Heidi Splete

ORLANDO – Three novel agents with three different targets cleared phase I hurdles in chronic lymphocytic leukemia.

These investigational agents, still known by their drug company labels, demonstrated varying degrees of activity in heavily pretreated patients. In all three presentations, investigators concluded that further trials are warranted.

PCI-32765 Hits Bruton’s Tyrosine Kinase

In the first presentation, PCI-32765 was described as a novel oral selective inhibitor of Bruton’s tyrosine kinase (Btk), a mediator of B-cell receptor signaling. Btk is not expressed in T cells or NK cells, which makes it "an ideal therapeutic target for B-cell malignancies dependent on BCR [gene] signaling," said Dr. Jan A. Burger of the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Burger presented pooled data from 54 patients (median age, 68 years), 47 of whom had chronic lymphocytic leukemia (CLL) and 7 of whom had small lymphocytic leukemia (SLL). Outcomes included 1 complete response and 16 partial responses in a population who had had a median of 3 previous therapies (range, 1-10). Nearly all (95%) had previously received a nucleoside analogue and anti-CD20 agents. In addition, 21% had prior bendamustine and 9% had alemtuzumab.

The trial divided these patients into the following two groups:

• Phase IA. Of 23 patients enrolled, 16 were treated in 28-day cycles with 7 days of rest. They received doses from 1.25 mg/kg per day to 12.5 mg/kg per day of the study drug. The other seven patients were treated for cycles of 35 days with no rest. In this group, six received 8.3 mg/kg per day, and one received a fixed dose of 560 mg/day. The median follow-up was 8 months.

Among the 13 evaluable patients in phase IA, 1 patient (8%) had a complete response, 8 (62%) had a partial response, and 2 (15%) had nodal response with lymphocytosis.

• Phase IB. Of 38 patients enrolled, 11 were treatment naive and 27 were relapsed or refractory patients. All received 420 mg/day in 28-day cycles. The median follow-up was 2 months.

Among the 32 evaluable patients in the phase IB group, none had complete response, 8 patients (25%) had a partial response, and 17 patients (53%) had nodal response with lymphocytosis.

All told, of 39 patients who were evaluated for changes in lymph node disease, 87% had a nodal response to PCI-32765. "Rapid lymph node responses are associated with a transient lymphocytosis, indicating a unique phenomenon of BCR-targeted therapy," Dr. Burger commented.

Overall, no renal or hepatic adverse events have been reported, and no evidence has been seen of cumulative toxicity in patients with at least 6 months of follow-up, Dr. Burger said. Reported adverse events included diarrhea, nausea, vomiting, headache, and rash.

Although the numbers are small and the results are preliminary, "the lack of drug-related myelosuppression or cumulative toxicity supports further investigation in various CLL treatment settings," Dr. Burger said.

Pharmacyclics sponsored the trial. Dr. Burger had no financial conflicts to disclose. Several coauthors reported serving as a consultant or receiving honoraria or research funding from the company; four were employees with equity ownership.

CAL-101 Blocks the PI3K-Delta Pathway

Novel CAL-101, an orally bioavailable small molecule, inhibits PI3K-delta activity, according to findings described in the second presentation.

"Constitutive activation of the PI3K-delta pathway drives proliferation, survival, and abnormal trafficking of malignant B-cells in chronic lymphocytic leukemia," said Dr. Richard R. Furman, director of the CLL and Waldenström’s macroglobulinemia programs at Cornell University in New York City.

In this study of patients with previously treated hematologic malignancies, 54 CLL patients received 50 mg to 150 mg of CAL-101 twice daily, with continuous oral dosing for an average of eight 28-day cycles. The median age of the patients was 63 years and 82% were male. All patients had been treated with fludarabine. In addition, 98% had received rituximab, 87% had received an alkylating agent, and 31% had received alemtuzumab.

The overall response rate was 26%, and the lymph node response rate was 80%. In addition, CAL-101 was associated with nodal shrinkage in all patients in an intent-to-treat analysis. Patients with baseline thrombocytopenia (defined as platelet counts less than 100,000/mcL) experienced sustained improvements in platelet count (that is, greater than 100,000/mcL, or greater than 50%), Dr. Furman said.

The most common grade 3/4 hematologic adverse event was neutropenia (24%), and the most common grade 3/4 nonhematologic event was pneumonia (24%). "Grade 3/4 adverse events were largely due to prior therapy or underlying CLL," said Dr. Furman. No pattern of drug-related symptomatic adverse events was observed, and patients showed no dose-limiting toxicities over periods of exposure beyond 1 year.

The results support further studies of CAL-101 at a dosage of 150 mg twice daily as a frontline therapy for CLL patients, or as a single agent or combined with chemoimmunotherapy for CLL patients, Dr. Furman added.

Calistoga Pharmaceuticals sponsored the trial. Dr. Furman had no financial conflicts to disclose. Several coauthors disclosed consultancy for, employment with, or research funding from Calistoga Pharmaceuticals; seven were employees and/or held equity ownership in the company.

TRU-016 Tackles CD37

Dr. Furman also presented results from a dose-escalation study of TRU-016, a novel humanized anti-CD37 small modular immunopharmaceutical (SMIP) protein.

Studies in mice have suggested that CD37 is involved in regulating B-cell function. TRU-016 offers direct apoptosis with greater cell-killing potential than rituximab and greater antibody-dependent cellular cytotoxicity than rituximab or alemtuzumab, he said.

In this dose-finding study, 57 patients with relapsed or refractory CLL or SLL received one of nine dosages, ranging from 0.03 mg/kg to 20 mg/kg, given intravenously once a week for 4-12 weekly doses. In a second dosing schedule, patients received 3, 6, or 10 mg/kg on days 1, 3, and 5 of the first week of treatment, followed by 3-11 weekly doses three times a week. The patients had no organ function problems, and their platelet counts were greater than 30,000/mcL.

The overall response rate was 13%, based on 1996 National Cancer Institute criteria. The overall median reduction in lymphocytes in the intent-to-treat population was 60%.

In the 16 patients with one to two prior therapies, the overall response rate was 40% and the clinical response rate was 44%. No clinical response was noted in patients with three or more prior therapies, but there was an overall median reduction in lymphocytes of 60% from baseline to the end of treatment, Dr. Furman said. The median progression-free survival for all patients was 134 days.

Neutropenia, the most common adverse event, was reported in nine patients (16%). There was no apparent relationship between drug dose and adverse events, and a maximum tolerated dose was not reached in this study.

"Given B-cell selective target, independent single agent activity, and synergy with CLL therapies, TRU-016 combination trials in CLL patients are planned," he said.

Trubion Pharmaceuticals (now Emergent Biosolutions) sponsored the trial. Dr. Furman had no financial conflicts to disclose. Several coinvestigators disclosed consultancy for, employment with equity ownership in, or research funding from Trubion.

ORLANDO – Three novel agents with three different targets cleared phase I hurdles in chronic lymphocytic leukemia.

These investigational agents, still known by their drug company labels, demonstrated varying degrees of activity in heavily pretreated patients. In all three presentations, investigators concluded that further trials are warranted.

PCI-32765 Hits Bruton’s Tyrosine Kinase

In the first presentation, PCI-32765 was described as a novel oral selective inhibitor of Bruton’s tyrosine kinase (Btk), a mediator of B-cell receptor signaling. Btk is not expressed in T cells or NK cells, which makes it "an ideal therapeutic target for B-cell malignancies dependent on BCR [gene] signaling," said Dr. Jan A. Burger of the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Burger presented pooled data from 54 patients (median age, 68 years), 47 of whom had chronic lymphocytic leukemia (CLL) and 7 of whom had small lymphocytic leukemia (SLL). Outcomes included 1 complete response and 16 partial responses in a population who had had a median of 3 previous therapies (range, 1-10). Nearly all (95%) had previously received a nucleoside analogue and anti-CD20 agents. In addition, 21% had prior bendamustine and 9% had alemtuzumab.

The trial divided these patients into the following two groups:

• Phase IA. Of 23 patients enrolled, 16 were treated in 28-day cycles with 7 days of rest. They received doses from 1.25 mg/kg per day to 12.5 mg/kg per day of the study drug. The other seven patients were treated for cycles of 35 days with no rest. In this group, six received 8.3 mg/kg per day, and one received a fixed dose of 560 mg/day. The median follow-up was 8 months.

Among the 13 evaluable patients in phase IA, 1 patient (8%) had a complete response, 8 (62%) had a partial response, and 2 (15%) had nodal response with lymphocytosis.

• Phase IB. Of 38 patients enrolled, 11 were treatment naive and 27 were relapsed or refractory patients. All received 420 mg/day in 28-day cycles. The median follow-up was 2 months.

Among the 32 evaluable patients in the phase IB group, none had complete response, 8 patients (25%) had a partial response, and 17 patients (53%) had nodal response with lymphocytosis.

All told, of 39 patients who were evaluated for changes in lymph node disease, 87% had a nodal response to PCI-32765. "Rapid lymph node responses are associated with a transient lymphocytosis, indicating a unique phenomenon of BCR-targeted therapy," Dr. Burger commented.

Overall, no renal or hepatic adverse events have been reported, and no evidence has been seen of cumulative toxicity in patients with at least 6 months of follow-up, Dr. Burger said. Reported adverse events included diarrhea, nausea, vomiting, headache, and rash.

Although the numbers are small and the results are preliminary, "the lack of drug-related myelosuppression or cumulative toxicity supports further investigation in various CLL treatment settings," Dr. Burger said.

Pharmacyclics sponsored the trial. Dr. Burger had no financial conflicts to disclose. Several coauthors reported serving as a consultant or receiving honoraria or research funding from the company; four were employees with equity ownership.

CAL-101 Blocks the PI3K-Delta Pathway

Novel CAL-101, an orally bioavailable small molecule, inhibits PI3K-delta activity, according to findings described in the second presentation.

"Constitutive activation of the PI3K-delta pathway drives proliferation, survival, and abnormal trafficking of malignant B-cells in chronic lymphocytic leukemia," said Dr. Richard R. Furman, director of the CLL and Waldenström’s macroglobulinemia programs at Cornell University in New York City.

In this study of patients with previously treated hematologic malignancies, 54 CLL patients received 50 mg to 150 mg of CAL-101 twice daily, with continuous oral dosing for an average of eight 28-day cycles. The median age of the patients was 63 years and 82% were male. All patients had been treated with fludarabine. In addition, 98% had received rituximab, 87% had received an alkylating agent, and 31% had received alemtuzumab.

The overall response rate was 26%, and the lymph node response rate was 80%. In addition, CAL-101 was associated with nodal shrinkage in all patients in an intent-to-treat analysis. Patients with baseline thrombocytopenia (defined as platelet counts less than 100,000/mcL) experienced sustained improvements in platelet count (that is, greater than 100,000/mcL, or greater than 50%), Dr. Furman said.

The most common grade 3/4 hematologic adverse event was neutropenia (24%), and the most common grade 3/4 nonhematologic event was pneumonia (24%). "Grade 3/4 adverse events were largely due to prior therapy or underlying CLL," said Dr. Furman. No pattern of drug-related symptomatic adverse events was observed, and patients showed no dose-limiting toxicities over periods of exposure beyond 1 year.

The results support further studies of CAL-101 at a dosage of 150 mg twice daily as a frontline therapy for CLL patients, or as a single agent or combined with chemoimmunotherapy for CLL patients, Dr. Furman added.

Calistoga Pharmaceuticals sponsored the trial. Dr. Furman had no financial conflicts to disclose. Several coauthors disclosed consultancy for, employment with, or research funding from Calistoga Pharmaceuticals; seven were employees and/or held equity ownership in the company.

TRU-016 Tackles CD37

Dr. Furman also presented results from a dose-escalation study of TRU-016, a novel humanized anti-CD37 small modular immunopharmaceutical (SMIP) protein.

Studies in mice have suggested that CD37 is involved in regulating B-cell function. TRU-016 offers direct apoptosis with greater cell-killing potential than rituximab and greater antibody-dependent cellular cytotoxicity than rituximab or alemtuzumab, he said.

In this dose-finding study, 57 patients with relapsed or refractory CLL or SLL received one of nine dosages, ranging from 0.03 mg/kg to 20 mg/kg, given intravenously once a week for 4-12 weekly doses. In a second dosing schedule, patients received 3, 6, or 10 mg/kg on days 1, 3, and 5 of the first week of treatment, followed by 3-11 weekly doses three times a week. The patients had no organ function problems, and their platelet counts were greater than 30,000/mcL.

The overall response rate was 13%, based on 1996 National Cancer Institute criteria. The overall median reduction in lymphocytes in the intent-to-treat population was 60%.

In the 16 patients with one to two prior therapies, the overall response rate was 40% and the clinical response rate was 44%. No clinical response was noted in patients with three or more prior therapies, but there was an overall median reduction in lymphocytes of 60% from baseline to the end of treatment, Dr. Furman said. The median progression-free survival for all patients was 134 days.

Neutropenia, the most common adverse event, was reported in nine patients (16%). There was no apparent relationship between drug dose and adverse events, and a maximum tolerated dose was not reached in this study.

"Given B-cell selective target, independent single agent activity, and synergy with CLL therapies, TRU-016 combination trials in CLL patients are planned," he said.

Trubion Pharmaceuticals (now Emergent Biosolutions) sponsored the trial. Dr. Furman had no financial conflicts to disclose. Several coinvestigators disclosed consultancy for, employment with equity ownership in, or research funding from Trubion.

ORLANDO – Three novel agents with three different targets cleared phase I hurdles in chronic lymphocytic leukemia.

These investigational agents, still known by their drug company labels, demonstrated varying degrees of activity in heavily pretreated patients. In all three presentations, investigators concluded that further trials are warranted.

PCI-32765 Hits Bruton’s Tyrosine Kinase

In the first presentation, PCI-32765 was described as a novel oral selective inhibitor of Bruton’s tyrosine kinase (Btk), a mediator of B-cell receptor signaling. Btk is not expressed in T cells or NK cells, which makes it "an ideal therapeutic target for B-cell malignancies dependent on BCR [gene] signaling," said Dr. Jan A. Burger of the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Burger presented pooled data from 54 patients (median age, 68 years), 47 of whom had chronic lymphocytic leukemia (CLL) and 7 of whom had small lymphocytic leukemia (SLL). Outcomes included 1 complete response and 16 partial responses in a population who had had a median of 3 previous therapies (range, 1-10). Nearly all (95%) had previously received a nucleoside analogue and anti-CD20 agents. In addition, 21% had prior bendamustine and 9% had alemtuzumab.

The trial divided these patients into the following two groups:

• Phase IA. Of 23 patients enrolled, 16 were treated in 28-day cycles with 7 days of rest. They received doses from 1.25 mg/kg per day to 12.5 mg/kg per day of the study drug. The other seven patients were treated for cycles of 35 days with no rest. In this group, six received 8.3 mg/kg per day, and one received a fixed dose of 560 mg/day. The median follow-up was 8 months.

Among the 13 evaluable patients in phase IA, 1 patient (8%) had a complete response, 8 (62%) had a partial response, and 2 (15%) had nodal response with lymphocytosis.

• Phase IB. Of 38 patients enrolled, 11 were treatment naive and 27 were relapsed or refractory patients. All received 420 mg/day in 28-day cycles. The median follow-up was 2 months.

Among the 32 evaluable patients in the phase IB group, none had complete response, 8 patients (25%) had a partial response, and 17 patients (53%) had nodal response with lymphocytosis.

All told, of 39 patients who were evaluated for changes in lymph node disease, 87% had a nodal response to PCI-32765. "Rapid lymph node responses are associated with a transient lymphocytosis, indicating a unique phenomenon of BCR-targeted therapy," Dr. Burger commented.

Overall, no renal or hepatic adverse events have been reported, and no evidence has been seen of cumulative toxicity in patients with at least 6 months of follow-up, Dr. Burger said. Reported adverse events included diarrhea, nausea, vomiting, headache, and rash.

Although the numbers are small and the results are preliminary, "the lack of drug-related myelosuppression or cumulative toxicity supports further investigation in various CLL treatment settings," Dr. Burger said.

Pharmacyclics sponsored the trial. Dr. Burger had no financial conflicts to disclose. Several coauthors reported serving as a consultant or receiving honoraria or research funding from the company; four were employees with equity ownership.

CAL-101 Blocks the PI3K-Delta Pathway

Novel CAL-101, an orally bioavailable small molecule, inhibits PI3K-delta activity, according to findings described in the second presentation.

"Constitutive activation of the PI3K-delta pathway drives proliferation, survival, and abnormal trafficking of malignant B-cells in chronic lymphocytic leukemia," said Dr. Richard R. Furman, director of the CLL and Waldenström’s macroglobulinemia programs at Cornell University in New York City.

In this study of patients with previously treated hematologic malignancies, 54 CLL patients received 50 mg to 150 mg of CAL-101 twice daily, with continuous oral dosing for an average of eight 28-day cycles. The median age of the patients was 63 years and 82% were male. All patients had been treated with fludarabine. In addition, 98% had received rituximab, 87% had received an alkylating agent, and 31% had received alemtuzumab.

The overall response rate was 26%, and the lymph node response rate was 80%. In addition, CAL-101 was associated with nodal shrinkage in all patients in an intent-to-treat analysis. Patients with baseline thrombocytopenia (defined as platelet counts less than 100,000/mcL) experienced sustained improvements in platelet count (that is, greater than 100,000/mcL, or greater than 50%), Dr. Furman said.

The most common grade 3/4 hematologic adverse event was neutropenia (24%), and the most common grade 3/4 nonhematologic event was pneumonia (24%). "Grade 3/4 adverse events were largely due to prior therapy or underlying CLL," said Dr. Furman. No pattern of drug-related symptomatic adverse events was observed, and patients showed no dose-limiting toxicities over periods of exposure beyond 1 year.

The results support further studies of CAL-101 at a dosage of 150 mg twice daily as a frontline therapy for CLL patients, or as a single agent or combined with chemoimmunotherapy for CLL patients, Dr. Furman added.

Calistoga Pharmaceuticals sponsored the trial. Dr. Furman had no financial conflicts to disclose. Several coauthors disclosed consultancy for, employment with, or research funding from Calistoga Pharmaceuticals; seven were employees and/or held equity ownership in the company.

TRU-016 Tackles CD37

Dr. Furman also presented results from a dose-escalation study of TRU-016, a novel humanized anti-CD37 small modular immunopharmaceutical (SMIP) protein.

Studies in mice have suggested that CD37 is involved in regulating B-cell function. TRU-016 offers direct apoptosis with greater cell-killing potential than rituximab and greater antibody-dependent cellular cytotoxicity than rituximab or alemtuzumab, he said.

In this dose-finding study, 57 patients with relapsed or refractory CLL or SLL received one of nine dosages, ranging from 0.03 mg/kg to 20 mg/kg, given intravenously once a week for 4-12 weekly doses. In a second dosing schedule, patients received 3, 6, or 10 mg/kg on days 1, 3, and 5 of the first week of treatment, followed by 3-11 weekly doses three times a week. The patients had no organ function problems, and their platelet counts were greater than 30,000/mcL.

The overall response rate was 13%, based on 1996 National Cancer Institute criteria. The overall median reduction in lymphocytes in the intent-to-treat population was 60%.

In the 16 patients with one to two prior therapies, the overall response rate was 40% and the clinical response rate was 44%. No clinical response was noted in patients with three or more prior therapies, but there was an overall median reduction in lymphocytes of 60% from baseline to the end of treatment, Dr. Furman said. The median progression-free survival for all patients was 134 days.

Neutropenia, the most common adverse event, was reported in nine patients (16%). There was no apparent relationship between drug dose and adverse events, and a maximum tolerated dose was not reached in this study.

"Given B-cell selective target, independent single agent activity, and synergy with CLL therapies, TRU-016 combination trials in CLL patients are planned," he said.

Trubion Pharmaceuticals (now Emergent Biosolutions) sponsored the trial. Dr. Furman had no financial conflicts to disclose. Several coinvestigators disclosed consultancy for, employment with equity ownership in, or research funding from Trubion.

The life expectancy of Americans falls short compared to that of their counterparts in other high-income countries, and smoking and obesity are key contributors to the difference, the National Research Council of the National Academies reported Jan. 25.

The life expectancy at birth for U.S. men increased from 65 years in 1950 to 76 years in 2006; for U.S. women, it increased from 71 to 81 years. Similarly, life expectancy at age 50 for men in the U.S. increased from 23 to 29 years. For American women, that figure rose from 27 to 33 years. Still, the improved life expectancy in the United States –the world’s top spender on health care -- fell below that of approximately nine other countries, including Australia, Japan, and Canada. (See graphic.)

The National Council on Aging commissioned the report, "Explaining Divergent Levels of Longevity in High-Income Countries," to identify factors behind the differences in life expectancy. The report focused on life expectancy at age 50, because at least 90% of newborns in high-income countries now survive to age 50 years. The data were based primarily on an analysis of cause-of-death statistics.

"Smoking appears to be responsible for a good deal of the divergence in female life expectancy," according to the report. The researchers estimated that 78% of the difference in life expectancy between American women and those in other high-income countries was attributable to smoking. Similarly, among men, smoking accounted for 41% of the difference.

The reduction in smoking in the United States over the past 20 years is likely to pay off in improved longevity trends in future decades, the researchers noted. A reduction or increase in smoking rates appears to take 20 to 30 years to impact mortality, they added.

Obesity also plays a significant role in the lagging U.S. longevity. Based on data from several studies, obesity accounts for approximately 20%-35% of the difference in longevity between Americans and residents of countries.

Physical inactivity, social integration, and healthcare systems also likely contribute to increased mortality and differences in life expectancy among countries, but evaluation of these risk factors has been limited to observational studies, the researchers noted.

The report was limited by a lack of markers to directly identify the impact on longevity of risk factors other than smoking, including obesity, physical inactivity, and stress, the researchers said.

The National Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering, which are private, nonprofit institutions. The report is available for purchase from the National Academies Press.

The life expectancy of Americans falls short compared to that of their counterparts in other high-income countries, and smoking and obesity are key contributors to the difference, the National Research Council of the National Academies reported Jan. 25.

The life expectancy at birth for U.S. men increased from 65 years in 1950 to 76 years in 2006; for U.S. women, it increased from 71 to 81 years. Similarly, life expectancy at age 50 for men in the U.S. increased from 23 to 29 years. For American women, that figure rose from 27 to 33 years. Still, the improved life expectancy in the United States –the world’s top spender on health care -- fell below that of approximately nine other countries, including Australia, Japan, and Canada. (See graphic.)

The National Council on Aging commissioned the report, "Explaining Divergent Levels of Longevity in High-Income Countries," to identify factors behind the differences in life expectancy. The report focused on life expectancy at age 50, because at least 90% of newborns in high-income countries now survive to age 50 years. The data were based primarily on an analysis of cause-of-death statistics.

"Smoking appears to be responsible for a good deal of the divergence in female life expectancy," according to the report. The researchers estimated that 78% of the difference in life expectancy between American women and those in other high-income countries was attributable to smoking. Similarly, among men, smoking accounted for 41% of the difference.

The reduction in smoking in the United States over the past 20 years is likely to pay off in improved longevity trends in future decades, the researchers noted. A reduction or increase in smoking rates appears to take 20 to 30 years to impact mortality, they added.

Obesity also plays a significant role in the lagging U.S. longevity. Based on data from several studies, obesity accounts for approximately 20%-35% of the difference in longevity between Americans and residents of countries.

Physical inactivity, social integration, and healthcare systems also likely contribute to increased mortality and differences in life expectancy among countries, but evaluation of these risk factors has been limited to observational studies, the researchers noted.

The report was limited by a lack of markers to directly identify the impact on longevity of risk factors other than smoking, including obesity, physical inactivity, and stress, the researchers said.

The National Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering, which are private, nonprofit institutions. The report is available for purchase from the National Academies Press.

The life expectancy of Americans falls short compared to that of their counterparts in other high-income countries, and smoking and obesity are key contributors to the difference, the National Research Council of the National Academies reported Jan. 25.

The life expectancy at birth for U.S. men increased from 65 years in 1950 to 76 years in 2006; for U.S. women, it increased from 71 to 81 years. Similarly, life expectancy at age 50 for men in the U.S. increased from 23 to 29 years. For American women, that figure rose from 27 to 33 years. Still, the improved life expectancy in the United States –the world’s top spender on health care -- fell below that of approximately nine other countries, including Australia, Japan, and Canada. (See graphic.)

The National Council on Aging commissioned the report, "Explaining Divergent Levels of Longevity in High-Income Countries," to identify factors behind the differences in life expectancy. The report focused on life expectancy at age 50, because at least 90% of newborns in high-income countries now survive to age 50 years. The data were based primarily on an analysis of cause-of-death statistics.

"Smoking appears to be responsible for a good deal of the divergence in female life expectancy," according to the report. The researchers estimated that 78% of the difference in life expectancy between American women and those in other high-income countries was attributable to smoking. Similarly, among men, smoking accounted for 41% of the difference.

The reduction in smoking in the United States over the past 20 years is likely to pay off in improved longevity trends in future decades, the researchers noted. A reduction or increase in smoking rates appears to take 20 to 30 years to impact mortality, they added.

Obesity also plays a significant role in the lagging U.S. longevity. Based on data from several studies, obesity accounts for approximately 20%-35% of the difference in longevity between Americans and residents of countries.

Physical inactivity, social integration, and healthcare systems also likely contribute to increased mortality and differences in life expectancy among countries, but evaluation of these risk factors has been limited to observational studies, the researchers noted.

The report was limited by a lack of markers to directly identify the impact on longevity of risk factors other than smoking, including obesity, physical inactivity, and stress, the researchers said.

The National Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering, which are private, nonprofit institutions. The report is available for purchase from the National Academies Press.

The life expectancy of Americans falls short compared to that of their counterparts in other high-income countries, and smoking and obesity are key contributors to the difference, the National Research Council of the National Academies reported Jan. 25.

The life expectancy at birth for U.S. men increased from 65 years in 1950 to 76 years in 2006; for U.S. women, it increased from 71 to 81 years. Similarly, life expectancy at age 50 for men in the U.S. increased from 23 to 29 years. For American women, that figure rose from 27 to 33 years. Still, the improved life expectancy in the United States –the world’s top spender on health care -- fell below that of approximately nine other countries, including Australia, Japan, and Canada. (See graphic.)

The National Council on Aging commissioned the report, "Explaining Divergent Levels of Longevity in High-Income Countries," to identify factors behind the differences in life expectancy. The report focused on life expectancy at age 50, because at least 90% of newborns in high-income countries now survive to age 50 years. The data were based primarily on an analysis of cause-of-death statistics.

"Smoking appears to be responsible for a good deal of the divergence in female life expectancy," according to the report. The researchers estimated that 78% of the difference in life expectancy between American women and those in other high-income countries was attributable to smoking. Similarly, among men, smoking accounted for 41% of the difference.

The reduction in smoking in the United States over the past 20 years is likely to pay off in improved longevity trends in future decades, the researchers noted. A reduction or increase in smoking rates appears to take 20 to 30 years to impact mortality, they added.

Obesity also plays a significant role in the lagging U.S. longevity. Based on data from several studies, obesity accounts for approximately 20%-35% of the difference in longevity between Americans and residents of countries.

Physical inactivity, social integration, and healthcare systems also likely contribute to increased mortality and differences in life expectancy among countries, but evaluation of these risk factors has been limited to observational studies, the researchers noted.

The report was limited by a lack of markers to directly identify the impact on longevity of risk factors other than smoking, including obesity, physical inactivity, and stress, the researchers said.

The National Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering, which are private, nonprofit institutions. The report is available for purchase from the National Academies Press.

The life expectancy of Americans falls short compared to that of their counterparts in other high-income countries, and smoking and obesity are key contributors to the difference, the National Research Council of the National Academies reported Jan. 25.

The life expectancy at birth for U.S. men increased from 65 years in 1950 to 76 years in 2006; for U.S. women, it increased from 71 to 81 years. Similarly, life expectancy at age 50 for men in the U.S. increased from 23 to 29 years. For American women, that figure rose from 27 to 33 years. Still, the improved life expectancy in the United States –the world’s top spender on health care -- fell below that of approximately nine other countries, including Australia, Japan, and Canada. (See graphic.)

The National Council on Aging commissioned the report, "Explaining Divergent Levels of Longevity in High-Income Countries," to identify factors behind the differences in life expectancy. The report focused on life expectancy at age 50, because at least 90% of newborns in high-income countries now survive to age 50 years. The data were based primarily on an analysis of cause-of-death statistics.

"Smoking appears to be responsible for a good deal of the divergence in female life expectancy," according to the report. The researchers estimated that 78% of the difference in life expectancy between American women and those in other high-income countries was attributable to smoking. Similarly, among men, smoking accounted for 41% of the difference.

The reduction in smoking in the United States over the past 20 years is likely to pay off in improved longevity trends in future decades, the researchers noted. A reduction or increase in smoking rates appears to take 20 to 30 years to impact mortality, they added.

Obesity also plays a significant role in the lagging U.S. longevity. Based on data from several studies, obesity accounts for approximately 20%-35% of the difference in longevity between Americans and residents of countries.

Physical inactivity, social integration, and healthcare systems also likely contribute to increased mortality and differences in life expectancy among countries, but evaluation of these risk factors has been limited to observational studies, the researchers noted.

The report was limited by a lack of markers to directly identify the impact on longevity of risk factors other than smoking, including obesity, physical inactivity, and stress, the researchers said.

The National Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering, which are private, nonprofit institutions. The report is available for purchase from the National Academies Press.

The life expectancy of Americans falls short compared to that of their counterparts in other high-income countries, and smoking and obesity are key contributors to the difference, the National Research Council of the National Academies reported Jan. 25.

The life expectancy at birth for U.S. men increased from 65 years in 1950 to 76 years in 2006; for U.S. women, it increased from 71 to 81 years. Similarly, life expectancy at age 50 for men in the U.S. increased from 23 to 29 years. For American women, that figure rose from 27 to 33 years. Still, the improved life expectancy in the United States –the world’s top spender on health care -- fell below that of approximately nine other countries, including Australia, Japan, and Canada. (See graphic.)

The National Council on Aging commissioned the report, "Explaining Divergent Levels of Longevity in High-Income Countries," to identify factors behind the differences in life expectancy. The report focused on life expectancy at age 50, because at least 90% of newborns in high-income countries now survive to age 50 years. The data were based primarily on an analysis of cause-of-death statistics.

"Smoking appears to be responsible for a good deal of the divergence in female life expectancy," according to the report. The researchers estimated that 78% of the difference in life expectancy between American women and those in other high-income countries was attributable to smoking. Similarly, among men, smoking accounted for 41% of the difference.

The reduction in smoking in the United States over the past 20 years is likely to pay off in improved longevity trends in future decades, the researchers noted. A reduction or increase in smoking rates appears to take 20 to 30 years to impact mortality, they added.

Obesity also plays a significant role in the lagging U.S. longevity. Based on data from several studies, obesity accounts for approximately 20%-35% of the difference in longevity between Americans and residents of countries.

Physical inactivity, social integration, and healthcare systems also likely contribute to increased mortality and differences in life expectancy among countries, but evaluation of these risk factors has been limited to observational studies, the researchers noted.

The report was limited by a lack of markers to directly identify the impact on longevity of risk factors other than smoking, including obesity, physical inactivity, and stress, the researchers said.

The National Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering, which are private, nonprofit institutions. The report is available for purchase from the National Academies Press.

WASHINGTON – Approximately 40% of the United States population could have some form of cardiovascular disease by the year 2030, based on data from a prediction model created by the American Heart Association. The findings were published online on Jan. 24 in an American Heart Association policy statement in Circulation.

If there’s a silver lining in these figures, it is that they are projections," Nancy Brown, chief executive officer of the AHA, said at a press conference. However, if current policies and prevention strategies go unchanged, the United States is facing "a cardiovascular crisis of alarming proportions," she said.

The aging U.S. population and the increase in medical spending are the main forces driving the disease prevalence and cost, wrote Dr. Paul Heidenreich, of the VA Palo Alto (Calif.) Health Care System, and colleagues.

Without changes in current prevention and treatment trends, the prevalence of cardiovascular disease in the United States will increase by about 10% over the next 20 years, and direct medical costs of cardiovascular disease will triple, from $273 billion to $818 billion, according to the policy statement.

The AHA statement projects an additional 27 million Americans with hypertension, 8 million with coronary heart disease, 4 million with stroke, and 3 million with heart failure between 2010 and 2030 (Circulation 2011 Jan. 24 [Epub doi: 10.1161/CIR.0b013e31820a55f5]).

According to the projections, hypertension will be the most expensive component of cardiovascular disease (CVD), with an estimated annual direct medical cost of $200 billion by 2030. The estimated direct medical cost for stroke is $96 billion, compared with $28 billion in 2010, but stroke represents the greatest relative increase in costs over the next 20 years (238%).

In addition, the indirect costs of all types of cardiovascular disease could increase by 61% (from $172 billion in 2010 to $276 billion in 2030).

However, previous studies have shown that many CVD cases are preventable, and individuals who maintain a healthy lifestyle and favorable levels of atherosclerotic risk are less likely to develop CVD. "Therefore, a greater focus on prevention may alter these CVD projections in the future," according to the statement.

Guidelines have been shown to have "a substantial impact on prevention and treatment and will be an important tool for limiting the burden of CVD," according to the statement. The AHA, the American College of Cardiology, and other organizations have previously published prevention-oriented CVD guidelines, but the implementation of such guidelines is often slow, the writing group noted.

Other factors that could hamper the improvement of CVD risk factors include a reported shortage of cardiologists, they added. Other shortages exist in nursing, pharmacy, and primary care, all of which are needed for a team approach to preventing CVD.

The take-home message for cardiologists is that they can "expect to see more demand for their services," Dr. Heidenreich said in an interview. In addition, primary care physicians will be seeing more patients with forms of heart disease. But the solution includes increasing the number of health professionals across all fields, not only cardiology, said Dr. Heidenreich. "The whole medical complex is insufficient to meet the demand" of the potential increases in CVD, he emphasized.

But, "through a combination of improved prevention of risk factors, and treatment of established risk factors, the dire projection of the health and economic impact of CVD can be diminished," the statement concluded.

The projections of CVD prevalence were based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006 and Census Bureau projections from 2010 to 2030. Projections of direct medical costs of CVD were based on data from the Medical Expenditure Panel Survey from 2001 to 2005. Indirect costs of CVD included lost productivity from morbidity and early mortality.

Dr. Heidenreich, chair of the writing group, had no financial conflicts to disclose. Several members of the writing group disclosed research funding from pharmaceutical companies including Boston Scientific, Eli Lilly and Company, Pfizer, Procter & Gamble, and Medtronic. Some members disclosed serving as consultants or advisory board members to companies including Sanofi-Aventis, Bristol Myers Squibb, and Daiichi Sankyo. Some members of the group received research support from organizations including the National Institutes of Health and the National Heart, Lung and Blood Institute.

WASHINGTON – Approximately 40% of the United States population could have some form of cardiovascular disease by the year 2030, based on data from a prediction model created by the American Heart Association. The findings were published online on Jan. 24 in an American Heart Association policy statement in Circulation.

If there’s a silver lining in these figures, it is that they are projections," Nancy Brown, chief executive officer of the AHA, said at a press conference. However, if current policies and prevention strategies go unchanged, the United States is facing "a cardiovascular crisis of alarming proportions," she said.

The aging U.S. population and the increase in medical spending are the main forces driving the disease prevalence and cost, wrote Dr. Paul Heidenreich, of the VA Palo Alto (Calif.) Health Care System, and colleagues.

Without changes in current prevention and treatment trends, the prevalence of cardiovascular disease in the United States will increase by about 10% over the next 20 years, and direct medical costs of cardiovascular disease will triple, from $273 billion to $818 billion, according to the policy statement.

The AHA statement projects an additional 27 million Americans with hypertension, 8 million with coronary heart disease, 4 million with stroke, and 3 million with heart failure between 2010 and 2030 (Circulation 2011 Jan. 24 [Epub doi: 10.1161/CIR.0b013e31820a55f5]).

According to the projections, hypertension will be the most expensive component of cardiovascular disease (CVD), with an estimated annual direct medical cost of $200 billion by 2030. The estimated direct medical cost for stroke is $96 billion, compared with $28 billion in 2010, but stroke represents the greatest relative increase in costs over the next 20 years (238%).

In addition, the indirect costs of all types of cardiovascular disease could increase by 61% (from $172 billion in 2010 to $276 billion in 2030).

However, previous studies have shown that many CVD cases are preventable, and individuals who maintain a healthy lifestyle and favorable levels of atherosclerotic risk are less likely to develop CVD. "Therefore, a greater focus on prevention may alter these CVD projections in the future," according to the statement.

Guidelines have been shown to have "a substantial impact on prevention and treatment and will be an important tool for limiting the burden of CVD," according to the statement. The AHA, the American College of Cardiology, and other organizations have previously published prevention-oriented CVD guidelines, but the implementation of such guidelines is often slow, the writing group noted.

Other factors that could hamper the improvement of CVD risk factors include a reported shortage of cardiologists, they added. Other shortages exist in nursing, pharmacy, and primary care, all of which are needed for a team approach to preventing CVD.

The take-home message for cardiologists is that they can "expect to see more demand for their services," Dr. Heidenreich said in an interview. In addition, primary care physicians will be seeing more patients with forms of heart disease. But the solution includes increasing the number of health professionals across all fields, not only cardiology, said Dr. Heidenreich. "The whole medical complex is insufficient to meet the demand" of the potential increases in CVD, he emphasized.

But, "through a combination of improved prevention of risk factors, and treatment of established risk factors, the dire projection of the health and economic impact of CVD can be diminished," the statement concluded.

The projections of CVD prevalence were based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006 and Census Bureau projections from 2010 to 2030. Projections of direct medical costs of CVD were based on data from the Medical Expenditure Panel Survey from 2001 to 2005. Indirect costs of CVD included lost productivity from morbidity and early mortality.

Dr. Heidenreich, chair of the writing group, had no financial conflicts to disclose. Several members of the writing group disclosed research funding from pharmaceutical companies including Boston Scientific, Eli Lilly and Company, Pfizer, Procter & Gamble, and Medtronic. Some members disclosed serving as consultants or advisory board members to companies including Sanofi-Aventis, Bristol Myers Squibb, and Daiichi Sankyo. Some members of the group received research support from organizations including the National Institutes of Health and the National Heart, Lung and Blood Institute.

WASHINGTON – Approximately 40% of the United States population could have some form of cardiovascular disease by the year 2030, based on data from a prediction model created by the American Heart Association. The findings were published online on Jan. 24 in an American Heart Association policy statement in Circulation.

If there’s a silver lining in these figures, it is that they are projections," Nancy Brown, chief executive officer of the AHA, said at a press conference. However, if current policies and prevention strategies go unchanged, the United States is facing "a cardiovascular crisis of alarming proportions," she said.

The aging U.S. population and the increase in medical spending are the main forces driving the disease prevalence and cost, wrote Dr. Paul Heidenreich, of the VA Palo Alto (Calif.) Health Care System, and colleagues.

Without changes in current prevention and treatment trends, the prevalence of cardiovascular disease in the United States will increase by about 10% over the next 20 years, and direct medical costs of cardiovascular disease will triple, from $273 billion to $818 billion, according to the policy statement.

The AHA statement projects an additional 27 million Americans with hypertension, 8 million with coronary heart disease, 4 million with stroke, and 3 million with heart failure between 2010 and 2030 (Circulation 2011 Jan. 24 [Epub doi: 10.1161/CIR.0b013e31820a55f5]).

According to the projections, hypertension will be the most expensive component of cardiovascular disease (CVD), with an estimated annual direct medical cost of $200 billion by 2030. The estimated direct medical cost for stroke is $96 billion, compared with $28 billion in 2010, but stroke represents the greatest relative increase in costs over the next 20 years (238%).

In addition, the indirect costs of all types of cardiovascular disease could increase by 61% (from $172 billion in 2010 to $276 billion in 2030).

However, previous studies have shown that many CVD cases are preventable, and individuals who maintain a healthy lifestyle and favorable levels of atherosclerotic risk are less likely to develop CVD. "Therefore, a greater focus on prevention may alter these CVD projections in the future," according to the statement.

Guidelines have been shown to have "a substantial impact on prevention and treatment and will be an important tool for limiting the burden of CVD," according to the statement. The AHA, the American College of Cardiology, and other organizations have previously published prevention-oriented CVD guidelines, but the implementation of such guidelines is often slow, the writing group noted.

Other factors that could hamper the improvement of CVD risk factors include a reported shortage of cardiologists, they added. Other shortages exist in nursing, pharmacy, and primary care, all of which are needed for a team approach to preventing CVD.

The take-home message for cardiologists is that they can "expect to see more demand for their services," Dr. Heidenreich said in an interview. In addition, primary care physicians will be seeing more patients with forms of heart disease. But the solution includes increasing the number of health professionals across all fields, not only cardiology, said Dr. Heidenreich. "The whole medical complex is insufficient to meet the demand" of the potential increases in CVD, he emphasized.

But, "through a combination of improved prevention of risk factors, and treatment of established risk factors, the dire projection of the health and economic impact of CVD can be diminished," the statement concluded.

The projections of CVD prevalence were based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006 and Census Bureau projections from 2010 to 2030. Projections of direct medical costs of CVD were based on data from the Medical Expenditure Panel Survey from 2001 to 2005. Indirect costs of CVD included lost productivity from morbidity and early mortality.

Dr. Heidenreich, chair of the writing group, had no financial conflicts to disclose. Several members of the writing group disclosed research funding from pharmaceutical companies including Boston Scientific, Eli Lilly and Company, Pfizer, Procter & Gamble, and Medtronic. Some members disclosed serving as consultants or advisory board members to companies including Sanofi-Aventis, Bristol Myers Squibb, and Daiichi Sankyo. Some members of the group received research support from organizations including the National Institutes of Health and the National Heart, Lung and Blood Institute.

WASHINGTON - Approximately 40% of the United States population could have some form of cardiovascular disease by the year 2030, based on data from a prediction model created by the American Heart Association. The findings were published online on Jan. 24 in an American Heart Association policy statement in Circulation.

If there’s a silver lining in these figures, it is that they are projections," Nancy Brown, chief executive officer of the AHA, said at a press conference. However, if current policies and prevention strategies go unchanged, the United States is facing "a cardiovascular crisis of alarming proportions," she said.

The aging U.S. population and the increase in medical spending are the main forces driving the disease prevalence and cost, wrote Dr. Paul Heidenreich, of the VA Palo Alto (Calif.) Health Care System, and colleagues.

Without changes in current prevention and treatment trends, the prevalence of cardiovascular disease in the United States will increase by about 10% over the next 20 years, and direct medical costs of cardiovascular disease will triple, from $273 billion to $818 billion, according to the policy statement.

The AHA statement projects an additional 27 million Americans with hypertension, 8 million with coronary heart disease, 4 million with stroke, and 3 million with heart failure between 2010 and 2030 (Circulation 2011 Jan. 24 [Epub doi: 10.1161/CIR.0b013e31820a55f5]).

According to the projections, hypertension will be the most expensive component of cardiovascular disease (CVD), with an estimated annual direct medical cost of $200 billion by 2030. The estimated direct medical cost for stroke is $96 billion, compared with $28 billion in 2010, but stroke represents the greatest relative increase in costs over the next 20 years (238%).

In addition, the indirect costs of all types of cardiovascular disease could increase by 61% (from $172 billion in 2010 to $276 billion in 2030).

However, previous studies have shown that many CVD cases are preventable, and individuals who maintain a healthy lifestyle and favorable levels of atherosclerotic risk are less likely to develop CVD. "Therefore, a greater focus on prevention may alter these CVD projections in the future," according to the statement.

Guidelines have been shown to have "a substantial impact on prevention and treatment and will be an important tool for limiting the burden of CVD," according to the statement. The AHA, the American College of Cardiology, and other organizations have previously published prevention-oriented CVD guidelines, but the implementation of such guidelines is often slow, the writing group noted.

Other factors that could hamper the improvement of CVD risk factors include a reported shortage of cardiologists, they added. Other shortages exist in nursing, pharmacy, and primary care, all of which are needed for a team approach to preventing CVD.

The take-home message for cardiologists is that they can "expect to see more demand for their services," Dr. Heidenreich said in an interview. In addition, primary care physicians will be seeing more patients with forms of heart disease. But the solution includes increasing the number of health professionals across all fields, not only cardiology, said Dr. Heidenreich. "The whole medical complex is insufficient to meet the demand" of the potential increases in CVD, he emphasized.

But, "through a combination of improved prevention of risk factors, and treatment of established risk factors, the dire projection of the health and economic impact of CVD can be diminished," the statement concluded.

The projections of CVD prevalence were based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006 and Census Bureau projections from 2010 to 2030. Projections of direct medical costs of CVD were based on data from the Medical Expenditure Panel Survey from 2001 to 2005. Indirect costs of CVD included lost productivity from morbidity and early mortality.

Dr. Heidenreich, chair of the writing group, had no financial conflicts to disclose. Several members of the writing group disclosed research funding from pharmaceutical companies including Boston Scientific, Eli Lilly and Company, Pfizer, Procter & Gamble, and Medtronic. Some members disclosed serving as consultants or advisory board members to companies including Sanofi-Aventis, Bristol Myers Squibb, and Daiichi Sankyo. Some members of the group received research support from organizations including the National Institutes of Health and the National Heart, Lung and Blood Institute.

WASHINGTON - Approximately 40% of the United States population could have some form of cardiovascular disease by the year 2030, based on data from a prediction model created by the American Heart Association. The findings were published online on Jan. 24 in an American Heart Association policy statement in Circulation.

If there’s a silver lining in these figures, it is that they are projections," Nancy Brown, chief executive officer of the AHA, said at a press conference. However, if current policies and prevention strategies go unchanged, the United States is facing "a cardiovascular crisis of alarming proportions," she said.

The aging U.S. population and the increase in medical spending are the main forces driving the disease prevalence and cost, wrote Dr. Paul Heidenreich, of the VA Palo Alto (Calif.) Health Care System, and colleagues.

Without changes in current prevention and treatment trends, the prevalence of cardiovascular disease in the United States will increase by about 10% over the next 20 years, and direct medical costs of cardiovascular disease will triple, from $273 billion to $818 billion, according to the policy statement.

The AHA statement projects an additional 27 million Americans with hypertension, 8 million with coronary heart disease, 4 million with stroke, and 3 million with heart failure between 2010 and 2030 (Circulation 2011 Jan. 24 [Epub doi: 10.1161/CIR.0b013e31820a55f5]).

According to the projections, hypertension will be the most expensive component of cardiovascular disease (CVD), with an estimated annual direct medical cost of $200 billion by 2030. The estimated direct medical cost for stroke is $96 billion, compared with $28 billion in 2010, but stroke represents the greatest relative increase in costs over the next 20 years (238%).

In addition, the indirect costs of all types of cardiovascular disease could increase by 61% (from $172 billion in 2010 to $276 billion in 2030).

However, previous studies have shown that many CVD cases are preventable, and individuals who maintain a healthy lifestyle and favorable levels of atherosclerotic risk are less likely to develop CVD. "Therefore, a greater focus on prevention may alter these CVD projections in the future," according to the statement.

Guidelines have been shown to have "a substantial impact on prevention and treatment and will be an important tool for limiting the burden of CVD," according to the statement. The AHA, the American College of Cardiology, and other organizations have previously published prevention-oriented CVD guidelines, but the implementation of such guidelines is often slow, the writing group noted.

Other factors that could hamper the improvement of CVD risk factors include a reported shortage of cardiologists, they added. Other shortages exist in nursing, pharmacy, and primary care, all of which are needed for a team approach to preventing CVD.

The take-home message for cardiologists is that they can "expect to see more demand for their services," Dr. Heidenreich said in an interview. In addition, primary care physicians will be seeing more patients with forms of heart disease. But the solution includes increasing the number of health professionals across all fields, not only cardiology, said Dr. Heidenreich. "The whole medical complex is insufficient to meet the demand" of the potential increases in CVD, he emphasized.

But, "through a combination of improved prevention of risk factors, and treatment of established risk factors, the dire projection of the health and economic impact of CVD can be diminished," the statement concluded.

The projections of CVD prevalence were based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006 and Census Bureau projections from 2010 to 2030. Projections of direct medical costs of CVD were based on data from the Medical Expenditure Panel Survey from 2001 to 2005. Indirect costs of CVD included lost productivity from morbidity and early mortality.

Dr. Heidenreich, chair of the writing group, had no financial conflicts to disclose. Several members of the writing group disclosed research funding from pharmaceutical companies including Boston Scientific, Eli Lilly and Company, Pfizer, Procter & Gamble, and Medtronic. Some members disclosed serving as consultants or advisory board members to companies including Sanofi-Aventis, Bristol Myers Squibb, and Daiichi Sankyo. Some members of the group received research support from organizations including the National Institutes of Health and the National Heart, Lung and Blood Institute.

WASHINGTON - Approximately 40% of the United States population could have some form of cardiovascular disease by the year 2030, based on data from a prediction model created by the American Heart Association. The findings were published online on Jan. 24 in an American Heart Association policy statement in Circulation.

If there’s a silver lining in these figures, it is that they are projections," Nancy Brown, chief executive officer of the AHA, said at a press conference. However, if current policies and prevention strategies go unchanged, the United States is facing "a cardiovascular crisis of alarming proportions," she said.

The aging U.S. population and the increase in medical spending are the main forces driving the disease prevalence and cost, wrote Dr. Paul Heidenreich, of the VA Palo Alto (Calif.) Health Care System, and colleagues.

Without changes in current prevention and treatment trends, the prevalence of cardiovascular disease in the United States will increase by about 10% over the next 20 years, and direct medical costs of cardiovascular disease will triple, from $273 billion to $818 billion, according to the policy statement.

The AHA statement projects an additional 27 million Americans with hypertension, 8 million with coronary heart disease, 4 million with stroke, and 3 million with heart failure between 2010 and 2030 (Circulation 2011 Jan. 24 [Epub doi: 10.1161/CIR.0b013e31820a55f5]).

According to the projections, hypertension will be the most expensive component of cardiovascular disease (CVD), with an estimated annual direct medical cost of $200 billion by 2030. The estimated direct medical cost for stroke is $96 billion, compared with $28 billion in 2010, but stroke represents the greatest relative increase in costs over the next 20 years (238%).

In addition, the indirect costs of all types of cardiovascular disease could increase by 61% (from $172 billion in 2010 to $276 billion in 2030).

However, previous studies have shown that many CVD cases are preventable, and individuals who maintain a healthy lifestyle and favorable levels of atherosclerotic risk are less likely to develop CVD. "Therefore, a greater focus on prevention may alter these CVD projections in the future," according to the statement.

Guidelines have been shown to have "a substantial impact on prevention and treatment and will be an important tool for limiting the burden of CVD," according to the statement. The AHA, the American College of Cardiology, and other organizations have previously published prevention-oriented CVD guidelines, but the implementation of such guidelines is often slow, the writing group noted.

Other factors that could hamper the improvement of CVD risk factors include a reported shortage of cardiologists, they added. Other shortages exist in nursing, pharmacy, and primary care, all of which are needed for a team approach to preventing CVD.

The take-home message for cardiologists is that they can "expect to see more demand for their services," Dr. Heidenreich said in an interview. In addition, primary care physicians will be seeing more patients with forms of heart disease. But the solution includes increasing the number of health professionals across all fields, not only cardiology, said Dr. Heidenreich. "The whole medical complex is insufficient to meet the demand" of the potential increases in CVD, he emphasized.

But, "through a combination of improved prevention of risk factors, and treatment of established risk factors, the dire projection of the health and economic impact of CVD can be diminished," the statement concluded.

The projections of CVD prevalence were based on data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006 and Census Bureau projections from 2010 to 2030. Projections of direct medical costs of CVD were based on data from the Medical Expenditure Panel Survey from 2001 to 2005. Indirect costs of CVD included lost productivity from morbidity and early mortality.

Dr. Heidenreich, chair of the writing group, had no financial conflicts to disclose. Several members of the writing group disclosed research funding from pharmaceutical companies including Boston Scientific, Eli Lilly and Company, Pfizer, Procter & Gamble, and Medtronic. Some members disclosed serving as consultants or advisory board members to companies including Sanofi-Aventis, Bristol Myers Squibb, and Daiichi Sankyo. Some members of the group received research support from organizations including the National Institutes of Health and the National Heart, Lung and Blood Institute.

Habitual heavy drinking is associated with a 51% increased risk of atrial fibrillation, according to findings from a meta-analysis of more than 130,000 adults, published online Jan. 17.

The impact of occasional heavy alcohol intake on AF, known as "holiday heart syndrome," is well known. The impact of consistent heavy alcohol intake on AF risk, however, has not been well studied, said Dr. Satoru Kodama of the University of Tsukuba Institute of Clinical Medicine in Ibaraki, Japan.

Dr. Kodama and colleagues analyzed data from 14 studies, involving a total of 130,820 participants and 7,558 cases of AF. Across the studies, a common scale of grams per day was used as the standard measure of alcohol intake.

Overall, participants who consumed the most alcohol were significantly more likely to have AF than were those who consumed the least, based on a pooled assessment of odds ratio and relative risk (1.51).

The lowest amount of alcohol consumed in the highest intake category for each of the studies ranged from 1.5 to 6 drinks daily.

Within the highest alcohol intake category, the AF risk was not significantly different between participants who consumed fewer than 4 alcoholic drinks daily, defined as 48 g (OR/RR 1.32), and those who had 4 or more drinks per day (1.74) (J. Am. Coll. Cardiol. 2011;57:427-36).

From an analysis of nine of the studies (involving 126,051 participants and 6,341 cases of AF), the researchers found a significant dose-response relationship between alcohol intake and AF risk, which translated into an increase in relative risk of 1.08 per 10 g of alcohol consumed per day.

Stratified analyses of the data, according to study methods, supported the significant association between the highest category of alcohol intake and AF risk.

The study is the first systematic review of habitual alcohol consumption and AF risk. Although the meta-analysis cannot prove causality, the researchers proposed two hypotheses for a cause and effect relationship. One theory, suggested by biological studies, is that high alcohol intake makes it more difficult for the body to maintain a normal heart rhythm.

"Another speculation is based on reports suggesting that the development of chronic heart failure accompanied by long-term alcohol consumption may result in elevated AF risk," the researchers said.

The results suggest that avoiding alcohol completely, as opposed to drinking moderately, is the best way to reduce AF risk, the researchers concluded.

The analysis was limited by the inability to adjust for various confounders across multiple studies, including the presence of hypertension, diabetes, and obstructive sleep apnea, they wrote. In addition, the strength of the findings is limited by the various definitions of heavy drinking, the lack of information about the validation of alcohol intake, and limited consideration of racial differences among study participants.

Further investigation is needed to determine a possible causal relationship between daily alcohol intake and AF risk, the authors wrote.

The researchers reported having no financial conflicts of interest.

Habitual heavy drinking is associated with a 51% increased risk of atrial fibrillation, according to findings from a meta-analysis of more than 130,000 adults, published online Jan. 17.

The impact of occasional heavy alcohol intake on AF, known as "holiday heart syndrome," is well known. The impact of consistent heavy alcohol intake on AF risk, however, has not been well studied, said Dr. Satoru Kodama of the University of Tsukuba Institute of Clinical Medicine in Ibaraki, Japan.

Dr. Kodama and colleagues analyzed data from 14 studies, involving a total of 130,820 participants and 7,558 cases of AF. Across the studies, a common scale of grams per day was used as the standard measure of alcohol intake.

Overall, participants who consumed the most alcohol were significantly more likely to have AF than were those who consumed the least, based on a pooled assessment of odds ratio and relative risk (1.51).

The lowest amount of alcohol consumed in the highest intake category for each of the studies ranged from 1.5 to 6 drinks daily.

Within the highest alcohol intake category, the AF risk was not significantly different between participants who consumed fewer than 4 alcoholic drinks daily, defined as 48 g (OR/RR 1.32), and those who had 4 or more drinks per day (1.74) (J. Am. Coll. Cardiol. 2011;57:427-36).

From an analysis of nine of the studies (involving 126,051 participants and 6,341 cases of AF), the researchers found a significant dose-response relationship between alcohol intake and AF risk, which translated into an increase in relative risk of 1.08 per 10 g of alcohol consumed per day.

Stratified analyses of the data, according to study methods, supported the significant association between the highest category of alcohol intake and AF risk.

The study is the first systematic review of habitual alcohol consumption and AF risk. Although the meta-analysis cannot prove causality, the researchers proposed two hypotheses for a cause and effect relationship. One theory, suggested by biological studies, is that high alcohol intake makes it more difficult for the body to maintain a normal heart rhythm.

"Another speculation is based on reports suggesting that the development of chronic heart failure accompanied by long-term alcohol consumption may result in elevated AF risk," the researchers said.

The results suggest that avoiding alcohol completely, as opposed to drinking moderately, is the best way to reduce AF risk, the researchers concluded.

The analysis was limited by the inability to adjust for various confounders across multiple studies, including the presence of hypertension, diabetes, and obstructive sleep apnea, they wrote. In addition, the strength of the findings is limited by the various definitions of heavy drinking, the lack of information about the validation of alcohol intake, and limited consideration of racial differences among study participants.

Further investigation is needed to determine a possible causal relationship between daily alcohol intake and AF risk, the authors wrote.

The researchers reported having no financial conflicts of interest.

Habitual heavy drinking is associated with a 51% increased risk of atrial fibrillation, according to findings from a meta-analysis of more than 130,000 adults, published online Jan. 17.

The impact of occasional heavy alcohol intake on AF, known as "holiday heart syndrome," is well known. The impact of consistent heavy alcohol intake on AF risk, however, has not been well studied, said Dr. Satoru Kodama of the University of Tsukuba Institute of Clinical Medicine in Ibaraki, Japan.

Dr. Kodama and colleagues analyzed data from 14 studies, involving a total of 130,820 participants and 7,558 cases of AF. Across the studies, a common scale of grams per day was used as the standard measure of alcohol intake.

Overall, participants who consumed the most alcohol were significantly more likely to have AF than were those who consumed the least, based on a pooled assessment of odds ratio and relative risk (1.51).

The lowest amount of alcohol consumed in the highest intake category for each of the studies ranged from 1.5 to 6 drinks daily.

Within the highest alcohol intake category, the AF risk was not significantly different between participants who consumed fewer than 4 alcoholic drinks daily, defined as 48 g (OR/RR 1.32), and those who had 4 or more drinks per day (1.74) (J. Am. Coll. Cardiol. 2011;57:427-36).

From an analysis of nine of the studies (involving 126,051 participants and 6,341 cases of AF), the researchers found a significant dose-response relationship between alcohol intake and AF risk, which translated into an increase in relative risk of 1.08 per 10 g of alcohol consumed per day.

Stratified analyses of the data, according to study methods, supported the significant association between the highest category of alcohol intake and AF risk.

The study is the first systematic review of habitual alcohol consumption and AF risk. Although the meta-analysis cannot prove causality, the researchers proposed two hypotheses for a cause and effect relationship. One theory, suggested by biological studies, is that high alcohol intake makes it more difficult for the body to maintain a normal heart rhythm.

"Another speculation is based on reports suggesting that the development of chronic heart failure accompanied by long-term alcohol consumption may result in elevated AF risk," the researchers said.

The results suggest that avoiding alcohol completely, as opposed to drinking moderately, is the best way to reduce AF risk, the researchers concluded.

The analysis was limited by the inability to adjust for various confounders across multiple studies, including the presence of hypertension, diabetes, and obstructive sleep apnea, they wrote. In addition, the strength of the findings is limited by the various definitions of heavy drinking, the lack of information about the validation of alcohol intake, and limited consideration of racial differences among study participants.

Further investigation is needed to determine a possible causal relationship between daily alcohol intake and AF risk, the authors wrote.

The researchers reported having no financial conflicts of interest.

Habitual heavy drinking is associated with a 51% increased risk of atrial fibrillation, according to findings from a meta-analysis of more than 130,000 adults, published online Jan. 17.

The impact of occasional heavy alcohol intake on AF, known as "holiday heart syndrome," is well known. The impact of consistent heavy alcohol intake on AF risk, however, has not been well studied, said Dr. Satoru Kodama of the University of Tsukuba Institute of Clinical Medicine in Ibaraki, Japan.

Dr. Kodama and colleagues analyzed data from 14 studies, involving a total of 130,820 participants and 7,558 cases of AF. Across the studies, a common scale of grams per day was used as the standard measure of alcohol intake.

Overall, participants who consumed the most alcohol were significantly more likely to have AF than were those who consumed the least, based on a pooled assessment of odds ratio and relative risk (1.51).

The lowest amount of alcohol consumed in the highest intake category for each of the studies ranged from 1.5 to 6 drinks daily.

Within the highest alcohol intake category, the AF risk was not significantly different between participants who consumed fewer than 4 alcoholic drinks daily, defined as 48 g (OR/RR 1.32), and those who had 4 or more drinks per day (1.74) (J. Am. Coll. Cardiol. 2011;57:427-36).

From an analysis of nine of the studies (involving 126,051 participants and 6,341 cases of AF), the researchers found a significant dose-response relationship between alcohol intake and AF risk, which translated into an increase in relative risk of 1.08 per 10 g of alcohol consumed per day.

Stratified analyses of the data, according to study methods, supported the significant association between the highest category of alcohol intake and AF risk.

The study is the first systematic review of habitual alcohol consumption and AF risk. Although the meta-analysis cannot prove causality, the researchers proposed two hypotheses for a cause and effect relationship. One theory, suggested by biological studies, is that high alcohol intake makes it more difficult for the body to maintain a normal heart rhythm.

"Another speculation is based on reports suggesting that the development of chronic heart failure accompanied by long-term alcohol consumption may result in elevated AF risk," the researchers said.

The results suggest that avoiding alcohol completely, as opposed to drinking moderately, is the best way to reduce AF risk, the researchers concluded.

The analysis was limited by the inability to adjust for various confounders across multiple studies, including the presence of hypertension, diabetes, and obstructive sleep apnea, they wrote. In addition, the strength of the findings is limited by the various definitions of heavy drinking, the lack of information about the validation of alcohol intake, and limited consideration of racial differences among study participants.

Further investigation is needed to determine a possible causal relationship between daily alcohol intake and AF risk, the authors wrote.

The researchers reported having no financial conflicts of interest.

Habitual heavy drinking is associated with a 51% increased risk of atrial fibrillation, according to findings from a meta-analysis of more than 130,000 adults, published online Jan. 17.

The impact of occasional heavy alcohol intake on AF, known as "holiday heart syndrome," is well known. The impact of consistent heavy alcohol intake on AF risk, however, has not been well studied, said Dr. Satoru Kodama of the University of Tsukuba Institute of Clinical Medicine in Ibaraki, Japan.

Dr. Kodama and colleagues analyzed data from 14 studies, involving a total of 130,820 participants and 7,558 cases of AF. Across the studies, a common scale of grams per day was used as the standard measure of alcohol intake.

Overall, participants who consumed the most alcohol were significantly more likely to have AF than were those who consumed the least, based on a pooled assessment of odds ratio and relative risk (1.51).

The lowest amount of alcohol consumed in the highest intake category for each of the studies ranged from 1.5 to 6 drinks daily.

Within the highest alcohol intake category, the AF risk was not significantly different between participants who consumed fewer than 4 alcoholic drinks daily, defined as 48 g (OR/RR 1.32), and those who had 4 or more drinks per day (1.74) (J. Am. Coll. Cardiol. 2011;57:427-36).

From an analysis of nine of the studies (involving 126,051 participants and 6,341 cases of AF), the researchers found a significant dose-response relationship between alcohol intake and AF risk, which translated into an increase in relative risk of 1.08 per 10 g of alcohol consumed per day.

Stratified analyses of the data, according to study methods, supported the significant association between the highest category of alcohol intake and AF risk.

The study is the first systematic review of habitual alcohol consumption and AF risk. Although the meta-analysis cannot prove causality, the researchers proposed two hypotheses for a cause and effect relationship. One theory, suggested by biological studies, is that high alcohol intake makes it more difficult for the body to maintain a normal heart rhythm.

"Another speculation is based on reports suggesting that the development of chronic heart failure accompanied by long-term alcohol consumption may result in elevated AF risk," the researchers said.

The results suggest that avoiding alcohol completely, as opposed to drinking moderately, is the best way to reduce AF risk, the researchers concluded.

The analysis was limited by the inability to adjust for various confounders across multiple studies, including the presence of hypertension, diabetes, and obstructive sleep apnea, they wrote. In addition, the strength of the findings is limited by the various definitions of heavy drinking, the lack of information about the validation of alcohol intake, and limited consideration of racial differences among study participants.

Further investigation is needed to determine a possible causal relationship between daily alcohol intake and AF risk, the authors wrote.

The researchers reported having no financial conflicts of interest.

Habitual heavy drinking is associated with a 51% increased risk of atrial fibrillation, according to findings from a meta-analysis of more than 130,000 adults, published online Jan. 17.

The impact of occasional heavy alcohol intake on AF, known as "holiday heart syndrome," is well known. The impact of consistent heavy alcohol intake on AF risk, however, has not been well studied, said Dr. Satoru Kodama of the University of Tsukuba Institute of Clinical Medicine in Ibaraki, Japan.

Dr. Kodama and colleagues analyzed data from 14 studies, involving a total of 130,820 participants and 7,558 cases of AF. Across the studies, a common scale of grams per day was used as the standard measure of alcohol intake.

Overall, participants who consumed the most alcohol were significantly more likely to have AF than were those who consumed the least, based on a pooled assessment of odds ratio and relative risk (1.51).

The lowest amount of alcohol consumed in the highest intake category for each of the studies ranged from 1.5 to 6 drinks daily.

Within the highest alcohol intake category, the AF risk was not significantly different between participants who consumed fewer than 4 alcoholic drinks daily, defined as 48 g (OR/RR 1.32), and those who had 4 or more drinks per day (1.74) (J. Am. Coll. Cardiol. 2011;57:427-36).

From an analysis of nine of the studies (involving 126,051 participants and 6,341 cases of AF), the researchers found a significant dose-response relationship between alcohol intake and AF risk, which translated into an increase in relative risk of 1.08 per 10 g of alcohol consumed per day.

Stratified analyses of the data, according to study methods, supported the significant association between the highest category of alcohol intake and AF risk.

The study is the first systematic review of habitual alcohol consumption and AF risk. Although the meta-analysis cannot prove causality, the researchers proposed two hypotheses for a cause and effect relationship. One theory, suggested by biological studies, is that high alcohol intake makes it more difficult for the body to maintain a normal heart rhythm.

"Another speculation is based on reports suggesting that the development of chronic heart failure accompanied by long-term alcohol consumption may result in elevated AF risk," the researchers said.

The results suggest that avoiding alcohol completely, as opposed to drinking moderately, is the best way to reduce AF risk, the researchers concluded.

The analysis was limited by the inability to adjust for various confounders across multiple studies, including the presence of hypertension, diabetes, and obstructive sleep apnea, they wrote. In addition, the strength of the findings is limited by the various definitions of heavy drinking, the lack of information about the validation of alcohol intake, and limited consideration of racial differences among study participants.

Further investigation is needed to determine a possible causal relationship between daily alcohol intake and AF risk, the authors wrote.

The researchers reported having no financial conflicts of interest.

ORLANDO – Enoxaparin and aspirin were equally effective at preventing thrombotic events in young, newly diagnosed myeloma patients who were treated with a lenalidomide-based regimen in a randomized trial.

Previous studies have shown that this patient population is at least three times as likely to develop thrombosis as patients not on a lenalidomide-based regimen, said Dr. Alberto Rocci of the University of Torino (Italy). "Randomized trials comparing different therapies for [venous thromboembolism] prophylaxis in young, newly diagnosed myeloma patients are still lacking," he said at the annual meeting of the American Society of Hematology.

[Check out our comprehensive coverage of the American Society of Hematology's annual meeting.]

In this study, Dr. Rocci and his colleagues enrolled 402 patients younger than 65 years from 62 cancer centers. All patients had symptomatic and measurable disease, with organ damage.

All patients underwent four 28-day cycles of lenalidomide (25 mg/day on days 1-21) and dexamethasone (40 mg/day on days 1, 8, 15, and 22). After this treatment, 202 patients were randomized to six 28-day cycles of melphalan (0.18 mg/kg on days 1-4), prednisone (2 mg/kg on days 1-4), and lenalidomide (10 mg/day on days 1-21); and 200 patients were randomized to two courses of melphalan (200 mg/m2, plus stem cell support). These groups were designated MPR and MEL 200, respectively.

In this substudy, the researchers further randomized eligible patients who received lenalidomide during induction and in the MPR consolidation regimen: 166 patients were assigned to 40 mg of enoxaparin (Lovenox) per day and 176 patients to 100 mg of aspirin per day. Sixty patients were excluded from this randomization because they had a high risk of bleeding or indications for anticoagulant or antiplatelet therapy. Patient demographics and risk factors for thrombotic events were similar between the two groups assessed for venous thromboembolism (VTE) prophylaxis.

The cumulative incidence of all thrombosis, major bleeding, acute cardiovascular events, and sudden deaths was 1.8% in the enoxaparin group and 5.2% in the aspirin group (P = .06). No incidents of major bleeding or sudden death were reported during the study.

During the induction phase of therapy, the incidence of any thrombosis was 1.2% in the enoxaparin group vs. 1.7% in the aspirin group. The events included three cases of deep vein thrombosis (two in the enoxaparin group and one in the aspirin group) and three pulmonary embolisms in the aspirin group.

The time to onset of any thrombotic events was similar between the groups, and the results suggest that the risk of thrombosis is highest during the first 4-6 months of treatment, Dr. Rocci noted.

The relatively low incidence of thrombosis confirms the safety of the dexamethasone/lenalidomide regimen, said Dr. Rocci. The findings also confirm the safety of low-molecular-weight heparin as the standard for preventing thrombosis in newly diagnosed multiple myeloma patients, he said. Aspirin can be a possible alternative in multiple myeloma patients with low risk for developing VTE, he added.

Dr. Rocci had no financial conflicts to disclose. Several of his coauthors disclosed receiving honoraria or research funding from, or serving as a consultant or member of an advisory committee or on the board of directors for, Celgene and Janssen-Cilag.

ORLANDO – Enoxaparin and aspirin were equally effective at preventing thrombotic events in young, newly diagnosed myeloma patients who were treated with a lenalidomide-based regimen in a randomized trial.

Previous studies have shown that this patient population is at least three times as likely to develop thrombosis as patients not on a lenalidomide-based regimen, said Dr. Alberto Rocci of the University of Torino (Italy). "Randomized trials comparing different therapies for [venous thromboembolism] prophylaxis in young, newly diagnosed myeloma patients are still lacking," he said at the annual meeting of the American Society of Hematology.

[Check out our comprehensive coverage of the American Society of Hematology's annual meeting.]

In this study, Dr. Rocci and his colleagues enrolled 402 patients younger than 65 years from 62 cancer centers. All patients had symptomatic and measurable disease, with organ damage.

All patients underwent four 28-day cycles of lenalidomide (25 mg/day on days 1-21) and dexamethasone (40 mg/day on days 1, 8, 15, and 22). After this treatment, 202 patients were randomized to six 28-day cycles of melphalan (0.18 mg/kg on days 1-4), prednisone (2 mg/kg on days 1-4), and lenalidomide (10 mg/day on days 1-21); and 200 patients were randomized to two courses of melphalan (200 mg/m2, plus stem cell support). These groups were designated MPR and MEL 200, respectively.

In this substudy, the researchers further randomized eligible patients who received lenalidomide during induction and in the MPR consolidation regimen: 166 patients were assigned to 40 mg of enoxaparin (Lovenox) per day and 176 patients to 100 mg of aspirin per day. Sixty patients were excluded from this randomization because they had a high risk of bleeding or indications for anticoagulant or antiplatelet therapy. Patient demographics and risk factors for thrombotic events were similar between the two groups assessed for venous thromboembolism (VTE) prophylaxis.

The cumulative incidence of all thrombosis, major bleeding, acute cardiovascular events, and sudden deaths was 1.8% in the enoxaparin group and 5.2% in the aspirin group (P = .06). No incidents of major bleeding or sudden death were reported during the study.

During the induction phase of therapy, the incidence of any thrombosis was 1.2% in the enoxaparin group vs. 1.7% in the aspirin group. The events included three cases of deep vein thrombosis (two in the enoxaparin group and one in the aspirin group) and three pulmonary embolisms in the aspirin group.

The time to onset of any thrombotic events was similar between the groups, and the results suggest that the risk of thrombosis is highest during the first 4-6 months of treatment, Dr. Rocci noted.

The relatively low incidence of thrombosis confirms the safety of the dexamethasone/lenalidomide regimen, said Dr. Rocci. The findings also confirm the safety of low-molecular-weight heparin as the standard for preventing thrombosis in newly diagnosed multiple myeloma patients, he said. Aspirin can be a possible alternative in multiple myeloma patients with low risk for developing VTE, he added.

Dr. Rocci had no financial conflicts to disclose. Several of his coauthors disclosed receiving honoraria or research funding from, or serving as a consultant or member of an advisory committee or on the board of directors for, Celgene and Janssen-Cilag.

ORLANDO – Enoxaparin and aspirin were equally effective at preventing thrombotic events in young, newly diagnosed myeloma patients who were treated with a lenalidomide-based regimen in a randomized trial.

Previous studies have shown that this patient population is at least three times as likely to develop thrombosis as patients not on a lenalidomide-based regimen, said Dr. Alberto Rocci of the University of Torino (Italy). "Randomized trials comparing different therapies for [venous thromboembolism] prophylaxis in young, newly diagnosed myeloma patients are still lacking," he said at the annual meeting of the American Society of Hematology.

[Check out our comprehensive coverage of the American Society of Hematology's annual meeting.]

In this study, Dr. Rocci and his colleagues enrolled 402 patients younger than 65 years from 62 cancer centers. All patients had symptomatic and measurable disease, with organ damage.

All patients underwent four 28-day cycles of lenalidomide (25 mg/day on days 1-21) and dexamethasone (40 mg/day on days 1, 8, 15, and 22). After this treatment, 202 patients were randomized to six 28-day cycles of melphalan (0.18 mg/kg on days 1-4), prednisone (2 mg/kg on days 1-4), and lenalidomide (10 mg/day on days 1-21); and 200 patients were randomized to two courses of melphalan (200 mg/m2, plus stem cell support). These groups were designated MPR and MEL 200, respectively.

In this substudy, the researchers further randomized eligible patients who received lenalidomide during induction and in the MPR consolidation regimen: 166 patients were assigned to 40 mg of enoxaparin (Lovenox) per day and 176 patients to 100 mg of aspirin per day. Sixty patients were excluded from this randomization because they had a high risk of bleeding or indications for anticoagulant or antiplatelet therapy. Patient demographics and risk factors for thrombotic events were similar between the two groups assessed for venous thromboembolism (VTE) prophylaxis.

The cumulative incidence of all thrombosis, major bleeding, acute cardiovascular events, and sudden deaths was 1.8% in the enoxaparin group and 5.2% in the aspirin group (P = .06). No incidents of major bleeding or sudden death were reported during the study.

During the induction phase of therapy, the incidence of any thrombosis was 1.2% in the enoxaparin group vs. 1.7% in the aspirin group. The events included three cases of deep vein thrombosis (two in the enoxaparin group and one in the aspirin group) and three pulmonary embolisms in the aspirin group.

The time to onset of any thrombotic events was similar between the groups, and the results suggest that the risk of thrombosis is highest during the first 4-6 months of treatment, Dr. Rocci noted.

The relatively low incidence of thrombosis confirms the safety of the dexamethasone/lenalidomide regimen, said Dr. Rocci. The findings also confirm the safety of low-molecular-weight heparin as the standard for preventing thrombosis in newly diagnosed multiple myeloma patients, he said. Aspirin can be a possible alternative in multiple myeloma patients with low risk for developing VTE, he added.

Dr. Rocci had no financial conflicts to disclose. Several of his coauthors disclosed receiving honoraria or research funding from, or serving as a consultant or member of an advisory committee or on the board of directors for, Celgene and Janssen-Cilag.

ORLANDO – Ten-year overall survival and event-free survival were significantly higher in adolescents and young adults with acute myeloid leukemia who were treated with a pediatric regimen vs. an adult regimen, based on data from 517 patients aged 16-21 years.

Previous studies have shown improved survival in young adults with acute lymphoblastic leukemia who were treated with a pediatric regimen, said Dr. Anna R.K. Franklin of the University of Texas M.D. Anderson Cancer Center in Houston at the annual meeting of the American Society of Hematology. Dr. Franklin and her coauthors hypothesized that survival trends might be similar in acute myeloid leukemia patients.

The researchers compared 281 young adult patients with AML in Children’s Oncology Group (COG) trials, all of whom received a pediatric regimen, vs. 149 young adults in Cancer and Leukemia Group B (CALGB) trials and 87 young adults in Southwest Oncology Group (SWOG) trials, all of whom received an adult regimen. The patients were treated in 1986-2008.

Overall survival 10 years after study entry was 45% in the COG patients vs. 34% in the CALGB/SWOG patients (P less than .05). A subgroup analysis breaking down the combined population by age showed that overall survival after 10 years was 43% in younger patients (aged 16-18 years) vs. 32% in older patients (aged 19-21 years).

The median age was 18 years overall, but the median age in the COG patients was significantly younger than the median age in the CALGB/SWOG patients (17 years vs. 20 years).

The 10-year overall survival rates by age and group were 45% for younger COG patients, 44% for older COG patients, 40% for younger CALGB/SWOG patients, and 31% for older CALGB/SWOG patients.

Overall, the 10-year event-free survival rates were 39% for younger COG patients and 17% for older COG patients vs. 23%, and 22% for younger and older CALGB/SWOG patients, respectively.

In contrast, 10-year treatment-related mortality rates were significantly higher in COG patients than CALGB/SWOG patients. The rates were 26% for younger COG patients and 30% for older COG patients vs. a constant 12% for younger and older CALGB/SWOG patients.

In this study, age was a confounding variable that made comparison of patients on adult vs. child regimens difficult, because 94% of the COG patients were younger than 19 years, Dr. Franklin noted. However, "COG studies have significantly more [treatment-related mortality] and significantly less risk of relapse than the adult trials," she said.

Significant improvements occurred in 10-year overall survival, event-free survival, and relapse risk in more recent studies compared with earlier studies, but treatment-related mortality also increased, said Dr. Franklin. Multivariate analysis of the data is ongoing to determine which specific factors impact patient outcomes in adult vs. pediatric protocols, she said.

Dr. Franklin had no financial conflicts to disclose.

ORLANDO – Ten-year overall survival and event-free survival were significantly higher in adolescents and young adults with acute myeloid leukemia who were treated with a pediatric regimen vs. an adult regimen, based on data from 517 patients aged 16-21 years.

Previous studies have shown improved survival in young adults with acute lymphoblastic leukemia who were treated with a pediatric regimen, said Dr. Anna R.K. Franklin of the University of Texas M.D. Anderson Cancer Center in Houston at the annual meeting of the American Society of Hematology. Dr. Franklin and her coauthors hypothesized that survival trends might be similar in acute myeloid leukemia patients.

The researchers compared 281 young adult patients with AML in Children’s Oncology Group (COG) trials, all of whom received a pediatric regimen, vs. 149 young adults in Cancer and Leukemia Group B (CALGB) trials and 87 young adults in Southwest Oncology Group (SWOG) trials, all of whom received an adult regimen. The patients were treated in 1986-2008.

Overall survival 10 years after study entry was 45% in the COG patients vs. 34% in the CALGB/SWOG patients (P less than .05). A subgroup analysis breaking down the combined population by age showed that overall survival after 10 years was 43% in younger patients (aged 16-18 years) vs. 32% in older patients (aged 19-21 years).

The median age was 18 years overall, but the median age in the COG patients was significantly younger than the median age in the CALGB/SWOG patients (17 years vs. 20 years).

The 10-year overall survival rates by age and group were 45% for younger COG patients, 44% for older COG patients, 40% for younger CALGB/SWOG patients, and 31% for older CALGB/SWOG patients.

Overall, the 10-year event-free survival rates were 39% for younger COG patients and 17% for older COG patients vs. 23%, and 22% for younger and older CALGB/SWOG patients, respectively.

In contrast, 10-year treatment-related mortality rates were significantly higher in COG patients than CALGB/SWOG patients. The rates were 26% for younger COG patients and 30% for older COG patients vs. a constant 12% for younger and older CALGB/SWOG patients.

In this study, age was a confounding variable that made comparison of patients on adult vs. child regimens difficult, because 94% of the COG patients were younger than 19 years, Dr. Franklin noted. However, "COG studies have significantly more [treatment-related mortality] and significantly less risk of relapse than the adult trials," she said.

Significant improvements occurred in 10-year overall survival, event-free survival, and relapse risk in more recent studies compared with earlier studies, but treatment-related mortality also increased, said Dr. Franklin. Multivariate analysis of the data is ongoing to determine which specific factors impact patient outcomes in adult vs. pediatric protocols, she said.

Dr. Franklin had no financial conflicts to disclose.

ORLANDO – Ten-year overall survival and event-free survival were significantly higher in adolescents and young adults with acute myeloid leukemia who were treated with a pediatric regimen vs. an adult regimen, based on data from 517 patients aged 16-21 years.

Previous studies have shown improved survival in young adults with acute lymphoblastic leukemia who were treated with a pediatric regimen, said Dr. Anna R.K. Franklin of the University of Texas M.D. Anderson Cancer Center in Houston at the annual meeting of the American Society of Hematology. Dr. Franklin and her coauthors hypothesized that survival trends might be similar in acute myeloid leukemia patients.

The researchers compared 281 young adult patients with AML in Children’s Oncology Group (COG) trials, all of whom received a pediatric regimen, vs. 149 young adults in Cancer and Leukemia Group B (CALGB) trials and 87 young adults in Southwest Oncology Group (SWOG) trials, all of whom received an adult regimen. The patients were treated in 1986-2008.

Overall survival 10 years after study entry was 45% in the COG patients vs. 34% in the CALGB/SWOG patients (P less than .05). A subgroup analysis breaking down the combined population by age showed that overall survival after 10 years was 43% in younger patients (aged 16-18 years) vs. 32% in older patients (aged 19-21 years).

The median age was 18 years overall, but the median age in the COG patients was significantly younger than the median age in the CALGB/SWOG patients (17 years vs. 20 years).

The 10-year overall survival rates by age and group were 45% for younger COG patients, 44% for older COG patients, 40% for younger CALGB/SWOG patients, and 31% for older CALGB/SWOG patients.

Overall, the 10-year event-free survival rates were 39% for younger COG patients and 17% for older COG patients vs. 23%, and 22% for younger and older CALGB/SWOG patients, respectively.

In contrast, 10-year treatment-related mortality rates were significantly higher in COG patients than CALGB/SWOG patients. The rates were 26% for younger COG patients and 30% for older COG patients vs. a constant 12% for younger and older CALGB/SWOG patients.

In this study, age was a confounding variable that made comparison of patients on adult vs. child regimens difficult, because 94% of the COG patients were younger than 19 years, Dr. Franklin noted. However, "COG studies have significantly more [treatment-related mortality] and significantly less risk of relapse than the adult trials," she said.

Significant improvements occurred in 10-year overall survival, event-free survival, and relapse risk in more recent studies compared with earlier studies, but treatment-related mortality also increased, said Dr. Franklin. Multivariate analysis of the data is ongoing to determine which specific factors impact patient outcomes in adult vs. pediatric protocols, she said.

Dr. Franklin had no financial conflicts to disclose.

ORLANDO – Ten-year overall survival and event-free survival were significantly higher in adolescents and young adults with acute myeloid leukemia who were treated with a pediatric regimen vs. an adult regimen, based on data from 517 patients aged 16-21 years.

Previous studies have shown improved survival in young adults with acute lymphoblastic leukemia who were treated with a pediatric regimen, said Dr. Anna R.K. Franklin of the University of Texas M.D. Anderson Cancer Center in Houston at the annual meeting of the American Society of Hematology. Dr. Franklin and her coauthors hypothesized that survival trends might be similar in acute myeloid leukemia patients.

The researchers compared 281 young adult patients with AML in Children’s Oncology Group (COG) trials, all of whom received a pediatric regimen, vs. 149 young adults in Cancer and Leukemia Group B (CALGB) trials and 87 young adults in Southwest Oncology Group (SWOG) trials, all of whom received an adult regimen. The patients were treated in 1986-2008.

Overall survival 10 years after study entry was 45% in the COG patients vs. 34% in the CALGB/SWOG patients (P less than .05). A subgroup analysis breaking down the combined population by age showed that overall survival after 10 years was 43% in younger patients (aged 16-18 years) vs. 32% in older patients (aged 19-21 years).

The median age was 18 years overall, but the median age in the COG patients was significantly younger than the median age in the CALGB/SWOG patients (17 years vs. 20 years).

The 10-year overall survival rates by age and group were 45% for younger COG patients, 44% for older COG patients, 40% for younger CALGB/SWOG patients, and 31% for older CALGB/SWOG patients.

Overall, the 10-year event-free survival rates were 39% for younger COG patients and 17% for older COG patients vs. 23%, and 22% for younger and older CALGB/SWOG patients, respectively.

In contrast, 10-year treatment-related mortality rates were significantly higher in COG patients than CALGB/SWOG patients. The rates were 26% for younger COG patients and 30% for older COG patients vs. a constant 12% for younger and older CALGB/SWOG patients.

In this study, age was a confounding variable that made comparison of patients on adult vs. child regimens difficult, because 94% of the COG patients were younger than 19 years, Dr. Franklin noted. However, "COG studies have significantly more [treatment-related mortality] and significantly less risk of relapse than the adult trials," she said.

Significant improvements occurred in 10-year overall survival, event-free survival, and relapse risk in more recent studies compared with earlier studies, but treatment-related mortality also increased, said Dr. Franklin. Multivariate analysis of the data is ongoing to determine which specific factors impact patient outcomes in adult vs. pediatric protocols, she said.

Dr. Franklin had no financial conflicts to disclose.

ORLANDO – Ten-year overall survival and event-free survival were significantly higher in adolescents and young adults with acute myeloid leukemia who were treated with a pediatric regimen vs. an adult regimen, based on data from 517 patients aged 16-21 years.

Previous studies have shown improved survival in young adults with acute lymphoblastic leukemia who were treated with a pediatric regimen, said Dr. Anna R.K. Franklin of the University of Texas M.D. Anderson Cancer Center in Houston at the annual meeting of the American Society of Hematology. Dr. Franklin and her coauthors hypothesized that survival trends might be similar in acute myeloid leukemia patients.

The researchers compared 281 young adult patients with AML in Children’s Oncology Group (COG) trials, all of whom received a pediatric regimen, vs. 149 young adults in Cancer and Leukemia Group B (CALGB) trials and 87 young adults in Southwest Oncology Group (SWOG) trials, all of whom received an adult regimen. The patients were treated in 1986-2008.

Overall survival 10 years after study entry was 45% in the COG patients vs. 34% in the CALGB/SWOG patients (P less than .05). A subgroup analysis breaking down the combined population by age showed that overall survival after 10 years was 43% in younger patients (aged 16-18 years) vs. 32% in older patients (aged 19-21 years).

The median age was 18 years overall, but the median age in the COG patients was significantly younger than the median age in the CALGB/SWOG patients (17 years vs. 20 years).

The 10-year overall survival rates by age and group were 45% for younger COG patients, 44% for older COG patients, 40% for younger CALGB/SWOG patients, and 31% for older CALGB/SWOG patients.

Overall, the 10-year event-free survival rates were 39% for younger COG patients and 17% for older COG patients vs. 23%, and 22% for younger and older CALGB/SWOG patients, respectively.

In contrast, 10-year treatment-related mortality rates were significantly higher in COG patients than CALGB/SWOG patients. The rates were 26% for younger COG patients and 30% for older COG patients vs. a constant 12% for younger and older CALGB/SWOG patients.

In this study, age was a confounding variable that made comparison of patients on adult vs. child regimens difficult, because 94% of the COG patients were younger than 19 years, Dr. Franklin noted. However, "COG studies have significantly more [treatment-related mortality] and significantly less risk of relapse than the adult trials," she said.

Significant improvements occurred in 10-year overall survival, event-free survival, and relapse risk in more recent studies compared with earlier studies, but treatment-related mortality also increased, said Dr. Franklin. Multivariate analysis of the data is ongoing to determine which specific factors impact patient outcomes in adult vs. pediatric protocols, she said.

Dr. Franklin had no financial conflicts to disclose.

ORLANDO – Ten-year overall survival and event-free survival were significantly higher in adolescents and young adults with acute myeloid leukemia who were treated with a pediatric regimen vs. an adult regimen, based on data from 517 patients aged 16-21 years.

Previous studies have shown improved survival in young adults with acute lymphoblastic leukemia who were treated with a pediatric regimen, said Dr. Anna R.K. Franklin of the University of Texas M.D. Anderson Cancer Center in Houston at the annual meeting of the American Society of Hematology. Dr. Franklin and her coauthors hypothesized that survival trends might be similar in acute myeloid leukemia patients.

The researchers compared 281 young adult patients with AML in Children’s Oncology Group (COG) trials, all of whom received a pediatric regimen, vs. 149 young adults in Cancer and Leukemia Group B (CALGB) trials and 87 young adults in Southwest Oncology Group (SWOG) trials, all of whom received an adult regimen. The patients were treated in 1986-2008.

Overall survival 10 years after study entry was 45% in the COG patients vs. 34% in the CALGB/SWOG patients (P less than .05). A subgroup analysis breaking down the combined population by age showed that overall survival after 10 years was 43% in younger patients (aged 16-18 years) vs. 32% in older patients (aged 19-21 years).

The median age was 18 years overall, but the median age in the COG patients was significantly younger than the median age in the CALGB/SWOG patients (17 years vs. 20 years).

The 10-year overall survival rates by age and group were 45% for younger COG patients, 44% for older COG patients, 40% for younger CALGB/SWOG patients, and 31% for older CALGB/SWOG patients.

Overall, the 10-year event-free survival rates were 39% for younger COG patients and 17% for older COG patients vs. 23%, and 22% for younger and older CALGB/SWOG patients, respectively.

In contrast, 10-year treatment-related mortality rates were significantly higher in COG patients than CALGB/SWOG patients. The rates were 26% for younger COG patients and 30% for older COG patients vs. a constant 12% for younger and older CALGB/SWOG patients.

In this study, age was a confounding variable that made comparison of patients on adult vs. child regimens difficult, because 94% of the COG patients were younger than 19 years, Dr. Franklin noted. However, "COG studies have significantly more [treatment-related mortality] and significantly less risk of relapse than the adult trials," she said.

Significant improvements occurred in 10-year overall survival, event-free survival, and relapse risk in more recent studies compared with earlier studies, but treatment-related mortality also increased, said Dr. Franklin. Multivariate analysis of the data is ongoing to determine which specific factors impact patient outcomes in adult vs. pediatric protocols, she said.

Dr. Franklin had no financial conflicts to disclose.