3,500 patients with diastolic heart failure sponsored by the National Heart, Lung, and Blood Institute.

Aldo-CHF enrolled patients aged 50 years or older with New York Heart Association class II or III heart failure and a left ventricular ejection fraction of at least 50%. Patients also needed to have echocardiographic evidence of diastolic dysfunction, and a peak oxygen consumption (VO₂) of less than 25 mL/kg per minute. The study excluded patients with a serum potassium level of 5.1 mmol/L or higher, and those with an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m² or a serum creatinine greater than 1.8 mg/dL. The patients averaged 67 years old, about 86% had class II heart failure, their average ejection fraction was about 67%, and their average GFR was about 79 mL/min per 1.73 m².

The researchers randomized 213 patients to received 25 mg of spironolactone daily, and 209 control patients to placebo. Patients also received other medications, with about three-quarters on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, about three-quarters receiving a beta-blocker, and slightly more than half receiving a diuretic.

The study had two primary end points. After 12 months, patients on spironolactone had an average reduction in the E/é ratio of 0.6 (a 5% drop from baseline), compared with an average rise among the control patients of 0.8 (a 6% rise from baseline) for this surrogate measure of filling pressure, a significant between-group difference. The second primary end point was change in peak VO₂, and for this measure the two groups showed very similar changes over the 12 months of the study without a significant between-group difference.

Patients on spironolactone also had a significant reduction in average blood pressure of 8/2 mm Hg at 12 months compared with baseline, but the beneficial effect that spironolactone had on myocardial reverse remodeling reflected in the change in E/é occurred independent of the drug’s blood pressure effect, Dr. Pieske said.

Secondary end points that showed beneficial effects from spironolactone treatment included a small but significant increase in left ventricular ejection fraction, and a significant reduction in serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), a marker of heart failure severity. But patients on spironolactone also had an average 15-m reduction in their 6-minute walk distance, a significant drop.

"We saw consistent structural and functional remodeling effects from spironolactone, and except for left ventricular size, all of the other measures improved. But we saw no benefit on exercise capacity, New York Heart Association class, or quality of life," Dr. Pieske said. "Somehow, the beneficial effects on the heart did not translate into an improved situation."

While the overall safety profile of spironolactone treatment was good, the results showed a few possible areas of concern. In the spironolactone group, 36% of patients had worsening renal function, compared with 21% in the control arm, a significant difference; and the average GFR fell by about 7 mL/min per 1.73 m² with spironolactone, compared with no change in the control patients. The incidence of new or worsening anemia was 16% among the spironolactone patients and 9% in the controls, a significant difference. And twice as many patients on spironolactone had an increase in their serum potassium compared with the controls. However, the incidence of severe hyperkalemia was low and similar in both arms of the study.

"To our knowledge, increased anemia was not seen before" with spironolactone. "Maybe the anemia or a mild decrease in hemoglobin contributed" to the lack of an effect of treatment on exercise capacity, Dr. Pieske suggested.

Aldo-DHF was sponsored by the German government. Dr. Pieske said that he and his associates had no disclosures. Dr. Anker said that he has received consulting fees from Amgen, Bosch Healthcare, and other companies.

MUNICH – Results from the largest study to ever assess treatment with spironolactone in patients with diastolic heart failure showed clear indications that the drug exerted beneficial structural, hemodynamic, and physiologic effects with a generally reasonable safety profile.

But the mottled results also showed a puzzling lack of efficacy for other end points, and when coupled with some worrisome signs of harm, most physicians will probably reserve judgment on using spironolactone on patients with heart failure and preserved left ventricular ejection fraction until results from an even larger, clinical end point trial are available next year.

Mitchel L. Zoler/IMNG Medical Media

Based on the results, "spironolactone can be considered in patients with diastolic heart failure for improving cardiac function and blood pressure control," Dr. Burkert M. Pieske said at the annual congress of the European Society of Cardiology.

Moreover, spironolactone’s performance in the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial with 422 patients randomized to treatment with spironolactone or placebo gives the drug a unique position in the world of diastolic heart failure: Spironolactone is now the only drug with any sort of positive track record in a prospective controlled trial.

"I can’t give a general recommendation to use it because patients [on spironolactone in the trial] did not feel better" after a year on treatment, Dr. Pieske acknowledged in an interview. "But if I had a [diastolic heart failure] patient on dual or triple antihypertensive therapy who still had high blood pressure, I would not hesitate to put the patient on spironolactone if their renal function and potassium level allowed it. This treatment will reduce blood pressure and improve cardiac structure and function," said Dr. Pieske, professor and head of the department of cardiology at the Medical University of Graz, Austria.

But other experts who heard the results had doubts.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Dr. Anker advised waiting for results that are expected to come out next year from TOPCAT, a U.S. study of spironolactone in more than 3,500 patients with diastolic heart failure sponsored by the National Heart, Lung, and Blood Institute.

Aldo-CHF enrolled patients aged 50 years or older with New York Heart Association class II or III heart failure and a left ventricular ejection fraction of at least 50%. Patients also needed to have echocardiographic evidence of diastolic dysfunction, and a peak oxygen consumption (VO₂) of less than 25 mL/kg per minute. The study excluded patients with a serum potassium level of 5.1 mmol/L or higher, and those with an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m² or a serum creatinine greater than 1.8 mg/dL. The patients averaged 67 years old, about 86% had class II heart failure, their average ejection fraction was about 67%, and their average GFR was about 79 mL/min per 1.73 m².

The researchers randomized 213 patients to received 25 mg of spironolactone daily, and 209 control patients to placebo. Patients also received other medications, with about three-quarters on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, about three-quarters receiving a beta-blocker, and slightly more than half receiving a diuretic.

The study had two primary end points. After 12 months, patients on spironolactone had an average reduction in the E/é ratio of 0.6 (a 5% drop from baseline), compared with an average rise among the control patients of 0.8 (a 6% rise from baseline) for this surrogate measure of filling pressure, a significant between-group difference. The second primary end point was change in peak VO₂, and for this measure the two groups showed very similar changes over the 12 months of the study without a significant between-group difference.

Patients on spironolactone also had a significant reduction in average blood pressure of 8/2 mm Hg at 12 months compared with baseline, but the beneficial effect that spironolactone had on myocardial reverse remodeling reflected in the change in E/é occurred independent of the drug’s blood pressure effect, Dr. Pieske said.

Secondary end points that showed beneficial effects from spironolactone treatment included a small but significant increase in left ventricular ejection fraction, and a significant reduction in serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), a marker of heart failure severity. But patients on spironolactone also had an average 15-m reduction in their 6-minute walk distance, a significant drop.

"We saw consistent structural and functional remodeling effects from spironolactone, and except for left ventricular size, all of the other measures improved. But we saw no benefit on exercise capacity, New York Heart Association class, or quality of life," Dr. Pieske said. "Somehow, the beneficial effects on the heart did not translate into an improved situation."

While the overall safety profile of spironolactone treatment was good, the results showed a few possible areas of concern. In the spironolactone group, 36% of patients had worsening renal function, compared with 21% in the control arm, a significant difference; and the average GFR fell by about 7 mL/min per 1.73 m² with spironolactone, compared with no change in the control patients. The incidence of new or worsening anemia was 16% among the spironolactone patients and 9% in the controls, a significant difference. And twice as many patients on spironolactone had an increase in their serum potassium compared with the controls. However, the incidence of severe hyperkalemia was low and similar in both arms of the study.

"To our knowledge, increased anemia was not seen before" with spironolactone. "Maybe the anemia or a mild decrease in hemoglobin contributed" to the lack of an effect of treatment on exercise capacity, Dr. Pieske suggested.

Aldo-DHF was sponsored by the German government. Dr. Pieske said that he and his associates had no disclosures. Dr. Anker said that he has received consulting fees from Amgen, Bosch Healthcare, and other companies.

MUNICH – Results from the largest study to ever assess treatment with spironolactone in patients with diastolic heart failure showed clear indications that the drug exerted beneficial structural, hemodynamic, and physiologic effects with a generally reasonable safety profile.

But the mottled results also showed a puzzling lack of efficacy for other end points, and when coupled with some worrisome signs of harm, most physicians will probably reserve judgment on using spironolactone on patients with heart failure and preserved left ventricular ejection fraction until results from an even larger, clinical end point trial are available next year.

Mitchel L. Zoler/IMNG Medical Media

Based on the results, "spironolactone can be considered in patients with diastolic heart failure for improving cardiac function and blood pressure control," Dr. Burkert M. Pieske said at the annual congress of the European Society of Cardiology.

Moreover, spironolactone’s performance in the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial with 422 patients randomized to treatment with spironolactone or placebo gives the drug a unique position in the world of diastolic heart failure: Spironolactone is now the only drug with any sort of positive track record in a prospective controlled trial.

"I can’t give a general recommendation to use it because patients [on spironolactone in the trial] did not feel better" after a year on treatment, Dr. Pieske acknowledged in an interview. "But if I had a [diastolic heart failure] patient on dual or triple antihypertensive therapy who still had high blood pressure, I would not hesitate to put the patient on spironolactone if their renal function and potassium level allowed it. This treatment will reduce blood pressure and improve cardiac structure and function," said Dr. Pieske, professor and head of the department of cardiology at the Medical University of Graz, Austria.

But other experts who heard the results had doubts.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Dr. Anker advised waiting for results that are expected to come out next year from TOPCAT, a U.S. study of spironolactone in more than 3,500 patients with diastolic heart failure sponsored by the National Heart, Lung, and Blood Institute.

Aldo-CHF enrolled patients aged 50 years or older with New York Heart Association class II or III heart failure and a left ventricular ejection fraction of at least 50%. Patients also needed to have echocardiographic evidence of diastolic dysfunction, and a peak oxygen consumption (VO₂) of less than 25 mL/kg per minute. The study excluded patients with a serum potassium level of 5.1 mmol/L or higher, and those with an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m² or a serum creatinine greater than 1.8 mg/dL. The patients averaged 67 years old, about 86% had class II heart failure, their average ejection fraction was about 67%, and their average GFR was about 79 mL/min per 1.73 m².

The researchers randomized 213 patients to received 25 mg of spironolactone daily, and 209 control patients to placebo. Patients also received other medications, with about three-quarters on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, about three-quarters receiving a beta-blocker, and slightly more than half receiving a diuretic.

The study had two primary end points. After 12 months, patients on spironolactone had an average reduction in the E/é ratio of 0.6 (a 5% drop from baseline), compared with an average rise among the control patients of 0.8 (a 6% rise from baseline) for this surrogate measure of filling pressure, a significant between-group difference. The second primary end point was change in peak VO₂, and for this measure the two groups showed very similar changes over the 12 months of the study without a significant between-group difference.

Patients on spironolactone also had a significant reduction in average blood pressure of 8/2 mm Hg at 12 months compared with baseline, but the beneficial effect that spironolactone had on myocardial reverse remodeling reflected in the change in E/é occurred independent of the drug’s blood pressure effect, Dr. Pieske said.

Secondary end points that showed beneficial effects from spironolactone treatment included a small but significant increase in left ventricular ejection fraction, and a significant reduction in serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), a marker of heart failure severity. But patients on spironolactone also had an average 15-m reduction in their 6-minute walk distance, a significant drop.

"We saw consistent structural and functional remodeling effects from spironolactone, and except for left ventricular size, all of the other measures improved. But we saw no benefit on exercise capacity, New York Heart Association class, or quality of life," Dr. Pieske said. "Somehow, the beneficial effects on the heart did not translate into an improved situation."

While the overall safety profile of spironolactone treatment was good, the results showed a few possible areas of concern. In the spironolactone group, 36% of patients had worsening renal function, compared with 21% in the control arm, a significant difference; and the average GFR fell by about 7 mL/min per 1.73 m² with spironolactone, compared with no change in the control patients. The incidence of new or worsening anemia was 16% among the spironolactone patients and 9% in the controls, a significant difference. And twice as many patients on spironolactone had an increase in their serum potassium compared with the controls. However, the incidence of severe hyperkalemia was low and similar in both arms of the study.

"To our knowledge, increased anemia was not seen before" with spironolactone. "Maybe the anemia or a mild decrease in hemoglobin contributed" to the lack of an effect of treatment on exercise capacity, Dr. Pieske suggested.

Aldo-DHF was sponsored by the German government. Dr. Pieske said that he and his associates had no disclosures. Dr. Anker said that he has received consulting fees from Amgen, Bosch Healthcare, and other companies.

MUNICH  – Obesity is a strong predictor of atrial fibrillation in otherwise healthy fertile women, according to an analysis of a nationwide Danish registry.

The findings showed that obese women had a twofold increase in the risk of developing atrial fibrillation, compared with healthy-weight women. The risk nearly tripled in very obese women.

"This is just one more study to show that obesity is bad," said Dr. Miguel Quinones, the 2013 American College of Cardiology meeting chair, who was not involved in the study. He added that the study presented very strong data.

Previous studies have shown that obesity increases the risk of new-onset AF in patients with known risk factors, such as genetic predisposition, obstructive sleep apnea, and inflammation, said the authors. The study sheds light on yet another population where obesity increases the risk of AF, and it applies to a broader population, said Dr. Deniz Karasoy, who presented the study.

"Previous studies conducted on individuals with established risk factors for developing atrial fibrillation have demonstrated higher relative risk of new-onset AF in men compared to women," he said, in an interview. "Although we have not examined this specific association, we believe that this association is also valid regarding the obese men."

Obesity and atrial fibrillation are among the largest public health related challenges in the Western world, according to the authors.

Dr. Karasoy predicted an increasing prevalence of atrial fibrillation, and in more resistant forms, due to the increasing prevalence of obesity worldwide.

To slow the trend, pervasive primary prevention efforts, such as strategies that would promote weight loss, are needed, said Dr. Karasoy, a research fellow at Cardiovascular Research Center Gentofte, in Denmark.

The study was based on nationwide registry of about 271,000 healthy Danish women, between the ages of 20 and 50 years, who had given birth during 2004-2009.

The women were followed for an average of 4.6 years. Researchers broke down the cohort to five groups: underweight (body mass index below 18.5 kg/m²); normal weight (BMI of 18.5-25); overweight (BMI: 25-30); obese (BMI: 30-35); and extremely obese (BMI greater than 35).

During this period, researchers identified 110 new cases of AF.

Overall AF incidence rate was 9.3 per 100,000 person-years. For normal weight, overweight, obese and very obese women, AF incidence rates were 7.4, 8.5, 15.8, and 27.3 per 100,000 person-years, respectively.

After adjustment for age, comorbidity, medication and smoking, the results showed that obese women had a twofold increase in the risk of developing AF, compared with healthy weight women (hazard ratio, 2.04). That risk more than tripled in very obese women (HR, 3.50). No significant risk increase was observed in the overweight group.

The study did not address obesity’s mechanism of action on atrial fibrillation.

Dr. Karasoy and Dr. Quinones said that they had no relevant disclosures.

MUNICH  – Obesity is a strong predictor of atrial fibrillation in otherwise healthy fertile women, according to an analysis of a nationwide Danish registry.

The findings showed that obese women had a twofold increase in the risk of developing atrial fibrillation, compared with healthy-weight women. The risk nearly tripled in very obese women.

"This is just one more study to show that obesity is bad," said Dr. Miguel Quinones, the 2013 American College of Cardiology meeting chair, who was not involved in the study. He added that the study presented very strong data.

Previous studies have shown that obesity increases the risk of new-onset AF in patients with known risk factors, such as genetic predisposition, obstructive sleep apnea, and inflammation, said the authors. The study sheds light on yet another population where obesity increases the risk of AF, and it applies to a broader population, said Dr. Deniz Karasoy, who presented the study.

"Previous studies conducted on individuals with established risk factors for developing atrial fibrillation have demonstrated higher relative risk of new-onset AF in men compared to women," he said, in an interview. "Although we have not examined this specific association, we believe that this association is also valid regarding the obese men."

Obesity and atrial fibrillation are among the largest public health related challenges in the Western world, according to the authors.

Dr. Karasoy predicted an increasing prevalence of atrial fibrillation, and in more resistant forms, due to the increasing prevalence of obesity worldwide.

To slow the trend, pervasive primary prevention efforts, such as strategies that would promote weight loss, are needed, said Dr. Karasoy, a research fellow at Cardiovascular Research Center Gentofte, in Denmark.

The study was based on nationwide registry of about 271,000 healthy Danish women, between the ages of 20 and 50 years, who had given birth during 2004-2009.

The women were followed for an average of 4.6 years. Researchers broke down the cohort to five groups: underweight (body mass index below 18.5 kg/m²); normal weight (BMI of 18.5-25); overweight (BMI: 25-30); obese (BMI: 30-35); and extremely obese (BMI greater than 35).

During this period, researchers identified 110 new cases of AF.

Overall AF incidence rate was 9.3 per 100,000 person-years. For normal weight, overweight, obese and very obese women, AF incidence rates were 7.4, 8.5, 15.8, and 27.3 per 100,000 person-years, respectively.

After adjustment for age, comorbidity, medication and smoking, the results showed that obese women had a twofold increase in the risk of developing AF, compared with healthy weight women (hazard ratio, 2.04). That risk more than tripled in very obese women (HR, 3.50). No significant risk increase was observed in the overweight group.

The study did not address obesity’s mechanism of action on atrial fibrillation.

Dr. Karasoy and Dr. Quinones said that they had no relevant disclosures.

MUNICH  – Obesity is a strong predictor of atrial fibrillation in otherwise healthy fertile women, according to an analysis of a nationwide Danish registry.

The findings showed that obese women had a twofold increase in the risk of developing atrial fibrillation, compared with healthy-weight women. The risk nearly tripled in very obese women.

"This is just one more study to show that obesity is bad," said Dr. Miguel Quinones, the 2013 American College of Cardiology meeting chair, who was not involved in the study. He added that the study presented very strong data.

Previous studies have shown that obesity increases the risk of new-onset AF in patients with known risk factors, such as genetic predisposition, obstructive sleep apnea, and inflammation, said the authors. The study sheds light on yet another population where obesity increases the risk of AF, and it applies to a broader population, said Dr. Deniz Karasoy, who presented the study.

"Previous studies conducted on individuals with established risk factors for developing atrial fibrillation have demonstrated higher relative risk of new-onset AF in men compared to women," he said, in an interview. "Although we have not examined this specific association, we believe that this association is also valid regarding the obese men."

Obesity and atrial fibrillation are among the largest public health related challenges in the Western world, according to the authors.

Dr. Karasoy predicted an increasing prevalence of atrial fibrillation, and in more resistant forms, due to the increasing prevalence of obesity worldwide.

To slow the trend, pervasive primary prevention efforts, such as strategies that would promote weight loss, are needed, said Dr. Karasoy, a research fellow at Cardiovascular Research Center Gentofte, in Denmark.

The study was based on nationwide registry of about 271,000 healthy Danish women, between the ages of 20 and 50 years, who had given birth during 2004-2009.

The women were followed for an average of 4.6 years. Researchers broke down the cohort to five groups: underweight (body mass index below 18.5 kg/m²); normal weight (BMI of 18.5-25); overweight (BMI: 25-30); obese (BMI: 30-35); and extremely obese (BMI greater than 35).

During this period, researchers identified 110 new cases of AF.

Overall AF incidence rate was 9.3 per 100,000 person-years. For normal weight, overweight, obese and very obese women, AF incidence rates were 7.4, 8.5, 15.8, and 27.3 per 100,000 person-years, respectively.

After adjustment for age, comorbidity, medication and smoking, the results showed that obese women had a twofold increase in the risk of developing AF, compared with healthy weight women (hazard ratio, 2.04). That risk more than tripled in very obese women (HR, 3.50). No significant risk increase was observed in the overweight group.

The study did not address obesity’s mechanism of action on atrial fibrillation.

Dr. Karasoy and Dr. Quinones said that they had no relevant disclosures.

MUNICH – Gender differences in comorbidities affected the medications prescribed to men and women hospitalized with acute heart failure, although their in-hospital mortality rate remained similar, according to a retrospective analysis of nearly 5,000 hospital charts.

The study showed that men who were hospitalized with acute heart failure (AHF) were more likely to receive beta-blockers and aspirin than were women. Meanwhile, women were more likely to be obese, have diabetes, or have atrial fibrillation.

"Perhaps there are differences in the pathophysiology of AHF between women and men, which should be taken into account in order to achieve gender-tailored management," said Dr. John Parissis, who presented the study at the annual congress of the European Society of Cardiology.

The study was a subanalysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF), a chart audit survey of 4,953 patients hospitalized for AHF in 666 hospitals in nine countries (France, Germany, Spain, Italy, Greece, United Kingdom, Turkey, Australia, and Mexico.)

Women made up 37% of the patients, consistent with ratios in other registries, said Dr. Parissis of Attikon University Hospital, Greece. They presented with AHF at an older age and had higher rates of de novo heart failure. They were also half as likely as were men to present with cardiogenic shock, but more than twice as likely to have right heart failure.

The study showed that women hospitalized with AHF had a higher prevalence of diabetes (47% v. 43%), obesity (30% v. 25%), anemia (17% v. 13%), atrial fibrillation or flutter (49% v. 42%), dementia (6% v. 3%), and depression (11% v. 7%), compared with men.

Meanwhile, men had a higher prevalence of chronic obstructive pulmonary disease (COPD) and asthma (27% v. 21%), and coronary artery disease (CAD) (35% v. 24%) compared with women.

Upon admission, women were less likely than were men to receive aspirin, clopidogrel, and beta-blockers, because of their comorbidities and lower rates of CAD. But compared with men, they were more likely to be on angiotensin receptors blockers and digitalis treatment, because of higher incidence of atrial fibrillation, according to the investigators.

There were no significant differences in use of ACE inhibitors, diuretics, and nitrates between genders, the analysis showed.

Both genders received continuous positive airway pressure (CPAP) and mechanical ventilation. Fewer women, however, were supported by intra-aortic balloon pump (IABP), underwent percutaneous coronary intervention, or had coronary artery bypass graft surgery.

In addition, in-hospital mortality was similar between genders (10.5% for men vs 11.1% for women). "The presence of higher ejection fraction and less CAD in women may positively affect survival in women," said Dr. Parissis.

But, "the existence of other serious comorbidities and underprescription of life saving medications such as beta-blockers may counteract this positive effect on their in-hospital survival," he added. "This point may explain the similar mortality rate between genders."

At discharge, the proportion of patients treated with medications increased. Nevertheless, the differences between genders remained significant, the authors wrote.

The differences in treatment call for "a more intensive implementation of heart failure guidelines to optimize life saving medications, especially in women," said Dr. Parissis.

Dr. Parissis is a member of the ALARM-HF Steering Committee and presented the study on the committee’s behalf. He said he had received research grants from Abbott and Orion Pharma.

MUNICH – Gender differences in comorbidities affected the medications prescribed to men and women hospitalized with acute heart failure, although their in-hospital mortality rate remained similar, according to a retrospective analysis of nearly 5,000 hospital charts.

The study showed that men who were hospitalized with acute heart failure (AHF) were more likely to receive beta-blockers and aspirin than were women. Meanwhile, women were more likely to be obese, have diabetes, or have atrial fibrillation.

"Perhaps there are differences in the pathophysiology of AHF between women and men, which should be taken into account in order to achieve gender-tailored management," said Dr. John Parissis, who presented the study at the annual congress of the European Society of Cardiology.

The study was a subanalysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF), a chart audit survey of 4,953 patients hospitalized for AHF in 666 hospitals in nine countries (France, Germany, Spain, Italy, Greece, United Kingdom, Turkey, Australia, and Mexico.)

Women made up 37% of the patients, consistent with ratios in other registries, said Dr. Parissis of Attikon University Hospital, Greece. They presented with AHF at an older age and had higher rates of de novo heart failure. They were also half as likely as were men to present with cardiogenic shock, but more than twice as likely to have right heart failure.

The study showed that women hospitalized with AHF had a higher prevalence of diabetes (47% v. 43%), obesity (30% v. 25%), anemia (17% v. 13%), atrial fibrillation or flutter (49% v. 42%), dementia (6% v. 3%), and depression (11% v. 7%), compared with men.

Meanwhile, men had a higher prevalence of chronic obstructive pulmonary disease (COPD) and asthma (27% v. 21%), and coronary artery disease (CAD) (35% v. 24%) compared with women.

Upon admission, women were less likely than were men to receive aspirin, clopidogrel, and beta-blockers, because of their comorbidities and lower rates of CAD. But compared with men, they were more likely to be on angiotensin receptors blockers and digitalis treatment, because of higher incidence of atrial fibrillation, according to the investigators.

There were no significant differences in use of ACE inhibitors, diuretics, and nitrates between genders, the analysis showed.

Both genders received continuous positive airway pressure (CPAP) and mechanical ventilation. Fewer women, however, were supported by intra-aortic balloon pump (IABP), underwent percutaneous coronary intervention, or had coronary artery bypass graft surgery.

In addition, in-hospital mortality was similar between genders (10.5% for men vs 11.1% for women). "The presence of higher ejection fraction and less CAD in women may positively affect survival in women," said Dr. Parissis.

But, "the existence of other serious comorbidities and underprescription of life saving medications such as beta-blockers may counteract this positive effect on their in-hospital survival," he added. "This point may explain the similar mortality rate between genders."

At discharge, the proportion of patients treated with medications increased. Nevertheless, the differences between genders remained significant, the authors wrote.

The differences in treatment call for "a more intensive implementation of heart failure guidelines to optimize life saving medications, especially in women," said Dr. Parissis.

Dr. Parissis is a member of the ALARM-HF Steering Committee and presented the study on the committee’s behalf. He said he had received research grants from Abbott and Orion Pharma.

MUNICH – Gender differences in comorbidities affected the medications prescribed to men and women hospitalized with acute heart failure, although their in-hospital mortality rate remained similar, according to a retrospective analysis of nearly 5,000 hospital charts.

The study showed that men who were hospitalized with acute heart failure (AHF) were more likely to receive beta-blockers and aspirin than were women. Meanwhile, women were more likely to be obese, have diabetes, or have atrial fibrillation.

"Perhaps there are differences in the pathophysiology of AHF between women and men, which should be taken into account in order to achieve gender-tailored management," said Dr. John Parissis, who presented the study at the annual congress of the European Society of Cardiology.

The study was a subanalysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF), a chart audit survey of 4,953 patients hospitalized for AHF in 666 hospitals in nine countries (France, Germany, Spain, Italy, Greece, United Kingdom, Turkey, Australia, and Mexico.)

Women made up 37% of the patients, consistent with ratios in other registries, said Dr. Parissis of Attikon University Hospital, Greece. They presented with AHF at an older age and had higher rates of de novo heart failure. They were also half as likely as were men to present with cardiogenic shock, but more than twice as likely to have right heart failure.

The study showed that women hospitalized with AHF had a higher prevalence of diabetes (47% v. 43%), obesity (30% v. 25%), anemia (17% v. 13%), atrial fibrillation or flutter (49% v. 42%), dementia (6% v. 3%), and depression (11% v. 7%), compared with men.

Meanwhile, men had a higher prevalence of chronic obstructive pulmonary disease (COPD) and asthma (27% v. 21%), and coronary artery disease (CAD) (35% v. 24%) compared with women.

Upon admission, women were less likely than were men to receive aspirin, clopidogrel, and beta-blockers, because of their comorbidities and lower rates of CAD. But compared with men, they were more likely to be on angiotensin receptors blockers and digitalis treatment, because of higher incidence of atrial fibrillation, according to the investigators.

There were no significant differences in use of ACE inhibitors, diuretics, and nitrates between genders, the analysis showed.

Both genders received continuous positive airway pressure (CPAP) and mechanical ventilation. Fewer women, however, were supported by intra-aortic balloon pump (IABP), underwent percutaneous coronary intervention, or had coronary artery bypass graft surgery.

In addition, in-hospital mortality was similar between genders (10.5% for men vs 11.1% for women). "The presence of higher ejection fraction and less CAD in women may positively affect survival in women," said Dr. Parissis.

But, "the existence of other serious comorbidities and underprescription of life saving medications such as beta-blockers may counteract this positive effect on their in-hospital survival," he added. "This point may explain the similar mortality rate between genders."

At discharge, the proportion of patients treated with medications increased. Nevertheless, the differences between genders remained significant, the authors wrote.

The differences in treatment call for "a more intensive implementation of heart failure guidelines to optimize life saving medications, especially in women," said Dr. Parissis.

Dr. Parissis is a member of the ALARM-HF Steering Committee and presented the study on the committee’s behalf. He said he had received research grants from Abbott and Orion Pharma.

MUNICH – Renal denervation remains investigational in the United States, where a large clinical trial testing its safety and efficacy is now in progress.

But in Europe, Australia, and elsewhere, renal denervation – an intravascular procedure that zaps the sympathetic innervation in a patient’s renal arteries with a few pulses of radiofrequency energy – is rapidly becoming the big new thing for treating patients with drug-resistant hypertension since marketing of a denervation catheter began in April 2010.

As of last spring, Medtronic, the company that sells the only renal denervation (RD) catheter currently commercially available, estimated that the 5,000th patient had been treated by RD, although Dr. Michael Böhm, who oversees what might be the most active RD program in the world, recently put his estimate upwards of 10,000 patients treated worldwide. Among the smaller number of closely followed patients included in this experience with reported outcomes data, perhaps 300-500 patients, the results have been striking: A drop in office blood pressure on the order of 28/10 mm Hg in patients who began treatment with pressures in the 180/100 mm Hg ballpark (despite treatment with as many as six antihypertensive drugs), that has been durable over follow-up as long as 36 months, with response rates among patients that rise over time and run over 90% once patients are followed longer than a year, and uniform reports of good safety during 6-36 months’ follow-up, with no evidence of impaired renal function or arterial sclerosis over time or other untoward effects.

And now emerging in new reports, both recently published and presented at the meeting in August, are hints of several effects beyond simple blood pressure reduction that hold promise for expanding the application of RD beyond just antihypertensive treatment and broadening the recognized benefits of this treatment.

RD "is a transformative area for treating hypertension, and now heart failure" and other disorders, commented Dr. Adrian Brady, a cardiologist and hypertension specialist in Glasgow, Scotland.

More Than Just Blood Pressure

Among the newest findings was a report on a small, controlled study with 43 normotensive patients with New York Heart Association class III or IV heart failure that showed RD could significantly raise left ventricular ejection fraction, reduce left ventricular end-systolic and end-diastolic volume index, and cut serum levels of brain natriuretic peptide during 12 months of follow-up. RD had these positive effects on surrogate markers of heart failure severity without causing hypotension or other adverse effects, and the treatment also cut the rate of heart failure hospitalizations over 12 months by more than half, although the study wasn’t powered to examine this end point, reported Dr. Milos Táborský, a cardiologist at Olomouc University Hospital in the Czech Republic.

For example, left ventricular ejection fraction rose from an average of 25% at baseline to an average of 31% 12 months after RD, compared with a 2% change in the control patients, a statistically significant difference, Dr. Táborský said.

In short, RD worked in normotensive patients with heart failure similar to a beta-blocker drug that cuts neurohormonal activation, commented Dr. José-Ramon Gonzalez-Juanatey, director of the cardiovascular department at the University Hospital of Santiago de Compostela in Spain. "This technique opens a new era in treating heart failure by decreasing sympathetic tone," he said.

In a similar vein, results reported at the meeting from another small, controlled study with 27 treatment-resistant hypertensive patients showed that by 6 months after RD, the treatment had significantly improved aortic augmentation index and aortic pulse-wave velocity, two markers of central vascular stiffness and central blood pressure. The average 1 m/sec improvement seen in aortic pulse-wave velocity 6 months after RD, reflecting a roughly 10% reduction in aortic stiffness, corresponds to about a10-year drop in the patients’ vascular age, said Klaas F. Franzen, a researcher at Schleswig-Holstein University Hospital in Lübeck, Germany.

"The idea is that by reducing whole-body sympathetic activity, you reduce vasoconstriction, and induce vasodilation in the renal arteries and central arteries," commented Dr. Felix Mahfoud, a cardiologist at Saarland University Hospital in Homburg, Germany.

The benefits from RD are not just cardiovascular. Another report at the meeting came from serial psychologic tests administered before and after 119 patients with drug-resistant hypertension underwent RD. In addition to producing an average drop in office blood pressure of 20/10 mm Hg, at both 3 and 6 months after treatment, RD also led to statistically and clinically significant drops in stress reaction, as measured on the Wiener Determination Task. In addition, among the roughly 20% of patients in the group of 119 who had clinically meaningful levels of anxiety or depression at baseline, RD also produced statistically and clinically significant falls in both anxiety and depression at both 3 and 6 months after treatment, reported Denise Fischer, Ph.D., a psychologist at Saarland University Hospital.

Another facet of her study looked at headache severity and found that at 3 and 6 months following RD all patients had statistically significant drops in headache intensity, and among the 20% of patients who entered the study with headaches self-rated as worse than 4 on a 0-10 visual analog scale, headache intensity fell from an average of about 8 before treatment to an average of less than 4 at 6 months after RD, Dr. Fischer said.

Follow-Ups to 18 Months, and Beyond

The most thorough assessment so far of RD as an antihypertensive treatment came in the Symplicity HTN-2 trial, a multicenter, multinational trial that randomized 106 patients with drug-resistant hypertension. In the 6-month results from the study, the primary end point showed that among 49 patients who underwent RD, office blood pressure fell by an average of 32/12 mm Hg, compared with virtually no change among 51 controls (Lancet 2010;376:1903-9).

During the August meeting, researchers from the study reported follow-up data, which included 18-month results from 43 patients in the original intervention arm of the study and from an additional 31 patients originally randomized to the control arm but who crossed over to RD treatment after the first 6 months.

The 18-month results showed stability of the initial blood pressure reduction in both subgroups of patients, with average reductions in office blood pressure remaining at 32/12 mm Hg compared with baseline in the 43 patients from the original intervention arm, and an average 28/11 mm Hg cut in office pressure in the 31 crossover patients, compared with their baseline levels, said Dr. Murray D. Esler, professor of medicine at Monash University in Melbourne, and lead investigator for the study. Patients in the initially treated arm also had an average 7 beats/min reduction in heart rate, compared with baseline that was statistically significant.

"In our experience at Saarland University Hospital with more than 400 patients, they all achieved a blood pressure response" following renal denervation.   --Dr. Michael Böhm.

For safety, the 18 month results showed "no signal that renal function was harmed," he said. One patient had a renal-artery dissection early in the study, caused by the stiff catheter tip used at the study’s start but since replaced with a more flexible tip, Dr. Esler said. Other safety events during follow-up included one episode of hypotension that required hospitalization, one "mild" incidence of "transient" acute renal failure, and two deaths unrelated to RD.

Dr. Esler and his collaborators also cited the 36-month follow-up results on 24 patients from the initial, uncontrolled study of RD using the Symplicity catheter, the Symplicity HTN1 study (Lancet 2009;373:1275-81). These patients continue to show a durable blood pressure response and no signs of adverse effects, renal or otherwise, in this small number of patients followed for a prolonged period, said Dr. Böhm, director of internal medicine at Saarland University Hospital. (The 3-year follow-up of these 24 patients was first reported last March at the annual scientific session of the American College of Cardiology.) A very encouraging finding was that among the small number of patients followed this long, the percentage of patients with clinically important blood pressure drops continued to accumulate, so that at 36 months 99% of treated patients responded, Dr. Böhm said.

"In our experience at Saarland University Hospital with more than 400 patients, they all achieved a blood pressure response" following RD, he said. "How long will [their response] last? No one knows, but if it lasts for at least 3 years, you can then justify a redo," a repeat treatment, although he also cautioned that so far, he knows of no patient who has undergone RD a second time.

In addition to the new evidence for pleiotropic effects from RD reported at the meeting, recently published reports from small studies provided preliminary documentation of other possible benefits. For example:

• RD led to a significantly reduced prevalence of albuminuria during 6-month follow-up in a study with 88 treated patients with drug-resistant hypertension (Hypertension 2012;60:419-24).

• RD led to significant improvements in glucose metabolism and insulin sensitivity during 3-month follow-up in a study with 37 treated patients with drug-resistant hypertension (Circulation 2011;123:1940-6).

• RD produced a reduction in blood pressure during exercise without affecting chronotropic competence during 3-month follow-up of 37 treated patients with drug-resistant hypertension (J. Amer. Coll. Cardiol. 2011;58:1176-83).

Novel Catheter May Speed Procedure Times

The Symplicity renal denervation catheter from Medtronic is not the only such device in clinical use. At the meeting, researchers reported 3-month follow-up results from a series of 46 patients with drug-resistant hypertension treated with a multielectrode catheter from St. Jude at four centers in Greece and Australia.

The main difference between the St. Jude EnligHTN device, which has four separate electrodes at its tip, and the Medtronic device, with a single electrode, is that the St. Jude device can denervate a renal artery with a single placement, as opposed to the four different placements, with rotation, used for the Medtronic device, meaning less arterial manipulation. Whether this will produce any discernable difference in safety, efficacy, or procedure time remains unclear.

The study enrolled patients with persistent hypertension, with an office systolic pressure above 160 mm Hg (150 mm Hg in patients with diabetes), despite treatment with at least three antihypertensive drugs, including at least one diuretic (similar enrollment criteria as the Symplicity studies). The patients’ averaged 60 years old, and their pressures averaged 176/98 mm Hg.

Average procedure time was 34 minutes, reported Dr. Costas Tsioufis, a professor of cardiology at the University of Athens, which may be modestly faster than the usual procedure time using the Symplicity catheter, which operators often estimate to require 40-50 minutes. Data from a series of 344 patients treated with the Symplicity catheter at Saarland University Hospital in Homburg showed an average procedure time of 44 minutes, said Dr. Felix Mahfoud, a cardiologist there.

Renal Denervation Shown Highly Cost Effective

Although renal denervation has an estimated up-front cost of about $12,500, the long-term benefits of the blood pressure reduction it usually produces are so potent that the treatment winds up costing about $3,000 for each additional quality-adjusted life-year it confers on patients, based on a cost-effectiveness analysis of data from the Symplicity HTN-2 trial.

This level of cost effectiveness is "more than an order of magnitude below the recognized threshold of $50,000/QALY [quality-adjusted life-year]," and provides fairly compelling evidence that "catheter-based renal denervation therapy is a cost-effective treatment strategy for resistant hypertension," Dr. Benjamin P. Geisler and his associates wrote in a report published online in September (J. Am. Coll. Cardiol. 2012 [doi:10.1016/j.jacc.2012.07.029]).

They based their cost-effectiveness model on data collected in the Symplicity HTN-2 trial (Lancet 2010;376:1903-9), described in the main story.

"When you look at societal decision making – how much a society is willing to pay for improved quality of life and increased duration of life – the recognized threshold in the United States is a cost of $50,000 or less/QALY. That means that $3,000/QALY is highly cost effective," said Jan B. Pietzsch, Ph.D., the lead investigator of the analysis. "It’s a very low incremental cost-effectiveness ratio compared with other innovative treatments," he said in an interview.

The model that Dr. Geisler, Dr. Pietzsch, and their associates produced estimated a sizeable impact that this blood-pressure reduction would have on improved survival, and on a reduced incidence of several cardiovascular disease end points presuming that the reduced blood pressure was sustained for 10 years, or for the rest of a patient’s life. For example, they estimated that over the 10 years following treatment, renal denervation would cut the incidence of stroke by 3.4 percentage points, the rate of coronary heart disease by 5.4 percentage points, the rate of cardiovascular mortality by 3.8 percentage points, and all-cause death by 3.5 percentage points. They also calculated an increase in median survival of 1.3 years.

They calculated a discounted, lifetime incremental cost-effectiveness ratio of $3,071/QALY. In addition, they found this incremental cost per quality-adjusted life-year was "quite robust" across a range of stating blood pressures, said Dr. Pietzsch, president of Wing Tech, a consulting company based in the United States and Germany.

At starting blood pressures of less than 172 mm Hg, renal denervation was actually cost saving. At a baseline pressure of 172 mm Hg or greater the cost per QALY increased steadily with baseline pressure, to a maximum or about $7,000/QALY in patients who had a systolic blood pressure of 200 mm Hg at the time they underwent renal denervation.

Dr. Pietzsch, Dr. Geisler, and another coauthors work for Wing Tech Inc., which provided consultant services to Medtronic Ardian to construct this health-economic model. (Medtronic Ardian is the company that markets the Symplicity catheter.) Another coauthor received salary support from Medtronic Ardian, a second coauthor received consultancy payments and travel expenses from Medtronic Ardian, and a third coauthor serves on the board of a group that received funding from Medtronic.

Official Recommendations Start Mainstreaming RD

The strikingly successful track record of RD so far led the European Society of Hypertension to last May issue recommendations on using the treatment in routine practice (J. Hypertens. 2012;30:837-41). The Society endorsed routinely treating patients who match the criteria for having dangerously high, treatment-resistant hypertension similar to the criteria that have been used in the Symplicity trials and other recent RD studies.

But investigator-driven research protocols at several European centers are now even moving beyond these criteria, as patients with milder levels of drug-resistant hypertension also clamor for RD.

"We are moving to treat less severe hypertension, but within a clinical study," said Dr. Roland E. Schmieder, professor of medicine and vice chairman of nephrology and hypertension at the University Hospital in Erlangen, Germany. He also stressed that these studies will still continue to exclude patients with impaired renal function at baseline. "Everyone in Germany agrees the focus must be on treatment-resistant hypertension, when physicians feel they have no other choice to offer patients. But as you move into patients with less severe hypertension you increase the need for hard–end-point trials" that are better able to prove an overall net benefit to patients from RD, he said in an interview.

"We have a lot of safety data" for RD, but long-term follow-up is still limited. "We don’t have experience with what happens when [RD-treated] patients become critically ill. They may still need some renal innervation to prevent traumatic shock," he said. "There are still unanswered safety questions, but so far the main concern, renal function, has improved" following RD.

Another caution about treating milder hypertension is that the treatment effect will generally be smaller than what’s seen in patients with more severe hypertension.

But Dr. Schmieder shares the enthusiasm of many of his colleagues who believe they now have an effective new tool for treating hypertension.

"Renal denervation is a very important step forward, because hypertension is killer No. 1 worldwide, and no new antihypertensive drugs are on the horizon," he said. We don’t expect any new antihypertensive drugs for at least the next 10 years. To have this new option is important, both for treating patients and to help increase awareness of the disease."

The Symplicity trials have been sponsored by Ardian, which first developed the Symplicity renal denervation catheter, and by Medtronic, which acquired Ardian and now produces and markets the catheter. Dr. Brady, Dr. Táborský, Mr. Franzen, Dr. Fischer, and Dr. Gonzalez-Juanatey did not have any relevant disclosures. Dr. Böhm, Dr. Esler, Dr. Mahfoud, and Dr. Schmieder said that they have received research, travel, and consultancy funding from Medtronic and Ardian. Dr. Mahfoud said that he has also received research funding from Vessix Vascular and ReCor Medical Technology, companies that are developing other devices for renal denervation.

MUNICH – Renal denervation remains investigational in the United States, where a large clinical trial testing its safety and efficacy is now in progress.

But in Europe, Australia, and elsewhere, renal denervation – an intravascular procedure that zaps the sympathetic innervation in a patient’s renal arteries with a few pulses of radiofrequency energy – is rapidly becoming the big new thing for treating patients with drug-resistant hypertension since marketing of a denervation catheter began in April 2010.

As of last spring, Medtronic, the company that sells the only renal denervation (RD) catheter currently commercially available, estimated that the 5,000th patient had been treated by RD, although Dr. Michael Böhm, who oversees what might be the most active RD program in the world, recently put his estimate upwards of 10,000 patients treated worldwide. Among the smaller number of closely followed patients included in this experience with reported outcomes data, perhaps 300-500 patients, the results have been striking: A drop in office blood pressure on the order of 28/10 mm Hg in patients who began treatment with pressures in the 180/100 mm Hg ballpark (despite treatment with as many as six antihypertensive drugs), that has been durable over follow-up as long as 36 months, with response rates among patients that rise over time and run over 90% once patients are followed longer than a year, and uniform reports of good safety during 6-36 months’ follow-up, with no evidence of impaired renal function or arterial sclerosis over time or other untoward effects.

And now emerging in new reports, both recently published and presented at the meeting in August, are hints of several effects beyond simple blood pressure reduction that hold promise for expanding the application of RD beyond just antihypertensive treatment and broadening the recognized benefits of this treatment.

RD "is a transformative area for treating hypertension, and now heart failure" and other disorders, commented Dr. Adrian Brady, a cardiologist and hypertension specialist in Glasgow, Scotland.

More Than Just Blood Pressure

Among the newest findings was a report on a small, controlled study with 43 normotensive patients with New York Heart Association class III or IV heart failure that showed RD could significantly raise left ventricular ejection fraction, reduce left ventricular end-systolic and end-diastolic volume index, and cut serum levels of brain natriuretic peptide during 12 months of follow-up. RD had these positive effects on surrogate markers of heart failure severity without causing hypotension or other adverse effects, and the treatment also cut the rate of heart failure hospitalizations over 12 months by more than half, although the study wasn’t powered to examine this end point, reported Dr. Milos Táborský, a cardiologist at Olomouc University Hospital in the Czech Republic.

For example, left ventricular ejection fraction rose from an average of 25% at baseline to an average of 31% 12 months after RD, compared with a 2% change in the control patients, a statistically significant difference, Dr. Táborský said.

In short, RD worked in normotensive patients with heart failure similar to a beta-blocker drug that cuts neurohormonal activation, commented Dr. José-Ramon Gonzalez-Juanatey, director of the cardiovascular department at the University Hospital of Santiago de Compostela in Spain. "This technique opens a new era in treating heart failure by decreasing sympathetic tone," he said.

In a similar vein, results reported at the meeting from another small, controlled study with 27 treatment-resistant hypertensive patients showed that by 6 months after RD, the treatment had significantly improved aortic augmentation index and aortic pulse-wave velocity, two markers of central vascular stiffness and central blood pressure. The average 1 m/sec improvement seen in aortic pulse-wave velocity 6 months after RD, reflecting a roughly 10% reduction in aortic stiffness, corresponds to about a10-year drop in the patients’ vascular age, said Klaas F. Franzen, a researcher at Schleswig-Holstein University Hospital in Lübeck, Germany.

"The idea is that by reducing whole-body sympathetic activity, you reduce vasoconstriction, and induce vasodilation in the renal arteries and central arteries," commented Dr. Felix Mahfoud, a cardiologist at Saarland University Hospital in Homburg, Germany.

The benefits from RD are not just cardiovascular. Another report at the meeting came from serial psychologic tests administered before and after 119 patients with drug-resistant hypertension underwent RD. In addition to producing an average drop in office blood pressure of 20/10 mm Hg, at both 3 and 6 months after treatment, RD also led to statistically and clinically significant drops in stress reaction, as measured on the Wiener Determination Task. In addition, among the roughly 20% of patients in the group of 119 who had clinically meaningful levels of anxiety or depression at baseline, RD also produced statistically and clinically significant falls in both anxiety and depression at both 3 and 6 months after treatment, reported Denise Fischer, Ph.D., a psychologist at Saarland University Hospital.

Another facet of her study looked at headache severity and found that at 3 and 6 months following RD all patients had statistically significant drops in headache intensity, and among the 20% of patients who entered the study with headaches self-rated as worse than 4 on a 0-10 visual analog scale, headache intensity fell from an average of about 8 before treatment to an average of less than 4 at 6 months after RD, Dr. Fischer said.

Follow-Ups to 18 Months, and Beyond

The most thorough assessment so far of RD as an antihypertensive treatment came in the Symplicity HTN-2 trial, a multicenter, multinational trial that randomized 106 patients with drug-resistant hypertension. In the 6-month results from the study, the primary end point showed that among 49 patients who underwent RD, office blood pressure fell by an average of 32/12 mm Hg, compared with virtually no change among 51 controls (Lancet 2010;376:1903-9).

During the August meeting, researchers from the study reported follow-up data, which included 18-month results from 43 patients in the original intervention arm of the study and from an additional 31 patients originally randomized to the control arm but who crossed over to RD treatment after the first 6 months.

The 18-month results showed stability of the initial blood pressure reduction in both subgroups of patients, with average reductions in office blood pressure remaining at 32/12 mm Hg compared with baseline in the 43 patients from the original intervention arm, and an average 28/11 mm Hg cut in office pressure in the 31 crossover patients, compared with their baseline levels, said Dr. Murray D. Esler, professor of medicine at Monash University in Melbourne, and lead investigator for the study. Patients in the initially treated arm also had an average 7 beats/min reduction in heart rate, compared with baseline that was statistically significant.

"In our experience at Saarland University Hospital with more than 400 patients, they all achieved a blood pressure response" following renal denervation.   --Dr. Michael Böhm.

For safety, the 18 month results showed "no signal that renal function was harmed," he said. One patient had a renal-artery dissection early in the study, caused by the stiff catheter tip used at the study’s start but since replaced with a more flexible tip, Dr. Esler said. Other safety events during follow-up included one episode of hypotension that required hospitalization, one "mild" incidence of "transient" acute renal failure, and two deaths unrelated to RD.

Dr. Esler and his collaborators also cited the 36-month follow-up results on 24 patients from the initial, uncontrolled study of RD using the Symplicity catheter, the Symplicity HTN1 study (Lancet 2009;373:1275-81). These patients continue to show a durable blood pressure response and no signs of adverse effects, renal or otherwise, in this small number of patients followed for a prolonged period, said Dr. Böhm, director of internal medicine at Saarland University Hospital. (The 3-year follow-up of these 24 patients was first reported last March at the annual scientific session of the American College of Cardiology.) A very encouraging finding was that among the small number of patients followed this long, the percentage of patients with clinically important blood pressure drops continued to accumulate, so that at 36 months 99% of treated patients responded, Dr. Böhm said.

"In our experience at Saarland University Hospital with more than 400 patients, they all achieved a blood pressure response" following RD, he said. "How long will [their response] last? No one knows, but if it lasts for at least 3 years, you can then justify a redo," a repeat treatment, although he also cautioned that so far, he knows of no patient who has undergone RD a second time.

In addition to the new evidence for pleiotropic effects from RD reported at the meeting, recently published reports from small studies provided preliminary documentation of other possible benefits. For example:

• RD led to a significantly reduced prevalence of albuminuria during 6-month follow-up in a study with 88 treated patients with drug-resistant hypertension (Hypertension 2012;60:419-24).

• RD led to significant improvements in glucose metabolism and insulin sensitivity during 3-month follow-up in a study with 37 treated patients with drug-resistant hypertension (Circulation 2011;123:1940-6).

• RD produced a reduction in blood pressure during exercise without affecting chronotropic competence during 3-month follow-up of 37 treated patients with drug-resistant hypertension (J. Amer. Coll. Cardiol. 2011;58:1176-83).

Novel Catheter May Speed Procedure Times

The Symplicity renal denervation catheter from Medtronic is not the only such device in clinical use. At the meeting, researchers reported 3-month follow-up results from a series of 46 patients with drug-resistant hypertension treated with a multielectrode catheter from St. Jude at four centers in Greece and Australia.

The main difference between the St. Jude EnligHTN device, which has four separate electrodes at its tip, and the Medtronic device, with a single electrode, is that the St. Jude device can denervate a renal artery with a single placement, as opposed to the four different placements, with rotation, used for the Medtronic device, meaning less arterial manipulation. Whether this will produce any discernable difference in safety, efficacy, or procedure time remains unclear.

The study enrolled patients with persistent hypertension, with an office systolic pressure above 160 mm Hg (150 mm Hg in patients with diabetes), despite treatment with at least three antihypertensive drugs, including at least one diuretic (similar enrollment criteria as the Symplicity studies). The patients’ averaged 60 years old, and their pressures averaged 176/98 mm Hg.

Average procedure time was 34 minutes, reported Dr. Costas Tsioufis, a professor of cardiology at the University of Athens, which may be modestly faster than the usual procedure time using the Symplicity catheter, which operators often estimate to require 40-50 minutes. Data from a series of 344 patients treated with the Symplicity catheter at Saarland University Hospital in Homburg showed an average procedure time of 44 minutes, said Dr. Felix Mahfoud, a cardiologist there.

Renal Denervation Shown Highly Cost Effective

Although renal denervation has an estimated up-front cost of about $12,500, the long-term benefits of the blood pressure reduction it usually produces are so potent that the treatment winds up costing about $3,000 for each additional quality-adjusted life-year it confers on patients, based on a cost-effectiveness analysis of data from the Symplicity HTN-2 trial.

This level of cost effectiveness is "more than an order of magnitude below the recognized threshold of $50,000/QALY [quality-adjusted life-year]," and provides fairly compelling evidence that "catheter-based renal denervation therapy is a cost-effective treatment strategy for resistant hypertension," Dr. Benjamin P. Geisler and his associates wrote in a report published online in September (J. Am. Coll. Cardiol. 2012 [doi:10.1016/j.jacc.2012.07.029]).

They based their cost-effectiveness model on data collected in the Symplicity HTN-2 trial (Lancet 2010;376:1903-9), described in the main story.

"When you look at societal decision making – how much a society is willing to pay for improved quality of life and increased duration of life – the recognized threshold in the United States is a cost of $50,000 or less/QALY. That means that $3,000/QALY is highly cost effective," said Jan B. Pietzsch, Ph.D., the lead investigator of the analysis. "It’s a very low incremental cost-effectiveness ratio compared with other innovative treatments," he said in an interview.

The model that Dr. Geisler, Dr. Pietzsch, and their associates produced estimated a sizeable impact that this blood-pressure reduction would have on improved survival, and on a reduced incidence of several cardiovascular disease end points presuming that the reduced blood pressure was sustained for 10 years, or for the rest of a patient’s life. For example, they estimated that over the 10 years following treatment, renal denervation would cut the incidence of stroke by 3.4 percentage points, the rate of coronary heart disease by 5.4 percentage points, the rate of cardiovascular mortality by 3.8 percentage points, and all-cause death by 3.5 percentage points. They also calculated an increase in median survival of 1.3 years.

They calculated a discounted, lifetime incremental cost-effectiveness ratio of $3,071/QALY. In addition, they found this incremental cost per quality-adjusted life-year was "quite robust" across a range of stating blood pressures, said Dr. Pietzsch, president of Wing Tech, a consulting company based in the United States and Germany.

At starting blood pressures of less than 172 mm Hg, renal denervation was actually cost saving. At a baseline pressure of 172 mm Hg or greater the cost per QALY increased steadily with baseline pressure, to a maximum or about $7,000/QALY in patients who had a systolic blood pressure of 200 mm Hg at the time they underwent renal denervation.

Dr. Pietzsch, Dr. Geisler, and another coauthors work for Wing Tech Inc., which provided consultant services to Medtronic Ardian to construct this health-economic model. (Medtronic Ardian is the company that markets the Symplicity catheter.) Another coauthor received salary support from Medtronic Ardian, a second coauthor received consultancy payments and travel expenses from Medtronic Ardian, and a third coauthor serves on the board of a group that received funding from Medtronic.

Official Recommendations Start Mainstreaming RD

The strikingly successful track record of RD so far led the European Society of Hypertension to last May issue recommendations on using the treatment in routine practice (J. Hypertens. 2012;30:837-41). The Society endorsed routinely treating patients who match the criteria for having dangerously high, treatment-resistant hypertension similar to the criteria that have been used in the Symplicity trials and other recent RD studies.

But investigator-driven research protocols at several European centers are now even moving beyond these criteria, as patients with milder levels of drug-resistant hypertension also clamor for RD.

"We are moving to treat less severe hypertension, but within a clinical study," said Dr. Roland E. Schmieder, professor of medicine and vice chairman of nephrology and hypertension at the University Hospital in Erlangen, Germany. He also stressed that these studies will still continue to exclude patients with impaired renal function at baseline. "Everyone in Germany agrees the focus must be on treatment-resistant hypertension, when physicians feel they have no other choice to offer patients. But as you move into patients with less severe hypertension you increase the need for hard–end-point trials" that are better able to prove an overall net benefit to patients from RD, he said in an interview.

"We have a lot of safety data" for RD, but long-term follow-up is still limited. "We don’t have experience with what happens when [RD-treated] patients become critically ill. They may still need some renal innervation to prevent traumatic shock," he said. "There are still unanswered safety questions, but so far the main concern, renal function, has improved" following RD.

Another caution about treating milder hypertension is that the treatment effect will generally be smaller than what’s seen in patients with more severe hypertension.

But Dr. Schmieder shares the enthusiasm of many of his colleagues who believe they now have an effective new tool for treating hypertension.

"Renal denervation is a very important step forward, because hypertension is killer No. 1 worldwide, and no new antihypertensive drugs are on the horizon," he said. We don’t expect any new antihypertensive drugs for at least the next 10 years. To have this new option is important, both for treating patients and to help increase awareness of the disease."

The Symplicity trials have been sponsored by Ardian, which first developed the Symplicity renal denervation catheter, and by Medtronic, which acquired Ardian and now produces and markets the catheter. Dr. Brady, Dr. Táborský, Mr. Franzen, Dr. Fischer, and Dr. Gonzalez-Juanatey did not have any relevant disclosures. Dr. Böhm, Dr. Esler, Dr. Mahfoud, and Dr. Schmieder said that they have received research, travel, and consultancy funding from Medtronic and Ardian. Dr. Mahfoud said that he has also received research funding from Vessix Vascular and ReCor Medical Technology, companies that are developing other devices for renal denervation.

MUNICH – Renal denervation remains investigational in the United States, where a large clinical trial testing its safety and efficacy is now in progress.

But in Europe, Australia, and elsewhere, renal denervation – an intravascular procedure that zaps the sympathetic innervation in a patient’s renal arteries with a few pulses of radiofrequency energy – is rapidly becoming the big new thing for treating patients with drug-resistant hypertension since marketing of a denervation catheter began in April 2010.

As of last spring, Medtronic, the company that sells the only renal denervation (RD) catheter currently commercially available, estimated that the 5,000th patient had been treated by RD, although Dr. Michael Böhm, who oversees what might be the most active RD program in the world, recently put his estimate upwards of 10,000 patients treated worldwide. Among the smaller number of closely followed patients included in this experience with reported outcomes data, perhaps 300-500 patients, the results have been striking: A drop in office blood pressure on the order of 28/10 mm Hg in patients who began treatment with pressures in the 180/100 mm Hg ballpark (despite treatment with as many as six antihypertensive drugs), that has been durable over follow-up as long as 36 months, with response rates among patients that rise over time and run over 90% once patients are followed longer than a year, and uniform reports of good safety during 6-36 months’ follow-up, with no evidence of impaired renal function or arterial sclerosis over time or other untoward effects.

And now emerging in new reports, both recently published and presented at the meeting in August, are hints of several effects beyond simple blood pressure reduction that hold promise for expanding the application of RD beyond just antihypertensive treatment and broadening the recognized benefits of this treatment.

RD "is a transformative area for treating hypertension, and now heart failure" and other disorders, commented Dr. Adrian Brady, a cardiologist and hypertension specialist in Glasgow, Scotland.

More Than Just Blood Pressure

Among the newest findings was a report on a small, controlled study with 43 normotensive patients with New York Heart Association class III or IV heart failure that showed RD could significantly raise left ventricular ejection fraction, reduce left ventricular end-systolic and end-diastolic volume index, and cut serum levels of brain natriuretic peptide during 12 months of follow-up. RD had these positive effects on surrogate markers of heart failure severity without causing hypotension or other adverse effects, and the treatment also cut the rate of heart failure hospitalizations over 12 months by more than half, although the study wasn’t powered to examine this end point, reported Dr. Milos Táborský, a cardiologist at Olomouc University Hospital in the Czech Republic.

For example, left ventricular ejection fraction rose from an average of 25% at baseline to an average of 31% 12 months after RD, compared with a 2% change in the control patients, a statistically significant difference, Dr. Táborský said.

In short, RD worked in normotensive patients with heart failure similar to a beta-blocker drug that cuts neurohormonal activation, commented Dr. José-Ramon Gonzalez-Juanatey, director of the cardiovascular department at the University Hospital of Santiago de Compostela in Spain. "This technique opens a new era in treating heart failure by decreasing sympathetic tone," he said.

In a similar vein, results reported at the meeting from another small, controlled study with 27 treatment-resistant hypertensive patients showed that by 6 months after RD, the treatment had significantly improved aortic augmentation index and aortic pulse-wave velocity, two markers of central vascular stiffness and central blood pressure. The average 1 m/sec improvement seen in aortic pulse-wave velocity 6 months after RD, reflecting a roughly 10% reduction in aortic stiffness, corresponds to about a10-year drop in the patients’ vascular age, said Klaas F. Franzen, a researcher at Schleswig-Holstein University Hospital in Lübeck, Germany.

"The idea is that by reducing whole-body sympathetic activity, you reduce vasoconstriction, and induce vasodilation in the renal arteries and central arteries," commented Dr. Felix Mahfoud, a cardiologist at Saarland University Hospital in Homburg, Germany.

The benefits from RD are not just cardiovascular. Another report at the meeting came from serial psychologic tests administered before and after 119 patients with drug-resistant hypertension underwent RD. In addition to producing an average drop in office blood pressure of 20/10 mm Hg, at both 3 and 6 months after treatment, RD also led to statistically and clinically significant drops in stress reaction, as measured on the Wiener Determination Task. In addition, among the roughly 20% of patients in the group of 119 who had clinically meaningful levels of anxiety or depression at baseline, RD also produced statistically and clinically significant falls in both anxiety and depression at both 3 and 6 months after treatment, reported Denise Fischer, Ph.D., a psychologist at Saarland University Hospital.

Another facet of her study looked at headache severity and found that at 3 and 6 months following RD all patients had statistically significant drops in headache intensity, and among the 20% of patients who entered the study with headaches self-rated as worse than 4 on a 0-10 visual analog scale, headache intensity fell from an average of about 8 before treatment to an average of less than 4 at 6 months after RD, Dr. Fischer said.

Follow-Ups to 18 Months, and Beyond

The most thorough assessment so far of RD as an antihypertensive treatment came in the Symplicity HTN-2 trial, a multicenter, multinational trial that randomized 106 patients with drug-resistant hypertension. In the 6-month results from the study, the primary end point showed that among 49 patients who underwent RD, office blood pressure fell by an average of 32/12 mm Hg, compared with virtually no change among 51 controls (Lancet 2010;376:1903-9).

During the August meeting, researchers from the study reported follow-up data, which included 18-month results from 43 patients in the original intervention arm of the study and from an additional 31 patients originally randomized to the control arm but who crossed over to RD treatment after the first 6 months.

The 18-month results showed stability of the initial blood pressure reduction in both subgroups of patients, with average reductions in office blood pressure remaining at 32/12 mm Hg compared with baseline in the 43 patients from the original intervention arm, and an average 28/11 mm Hg cut in office pressure in the 31 crossover patients, compared with their baseline levels, said Dr. Murray D. Esler, professor of medicine at Monash University in Melbourne, and lead investigator for the study. Patients in the initially treated arm also had an average 7 beats/min reduction in heart rate, compared with baseline that was statistically significant.

"In our experience at Saarland University Hospital with more than 400 patients, they all achieved a blood pressure response" following renal denervation.   --Dr. Michael Böhm.

For safety, the 18 month results showed "no signal that renal function was harmed," he said. One patient had a renal-artery dissection early in the study, caused by the stiff catheter tip used at the study’s start but since replaced with a more flexible tip, Dr. Esler said. Other safety events during follow-up included one episode of hypotension that required hospitalization, one "mild" incidence of "transient" acute renal failure, and two deaths unrelated to RD.

Dr. Esler and his collaborators also cited the 36-month follow-up results on 24 patients from the initial, uncontrolled study of RD using the Symplicity catheter, the Symplicity HTN1 study (Lancet 2009;373:1275-81). These patients continue to show a durable blood pressure response and no signs of adverse effects, renal or otherwise, in this small number of patients followed for a prolonged period, said Dr. Böhm, director of internal medicine at Saarland University Hospital. (The 3-year follow-up of these 24 patients was first reported last March at the annual scientific session of the American College of Cardiology.) A very encouraging finding was that among the small number of patients followed this long, the percentage of patients with clinically important blood pressure drops continued to accumulate, so that at 36 months 99% of treated patients responded, Dr. Böhm said.

"In our experience at Saarland University Hospital with more than 400 patients, they all achieved a blood pressure response" following RD, he said. "How long will [their response] last? No one knows, but if it lasts for at least 3 years, you can then justify a redo," a repeat treatment, although he also cautioned that so far, he knows of no patient who has undergone RD a second time.

In addition to the new evidence for pleiotropic effects from RD reported at the meeting, recently published reports from small studies provided preliminary documentation of other possible benefits. For example:

• RD led to a significantly reduced prevalence of albuminuria during 6-month follow-up in a study with 88 treated patients with drug-resistant hypertension (Hypertension 2012;60:419-24).

• RD led to significant improvements in glucose metabolism and insulin sensitivity during 3-month follow-up in a study with 37 treated patients with drug-resistant hypertension (Circulation 2011;123:1940-6).

• RD produced a reduction in blood pressure during exercise without affecting chronotropic competence during 3-month follow-up of 37 treated patients with drug-resistant hypertension (J. Amer. Coll. Cardiol. 2011;58:1176-83).

Novel Catheter May Speed Procedure Times

The Symplicity renal denervation catheter from Medtronic is not the only such device in clinical use. At the meeting, researchers reported 3-month follow-up results from a series of 46 patients with drug-resistant hypertension treated with a multielectrode catheter from St. Jude at four centers in Greece and Australia.

The main difference between the St. Jude EnligHTN device, which has four separate electrodes at its tip, and the Medtronic device, with a single electrode, is that the St. Jude device can denervate a renal artery with a single placement, as opposed to the four different placements, with rotation, used for the Medtronic device, meaning less arterial manipulation. Whether this will produce any discernable difference in safety, efficacy, or procedure time remains unclear.

The study enrolled patients with persistent hypertension, with an office systolic pressure above 160 mm Hg (150 mm Hg in patients with diabetes), despite treatment with at least three antihypertensive drugs, including at least one diuretic (similar enrollment criteria as the Symplicity studies). The patients’ averaged 60 years old, and their pressures averaged 176/98 mm Hg.

Average procedure time was 34 minutes, reported Dr. Costas Tsioufis, a professor of cardiology at the University of Athens, which may be modestly faster than the usual procedure time using the Symplicity catheter, which operators often estimate to require 40-50 minutes. Data from a series of 344 patients treated with the Symplicity catheter at Saarland University Hospital in Homburg showed an average procedure time of 44 minutes, said Dr. Felix Mahfoud, a cardiologist there.

Renal Denervation Shown Highly Cost Effective

Although renal denervation has an estimated up-front cost of about $12,500, the long-term benefits of the blood pressure reduction it usually produces are so potent that the treatment winds up costing about $3,000 for each additional quality-adjusted life-year it confers on patients, based on a cost-effectiveness analysis of data from the Symplicity HTN-2 trial.

This level of cost effectiveness is "more than an order of magnitude below the recognized threshold of $50,000/QALY [quality-adjusted life-year]," and provides fairly compelling evidence that "catheter-based renal denervation therapy is a cost-effective treatment strategy for resistant hypertension," Dr. Benjamin P. Geisler and his associates wrote in a report published online in September (J. Am. Coll. Cardiol. 2012 [doi:10.1016/j.jacc.2012.07.029]).

They based their cost-effectiveness model on data collected in the Symplicity HTN-2 trial (Lancet 2010;376:1903-9), described in the main story.

"When you look at societal decision making – how much a society is willing to pay for improved quality of life and increased duration of life – the recognized threshold in the United States is a cost of $50,000 or less/QALY. That means that $3,000/QALY is highly cost effective," said Jan B. Pietzsch, Ph.D., the lead investigator of the analysis. "It’s a very low incremental cost-effectiveness ratio compared with other innovative treatments," he said in an interview.

The model that Dr. Geisler, Dr. Pietzsch, and their associates produced estimated a sizeable impact that this blood-pressure reduction would have on improved survival, and on a reduced incidence of several cardiovascular disease end points presuming that the reduced blood pressure was sustained for 10 years, or for the rest of a patient’s life. For example, they estimated that over the 10 years following treatment, renal denervation would cut the incidence of stroke by 3.4 percentage points, the rate of coronary heart disease by 5.4 percentage points, the rate of cardiovascular mortality by 3.8 percentage points, and all-cause death by 3.5 percentage points. They also calculated an increase in median survival of 1.3 years.

They calculated a discounted, lifetime incremental cost-effectiveness ratio of $3,071/QALY. In addition, they found this incremental cost per quality-adjusted life-year was "quite robust" across a range of stating blood pressures, said Dr. Pietzsch, president of Wing Tech, a consulting company based in the United States and Germany.

At starting blood pressures of less than 172 mm Hg, renal denervation was actually cost saving. At a baseline pressure of 172 mm Hg or greater the cost per QALY increased steadily with baseline pressure, to a maximum or about $7,000/QALY in patients who had a systolic blood pressure of 200 mm Hg at the time they underwent renal denervation.

Dr. Pietzsch, Dr. Geisler, and another coauthors work for Wing Tech Inc., which provided consultant services to Medtronic Ardian to construct this health-economic model. (Medtronic Ardian is the company that markets the Symplicity catheter.) Another coauthor received salary support from Medtronic Ardian, a second coauthor received consultancy payments and travel expenses from Medtronic Ardian, and a third coauthor serves on the board of a group that received funding from Medtronic.

Official Recommendations Start Mainstreaming RD

The strikingly successful track record of RD so far led the European Society of Hypertension to last May issue recommendations on using the treatment in routine practice (J. Hypertens. 2012;30:837-41). The Society endorsed routinely treating patients who match the criteria for having dangerously high, treatment-resistant hypertension similar to the criteria that have been used in the Symplicity trials and other recent RD studies.

But investigator-driven research protocols at several European centers are now even moving beyond these criteria, as patients with milder levels of drug-resistant hypertension also clamor for RD.

"We are moving to treat less severe hypertension, but within a clinical study," said Dr. Roland E. Schmieder, professor of medicine and vice chairman of nephrology and hypertension at the University Hospital in Erlangen, Germany. He also stressed that these studies will still continue to exclude patients with impaired renal function at baseline. "Everyone in Germany agrees the focus must be on treatment-resistant hypertension, when physicians feel they have no other choice to offer patients. But as you move into patients with less severe hypertension you increase the need for hard–end-point trials" that are better able to prove an overall net benefit to patients from RD, he said in an interview.

"We have a lot of safety data" for RD, but long-term follow-up is still limited. "We don’t have experience with what happens when [RD-treated] patients become critically ill. They may still need some renal innervation to prevent traumatic shock," he said. "There are still unanswered safety questions, but so far the main concern, renal function, has improved" following RD.

Another caution about treating milder hypertension is that the treatment effect will generally be smaller than what’s seen in patients with more severe hypertension.

But Dr. Schmieder shares the enthusiasm of many of his colleagues who believe they now have an effective new tool for treating hypertension.

"Renal denervation is a very important step forward, because hypertension is killer No. 1 worldwide, and no new antihypertensive drugs are on the horizon," he said. We don’t expect any new antihypertensive drugs for at least the next 10 years. To have this new option is important, both for treating patients and to help increase awareness of the disease."

The Symplicity trials have been sponsored by Ardian, which first developed the Symplicity renal denervation catheter, and by Medtronic, which acquired Ardian and now produces and markets the catheter. Dr. Brady, Dr. Táborský, Mr. Franzen, Dr. Fischer, and Dr. Gonzalez-Juanatey did not have any relevant disclosures. Dr. Böhm, Dr. Esler, Dr. Mahfoud, and Dr. Schmieder said that they have received research, travel, and consultancy funding from Medtronic and Ardian. Dr. Mahfoud said that he has also received research funding from Vessix Vascular and ReCor Medical Technology, companies that are developing other devices for renal denervation.

MUNICH - Patients with renal dysfunction as well as atrial fibrillation who received apixaban to prevent strokes and systemic embolism had the biggest drop in major bleeding events compared with control patients on warfarin in a prespecified substudy of the ARISTOTLE trial.

"Our findings suggest that apixaban may be particularly suited to address the unmet need for more effective and safe stroke prevention in patients with atrial fibrillation and renal dysfunction," Dr. Stefan H. Hohnloser said at the annual congress of the European Society of Cardiology.

The finding is especially relevant to practice because of the high coprevalence of atrial fibrillation and chronic kidney disease. A recent U.S. study of patients with chronic kidney disease found an 18% prevalence of atrial fibrillation – two- to threefold higher than in the general population – and a greater than 25% prevalence of atrial fibrillation among patients with renal dysfunction who were at least 70 year old (Am. Heart J. 2010;159:1102-7).

But while apixiban triggered significantly fewer major bleeds compared with warfarin among patients with renal dysfunction enrolled in the pivotal Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban’s efficacy for stroke and embolism protection in atrial fibrillation patients with renal dysfunction was just as good as it was in patients with normal renal activity.

"When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function," Dr. Hohnloser and his associates wrote in a published report on their findings that appeared online concurrent with his report at the meeting (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs274]).

"We know that patients with atrial fibrillation and impaired renal function not only have a high stroke rate, but also have a significantly higher bleeding rate with respect to patients with normal renal function. The message from the new analysis is that, in patients with impaired renal function, apixaban is superior to warfarin with respect to the risk of major bleeding," said Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.

The new findings also drew a sharp contrast between apixaban and another new oral anticoagulant, dabigatran, noted Dr. Hindricks and Dr. Jan Steffel of University Hospital Zurich in an editorial they wrote that appeared online concurrent with the main report (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs267]).

"Dabigatran, which is 80% renally cleared, has a significant potential for severe bleeding in patients with reduced renal function," they wrote.

In addition, they added, "major bleeding events are the single most prevalent reason why proper anticoagulation is withheld in patients with atrial fibrillation, especially those with impaired renal function. ... Chronic kidney disease certainly appears to be the ‘Achilles heel’ of dabigatran, as accumulation is likely to occur due to mainly renal elimination. Hence, in our view of the available data, apixaban would probably be the preferred agent over dabigatran in these patients."

Dr. Hindricks and Dr. Steffel concluded that the new findings from ARISTOTLE provide "solid evidence for the superiority of apixaban in patients with atrial fibrillation and chronic kidney disease. In the light of these data, apixaban appears to be a very appealing option for these individuals, potentially leading to a substantial increase in the numbers of appropriately anticoagulated patients."

The substudy analysis calculated estimated glomerular filtration rates (eGFR) for patients enrolled in ARISTOTLE by three difference methods: the Cockcroft-Gault formula, the Chronic Kidney Disease-Epidemiology Collaboration formula, and based on cystatin C measurement. It focused on 18,122 of the patients enrolled in ARISTOTLE who had data available that allowed calculation of their eGFR. All three methods found that about 15% of the enrolled patients had an eGFR of 50 mL/min per 1.73 m² or less.

The new analysis showed that patients with an eGFR of 50 mL/min or less had the greatest reduction in major bleeding episodes during apixaban treatment, compared with warfarin treatment. Among patients with impaired renal function, the bleeding risk on apixaban dropped by 35%-52%, depending on which formula the researchers used to identify patients with an eGFR that low, reported Dr. Hohnloser, professor and director of the department of clinical electrophysiology at J.W. Goethe University in Frankfurt, Germany.

In contrast, the primary efficacy end point of stroke or systemic embolism occurred consistently less often among patients treated with apixaban than in those on warfarin regardless of their eGFR.

The ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Hohnloser said that he has received consulting and lecture fees from Bristol-Myers Squibb, Pfizer, and other drug companies and research grants from Sanofi-Aventis and St. Jude. Dr. Hindricks said that he has received honoraria from and has been a consultant to Biosense, Stereotaxis, St. Jude, and Biotronik.

MUNICH - Patients with renal dysfunction as well as atrial fibrillation who received apixaban to prevent strokes and systemic embolism had the biggest drop in major bleeding events compared with control patients on warfarin in a prespecified substudy of the ARISTOTLE trial.

"Our findings suggest that apixaban may be particularly suited to address the unmet need for more effective and safe stroke prevention in patients with atrial fibrillation and renal dysfunction," Dr. Stefan H. Hohnloser said at the annual congress of the European Society of Cardiology.

The finding is especially relevant to practice because of the high coprevalence of atrial fibrillation and chronic kidney disease. A recent U.S. study of patients with chronic kidney disease found an 18% prevalence of atrial fibrillation – two- to threefold higher than in the general population – and a greater than 25% prevalence of atrial fibrillation among patients with renal dysfunction who were at least 70 year old (Am. Heart J. 2010;159:1102-7).

But while apixiban triggered significantly fewer major bleeds compared with warfarin among patients with renal dysfunction enrolled in the pivotal Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban’s efficacy for stroke and embolism protection in atrial fibrillation patients with renal dysfunction was just as good as it was in patients with normal renal activity.

"When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function," Dr. Hohnloser and his associates wrote in a published report on their findings that appeared online concurrent with his report at the meeting (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs274]).

"We know that patients with atrial fibrillation and impaired renal function not only have a high stroke rate, but also have a significantly higher bleeding rate with respect to patients with normal renal function. The message from the new analysis is that, in patients with impaired renal function, apixaban is superior to warfarin with respect to the risk of major bleeding," said Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.

The new findings also drew a sharp contrast between apixaban and another new oral anticoagulant, dabigatran, noted Dr. Hindricks and Dr. Jan Steffel of University Hospital Zurich in an editorial they wrote that appeared online concurrent with the main report (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs267]).

"Dabigatran, which is 80% renally cleared, has a significant potential for severe bleeding in patients with reduced renal function," they wrote.

In addition, they added, "major bleeding events are the single most prevalent reason why proper anticoagulation is withheld in patients with atrial fibrillation, especially those with impaired renal function. ... Chronic kidney disease certainly appears to be the ‘Achilles heel’ of dabigatran, as accumulation is likely to occur due to mainly renal elimination. Hence, in our view of the available data, apixaban would probably be the preferred agent over dabigatran in these patients."

Dr. Hindricks and Dr. Steffel concluded that the new findings from ARISTOTLE provide "solid evidence for the superiority of apixaban in patients with atrial fibrillation and chronic kidney disease. In the light of these data, apixaban appears to be a very appealing option for these individuals, potentially leading to a substantial increase in the numbers of appropriately anticoagulated patients."

The substudy analysis calculated estimated glomerular filtration rates (eGFR) for patients enrolled in ARISTOTLE by three difference methods: the Cockcroft-Gault formula, the Chronic Kidney Disease-Epidemiology Collaboration formula, and based on cystatin C measurement. It focused on 18,122 of the patients enrolled in ARISTOTLE who had data available that allowed calculation of their eGFR. All three methods found that about 15% of the enrolled patients had an eGFR of 50 mL/min per 1.73 m² or less.

The new analysis showed that patients with an eGFR of 50 mL/min or less had the greatest reduction in major bleeding episodes during apixaban treatment, compared with warfarin treatment. Among patients with impaired renal function, the bleeding risk on apixaban dropped by 35%-52%, depending on which formula the researchers used to identify patients with an eGFR that low, reported Dr. Hohnloser, professor and director of the department of clinical electrophysiology at J.W. Goethe University in Frankfurt, Germany.

In contrast, the primary efficacy end point of stroke or systemic embolism occurred consistently less often among patients treated with apixaban than in those on warfarin regardless of their eGFR.

The ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Hohnloser said that he has received consulting and lecture fees from Bristol-Myers Squibb, Pfizer, and other drug companies and research grants from Sanofi-Aventis and St. Jude. Dr. Hindricks said that he has received honoraria from and has been a consultant to Biosense, Stereotaxis, St. Jude, and Biotronik.

MUNICH - Patients with renal dysfunction as well as atrial fibrillation who received apixaban to prevent strokes and systemic embolism had the biggest drop in major bleeding events compared with control patients on warfarin in a prespecified substudy of the ARISTOTLE trial.

"Our findings suggest that apixaban may be particularly suited to address the unmet need for more effective and safe stroke prevention in patients with atrial fibrillation and renal dysfunction," Dr. Stefan H. Hohnloser said at the annual congress of the European Society of Cardiology.

The finding is especially relevant to practice because of the high coprevalence of atrial fibrillation and chronic kidney disease. A recent U.S. study of patients with chronic kidney disease found an 18% prevalence of atrial fibrillation – two- to threefold higher than in the general population – and a greater than 25% prevalence of atrial fibrillation among patients with renal dysfunction who were at least 70 year old (Am. Heart J. 2010;159:1102-7).

But while apixiban triggered significantly fewer major bleeds compared with warfarin among patients with renal dysfunction enrolled in the pivotal Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban’s efficacy for stroke and embolism protection in atrial fibrillation patients with renal dysfunction was just as good as it was in patients with normal renal activity.

"When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function," Dr. Hohnloser and his associates wrote in a published report on their findings that appeared online concurrent with his report at the meeting (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs274]).

"We know that patients with atrial fibrillation and impaired renal function not only have a high stroke rate, but also have a significantly higher bleeding rate with respect to patients with normal renal function. The message from the new analysis is that, in patients with impaired renal function, apixaban is superior to warfarin with respect to the risk of major bleeding," said Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.

The new findings also drew a sharp contrast between apixaban and another new oral anticoagulant, dabigatran, noted Dr. Hindricks and Dr. Jan Steffel of University Hospital Zurich in an editorial they wrote that appeared online concurrent with the main report (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs267]).

"Dabigatran, which is 80% renally cleared, has a significant potential for severe bleeding in patients with reduced renal function," they wrote.

In addition, they added, "major bleeding events are the single most prevalent reason why proper anticoagulation is withheld in patients with atrial fibrillation, especially those with impaired renal function. ... Chronic kidney disease certainly appears to be the ‘Achilles heel’ of dabigatran, as accumulation is likely to occur due to mainly renal elimination. Hence, in our view of the available data, apixaban would probably be the preferred agent over dabigatran in these patients."

Dr. Hindricks and Dr. Steffel concluded that the new findings from ARISTOTLE provide "solid evidence for the superiority of apixaban in patients with atrial fibrillation and chronic kidney disease. In the light of these data, apixaban appears to be a very appealing option for these individuals, potentially leading to a substantial increase in the numbers of appropriately anticoagulated patients."

The substudy analysis calculated estimated glomerular filtration rates (eGFR) for patients enrolled in ARISTOTLE by three difference methods: the Cockcroft-Gault formula, the Chronic Kidney Disease-Epidemiology Collaboration formula, and based on cystatin C measurement. It focused on 18,122 of the patients enrolled in ARISTOTLE who had data available that allowed calculation of their eGFR. All three methods found that about 15% of the enrolled patients had an eGFR of 50 mL/min per 1.73 m² or less.

The new analysis showed that patients with an eGFR of 50 mL/min or less had the greatest reduction in major bleeding episodes during apixaban treatment, compared with warfarin treatment. Among patients with impaired renal function, the bleeding risk on apixaban dropped by 35%-52%, depending on which formula the researchers used to identify patients with an eGFR that low, reported Dr. Hohnloser, professor and director of the department of clinical electrophysiology at J.W. Goethe University in Frankfurt, Germany.

In contrast, the primary efficacy end point of stroke or systemic embolism occurred consistently less often among patients treated with apixaban than in those on warfarin regardless of their eGFR.

The ARISTOTLE trial was sponsored by Bristol-Myers Squibb and Pfizer, the companies that market apixaban (Eliquis). Dr. Hohnloser said that he has received consulting and lecture fees from Bristol-Myers Squibb, Pfizer, and other drug companies and research grants from Sanofi-Aventis and St. Jude. Dr. Hindricks said that he has received honoraria from and has been a consultant to Biosense, Stereotaxis, St. Jude, and Biotronik.

MUNICH – Cardiac resynchronization in patients with mild heart failure produced durable benefits during an average 4.5 years of follow-up, with evidence for ongoing cardiac remodeling and reduced disease progression in a series of 419 patients.

"The benefits of CRT [cardiac-resynchronization therapy] persisted, indicating that CRT attenuates disease progression in mildly symptomatic heart failure patients with wide QRS," Dr. Cecilia Linde said at the annual congress of the European Society of Cardiology.

"The results clearly show that the reverse remodeling produced by CRT was sustained over 5 years, and that’s good news for the treatment of patients with heart failure and an indication for cardiac resynchronization," commented Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.

The findings "confirm the results from RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (N. Engl. J. Med. 2010;363:2385-95)] with respect to the long-term outcome of CRT in patients with NYHA [New York Heart Association] class II heart failure for survival and heart failure hospitalization, and provide novel, long-term information on reverse remodeling" from CRT in these patients, commented Dr. Angelo Auricchio, director of the cardiac electrophysiology program at the Ticino Cardiac Center in Lugano, Switzerland.

The data analyzed by Dr. Linde and her associates came from 419 patients originally enrolled in the "CRT on" arm of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial, which enrolled patients with NYHA class I or II heart failure and a QRS duration or at least 120 msec. The primary end point of the study was the composite of death or heart failure hospitalization during the first 12 months of active CRT use compared with patients who received a CRT device that had not been turned on (J. Am. Coll. Cardiol. 2008;52:1834-43). The new analysis reported by Dr. Linde focused on 419 patients initially randomized to the CRT-on arm who continued on active CRT use for up to 5 years, with an average follow-up of 4.5 years. The researchers collected complete follow-up data for 95% of these patients through 3 years, for 89% through 4 years, and for 85% through 5 years.

At baseline, the patients had an average age of 63 years; 78% were men, and 82% had NYHA class I heart failure, with a average left ventricular ejection fraction of 27%. Their average QRS duration at entry was 153 msec, and 56% of the patients had an ischemic etiology for their heart failure.

Annual follow-up findings showed a consistent, linear rate of death and first heart failure hospitalization throughout follow-up, with an annual mortality rate of 3% and an annual rate of death or first heart-failure hospitalization of 6%, said Dr. Linde, a cardiologist at the Karolinska Institute in Stockholm.

The results also showed a stable pattern of left-ventricular reverse remodeling following the first year on CRT. After 12 months, patients had an average cut in the left ventricular end diastolic volume index of 19 mL/m²; 25 mL/m² after 24 months; and 23 mL/m² after 5 years. The average drop in left ventricular end systolic volume index was 18 mL/m² after 12 months; 24 mL/m² after 24 months; and 23 mL/m² at 5 years. Other measures of heart failure severity – the 6-minute walk, the Minnesota Living With Heart Failure score, and the Kansas City Cardiomyopathy Questionnaire score all improved significantly during the first 12 months on CRT therapy, and then held fairly steady during the subsequent 4 years. At 12 months, about 43% of patients had NYHA class I disease, about 53% had class II disease, and the rest had class III disease (which compared with rates of 18% with class I and 82% with class II at baseline). After 5 years, roughly 34% of patients had NYHA class I heart failure, about 56% had class II, about 9% had class III, and about 1% had class IV disease.

The majority of left-ventricular lead complications – the main adverse event of treatment – occurred during the first 12 months, with a cumulative incidence of 9% after 1 year. At 5 years, 13% of patients had experienced a lead complication.

The REVERSE trial was sponsored by Medtronic. Dr. Linde said that she has been a consultant to Medtronic and St. Jude and received research grants from Medtronic. Dr. Hindricks said that he received honoraria from and served on advisory boards for Biosense, Stereotaxis, St. Jude, and Biotronik. Dr. Auricchio said that he was a speaker for, consultant to, and received honoraria from Medtronic, St. Jude, and several other device and drug companies.

MUNICH – Cardiac resynchronization in patients with mild heart failure produced durable benefits during an average 4.5 years of follow-up, with evidence for ongoing cardiac remodeling and reduced disease progression in a series of 419 patients.

"The benefits of CRT [cardiac-resynchronization therapy] persisted, indicating that CRT attenuates disease progression in mildly symptomatic heart failure patients with wide QRS," Dr. Cecilia Linde said at the annual congress of the European Society of Cardiology.

"The results clearly show that the reverse remodeling produced by CRT was sustained over 5 years, and that’s good news for the treatment of patients with heart failure and an indication for cardiac resynchronization," commented Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.

The findings "confirm the results from RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (N. Engl. J. Med. 2010;363:2385-95)] with respect to the long-term outcome of CRT in patients with NYHA [New York Heart Association] class II heart failure for survival and heart failure hospitalization, and provide novel, long-term information on reverse remodeling" from CRT in these patients, commented Dr. Angelo Auricchio, director of the cardiac electrophysiology program at the Ticino Cardiac Center in Lugano, Switzerland.

The data analyzed by Dr. Linde and her associates came from 419 patients originally enrolled in the "CRT on" arm of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial, which enrolled patients with NYHA class I or II heart failure and a QRS duration or at least 120 msec. The primary end point of the study was the composite of death or heart failure hospitalization during the first 12 months of active CRT use compared with patients who received a CRT device that had not been turned on (J. Am. Coll. Cardiol. 2008;52:1834-43). The new analysis reported by Dr. Linde focused on 419 patients initially randomized to the CRT-on arm who continued on active CRT use for up to 5 years, with an average follow-up of 4.5 years. The researchers collected complete follow-up data for 95% of these patients through 3 years, for 89% through 4 years, and for 85% through 5 years.

At baseline, the patients had an average age of 63 years; 78% were men, and 82% had NYHA class I heart failure, with a average left ventricular ejection fraction of 27%. Their average QRS duration at entry was 153 msec, and 56% of the patients had an ischemic etiology for their heart failure.

Annual follow-up findings showed a consistent, linear rate of death and first heart failure hospitalization throughout follow-up, with an annual mortality rate of 3% and an annual rate of death or first heart-failure hospitalization of 6%, said Dr. Linde, a cardiologist at the Karolinska Institute in Stockholm.

The results also showed a stable pattern of left-ventricular reverse remodeling following the first year on CRT. After 12 months, patients had an average cut in the left ventricular end diastolic volume index of 19 mL/m²; 25 mL/m² after 24 months; and 23 mL/m² after 5 years. The average drop in left ventricular end systolic volume index was 18 mL/m² after 12 months; 24 mL/m² after 24 months; and 23 mL/m² at 5 years. Other measures of heart failure severity – the 6-minute walk, the Minnesota Living With Heart Failure score, and the Kansas City Cardiomyopathy Questionnaire score all improved significantly during the first 12 months on CRT therapy, and then held fairly steady during the subsequent 4 years. At 12 months, about 43% of patients had NYHA class I disease, about 53% had class II disease, and the rest had class III disease (which compared with rates of 18% with class I and 82% with class II at baseline). After 5 years, roughly 34% of patients had NYHA class I heart failure, about 56% had class II, about 9% had class III, and about 1% had class IV disease.

The majority of left-ventricular lead complications – the main adverse event of treatment – occurred during the first 12 months, with a cumulative incidence of 9% after 1 year. At 5 years, 13% of patients had experienced a lead complication.

The REVERSE trial was sponsored by Medtronic. Dr. Linde said that she has been a consultant to Medtronic and St. Jude and received research grants from Medtronic. Dr. Hindricks said that he received honoraria from and served on advisory boards for Biosense, Stereotaxis, St. Jude, and Biotronik. Dr. Auricchio said that he was a speaker for, consultant to, and received honoraria from Medtronic, St. Jude, and several other device and drug companies.

MUNICH – Cardiac resynchronization in patients with mild heart failure produced durable benefits during an average 4.5 years of follow-up, with evidence for ongoing cardiac remodeling and reduced disease progression in a series of 419 patients.

"The benefits of CRT [cardiac-resynchronization therapy] persisted, indicating that CRT attenuates disease progression in mildly symptomatic heart failure patients with wide QRS," Dr. Cecilia Linde said at the annual congress of the European Society of Cardiology.

"The results clearly show that the reverse remodeling produced by CRT was sustained over 5 years, and that’s good news for the treatment of patients with heart failure and an indication for cardiac resynchronization," commented Dr. Gerhard Hindricks, professor and director of the department of electrophysiology at the Leipzig (Germany) University Heart Center.

The findings "confirm the results from RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (N. Engl. J. Med. 2010;363:2385-95)] with respect to the long-term outcome of CRT in patients with NYHA [New York Heart Association] class II heart failure for survival and heart failure hospitalization, and provide novel, long-term information on reverse remodeling" from CRT in these patients, commented Dr. Angelo Auricchio, director of the cardiac electrophysiology program at the Ticino Cardiac Center in Lugano, Switzerland.

The data analyzed by Dr. Linde and her associates came from 419 patients originally enrolled in the "CRT on" arm of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial, which enrolled patients with NYHA class I or II heart failure and a QRS duration or at least 120 msec. The primary end point of the study was the composite of death or heart failure hospitalization during the first 12 months of active CRT use compared with patients who received a CRT device that had not been turned on (J. Am. Coll. Cardiol. 2008;52:1834-43). The new analysis reported by Dr. Linde focused on 419 patients initially randomized to the CRT-on arm who continued on active CRT use for up to 5 years, with an average follow-up of 4.5 years. The researchers collected complete follow-up data for 95% of these patients through 3 years, for 89% through 4 years, and for 85% through 5 years.

At baseline, the patients had an average age of 63 years; 78% were men, and 82% had NYHA class I heart failure, with a average left ventricular ejection fraction of 27%. Their average QRS duration at entry was 153 msec, and 56% of the patients had an ischemic etiology for their heart failure.

Annual follow-up findings showed a consistent, linear rate of death and first heart failure hospitalization throughout follow-up, with an annual mortality rate of 3% and an annual rate of death or first heart-failure hospitalization of 6%, said Dr. Linde, a cardiologist at the Karolinska Institute in Stockholm.

The results also showed a stable pattern of left-ventricular reverse remodeling following the first year on CRT. After 12 months, patients had an average cut in the left ventricular end diastolic volume index of 19 mL/m²; 25 mL/m² after 24 months; and 23 mL/m² after 5 years. The average drop in left ventricular end systolic volume index was 18 mL/m² after 12 months; 24 mL/m² after 24 months; and 23 mL/m² at 5 years. Other measures of heart failure severity – the 6-minute walk, the Minnesota Living With Heart Failure score, and the Kansas City Cardiomyopathy Questionnaire score all improved significantly during the first 12 months on CRT therapy, and then held fairly steady during the subsequent 4 years. At 12 months, about 43% of patients had NYHA class I disease, about 53% had class II disease, and the rest had class III disease (which compared with rates of 18% with class I and 82% with class II at baseline). After 5 years, roughly 34% of patients had NYHA class I heart failure, about 56% had class II, about 9% had class III, and about 1% had class IV disease.

The majority of left-ventricular lead complications – the main adverse event of treatment – occurred during the first 12 months, with a cumulative incidence of 9% after 1 year. At 5 years, 13% of patients had experienced a lead complication.

The REVERSE trial was sponsored by Medtronic. Dr. Linde said that she has been a consultant to Medtronic and St. Jude and received research grants from Medtronic. Dr. Hindricks said that he received honoraria from and served on advisory boards for Biosense, Stereotaxis, St. Jude, and Biotronik. Dr. Auricchio said that he was a speaker for, consultant to, and received honoraria from Medtronic, St. Jude, and several other device and drug companies.

MUNICH – One-year results of the ACCESS-EUROPE study confirm the safety and benefits of percutaneous mitral valve repair with the MitraClip in high-risk patients with heart failure, although patient selection remains a critical issue going forward.

The severity of mitral regurgitation was improved to a meaningful extent in about 80% of patients, and was accompanied by significant improvements at 1 year in New York Heart Association (NYHA) functional class, quality of life, and 6-minute walk test distance in about 70%.

Patrice Wendling/IMNG Medical Media

"The MitraClip therapy therefore provides a treatment option for a patient population with an important unmet clinical need," Dr. Wolfgang Schillinger said at the annual congress of the European Society of Cardiology.

The MitraClip device has been approved in Europe since 2008 and implanted in more than 6,000 patients worldwide, but is not commercially available in the United States.

Dr. Schillinger pointed out that the results provide a "picture of the real-world treatment in Europe," and are consistent with those from clinical trials, even though ACCESS-EU patients were older and sicker than those in the pivotal, randomized EVEREST II trial.

The 567 patients enrolled in the ACCESS-EU registry were described as having abundant comorbidities, including coronary artery disease in 63% and moderate to severe renal failure in 42%, and severe symptoms of end-stage heart failure, with 85% in NYHA functional class III or IV. The average logistic EuroSCORE was 23, 77% presented with functional mitral regurgitation (MR), and 98% had MR grade 3+ or higher. Their mean age was 74 years.

In contrast, the average age was 67 years in the phase II EVEREST II study, where 73% of the device patients had degenerative MR. Less than half (47%) had coronary artery disease, and only 3% had moderate/severe renal failure.

Study discussant Dr. Simon Ray, with the Manchester (U.K.) Academic Health Science Centre, said ACCESS-EU confirms data from smaller registries and that the majority of MitraClip procedures are now performed in comorbid, sick patients with functional MR, and not in the patients included in EVEREST II.

Patrice Wendling/IMNG Medical Media

"So clinical practice has evolved beyond the envelope provided by the evidenced-based, single randomized controlled trial in this field," he said.

The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines state that in patients with an indication for valve repair, but judged inoperable or at unacceptably high surgical risk, percutaneous edge-to-edge repair "may be considered" in order to improve symptoms.

The key going forward is to make sure patients undergoing this procedure genuinely have severe MR, that the assessment of operative risk reflects that of surgeons involved in the decision-making, and that the procedure is only done to improve symptoms, Dr. Ray said.

"There is no evidence that percutaneous edge-to-edge repair improves survival in this patient group," he said.

The decision to choose the less invasive catheter-based therapy over surgery was left up to the 14 ACCESS-EU registry sites.

The MitraClip device was successfully implanted in 99.6% of patients, an improvement over the 86% procedural rate during early experience with the implant in EVEREST II (N. Engl. J. Med. 2011;364:1395-406).

Mortality was low at 3.4% at 30 days, "which is a very good result in view of the comorbidities and the increased risk of the procedures," said Dr. Schillinger, with the University Medical Center Göttingen, Germany.

The most frequently reported safety events were moderate to severe renal failure in 4.8% of patients and bleeding complications in 4%, and the event rates remained low even in higher-risk patients with a EuroSCORE above 20.

At 1 year, 82% of patients were free from death, 79% had MR grade 2 or lower, and 72% were NYHA class I or II.

Significant gains were also made in quality of life scores, averaging 13.5 points from baseline on the Minnesota Living with Heart Failure Questionnaire (from 41.6 to 28.1), and averaging 59.5 m (from 275 to 334 m) in the 6-minute walk test, he said.

"What this registry does, and it is very important, is to raise perhaps more questions than it provides answers, and a number of these are around patient selection," Dr. Ray said.

What’s known from the current registry and others is that 25%-35% of patients will derive little or no symptomatic benefit from percutaneous repair. What’s not clear is whether this is due to incorrect or insufficiently sophisticated assessment of valve anatomy or overestimation of the severity of the MR because quantitative techniques have not generally been used in the registries, he said. It’s also possible that patients are being included with such severe degrees of left ventricular dysfunction that they are unlikely to benefit.

"We also need to have an eye on what constitutes success, because a technically successful procedure leading to a reduction in mitral valve regurgitation in these patients is coincidental, if they do not also have some symptomatic and functional benefit," he added.

Finally, Dr. Ray called for a pragmatic randomized trial, driven by a heart team, comparing optimized medical therapy with the addition of cardiac resynchronization therapy, where indicated, against that treatment plus the MitraClip device.

The phase III COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients) trial in moderate to severe or severe functional MR patients is not yet recruiting, but will compare the MitraClip device with patients managed nonsurgically based on standard hospital practice. REALISM (Real World Expanded Multicenter Study of the MitraClip System), the phase III follow-up to EVEREST II, continues to enroll patients in the United States and Canada, with a final completion date of December 2016.

Dr. Schillinger reported receiving consulting fees/honoraria from study sponsor Abbott Vascular, as well as Abiomed, AstraZeneca, Edwards Lifesciences, Servier, and St. Jude Medical. Dr. Ray reported no relevant conflicts of interest.

MUNICH – One-year results of the ACCESS-EUROPE study confirm the safety and benefits of percutaneous mitral valve repair with the MitraClip in high-risk patients with heart failure, although patient selection remains a critical issue going forward.

The severity of mitral regurgitation was improved to a meaningful extent in about 80% of patients, and was accompanied by significant improvements at 1 year in New York Heart Association (NYHA) functional class, quality of life, and 6-minute walk test distance in about 70%.

Patrice Wendling/IMNG Medical Media

"The MitraClip therapy therefore provides a treatment option for a patient population with an important unmet clinical need," Dr. Wolfgang Schillinger said at the annual congress of the European Society of Cardiology.

The MitraClip device has been approved in Europe since 2008 and implanted in more than 6,000 patients worldwide, but is not commercially available in the United States.

Dr. Schillinger pointed out that the results provide a "picture of the real-world treatment in Europe," and are consistent with those from clinical trials, even though ACCESS-EU patients were older and sicker than those in the pivotal, randomized EVEREST II trial.

The 567 patients enrolled in the ACCESS-EU registry were described as having abundant comorbidities, including coronary artery disease in 63% and moderate to severe renal failure in 42%, and severe symptoms of end-stage heart failure, with 85% in NYHA functional class III or IV. The average logistic EuroSCORE was 23, 77% presented with functional mitral regurgitation (MR), and 98% had MR grade 3+ or higher. Their mean age was 74 years.

In contrast, the average age was 67 years in the phase II EVEREST II study, where 73% of the device patients had degenerative MR. Less than half (47%) had coronary artery disease, and only 3% had moderate/severe renal failure.

Study discussant Dr. Simon Ray, with the Manchester (U.K.) Academic Health Science Centre, said ACCESS-EU confirms data from smaller registries and that the majority of MitraClip procedures are now performed in comorbid, sick patients with functional MR, and not in the patients included in EVEREST II.

Patrice Wendling/IMNG Medical Media

"So clinical practice has evolved beyond the envelope provided by the evidenced-based, single randomized controlled trial in this field," he said.

The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines state that in patients with an indication for valve repair, but judged inoperable or at unacceptably high surgical risk, percutaneous edge-to-edge repair "may be considered" in order to improve symptoms.

The key going forward is to make sure patients undergoing this procedure genuinely have severe MR, that the assessment of operative risk reflects that of surgeons involved in the decision-making, and that the procedure is only done to improve symptoms, Dr. Ray said.

"There is no evidence that percutaneous edge-to-edge repair improves survival in this patient group," he said.

The decision to choose the less invasive catheter-based therapy over surgery was left up to the 14 ACCESS-EU registry sites.

The MitraClip device was successfully implanted in 99.6% of patients, an improvement over the 86% procedural rate during early experience with the implant in EVEREST II (N. Engl. J. Med. 2011;364:1395-406).

Mortality was low at 3.4% at 30 days, "which is a very good result in view of the comorbidities and the increased risk of the procedures," said Dr. Schillinger, with the University Medical Center Göttingen, Germany.

The most frequently reported safety events were moderate to severe renal failure in 4.8% of patients and bleeding complications in 4%, and the event rates remained low even in higher-risk patients with a EuroSCORE above 20.

At 1 year, 82% of patients were free from death, 79% had MR grade 2 or lower, and 72% were NYHA class I or II.

Significant gains were also made in quality of life scores, averaging 13.5 points from baseline on the Minnesota Living with Heart Failure Questionnaire (from 41.6 to 28.1), and averaging 59.5 m (from 275 to 334 m) in the 6-minute walk test, he said.

"What this registry does, and it is very important, is to raise perhaps more questions than it provides answers, and a number of these are around patient selection," Dr. Ray said.

What’s known from the current registry and others is that 25%-35% of patients will derive little or no symptomatic benefit from percutaneous repair. What’s not clear is whether this is due to incorrect or insufficiently sophisticated assessment of valve anatomy or overestimation of the severity of the MR because quantitative techniques have not generally been used in the registries, he said. It’s also possible that patients are being included with such severe degrees of left ventricular dysfunction that they are unlikely to benefit.

"We also need to have an eye on what constitutes success, because a technically successful procedure leading to a reduction in mitral valve regurgitation in these patients is coincidental, if they do not also have some symptomatic and functional benefit," he added.

Finally, Dr. Ray called for a pragmatic randomized trial, driven by a heart team, comparing optimized medical therapy with the addition of cardiac resynchronization therapy, where indicated, against that treatment plus the MitraClip device.

The phase III COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients) trial in moderate to severe or severe functional MR patients is not yet recruiting, but will compare the MitraClip device with patients managed nonsurgically based on standard hospital practice. REALISM (Real World Expanded Multicenter Study of the MitraClip System), the phase III follow-up to EVEREST II, continues to enroll patients in the United States and Canada, with a final completion date of December 2016.

Dr. Schillinger reported receiving consulting fees/honoraria from study sponsor Abbott Vascular, as well as Abiomed, AstraZeneca, Edwards Lifesciences, Servier, and St. Jude Medical. Dr. Ray reported no relevant conflicts of interest.

MUNICH – One-year results of the ACCESS-EUROPE study confirm the safety and benefits of percutaneous mitral valve repair with the MitraClip in high-risk patients with heart failure, although patient selection remains a critical issue going forward.

The severity of mitral regurgitation was improved to a meaningful extent in about 80% of patients, and was accompanied by significant improvements at 1 year in New York Heart Association (NYHA) functional class, quality of life, and 6-minute walk test distance in about 70%.

Patrice Wendling/IMNG Medical Media

"The MitraClip therapy therefore provides a treatment option for a patient population with an important unmet clinical need," Dr. Wolfgang Schillinger said at the annual congress of the European Society of Cardiology.

The MitraClip device has been approved in Europe since 2008 and implanted in more than 6,000 patients worldwide, but is not commercially available in the United States.

Dr. Schillinger pointed out that the results provide a "picture of the real-world treatment in Europe," and are consistent with those from clinical trials, even though ACCESS-EU patients were older and sicker than those in the pivotal, randomized EVEREST II trial.

The 567 patients enrolled in the ACCESS-EU registry were described as having abundant comorbidities, including coronary artery disease in 63% and moderate to severe renal failure in 42%, and severe symptoms of end-stage heart failure, with 85% in NYHA functional class III or IV. The average logistic EuroSCORE was 23, 77% presented with functional mitral regurgitation (MR), and 98% had MR grade 3+ or higher. Their mean age was 74 years.

In contrast, the average age was 67 years in the phase II EVEREST II study, where 73% of the device patients had degenerative MR. Less than half (47%) had coronary artery disease, and only 3% had moderate/severe renal failure.

Study discussant Dr. Simon Ray, with the Manchester (U.K.) Academic Health Science Centre, said ACCESS-EU confirms data from smaller registries and that the majority of MitraClip procedures are now performed in comorbid, sick patients with functional MR, and not in the patients included in EVEREST II.

Patrice Wendling/IMNG Medical Media

"So clinical practice has evolved beyond the envelope provided by the evidenced-based, single randomized controlled trial in this field," he said.

The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines state that in patients with an indication for valve repair, but judged inoperable or at unacceptably high surgical risk, percutaneous edge-to-edge repair "may be considered" in order to improve symptoms.

The key going forward is to make sure patients undergoing this procedure genuinely have severe MR, that the assessment of operative risk reflects that of surgeons involved in the decision-making, and that the procedure is only done to improve symptoms, Dr. Ray said.

"There is no evidence that percutaneous edge-to-edge repair improves survival in this patient group," he said.

The decision to choose the less invasive catheter-based therapy over surgery was left up to the 14 ACCESS-EU registry sites.

The MitraClip device was successfully implanted in 99.6% of patients, an improvement over the 86% procedural rate during early experience with the implant in EVEREST II (N. Engl. J. Med. 2011;364:1395-406).

Mortality was low at 3.4% at 30 days, "which is a very good result in view of the comorbidities and the increased risk of the procedures," said Dr. Schillinger, with the University Medical Center Göttingen, Germany.

The most frequently reported safety events were moderate to severe renal failure in 4.8% of patients and bleeding complications in 4%, and the event rates remained low even in higher-risk patients with a EuroSCORE above 20.

At 1 year, 82% of patients were free from death, 79% had MR grade 2 or lower, and 72% were NYHA class I or II.

Significant gains were also made in quality of life scores, averaging 13.5 points from baseline on the Minnesota Living with Heart Failure Questionnaire (from 41.6 to 28.1), and averaging 59.5 m (from 275 to 334 m) in the 6-minute walk test, he said.

"What this registry does, and it is very important, is to raise perhaps more questions than it provides answers, and a number of these are around patient selection," Dr. Ray said.

What’s known from the current registry and others is that 25%-35% of patients will derive little or no symptomatic benefit from percutaneous repair. What’s not clear is whether this is due to incorrect or insufficiently sophisticated assessment of valve anatomy or overestimation of the severity of the MR because quantitative techniques have not generally been used in the registries, he said. It’s also possible that patients are being included with such severe degrees of left ventricular dysfunction that they are unlikely to benefit.

"We also need to have an eye on what constitutes success, because a technically successful procedure leading to a reduction in mitral valve regurgitation in these patients is coincidental, if they do not also have some symptomatic and functional benefit," he added.

Finally, Dr. Ray called for a pragmatic randomized trial, driven by a heart team, comparing optimized medical therapy with the addition of cardiac resynchronization therapy, where indicated, against that treatment plus the MitraClip device.

The phase III COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients) trial in moderate to severe or severe functional MR patients is not yet recruiting, but will compare the MitraClip device with patients managed nonsurgically based on standard hospital practice. REALISM (Real World Expanded Multicenter Study of the MitraClip System), the phase III follow-up to EVEREST II, continues to enroll patients in the United States and Canada, with a final completion date of December 2016.

Dr. Schillinger reported receiving consulting fees/honoraria from study sponsor Abbott Vascular, as well as Abiomed, AstraZeneca, Edwards Lifesciences, Servier, and St. Jude Medical. Dr. Ray reported no relevant conflicts of interest.

MUNICH – Patients with severe psoriasis have a twofold increased risk of developing new-onset diabetes based on a review of more than 4 million Danish children and adults, the first nationwide cohort to be evaluated for a link between the two diseases.

"Our results underline the importance of considering psoriatic patients as a high-risk population in terms of diabetes and cardiovascular risk," Mr. Usman Khalid said at the Annual Congress of the European Society of Cardiology. "Screening for diabetes and cardiovascular risk factors in patients with psoriasis is warranted," and follows existing guidelines for managing patients with psoriasis, said Mr. Khalid, a researcher in the cardiovascular research unit of Gentofte Hospital in Copenhagen.

The likely mechanism underlying the association is the inflammatory state of patients with psoriasis, he added.

"These observations are new, interesting, and important," commented Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm. Physicians should add "carefully looking for diabetes" to their existing routine screening in psoriasis patients, he said.

The study used Danish national population and patient records for more than 4.6 million Danish citizens aged 10 years or older from 1997 through the end of 2009. The researchers excluded the 97,000 people who had diabetes, psoriasis, or both at entry into the database, which left just more than 4.5 million people, of whom 52,613 developed new-onset psoriasis during follow-up, and 4,465,643 people without psoriasis who served as the reference population. The researchers defined severe psoriasis as a case that required hospitalization at least three times, or patients diagnosed with psoriatic arthritis. The cohort of children and adults with incidence psoriasis included 45,829 mild cases, and 6,784 severe cases.

The researchers tallied the number of people who developed new-onset diabetes, both among those who never had psoriasis during the study period, and among those who developed psoriasis. They identified new diabetes cases based on initiation of treatment with one or more glucose-lowering drugs. During follow-up, the number of new cases of diabetes was 3.67/1,000 person-years among those with no psoriasis, 6.93/1,000 patient-years among patients with mild psoriasis, and 9.65/1,000 patient-years among patients with severe psoriasis. The vast majority of the diabetes that developed was type 2.

Using adjustments that controlled for potential confounders at baseline, including age, sex, comorbidities, medications, and socioeconomic status, the researchers found that, compared with the people without psoriasis, those with mild psoriasis had a statistically significant 47% increased incidence of diabetes, and severe psoriasis linked with a statistically significant twofold increased risk for diabetes, Mr. Khalid reported. The median time from onset of psoriasis to the first treatment for diabetes was about 6 years.

The analysis notably focused on patients who developed diabetes following initial development of psoriasis, which provided insight into the sequence of the two diseases that had not been available in previously-reported studies, noted Dr. Ole Ahlehoff, a cardiology researcher at Gentofte Hospital and collaborator on the study.

"I suggest screening patients with psoriasis once a year for cardiovascular risk factors, including hypertension, dyslipidemia, lifestyle factors, and diabetes based on their glucose level," said Dr. Ahlehoff, who spoke about the research at a press conference. Medical groups have released guidelines that recommend annual risk assessment for patients with severe psoriasis, such as psoriatic arthritis, including the European League Against Arthritis (Ann. Rheum. Dis. 2010;69:325-31), and the Scottish Intercollegiate Guidelines Network.

Mr. Khalid and Dr. Ahlehoff said that they had no disclosures. Dr. Rydén had no relevant disclosures.

MUNICH – Patients with severe psoriasis have a twofold increased risk of developing new-onset diabetes based on a review of more than 4 million Danish children and adults, the first nationwide cohort to be evaluated for a link between the two diseases.

"Our results underline the importance of considering psoriatic patients as a high-risk population in terms of diabetes and cardiovascular risk," Mr. Usman Khalid said at the Annual Congress of the European Society of Cardiology. "Screening for diabetes and cardiovascular risk factors in patients with psoriasis is warranted," and follows existing guidelines for managing patients with psoriasis, said Mr. Khalid, a researcher in the cardiovascular research unit of Gentofte Hospital in Copenhagen.

The likely mechanism underlying the association is the inflammatory state of patients with psoriasis, he added.

"These observations are new, interesting, and important," commented Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm. Physicians should add "carefully looking for diabetes" to their existing routine screening in psoriasis patients, he said.

The study used Danish national population and patient records for more than 4.6 million Danish citizens aged 10 years or older from 1997 through the end of 2009. The researchers excluded the 97,000 people who had diabetes, psoriasis, or both at entry into the database, which left just more than 4.5 million people, of whom 52,613 developed new-onset psoriasis during follow-up, and 4,465,643 people without psoriasis who served as the reference population. The researchers defined severe psoriasis as a case that required hospitalization at least three times, or patients diagnosed with psoriatic arthritis. The cohort of children and adults with incidence psoriasis included 45,829 mild cases, and 6,784 severe cases.

The researchers tallied the number of people who developed new-onset diabetes, both among those who never had psoriasis during the study period, and among those who developed psoriasis. They identified new diabetes cases based on initiation of treatment with one or more glucose-lowering drugs. During follow-up, the number of new cases of diabetes was 3.67/1,000 person-years among those with no psoriasis, 6.93/1,000 patient-years among patients with mild psoriasis, and 9.65/1,000 patient-years among patients with severe psoriasis. The vast majority of the diabetes that developed was type 2.

Using adjustments that controlled for potential confounders at baseline, including age, sex, comorbidities, medications, and socioeconomic status, the researchers found that, compared with the people without psoriasis, those with mild psoriasis had a statistically significant 47% increased incidence of diabetes, and severe psoriasis linked with a statistically significant twofold increased risk for diabetes, Mr. Khalid reported. The median time from onset of psoriasis to the first treatment for diabetes was about 6 years.

The analysis notably focused on patients who developed diabetes following initial development of psoriasis, which provided insight into the sequence of the two diseases that had not been available in previously-reported studies, noted Dr. Ole Ahlehoff, a cardiology researcher at Gentofte Hospital and collaborator on the study.

"I suggest screening patients with psoriasis once a year for cardiovascular risk factors, including hypertension, dyslipidemia, lifestyle factors, and diabetes based on their glucose level," said Dr. Ahlehoff, who spoke about the research at a press conference. Medical groups have released guidelines that recommend annual risk assessment for patients with severe psoriasis, such as psoriatic arthritis, including the European League Against Arthritis (Ann. Rheum. Dis. 2010;69:325-31), and the Scottish Intercollegiate Guidelines Network.

Mr. Khalid and Dr. Ahlehoff said that they had no disclosures. Dr. Rydén had no relevant disclosures.

MUNICH – Patients with severe psoriasis have a twofold increased risk of developing new-onset diabetes based on a review of more than 4 million Danish children and adults, the first nationwide cohort to be evaluated for a link between the two diseases.

"Our results underline the importance of considering psoriatic patients as a high-risk population in terms of diabetes and cardiovascular risk," Mr. Usman Khalid said at the Annual Congress of the European Society of Cardiology. "Screening for diabetes and cardiovascular risk factors in patients with psoriasis is warranted," and follows existing guidelines for managing patients with psoriasis, said Mr. Khalid, a researcher in the cardiovascular research unit of Gentofte Hospital in Copenhagen.

The likely mechanism underlying the association is the inflammatory state of patients with psoriasis, he added.

"These observations are new, interesting, and important," commented Dr. Lars Rydén, professor of cardiology at the Karolinska Institute in Stockholm. Physicians should add "carefully looking for diabetes" to their existing routine screening in psoriasis patients, he said.

The study used Danish national population and patient records for more than 4.6 million Danish citizens aged 10 years or older from 1997 through the end of 2009. The researchers excluded the 97,000 people who had diabetes, psoriasis, or both at entry into the database, which left just more than 4.5 million people, of whom 52,613 developed new-onset psoriasis during follow-up, and 4,465,643 people without psoriasis who served as the reference population. The researchers defined severe psoriasis as a case that required hospitalization at least three times, or patients diagnosed with psoriatic arthritis. The cohort of children and adults with incidence psoriasis included 45,829 mild cases, and 6,784 severe cases.

The researchers tallied the number of people who developed new-onset diabetes, both among those who never had psoriasis during the study period, and among those who developed psoriasis. They identified new diabetes cases based on initiation of treatment with one or more glucose-lowering drugs. During follow-up, the number of new cases of diabetes was 3.67/1,000 person-years among those with no psoriasis, 6.93/1,000 patient-years among patients with mild psoriasis, and 9.65/1,000 patient-years among patients with severe psoriasis. The vast majority of the diabetes that developed was type 2.

Using adjustments that controlled for potential confounders at baseline, including age, sex, comorbidities, medications, and socioeconomic status, the researchers found that, compared with the people without psoriasis, those with mild psoriasis had a statistically significant 47% increased incidence of diabetes, and severe psoriasis linked with a statistically significant twofold increased risk for diabetes, Mr. Khalid reported. The median time from onset of psoriasis to the first treatment for diabetes was about 6 years.

The analysis notably focused on patients who developed diabetes following initial development of psoriasis, which provided insight into the sequence of the two diseases that had not been available in previously-reported studies, noted Dr. Ole Ahlehoff, a cardiology researcher at Gentofte Hospital and collaborator on the study.

"I suggest screening patients with psoriasis once a year for cardiovascular risk factors, including hypertension, dyslipidemia, lifestyle factors, and diabetes based on their glucose level," said Dr. Ahlehoff, who spoke about the research at a press conference. Medical groups have released guidelines that recommend annual risk assessment for patients with severe psoriasis, such as psoriatic arthritis, including the European League Against Arthritis (Ann. Rheum. Dis. 2010;69:325-31), and the Scottish Intercollegiate Guidelines Network.

Mr. Khalid and Dr. Ahlehoff said that they had no disclosures. Dr. Rydén had no relevant disclosures.

MUNICH – Patients who resume smoking after an ischemic stroke raise their risk of dying by roughly threefold within 1 year, a prospective, observational study has shown.

Moreover, the risk of dying increases the sooner the relapse occurs. Patients who resume smoking within 10 days of leaving the hospital are five times more likely to die within a year than are those who remain smoke free.

Patrice Wendling/IMNG Medical Media

"Smoking relapse is extremely dangerous after an acute ischemic stroke," said Dr. Furio Colivicchi of the cardiovascular department at San Filippo Neri Hospital, Rome.

Cardiologists at San Filippo, in collaboration with neurologists from the Santa Lucia Foundation of Rome, enrolled 921 consecutive active smokers who ceased smoking after admission to the hospital for acute ischemic stroke and reported being motivated to continue abstaining once discharged.

All patients received a brief in-hospital smoking cessation counseling session lasting 5-20 minutes and delivered by trained nurses (73%) or physicians (27%).

Patients did not receive any specific postdischarge support or pharmacotherapy for smoking cessation. One-third of patients (34%), however, were referred to a hospital-based rehabilitation program after their stroke.

The cohort of 584 men and 337 women had an average National Institutes of Health Stroke Scale score of 9.1, 11% had had a previous stroke, 18% had a previous myocardial infarction, 69% had hypertension, and 20% were obese. Their average age was 67 years.

During the 12-month follow-up, 54% of all patients resumed regular cigarette smoking, with 50% relapsing within 3 weeks of discharge, Dr. Colivicchi reported at the annual congress of the European Society of Cardiology.

Patients who relapsed were significantly more likely to be older (69 years vs. 65 years) and female (44% vs. 28%), and were less likely to do so if referred to a hospital-based stroke rehabilitation program (25% vs. 44%), all highly significant differences.

During the 12-month follow-up, 89 patients (9.7%) died. Most of the deaths were due to ischemic events, both coronary and stroke recurrences, Dr. Colivicchi told the media at the meeting.

"The causal link between smoke and further ischemic events is complex," he said. "But we do know that smoking has a negative impact on the cardiovascular system, and it increases the ability of the platelets to aggregate, for instance, which is a crucial point in these ischemic syndromes."

After adjustment for confounding interactions including clinical variables and variables related to the acute event, a strong relationship was found between smoking relapse and all-cause mortality, Dr. Colivicchi said. The risk of death was 5.1-fold higher at 10 days, 3.8-fold higher at 120 days, and 2.6-fold higher at roughly 1 year.

A linear correlation exists between the number of cigarettes and the probability of suffering an acute cardiovascular event, but even small amounts, such as fewer than five cigarettes per day, have been linked to increased cardiovascular events, he noted. Most of the patients in the study were heavy smokers, smoking more than 10 cigarettes per day prior to the index event and typically relapsing to their original amount.

"We must be very careful and provide a more comprehensive approach because individual counseling is not fully effective if it is not followed by postdischarge support for this specific problem and possibly, in selected cases, by pharmacological treatment aimed at reducing the risk of relapse," he said.

A recent study in 4,834 patients with acute coronary syndrome (ACS) reported that while 20% were smokers at the time of their ACS, only 24% received any smoking intervention from their general practitioner within 3 months of the event. Of these, 9% received advice only and 15% received pharmacological intervention (Eur. J. Prev. Cardiol. 2012 Sept. 5 [epub ahead of print]).

Dr. Colivicchi reported no relevant financial conflicts.

MUNICH – Patients who resume smoking after an ischemic stroke raise their risk of dying by roughly threefold within 1 year, a prospective, observational study has shown.

Moreover, the risk of dying increases the sooner the relapse occurs. Patients who resume smoking within 10 days of leaving the hospital are five times more likely to die within a year than are those who remain smoke free.

Patrice Wendling/IMNG Medical Media

"Smoking relapse is extremely dangerous after an acute ischemic stroke," said Dr. Furio Colivicchi of the cardiovascular department at San Filippo Neri Hospital, Rome.

Cardiologists at San Filippo, in collaboration with neurologists from the Santa Lucia Foundation of Rome, enrolled 921 consecutive active smokers who ceased smoking after admission to the hospital for acute ischemic stroke and reported being motivated to continue abstaining once discharged.

All patients received a brief in-hospital smoking cessation counseling session lasting 5-20 minutes and delivered by trained nurses (73%) or physicians (27%).

Patients did not receive any specific postdischarge support or pharmacotherapy for smoking cessation. One-third of patients (34%), however, were referred to a hospital-based rehabilitation program after their stroke.

The cohort of 584 men and 337 women had an average National Institutes of Health Stroke Scale score of 9.1, 11% had had a previous stroke, 18% had a previous myocardial infarction, 69% had hypertension, and 20% were obese. Their average age was 67 years.

During the 12-month follow-up, 54% of all patients resumed regular cigarette smoking, with 50% relapsing within 3 weeks of discharge, Dr. Colivicchi reported at the annual congress of the European Society of Cardiology.

Patients who relapsed were significantly more likely to be older (69 years vs. 65 years) and female (44% vs. 28%), and were less likely to do so if referred to a hospital-based stroke rehabilitation program (25% vs. 44%), all highly significant differences.

During the 12-month follow-up, 89 patients (9.7%) died. Most of the deaths were due to ischemic events, both coronary and stroke recurrences, Dr. Colivicchi told the media at the meeting.

"The causal link between smoke and further ischemic events is complex," he said. "But we do know that smoking has a negative impact on the cardiovascular system, and it increases the ability of the platelets to aggregate, for instance, which is a crucial point in these ischemic syndromes."

After adjustment for confounding interactions including clinical variables and variables related to the acute event, a strong relationship was found between smoking relapse and all-cause mortality, Dr. Colivicchi said. The risk of death was 5.1-fold higher at 10 days, 3.8-fold higher at 120 days, and 2.6-fold higher at roughly 1 year.

A linear correlation exists between the number of cigarettes and the probability of suffering an acute cardiovascular event, but even small amounts, such as fewer than five cigarettes per day, have been linked to increased cardiovascular events, he noted. Most of the patients in the study were heavy smokers, smoking more than 10 cigarettes per day prior to the index event and typically relapsing to their original amount.

"We must be very careful and provide a more comprehensive approach because individual counseling is not fully effective if it is not followed by postdischarge support for this specific problem and possibly, in selected cases, by pharmacological treatment aimed at reducing the risk of relapse," he said.

A recent study in 4,834 patients with acute coronary syndrome (ACS) reported that while 20% were smokers at the time of their ACS, only 24% received any smoking intervention from their general practitioner within 3 months of the event. Of these, 9% received advice only and 15% received pharmacological intervention (Eur. J. Prev. Cardiol. 2012 Sept. 5 [epub ahead of print]).

Dr. Colivicchi reported no relevant financial conflicts.

MUNICH – Patients who resume smoking after an ischemic stroke raise their risk of dying by roughly threefold within 1 year, a prospective, observational study has shown.

Moreover, the risk of dying increases the sooner the relapse occurs. Patients who resume smoking within 10 days of leaving the hospital are five times more likely to die within a year than are those who remain smoke free.

Patrice Wendling/IMNG Medical Media

"Smoking relapse is extremely dangerous after an acute ischemic stroke," said Dr. Furio Colivicchi of the cardiovascular department at San Filippo Neri Hospital, Rome.

Cardiologists at San Filippo, in collaboration with neurologists from the Santa Lucia Foundation of Rome, enrolled 921 consecutive active smokers who ceased smoking after admission to the hospital for acute ischemic stroke and reported being motivated to continue abstaining once discharged.

All patients received a brief in-hospital smoking cessation counseling session lasting 5-20 minutes and delivered by trained nurses (73%) or physicians (27%).

Patients did not receive any specific postdischarge support or pharmacotherapy for smoking cessation. One-third of patients (34%), however, were referred to a hospital-based rehabilitation program after their stroke.

The cohort of 584 men and 337 women had an average National Institutes of Health Stroke Scale score of 9.1, 11% had had a previous stroke, 18% had a previous myocardial infarction, 69% had hypertension, and 20% were obese. Their average age was 67 years.

During the 12-month follow-up, 54% of all patients resumed regular cigarette smoking, with 50% relapsing within 3 weeks of discharge, Dr. Colivicchi reported at the annual congress of the European Society of Cardiology.

Patients who relapsed were significantly more likely to be older (69 years vs. 65 years) and female (44% vs. 28%), and were less likely to do so if referred to a hospital-based stroke rehabilitation program (25% vs. 44%), all highly significant differences.

During the 12-month follow-up, 89 patients (9.7%) died. Most of the deaths were due to ischemic events, both coronary and stroke recurrences, Dr. Colivicchi told the media at the meeting.

"The causal link between smoke and further ischemic events is complex," he said. "But we do know that smoking has a negative impact on the cardiovascular system, and it increases the ability of the platelets to aggregate, for instance, which is a crucial point in these ischemic syndromes."

After adjustment for confounding interactions including clinical variables and variables related to the acute event, a strong relationship was found between smoking relapse and all-cause mortality, Dr. Colivicchi said. The risk of death was 5.1-fold higher at 10 days, 3.8-fold higher at 120 days, and 2.6-fold higher at roughly 1 year.

A linear correlation exists between the number of cigarettes and the probability of suffering an acute cardiovascular event, but even small amounts, such as fewer than five cigarettes per day, have been linked to increased cardiovascular events, he noted. Most of the patients in the study were heavy smokers, smoking more than 10 cigarettes per day prior to the index event and typically relapsing to their original amount.

"We must be very careful and provide a more comprehensive approach because individual counseling is not fully effective if it is not followed by postdischarge support for this specific problem and possibly, in selected cases, by pharmacological treatment aimed at reducing the risk of relapse," he said.

A recent study in 4,834 patients with acute coronary syndrome (ACS) reported that while 20% were smokers at the time of their ACS, only 24% received any smoking intervention from their general practitioner within 3 months of the event. Of these, 9% received advice only and 15% received pharmacological intervention (Eur. J. Prev. Cardiol. 2012 Sept. 5 [epub ahead of print]).

Dr. Colivicchi reported no relevant financial conflicts.