Heart Failure

DALLAS — The obesity paradox previously described in patients with chronic systolic heart failure has, for the first time, been shown to be strikingly evident in acute heart failure as well, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association.

An analysis of 108,927 hospitalizations recorded in the Acute Decompensated Heart Failure Registry (ADHERE) showed that in-hospital mortality decreased in near-linear fashion with increasing body mass index (BMI) quartile. (See box.)

The same marked reduction in in-hospital mortality that was seen in heavier ADHERE participants who had reduced systolic function was also seen in those with preserved systolic function, added Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The paradox lies in the fact that obesity is a well-recognized independent cardiovascular risk factor in the general population, yet in the setting of chronic or acute heart failure, it is somehow protective.

The bottom line is that the paradox in acute heart failure is a real phenomenon. “Given the huge number of hospital episodes we're looking at here, the results are irrefutable,” Dr. Fonarow said.

The obesity paradox has potentially enormous clinical implications for the management of acute decompensated heart failure, a condition that constitutes the primary or secondary diagnosis in an estimated 3 million hospitalizations annually in the United States. The next step in the research is to provide acute nutritional support when normal-weight or underweight patients—those with, say, a BMI below 27 kg/m

“The broad implication is that this represents half of all acute heart failure hospitalizations, and they could potentially be amenable to having their acute mortality rates cut by one-third to one-half if this therapy pans out,” Dr. Fonarow said in an interview.

“We're seriously thinking of doing some pilot studies looking at whether we can improve measures of cardiac function and nutritional status in these patients through acute nutritional support—and if that looks promising, to go forward with an interventional trial,” he said.

Only through such studies will physicians learn whether obesity is causative of reduced mortality in acute heart failure patients or whether it is merely a marker for lower risk. It is worth noting, though, that even after adjustment for known predictors of in-hospital mortality in acute heart failure—including age, gender, blood urea nitrogen, creatinine, blood pressure, and dyspnea at rest—patients in the lowest BMI quartile had a highly significant 46% greater in-hospital mortality than did those in the top quartile, who had a BMI of at least 33.4.

The same held true when patients were grouped by World Health Organization BMI category rather than by quartile. Underweight patients—those with a BMI less than 18.5—had an in-hospital mortality of 6.3%. The rate was 4.6% in normal-weight patients (BMI 18.5–24.9), 3.4% in overweight patients (BMI 25.0–29.9), and 2.4% in obese patients.

The obesity paradox in acute heart failure cannot be explained merely as a reflection of cachectic patients being unable to handle the stress of acute illness. After all, in-hospital mortality was increased even in normal-weight patients, compared with those who were overweight or obese, Dr. Fonarow said.

ADHERE is funded by Scios Inc.

KEVIN FOLEY, RESEARCH

DALLAS — The obesity paradox previously described in patients with chronic systolic heart failure has, for the first time, been shown to be strikingly evident in acute heart failure as well, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association.

An analysis of 108,927 hospitalizations recorded in the Acute Decompensated Heart Failure Registry (ADHERE) showed that in-hospital mortality decreased in near-linear fashion with increasing body mass index (BMI) quartile. (See box.)

The same marked reduction in in-hospital mortality that was seen in heavier ADHERE participants who had reduced systolic function was also seen in those with preserved systolic function, added Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The paradox lies in the fact that obesity is a well-recognized independent cardiovascular risk factor in the general population, yet in the setting of chronic or acute heart failure, it is somehow protective.

The bottom line is that the paradox in acute heart failure is a real phenomenon. “Given the huge number of hospital episodes we're looking at here, the results are irrefutable,” Dr. Fonarow said.

The obesity paradox has potentially enormous clinical implications for the management of acute decompensated heart failure, a condition that constitutes the primary or secondary diagnosis in an estimated 3 million hospitalizations annually in the United States. The next step in the research is to provide acute nutritional support when normal-weight or underweight patients—those with, say, a BMI below 27 kg/m

“The broad implication is that this represents half of all acute heart failure hospitalizations, and they could potentially be amenable to having their acute mortality rates cut by one-third to one-half if this therapy pans out,” Dr. Fonarow said in an interview.

“We're seriously thinking of doing some pilot studies looking at whether we can improve measures of cardiac function and nutritional status in these patients through acute nutritional support—and if that looks promising, to go forward with an interventional trial,” he said.

Only through such studies will physicians learn whether obesity is causative of reduced mortality in acute heart failure patients or whether it is merely a marker for lower risk. It is worth noting, though, that even after adjustment for known predictors of in-hospital mortality in acute heart failure—including age, gender, blood urea nitrogen, creatinine, blood pressure, and dyspnea at rest—patients in the lowest BMI quartile had a highly significant 46% greater in-hospital mortality than did those in the top quartile, who had a BMI of at least 33.4.

The same held true when patients were grouped by World Health Organization BMI category rather than by quartile. Underweight patients—those with a BMI less than 18.5—had an in-hospital mortality of 6.3%. The rate was 4.6% in normal-weight patients (BMI 18.5–24.9), 3.4% in overweight patients (BMI 25.0–29.9), and 2.4% in obese patients.

The obesity paradox in acute heart failure cannot be explained merely as a reflection of cachectic patients being unable to handle the stress of acute illness. After all, in-hospital mortality was increased even in normal-weight patients, compared with those who were overweight or obese, Dr. Fonarow said.

ADHERE is funded by Scios Inc.

KEVIN FOLEY, RESEARCH

DALLAS — The obesity paradox previously described in patients with chronic systolic heart failure has, for the first time, been shown to be strikingly evident in acute heart failure as well, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association.

An analysis of 108,927 hospitalizations recorded in the Acute Decompensated Heart Failure Registry (ADHERE) showed that in-hospital mortality decreased in near-linear fashion with increasing body mass index (BMI) quartile. (See box.)

The same marked reduction in in-hospital mortality that was seen in heavier ADHERE participants who had reduced systolic function was also seen in those with preserved systolic function, added Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The paradox lies in the fact that obesity is a well-recognized independent cardiovascular risk factor in the general population, yet in the setting of chronic or acute heart failure, it is somehow protective.

The bottom line is that the paradox in acute heart failure is a real phenomenon. “Given the huge number of hospital episodes we're looking at here, the results are irrefutable,” Dr. Fonarow said.

The obesity paradox has potentially enormous clinical implications for the management of acute decompensated heart failure, a condition that constitutes the primary or secondary diagnosis in an estimated 3 million hospitalizations annually in the United States. The next step in the research is to provide acute nutritional support when normal-weight or underweight patients—those with, say, a BMI below 27 kg/m

“The broad implication is that this represents half of all acute heart failure hospitalizations, and they could potentially be amenable to having their acute mortality rates cut by one-third to one-half if this therapy pans out,” Dr. Fonarow said in an interview.

“We're seriously thinking of doing some pilot studies looking at whether we can improve measures of cardiac function and nutritional status in these patients through acute nutritional support—and if that looks promising, to go forward with an interventional trial,” he said.

Only through such studies will physicians learn whether obesity is causative of reduced mortality in acute heart failure patients or whether it is merely a marker for lower risk. It is worth noting, though, that even after adjustment for known predictors of in-hospital mortality in acute heart failure—including age, gender, blood urea nitrogen, creatinine, blood pressure, and dyspnea at rest—patients in the lowest BMI quartile had a highly significant 46% greater in-hospital mortality than did those in the top quartile, who had a BMI of at least 33.4.

The same held true when patients were grouped by World Health Organization BMI category rather than by quartile. Underweight patients—those with a BMI less than 18.5—had an in-hospital mortality of 6.3%. The rate was 4.6% in normal-weight patients (BMI 18.5–24.9), 3.4% in overweight patients (BMI 25.0–29.9), and 2.4% in obese patients.

The obesity paradox in acute heart failure cannot be explained merely as a reflection of cachectic patients being unable to handle the stress of acute illness. After all, in-hospital mortality was increased even in normal-weight patients, compared with those who were overweight or obese, Dr. Fonarow said.

ADHERE is funded by Scios Inc.

KEVIN FOLEY, RESEARCH

DALLAS — The investigational acute decompensated heart failure drug levosimendan garnered mixed reviews for its less-than-stellar performance in two large, multinational, double-blind, randomized clinical trials presented at the annual scientific sessions of the American Heart Association.

Levosimendan has both inotropic and vasodilator properties. But unlike other positive inotropes, whose action is mediated by increased intracellular calcium, levosimendan enhances cardiac myofilament sensitivity to an unchanged concentration of calcium. The drug also possesses peripheral vasodilator action mediated by an agonist effect on potassium channels.

Dr. Milton Packer reported on 600 patients in the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE II) trial who were hospitalized for acute decompensated heart failure (ADHF) not adequately responsive to intravenous diuretics. They were randomized to a 24-hour infusion of levosimendan or placebo, with intensification of standard background therapies as needed.

The primary end point in REVIVE II was a composite measure of clinical status during the first 5 days of hospitalization. The levosimendan group fared significantly better in this regard than did the controls, even though levosimendan had been stopped after the first 24 hours. Of those in the levosimendan arm, 76% showed moderate or marked improvement in a composite global assessment score, compared with 65% of controls. In the levosimendan arm, 15% required rescue therapy because their condition worsened, compared with 26% in the placebo arm. Levels of brain natriuretic peptide, a surrogate for heart failure severity, were halved in the levosimendan group and stayed low. Patients treated with Levosimendan felt better in as little as 6 hours, and that feeling persisted through 5 days.

But 28 levosimendan-treated patients developed atrial fibrillation and 72 experienced ventricular arrhythmias, compared with 6 and 51, respectively, on placebo. Symptomatic hypotension and headaches were also more common with levosimendan. There were 49 deaths within 90 days with levosimendan and 40 with placebo, said Dr. Packer, professor of medicine and director of the Center for Biostatistics and Clinical Science at the University of Texas Southwestern Medical Center, Dallas.

He stressed that intravenous diuretics—a fast-acting, safe, and relatively inexpensive treatment—will remain the initial intervention for patients who present with ADHF. He estimated, however, that this therapy achieves an adequate response—relief of shortness of breath at rest—in only about half of the 3 million U.S. hospitalizations per year with ADHF as the primary or secondary diagnosis. It's in the other half that he sees levosimendan as potentially playing a major role.

Dr. Alexandre Mebazaa presented the results of the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study, the first large-scale study to examine the survival impact of medications used to treat ADHF. SURVIVE involved 1,327 patients in eight countries who were randomized to levosimendan or dobutamine along with standard background treatments.

In SURVIVE, the primary end point was 6-month all-cause mortality, which was 26% in the levosimendan arm and 28% with dobutamine, a nonsignificant difference. But it was unrealistic to expect a mortality difference so long after a single 24-hour drug infusion, said Dr. Mebazaa, professor and director of the department of anesthesia and critical care medicine at Lariboisière Hospital, Paris.

The results were more impressive closer to the treatment period. At day 5, for example, mortality was 4.4% in the levosimendan group and 6.0% with dobutamine, a 28% reduction in relative risk. As in REVIVE II, there was an increased incidence of atrial fibrillation with levosimendan, he said.

Some audience members were enthused that the levosimendan trials had raised the bar in terms of the rigor with which ADHF drugs are evaluated. All currently available drugs were approved on the basis of hemodynamic gains rather than evidence of the more meaningful end points of improved clinical status or outcomes.

Dr. Gordon F. Tomaselli, vice chairman of the AHA scientific sessions program committee, said in an interview that given the high lethality of ADHF (more than one-quarter of SURVIVE participants died within 6 months) and the very limited current treatment options, levosimendan “probably does have a place in the armamentarium.”

But Dr. Gregg C. Fonarow was skeptical. “It's hard to conceive that with this dosing regimen this would be a treatment that physicians would want to use for their patients. A reduction in symptoms is not going to be acceptable if it comes at a price of substantial increased risk of severe adverse events,” said Dr Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“If you compare the serious adverse events seen in REVIVE II with what was observed in the largest trial with nesiritide, levosimendan comes nowhere close to being as safe as nesiritide,” he said. Nesiritide (Natrecor) has come under fire in the past year after assertions it may worsen renal function and increase mortality.

Dr. Packer is a consultant to Abbott Laboratories and Orion Pharma, which funded REVIVE II and SURVIVE. Dr. Mebazaa is a consultant to Abbott.

Intravenous diuretics will remain the initial intervention for patients who present with ADHF. DR. PACKER

DALLAS — The investigational acute decompensated heart failure drug levosimendan garnered mixed reviews for its less-than-stellar performance in two large, multinational, double-blind, randomized clinical trials presented at the annual scientific sessions of the American Heart Association.

Levosimendan has both inotropic and vasodilator properties. But unlike other positive inotropes, whose action is mediated by increased intracellular calcium, levosimendan enhances cardiac myofilament sensitivity to an unchanged concentration of calcium. The drug also possesses peripheral vasodilator action mediated by an agonist effect on potassium channels.

Dr. Milton Packer reported on 600 patients in the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE II) trial who were hospitalized for acute decompensated heart failure (ADHF) not adequately responsive to intravenous diuretics. They were randomized to a 24-hour infusion of levosimendan or placebo, with intensification of standard background therapies as needed.

The primary end point in REVIVE II was a composite measure of clinical status during the first 5 days of hospitalization. The levosimendan group fared significantly better in this regard than did the controls, even though levosimendan had been stopped after the first 24 hours. Of those in the levosimendan arm, 76% showed moderate or marked improvement in a composite global assessment score, compared with 65% of controls. In the levosimendan arm, 15% required rescue therapy because their condition worsened, compared with 26% in the placebo arm. Levels of brain natriuretic peptide, a surrogate for heart failure severity, were halved in the levosimendan group and stayed low. Patients treated with Levosimendan felt better in as little as 6 hours, and that feeling persisted through 5 days.

But 28 levosimendan-treated patients developed atrial fibrillation and 72 experienced ventricular arrhythmias, compared with 6 and 51, respectively, on placebo. Symptomatic hypotension and headaches were also more common with levosimendan. There were 49 deaths within 90 days with levosimendan and 40 with placebo, said Dr. Packer, professor of medicine and director of the Center for Biostatistics and Clinical Science at the University of Texas Southwestern Medical Center, Dallas.

He stressed that intravenous diuretics—a fast-acting, safe, and relatively inexpensive treatment—will remain the initial intervention for patients who present with ADHF. He estimated, however, that this therapy achieves an adequate response—relief of shortness of breath at rest—in only about half of the 3 million U.S. hospitalizations per year with ADHF as the primary or secondary diagnosis. It's in the other half that he sees levosimendan as potentially playing a major role.

Dr. Alexandre Mebazaa presented the results of the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study, the first large-scale study to examine the survival impact of medications used to treat ADHF. SURVIVE involved 1,327 patients in eight countries who were randomized to levosimendan or dobutamine along with standard background treatments.

In SURVIVE, the primary end point was 6-month all-cause mortality, which was 26% in the levosimendan arm and 28% with dobutamine, a nonsignificant difference. But it was unrealistic to expect a mortality difference so long after a single 24-hour drug infusion, said Dr. Mebazaa, professor and director of the department of anesthesia and critical care medicine at Lariboisière Hospital, Paris.

The results were more impressive closer to the treatment period. At day 5, for example, mortality was 4.4% in the levosimendan group and 6.0% with dobutamine, a 28% reduction in relative risk. As in REVIVE II, there was an increased incidence of atrial fibrillation with levosimendan, he said.

Some audience members were enthused that the levosimendan trials had raised the bar in terms of the rigor with which ADHF drugs are evaluated. All currently available drugs were approved on the basis of hemodynamic gains rather than evidence of the more meaningful end points of improved clinical status or outcomes.

Dr. Gordon F. Tomaselli, vice chairman of the AHA scientific sessions program committee, said in an interview that given the high lethality of ADHF (more than one-quarter of SURVIVE participants died within 6 months) and the very limited current treatment options, levosimendan “probably does have a place in the armamentarium.”

But Dr. Gregg C. Fonarow was skeptical. “It's hard to conceive that with this dosing regimen this would be a treatment that physicians would want to use for their patients. A reduction in symptoms is not going to be acceptable if it comes at a price of substantial increased risk of severe adverse events,” said Dr Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“If you compare the serious adverse events seen in REVIVE II with what was observed in the largest trial with nesiritide, levosimendan comes nowhere close to being as safe as nesiritide,” he said. Nesiritide (Natrecor) has come under fire in the past year after assertions it may worsen renal function and increase mortality.

Dr. Packer is a consultant to Abbott Laboratories and Orion Pharma, which funded REVIVE II and SURVIVE. Dr. Mebazaa is a consultant to Abbott.

Intravenous diuretics will remain the initial intervention for patients who present with ADHF. DR. PACKER

DALLAS — The investigational acute decompensated heart failure drug levosimendan garnered mixed reviews for its less-than-stellar performance in two large, multinational, double-blind, randomized clinical trials presented at the annual scientific sessions of the American Heart Association.

Levosimendan has both inotropic and vasodilator properties. But unlike other positive inotropes, whose action is mediated by increased intracellular calcium, levosimendan enhances cardiac myofilament sensitivity to an unchanged concentration of calcium. The drug also possesses peripheral vasodilator action mediated by an agonist effect on potassium channels.

Dr. Milton Packer reported on 600 patients in the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE II) trial who were hospitalized for acute decompensated heart failure (ADHF) not adequately responsive to intravenous diuretics. They were randomized to a 24-hour infusion of levosimendan or placebo, with intensification of standard background therapies as needed.

The primary end point in REVIVE II was a composite measure of clinical status during the first 5 days of hospitalization. The levosimendan group fared significantly better in this regard than did the controls, even though levosimendan had been stopped after the first 24 hours. Of those in the levosimendan arm, 76% showed moderate or marked improvement in a composite global assessment score, compared with 65% of controls. In the levosimendan arm, 15% required rescue therapy because their condition worsened, compared with 26% in the placebo arm. Levels of brain natriuretic peptide, a surrogate for heart failure severity, were halved in the levosimendan group and stayed low. Patients treated with Levosimendan felt better in as little as 6 hours, and that feeling persisted through 5 days.

But 28 levosimendan-treated patients developed atrial fibrillation and 72 experienced ventricular arrhythmias, compared with 6 and 51, respectively, on placebo. Symptomatic hypotension and headaches were also more common with levosimendan. There were 49 deaths within 90 days with levosimendan and 40 with placebo, said Dr. Packer, professor of medicine and director of the Center for Biostatistics and Clinical Science at the University of Texas Southwestern Medical Center, Dallas.

He stressed that intravenous diuretics—a fast-acting, safe, and relatively inexpensive treatment—will remain the initial intervention for patients who present with ADHF. He estimated, however, that this therapy achieves an adequate response—relief of shortness of breath at rest—in only about half of the 3 million U.S. hospitalizations per year with ADHF as the primary or secondary diagnosis. It's in the other half that he sees levosimendan as potentially playing a major role.

Dr. Alexandre Mebazaa presented the results of the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study, the first large-scale study to examine the survival impact of medications used to treat ADHF. SURVIVE involved 1,327 patients in eight countries who were randomized to levosimendan or dobutamine along with standard background treatments.

In SURVIVE, the primary end point was 6-month all-cause mortality, which was 26% in the levosimendan arm and 28% with dobutamine, a nonsignificant difference. But it was unrealistic to expect a mortality difference so long after a single 24-hour drug infusion, said Dr. Mebazaa, professor and director of the department of anesthesia and critical care medicine at Lariboisière Hospital, Paris.

The results were more impressive closer to the treatment period. At day 5, for example, mortality was 4.4% in the levosimendan group and 6.0% with dobutamine, a 28% reduction in relative risk. As in REVIVE II, there was an increased incidence of atrial fibrillation with levosimendan, he said.

Some audience members were enthused that the levosimendan trials had raised the bar in terms of the rigor with which ADHF drugs are evaluated. All currently available drugs were approved on the basis of hemodynamic gains rather than evidence of the more meaningful end points of improved clinical status or outcomes.

Dr. Gordon F. Tomaselli, vice chairman of the AHA scientific sessions program committee, said in an interview that given the high lethality of ADHF (more than one-quarter of SURVIVE participants died within 6 months) and the very limited current treatment options, levosimendan “probably does have a place in the armamentarium.”

But Dr. Gregg C. Fonarow was skeptical. “It's hard to conceive that with this dosing regimen this would be a treatment that physicians would want to use for their patients. A reduction in symptoms is not going to be acceptable if it comes at a price of substantial increased risk of severe adverse events,” said Dr Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“If you compare the serious adverse events seen in REVIVE II with what was observed in the largest trial with nesiritide, levosimendan comes nowhere close to being as safe as nesiritide,” he said. Nesiritide (Natrecor) has come under fire in the past year after assertions it may worsen renal function and increase mortality.

Dr. Packer is a consultant to Abbott Laboratories and Orion Pharma, which funded REVIVE II and SURVIVE. Dr. Mebazaa is a consultant to Abbott.

Intravenous diuretics will remain the initial intervention for patients who present with ADHF. DR. PACKER

BOCA RATON, FLA. — Automated home monitoring improved short-term outcomes for patients with heart failure, compared with standard disease management alone, in a multicenter, randomized study, Dr. Andrew R. Weintraub reported at the annual meeting of the Heart Failure Society of America.

Previously, researchers showed the benefit of disease management for heart failure patients, but the studies were nonrandomized, single-center, or assessed nonspecialized teams. Then the prospective, randomized Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) study demonstrated a significant reduction in hospitalizations from heart failure and cardiovascular disease, as well as a shorter length of stay with disease management (Circulation 2004;110:1450–5), said Dr. Weintraub, director of the Coronary Care Unit at the Tufts-New England Medical Center, Boston.

To determine whether the addition of automated home monitoring would further reduce hospitalization and resource use for patients enrolled in the disease management program, Dr. Weintraub and his associates randomized 93 patients to a control group of disease management and another 95 to an intervention group with home monitoring.

The control patients received the same disease management as in the SPAN-CHF study, which included an initial nurse home visit, weekly or biweekly telephone monitoring, and the availability of a nurse manager 24 hours a day via pager. Intervention patients received the same services, but also weighed themselves on an interactive scale, measured their blood pressure, and took their pulse daily using an automated home monitor (Philips Medical Systems, Bothell, Wash.). They also answered health status and compliance questions daily via text messaging (Health Hero Network, Mountain View, Calif.).

The investigators enrolled patients within 2 weeks of discharge after their first episode of heart failure. All had a measurement of left ventricular function within 6 months (mean 30%). They were aged 18–90 years. There was a high incidence of ACE inhibitor, angiotensin receptor blocker, and β-blocker use. Patient demographics were similar. Both groups had a wide range in baseline ejection fractions, said Dr. Weintraub.

“We detected a trend in reduction with intervention of heart failure hospitalized days, cardiac hospitalized days, and all-cause hospitalized days,” he said.

The number of hospitalizations for heart failure more than 90 days in the intervention group was a mean 0.5, compared with 1.8 for the control group (relative risk 0.28). Hospitalizations for all cardiac causes were 0.8 in the intervention group, compared with 2.2 in the control group (RR 0.37). There were no significant differences between groups in all-cause hospitalizations.

There were no differences in hospitalization rates according to gender, age, left ventricular ejection fraction, New York Heart Association classification, or hypertension. However, “our patients with diabetes at baseline were significantly more likely to be hospitalized for heart failure,” Dr. Weintraub added (odds ratio 4.3).

“We documented the 90-day benefit of adding an automated-home-monitoring system to a previously validated telephonic disease management program,” said Dr. Weintraub, who received research support from GlaxoSmithKline Inc., Agilent Technologies/Philips Medical Systems, and the Health Hero Network. “The addition … produced further improvement in the short-term, heart failure-related clinical outcomes in patients recently hospitalized for heart failure.”

An attendee asked whether the benefits were a result of self-management or the increase in nurse-patient interaction. Nurse managers reported spending 15%–20% above the normal standard care time with automated-home-monitoring patients, Dr. Weintraub said. But the benefit was from self- management and “the nurses facilitated that benefit,” he asserted.

BOCA RATON, FLA. — Automated home monitoring improved short-term outcomes for patients with heart failure, compared with standard disease management alone, in a multicenter, randomized study, Dr. Andrew R. Weintraub reported at the annual meeting of the Heart Failure Society of America.

Previously, researchers showed the benefit of disease management for heart failure patients, but the studies were nonrandomized, single-center, or assessed nonspecialized teams. Then the prospective, randomized Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) study demonstrated a significant reduction in hospitalizations from heart failure and cardiovascular disease, as well as a shorter length of stay with disease management (Circulation 2004;110:1450–5), said Dr. Weintraub, director of the Coronary Care Unit at the Tufts-New England Medical Center, Boston.

To determine whether the addition of automated home monitoring would further reduce hospitalization and resource use for patients enrolled in the disease management program, Dr. Weintraub and his associates randomized 93 patients to a control group of disease management and another 95 to an intervention group with home monitoring.

The control patients received the same disease management as in the SPAN-CHF study, which included an initial nurse home visit, weekly or biweekly telephone monitoring, and the availability of a nurse manager 24 hours a day via pager. Intervention patients received the same services, but also weighed themselves on an interactive scale, measured their blood pressure, and took their pulse daily using an automated home monitor (Philips Medical Systems, Bothell, Wash.). They also answered health status and compliance questions daily via text messaging (Health Hero Network, Mountain View, Calif.).

The investigators enrolled patients within 2 weeks of discharge after their first episode of heart failure. All had a measurement of left ventricular function within 6 months (mean 30%). They were aged 18–90 years. There was a high incidence of ACE inhibitor, angiotensin receptor blocker, and β-blocker use. Patient demographics were similar. Both groups had a wide range in baseline ejection fractions, said Dr. Weintraub.

“We detected a trend in reduction with intervention of heart failure hospitalized days, cardiac hospitalized days, and all-cause hospitalized days,” he said.

The number of hospitalizations for heart failure more than 90 days in the intervention group was a mean 0.5, compared with 1.8 for the control group (relative risk 0.28). Hospitalizations for all cardiac causes were 0.8 in the intervention group, compared with 2.2 in the control group (RR 0.37). There were no significant differences between groups in all-cause hospitalizations.

There were no differences in hospitalization rates according to gender, age, left ventricular ejection fraction, New York Heart Association classification, or hypertension. However, “our patients with diabetes at baseline were significantly more likely to be hospitalized for heart failure,” Dr. Weintraub added (odds ratio 4.3).

“We documented the 90-day benefit of adding an automated-home-monitoring system to a previously validated telephonic disease management program,” said Dr. Weintraub, who received research support from GlaxoSmithKline Inc., Agilent Technologies/Philips Medical Systems, and the Health Hero Network. “The addition … produced further improvement in the short-term, heart failure-related clinical outcomes in patients recently hospitalized for heart failure.”

An attendee asked whether the benefits were a result of self-management or the increase in nurse-patient interaction. Nurse managers reported spending 15%–20% above the normal standard care time with automated-home-monitoring patients, Dr. Weintraub said. But the benefit was from self- management and “the nurses facilitated that benefit,” he asserted.

BOCA RATON, FLA. — Automated home monitoring improved short-term outcomes for patients with heart failure, compared with standard disease management alone, in a multicenter, randomized study, Dr. Andrew R. Weintraub reported at the annual meeting of the Heart Failure Society of America.

Previously, researchers showed the benefit of disease management for heart failure patients, but the studies were nonrandomized, single-center, or assessed nonspecialized teams. Then the prospective, randomized Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) study demonstrated a significant reduction in hospitalizations from heart failure and cardiovascular disease, as well as a shorter length of stay with disease management (Circulation 2004;110:1450–5), said Dr. Weintraub, director of the Coronary Care Unit at the Tufts-New England Medical Center, Boston.

To determine whether the addition of automated home monitoring would further reduce hospitalization and resource use for patients enrolled in the disease management program, Dr. Weintraub and his associates randomized 93 patients to a control group of disease management and another 95 to an intervention group with home monitoring.

The control patients received the same disease management as in the SPAN-CHF study, which included an initial nurse home visit, weekly or biweekly telephone monitoring, and the availability of a nurse manager 24 hours a day via pager. Intervention patients received the same services, but also weighed themselves on an interactive scale, measured their blood pressure, and took their pulse daily using an automated home monitor (Philips Medical Systems, Bothell, Wash.). They also answered health status and compliance questions daily via text messaging (Health Hero Network, Mountain View, Calif.).

The investigators enrolled patients within 2 weeks of discharge after their first episode of heart failure. All had a measurement of left ventricular function within 6 months (mean 30%). They were aged 18–90 years. There was a high incidence of ACE inhibitor, angiotensin receptor blocker, and β-blocker use. Patient demographics were similar. Both groups had a wide range in baseline ejection fractions, said Dr. Weintraub.

“We detected a trend in reduction with intervention of heart failure hospitalized days, cardiac hospitalized days, and all-cause hospitalized days,” he said.

The number of hospitalizations for heart failure more than 90 days in the intervention group was a mean 0.5, compared with 1.8 for the control group (relative risk 0.28). Hospitalizations for all cardiac causes were 0.8 in the intervention group, compared with 2.2 in the control group (RR 0.37). There were no significant differences between groups in all-cause hospitalizations.

There were no differences in hospitalization rates according to gender, age, left ventricular ejection fraction, New York Heart Association classification, or hypertension. However, “our patients with diabetes at baseline were significantly more likely to be hospitalized for heart failure,” Dr. Weintraub added (odds ratio 4.3).

“We documented the 90-day benefit of adding an automated-home-monitoring system to a previously validated telephonic disease management program,” said Dr. Weintraub, who received research support from GlaxoSmithKline Inc., Agilent Technologies/Philips Medical Systems, and the Health Hero Network. “The addition … produced further improvement in the short-term, heart failure-related clinical outcomes in patients recently hospitalized for heart failure.”

An attendee asked whether the benefits were a result of self-management or the increase in nurse-patient interaction. Nurse managers reported spending 15%–20% above the normal standard care time with automated-home-monitoring patients, Dr. Weintraub said. But the benefit was from self- management and “the nurses facilitated that benefit,” he asserted.

DALLAS — An elevated B-type natriuretic peptide level upon admission for acute decompensated heart failure is an independent predictor of in-hospital mortality, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association. Moreover, B-type natriuretic peptide (BNP) is an equally robust predictor of in-hospital mortality regardless of whether the patient has preserved or reduced left ventricular systolic function, added Dr. Fonarow, professor of cardiovascular medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“These data suggest that the BNP assay should be part of the standard admission assessment of the acute decompensated heart failure patient,” he said.

Dr. Fonarow analyzed the relationship between admission BNP level and in-hospital mortality in 48,629 hospitalizations for acute decompensated heart failure (HF) during 2003–2004 at more than 275 U.S. hospitals participating in the Acute Decompensated Heart Failure National Registry (ADHERE).

He found a near-linear relationship between BNP quartile and in-hospital mortality. (See box.) The relationship was similar in the 52% of patients with a left ventricular ejection fraction of less than 40% and in those with preserved systolic function. The median hospital length of stay rose from 4.0 days in patients in the lowest quartile of BNP to 4.9 days in those in the top quartile, a difference that was highly significant because of the huge number of patients involved in the study. ICU admission was required for 12.8% of patients in BNP quartile 1, compared with 19.6% in quartile 4.

In an earlier study from ADHERE, Dr. Fonarow and coworkers developed and validated a practical bedside tool for mortality risk stratification in patients with acute decompensated heart failure (JAMA 2005;293:572–80).

The strongest in-hospital mortality predictors in this risk stratification method were admission blood urea nitrogen level, systolic blood pressure, and serum creatinine. Other significant predictors included in the bedside assessment tool were age, gender, serum sodium, pulse, and the presence of dyspnea at rest.

After adjustment for all of these other predictive factors, admission BNP quartile remained a highly significant independent predictor of in-hospital mortality. In fact, patients in the highest BNP quartile were 2.2-fold more likely to die during that hospitalization than were those in the lowest quartile, even after adjustment for the other eight predictors.

BNP has previously been shown to facilitate diagnosis of HF and predict long-term mortality risk in patients with chronic heart failure. However, the lab assay's prognostic utility in acute decompensated heart failure had not been studied.

The next step will be to see whether acutely decompensated patients with higher admission BNP levels benefit from a more aggressive monitoring and treatment strategy. If this hypothesis is shown to be sound, then it's possible that treatment regimens will be stratified based upon a patient's admission BNP, said Dr. Fonarow.

ADHERE is funded by Scios Inc.

DALLAS — An elevated B-type natriuretic peptide level upon admission for acute decompensated heart failure is an independent predictor of in-hospital mortality, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association. Moreover, B-type natriuretic peptide (BNP) is an equally robust predictor of in-hospital mortality regardless of whether the patient has preserved or reduced left ventricular systolic function, added Dr. Fonarow, professor of cardiovascular medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“These data suggest that the BNP assay should be part of the standard admission assessment of the acute decompensated heart failure patient,” he said.

Dr. Fonarow analyzed the relationship between admission BNP level and in-hospital mortality in 48,629 hospitalizations for acute decompensated heart failure (HF) during 2003–2004 at more than 275 U.S. hospitals participating in the Acute Decompensated Heart Failure National Registry (ADHERE).

He found a near-linear relationship between BNP quartile and in-hospital mortality. (See box.) The relationship was similar in the 52% of patients with a left ventricular ejection fraction of less than 40% and in those with preserved systolic function. The median hospital length of stay rose from 4.0 days in patients in the lowest quartile of BNP to 4.9 days in those in the top quartile, a difference that was highly significant because of the huge number of patients involved in the study. ICU admission was required for 12.8% of patients in BNP quartile 1, compared with 19.6% in quartile 4.

In an earlier study from ADHERE, Dr. Fonarow and coworkers developed and validated a practical bedside tool for mortality risk stratification in patients with acute decompensated heart failure (JAMA 2005;293:572–80).

The strongest in-hospital mortality predictors in this risk stratification method were admission blood urea nitrogen level, systolic blood pressure, and serum creatinine. Other significant predictors included in the bedside assessment tool were age, gender, serum sodium, pulse, and the presence of dyspnea at rest.

After adjustment for all of these other predictive factors, admission BNP quartile remained a highly significant independent predictor of in-hospital mortality. In fact, patients in the highest BNP quartile were 2.2-fold more likely to die during that hospitalization than were those in the lowest quartile, even after adjustment for the other eight predictors.

BNP has previously been shown to facilitate diagnosis of HF and predict long-term mortality risk in patients with chronic heart failure. However, the lab assay's prognostic utility in acute decompensated heart failure had not been studied.

The next step will be to see whether acutely decompensated patients with higher admission BNP levels benefit from a more aggressive monitoring and treatment strategy. If this hypothesis is shown to be sound, then it's possible that treatment regimens will be stratified based upon a patient's admission BNP, said Dr. Fonarow.

ADHERE is funded by Scios Inc.

DALLAS — An elevated B-type natriuretic peptide level upon admission for acute decompensated heart failure is an independent predictor of in-hospital mortality, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association. Moreover, B-type natriuretic peptide (BNP) is an equally robust predictor of in-hospital mortality regardless of whether the patient has preserved or reduced left ventricular systolic function, added Dr. Fonarow, professor of cardiovascular medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“These data suggest that the BNP assay should be part of the standard admission assessment of the acute decompensated heart failure patient,” he said.

Dr. Fonarow analyzed the relationship between admission BNP level and in-hospital mortality in 48,629 hospitalizations for acute decompensated heart failure (HF) during 2003–2004 at more than 275 U.S. hospitals participating in the Acute Decompensated Heart Failure National Registry (ADHERE).

He found a near-linear relationship between BNP quartile and in-hospital mortality. (See box.) The relationship was similar in the 52% of patients with a left ventricular ejection fraction of less than 40% and in those with preserved systolic function. The median hospital length of stay rose from 4.0 days in patients in the lowest quartile of BNP to 4.9 days in those in the top quartile, a difference that was highly significant because of the huge number of patients involved in the study. ICU admission was required for 12.8% of patients in BNP quartile 1, compared with 19.6% in quartile 4.

In an earlier study from ADHERE, Dr. Fonarow and coworkers developed and validated a practical bedside tool for mortality risk stratification in patients with acute decompensated heart failure (JAMA 2005;293:572–80).

The strongest in-hospital mortality predictors in this risk stratification method were admission blood urea nitrogen level, systolic blood pressure, and serum creatinine. Other significant predictors included in the bedside assessment tool were age, gender, serum sodium, pulse, and the presence of dyspnea at rest.

After adjustment for all of these other predictive factors, admission BNP quartile remained a highly significant independent predictor of in-hospital mortality. In fact, patients in the highest BNP quartile were 2.2-fold more likely to die during that hospitalization than were those in the lowest quartile, even after adjustment for the other eight predictors.

BNP has previously been shown to facilitate diagnosis of HF and predict long-term mortality risk in patients with chronic heart failure. However, the lab assay's prognostic utility in acute decompensated heart failure had not been studied.

The next step will be to see whether acutely decompensated patients with higher admission BNP levels benefit from a more aggressive monitoring and treatment strategy. If this hypothesis is shown to be sound, then it's possible that treatment regimens will be stratified based upon a patient's admission BNP, said Dr. Fonarow.

ADHERE is funded by Scios Inc.

DALLAS — Intensive treatment with atorvastatin in patients with stable coronary heart disease led to a significant reduction in hospitalization for heart failure in a secondary analysis of results from a study with 10,000 patients.

The results are the best evidence so far that statin treatment confers a heart-failure benefit. The findings also suggest that the benefit is not mediated by a reduction in ischemic coronary events but by another, as-yet unknown, mechanism, Dr. David D. Waters said at the annual scientific sessions of the American Heart Association.

“Randomized, controlled trials of statins in patients with heart failure will likely yield important findings,” reported Dr. Waters, who is chief of the division of cardiology at San Francisco General Hospital.

The heart failure analysis was a prespecified, secondary analysis of the Treating to New Targets (TNT) study, which randomized 10,001 patients with stable coronary disease to daily treatment with 10 mg or 80 mg atorvastatin (Lipitor) and then followed them for a median of 4.9 years.

The primary end point of the study was the combined rate of coronary death, nonfatal myocardial infarction, resuscitated cardiac arrest, and stroke. The 80-mg daily dose of atorvastatin was significantly more effective than the 10-mg daily dose for preventing this end point (N. Engl. J. Med. 2005;352:1425–35).

The study was sponsored by Pfizer, which markets Lipitor. Dr. Waters has been a consultant to and a speaker for Pfizer, and he has also received research grants from the company.

The impact of treatment on heart failure was assessed by the number of hospitalizations for heart failure during the study.

A total of 164 patients (3.3%) on the 10-mg dose were hospitalized for heart failure, compared with 122 patients (2.4%) in the 80-mg group, a 26% relative risk reduction that was statistically significant, Dr. Waters said.

The study excluded those patients with New York Heart Association class IIIb and class IV heart failure, as well as patients who had a left ventricular ejection fraction at baseline of less than 30%. Among those who enrolled, 8% of the patients had heart failure at baseline, but this subgroup accounted for 38% of the hospital admissions for heart failure. Among those who entered the trial without heart failure, the incidence of heart-failure hospitalizations was 1.9%.

In the subgroup with preexisting heart failure, the impact of high-dose atorvastatin was even greater. The hospitalization rate was 17.3% among those who were on 10 mg, compared with 10.6% among those on 80 mg, a “very large” absolute reduction of 6.7%, and a relative risk reduction of 41% that was statistically significant, Dr. Waters said.

In a multivariate analysis, the reduction of low-density lipoprotein (LDL) cholesterol was a significant modifier of risk after adjustment for other clinical and demographic variables. For every 1% drop in the serum level of LDL cholesterol, the risk of hospitalization for heart failure fell by 0.6%.

There was no indication that the drop in heart failure hospitalizations was mediated by an effect of high-dose atorvastatin on the incidence of myocardial infarctions and other ischemic events. During the 3 months prior to their first hospitalization for heart failure, only 15% of the patients had an acute coronary event. That meant that 85% of the hospitalizations for heart failure were not triggered by a coronary event, Dr. Waters noted.

Several other beneficial effects of statins might explain an effect on heart failure, including improved endothelial function, inhibited production of inflammatory cytokines, and direct antifibrotic, antihypertrophic, or antioxidant effects.

DALLAS — Intensive treatment with atorvastatin in patients with stable coronary heart disease led to a significant reduction in hospitalization for heart failure in a secondary analysis of results from a study with 10,000 patients.

The results are the best evidence so far that statin treatment confers a heart-failure benefit. The findings also suggest that the benefit is not mediated by a reduction in ischemic coronary events but by another, as-yet unknown, mechanism, Dr. David D. Waters said at the annual scientific sessions of the American Heart Association.

“Randomized, controlled trials of statins in patients with heart failure will likely yield important findings,” reported Dr. Waters, who is chief of the division of cardiology at San Francisco General Hospital.

The heart failure analysis was a prespecified, secondary analysis of the Treating to New Targets (TNT) study, which randomized 10,001 patients with stable coronary disease to daily treatment with 10 mg or 80 mg atorvastatin (Lipitor) and then followed them for a median of 4.9 years.

The primary end point of the study was the combined rate of coronary death, nonfatal myocardial infarction, resuscitated cardiac arrest, and stroke. The 80-mg daily dose of atorvastatin was significantly more effective than the 10-mg daily dose for preventing this end point (N. Engl. J. Med. 2005;352:1425–35).

The study was sponsored by Pfizer, which markets Lipitor. Dr. Waters has been a consultant to and a speaker for Pfizer, and he has also received research grants from the company.

The impact of treatment on heart failure was assessed by the number of hospitalizations for heart failure during the study.

A total of 164 patients (3.3%) on the 10-mg dose were hospitalized for heart failure, compared with 122 patients (2.4%) in the 80-mg group, a 26% relative risk reduction that was statistically significant, Dr. Waters said.

The study excluded those patients with New York Heart Association class IIIb and class IV heart failure, as well as patients who had a left ventricular ejection fraction at baseline of less than 30%. Among those who enrolled, 8% of the patients had heart failure at baseline, but this subgroup accounted for 38% of the hospital admissions for heart failure. Among those who entered the trial without heart failure, the incidence of heart-failure hospitalizations was 1.9%.

In the subgroup with preexisting heart failure, the impact of high-dose atorvastatin was even greater. The hospitalization rate was 17.3% among those who were on 10 mg, compared with 10.6% among those on 80 mg, a “very large” absolute reduction of 6.7%, and a relative risk reduction of 41% that was statistically significant, Dr. Waters said.

In a multivariate analysis, the reduction of low-density lipoprotein (LDL) cholesterol was a significant modifier of risk after adjustment for other clinical and demographic variables. For every 1% drop in the serum level of LDL cholesterol, the risk of hospitalization for heart failure fell by 0.6%.

There was no indication that the drop in heart failure hospitalizations was mediated by an effect of high-dose atorvastatin on the incidence of myocardial infarctions and other ischemic events. During the 3 months prior to their first hospitalization for heart failure, only 15% of the patients had an acute coronary event. That meant that 85% of the hospitalizations for heart failure were not triggered by a coronary event, Dr. Waters noted.

Several other beneficial effects of statins might explain an effect on heart failure, including improved endothelial function, inhibited production of inflammatory cytokines, and direct antifibrotic, antihypertrophic, or antioxidant effects.

DALLAS — Intensive treatment with atorvastatin in patients with stable coronary heart disease led to a significant reduction in hospitalization for heart failure in a secondary analysis of results from a study with 10,000 patients.

The results are the best evidence so far that statin treatment confers a heart-failure benefit. The findings also suggest that the benefit is not mediated by a reduction in ischemic coronary events but by another, as-yet unknown, mechanism, Dr. David D. Waters said at the annual scientific sessions of the American Heart Association.

“Randomized, controlled trials of statins in patients with heart failure will likely yield important findings,” reported Dr. Waters, who is chief of the division of cardiology at San Francisco General Hospital.

The heart failure analysis was a prespecified, secondary analysis of the Treating to New Targets (TNT) study, which randomized 10,001 patients with stable coronary disease to daily treatment with 10 mg or 80 mg atorvastatin (Lipitor) and then followed them for a median of 4.9 years.

The primary end point of the study was the combined rate of coronary death, nonfatal myocardial infarction, resuscitated cardiac arrest, and stroke. The 80-mg daily dose of atorvastatin was significantly more effective than the 10-mg daily dose for preventing this end point (N. Engl. J. Med. 2005;352:1425–35).

The study was sponsored by Pfizer, which markets Lipitor. Dr. Waters has been a consultant to and a speaker for Pfizer, and he has also received research grants from the company.

The impact of treatment on heart failure was assessed by the number of hospitalizations for heart failure during the study.

A total of 164 patients (3.3%) on the 10-mg dose were hospitalized for heart failure, compared with 122 patients (2.4%) in the 80-mg group, a 26% relative risk reduction that was statistically significant, Dr. Waters said.

The study excluded those patients with New York Heart Association class IIIb and class IV heart failure, as well as patients who had a left ventricular ejection fraction at baseline of less than 30%. Among those who enrolled, 8% of the patients had heart failure at baseline, but this subgroup accounted for 38% of the hospital admissions for heart failure. Among those who entered the trial without heart failure, the incidence of heart-failure hospitalizations was 1.9%.

In the subgroup with preexisting heart failure, the impact of high-dose atorvastatin was even greater. The hospitalization rate was 17.3% among those who were on 10 mg, compared with 10.6% among those on 80 mg, a “very large” absolute reduction of 6.7%, and a relative risk reduction of 41% that was statistically significant, Dr. Waters said.

In a multivariate analysis, the reduction of low-density lipoprotein (LDL) cholesterol was a significant modifier of risk after adjustment for other clinical and demographic variables. For every 1% drop in the serum level of LDL cholesterol, the risk of hospitalization for heart failure fell by 0.6%.

There was no indication that the drop in heart failure hospitalizations was mediated by an effect of high-dose atorvastatin on the incidence of myocardial infarctions and other ischemic events. During the 3 months prior to their first hospitalization for heart failure, only 15% of the patients had an acute coronary event. That meant that 85% of the hospitalizations for heart failure were not triggered by a coronary event, Dr. Waters noted.

Several other beneficial effects of statins might explain an effect on heart failure, including improved endothelial function, inhibited production of inflammatory cytokines, and direct antifibrotic, antihypertrophic, or antioxidant effects.

STOCKHOLM — A natriuretic peptide was safe and effective for treating patients with acute, decompensated heart failure in a phase II study with a total of 221 patients.

Ularitide, given intravenously, reduced pulmonary capillary wedge pressure, improved dyspnea, and did not worsen renal function when given to patients for 24 hours of continuous infusion, Veselin Mitrovic, M.D., said at the annual congress of the European Society of Cardiology.

A synthetic form of a natriuretic peptide made in human kidneys, ularitide, “was associated with a seemingly greater hemodynamic effect than nesiritide [Natrecor], but this must be validated by a direct comparison,” commented Marco Metra, M.D., a professor of cardiology at the University of Brescia (Italy).

The study enrolled patients with symptomatic decompensated heart failure and a pulmonary capillary wedge pressure (PCWP) of at least 18 mm Hg. They were randomized to treatment with one of three dosages of ularitide or placebo. The drug dosages were 7.5, 15, or 30 ng/kg per minute. The study was done at 19 centers in Germany, Russia, and Serbia.

One primary end point was the change from baseline in PCWP after 6 hours of treatment. All three ularitide dosages resulted in significantly larger declines in PCWP, compared with patients treated with placebo. In the two groups that received the largest ularitide dosages, the average drop in PCWP was about 10 mm Hg, reported Dr. Mitrovic, medical director of the research unit at the Kerckhoff Clinic in Bad Nauheim, Germany.

The second primary end point was patients' self-assessed improvement in dyspnea after 6 hours of treatment. About 45% of the patients who received either of the two highest dosages reported a moderate or marked improvement in their dyspnea, compared with 38% who reported this degree of improvement on the lowest dosage, and 25% with this level of improvement in the placebo group.

Ularitide also produced a dose-related increase in cardiac index and a reduction in systemic vascular resistance.

The drug had no detectable impact on urine output, serum creatinine level, or creatinine clearance. The apparent absence of an effect on kidney function may mean that ularitide acts differently from nesiritide. Evidence from a metaanalysis published earlier this year indicated that a single dose of nesiritide worsens renal function in some patients with acute, decompensated heart failure (Circulation 2005;111:1487–91).

In the new study, treatment with ularitide was associated with fewer serious adverse events and fewer deaths, compared with the placebo group.

The short- and long-term effects of ularitide must be further examined in larger studies that allow assessment of morbidity and mortality events as the primary end points, Dr. Metra said.

The new results did not establish the optimal ularitide dosage, Dr. Mitrovic said. The 30 ng/kg per minute dosage may be best suited for patients with a relatively high systemic blood pressure at baseline, he said. A lower dosage, such as 15 ng/kg per minute, might work best for patients with a lower systemic blood pressure at the start of treatment.

The study was sponsored by Protein Design Labs, which holds worldwide development and marketing rights for ularitide.

STOCKHOLM — A natriuretic peptide was safe and effective for treating patients with acute, decompensated heart failure in a phase II study with a total of 221 patients.

Ularitide, given intravenously, reduced pulmonary capillary wedge pressure, improved dyspnea, and did not worsen renal function when given to patients for 24 hours of continuous infusion, Veselin Mitrovic, M.D., said at the annual congress of the European Society of Cardiology.

A synthetic form of a natriuretic peptide made in human kidneys, ularitide, “was associated with a seemingly greater hemodynamic effect than nesiritide [Natrecor], but this must be validated by a direct comparison,” commented Marco Metra, M.D., a professor of cardiology at the University of Brescia (Italy).

The study enrolled patients with symptomatic decompensated heart failure and a pulmonary capillary wedge pressure (PCWP) of at least 18 mm Hg. They were randomized to treatment with one of three dosages of ularitide or placebo. The drug dosages were 7.5, 15, or 30 ng/kg per minute. The study was done at 19 centers in Germany, Russia, and Serbia.

One primary end point was the change from baseline in PCWP after 6 hours of treatment. All three ularitide dosages resulted in significantly larger declines in PCWP, compared with patients treated with placebo. In the two groups that received the largest ularitide dosages, the average drop in PCWP was about 10 mm Hg, reported Dr. Mitrovic, medical director of the research unit at the Kerckhoff Clinic in Bad Nauheim, Germany.

The second primary end point was patients' self-assessed improvement in dyspnea after 6 hours of treatment. About 45% of the patients who received either of the two highest dosages reported a moderate or marked improvement in their dyspnea, compared with 38% who reported this degree of improvement on the lowest dosage, and 25% with this level of improvement in the placebo group.

Ularitide also produced a dose-related increase in cardiac index and a reduction in systemic vascular resistance.

The drug had no detectable impact on urine output, serum creatinine level, or creatinine clearance. The apparent absence of an effect on kidney function may mean that ularitide acts differently from nesiritide. Evidence from a metaanalysis published earlier this year indicated that a single dose of nesiritide worsens renal function in some patients with acute, decompensated heart failure (Circulation 2005;111:1487–91).

In the new study, treatment with ularitide was associated with fewer serious adverse events and fewer deaths, compared with the placebo group.

The short- and long-term effects of ularitide must be further examined in larger studies that allow assessment of morbidity and mortality events as the primary end points, Dr. Metra said.

The new results did not establish the optimal ularitide dosage, Dr. Mitrovic said. The 30 ng/kg per minute dosage may be best suited for patients with a relatively high systemic blood pressure at baseline, he said. A lower dosage, such as 15 ng/kg per minute, might work best for patients with a lower systemic blood pressure at the start of treatment.

The study was sponsored by Protein Design Labs, which holds worldwide development and marketing rights for ularitide.

STOCKHOLM — A natriuretic peptide was safe and effective for treating patients with acute, decompensated heart failure in a phase II study with a total of 221 patients.

Ularitide, given intravenously, reduced pulmonary capillary wedge pressure, improved dyspnea, and did not worsen renal function when given to patients for 24 hours of continuous infusion, Veselin Mitrovic, M.D., said at the annual congress of the European Society of Cardiology.

A synthetic form of a natriuretic peptide made in human kidneys, ularitide, “was associated with a seemingly greater hemodynamic effect than nesiritide [Natrecor], but this must be validated by a direct comparison,” commented Marco Metra, M.D., a professor of cardiology at the University of Brescia (Italy).

The study enrolled patients with symptomatic decompensated heart failure and a pulmonary capillary wedge pressure (PCWP) of at least 18 mm Hg. They were randomized to treatment with one of three dosages of ularitide or placebo. The drug dosages were 7.5, 15, or 30 ng/kg per minute. The study was done at 19 centers in Germany, Russia, and Serbia.

One primary end point was the change from baseline in PCWP after 6 hours of treatment. All three ularitide dosages resulted in significantly larger declines in PCWP, compared with patients treated with placebo. In the two groups that received the largest ularitide dosages, the average drop in PCWP was about 10 mm Hg, reported Dr. Mitrovic, medical director of the research unit at the Kerckhoff Clinic in Bad Nauheim, Germany.

The second primary end point was patients' self-assessed improvement in dyspnea after 6 hours of treatment. About 45% of the patients who received either of the two highest dosages reported a moderate or marked improvement in their dyspnea, compared with 38% who reported this degree of improvement on the lowest dosage, and 25% with this level of improvement in the placebo group.

Ularitide also produced a dose-related increase in cardiac index and a reduction in systemic vascular resistance.

The drug had no detectable impact on urine output, serum creatinine level, or creatinine clearance. The apparent absence of an effect on kidney function may mean that ularitide acts differently from nesiritide. Evidence from a metaanalysis published earlier this year indicated that a single dose of nesiritide worsens renal function in some patients with acute, decompensated heart failure (Circulation 2005;111:1487–91).

In the new study, treatment with ularitide was associated with fewer serious adverse events and fewer deaths, compared with the placebo group.

The short- and long-term effects of ularitide must be further examined in larger studies that allow assessment of morbidity and mortality events as the primary end points, Dr. Metra said.

The new results did not establish the optimal ularitide dosage, Dr. Mitrovic said. The 30 ng/kg per minute dosage may be best suited for patients with a relatively high systemic blood pressure at baseline, he said. A lower dosage, such as 15 ng/kg per minute, might work best for patients with a lower systemic blood pressure at the start of treatment.

The study was sponsored by Protein Design Labs, which holds worldwide development and marketing rights for ularitide.

BOCA RATON, FLA. — The brain natriuretic peptide, nesiritide, which is used to treat acute heart failure symptoms, did not facilitate diuresis or protect renal function in a small study of stable hospitalized patients.

Many clinicians believe nesiritide (Natrecor, Scios Inc.) facilitates furosemide diuresis and prevents renal dysfunction, Margaret M. Redfield, M.D., said in an interview. However, a recent metaanalysis indicated that the agent might actually increase the risk of renal dysfunction (Circulation 2005;111:1487–91).

To sort it out, Dr. Redfield and her associates studied 65 patients who were hospitalized for decompensated heart failure and who were treated with a standard dose of nesiritide for relief of their heart failure symptoms. They were randomized to nesiritide as a 2-mcg/kg bolus at admission and a 0.01-mcg/kg per minute infusion at 48 hours (34 patients) or to standard therapy (31 patients).

The participants also received 40-mg b.i.d. intravenous furosemide if they had mild renal dysfunction at baseline, defined as a creatinine clearance of 40–60 mL/min. They received 80-mg b.i.d. intravenous furosemide if they had moderate renal dysfunction, or a creatinine clearance of 20–39 mL/min.

“We looked at nesiritide in the broader heart failure population where you don't need an acute effect,” said Dr. Redfield, professor of medicine, Mayo Clinic College of Medicine, Rochester, Minn.

Approximately one-quarter of heart failure patients experience renal dysfunction during hospitalization, and the researchers sought to determine if nesiritide is protective, Dr. Redfield said during a poster session at the annual meeting of the Heart Failure Society of America.

A secondary objective was to determine if the agent could obviate the need for furosemide diuresis in some patients.

Mean baseline creatinine was 1.8 mg/dL in the nesiritide group and 1.7 mg/dL in the standard therapy group; by 48 hours, the mean changes were increases of 0.12 mg/dL and 0.07 mg/dL, respectively. Mean baseline brain natriuretic peptide level was 640 pg/mL for the nesiritide group and 538 pg/mL for the standard therapy group; by 48 hours, the mean changes were a 474 pg/mL increase in the nesiritide group and a 59 pg/mL decrease in the control group. Total furosemide use was 272 mg in the nesiritide group and 255 mg in the standard treatment group at 48 hours.

“Nesiritide causes no harm, but has no significant benefit,” Dr. Redfield said. “Nesiritide did not enhance the response to furosemide. We hypothesized that nesiritide should have a beneficial effect on renal function—we didn't see that either.”

Systolic blood pressure was lower in the nesiritide group at 24 hours, but not significantly different between groups by 48 hours.

“The standard dose was designed for hemodynamic effects,” Dr. Redfield commented. “The next step is to look at a lower dose, which might provide renal protection.”

BOCA RATON, FLA. — The brain natriuretic peptide, nesiritide, which is used to treat acute heart failure symptoms, did not facilitate diuresis or protect renal function in a small study of stable hospitalized patients.

Many clinicians believe nesiritide (Natrecor, Scios Inc.) facilitates furosemide diuresis and prevents renal dysfunction, Margaret M. Redfield, M.D., said in an interview. However, a recent metaanalysis indicated that the agent might actually increase the risk of renal dysfunction (Circulation 2005;111:1487–91).

To sort it out, Dr. Redfield and her associates studied 65 patients who were hospitalized for decompensated heart failure and who were treated with a standard dose of nesiritide for relief of their heart failure symptoms. They were randomized to nesiritide as a 2-mcg/kg bolus at admission and a 0.01-mcg/kg per minute infusion at 48 hours (34 patients) or to standard therapy (31 patients).

The participants also received 40-mg b.i.d. intravenous furosemide if they had mild renal dysfunction at baseline, defined as a creatinine clearance of 40–60 mL/min. They received 80-mg b.i.d. intravenous furosemide if they had moderate renal dysfunction, or a creatinine clearance of 20–39 mL/min.

“We looked at nesiritide in the broader heart failure population where you don't need an acute effect,” said Dr. Redfield, professor of medicine, Mayo Clinic College of Medicine, Rochester, Minn.

Approximately one-quarter of heart failure patients experience renal dysfunction during hospitalization, and the researchers sought to determine if nesiritide is protective, Dr. Redfield said during a poster session at the annual meeting of the Heart Failure Society of America.

A secondary objective was to determine if the agent could obviate the need for furosemide diuresis in some patients.

Mean baseline creatinine was 1.8 mg/dL in the nesiritide group and 1.7 mg/dL in the standard therapy group; by 48 hours, the mean changes were increases of 0.12 mg/dL and 0.07 mg/dL, respectively. Mean baseline brain natriuretic peptide level was 640 pg/mL for the nesiritide group and 538 pg/mL for the standard therapy group; by 48 hours, the mean changes were a 474 pg/mL increase in the nesiritide group and a 59 pg/mL decrease in the control group. Total furosemide use was 272 mg in the nesiritide group and 255 mg in the standard treatment group at 48 hours.

“Nesiritide causes no harm, but has no significant benefit,” Dr. Redfield said. “Nesiritide did not enhance the response to furosemide. We hypothesized that nesiritide should have a beneficial effect on renal function—we didn't see that either.”

Systolic blood pressure was lower in the nesiritide group at 24 hours, but not significantly different between groups by 48 hours.

“The standard dose was designed for hemodynamic effects,” Dr. Redfield commented. “The next step is to look at a lower dose, which might provide renal protection.”

BOCA RATON, FLA. — The brain natriuretic peptide, nesiritide, which is used to treat acute heart failure symptoms, did not facilitate diuresis or protect renal function in a small study of stable hospitalized patients.

Many clinicians believe nesiritide (Natrecor, Scios Inc.) facilitates furosemide diuresis and prevents renal dysfunction, Margaret M. Redfield, M.D., said in an interview. However, a recent metaanalysis indicated that the agent might actually increase the risk of renal dysfunction (Circulation 2005;111:1487–91).

To sort it out, Dr. Redfield and her associates studied 65 patients who were hospitalized for decompensated heart failure and who were treated with a standard dose of nesiritide for relief of their heart failure symptoms. They were randomized to nesiritide as a 2-mcg/kg bolus at admission and a 0.01-mcg/kg per minute infusion at 48 hours (34 patients) or to standard therapy (31 patients).

The participants also received 40-mg b.i.d. intravenous furosemide if they had mild renal dysfunction at baseline, defined as a creatinine clearance of 40–60 mL/min. They received 80-mg b.i.d. intravenous furosemide if they had moderate renal dysfunction, or a creatinine clearance of 20–39 mL/min.

“We looked at nesiritide in the broader heart failure population where you don't need an acute effect,” said Dr. Redfield, professor of medicine, Mayo Clinic College of Medicine, Rochester, Minn.

Approximately one-quarter of heart failure patients experience renal dysfunction during hospitalization, and the researchers sought to determine if nesiritide is protective, Dr. Redfield said during a poster session at the annual meeting of the Heart Failure Society of America.

A secondary objective was to determine if the agent could obviate the need for furosemide diuresis in some patients.

Mean baseline creatinine was 1.8 mg/dL in the nesiritide group and 1.7 mg/dL in the standard therapy group; by 48 hours, the mean changes were increases of 0.12 mg/dL and 0.07 mg/dL, respectively. Mean baseline brain natriuretic peptide level was 640 pg/mL for the nesiritide group and 538 pg/mL for the standard therapy group; by 48 hours, the mean changes were a 474 pg/mL increase in the nesiritide group and a 59 pg/mL decrease in the control group. Total furosemide use was 272 mg in the nesiritide group and 255 mg in the standard treatment group at 48 hours.

“Nesiritide causes no harm, but has no significant benefit,” Dr. Redfield said. “Nesiritide did not enhance the response to furosemide. We hypothesized that nesiritide should have a beneficial effect on renal function—we didn't see that either.”

Systolic blood pressure was lower in the nesiritide group at 24 hours, but not significantly different between groups by 48 hours.

“The standard dose was designed for hemodynamic effects,” Dr. Redfield commented. “The next step is to look at a lower dose, which might provide renal protection.”

STOCKHOLM — A β-blocker and an ACE inhibitor, the two mainstays of heart failure treatment, can be started in either order and be safe and effective, according to results from more than 1,000 patients.

Until now, treatment of patients with heart failure usually began with an ACE inhibitor or an angiotensin-receptor blocker, primarily for historic reasons: ACE inhibitors were proven effective for treating heart failure first. But results from a head-to-head trial now show that both options are equivalent. An ACE inhibitor or a β-blocker can be started first, followed by the other drug, and patients have similar outcomes, Ronnie Willenheimer, M.D., reported at the annual congress of the European Society of Cardiology.

“I think this will possibly change practice. The data support using a β-blocker first in selected patients,” commented Kenneth Dickstein, M.D., a cardiologist at the University of Bergen (Norway). “It remains a clinical question [as to] who should get a β-blocker first and who should first get an ACE inhibitor or angiotensin-receptor blocker.”

“The results suggest free choice. A physician can start treatment based on individual judgment of each patient,” said Dr. Willenheimer, a cardiologist at University Hospital Malmö (Sweden). “For patients with tachycardia or ischemic cardiomyopathy, I'd start with a β-blocker,” he told this newspaper.

Dr. Willenheimer has received honoraria from the German division of Merck, which sponsored the study and markets a formulation of the β-blocker bisoprolol (Concor) that is approved in many countries (but not the United States) for treating heart failure. In the United States, generic bisoprolol and its trade formulation (Zebeta) are approved only for treating hypertension. β-Blockers approved for treating heart failure in the United States are carvedilol (Coreg) and metoprolol succinate (Toprol-XL).

The study enrolled 1,010 patients aged 65 years or older (the mean age was 72 years) with New York Heart Association class II or III heart failure at 128 centers in 20 countries. Their average left ventricular ejection fraction was 29%. Patients were randomized to start treatment with either 1.25 mg of bisoprolol once daily or 2.5 mg of the ACE inhibitor enalapril b.i.d. Their monotherapy dosage was increased every 2 weeks until the bisoprolol dosage was 10 mg once daily or the enalapril dosage was 10 mg b.i.d. Monotherapy was continued to a total duration of 6 months, after which the second drug was begun with a similar up-titration scheme. Patients were followed for an average of 1.2 years.

By all efficacy measures used, the bisoprolol-first strategy was not inferior to the enalapril-first regimen. The study's primary end point was the time to first all-cause death or all-cause hospitalization. During follow-up on an intention-to-treat basis, these events occurred in 35.2% of patients in the bisoprolol-first arm and in 36.8% of those in the enalapril-first arm. On a per-protocol basis, the event rates were 32.4% in the bisoprolol-first patients and 33.1% in the enalapril-first group (Circulation 2005;112:2426–35).

The incidence of treatment-related adverse events was also similar in both groups. However, in patients treated with bisoprolol first, the results showed a trend toward an improved survival benefit and a trend toward a higher frequency of worsening heart failure requiring hospitalization, especially early in the study.

These findings are probably class effects, Dr. Willenheimer said. In both treatment groups, the drug that was started first was given in higher dosages during the combined therapy phase. The study was limited by several factors, Dr. Dickstein noted. It was done on an open-label basis, it did not include patients with class IV disease, and patients were maintained on monotherapy for the relatively long period of 6 months. Nonetheless, he said that on the basis of the results, he believes that the two strategies probably have comparable efficacy and safety.

A physician can start treatment based on individual judgment of each patient. DR. WILLENHEIMER

STOCKHOLM — A β-blocker and an ACE inhibitor, the two mainstays of heart failure treatment, can be started in either order and be safe and effective, according to results from more than 1,000 patients.

Until now, treatment of patients with heart failure usually began with an ACE inhibitor or an angiotensin-receptor blocker, primarily for historic reasons: ACE inhibitors were proven effective for treating heart failure first. But results from a head-to-head trial now show that both options are equivalent. An ACE inhibitor or a β-blocker can be started first, followed by the other drug, and patients have similar outcomes, Ronnie Willenheimer, M.D., reported at the annual congress of the European Society of Cardiology.

“I think this will possibly change practice. The data support using a β-blocker first in selected patients,” commented Kenneth Dickstein, M.D., a cardiologist at the University of Bergen (Norway). “It remains a clinical question [as to] who should get a β-blocker first and who should first get an ACE inhibitor or angiotensin-receptor blocker.”

“The results suggest free choice. A physician can start treatment based on individual judgment of each patient,” said Dr. Willenheimer, a cardiologist at University Hospital Malmö (Sweden). “For patients with tachycardia or ischemic cardiomyopathy, I'd start with a β-blocker,” he told this newspaper.

Dr. Willenheimer has received honoraria from the German division of Merck, which sponsored the study and markets a formulation of the β-blocker bisoprolol (Concor) that is approved in many countries (but not the United States) for treating heart failure. In the United States, generic bisoprolol and its trade formulation (Zebeta) are approved only for treating hypertension. β-Blockers approved for treating heart failure in the United States are carvedilol (Coreg) and metoprolol succinate (Toprol-XL).

The study enrolled 1,010 patients aged 65 years or older (the mean age was 72 years) with New York Heart Association class II or III heart failure at 128 centers in 20 countries. Their average left ventricular ejection fraction was 29%. Patients were randomized to start treatment with either 1.25 mg of bisoprolol once daily or 2.5 mg of the ACE inhibitor enalapril b.i.d. Their monotherapy dosage was increased every 2 weeks until the bisoprolol dosage was 10 mg once daily or the enalapril dosage was 10 mg b.i.d. Monotherapy was continued to a total duration of 6 months, after which the second drug was begun with a similar up-titration scheme. Patients were followed for an average of 1.2 years.

By all efficacy measures used, the bisoprolol-first strategy was not inferior to the enalapril-first regimen. The study's primary end point was the time to first all-cause death or all-cause hospitalization. During follow-up on an intention-to-treat basis, these events occurred in 35.2% of patients in the bisoprolol-first arm and in 36.8% of those in the enalapril-first arm. On a per-protocol basis, the event rates were 32.4% in the bisoprolol-first patients and 33.1% in the enalapril-first group (Circulation 2005;112:2426–35).

The incidence of treatment-related adverse events was also similar in both groups. However, in patients treated with bisoprolol first, the results showed a trend toward an improved survival benefit and a trend toward a higher frequency of worsening heart failure requiring hospitalization, especially early in the study.

These findings are probably class effects, Dr. Willenheimer said. In both treatment groups, the drug that was started first was given in higher dosages during the combined therapy phase. The study was limited by several factors, Dr. Dickstein noted. It was done on an open-label basis, it did not include patients with class IV disease, and patients were maintained on monotherapy for the relatively long period of 6 months. Nonetheless, he said that on the basis of the results, he believes that the two strategies probably have comparable efficacy and safety.

A physician can start treatment based on individual judgment of each patient. DR. WILLENHEIMER

STOCKHOLM — A β-blocker and an ACE inhibitor, the two mainstays of heart failure treatment, can be started in either order and be safe and effective, according to results from more than 1,000 patients.

Until now, treatment of patients with heart failure usually began with an ACE inhibitor or an angiotensin-receptor blocker, primarily for historic reasons: ACE inhibitors were proven effective for treating heart failure first. But results from a head-to-head trial now show that both options are equivalent. An ACE inhibitor or a β-blocker can be started first, followed by the other drug, and patients have similar outcomes, Ronnie Willenheimer, M.D., reported at the annual congress of the European Society of Cardiology.

“I think this will possibly change practice. The data support using a β-blocker first in selected patients,” commented Kenneth Dickstein, M.D., a cardiologist at the University of Bergen (Norway). “It remains a clinical question [as to] who should get a β-blocker first and who should first get an ACE inhibitor or angiotensin-receptor blocker.”

“The results suggest free choice. A physician can start treatment based on individual judgment of each patient,” said Dr. Willenheimer, a cardiologist at University Hospital Malmö (Sweden). “For patients with tachycardia or ischemic cardiomyopathy, I'd start with a β-blocker,” he told this newspaper.

Dr. Willenheimer has received honoraria from the German division of Merck, which sponsored the study and markets a formulation of the β-blocker bisoprolol (Concor) that is approved in many countries (but not the United States) for treating heart failure. In the United States, generic bisoprolol and its trade formulation (Zebeta) are approved only for treating hypertension. β-Blockers approved for treating heart failure in the United States are carvedilol (Coreg) and metoprolol succinate (Toprol-XL).

The study enrolled 1,010 patients aged 65 years or older (the mean age was 72 years) with New York Heart Association class II or III heart failure at 128 centers in 20 countries. Their average left ventricular ejection fraction was 29%. Patients were randomized to start treatment with either 1.25 mg of bisoprolol once daily or 2.5 mg of the ACE inhibitor enalapril b.i.d. Their monotherapy dosage was increased every 2 weeks until the bisoprolol dosage was 10 mg once daily or the enalapril dosage was 10 mg b.i.d. Monotherapy was continued to a total duration of 6 months, after which the second drug was begun with a similar up-titration scheme. Patients were followed for an average of 1.2 years.

By all efficacy measures used, the bisoprolol-first strategy was not inferior to the enalapril-first regimen. The study's primary end point was the time to first all-cause death or all-cause hospitalization. During follow-up on an intention-to-treat basis, these events occurred in 35.2% of patients in the bisoprolol-first arm and in 36.8% of those in the enalapril-first arm. On a per-protocol basis, the event rates were 32.4% in the bisoprolol-first patients and 33.1% in the enalapril-first group (Circulation 2005;112:2426–35).

The incidence of treatment-related adverse events was also similar in both groups. However, in patients treated with bisoprolol first, the results showed a trend toward an improved survival benefit and a trend toward a higher frequency of worsening heart failure requiring hospitalization, especially early in the study.

These findings are probably class effects, Dr. Willenheimer said. In both treatment groups, the drug that was started first was given in higher dosages during the combined therapy phase. The study was limited by several factors, Dr. Dickstein noted. It was done on an open-label basis, it did not include patients with class IV disease, and patients were maintained on monotherapy for the relatively long period of 6 months. Nonetheless, he said that on the basis of the results, he believes that the two strategies probably have comparable efficacy and safety.

A physician can start treatment based on individual judgment of each patient. DR. WILLENHEIMER

STOCKHOLM — Body temperature gauged prognosis in a retrospective analysis of patients hospitalized for heart failure.

Patients hospitalized for heart failure with hypothermia (a body temperature of 96.5°F or less) at admission were fourfold more likely to die during follow-up as were normathermic patients, Mihai Gheorghiade, M.D., said at the annual congress of the European Society of Cardiology.

“This is the first report [of the link with hypothermia], so it needs validation before making any conclusion that temperature is a prognostic factor,” said Dr. Gheorghiade, professor of medicine at Northwestern University, Chicago.

The correlation was made by reviewing data collected in a study designed to test the safety and efficacy of tolvaptan, an oral vasopressin receptor antagonist, in patients with systolic dysfunction who were hospitalized for worsening heart failure. Of 319 patients enrolled, body temperature readings on admission were available for 315.

Of those patients, 32 had hypothermia. At 60 days, mortality was 9.4% in patients with hypothermia and 5.9% in those with normothermia. After adjustment for baseline differences in blood urea nitrogen, age, and tolvaptan treatment, the patients with hypothermia were 3.9 times more likely to die.

In clinical trials, body temperature should be measured at admission and daily to correlate temperature and heart failure status, Dr. Gheorghiade said.

STOCKHOLM — Body temperature gauged prognosis in a retrospective analysis of patients hospitalized for heart failure.

Patients hospitalized for heart failure with hypothermia (a body temperature of 96.5°F or less) at admission were fourfold more likely to die during follow-up as were normathermic patients, Mihai Gheorghiade, M.D., said at the annual congress of the European Society of Cardiology.

“This is the first report [of the link with hypothermia], so it needs validation before making any conclusion that temperature is a prognostic factor,” said Dr. Gheorghiade, professor of medicine at Northwestern University, Chicago.

The correlation was made by reviewing data collected in a study designed to test the safety and efficacy of tolvaptan, an oral vasopressin receptor antagonist, in patients with systolic dysfunction who were hospitalized for worsening heart failure. Of 319 patients enrolled, body temperature readings on admission were available for 315.

Of those patients, 32 had hypothermia. At 60 days, mortality was 9.4% in patients with hypothermia and 5.9% in those with normothermia. After adjustment for baseline differences in blood urea nitrogen, age, and tolvaptan treatment, the patients with hypothermia were 3.9 times more likely to die.

In clinical trials, body temperature should be measured at admission and daily to correlate temperature and heart failure status, Dr. Gheorghiade said.

STOCKHOLM — Body temperature gauged prognosis in a retrospective analysis of patients hospitalized for heart failure.

Patients hospitalized for heart failure with hypothermia (a body temperature of 96.5°F or less) at admission were fourfold more likely to die during follow-up as were normathermic patients, Mihai Gheorghiade, M.D., said at the annual congress of the European Society of Cardiology.

“This is the first report [of the link with hypothermia], so it needs validation before making any conclusion that temperature is a prognostic factor,” said Dr. Gheorghiade, professor of medicine at Northwestern University, Chicago.

The correlation was made by reviewing data collected in a study designed to test the safety and efficacy of tolvaptan, an oral vasopressin receptor antagonist, in patients with systolic dysfunction who were hospitalized for worsening heart failure. Of 319 patients enrolled, body temperature readings on admission were available for 315.

Of those patients, 32 had hypothermia. At 60 days, mortality was 9.4% in patients with hypothermia and 5.9% in those with normothermia. After adjustment for baseline differences in blood urea nitrogen, age, and tolvaptan treatment, the patients with hypothermia were 3.9 times more likely to die.

In clinical trials, body temperature should be measured at admission and daily to correlate temperature and heart failure status, Dr. Gheorghiade said.

STOCKHOLM — Treatment with the ACE inhibitor perindopril cut the incidence of left ventricular remodeling following myocardial infarction in a study with more than 1,200 elderly patients with preserved left ventricular function.

Perindopril, at a dosage of 8 mg/day, “may be suggested as standard treatment in this clinical setting,” Roberto Ferrari, M.D., said at the annual congress of the European Society of Cardiology.

Based on the results of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study and those of seven previous studies, “we now have convincing evidence that all patients with coronary artery disease should get treated with an ACE inhibitor,” commented Nicolas Danchin, M.D., a professor of medicine at the European Hospital Georges Pompidou in Paris.

The PREAMI study enrolled 1,252 patients, average age 72 years, at 109 centers in five European countries. All had a left ventricular ejection fraction of at least 40%; the average ejection fraction was 59%. About 80% of patients had New York Heart Association class I heart failure.

Patients were enrolled 7–20 days (a mean of 11 days) after their MI. Patients who had already begun treatment with an ACE inhibitor were withdrawn from the drug for at least 24 hours before entering the study. Three-quarters were on a β-blocker, which they continued to take.

Patients were randomized to treatment with either 4-mg perindopril daily or placebo for the first month of the study, after which the drug dosage was raised to 8 mg daily. Patients were followed for a total of 12 months. The study's primary end point was the combined incidence of death, hospitalization for heart failure, or left ventricular remodeling. Remodeling was defined as a rise of at least 8% in left ventricular and diastolic volumes. Echocardiographs were available a year after treatment started for 455 perindopril and 441 placebo patients.

The incidence of the primary end point was cut by 38% in patients on perindopril, compared with those on placebo, a statistically significant difference, reported Dr. Ferrari, head of cardiology at the University of Ferrara (Italy). But the result was driven entirely by a 46% relative drop in the rate of ventricular remodeling in the perindopril-treated patients (28%), compared with the controls (51%). There was no difference in the mortality rate.

The study was sponsored by Servier, marketer of perindopril (Coversyl) in Europe and elsewhere. In the United States, perindopril is marketed as Aceon by a partnership of Solvay Pharmaceuticals Inc. and CV Therapeutics Inc.

STOCKHOLM — Treatment with the ACE inhibitor perindopril cut the incidence of left ventricular remodeling following myocardial infarction in a study with more than 1,200 elderly patients with preserved left ventricular function.

Perindopril, at a dosage of 8 mg/day, “may be suggested as standard treatment in this clinical setting,” Roberto Ferrari, M.D., said at the annual congress of the European Society of Cardiology.

Based on the results of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study and those of seven previous studies, “we now have convincing evidence that all patients with coronary artery disease should get treated with an ACE inhibitor,” commented Nicolas Danchin, M.D., a professor of medicine at the European Hospital Georges Pompidou in Paris.

The PREAMI study enrolled 1,252 patients, average age 72 years, at 109 centers in five European countries. All had a left ventricular ejection fraction of at least 40%; the average ejection fraction was 59%. About 80% of patients had New York Heart Association class I heart failure.

Patients were enrolled 7–20 days (a mean of 11 days) after their MI. Patients who had already begun treatment with an ACE inhibitor were withdrawn from the drug for at least 24 hours before entering the study. Three-quarters were on a β-blocker, which they continued to take.

Patients were randomized to treatment with either 4-mg perindopril daily or placebo for the first month of the study, after which the drug dosage was raised to 8 mg daily. Patients were followed for a total of 12 months. The study's primary end point was the combined incidence of death, hospitalization for heart failure, or left ventricular remodeling. Remodeling was defined as a rise of at least 8% in left ventricular and diastolic volumes. Echocardiographs were available a year after treatment started for 455 perindopril and 441 placebo patients.

The incidence of the primary end point was cut by 38% in patients on perindopril, compared with those on placebo, a statistically significant difference, reported Dr. Ferrari, head of cardiology at the University of Ferrara (Italy). But the result was driven entirely by a 46% relative drop in the rate of ventricular remodeling in the perindopril-treated patients (28%), compared with the controls (51%). There was no difference in the mortality rate.

The study was sponsored by Servier, marketer of perindopril (Coversyl) in Europe and elsewhere. In the United States, perindopril is marketed as Aceon by a partnership of Solvay Pharmaceuticals Inc. and CV Therapeutics Inc.

STOCKHOLM — Treatment with the ACE inhibitor perindopril cut the incidence of left ventricular remodeling following myocardial infarction in a study with more than 1,200 elderly patients with preserved left ventricular function.

Perindopril, at a dosage of 8 mg/day, “may be suggested as standard treatment in this clinical setting,” Roberto Ferrari, M.D., said at the annual congress of the European Society of Cardiology.

Based on the results of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study and those of seven previous studies, “we now have convincing evidence that all patients with coronary artery disease should get treated with an ACE inhibitor,” commented Nicolas Danchin, M.D., a professor of medicine at the European Hospital Georges Pompidou in Paris.

The PREAMI study enrolled 1,252 patients, average age 72 years, at 109 centers in five European countries. All had a left ventricular ejection fraction of at least 40%; the average ejection fraction was 59%. About 80% of patients had New York Heart Association class I heart failure.

Patients were enrolled 7–20 days (a mean of 11 days) after their MI. Patients who had already begun treatment with an ACE inhibitor were withdrawn from the drug for at least 24 hours before entering the study. Three-quarters were on a β-blocker, which they continued to take.

Patients were randomized to treatment with either 4-mg perindopril daily or placebo for the first month of the study, after which the drug dosage was raised to 8 mg daily. Patients were followed for a total of 12 months. The study's primary end point was the combined incidence of death, hospitalization for heart failure, or left ventricular remodeling. Remodeling was defined as a rise of at least 8% in left ventricular and diastolic volumes. Echocardiographs were available a year after treatment started for 455 perindopril and 441 placebo patients.

The incidence of the primary end point was cut by 38% in patients on perindopril, compared with those on placebo, a statistically significant difference, reported Dr. Ferrari, head of cardiology at the University of Ferrara (Italy). But the result was driven entirely by a 46% relative drop in the rate of ventricular remodeling in the perindopril-treated patients (28%), compared with the controls (51%). There was no difference in the mortality rate.

The study was sponsored by Servier, marketer of perindopril (Coversyl) in Europe and elsewhere. In the United States, perindopril is marketed as Aceon by a partnership of Solvay Pharmaceuticals Inc. and CV Therapeutics Inc.