As for many solid tumors, major advances in the treatment of ovarian cancer are more likely to be made through the introduction of novel targeted approaches rather than by manipulating cytotoxic chemotherapy regimens. Farletuzumab is a monoclonal antibody that binds to and blocks the function of folate receptor alpha, which is expressed in at least 90% of ovarian cancer patients. In platinum-sensitive patients experiencing the first relapse of their disease, farletuzumab enhances CA-125 responses as well as tumor response, as determined by RECIST criteria, compared with historic controls. Farletuzumab therefore represents a promising candidate for evaluation in phase III trials. The FAR-131 study is a multicenter, double-blind, randomized, placebo-controlled trial examining the safety and efficacy of two dose levels of farletuzumab in combination with carboplatin and a taxane in patients with platinum-sensitive ovarian cancer in first relapse. The primary endpoint is progression-free survival; the effects of this combination on overall survival, CA-125 response, duration of second remission, and quality of life are among the secondary objectives of this study.

As for many solid tumors, major advances in the treatment of ovarian cancer are more likely to be made through the introduction of novel targeted approaches rather than by manipulating cytotoxic chemotherapy regimens. Farletuzumab is a monoclonal antibody that binds to and blocks the function of folate receptor alpha, which is expressed in at least 90% of ovarian cancer patients. In platinum-sensitive patients experiencing the first relapse of their disease, farletuzumab enhances CA-125 responses as well as tumor response, as determined by RECIST criteria, compared with historic controls. Farletuzumab therefore represents a promising candidate for evaluation in phase III trials. The FAR-131 study is a multicenter, double-blind, randomized, placebo-controlled trial examining the safety and efficacy of two dose levels of farletuzumab in combination with carboplatin and a taxane in patients with platinum-sensitive ovarian cancer in first relapse. The primary endpoint is progression-free survival; the effects of this combination on overall survival, CA-125 response, duration of second remission, and quality of life are among the secondary objectives of this study.

As for many solid tumors, major advances in the treatment of ovarian cancer are more likely to be made through the introduction of novel targeted approaches rather than by manipulating cytotoxic chemotherapy regimens. Farletuzumab is a monoclonal antibody that binds to and blocks the function of folate receptor alpha, which is expressed in at least 90% of ovarian cancer patients. In platinum-sensitive patients experiencing the first relapse of their disease, farletuzumab enhances CA-125 responses as well as tumor response, as determined by RECIST criteria, compared with historic controls. Farletuzumab therefore represents a promising candidate for evaluation in phase III trials. The FAR-131 study is a multicenter, double-blind, randomized, placebo-controlled trial examining the safety and efficacy of two dose levels of farletuzumab in combination with carboplatin and a taxane in patients with platinum-sensitive ovarian cancer in first relapse. The primary endpoint is progression-free survival; the effects of this combination on overall survival, CA-125 response, duration of second remission, and quality of life are among the secondary objectives of this study.

Major Finding: Among diabetes patients at high cardiovascular risk, those treated to a mean systolic blood pressure of 119.3 mm Hg had a 1.87%/year rate of nonfatal MI, nonfatal stroke, or cardiovascular death over 4.7 years, compared with 2.09%/year in patients treated to a mean systolic blood pressure of 133.5 mm Hg. The difference was not statistically significant.

Data Source: ACCORD blood pressure trial, a randomized, controlled study of 4,733 patients with type 2 diabetes.

Disclosures: Dr. Cushman has received consultant fees and honoraria from Novartis, Sanofi-Aventis, Theravance, and Takeda, and served on data and safety monitoring boards of Novartis and Gilead. Dr. Bakris reported financial relationships with Abbott, GlaxoSmithKline, Novartis, Merck, Gilead, and other companies. Dr. Cooper-DeHoff and Dr. Simons-Morton had no disclosures.

ATLANTA — The official U.S. guideline that patients with diabetes should receive treatment to a blood pressure target of less than 130/80 mm Hg became suspect following reports from a pair of large studies showing no benefit in these patients beyond a goal systolic pressure of less than 140 mm Hg.

In a controlled trial with more than 4,700 U.S. patients with type 2 diabetes randomized to an intensive antihypertensive regimen with a goal systolic pressure of less than 120 mm Hg or to a standard-therapy arm aiming for less than 140 mm Hg, “the results provided no conclusive evidence that the intensive blood pressure control strategy reduces the rate of a composite of major cardiovascular disease events,” Dr. William C. Cushman said at the annual meeting of the American College of Cardiology.

“We were surprised by the findings” from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial, said Dr. Cushman, chief of the preventive medicine section at the VA Medical Center in Memphis. “The evidence supports less than 140 mm Hg. There generally was thinking that if you're dealing with [high cardiovascular risk], such as patients with diabetes, it makes sense that their goal pressure should be more intense.” The results “clearly say that we can't think that way anymore” and should influence recommendations expected in about a year from the Eighth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8), he said in an interview.

The existing hypertension treatment guidelines of the National Heart, Blood, and Lung Institute, JNC 7, have a blood pressure treatment target of less than 130/80 mm Hg for patients with diabetes (JAMA 2003;289:2560-71). Dr. Cushman was a member of the JNC 7 panel, and is a member of the group now working on JNC 8.

The JNC 7 blood pressure target for patients with diabetes “was an extrapolation based on observational data. The guidelines were beyond evidence from randomized, controlled trials,” said Dr. Denise Simons-Morton, project director for ACCORD and director of the NHLBI division responsible for the JNC guidelines. The new ACCORD findings show that this extrapolation was a mistake, and that current evidence cannot support a goal systolic pressure that is more aggressive than the target of less than 140 mm Hg, she said in an interview.

Because of the way that JNC 8 is being prepared, the ACCORD results may be too late for inclusion in the new guidelines, said Dr. George Bakris, professor of medicine at the University of Chicago, who was a member of the JNC 7 writing committee but is not a member of the JNC 8 panel. But, he added in an interview, “all other guidelines” on treating hypertension in patients with diabetes, including those from the American Diabetes Association and various international societies, “will have to revise their blood pressure goals” based on the ACCORD results. In an editorial last year, Dr. Bakris and an associate called the goal of a systolic pressure below 130 mm Hg in patients with chronic kidney disease “questionable” (J. Clin. Hypertension 2009;11:345-7).

The 2,362 patients in the intensive-treatment arm of the ACCORD blood pressure trial reached a mean systolic pressure of 119.3 mm Hg after the first year while receiving an average of 3.4 antihypertensive drugs; those patients had a 1.87%/year rate of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death during an average follow-up of 4.7 years. The 2,371 patients in the standard-therapy arm reached a mean systolic pressure of 133.5 mm Hg after the first year and received an average of 2.1 drugs; they had a 2.09%/year rate for the combined end point. The difference in rates between the two groups was not statistically significant. Concurrently with Dr. Cushman's report at the meeting, the results were posted online (N. Engl. J. Med. 2010 March 14 [doi:10.1056/NEJMoa1001286]).

“Less than 140 mm Hg is the message we need to put out, and less than 130 mm Hg is probably not necessary to achieve benefit and may be harmful in certain populations,” said Rhonda M. Cooper-DeHoff, Pharm.D., associate director of the cardiovascular clinical research program at the University of Florida, Gainesville.

Dr. DeHoff presented results from a second study that also called into question a systolic blood pressure goal of less than 130 mm Hg for patients with diabetes. Her study used long-term follow-up data from the 6,400 patients with diabetes who had participated in the International Verapamil SR-Trandolapril (INVEST) study, with an overall enrollment of more than 22,000 patients that compared two different antihypertensive regimens (JAMA 2003;290:2805-16).

Using data collected during the trial plus 5 years of follow-up, Dr. DeHoff and her associates showed that the 2,255 patients with diabetes maintained at a systolic blood pressure below 130 mm Hg had cardiovascular disease event rates similar to the 1,970 patients with diabetes maintained at a systolic blood pressure of 130-139 mm Hg; patients in both groups did significantly better than did a third group of 2,175 patients with diabetes whose systolic pressure consistently remained at 140 mm Hg or higher. Among the 5,077 U.S. patients with diabetes in INVEST, those kept at a systolic pressure of less than 130 mm Hg had a significant 15% increase in the rate of all-cause death, compared with the patients kept at a systolic pressure of 130-139 mm Hg.

“Based on the results from ACCORD and INVEST, is it time to rethink lower blood pressure goals in patients with diabetes and coronary artery disease?” Dr. DeHoff asked as she concluded her report at the meeting.

To apply the ACCORD results in practice, Dr. Cushman advises physicians to prescribe for patients with diabetes a “maximum” dosage of a renin-angiotensin-aldosterone system (RAAS) blocker drug, such as an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, plus a diuretic such as chlorthalidone. He also urges physicians to prescribe other drugs with antihypertensive effects, such as certain beta-blockers or calcium channel blockers, that patients with diabetes and a high risk for cardiovascular disease events might need for specific risk indications.

If a patient's systolic pressure remains above 140 mm Hg despite these treatments, then another agent should be added; if the indicated drugs bring the patient's systolic pressure below 140 mm Hg, then additional treatments should stop. However, if the indicated drugs bring the patient's pressure moderately below 130 mm Hg, “I wouldn't back off,” and withdraw drugs that the patient might otherwise need, he said.

In this way, practice should not fully mimic the ACCORD trial design. In that trial, patients in the standard-therapy arm came off one or more of their medications if their systolic pressure fell below 130 mm Hg, noted Dr. Cushman, who also is professor of medicine at the University of Tennessee in Memphis.

Intensive blood pressure control did not reduce the rate of major cardiovascular disease events in patients with diabetes, Dr. William C. Cushman reported.

Source Courtesy Memphis VAMC

If the indicated drugs bring a patient's pressure moderately below 130 mm Hg, 'I wouldn't back off.'

Source Dr. Cushman

This Month's Talk Back Question

How low do you try to get blood pressure in your patients with diabetes?

My Take

Study Findings Diverge From Observational Data

We would have predicted that the lower a patient's blood pressure the better the outcome, and we have therefore sought to get blood pressures lower.

Normal blood pressure is less than 120/80 mm Hg, but we had no data on treating patients to blood pressures that low. Nature says that high blood pressure is not good, and we try to simulate nature by using treatments that lower blood pressure by lifestyle and drugs. There is no question that lower blood pressure benefits patients, but where is the floor? Is a pressure of 140 mm Hg good enough?

For patients with diabetes, chronic kidney disease, or dyslipidemia the guidelines set a lower target pressure. But in this large trial we did not see a difference from bringing the pressure lower. We need to look at the results further to try to explain them.

ELIJAH SAUNDERS, M.D., is professor of medicine and head of the division of hypertension at the University of Maryland in Baltimore. He has been a consultant to, served on the speakers bureau for, and has received research support from Bristol-Myers Squibb, Forest, Novartis, Pfizer, and Sanofi-Aventis.

Major Finding: Among diabetes patients at high cardiovascular risk, those treated to a mean systolic blood pressure of 119.3 mm Hg had a 1.87%/year rate of nonfatal MI, nonfatal stroke, or cardiovascular death over 4.7 years, compared with 2.09%/year in patients treated to a mean systolic blood pressure of 133.5 mm Hg. The difference was not statistically significant.

Data Source: ACCORD blood pressure trial, a randomized, controlled study of 4,733 patients with type 2 diabetes.

Disclosures: Dr. Cushman has received consultant fees and honoraria from Novartis, Sanofi-Aventis, Theravance, and Takeda, and served on data and safety monitoring boards of Novartis and Gilead. Dr. Bakris reported financial relationships with Abbott, GlaxoSmithKline, Novartis, Merck, Gilead, and other companies. Dr. Cooper-DeHoff and Dr. Simons-Morton had no disclosures.

ATLANTA — The official U.S. guideline that patients with diabetes should receive treatment to a blood pressure target of less than 130/80 mm Hg became suspect following reports from a pair of large studies showing no benefit in these patients beyond a goal systolic pressure of less than 140 mm Hg.

In a controlled trial with more than 4,700 U.S. patients with type 2 diabetes randomized to an intensive antihypertensive regimen with a goal systolic pressure of less than 120 mm Hg or to a standard-therapy arm aiming for less than 140 mm Hg, “the results provided no conclusive evidence that the intensive blood pressure control strategy reduces the rate of a composite of major cardiovascular disease events,” Dr. William C. Cushman said at the annual meeting of the American College of Cardiology.

“We were surprised by the findings” from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial, said Dr. Cushman, chief of the preventive medicine section at the VA Medical Center in Memphis. “The evidence supports less than 140 mm Hg. There generally was thinking that if you're dealing with [high cardiovascular risk], such as patients with diabetes, it makes sense that their goal pressure should be more intense.” The results “clearly say that we can't think that way anymore” and should influence recommendations expected in about a year from the Eighth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8), he said in an interview.

The existing hypertension treatment guidelines of the National Heart, Blood, and Lung Institute, JNC 7, have a blood pressure treatment target of less than 130/80 mm Hg for patients with diabetes (JAMA 2003;289:2560-71). Dr. Cushman was a member of the JNC 7 panel, and is a member of the group now working on JNC 8.

The JNC 7 blood pressure target for patients with diabetes “was an extrapolation based on observational data. The guidelines were beyond evidence from randomized, controlled trials,” said Dr. Denise Simons-Morton, project director for ACCORD and director of the NHLBI division responsible for the JNC guidelines. The new ACCORD findings show that this extrapolation was a mistake, and that current evidence cannot support a goal systolic pressure that is more aggressive than the target of less than 140 mm Hg, she said in an interview.

Because of the way that JNC 8 is being prepared, the ACCORD results may be too late for inclusion in the new guidelines, said Dr. George Bakris, professor of medicine at the University of Chicago, who was a member of the JNC 7 writing committee but is not a member of the JNC 8 panel. But, he added in an interview, “all other guidelines” on treating hypertension in patients with diabetes, including those from the American Diabetes Association and various international societies, “will have to revise their blood pressure goals” based on the ACCORD results. In an editorial last year, Dr. Bakris and an associate called the goal of a systolic pressure below 130 mm Hg in patients with chronic kidney disease “questionable” (J. Clin. Hypertension 2009;11:345-7).

The 2,362 patients in the intensive-treatment arm of the ACCORD blood pressure trial reached a mean systolic pressure of 119.3 mm Hg after the first year while receiving an average of 3.4 antihypertensive drugs; those patients had a 1.87%/year rate of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death during an average follow-up of 4.7 years. The 2,371 patients in the standard-therapy arm reached a mean systolic pressure of 133.5 mm Hg after the first year and received an average of 2.1 drugs; they had a 2.09%/year rate for the combined end point. The difference in rates between the two groups was not statistically significant. Concurrently with Dr. Cushman's report at the meeting, the results were posted online (N. Engl. J. Med. 2010 March 14 [doi:10.1056/NEJMoa1001286]).

“Less than 140 mm Hg is the message we need to put out, and less than 130 mm Hg is probably not necessary to achieve benefit and may be harmful in certain populations,” said Rhonda M. Cooper-DeHoff, Pharm.D., associate director of the cardiovascular clinical research program at the University of Florida, Gainesville.

Dr. DeHoff presented results from a second study that also called into question a systolic blood pressure goal of less than 130 mm Hg for patients with diabetes. Her study used long-term follow-up data from the 6,400 patients with diabetes who had participated in the International Verapamil SR-Trandolapril (INVEST) study, with an overall enrollment of more than 22,000 patients that compared two different antihypertensive regimens (JAMA 2003;290:2805-16).

Using data collected during the trial plus 5 years of follow-up, Dr. DeHoff and her associates showed that the 2,255 patients with diabetes maintained at a systolic blood pressure below 130 mm Hg had cardiovascular disease event rates similar to the 1,970 patients with diabetes maintained at a systolic blood pressure of 130-139 mm Hg; patients in both groups did significantly better than did a third group of 2,175 patients with diabetes whose systolic pressure consistently remained at 140 mm Hg or higher. Among the 5,077 U.S. patients with diabetes in INVEST, those kept at a systolic pressure of less than 130 mm Hg had a significant 15% increase in the rate of all-cause death, compared with the patients kept at a systolic pressure of 130-139 mm Hg.

“Based on the results from ACCORD and INVEST, is it time to rethink lower blood pressure goals in patients with diabetes and coronary artery disease?” Dr. DeHoff asked as she concluded her report at the meeting.

To apply the ACCORD results in practice, Dr. Cushman advises physicians to prescribe for patients with diabetes a “maximum” dosage of a renin-angiotensin-aldosterone system (RAAS) blocker drug, such as an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, plus a diuretic such as chlorthalidone. He also urges physicians to prescribe other drugs with antihypertensive effects, such as certain beta-blockers or calcium channel blockers, that patients with diabetes and a high risk for cardiovascular disease events might need for specific risk indications.

If a patient's systolic pressure remains above 140 mm Hg despite these treatments, then another agent should be added; if the indicated drugs bring the patient's systolic pressure below 140 mm Hg, then additional treatments should stop. However, if the indicated drugs bring the patient's pressure moderately below 130 mm Hg, “I wouldn't back off,” and withdraw drugs that the patient might otherwise need, he said.

In this way, practice should not fully mimic the ACCORD trial design. In that trial, patients in the standard-therapy arm came off one or more of their medications if their systolic pressure fell below 130 mm Hg, noted Dr. Cushman, who also is professor of medicine at the University of Tennessee in Memphis.

Intensive blood pressure control did not reduce the rate of major cardiovascular disease events in patients with diabetes, Dr. William C. Cushman reported.

Source Courtesy Memphis VAMC

If the indicated drugs bring a patient's pressure moderately below 130 mm Hg, 'I wouldn't back off.'

Source Dr. Cushman

This Month's Talk Back Question

How low do you try to get blood pressure in your patients with diabetes?

My Take

Study Findings Diverge From Observational Data

We would have predicted that the lower a patient's blood pressure the better the outcome, and we have therefore sought to get blood pressures lower.

Normal blood pressure is less than 120/80 mm Hg, but we had no data on treating patients to blood pressures that low. Nature says that high blood pressure is not good, and we try to simulate nature by using treatments that lower blood pressure by lifestyle and drugs. There is no question that lower blood pressure benefits patients, but where is the floor? Is a pressure of 140 mm Hg good enough?

For patients with diabetes, chronic kidney disease, or dyslipidemia the guidelines set a lower target pressure. But in this large trial we did not see a difference from bringing the pressure lower. We need to look at the results further to try to explain them.

ELIJAH SAUNDERS, M.D., is professor of medicine and head of the division of hypertension at the University of Maryland in Baltimore. He has been a consultant to, served on the speakers bureau for, and has received research support from Bristol-Myers Squibb, Forest, Novartis, Pfizer, and Sanofi-Aventis.

Major Finding: Among diabetes patients at high cardiovascular risk, those treated to a mean systolic blood pressure of 119.3 mm Hg had a 1.87%/year rate of nonfatal MI, nonfatal stroke, or cardiovascular death over 4.7 years, compared with 2.09%/year in patients treated to a mean systolic blood pressure of 133.5 mm Hg. The difference was not statistically significant.

Data Source: ACCORD blood pressure trial, a randomized, controlled study of 4,733 patients with type 2 diabetes.

Disclosures: Dr. Cushman has received consultant fees and honoraria from Novartis, Sanofi-Aventis, Theravance, and Takeda, and served on data and safety monitoring boards of Novartis and Gilead. Dr. Bakris reported financial relationships with Abbott, GlaxoSmithKline, Novartis, Merck, Gilead, and other companies. Dr. Cooper-DeHoff and Dr. Simons-Morton had no disclosures.

ATLANTA — The official U.S. guideline that patients with diabetes should receive treatment to a blood pressure target of less than 130/80 mm Hg became suspect following reports from a pair of large studies showing no benefit in these patients beyond a goal systolic pressure of less than 140 mm Hg.

In a controlled trial with more than 4,700 U.S. patients with type 2 diabetes randomized to an intensive antihypertensive regimen with a goal systolic pressure of less than 120 mm Hg or to a standard-therapy arm aiming for less than 140 mm Hg, “the results provided no conclusive evidence that the intensive blood pressure control strategy reduces the rate of a composite of major cardiovascular disease events,” Dr. William C. Cushman said at the annual meeting of the American College of Cardiology.

“We were surprised by the findings” from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial, said Dr. Cushman, chief of the preventive medicine section at the VA Medical Center in Memphis. “The evidence supports less than 140 mm Hg. There generally was thinking that if you're dealing with [high cardiovascular risk], such as patients with diabetes, it makes sense that their goal pressure should be more intense.” The results “clearly say that we can't think that way anymore” and should influence recommendations expected in about a year from the Eighth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8), he said in an interview.

The existing hypertension treatment guidelines of the National Heart, Blood, and Lung Institute, JNC 7, have a blood pressure treatment target of less than 130/80 mm Hg for patients with diabetes (JAMA 2003;289:2560-71). Dr. Cushman was a member of the JNC 7 panel, and is a member of the group now working on JNC 8.

The JNC 7 blood pressure target for patients with diabetes “was an extrapolation based on observational data. The guidelines were beyond evidence from randomized, controlled trials,” said Dr. Denise Simons-Morton, project director for ACCORD and director of the NHLBI division responsible for the JNC guidelines. The new ACCORD findings show that this extrapolation was a mistake, and that current evidence cannot support a goal systolic pressure that is more aggressive than the target of less than 140 mm Hg, she said in an interview.

Because of the way that JNC 8 is being prepared, the ACCORD results may be too late for inclusion in the new guidelines, said Dr. George Bakris, professor of medicine at the University of Chicago, who was a member of the JNC 7 writing committee but is not a member of the JNC 8 panel. But, he added in an interview, “all other guidelines” on treating hypertension in patients with diabetes, including those from the American Diabetes Association and various international societies, “will have to revise their blood pressure goals” based on the ACCORD results. In an editorial last year, Dr. Bakris and an associate called the goal of a systolic pressure below 130 mm Hg in patients with chronic kidney disease “questionable” (J. Clin. Hypertension 2009;11:345-7).

The 2,362 patients in the intensive-treatment arm of the ACCORD blood pressure trial reached a mean systolic pressure of 119.3 mm Hg after the first year while receiving an average of 3.4 antihypertensive drugs; those patients had a 1.87%/year rate of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death during an average follow-up of 4.7 years. The 2,371 patients in the standard-therapy arm reached a mean systolic pressure of 133.5 mm Hg after the first year and received an average of 2.1 drugs; they had a 2.09%/year rate for the combined end point. The difference in rates between the two groups was not statistically significant. Concurrently with Dr. Cushman's report at the meeting, the results were posted online (N. Engl. J. Med. 2010 March 14 [doi:10.1056/NEJMoa1001286]).

“Less than 140 mm Hg is the message we need to put out, and less than 130 mm Hg is probably not necessary to achieve benefit and may be harmful in certain populations,” said Rhonda M. Cooper-DeHoff, Pharm.D., associate director of the cardiovascular clinical research program at the University of Florida, Gainesville.

Dr. DeHoff presented results from a second study that also called into question a systolic blood pressure goal of less than 130 mm Hg for patients with diabetes. Her study used long-term follow-up data from the 6,400 patients with diabetes who had participated in the International Verapamil SR-Trandolapril (INVEST) study, with an overall enrollment of more than 22,000 patients that compared two different antihypertensive regimens (JAMA 2003;290:2805-16).

Using data collected during the trial plus 5 years of follow-up, Dr. DeHoff and her associates showed that the 2,255 patients with diabetes maintained at a systolic blood pressure below 130 mm Hg had cardiovascular disease event rates similar to the 1,970 patients with diabetes maintained at a systolic blood pressure of 130-139 mm Hg; patients in both groups did significantly better than did a third group of 2,175 patients with diabetes whose systolic pressure consistently remained at 140 mm Hg or higher. Among the 5,077 U.S. patients with diabetes in INVEST, those kept at a systolic pressure of less than 130 mm Hg had a significant 15% increase in the rate of all-cause death, compared with the patients kept at a systolic pressure of 130-139 mm Hg.

“Based on the results from ACCORD and INVEST, is it time to rethink lower blood pressure goals in patients with diabetes and coronary artery disease?” Dr. DeHoff asked as she concluded her report at the meeting.

To apply the ACCORD results in practice, Dr. Cushman advises physicians to prescribe for patients with diabetes a “maximum” dosage of a renin-angiotensin-aldosterone system (RAAS) blocker drug, such as an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, plus a diuretic such as chlorthalidone. He also urges physicians to prescribe other drugs with antihypertensive effects, such as certain beta-blockers or calcium channel blockers, that patients with diabetes and a high risk for cardiovascular disease events might need for specific risk indications.

If a patient's systolic pressure remains above 140 mm Hg despite these treatments, then another agent should be added; if the indicated drugs bring the patient's systolic pressure below 140 mm Hg, then additional treatments should stop. However, if the indicated drugs bring the patient's pressure moderately below 130 mm Hg, “I wouldn't back off,” and withdraw drugs that the patient might otherwise need, he said.

In this way, practice should not fully mimic the ACCORD trial design. In that trial, patients in the standard-therapy arm came off one or more of their medications if their systolic pressure fell below 130 mm Hg, noted Dr. Cushman, who also is professor of medicine at the University of Tennessee in Memphis.

Intensive blood pressure control did not reduce the rate of major cardiovascular disease events in patients with diabetes, Dr. William C. Cushman reported.

Source Courtesy Memphis VAMC

If the indicated drugs bring a patient's pressure moderately below 130 mm Hg, 'I wouldn't back off.'

Source Dr. Cushman

This Month's Talk Back Question

How low do you try to get blood pressure in your patients with diabetes?

My Take

Study Findings Diverge From Observational Data

We would have predicted that the lower a patient's blood pressure the better the outcome, and we have therefore sought to get blood pressures lower.

Normal blood pressure is less than 120/80 mm Hg, but we had no data on treating patients to blood pressures that low. Nature says that high blood pressure is not good, and we try to simulate nature by using treatments that lower blood pressure by lifestyle and drugs. There is no question that lower blood pressure benefits patients, but where is the floor? Is a pressure of 140 mm Hg good enough?

For patients with diabetes, chronic kidney disease, or dyslipidemia the guidelines set a lower target pressure. But in this large trial we did not see a difference from bringing the pressure lower. We need to look at the results further to try to explain them.

ELIJAH SAUNDERS, M.D., is professor of medicine and head of the division of hypertension at the University of Maryland in Baltimore. He has been a consultant to, served on the speakers bureau for, and has received research support from Bristol-Myers Squibb, Forest, Novartis, Pfizer, and Sanofi-Aventis.

The cost of healthcare varies widely from hospital to hospital and doesn't appear to be inherently linked to the quality of patient care, according to a study in the Archives of Internal Medicine.

"It's particularly perplexing because the differences in cost are quite substantial," says Mitchell Katz, MD, director of San Francisco's public-health program and the author of an accompanying editorial calling for more research.

The Feb. 22 report found wide disparities in the costs of care but no strong correlation in the context of patient care or the risk of death within 30 days. The nationwide study by researchers at the University of Michigan reviewed some 3,150 hospitals that discharged Medicare patients admitted for congestive heart failure or pneumonia in 2006. Data were studied in association with variables including readmission rates and quality scores.

Compared with hospitals in the lowest-cost quartile for congestive heart failure care, the researchers found that hospitals in the highest-cost quartile had higher quality-of-care scores (89.9% vs. 85.5%) and lower mortality for congestive heart failure (9.8% vs. 10.8%). For pneumonia, however, the converse was true. Compared with lower-cost hospitals, high-cost hospitals had lower quality-of-care scores (85.7% vs. 86.6%) and higher mortality (11.7% vs. 10.9%).

Dr. Katz is heartened that the study found longer length-of-stay (LOS) at high-cost hospitals, suggesting that decreased LOS—a staple of HM's value-added services—will slash hospital costs. But he says more randomized, comparative-effectiveness studies need to be published. Hospitalists are in a natural position to author those examinations, he says. "One of the roles of a hospitalist can be to be advocates of 'Yes, we think it can be done,' " Dr. Katz says. "Because there are a lot of doctors who want to say, ‘No, it can’t be done.' "

The cost of healthcare varies widely from hospital to hospital and doesn't appear to be inherently linked to the quality of patient care, according to a study in the Archives of Internal Medicine.

"It's particularly perplexing because the differences in cost are quite substantial," says Mitchell Katz, MD, director of San Francisco's public-health program and the author of an accompanying editorial calling for more research.

The Feb. 22 report found wide disparities in the costs of care but no strong correlation in the context of patient care or the risk of death within 30 days. The nationwide study by researchers at the University of Michigan reviewed some 3,150 hospitals that discharged Medicare patients admitted for congestive heart failure or pneumonia in 2006. Data were studied in association with variables including readmission rates and quality scores.

Compared with hospitals in the lowest-cost quartile for congestive heart failure care, the researchers found that hospitals in the highest-cost quartile had higher quality-of-care scores (89.9% vs. 85.5%) and lower mortality for congestive heart failure (9.8% vs. 10.8%). For pneumonia, however, the converse was true. Compared with lower-cost hospitals, high-cost hospitals had lower quality-of-care scores (85.7% vs. 86.6%) and higher mortality (11.7% vs. 10.9%).

Dr. Katz is heartened that the study found longer length-of-stay (LOS) at high-cost hospitals, suggesting that decreased LOS—a staple of HM's value-added services—will slash hospital costs. But he says more randomized, comparative-effectiveness studies need to be published. Hospitalists are in a natural position to author those examinations, he says. "One of the roles of a hospitalist can be to be advocates of 'Yes, we think it can be done,' " Dr. Katz says. "Because there are a lot of doctors who want to say, ‘No, it can’t be done.' "

The cost of healthcare varies widely from hospital to hospital and doesn't appear to be inherently linked to the quality of patient care, according to a study in the Archives of Internal Medicine.

"It's particularly perplexing because the differences in cost are quite substantial," says Mitchell Katz, MD, director of San Francisco's public-health program and the author of an accompanying editorial calling for more research.

The Feb. 22 report found wide disparities in the costs of care but no strong correlation in the context of patient care or the risk of death within 30 days. The nationwide study by researchers at the University of Michigan reviewed some 3,150 hospitals that discharged Medicare patients admitted for congestive heart failure or pneumonia in 2006. Data were studied in association with variables including readmission rates and quality scores.

Compared with hospitals in the lowest-cost quartile for congestive heart failure care, the researchers found that hospitals in the highest-cost quartile had higher quality-of-care scores (89.9% vs. 85.5%) and lower mortality for congestive heart failure (9.8% vs. 10.8%). For pneumonia, however, the converse was true. Compared with lower-cost hospitals, high-cost hospitals had lower quality-of-care scores (85.7% vs. 86.6%) and higher mortality (11.7% vs. 10.9%).

Dr. Katz is heartened that the study found longer length-of-stay (LOS) at high-cost hospitals, suggesting that decreased LOS—a staple of HM's value-added services—will slash hospital costs. But he says more randomized, comparative-effectiveness studies need to be published. Hospitalists are in a natural position to author those examinations, he says. "One of the roles of a hospitalist can be to be advocates of 'Yes, we think it can be done,' " Dr. Katz says. "Because there are a lot of doctors who want to say, ‘No, it can’t be done.' "

Clinical question: Does the appropriateness of the initial empiric antimicrobial agents started at the onset of septic shock have an impact on outcomes in this clinical syndrome?

Background: Septic shock is a common cause of death among ICU patients. Prompt initiation of appropriate antimicrobial therapy is key to improving outcomes. This study evaluates the effects of initiating inappropriate empiric antimicrobial therapy.

Study design: Retrospective cohort study.

Setting: Twenty-two hospitals in the U.S., Canada, and Saudi Arabia.

Synopsis: Records of more than 5,700 patients with septic shock were reviewed. Appropriate antimicrobial therapy was defined as agents with in vitro activity for the isolated microorganism(s), or if the antimicrobial agents provided adequate empiric coverage for local community and nosocomial flora in culture-negative shock. The main outcome variable was survival to hospital discharge.

The overall survival-to-hospital discharge was 43.7%, and 80.1% of patients received appropriate empiric antimicrobial therapy. Of those who died, 4.8% did not receive appropriate therapy. Inappropriate antimicrobial regimens caused survival to fall to 10.3% from 52.0% (OR 9.45; 95% CI, 7.74 to 11.54; p<0.0001).

After adjusting for potential confounding variables, the inappropriateness of initial antimicrobial therapy remained strongly associated with risk of death (OR 8.99; 95% CI, 6.60 to 12.23; p<0.0001).

The primary weakness of the study is that it was observational.

Bottom line: The choice of an appropriate empiric antimicrobial agent is a critical determinant of survival in patients with septic shock.

Citation: Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136(5):1237-1248.

Reviewed for TH eWire by Sameer Badlani, MD, Stacy S. Banerjee, MD, Alan J. Jung, MD, Elizabeth Marlow, MD, MPP, Valerie G. Press, MD, MPH, Milda R. Saunders, MD, MPH, Nilam J. Soni, MD, Srilaxmi Tumuluri, MD, Section of Hospital Medicine, University of Chicago

For more reviews of HM-related literature, visit our Web site.

Clinical question: Does the appropriateness of the initial empiric antimicrobial agents started at the onset of septic shock have an impact on outcomes in this clinical syndrome?

Background: Septic shock is a common cause of death among ICU patients. Prompt initiation of appropriate antimicrobial therapy is key to improving outcomes. This study evaluates the effects of initiating inappropriate empiric antimicrobial therapy.

Study design: Retrospective cohort study.

Setting: Twenty-two hospitals in the U.S., Canada, and Saudi Arabia.

Synopsis: Records of more than 5,700 patients with septic shock were reviewed. Appropriate antimicrobial therapy was defined as agents with in vitro activity for the isolated microorganism(s), or if the antimicrobial agents provided adequate empiric coverage for local community and nosocomial flora in culture-negative shock. The main outcome variable was survival to hospital discharge.

The overall survival-to-hospital discharge was 43.7%, and 80.1% of patients received appropriate empiric antimicrobial therapy. Of those who died, 4.8% did not receive appropriate therapy. Inappropriate antimicrobial regimens caused survival to fall to 10.3% from 52.0% (OR 9.45; 95% CI, 7.74 to 11.54; p<0.0001).

After adjusting for potential confounding variables, the inappropriateness of initial antimicrobial therapy remained strongly associated with risk of death (OR 8.99; 95% CI, 6.60 to 12.23; p<0.0001).

The primary weakness of the study is that it was observational.

Bottom line: The choice of an appropriate empiric antimicrobial agent is a critical determinant of survival in patients with septic shock.

Citation: Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136(5):1237-1248.

Reviewed for TH eWire by Sameer Badlani, MD, Stacy S. Banerjee, MD, Alan J. Jung, MD, Elizabeth Marlow, MD, MPP, Valerie G. Press, MD, MPH, Milda R. Saunders, MD, MPH, Nilam J. Soni, MD, Srilaxmi Tumuluri, MD, Section of Hospital Medicine, University of Chicago

For more reviews of HM-related literature, visit our Web site.

Clinical question: Does the appropriateness of the initial empiric antimicrobial agents started at the onset of septic shock have an impact on outcomes in this clinical syndrome?

Background: Septic shock is a common cause of death among ICU patients. Prompt initiation of appropriate antimicrobial therapy is key to improving outcomes. This study evaluates the effects of initiating inappropriate empiric antimicrobial therapy.

Study design: Retrospective cohort study.

Setting: Twenty-two hospitals in the U.S., Canada, and Saudi Arabia.

Synopsis: Records of more than 5,700 patients with septic shock were reviewed. Appropriate antimicrobial therapy was defined as agents with in vitro activity for the isolated microorganism(s), or if the antimicrobial agents provided adequate empiric coverage for local community and nosocomial flora in culture-negative shock. The main outcome variable was survival to hospital discharge.

The overall survival-to-hospital discharge was 43.7%, and 80.1% of patients received appropriate empiric antimicrobial therapy. Of those who died, 4.8% did not receive appropriate therapy. Inappropriate antimicrobial regimens caused survival to fall to 10.3% from 52.0% (OR 9.45; 95% CI, 7.74 to 11.54; p<0.0001).

After adjusting for potential confounding variables, the inappropriateness of initial antimicrobial therapy remained strongly associated with risk of death (OR 8.99; 95% CI, 6.60 to 12.23; p<0.0001).

The primary weakness of the study is that it was observational.

Bottom line: The choice of an appropriate empiric antimicrobial agent is a critical determinant of survival in patients with septic shock.

Citation: Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009;136(5):1237-1248.

Reviewed for TH eWire by Sameer Badlani, MD, Stacy S. Banerjee, MD, Alan J. Jung, MD, Elizabeth Marlow, MD, MPP, Valerie G. Press, MD, MPH, Milda R. Saunders, MD, MPH, Nilam J. Soni, MD, Srilaxmi Tumuluri, MD, Section of Hospital Medicine, University of Chicago

For more reviews of HM-related literature, visit our Web site.

Upper gastrointestinal hemorrhage (UGIH) patients attended by academic hospitalists and nonhospitalists exhibited similar outcomes and length of stay (LOS), but those cared for by the hospitalists required higher costs for care, according to a study published in this month's Journal of Hospital Medicine.

The report,"Do Hospitalists Affect Clinical Outcomes and Efficiency for Patients with Acute Upper Gastrointestinal Hemorrhage (UGIH)?" (2010;5(3):132-138), says "median LOS was similar for hospitalists and non-hospitalists (4 days; P=0.69), but patients cared for by hospitalists had higher median costs ($7,359 vs. $6,181; P

"Our hypothesis going into it was that the presence of a hospitalist may impact the efficiency of the quality of care for this type of condition," says senior author Peter Kaboli, MD, MS, FHM, a hospitalist at the Center for Research in the Implementation of Innovative Strategies in Practice (CRIISP) at the VA Medical Center in Iowa City, Iowa. "But we weren't sure, because this condition is so dependent on subspecialty care that our thought was possibly the need for subspecialists would attenuate that potential hospitalist effect we see in many other studies."

Dr. Kaboli and colleagues could not draw a specific conclusion for why the disparity of costs existed. He suggests that the higher intensity of costs in HM models is one contributing factor, as is the co-management model that eliminates a hospitalist's ability to unilaterally—and more quickly—make decisions that affect care and costs.

Regardless, Dr. Kaboli is hopeful the study spurs more research into why the cost variation exists and encourages HM leaders to review their UGIH care standards.

"Look at lengths of stay. Look at time to endoscopy," Dr. Kaboli says. "Look to see what you can do to improve that efficiency and improve that coordination of care. And, frankly, because so much of what we do is on a DRG-based payment system, we all do better and patients do better if we have highly efficient care."

Upper gastrointestinal hemorrhage (UGIH) patients attended by academic hospitalists and nonhospitalists exhibited similar outcomes and length of stay (LOS), but those cared for by the hospitalists required higher costs for care, according to a study published in this month's Journal of Hospital Medicine.

The report,"Do Hospitalists Affect Clinical Outcomes and Efficiency for Patients with Acute Upper Gastrointestinal Hemorrhage (UGIH)?" (2010;5(3):132-138), says "median LOS was similar for hospitalists and non-hospitalists (4 days; P=0.69), but patients cared for by hospitalists had higher median costs ($7,359 vs. $6,181; P

"Our hypothesis going into it was that the presence of a hospitalist may impact the efficiency of the quality of care for this type of condition," says senior author Peter Kaboli, MD, MS, FHM, a hospitalist at the Center for Research in the Implementation of Innovative Strategies in Practice (CRIISP) at the VA Medical Center in Iowa City, Iowa. "But we weren't sure, because this condition is so dependent on subspecialty care that our thought was possibly the need for subspecialists would attenuate that potential hospitalist effect we see in many other studies."

Dr. Kaboli and colleagues could not draw a specific conclusion for why the disparity of costs existed. He suggests that the higher intensity of costs in HM models is one contributing factor, as is the co-management model that eliminates a hospitalist's ability to unilaterally—and more quickly—make decisions that affect care and costs.

Regardless, Dr. Kaboli is hopeful the study spurs more research into why the cost variation exists and encourages HM leaders to review their UGIH care standards.

"Look at lengths of stay. Look at time to endoscopy," Dr. Kaboli says. "Look to see what you can do to improve that efficiency and improve that coordination of care. And, frankly, because so much of what we do is on a DRG-based payment system, we all do better and patients do better if we have highly efficient care."

Upper gastrointestinal hemorrhage (UGIH) patients attended by academic hospitalists and nonhospitalists exhibited similar outcomes and length of stay (LOS), but those cared for by the hospitalists required higher costs for care, according to a study published in this month's Journal of Hospital Medicine.

The report,"Do Hospitalists Affect Clinical Outcomes and Efficiency for Patients with Acute Upper Gastrointestinal Hemorrhage (UGIH)?" (2010;5(3):132-138), says "median LOS was similar for hospitalists and non-hospitalists (4 days; P=0.69), but patients cared for by hospitalists had higher median costs ($7,359 vs. $6,181; P

"Our hypothesis going into it was that the presence of a hospitalist may impact the efficiency of the quality of care for this type of condition," says senior author Peter Kaboli, MD, MS, FHM, a hospitalist at the Center for Research in the Implementation of Innovative Strategies in Practice (CRIISP) at the VA Medical Center in Iowa City, Iowa. "But we weren't sure, because this condition is so dependent on subspecialty care that our thought was possibly the need for subspecialists would attenuate that potential hospitalist effect we see in many other studies."

Dr. Kaboli and colleagues could not draw a specific conclusion for why the disparity of costs existed. He suggests that the higher intensity of costs in HM models is one contributing factor, as is the co-management model that eliminates a hospitalist's ability to unilaterally—and more quickly—make decisions that affect care and costs.

Regardless, Dr. Kaboli is hopeful the study spurs more research into why the cost variation exists and encourages HM leaders to review their UGIH care standards.

"Look at lengths of stay. Look at time to endoscopy," Dr. Kaboli says. "Look to see what you can do to improve that efficiency and improve that coordination of care. And, frankly, because so much of what we do is on a DRG-based payment system, we all do better and patients do better if we have highly efficient care."

Ever wonder whether a new drug is as good as the one you’ve been prescribing for years? Alec B. O'Connor, MD, MPH, wonders all the time. In a commentary published in the March 1 issue of the Journal of the American Medical Association, Dr. O’Connor calls on the FDA to help physicians answer such questions.

Dr. O’Connor, associate medicine residency program director for inpatient services at the University of Rochester Medical Center in Rochester, N.Y., says that as part of the drug-approval process, the FDA should require pharmaceutical companies to submit data comparing the efficacy and safety of a new drug to an established first-line drug.

TH eWire recently asked Dr. O’Connor about his proposal.

Question: What propelled you to write this editorial?

Answer: I’ve observed that physician tendencies and patient tendencies are to try new drugs, regardless of what they were taking before the new drug came out. … When new drugs come to market, they are compared only against placebo and, in reality, that is not a comparison. What I need to see is how the new drug compares to what I’m already using to treat the patient for the same indication. … For all we know, if we stop using the old drug and prescribe the new drug, we may be harming the patient, in addition to increasing drug costs.

Q: Is it possible these requirements could increase drug development costs?

A: [The increase] will likely be quite small because there are so many drug development costs that happen before you get to the trial. I think the bigger risk would just be that they would get to the end of the drug development process and discover they have a drug that can’t be approved because it’s not as good as what we are currently using. … The flip side is that if that happens, then we prevent the drug from coming to market and replacing a current treatment with a drug that was shown to be inferior. I think companies would find that if they get to that point, they can find niches for the drug where it’s added to an existing treatment. They can also determine what patient population the drug makes the most sense for and do a trial that shows it does have a clinical effect that is just as good as what is already out there. So they’ll still have a drug they can sell.

Q: Will the policy incentivize pharmaceutical companies to develop orphan drugs or new classes of drugs?

A: It might. They would see it as a potentially less-risky development. Unfortunately, drug companies have to invest a lot of money in a potential new drug before they get to the Phase III trials where they are comparing them. It’s possible that drug companies might strategize about choosing more orphan indications, where all they would have to do is compare the drug to placebo, because there is no other treatment option.

Ever wonder whether a new drug is as good as the one you’ve been prescribing for years? Alec B. O'Connor, MD, MPH, wonders all the time. In a commentary published in the March 1 issue of the Journal of the American Medical Association, Dr. O’Connor calls on the FDA to help physicians answer such questions.

Dr. O’Connor, associate medicine residency program director for inpatient services at the University of Rochester Medical Center in Rochester, N.Y., says that as part of the drug-approval process, the FDA should require pharmaceutical companies to submit data comparing the efficacy and safety of a new drug to an established first-line drug.

TH eWire recently asked Dr. O’Connor about his proposal.

Question: What propelled you to write this editorial?

Answer: I’ve observed that physician tendencies and patient tendencies are to try new drugs, regardless of what they were taking before the new drug came out. … When new drugs come to market, they are compared only against placebo and, in reality, that is not a comparison. What I need to see is how the new drug compares to what I’m already using to treat the patient for the same indication. … For all we know, if we stop using the old drug and prescribe the new drug, we may be harming the patient, in addition to increasing drug costs.

Q: Is it possible these requirements could increase drug development costs?

A: [The increase] will likely be quite small because there are so many drug development costs that happen before you get to the trial. I think the bigger risk would just be that they would get to the end of the drug development process and discover they have a drug that can’t be approved because it’s not as good as what we are currently using. … The flip side is that if that happens, then we prevent the drug from coming to market and replacing a current treatment with a drug that was shown to be inferior. I think companies would find that if they get to that point, they can find niches for the drug where it’s added to an existing treatment. They can also determine what patient population the drug makes the most sense for and do a trial that shows it does have a clinical effect that is just as good as what is already out there. So they’ll still have a drug they can sell.

Q: Will the policy incentivize pharmaceutical companies to develop orphan drugs or new classes of drugs?

A: It might. They would see it as a potentially less-risky development. Unfortunately, drug companies have to invest a lot of money in a potential new drug before they get to the Phase III trials where they are comparing them. It’s possible that drug companies might strategize about choosing more orphan indications, where all they would have to do is compare the drug to placebo, because there is no other treatment option.

Ever wonder whether a new drug is as good as the one you’ve been prescribing for years? Alec B. O'Connor, MD, MPH, wonders all the time. In a commentary published in the March 1 issue of the Journal of the American Medical Association, Dr. O’Connor calls on the FDA to help physicians answer such questions.

Dr. O’Connor, associate medicine residency program director for inpatient services at the University of Rochester Medical Center in Rochester, N.Y., says that as part of the drug-approval process, the FDA should require pharmaceutical companies to submit data comparing the efficacy and safety of a new drug to an established first-line drug.

TH eWire recently asked Dr. O’Connor about his proposal.

Question: What propelled you to write this editorial?

Answer: I’ve observed that physician tendencies and patient tendencies are to try new drugs, regardless of what they were taking before the new drug came out. … When new drugs come to market, they are compared only against placebo and, in reality, that is not a comparison. What I need to see is how the new drug compares to what I’m already using to treat the patient for the same indication. … For all we know, if we stop using the old drug and prescribe the new drug, we may be harming the patient, in addition to increasing drug costs.

Q: Is it possible these requirements could increase drug development costs?

A: [The increase] will likely be quite small because there are so many drug development costs that happen before you get to the trial. I think the bigger risk would just be that they would get to the end of the drug development process and discover they have a drug that can’t be approved because it’s not as good as what we are currently using. … The flip side is that if that happens, then we prevent the drug from coming to market and replacing a current treatment with a drug that was shown to be inferior. I think companies would find that if they get to that point, they can find niches for the drug where it’s added to an existing treatment. They can also determine what patient population the drug makes the most sense for and do a trial that shows it does have a clinical effect that is just as good as what is already out there. So they’ll still have a drug they can sell.

Q: Will the policy incentivize pharmaceutical companies to develop orphan drugs or new classes of drugs?

A: It might. They would see it as a potentially less-risky development. Unfortunately, drug companies have to invest a lot of money in a potential new drug before they get to the Phase III trials where they are comparing them. It’s possible that drug companies might strategize about choosing more orphan indications, where all they would have to do is compare the drug to placebo, because there is no other treatment option.

The Oncologic Drugs Advisory Committee (ODAC) recommended yesterday against approval of pixantrone for the treatment of recurrent or refractory aggressive non-Hodgkin’s lymphoma (NHL).

ODAC voted unanimously against the approval of pixantrone, saying that the drug did not demonstrate a statistically significant improvement over the control arm. The complete response rate was 20.0% with pixantrone and 5.7% with the comparator therapies.

ODAC also expressed concern that the phase 3 trial was stopped early at 44% of planned enrollment due to poor accrual. And only 8 of the 70 patients enrolled were US patients, raising concern about whether the results held true for the US population.

Pixantrone dimaleate, an aza-anthracenedione, is developed by the Seattle-based Cell Therapeutics, Inc.

ODAC also considered the application of Australian drug maker ChemGenex Pharmaceuticals for omacetaxine mepesuccinate. In a 7-1 decision, ODAC recommended a single genetic test be developed and approved prior to consideration of omacetaxine for the treatment of adults with chronic myeloid leukemia with the Bcr-Abl T3151 mutation.

The drug maker used 2 different tests to identify patients with the mutation. In addition, 23 of 66 patients did not have central laboratory confirmation of the mutation. ODAC was concerned that the comparability of the tests was unknown. 

The applicant had submitted data on efficacy and safety prior to completing the planned enrollment of 100 patients, which meant that data from approximately a third of the planned population were missing at the time of consideration.

The US Food and Drug Administration usually follows the recommendations of ODAC.

The Oncologic Drugs Advisory Committee (ODAC) recommended yesterday against approval of pixantrone for the treatment of recurrent or refractory aggressive non-Hodgkin’s lymphoma (NHL).

ODAC voted unanimously against the approval of pixantrone, saying that the drug did not demonstrate a statistically significant improvement over the control arm. The complete response rate was 20.0% with pixantrone and 5.7% with the comparator therapies.

ODAC also expressed concern that the phase 3 trial was stopped early at 44% of planned enrollment due to poor accrual. And only 8 of the 70 patients enrolled were US patients, raising concern about whether the results held true for the US population.

Pixantrone dimaleate, an aza-anthracenedione, is developed by the Seattle-based Cell Therapeutics, Inc.

ODAC also considered the application of Australian drug maker ChemGenex Pharmaceuticals for omacetaxine mepesuccinate. In a 7-1 decision, ODAC recommended a single genetic test be developed and approved prior to consideration of omacetaxine for the treatment of adults with chronic myeloid leukemia with the Bcr-Abl T3151 mutation.

The drug maker used 2 different tests to identify patients with the mutation. In addition, 23 of 66 patients did not have central laboratory confirmation of the mutation. ODAC was concerned that the comparability of the tests was unknown. 

The applicant had submitted data on efficacy and safety prior to completing the planned enrollment of 100 patients, which meant that data from approximately a third of the planned population were missing at the time of consideration.

The US Food and Drug Administration usually follows the recommendations of ODAC.

The Oncologic Drugs Advisory Committee (ODAC) recommended yesterday against approval of pixantrone for the treatment of recurrent or refractory aggressive non-Hodgkin’s lymphoma (NHL).

ODAC voted unanimously against the approval of pixantrone, saying that the drug did not demonstrate a statistically significant improvement over the control arm. The complete response rate was 20.0% with pixantrone and 5.7% with the comparator therapies.

ODAC also expressed concern that the phase 3 trial was stopped early at 44% of planned enrollment due to poor accrual. And only 8 of the 70 patients enrolled were US patients, raising concern about whether the results held true for the US population.

Pixantrone dimaleate, an aza-anthracenedione, is developed by the Seattle-based Cell Therapeutics, Inc.

ODAC also considered the application of Australian drug maker ChemGenex Pharmaceuticals for omacetaxine mepesuccinate. In a 7-1 decision, ODAC recommended a single genetic test be developed and approved prior to consideration of omacetaxine for the treatment of adults with chronic myeloid leukemia with the Bcr-Abl T3151 mutation.

The drug maker used 2 different tests to identify patients with the mutation. In addition, 23 of 66 patients did not have central laboratory confirmation of the mutation. ODAC was concerned that the comparability of the tests was unknown. 

The applicant had submitted data on efficacy and safety prior to completing the planned enrollment of 100 patients, which meant that data from approximately a third of the planned population were missing at the time of consideration.

The US Food and Drug Administration usually follows the recommendations of ODAC.

A national summit on the future of healthcare will take center stage in Washington, D.C., next month—but Congress won't be involved in this discussion. SHM's 13th annual meeting is April 8-11 at the Gaylord National Harbor Resort & Convention Center in National Harbor, Md. The four-day event is expected to draw more than 2,300 hospitalists.

"It's pretty exciting that we're coming to Washington this year with all the activity in healthcare reform," says Larry Wellikson, MD, FHM, CEO of SHM.

SHM leaders say HM10 will offer new features, including:

• Induction of the first classes of Senior Fellows in Hospital Medicine (SFHM) and Master in Hospital Medicine (MHM); 
• Two new pre-courses slated for April 8: "Essential Neurology for the Hospitalist" and "Early Career Hospitalist: Skills for Success";
• An expanded research and innovation platform that will include visiting professor Mark Zeidel, MD, chair of the Department of Medicine at Beth Israel Deaconess Medical Center in Boston; 
• A limited-seating workshop track; and
• A keynote address from Paul Levy, president and CEO of Beth Israel in Boston and a respected commentator in the arena of healthcare QI and patient safety. The speech is titled "The Hospitalist's Role in the Hospital of the Future."

 

SHM leaders say that despite the economic downturn, attendance at this year's conference is expected to significantly exceed the record crowd that trekked to Chicago last spring. "Even though there are travel-budget cuts and education-budget cuts, the one meeting that hospitalists continue to go to is SHM's annual conference," says Geri Barnes, SHM senior director of education and meetings. “That’s where they get their education and are able to network at the largest gathering of hospitalists every year."

Visit www.the-hospitalist.org for extensive meeting coverage.

A national summit on the future of healthcare will take center stage in Washington, D.C., next month—but Congress won't be involved in this discussion. SHM's 13th annual meeting is April 8-11 at the Gaylord National Harbor Resort & Convention Center in National Harbor, Md. The four-day event is expected to draw more than 2,300 hospitalists.

"It's pretty exciting that we're coming to Washington this year with all the activity in healthcare reform," says Larry Wellikson, MD, FHM, CEO of SHM.

SHM leaders say HM10 will offer new features, including:

• Induction of the first classes of Senior Fellows in Hospital Medicine (SFHM) and Master in Hospital Medicine (MHM); 
• Two new pre-courses slated for April 8: "Essential Neurology for the Hospitalist" and "Early Career Hospitalist: Skills for Success";
• An expanded research and innovation platform that will include visiting professor Mark Zeidel, MD, chair of the Department of Medicine at Beth Israel Deaconess Medical Center in Boston; 
• A limited-seating workshop track; and
• A keynote address from Paul Levy, president and CEO of Beth Israel in Boston and a respected commentator in the arena of healthcare QI and patient safety. The speech is titled "The Hospitalist's Role in the Hospital of the Future."

 

SHM leaders say that despite the economic downturn, attendance at this year's conference is expected to significantly exceed the record crowd that trekked to Chicago last spring. "Even though there are travel-budget cuts and education-budget cuts, the one meeting that hospitalists continue to go to is SHM's annual conference," says Geri Barnes, SHM senior director of education and meetings. “That’s where they get their education and are able to network at the largest gathering of hospitalists every year."

Visit www.the-hospitalist.org for extensive meeting coverage.

A national summit on the future of healthcare will take center stage in Washington, D.C., next month—but Congress won't be involved in this discussion. SHM's 13th annual meeting is April 8-11 at the Gaylord National Harbor Resort & Convention Center in National Harbor, Md. The four-day event is expected to draw more than 2,300 hospitalists.

"It's pretty exciting that we're coming to Washington this year with all the activity in healthcare reform," says Larry Wellikson, MD, FHM, CEO of SHM.

SHM leaders say HM10 will offer new features, including:

• Induction of the first classes of Senior Fellows in Hospital Medicine (SFHM) and Master in Hospital Medicine (MHM); 
• Two new pre-courses slated for April 8: "Essential Neurology for the Hospitalist" and "Early Career Hospitalist: Skills for Success";
• An expanded research and innovation platform that will include visiting professor Mark Zeidel, MD, chair of the Department of Medicine at Beth Israel Deaconess Medical Center in Boston; 
• A limited-seating workshop track; and
• A keynote address from Paul Levy, president and CEO of Beth Israel in Boston and a respected commentator in the arena of healthcare QI and patient safety. The speech is titled "The Hospitalist's Role in the Hospital of the Future."

 

SHM leaders say that despite the economic downturn, attendance at this year's conference is expected to significantly exceed the record crowd that trekked to Chicago last spring. "Even though there are travel-budget cuts and education-budget cuts, the one meeting that hospitalists continue to go to is SHM's annual conference," says Geri Barnes, SHM senior director of education and meetings. “That’s where they get their education and are able to network at the largest gathering of hospitalists every year."

Visit www.the-hospitalist.org for extensive meeting coverage.

Clinical question: Do certain patient characteristics predict increased risk for mechanical ventilation or death among patients with acute exacerbations of chronic obstructive pulmonary disease (COPD)?

Background: Hospitalizations for acute COPD exacerbations are costly and impair quality of life. A validated tool has not been developed to help physicians risk-stratify and predict outcomes for patients presenting with acute exacerbations of COPD.

Study design: Retrospective cohort.

Setting: 191 U.S. hospitals, of which 41% were academic hospitals and 76% were urban hospitals.

Synopsis: Researchers used the Cardinal Health Clinical Outcomes Research Database to analyze the hospital admissions of 88,074 patients aged 40 years and older with acute exacerbations of COPD. The research team identified risk factors that predicted in-hospital mortality (primary endpoint) and the need for mechanical ventilation (secondary endpoint).

The main risk factors were a BUN level higher than 25 mg/dL, altered mental status, and pulse >109/minute. Patients <65 were found to be at lowest risk. Patients age <65 without any of the three main risk factors had a mortality rate of 0.3%, while patients with all three main risk factors had a mortality rate of 13.8%.

Similarly, patients with two or three primary risk characteristics were more likely to undergo mechanical ventilation. Researchers proposed a risk score known as BAP-65 (BUN, altered mental status, pulse, and age), and patients were placed into risk classes 1 through 5 based on their risk factors.

Bottom line: The BAP-65 score might be useful to predict the risk of death or need for mechanical ventilation in COPD patients with acute exacerbation.

Citation: Tabak YP, Sun X, Johannes RS, Gupta V, Shorr AF. Mortality and need for mechanical ventilation in acute exacerbations of chronic obstructive pulmonary disease: development and validation of a simple risk score. Arch Intern Med. 2009;169(17):1595-1602.

Reviewed for TH eWire by Anneliese M. Schleyer, MD, MHA, Mark C. Zaros, MD, Angelena Labella, MD, Heather L. Davidson, MD, Reena K. Julka, MD, Anna S. Loge, MD, and Paul R. Sutton, MD, PhD, University of Washington Medicine Hospital and Consultative Medicine Program, Seattle

For more HM-related literature reviews, visit our Web site.

Clinical question: Do certain patient characteristics predict increased risk for mechanical ventilation or death among patients with acute exacerbations of chronic obstructive pulmonary disease (COPD)?

Background: Hospitalizations for acute COPD exacerbations are costly and impair quality of life. A validated tool has not been developed to help physicians risk-stratify and predict outcomes for patients presenting with acute exacerbations of COPD.

Study design: Retrospective cohort.

Setting: 191 U.S. hospitals, of which 41% were academic hospitals and 76% were urban hospitals.

Synopsis: Researchers used the Cardinal Health Clinical Outcomes Research Database to analyze the hospital admissions of 88,074 patients aged 40 years and older with acute exacerbations of COPD. The research team identified risk factors that predicted in-hospital mortality (primary endpoint) and the need for mechanical ventilation (secondary endpoint).

The main risk factors were a BUN level higher than 25 mg/dL, altered mental status, and pulse >109/minute. Patients <65 were found to be at lowest risk. Patients age <65 without any of the three main risk factors had a mortality rate of 0.3%, while patients with all three main risk factors had a mortality rate of 13.8%.

Similarly, patients with two or three primary risk characteristics were more likely to undergo mechanical ventilation. Researchers proposed a risk score known as BAP-65 (BUN, altered mental status, pulse, and age), and patients were placed into risk classes 1 through 5 based on their risk factors.

Bottom line: The BAP-65 score might be useful to predict the risk of death or need for mechanical ventilation in COPD patients with acute exacerbation.

Citation: Tabak YP, Sun X, Johannes RS, Gupta V, Shorr AF. Mortality and need for mechanical ventilation in acute exacerbations of chronic obstructive pulmonary disease: development and validation of a simple risk score. Arch Intern Med. 2009;169(17):1595-1602.

Reviewed for TH eWire by Anneliese M. Schleyer, MD, MHA, Mark C. Zaros, MD, Angelena Labella, MD, Heather L. Davidson, MD, Reena K. Julka, MD, Anna S. Loge, MD, and Paul R. Sutton, MD, PhD, University of Washington Medicine Hospital and Consultative Medicine Program, Seattle

For more HM-related literature reviews, visit our Web site.

Clinical question: Do certain patient characteristics predict increased risk for mechanical ventilation or death among patients with acute exacerbations of chronic obstructive pulmonary disease (COPD)?

Background: Hospitalizations for acute COPD exacerbations are costly and impair quality of life. A validated tool has not been developed to help physicians risk-stratify and predict outcomes for patients presenting with acute exacerbations of COPD.

Study design: Retrospective cohort.

Setting: 191 U.S. hospitals, of which 41% were academic hospitals and 76% were urban hospitals.

Synopsis: Researchers used the Cardinal Health Clinical Outcomes Research Database to analyze the hospital admissions of 88,074 patients aged 40 years and older with acute exacerbations of COPD. The research team identified risk factors that predicted in-hospital mortality (primary endpoint) and the need for mechanical ventilation (secondary endpoint).

The main risk factors were a BUN level higher than 25 mg/dL, altered mental status, and pulse >109/minute. Patients <65 were found to be at lowest risk. Patients age <65 without any of the three main risk factors had a mortality rate of 0.3%, while patients with all three main risk factors had a mortality rate of 13.8%.

Similarly, patients with two or three primary risk characteristics were more likely to undergo mechanical ventilation. Researchers proposed a risk score known as BAP-65 (BUN, altered mental status, pulse, and age), and patients were placed into risk classes 1 through 5 based on their risk factors.

Bottom line: The BAP-65 score might be useful to predict the risk of death or need for mechanical ventilation in COPD patients with acute exacerbation.

Citation: Tabak YP, Sun X, Johannes RS, Gupta V, Shorr AF. Mortality and need for mechanical ventilation in acute exacerbations of chronic obstructive pulmonary disease: development and validation of a simple risk score. Arch Intern Med. 2009;169(17):1595-1602.

Reviewed for TH eWire by Anneliese M. Schleyer, MD, MHA, Mark C. Zaros, MD, Angelena Labella, MD, Heather L. Davidson, MD, Reena K. Julka, MD, Anna S. Loge, MD, and Paul R. Sutton, MD, PhD, University of Washington Medicine Hospital and Consultative Medicine Program, Seattle

For more HM-related literature reviews, visit our Web site.

A supplement to Skin & Allergy News. This supplement was supported by Ferndale Laboratories Inc.

• Impact of Pruritus on Quality of Life

• Screening for Psychogenic Causes

• Palpation

• Medication History

• Xerosis (dry skin)

• Cutaneous Infestations

• Systemic Diseases

• Malignancy

• Neuropathic Pruritus

• Atypical Causes

• Diagnostic Workup

• Managing Pruritus

• Summary

Faculty/Faculty Disclosure

Joseph B. Bikowski, MD
Clinical Assistant Professor
Dermatology
Ohio State University
Columbus, OH
Director
Bikowski Skin Care Center
Sewickley, PA
Dr. Bikowski has received honoraria from Allergan, Inc., Coria Laboratories, Ltd., Galderma Laboratories, L.P., Intendis GmbH, Medicis Pharmaceutical Corporation, OrthoDermatologics, Quinnova Pharmaceuticals, Inc., Stiefel Laboratories, Inc., and Warner Chilcott; served on advisory boards for Coria, Galderma, Intendis, Ranbaxy Pharmaceuticals Inc., Stiefel, and Warner Chilcott; has been a speaker for Allergan, Coria, Galderma, Intendis, Promius Pharma, LLC, Ranbaxy, and Stiefel; has a consulting agreement with Allergan, Coria, Galderma, Intendis, Medicis, Promius, OrthoDermatologics, and Stiefel; and is a stockholder for Quinnova.

To view the supplement, click the image above.

A supplement to Skin & Allergy News. This supplement was supported by Ferndale Laboratories Inc.

• Impact of Pruritus on Quality of Life

• Screening for Psychogenic Causes

• Palpation

• Medication History

• Xerosis (dry skin)

• Cutaneous Infestations

• Systemic Diseases

• Malignancy

• Neuropathic Pruritus

• Atypical Causes

• Diagnostic Workup

• Managing Pruritus

• Summary

Faculty/Faculty Disclosure

Joseph B. Bikowski, MD
Clinical Assistant Professor
Dermatology
Ohio State University
Columbus, OH
Director
Bikowski Skin Care Center
Sewickley, PA
Dr. Bikowski has received honoraria from Allergan, Inc., Coria Laboratories, Ltd., Galderma Laboratories, L.P., Intendis GmbH, Medicis Pharmaceutical Corporation, OrthoDermatologics, Quinnova Pharmaceuticals, Inc., Stiefel Laboratories, Inc., and Warner Chilcott; served on advisory boards for Coria, Galderma, Intendis, Ranbaxy Pharmaceuticals Inc., Stiefel, and Warner Chilcott; has been a speaker for Allergan, Coria, Galderma, Intendis, Promius Pharma, LLC, Ranbaxy, and Stiefel; has a consulting agreement with Allergan, Coria, Galderma, Intendis, Medicis, Promius, OrthoDermatologics, and Stiefel; and is a stockholder for Quinnova.

To view the supplement, click the image above.

A supplement to Skin & Allergy News. This supplement was supported by Ferndale Laboratories Inc.

• Impact of Pruritus on Quality of Life

• Screening for Psychogenic Causes

• Palpation

• Medication History

• Xerosis (dry skin)

• Cutaneous Infestations

• Systemic Diseases

• Malignancy

• Neuropathic Pruritus

• Atypical Causes

• Diagnostic Workup

• Managing Pruritus

• Summary

Faculty/Faculty Disclosure

Joseph B. Bikowski, MD
Clinical Assistant Professor
Dermatology
Ohio State University
Columbus, OH
Director
Bikowski Skin Care Center
Sewickley, PA
Dr. Bikowski has received honoraria from Allergan, Inc., Coria Laboratories, Ltd., Galderma Laboratories, L.P., Intendis GmbH, Medicis Pharmaceutical Corporation, OrthoDermatologics, Quinnova Pharmaceuticals, Inc., Stiefel Laboratories, Inc., and Warner Chilcott; served on advisory boards for Coria, Galderma, Intendis, Ranbaxy Pharmaceuticals Inc., Stiefel, and Warner Chilcott; has been a speaker for Allergan, Coria, Galderma, Intendis, Promius Pharma, LLC, Ranbaxy, and Stiefel; has a consulting agreement with Allergan, Coria, Galderma, Intendis, Medicis, Promius, OrthoDermatologics, and Stiefel; and is a stockholder for Quinnova.

To view the supplement, click the image above.