Alicia Ault

Hospitals that have been lagging on prevention of venous thromboembolism (VTE) might find themselves increasingly at risk for lower reimbursement or downgrades in quality ratings, but a new Society of Hospital Medicine (SHM) program may help some facilities start measuring up.

The Joint Commission is close to implementing a set of VTE measures looking at whether prophylaxis is in place within 24 hours of admission. The Centers for Medicare and Medicaid Services already refuses to pay for any VTE incurred as a complication of hip or knee replacement.

But these sticks have not been huge motivating factors for facilities when it comes to VTE, said Dr. Gregory A. Maynard, chief of the division of hospital medicine at the University of California, San Diego.

The biggest hurdle still seems to be the lack of physician awareness about which populations are vulnerable, said Dr. Maynard, who has been involved in collaboratives backed by the Institute for Healthcare Improvement (IHI) and the Agency for Healthcare Research and Quality (AHRQ). That’s partly because while these events are common, an individual physician might not have many VTEs in his or her own practice, he said.

Dr. Maynard has been a key architect of the SHM’s efforts to help hospitalists improve VTE prevention. The VTE Prevention Collaborative, which launches in September, is supported in part by Sanofi-Aventis U.S. Participants will have access to a toolkit, resources, and individualized mentoring and support, as part of the program developed by Dr. Maynard and Dr. Jason Stein, director of the Clinical Research Program for the section of hospital medicine at Emory University, Atlanta.

According to Dr. Maynard, nearly every hospitalized patient is at risk for VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Most patients have four to six risk factors, he said. The three big risk categories are stasis (related to age greater than 40 years, immobility, anesthesia, obesity, stroke, or heart failure), hypercoagulability (associated with cancer, sepsis, smoking, and pregnancy), and endothelial damage (surgery, central lines, trauma, or prior VTE).

PE is the cause of death in more than 100,000 hospitalized patients each year, and a contributing factor in the death of 100,000 additional inpatients annually, the SHM estimates.

And yet, studies have found that only about 30%-50% of inpatients are given appropriate prophylaxis – this, despite the availability of guidelines and protocols that make the process more efficient, and of effective pharmacologic agents. The ENDORSE trial, for instance, found that among 70,000 inpatients, only 59% of surgical patients and 40% of medical patients were given appropriate prophylaxis (Lancet 2008;371:387-94).

At UCSD, Dr. Maynard and Dr. Stein (who was previously at UCSD) leveraged an AHRQ grant to build a protocol for VTE prevention. It was designed with the aim that it would be universally applicable to any and all hospitalist programs, he said. The protocol increased prophylaxis rates from 50% of patients in 2005 to 98% in 2007 at UCSD (J. Hospital Medicine 2010;5:10-8).

Essentially, it was a simple model that stratified patients into low-, moderate- and high-risk categories. Almost no patients fall into the low-risk category; most are classified as moderate risk, Dr. Maynard said.

The risk assessment can be completed by a physician in seconds and can be done either on paper or as part of an electronic health record. Once determined, the risk level is linked to a menu of prophylaxis options, either in chart form, on paper, or electronically. Importantly, these options very specifically say which pharmacologic agents, and at what dose, are most appropriate for the patient, given their risk and taking into account other factors. The protocol also recommends that mechanical prophylaxis only be used as an adjunct, not as a first-line therapy.

To ensure the protocol was followed, Dr. Maynard and Dr. Stein created a method they dubbed “Measure-vention” – that is, the prophylaxis is monitored on a real-time basis and the intervention is done in real time, as well. The program also automatically collects data that can be used for quality improvement.

If a patient is indicated to need prophylaxis but is not identified as having received it on the medication record, the nurse or pharmacist receives an automated note. They in turn notify the physician via text message or page. About half the time, the physician changes the order, and the rest of the time, there is a valid reason for no prevention – or the physician simply does not want to be told what to do, Dr. Maynard observed.

At Emory, the Measure-vention strategy was adopted in 2009 as the final piece of the VTE prevention program, which started in 2006. Patients are color coded on a “dashboard” that is refreshed hourly. Red means no prophylaxis ordered, yellow means mechanical only has been ordered, and green means the patient is receiving a pharmacologic agent.

Six months after it was implemented, the dashboard helped pull prophylaxis rates above 90% in the 15 inpatient units at Emory University Hospital that were using the strategy, triple the rate before the dashboard, Dr. Stein said.

A year after starting the real-time monitoring in 2008, one 20-bed intensive care unit had a 75% reduction in potentially preventable hospital-acquired VTE, “attributable to a similarly significant rise in VTE prophylaxis from 73% to 94%,” he said.

There were nine fewer clots in that unit, which “represents real morbidity prevention and real cost savings, and very possibly represents preventable deaths from pulmonary embolism,” he said.

The implementation of the dashboard – which is now available to nurses and physicians at five Emory hospitals – has created new channels of communication between clinical and information services and contributed to an increased sense of pride in frontline nurses and clinicians, Dr. Stein observed.

“Ultimately, we’ve developed a new mindset for how performance is measured and improved at Emory,” he said.

Emory was recognized at the SHM annual meeting in April with an Excellence in Teamwork in Quality Improvement Award.

SHM hopes that other facilities can replicate the Emory experience. It has enrolled 80 facilities in the Prevention Collaborative.

Dr. Maynard said that awareness may also increase throughout the Department of Veterans Affairs, which initially had six hospitals take part in a pilot that he and Dr. Stein helped launch. Now, “many, many sites in the VA” are using the VTE prevention toolkit, he said.

The IHI and AHRQ also have enrolled dozens of hospitals in collaborations to reduce VTE.

VTE prophylaxis has been “suboptimal for a long time,” said Dr. Maynard. But, “it’s getting there.”

Hospitals that have been lagging on prevention of venous thromboembolism (VTE) might find themselves increasingly at risk for lower reimbursement or downgrades in quality ratings, but a new Society of Hospital Medicine (SHM) program may help some facilities start measuring up.

The Joint Commission is close to implementing a set of VTE measures looking at whether prophylaxis is in place within 24 hours of admission. The Centers for Medicare and Medicaid Services already refuses to pay for any VTE incurred as a complication of hip or knee replacement.

But these sticks have not been huge motivating factors for facilities when it comes to VTE, said Dr. Gregory A. Maynard, chief of the division of hospital medicine at the University of California, San Diego.

The biggest hurdle still seems to be the lack of physician awareness about which populations are vulnerable, said Dr. Maynard, who has been involved in collaboratives backed by the Institute for Healthcare Improvement (IHI) and the Agency for Healthcare Research and Quality (AHRQ). That’s partly because while these events are common, an individual physician might not have many VTEs in his or her own practice, he said.

Dr. Maynard has been a key architect of the SHM’s efforts to help hospitalists improve VTE prevention. The VTE Prevention Collaborative, which launches in September, is supported in part by Sanofi-Aventis U.S. Participants will have access to a toolkit, resources, and individualized mentoring and support, as part of the program developed by Dr. Maynard and Dr. Jason Stein, director of the Clinical Research Program for the section of hospital medicine at Emory University, Atlanta.

According to Dr. Maynard, nearly every hospitalized patient is at risk for VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Most patients have four to six risk factors, he said. The three big risk categories are stasis (related to age greater than 40 years, immobility, anesthesia, obesity, stroke, or heart failure), hypercoagulability (associated with cancer, sepsis, smoking, and pregnancy), and endothelial damage (surgery, central lines, trauma, or prior VTE).

PE is the cause of death in more than 100,000 hospitalized patients each year, and a contributing factor in the death of 100,000 additional inpatients annually, the SHM estimates.

And yet, studies have found that only about 30%-50% of inpatients are given appropriate prophylaxis – this, despite the availability of guidelines and protocols that make the process more efficient, and of effective pharmacologic agents. The ENDORSE trial, for instance, found that among 70,000 inpatients, only 59% of surgical patients and 40% of medical patients were given appropriate prophylaxis (Lancet 2008;371:387-94).

At UCSD, Dr. Maynard and Dr. Stein (who was previously at UCSD) leveraged an AHRQ grant to build a protocol for VTE prevention. It was designed with the aim that it would be universally applicable to any and all hospitalist programs, he said. The protocol increased prophylaxis rates from 50% of patients in 2005 to 98% in 2007 at UCSD (J. Hospital Medicine 2010;5:10-8).

Essentially, it was a simple model that stratified patients into low-, moderate- and high-risk categories. Almost no patients fall into the low-risk category; most are classified as moderate risk, Dr. Maynard said.

The risk assessment can be completed by a physician in seconds and can be done either on paper or as part of an electronic health record. Once determined, the risk level is linked to a menu of prophylaxis options, either in chart form, on paper, or electronically. Importantly, these options very specifically say which pharmacologic agents, and at what dose, are most appropriate for the patient, given their risk and taking into account other factors. The protocol also recommends that mechanical prophylaxis only be used as an adjunct, not as a first-line therapy.

To ensure the protocol was followed, Dr. Maynard and Dr. Stein created a method they dubbed “Measure-vention” – that is, the prophylaxis is monitored on a real-time basis and the intervention is done in real time, as well. The program also automatically collects data that can be used for quality improvement.

If a patient is indicated to need prophylaxis but is not identified as having received it on the medication record, the nurse or pharmacist receives an automated note. They in turn notify the physician via text message or page. About half the time, the physician changes the order, and the rest of the time, there is a valid reason for no prevention – or the physician simply does not want to be told what to do, Dr. Maynard observed.

At Emory, the Measure-vention strategy was adopted in 2009 as the final piece of the VTE prevention program, which started in 2006. Patients are color coded on a “dashboard” that is refreshed hourly. Red means no prophylaxis ordered, yellow means mechanical only has been ordered, and green means the patient is receiving a pharmacologic agent.

Six months after it was implemented, the dashboard helped pull prophylaxis rates above 90% in the 15 inpatient units at Emory University Hospital that were using the strategy, triple the rate before the dashboard, Dr. Stein said.

A year after starting the real-time monitoring in 2008, one 20-bed intensive care unit had a 75% reduction in potentially preventable hospital-acquired VTE, “attributable to a similarly significant rise in VTE prophylaxis from 73% to 94%,” he said.

There were nine fewer clots in that unit, which “represents real morbidity prevention and real cost savings, and very possibly represents preventable deaths from pulmonary embolism,” he said.

The implementation of the dashboard – which is now available to nurses and physicians at five Emory hospitals – has created new channels of communication between clinical and information services and contributed to an increased sense of pride in frontline nurses and clinicians, Dr. Stein observed.

“Ultimately, we’ve developed a new mindset for how performance is measured and improved at Emory,” he said.

Emory was recognized at the SHM annual meeting in April with an Excellence in Teamwork in Quality Improvement Award.

SHM hopes that other facilities can replicate the Emory experience. It has enrolled 80 facilities in the Prevention Collaborative.

Dr. Maynard said that awareness may also increase throughout the Department of Veterans Affairs, which initially had six hospitals take part in a pilot that he and Dr. Stein helped launch. Now, “many, many sites in the VA” are using the VTE prevention toolkit, he said.

The IHI and AHRQ also have enrolled dozens of hospitals in collaborations to reduce VTE.

VTE prophylaxis has been “suboptimal for a long time,” said Dr. Maynard. But, “it’s getting there.”

Hospitals that have been lagging on prevention of venous thromboembolism (VTE) might find themselves increasingly at risk for lower reimbursement or downgrades in quality ratings, but a new Society of Hospital Medicine (SHM) program may help some facilities start measuring up.

The Joint Commission is close to implementing a set of VTE measures looking at whether prophylaxis is in place within 24 hours of admission. The Centers for Medicare and Medicaid Services already refuses to pay for any VTE incurred as a complication of hip or knee replacement.

But these sticks have not been huge motivating factors for facilities when it comes to VTE, said Dr. Gregory A. Maynard, chief of the division of hospital medicine at the University of California, San Diego.

The biggest hurdle still seems to be the lack of physician awareness about which populations are vulnerable, said Dr. Maynard, who has been involved in collaboratives backed by the Institute for Healthcare Improvement (IHI) and the Agency for Healthcare Research and Quality (AHRQ). That’s partly because while these events are common, an individual physician might not have many VTEs in his or her own practice, he said.

Dr. Maynard has been a key architect of the SHM’s efforts to help hospitalists improve VTE prevention. The VTE Prevention Collaborative, which launches in September, is supported in part by Sanofi-Aventis U.S. Participants will have access to a toolkit, resources, and individualized mentoring and support, as part of the program developed by Dr. Maynard and Dr. Jason Stein, director of the Clinical Research Program for the section of hospital medicine at Emory University, Atlanta.

According to Dr. Maynard, nearly every hospitalized patient is at risk for VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Most patients have four to six risk factors, he said. The three big risk categories are stasis (related to age greater than 40 years, immobility, anesthesia, obesity, stroke, or heart failure), hypercoagulability (associated with cancer, sepsis, smoking, and pregnancy), and endothelial damage (surgery, central lines, trauma, or prior VTE).

PE is the cause of death in more than 100,000 hospitalized patients each year, and a contributing factor in the death of 100,000 additional inpatients annually, the SHM estimates.

And yet, studies have found that only about 30%-50% of inpatients are given appropriate prophylaxis – this, despite the availability of guidelines and protocols that make the process more efficient, and of effective pharmacologic agents. The ENDORSE trial, for instance, found that among 70,000 inpatients, only 59% of surgical patients and 40% of medical patients were given appropriate prophylaxis (Lancet 2008;371:387-94).

At UCSD, Dr. Maynard and Dr. Stein (who was previously at UCSD) leveraged an AHRQ grant to build a protocol for VTE prevention. It was designed with the aim that it would be universally applicable to any and all hospitalist programs, he said. The protocol increased prophylaxis rates from 50% of patients in 2005 to 98% in 2007 at UCSD (J. Hospital Medicine 2010;5:10-8).

Essentially, it was a simple model that stratified patients into low-, moderate- and high-risk categories. Almost no patients fall into the low-risk category; most are classified as moderate risk, Dr. Maynard said.

The risk assessment can be completed by a physician in seconds and can be done either on paper or as part of an electronic health record. Once determined, the risk level is linked to a menu of prophylaxis options, either in chart form, on paper, or electronically. Importantly, these options very specifically say which pharmacologic agents, and at what dose, are most appropriate for the patient, given their risk and taking into account other factors. The protocol also recommends that mechanical prophylaxis only be used as an adjunct, not as a first-line therapy.

To ensure the protocol was followed, Dr. Maynard and Dr. Stein created a method they dubbed “Measure-vention” – that is, the prophylaxis is monitored on a real-time basis and the intervention is done in real time, as well. The program also automatically collects data that can be used for quality improvement.

If a patient is indicated to need prophylaxis but is not identified as having received it on the medication record, the nurse or pharmacist receives an automated note. They in turn notify the physician via text message or page. About half the time, the physician changes the order, and the rest of the time, there is a valid reason for no prevention – or the physician simply does not want to be told what to do, Dr. Maynard observed.

At Emory, the Measure-vention strategy was adopted in 2009 as the final piece of the VTE prevention program, which started in 2006. Patients are color coded on a “dashboard” that is refreshed hourly. Red means no prophylaxis ordered, yellow means mechanical only has been ordered, and green means the patient is receiving a pharmacologic agent.

Six months after it was implemented, the dashboard helped pull prophylaxis rates above 90% in the 15 inpatient units at Emory University Hospital that were using the strategy, triple the rate before the dashboard, Dr. Stein said.

A year after starting the real-time monitoring in 2008, one 20-bed intensive care unit had a 75% reduction in potentially preventable hospital-acquired VTE, “attributable to a similarly significant rise in VTE prophylaxis from 73% to 94%,” he said.

There were nine fewer clots in that unit, which “represents real morbidity prevention and real cost savings, and very possibly represents preventable deaths from pulmonary embolism,” he said.

The implementation of the dashboard – which is now available to nurses and physicians at five Emory hospitals – has created new channels of communication between clinical and information services and contributed to an increased sense of pride in frontline nurses and clinicians, Dr. Stein observed.

“Ultimately, we’ve developed a new mindset for how performance is measured and improved at Emory,” he said.

Emory was recognized at the SHM annual meeting in April with an Excellence in Teamwork in Quality Improvement Award.

SHM hopes that other facilities can replicate the Emory experience. It has enrolled 80 facilities in the Prevention Collaborative.

Dr. Maynard said that awareness may also increase throughout the Department of Veterans Affairs, which initially had six hospitals take part in a pilot that he and Dr. Stein helped launch. Now, “many, many sites in the VA” are using the VTE prevention toolkit, he said.

The IHI and AHRQ also have enrolled dozens of hospitals in collaborations to reduce VTE.

VTE prophylaxis has been “suboptimal for a long time,” said Dr. Maynard. But, “it’s getting there.”

The Food and Drug Administration is warning physicians and patients that the intravenous antibiotic daptomycin has been associated with an increased risk of eosinophilic pneumonia.

Daptomycin (Cubicin), a once-daily drug, is approved for complicated skin and skin structure infections caused by Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant strains) and for treatment of S. aureus bloodstream infections, including infective endocarditis.

The FDA said a review of published case reports and post-marketing adverse event reports turned up seven cases of eosinophilic pneumonia between 2004 and 2010 that seemed to be associated with use of daptomycin.

The agency is asking daptomycin manufacturer Cubist Pharmaceuticals, based in Lexington, Mass., to add new warnings to the drug’s label about the increased potential for developing eosinophilic pneumonia.  The condition is rare but can lead to progressive respiratory failure and death if not recognized and treated, according to the FDA.

Symptoms to watch for include fever, cough, shortness of breath or difficulty breathing.  The FDA urged patients taking daptomycin who have those symptoms to immediately talk with their physician

The Food and Drug Administration is warning physicians and patients that the intravenous antibiotic daptomycin has been associated with an increased risk of eosinophilic pneumonia.

Daptomycin (Cubicin), a once-daily drug, is approved for complicated skin and skin structure infections caused by Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant strains) and for treatment of S. aureus bloodstream infections, including infective endocarditis.

The FDA said a review of published case reports and post-marketing adverse event reports turned up seven cases of eosinophilic pneumonia between 2004 and 2010 that seemed to be associated with use of daptomycin.

The agency is asking daptomycin manufacturer Cubist Pharmaceuticals, based in Lexington, Mass., to add new warnings to the drug’s label about the increased potential for developing eosinophilic pneumonia.  The condition is rare but can lead to progressive respiratory failure and death if not recognized and treated, according to the FDA.

Symptoms to watch for include fever, cough, shortness of breath or difficulty breathing.  The FDA urged patients taking daptomycin who have those symptoms to immediately talk with their physician

The Food and Drug Administration is warning physicians and patients that the intravenous antibiotic daptomycin has been associated with an increased risk of eosinophilic pneumonia.

Daptomycin (Cubicin), a once-daily drug, is approved for complicated skin and skin structure infections caused by Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant strains) and for treatment of S. aureus bloodstream infections, including infective endocarditis.

The FDA said a review of published case reports and post-marketing adverse event reports turned up seven cases of eosinophilic pneumonia between 2004 and 2010 that seemed to be associated with use of daptomycin.

The agency is asking daptomycin manufacturer Cubist Pharmaceuticals, based in Lexington, Mass., to add new warnings to the drug’s label about the increased potential for developing eosinophilic pneumonia.  The condition is rare but can lead to progressive respiratory failure and death if not recognized and treated, according to the FDA.

Symptoms to watch for include fever, cough, shortness of breath or difficulty breathing.  The FDA urged patients taking daptomycin who have those symptoms to immediately talk with their physician

COLLEGE PARK, Md. –The Food and Drug Administration’s Cardiovascular and Renal Drugs Advisory Committee voted 7-1 to recommend approval of the platelet inhibitor ticagrelor to treat non–ST elevation myocardial infarction and ST-elevation myocardial infarction in patients intended to receive primary coronary intervention or who would be managed medically.

The panel did not directly address other indications being sought by ticagrelor’s maker, AstraZeneca, including use in unstable angina and after a coronary artery bypass graft (CABG). But in an interview after the meeting, FDA official Robert Temple said that the panel had basically covered all the populations that would be considered under the rubric of acute coronary syndrome. As the agency weighs approval, it will decide whether to grant specific indications, said Dr. Temple, who is head of the office reviewing ticagrelor (Brilinta).

According to the company, ticagrelor is the first reversibly binding oral adenosine diphosphate receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP.

FDA committee member Mori J. Krantz was the lone panelist who voted against approval. He said that he was concerned about data from the pivotal PLATO (A Study of Platelet Inhibition and Patient Outcomes) trial showing that patients in the United States did not fare as well as those in overseas sites. “That it went in the opposite direction is a little discomforting,” said Dr. Krantz of the University of Colorado, Denver.

Committee chairman Sanjay Kaul voted in favor of approval, but said, “I am concerned, however, about the data going in the wrong direction in the United States.” He urged the FDA to require a post-approval study that would include a substantial number of Americans and look in particular at unstable angina.

The FDA generally follows its panels’ advice.

The PLATO data was first presented at the European Society of Cardiology in 2009 and published online in the New England Journal of Medicine in August 2009. The randomized, double-blind trial compared ticagrelor to clopidogrel in all-comer ACS patients. The study enrolled 18,624 patients at 862 centers in 43 countries.

AstraZeneca said that PLATO proved that ticagrelor was superior to clopidogrel, with a 16% reduction in relative risk for the primary composite end point of cardiovascular death, myocardial infarction, or stroke. The company claimed there was no difference in major bleeding as defined by the trial, but acknowledged that there was a slightly higher number of patients with intracranial hemorrhage, including fatal hemorrhage.

The FDA reviewers said that they also found a higher rate of bleeding after CABG.

But the main concern – and the primary reason for the panel meeting – was why there were more cardiovascular events in Americans. AstraZeneca said that a post hoc analysis determined that Americans were taking higher doses of aspirin, which led to more heart attacks, strokes, and deaths.

After lengthy debate, the committee said the difference could not be attributed to chance alone or to the aspirin dosages. Differences in clinical practice in the United States were the more likely explanation, said a number of panelists.

Members of FDA advisory panels have been cleared of conflicts related to the topic under discussion.

The agency is due to make a decision on the application for approval by Sept. 18.

COLLEGE PARK, Md. –The Food and Drug Administration’s Cardiovascular and Renal Drugs Advisory Committee voted 7-1 to recommend approval of the platelet inhibitor ticagrelor to treat non–ST elevation myocardial infarction and ST-elevation myocardial infarction in patients intended to receive primary coronary intervention or who would be managed medically.

The panel did not directly address other indications being sought by ticagrelor’s maker, AstraZeneca, including use in unstable angina and after a coronary artery bypass graft (CABG). But in an interview after the meeting, FDA official Robert Temple said that the panel had basically covered all the populations that would be considered under the rubric of acute coronary syndrome. As the agency weighs approval, it will decide whether to grant specific indications, said Dr. Temple, who is head of the office reviewing ticagrelor (Brilinta).

According to the company, ticagrelor is the first reversibly binding oral adenosine diphosphate receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP.

FDA committee member Mori J. Krantz was the lone panelist who voted against approval. He said that he was concerned about data from the pivotal PLATO (A Study of Platelet Inhibition and Patient Outcomes) trial showing that patients in the United States did not fare as well as those in overseas sites. “That it went in the opposite direction is a little discomforting,” said Dr. Krantz of the University of Colorado, Denver.

Committee chairman Sanjay Kaul voted in favor of approval, but said, “I am concerned, however, about the data going in the wrong direction in the United States.” He urged the FDA to require a post-approval study that would include a substantial number of Americans and look in particular at unstable angina.

The FDA generally follows its panels’ advice.

The PLATO data was first presented at the European Society of Cardiology in 2009 and published online in the New England Journal of Medicine in August 2009. The randomized, double-blind trial compared ticagrelor to clopidogrel in all-comer ACS patients. The study enrolled 18,624 patients at 862 centers in 43 countries.

AstraZeneca said that PLATO proved that ticagrelor was superior to clopidogrel, with a 16% reduction in relative risk for the primary composite end point of cardiovascular death, myocardial infarction, or stroke. The company claimed there was no difference in major bleeding as defined by the trial, but acknowledged that there was a slightly higher number of patients with intracranial hemorrhage, including fatal hemorrhage.

The FDA reviewers said that they also found a higher rate of bleeding after CABG.

But the main concern – and the primary reason for the panel meeting – was why there were more cardiovascular events in Americans. AstraZeneca said that a post hoc analysis determined that Americans were taking higher doses of aspirin, which led to more heart attacks, strokes, and deaths.

After lengthy debate, the committee said the difference could not be attributed to chance alone or to the aspirin dosages. Differences in clinical practice in the United States were the more likely explanation, said a number of panelists.

Members of FDA advisory panels have been cleared of conflicts related to the topic under discussion.

The agency is due to make a decision on the application for approval by Sept. 18.

COLLEGE PARK, Md. –The Food and Drug Administration’s Cardiovascular and Renal Drugs Advisory Committee voted 7-1 to recommend approval of the platelet inhibitor ticagrelor to treat non–ST elevation myocardial infarction and ST-elevation myocardial infarction in patients intended to receive primary coronary intervention or who would be managed medically.

The panel did not directly address other indications being sought by ticagrelor’s maker, AstraZeneca, including use in unstable angina and after a coronary artery bypass graft (CABG). But in an interview after the meeting, FDA official Robert Temple said that the panel had basically covered all the populations that would be considered under the rubric of acute coronary syndrome. As the agency weighs approval, it will decide whether to grant specific indications, said Dr. Temple, who is head of the office reviewing ticagrelor (Brilinta).

According to the company, ticagrelor is the first reversibly binding oral adenosine diphosphate receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP.

FDA committee member Mori J. Krantz was the lone panelist who voted against approval. He said that he was concerned about data from the pivotal PLATO (A Study of Platelet Inhibition and Patient Outcomes) trial showing that patients in the United States did not fare as well as those in overseas sites. “That it went in the opposite direction is a little discomforting,” said Dr. Krantz of the University of Colorado, Denver.

Committee chairman Sanjay Kaul voted in favor of approval, but said, “I am concerned, however, about the data going in the wrong direction in the United States.” He urged the FDA to require a post-approval study that would include a substantial number of Americans and look in particular at unstable angina.

The FDA generally follows its panels’ advice.

The PLATO data was first presented at the European Society of Cardiology in 2009 and published online in the New England Journal of Medicine in August 2009. The randomized, double-blind trial compared ticagrelor to clopidogrel in all-comer ACS patients. The study enrolled 18,624 patients at 862 centers in 43 countries.

AstraZeneca said that PLATO proved that ticagrelor was superior to clopidogrel, with a 16% reduction in relative risk for the primary composite end point of cardiovascular death, myocardial infarction, or stroke. The company claimed there was no difference in major bleeding as defined by the trial, but acknowledged that there was a slightly higher number of patients with intracranial hemorrhage, including fatal hemorrhage.

The FDA reviewers said that they also found a higher rate of bleeding after CABG.

But the main concern – and the primary reason for the panel meeting – was why there were more cardiovascular events in Americans. AstraZeneca said that a post hoc analysis determined that Americans were taking higher doses of aspirin, which led to more heart attacks, strokes, and deaths.

After lengthy debate, the committee said the difference could not be attributed to chance alone or to the aspirin dosages. Differences in clinical practice in the United States were the more likely explanation, said a number of panelists.

Members of FDA advisory panels have been cleared of conflicts related to the topic under discussion.

The agency is due to make a decision on the application for approval by Sept. 18.

The Food and Drug Administration is warning physicians and patients that the intravenous antibiotic daptomycin has been associated with an increased risk of eosinophilic pneumonia.

Daptomycin (Cubicin), a once-daily drug, is approved for complicated skin and skin structure infections caused by Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant strains) and for treatment of S. aureus bloodstream infections, including infective endocarditis.

The FDA said a review of published case reports and post-marketing adverse event reports turned up seven cases of eosinophilic pneumonia between 2004 and 2010 that seemed to be associated with use of daptomycin.

The agency is asking daptomycin manufacturer Cubist Pharmaceuticals, based in Lexington, Mass., to add new warnings to the drug’s label about the increased potential for developing eosinophilic pneumonia. The condition is rare but can lead to progressive respiratory failure and death if not recognized and treated, according to the FDA.

Symptoms to watch for include fever, cough, shortness of breath or difficulty breathing. The FDA urged patients taking daptomycin who have those symptoms to immediately talk with their physician.

The Food and Drug Administration is warning physicians and patients that the intravenous antibiotic daptomycin has been associated with an increased risk of eosinophilic pneumonia.

Daptomycin (Cubicin), a once-daily drug, is approved for complicated skin and skin structure infections caused by Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant strains) and for treatment of S. aureus bloodstream infections, including infective endocarditis.

The FDA said a review of published case reports and post-marketing adverse event reports turned up seven cases of eosinophilic pneumonia between 2004 and 2010 that seemed to be associated with use of daptomycin.

The agency is asking daptomycin manufacturer Cubist Pharmaceuticals, based in Lexington, Mass., to add new warnings to the drug’s label about the increased potential for developing eosinophilic pneumonia. The condition is rare but can lead to progressive respiratory failure and death if not recognized and treated, according to the FDA.

Symptoms to watch for include fever, cough, shortness of breath or difficulty breathing. The FDA urged patients taking daptomycin who have those symptoms to immediately talk with their physician.

The Food and Drug Administration is warning physicians and patients that the intravenous antibiotic daptomycin has been associated with an increased risk of eosinophilic pneumonia.

Daptomycin (Cubicin), a once-daily drug, is approved for complicated skin and skin structure infections caused by Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant strains) and for treatment of S. aureus bloodstream infections, including infective endocarditis.

The FDA said a review of published case reports and post-marketing adverse event reports turned up seven cases of eosinophilic pneumonia between 2004 and 2010 that seemed to be associated with use of daptomycin.

The agency is asking daptomycin manufacturer Cubist Pharmaceuticals, based in Lexington, Mass., to add new warnings to the drug’s label about the increased potential for developing eosinophilic pneumonia. The condition is rare but can lead to progressive respiratory failure and death if not recognized and treated, according to the FDA.

Symptoms to watch for include fever, cough, shortness of breath or difficulty breathing. The FDA urged patients taking daptomycin who have those symptoms to immediately talk with their physician.

The Accreditation Council for Graduate Medical Education has revisited its standards for resident duty hours and determined that some modifications should be made, mostly for first-year residents. All other residents should still be subject to an 80-hour work week and up to 24 hours of continuous duty, according to an article published online in the New England Journal of Medicine.

The 16-member ACGME task force that wrote the standards will review public comments and make any modifications considered necessary before July 2011, when the new standards will go into effect.

The American College of Surgeons Task Force on Resident Duty Hours has analyzed the recommendations and submitted its comments to the ACGME, said Dr. L.D. Britt, chairman of the task force and chairman of the Dept. of Surgery at the Eastern Virginia Medical School, Norfolk, Va. The 34-member task force represented a variety of organizations and specialties. Dr. Britt said that the task force would discuss its comments after the ACGME had a chance to review them.

The original ACGME standards, established in 2003, have been the subject of much consternation in the medical community, with opinions differing over whether they have been too restrictive or too loose to properly protect patients and ensure a good quality of life for residents.

According to the latest report, written by Dr. Thomas J. Nasca, Dr. Susan H. Day, and Dr. E. Stephen Amis Jr. on behalf of the ACGME task force, the 2003 standards had the following three “problematic” elements, as identified by the educational community and the public:

▸ The limits on duty hours may have created a shift mentality among residents, which tends to conflict with the duty to serve patients.

▸ Many academic programs began focusing on meeting the duty hour restrictions, perhaps at the expense of education.

▸ The 80-hour work week, with up to 24 hours of continuous duty, was seen by many as compromising patient safety.

In 2008, the Institute of Medicine took a hard look at the ACGME standards and, among other things, recommended that no residents should exceed 16 hours of continuous duty.

The ACGME convened the task force to consider the IOM recommendations. One of the biggest challenges, according to the authors, was to reconcile the IOM's suggestion for an across-the-board restriction on duty hours with the continuing plea from academic programs that duty hours needed to be tailored to each specialty (N. Engl. J. Med. 2010 [doi:10.1056/NEJMsb1005800]).

For surgery, in particular, it would be difficult—and contrary to learning—to have a resident leave in the midst of a procedure because his or her duty hours had been reached.

The ACGME panel also had to weigh whether there was sufficient evidence to show that working more than 16 hours or up to 30 hours continuously led to more medical errors, as has been suggested by many critics of the duty hour standards.

According to the ACGME panel, the data thus far indicate only that first-year residents are more prone to mistakes as a result of sleep deprivation. Therefore, the task force urged a new paradigm for the first year of residency, whereby residents cannot be on duty for longer than 16 hours continuously and should have 10 hours off and 8 hours free of duty between their scheduled duty periods. First-year residents are not allowed to moonlight, and they must have direct, in-house, attending-level supervision.

All residents are allowed to work up to an additional 4 hours to facilitate patient handoffs—an area of concern for patient safety.

The panel decided not to tailor duty hours to specialties “because studies have not shown that the safety effect of current standards varies with specialty,” said the authors.

The IOM had also criticized the ACGME for not properly enforcing the duty hours. The task force said that enforcement is an “inherent” challenge, partly because there are some 9,000 accredited programs.

However, the ACGME is now undertaking annual site visits and analyzing whether institutions can comply. Eventually, the organization will give each institution a report on its compliance status and recommendations for resolving problems. The reports will be made available to the public, said the authors.

Wake Up Doctor, a coalition of public interest and patient safety groups that has been pushing the ACGME to further restrict resident hours, said that the new standards don't go far enough. The group gave the ACGME an “F” for failing to comply with the IOM recommendation that continuous duty be restricted to 16 hours for all residents.

The coalition also gave a failing grade to the ACGME's plans for better monitoring compliance with the standards. However, the recommendation for greater supervision of first-year residents got higher marks.

The revised standards represent an important step, but “I think the acid test will be in the details,” Helen Haskell, founder and president of Mothers Against Medical Error, and a coalition member, said in a statement. “We need to be sure that residents of all levels have sufficient backup and reasonable limits on their workloads.”

The Accreditation Council for Graduate Medical Education has revisited its standards for resident duty hours and determined that some modifications should be made, mostly for first-year residents. All other residents should still be subject to an 80-hour work week and up to 24 hours of continuous duty, according to an article published online in the New England Journal of Medicine.

The 16-member ACGME task force that wrote the standards will review public comments and make any modifications considered necessary before July 2011, when the new standards will go into effect.

The American College of Surgeons Task Force on Resident Duty Hours has analyzed the recommendations and submitted its comments to the ACGME, said Dr. L.D. Britt, chairman of the task force and chairman of the Dept. of Surgery at the Eastern Virginia Medical School, Norfolk, Va. The 34-member task force represented a variety of organizations and specialties. Dr. Britt said that the task force would discuss its comments after the ACGME had a chance to review them.

The original ACGME standards, established in 2003, have been the subject of much consternation in the medical community, with opinions differing over whether they have been too restrictive or too loose to properly protect patients and ensure a good quality of life for residents.

According to the latest report, written by Dr. Thomas J. Nasca, Dr. Susan H. Day, and Dr. E. Stephen Amis Jr. on behalf of the ACGME task force, the 2003 standards had the following three “problematic” elements, as identified by the educational community and the public:

▸ The limits on duty hours may have created a shift mentality among residents, which tends to conflict with the duty to serve patients.

▸ Many academic programs began focusing on meeting the duty hour restrictions, perhaps at the expense of education.

▸ The 80-hour work week, with up to 24 hours of continuous duty, was seen by many as compromising patient safety.

In 2008, the Institute of Medicine took a hard look at the ACGME standards and, among other things, recommended that no residents should exceed 16 hours of continuous duty.

The ACGME convened the task force to consider the IOM recommendations. One of the biggest challenges, according to the authors, was to reconcile the IOM's suggestion for an across-the-board restriction on duty hours with the continuing plea from academic programs that duty hours needed to be tailored to each specialty (N. Engl. J. Med. 2010 [doi:10.1056/NEJMsb1005800]).

For surgery, in particular, it would be difficult—and contrary to learning—to have a resident leave in the midst of a procedure because his or her duty hours had been reached.

The ACGME panel also had to weigh whether there was sufficient evidence to show that working more than 16 hours or up to 30 hours continuously led to more medical errors, as has been suggested by many critics of the duty hour standards.

According to the ACGME panel, the data thus far indicate only that first-year residents are more prone to mistakes as a result of sleep deprivation. Therefore, the task force urged a new paradigm for the first year of residency, whereby residents cannot be on duty for longer than 16 hours continuously and should have 10 hours off and 8 hours free of duty between their scheduled duty periods. First-year residents are not allowed to moonlight, and they must have direct, in-house, attending-level supervision.

All residents are allowed to work up to an additional 4 hours to facilitate patient handoffs—an area of concern for patient safety.

The panel decided not to tailor duty hours to specialties “because studies have not shown that the safety effect of current standards varies with specialty,” said the authors.

The IOM had also criticized the ACGME for not properly enforcing the duty hours. The task force said that enforcement is an “inherent” challenge, partly because there are some 9,000 accredited programs.

However, the ACGME is now undertaking annual site visits and analyzing whether institutions can comply. Eventually, the organization will give each institution a report on its compliance status and recommendations for resolving problems. The reports will be made available to the public, said the authors.

Wake Up Doctor, a coalition of public interest and patient safety groups that has been pushing the ACGME to further restrict resident hours, said that the new standards don't go far enough. The group gave the ACGME an “F” for failing to comply with the IOM recommendation that continuous duty be restricted to 16 hours for all residents.

The coalition also gave a failing grade to the ACGME's plans for better monitoring compliance with the standards. However, the recommendation for greater supervision of first-year residents got higher marks.

The revised standards represent an important step, but “I think the acid test will be in the details,” Helen Haskell, founder and president of Mothers Against Medical Error, and a coalition member, said in a statement. “We need to be sure that residents of all levels have sufficient backup and reasonable limits on their workloads.”

The Accreditation Council for Graduate Medical Education has revisited its standards for resident duty hours and determined that some modifications should be made, mostly for first-year residents. All other residents should still be subject to an 80-hour work week and up to 24 hours of continuous duty, according to an article published online in the New England Journal of Medicine.

The 16-member ACGME task force that wrote the standards will review public comments and make any modifications considered necessary before July 2011, when the new standards will go into effect.

The American College of Surgeons Task Force on Resident Duty Hours has analyzed the recommendations and submitted its comments to the ACGME, said Dr. L.D. Britt, chairman of the task force and chairman of the Dept. of Surgery at the Eastern Virginia Medical School, Norfolk, Va. The 34-member task force represented a variety of organizations and specialties. Dr. Britt said that the task force would discuss its comments after the ACGME had a chance to review them.

The original ACGME standards, established in 2003, have been the subject of much consternation in the medical community, with opinions differing over whether they have been too restrictive or too loose to properly protect patients and ensure a good quality of life for residents.

According to the latest report, written by Dr. Thomas J. Nasca, Dr. Susan H. Day, and Dr. E. Stephen Amis Jr. on behalf of the ACGME task force, the 2003 standards had the following three “problematic” elements, as identified by the educational community and the public:

▸ The limits on duty hours may have created a shift mentality among residents, which tends to conflict with the duty to serve patients.

▸ Many academic programs began focusing on meeting the duty hour restrictions, perhaps at the expense of education.

▸ The 80-hour work week, with up to 24 hours of continuous duty, was seen by many as compromising patient safety.

In 2008, the Institute of Medicine took a hard look at the ACGME standards and, among other things, recommended that no residents should exceed 16 hours of continuous duty.

The ACGME convened the task force to consider the IOM recommendations. One of the biggest challenges, according to the authors, was to reconcile the IOM's suggestion for an across-the-board restriction on duty hours with the continuing plea from academic programs that duty hours needed to be tailored to each specialty (N. Engl. J. Med. 2010 [doi:10.1056/NEJMsb1005800]).

For surgery, in particular, it would be difficult—and contrary to learning—to have a resident leave in the midst of a procedure because his or her duty hours had been reached.

The ACGME panel also had to weigh whether there was sufficient evidence to show that working more than 16 hours or up to 30 hours continuously led to more medical errors, as has been suggested by many critics of the duty hour standards.

According to the ACGME panel, the data thus far indicate only that first-year residents are more prone to mistakes as a result of sleep deprivation. Therefore, the task force urged a new paradigm for the first year of residency, whereby residents cannot be on duty for longer than 16 hours continuously and should have 10 hours off and 8 hours free of duty between their scheduled duty periods. First-year residents are not allowed to moonlight, and they must have direct, in-house, attending-level supervision.

All residents are allowed to work up to an additional 4 hours to facilitate patient handoffs—an area of concern for patient safety.

The panel decided not to tailor duty hours to specialties “because studies have not shown that the safety effect of current standards varies with specialty,” said the authors.

The IOM had also criticized the ACGME for not properly enforcing the duty hours. The task force said that enforcement is an “inherent” challenge, partly because there are some 9,000 accredited programs.

However, the ACGME is now undertaking annual site visits and analyzing whether institutions can comply. Eventually, the organization will give each institution a report on its compliance status and recommendations for resolving problems. The reports will be made available to the public, said the authors.

Wake Up Doctor, a coalition of public interest and patient safety groups that has been pushing the ACGME to further restrict resident hours, said that the new standards don't go far enough. The group gave the ACGME an “F” for failing to comply with the IOM recommendation that continuous duty be restricted to 16 hours for all residents.

The coalition also gave a failing grade to the ACGME's plans for better monitoring compliance with the standards. However, the recommendation for greater supervision of first-year residents got higher marks.

The revised standards represent an important step, but “I think the acid test will be in the details,” Helen Haskell, founder and president of Mothers Against Medical Error, and a coalition member, said in a statement. “We need to be sure that residents of all levels have sufficient backup and reasonable limits on their workloads.”

The Food and Drug Administration issued a warning to physicians and consumers that proton pump inhibitors may increase the risk of hip, wrist, and spine fractures.

The agency said that it is changing the labeling for prescription and over-the-counter versions of proton pump inhibitors (PPIs) to reflect new safety information that is the result of the FDA's review of seven epidemiologic studies. Most of the observed risk was in people older than age 50 years and those who took high doses or used the drugs for more than a year, said the agency.

Prescription PPIs include esomeprazole (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec, Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix), and rabeprazole (Aciphex). There are OTC versions of Prilosec, Zegerid, and Prevacid.

“When prescribing proton pump inhibitors, health care professionals should consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition,” Dr. Joyce Korvick, the deputy director for safety in the FDA's Division of Gastroenterology Products, in a statement.

The agency did not have access to the raw data in the studies; it merely reviewed what was published. However, said the FDA, it accepted the results because the studies appear to be well designed.

The full agency communication is online located at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm

The Food and Drug Administration issued a warning to physicians and consumers that proton pump inhibitors may increase the risk of hip, wrist, and spine fractures.

The agency said that it is changing the labeling for prescription and over-the-counter versions of proton pump inhibitors (PPIs) to reflect new safety information that is the result of the FDA's review of seven epidemiologic studies. Most of the observed risk was in people older than age 50 years and those who took high doses or used the drugs for more than a year, said the agency.

Prescription PPIs include esomeprazole (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec, Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix), and rabeprazole (Aciphex). There are OTC versions of Prilosec, Zegerid, and Prevacid.

“When prescribing proton pump inhibitors, health care professionals should consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition,” Dr. Joyce Korvick, the deputy director for safety in the FDA's Division of Gastroenterology Products, in a statement.

The agency did not have access to the raw data in the studies; it merely reviewed what was published. However, said the FDA, it accepted the results because the studies appear to be well designed.

The full agency communication is online located at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm

The Food and Drug Administration issued a warning to physicians and consumers that proton pump inhibitors may increase the risk of hip, wrist, and spine fractures.

The agency said that it is changing the labeling for prescription and over-the-counter versions of proton pump inhibitors (PPIs) to reflect new safety information that is the result of the FDA's review of seven epidemiologic studies. Most of the observed risk was in people older than age 50 years and those who took high doses or used the drugs for more than a year, said the agency.

Prescription PPIs include esomeprazole (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec, Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix), and rabeprazole (Aciphex). There are OTC versions of Prilosec, Zegerid, and Prevacid.

“When prescribing proton pump inhibitors, health care professionals should consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition,” Dr. Joyce Korvick, the deputy director for safety in the FDA's Division of Gastroenterology Products, in a statement.

The agency did not have access to the raw data in the studies; it merely reviewed what was published. However, said the FDA, it accepted the results because the studies appear to be well designed.

The full agency communication is online located at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm

ISMP: Avandia at Top in Drug Deaths

Type 2 diabetes drug rosiglitazone (Avandia) accounted for 1,354 patient deaths in 2009, more than any other prescription drug, according to a June report from the Institute for Safe Medication Practices. However, the institute blamed publicity about the drug's cardiovascular risks in part for the large number of fatalities reported to the Food and Drug Administration (see page 1 article for more on Avandia). “The manufacturer, GlaxoSmithKline, told us earlier that it believed many of the adverse drug event reports for rosiglitazone were associated with possible lawsuits against the company,” the report said. The institute excluded reports it knew involved legal claims but said it couldn't rule out the bad publicity as the reason for some other reports of cardiovascular events and deaths associated with rosiglitazone. Other drugs tied to large numbers of deaths last year include deferasirox (1,320 deaths), digoxin (506 deaths), and fentanyl (397). Almost 20,000 medication-associated deaths were reported to the FDA, a 14% increase over 2008 and a threefold increase over 2000, according to the institute. The report attributed the drug-related mortality increase to three factors: increased awareness of drug risks, lack of progress in managing drugs with known risks, and reports of discontinued treatment and death stemming from increasingly common direct company-consumer contacts. The full report is available at

www.ismp.org/quarterwatch/2009Q4.pdf

CMS Reconsiders MRI Coverage

The Centers for Medicare and Medicaid Services is taking another look at its decision to bar coverage of magnetic resonance imaging for people who have cardiac pacemakers or metallic clips on vascular aneurysms. Dr. Robert Russo, director of the cardiac MRI program at the Scripps Clinic in San Diego asked the CMS to reopen the issue of coverage for those patients. He is seeking to have it approved if the MRI is performed on people bearing the devices as part of an FDA-approved, prospective trial to determine the risk of the procedure. Comments on the proposal were being accepted through July 28, and the CMS said that it expected to issue a preliminary decision by Dec. 28.

FDA to Share Drug-Risk Findings

The FDA will post on its Web site summaries of postmarketing safety analyses on recently approved drugs and biologics, including brief discussions of steps being taken to address identified safety issues. The new summaries will cover side effects that might not become apparent until after a medicine becomes available to a large, diverse population, including previously unidentified risks and known adverse events that occur more frequently than expected. The initial reports will contain information on drugs and biologics approved since September 2007, including several drugs for infections, hypertension, and depression, the agency said.

J&J Discloses Physician Payments

Following in the footsteps of Pfizer, GlaxoSmithKline, and, most recently, Medtronic, Johnson & Johnson said that it is disclosing how much it pays physician speakers and consultants, at least for a number of its pharmaceutical subsidiaries. Unlike at other companies, however, the data cover only J&J divisions that were subject to corporate integrity agreements with the federal government, according to a company spokesman. Those divisions are PriCara, Ortho-McNeil Pharmaceutical, Ortho-McNeil Neurologics, Janssen, and McNeil Pediatrics. Payment disclosures are listed at those units' individual Web sites, such as

www.janssen.com/transparency.html

Men Less Likely to Get Care

Men are much less likely than are women to seek routine medical care: Just over half of U.S. men see a doctor, nurse practitioner, or physician assistant for routine care, compared with nearly three-quarters of women, according to the Agency for Healthcare Research and Quality. Only about 35% of Hispanic men and 43% of black men made routine appointments, compared with 63% of white men, and uninsured people were only about half as likely as were those with private insurance to make a routine care appointment, the agency said.

State Expands Medicaid to Adults

Connecticut has added low-income, childless adults to its Medicaid program under the nation's new health care reform law. It's the first state to take advantage of the law's incentives to expand “permanent” coverage to such individuals, which could previously be covered only under Medicaid waivers. Connecticut said it initially will cover childless adults who make up to 56% of the federal poverty level, or $6,650 per year, estimated to be about 45,000 extra people. Health care reform requires states to cover all low-income individuals in Medicaid starting in 2014, but also allows states to get federal funding to enroll them early.

ISMP: Avandia at Top in Drug Deaths

Type 2 diabetes drug rosiglitazone (Avandia) accounted for 1,354 patient deaths in 2009, more than any other prescription drug, according to a June report from the Institute for Safe Medication Practices. However, the institute blamed publicity about the drug's cardiovascular risks in part for the large number of fatalities reported to the Food and Drug Administration (see page 1 article for more on Avandia). “The manufacturer, GlaxoSmithKline, told us earlier that it believed many of the adverse drug event reports for rosiglitazone were associated with possible lawsuits against the company,” the report said. The institute excluded reports it knew involved legal claims but said it couldn't rule out the bad publicity as the reason for some other reports of cardiovascular events and deaths associated with rosiglitazone. Other drugs tied to large numbers of deaths last year include deferasirox (1,320 deaths), digoxin (506 deaths), and fentanyl (397). Almost 20,000 medication-associated deaths were reported to the FDA, a 14% increase over 2008 and a threefold increase over 2000, according to the institute. The report attributed the drug-related mortality increase to three factors: increased awareness of drug risks, lack of progress in managing drugs with known risks, and reports of discontinued treatment and death stemming from increasingly common direct company-consumer contacts. The full report is available at

www.ismp.org/quarterwatch/2009Q4.pdf

CMS Reconsiders MRI Coverage

The Centers for Medicare and Medicaid Services is taking another look at its decision to bar coverage of magnetic resonance imaging for people who have cardiac pacemakers or metallic clips on vascular aneurysms. Dr. Robert Russo, director of the cardiac MRI program at the Scripps Clinic in San Diego asked the CMS to reopen the issue of coverage for those patients. He is seeking to have it approved if the MRI is performed on people bearing the devices as part of an FDA-approved, prospective trial to determine the risk of the procedure. Comments on the proposal were being accepted through July 28, and the CMS said that it expected to issue a preliminary decision by Dec. 28.

FDA to Share Drug-Risk Findings

The FDA will post on its Web site summaries of postmarketing safety analyses on recently approved drugs and biologics, including brief discussions of steps being taken to address identified safety issues. The new summaries will cover side effects that might not become apparent until after a medicine becomes available to a large, diverse population, including previously unidentified risks and known adverse events that occur more frequently than expected. The initial reports will contain information on drugs and biologics approved since September 2007, including several drugs for infections, hypertension, and depression, the agency said.

J&J Discloses Physician Payments

Following in the footsteps of Pfizer, GlaxoSmithKline, and, most recently, Medtronic, Johnson & Johnson said that it is disclosing how much it pays physician speakers and consultants, at least for a number of its pharmaceutical subsidiaries. Unlike at other companies, however, the data cover only J&J divisions that were subject to corporate integrity agreements with the federal government, according to a company spokesman. Those divisions are PriCara, Ortho-McNeil Pharmaceutical, Ortho-McNeil Neurologics, Janssen, and McNeil Pediatrics. Payment disclosures are listed at those units' individual Web sites, such as

www.janssen.com/transparency.html

Men Less Likely to Get Care

Men are much less likely than are women to seek routine medical care: Just over half of U.S. men see a doctor, nurse practitioner, or physician assistant for routine care, compared with nearly three-quarters of women, according to the Agency for Healthcare Research and Quality. Only about 35% of Hispanic men and 43% of black men made routine appointments, compared with 63% of white men, and uninsured people were only about half as likely as were those with private insurance to make a routine care appointment, the agency said.

State Expands Medicaid to Adults

Connecticut has added low-income, childless adults to its Medicaid program under the nation's new health care reform law. It's the first state to take advantage of the law's incentives to expand “permanent” coverage to such individuals, which could previously be covered only under Medicaid waivers. Connecticut said it initially will cover childless adults who make up to 56% of the federal poverty level, or $6,650 per year, estimated to be about 45,000 extra people. Health care reform requires states to cover all low-income individuals in Medicaid starting in 2014, but also allows states to get federal funding to enroll them early.

ISMP: Avandia at Top in Drug Deaths

Type 2 diabetes drug rosiglitazone (Avandia) accounted for 1,354 patient deaths in 2009, more than any other prescription drug, according to a June report from the Institute for Safe Medication Practices. However, the institute blamed publicity about the drug's cardiovascular risks in part for the large number of fatalities reported to the Food and Drug Administration (see page 1 article for more on Avandia). “The manufacturer, GlaxoSmithKline, told us earlier that it believed many of the adverse drug event reports for rosiglitazone were associated with possible lawsuits against the company,” the report said. The institute excluded reports it knew involved legal claims but said it couldn't rule out the bad publicity as the reason for some other reports of cardiovascular events and deaths associated with rosiglitazone. Other drugs tied to large numbers of deaths last year include deferasirox (1,320 deaths), digoxin (506 deaths), and fentanyl (397). Almost 20,000 medication-associated deaths were reported to the FDA, a 14% increase over 2008 and a threefold increase over 2000, according to the institute. The report attributed the drug-related mortality increase to three factors: increased awareness of drug risks, lack of progress in managing drugs with known risks, and reports of discontinued treatment and death stemming from increasingly common direct company-consumer contacts. The full report is available at

www.ismp.org/quarterwatch/2009Q4.pdf

CMS Reconsiders MRI Coverage

The Centers for Medicare and Medicaid Services is taking another look at its decision to bar coverage of magnetic resonance imaging for people who have cardiac pacemakers or metallic clips on vascular aneurysms. Dr. Robert Russo, director of the cardiac MRI program at the Scripps Clinic in San Diego asked the CMS to reopen the issue of coverage for those patients. He is seeking to have it approved if the MRI is performed on people bearing the devices as part of an FDA-approved, prospective trial to determine the risk of the procedure. Comments on the proposal were being accepted through July 28, and the CMS said that it expected to issue a preliminary decision by Dec. 28.

FDA to Share Drug-Risk Findings

The FDA will post on its Web site summaries of postmarketing safety analyses on recently approved drugs and biologics, including brief discussions of steps being taken to address identified safety issues. The new summaries will cover side effects that might not become apparent until after a medicine becomes available to a large, diverse population, including previously unidentified risks and known adverse events that occur more frequently than expected. The initial reports will contain information on drugs and biologics approved since September 2007, including several drugs for infections, hypertension, and depression, the agency said.

J&J Discloses Physician Payments

Following in the footsteps of Pfizer, GlaxoSmithKline, and, most recently, Medtronic, Johnson & Johnson said that it is disclosing how much it pays physician speakers and consultants, at least for a number of its pharmaceutical subsidiaries. Unlike at other companies, however, the data cover only J&J divisions that were subject to corporate integrity agreements with the federal government, according to a company spokesman. Those divisions are PriCara, Ortho-McNeil Pharmaceutical, Ortho-McNeil Neurologics, Janssen, and McNeil Pediatrics. Payment disclosures are listed at those units' individual Web sites, such as

www.janssen.com/transparency.html

Men Less Likely to Get Care

Men are much less likely than are women to seek routine medical care: Just over half of U.S. men see a doctor, nurse practitioner, or physician assistant for routine care, compared with nearly three-quarters of women, according to the Agency for Healthcare Research and Quality. Only about 35% of Hispanic men and 43% of black men made routine appointments, compared with 63% of white men, and uninsured people were only about half as likely as were those with private insurance to make a routine care appointment, the agency said.

State Expands Medicaid to Adults

Connecticut has added low-income, childless adults to its Medicaid program under the nation's new health care reform law. It's the first state to take advantage of the law's incentives to expand “permanent” coverage to such individuals, which could previously be covered only under Medicaid waivers. Connecticut said it initially will cover childless adults who make up to 56% of the federal poverty level, or $6,650 per year, estimated to be about 45,000 extra people. Health care reform requires states to cover all low-income individuals in Medicaid starting in 2014, but also allows states to get federal funding to enroll them early.

The number of uninsured Americans rose last year, with 21% of all adults aged 18–64 years reporting that they were uninsured at the time that they were interviewed for the National Health Interview Survey, federal officials reported June 16.

That's up from 19.7% the previous year and reflects a trend over the past decade of an increasing lack of health insurance, at least among adults, according to a survey by the National Center for Health Statistics, a part of the Centers for Disease Control and Prevention. Rates of coverage for children, on the other hand, have mostly improved.

Since 1999, increasing proportions of people have reported that they were uninsured at the time of the annual survey, for part of the year prior to their interviews, and for a year or more, said the NCHS in its report, which was released early and will be published in CDC's Morbidity and Mortality Weekly Report.

Overall, 46.3 million people—or 15.4% of the population—were uninsured at the time they were interviewed in 2009. The survey found that even greater numbers of people reported that they were uninsured for at least part of the year before the interview—some 58.5 million—but that a slightly smaller number, 32.8 million, had been uninsured for more than a year at the time they were queried.

A greater proportion of children than adults were covered by public health plans, which could explain the children's higher rate of coverage, according to the survey. In 2009, 37.7% of children under age 18 were covered by a public plan, up from 34.2% the previous year. Rates of public coverage for low-income children increased. Federal officials in both the Obama and Bush administrations have emphasized enrolling more eligible children in the public Children's Health Insurance Plan, which is administered by states.

Conversely, only 14.4% of adults aged 18–64 years had public coverage. And private coverage for adults declined from 68% in 2008 to 66% in 2009, according to the survey. There was no significant change in private coverage for children of any income level.

Hispanics were least likely to have insurance, with one-third reporting no insurance at the time of the interview or for part of the past year. A quarter had had no coverage for more than a year.

Not surprisingly, states with larger Hispanic populations had greater proportions of uninsured. One-quarter of Texas and Florida residents under age 65 years were uninsured at the time of the interview. One-fifth did not have coverage in California and Georgia. In Florida, 13% of children lacked coverage when interviewed, and in Texas, that number was almost 17%.

Nine states had lower rates of uninsured than the national average of 17.5%: Illinois, Massachusetts, Michigan, New Jersey, New York, Ohio, Pennsylvania, Washington, and Wisconsin.

For more information, go to www.cdc.gov/nchs

The number of uninsured Americans rose last year, with 21% of all adults aged 18–64 years reporting that they were uninsured at the time that they were interviewed for the National Health Interview Survey, federal officials reported June 16.

That's up from 19.7% the previous year and reflects a trend over the past decade of an increasing lack of health insurance, at least among adults, according to a survey by the National Center for Health Statistics, a part of the Centers for Disease Control and Prevention. Rates of coverage for children, on the other hand, have mostly improved.

Since 1999, increasing proportions of people have reported that they were uninsured at the time of the annual survey, for part of the year prior to their interviews, and for a year or more, said the NCHS in its report, which was released early and will be published in CDC's Morbidity and Mortality Weekly Report.

Overall, 46.3 million people—or 15.4% of the population—were uninsured at the time they were interviewed in 2009. The survey found that even greater numbers of people reported that they were uninsured for at least part of the year before the interview—some 58.5 million—but that a slightly smaller number, 32.8 million, had been uninsured for more than a year at the time they were queried.

A greater proportion of children than adults were covered by public health plans, which could explain the children's higher rate of coverage, according to the survey. In 2009, 37.7% of children under age 18 were covered by a public plan, up from 34.2% the previous year. Rates of public coverage for low-income children increased. Federal officials in both the Obama and Bush administrations have emphasized enrolling more eligible children in the public Children's Health Insurance Plan, which is administered by states.

Conversely, only 14.4% of adults aged 18–64 years had public coverage. And private coverage for adults declined from 68% in 2008 to 66% in 2009, according to the survey. There was no significant change in private coverage for children of any income level.

Hispanics were least likely to have insurance, with one-third reporting no insurance at the time of the interview or for part of the past year. A quarter had had no coverage for more than a year.

Not surprisingly, states with larger Hispanic populations had greater proportions of uninsured. One-quarter of Texas and Florida residents under age 65 years were uninsured at the time of the interview. One-fifth did not have coverage in California and Georgia. In Florida, 13% of children lacked coverage when interviewed, and in Texas, that number was almost 17%.

Nine states had lower rates of uninsured than the national average of 17.5%: Illinois, Massachusetts, Michigan, New Jersey, New York, Ohio, Pennsylvania, Washington, and Wisconsin.

For more information, go to www.cdc.gov/nchs

The number of uninsured Americans rose last year, with 21% of all adults aged 18–64 years reporting that they were uninsured at the time that they were interviewed for the National Health Interview Survey, federal officials reported June 16.

That's up from 19.7% the previous year and reflects a trend over the past decade of an increasing lack of health insurance, at least among adults, according to a survey by the National Center for Health Statistics, a part of the Centers for Disease Control and Prevention. Rates of coverage for children, on the other hand, have mostly improved.

Since 1999, increasing proportions of people have reported that they were uninsured at the time of the annual survey, for part of the year prior to their interviews, and for a year or more, said the NCHS in its report, which was released early and will be published in CDC's Morbidity and Mortality Weekly Report.

Overall, 46.3 million people—or 15.4% of the population—were uninsured at the time they were interviewed in 2009. The survey found that even greater numbers of people reported that they were uninsured for at least part of the year before the interview—some 58.5 million—but that a slightly smaller number, 32.8 million, had been uninsured for more than a year at the time they were queried.

A greater proportion of children than adults were covered by public health plans, which could explain the children's higher rate of coverage, according to the survey. In 2009, 37.7% of children under age 18 were covered by a public plan, up from 34.2% the previous year. Rates of public coverage for low-income children increased. Federal officials in both the Obama and Bush administrations have emphasized enrolling more eligible children in the public Children's Health Insurance Plan, which is administered by states.

Conversely, only 14.4% of adults aged 18–64 years had public coverage. And private coverage for adults declined from 68% in 2008 to 66% in 2009, according to the survey. There was no significant change in private coverage for children of any income level.

Hispanics were least likely to have insurance, with one-third reporting no insurance at the time of the interview or for part of the past year. A quarter had had no coverage for more than a year.

Not surprisingly, states with larger Hispanic populations had greater proportions of uninsured. One-quarter of Texas and Florida residents under age 65 years were uninsured at the time of the interview. One-fifth did not have coverage in California and Georgia. In Florida, 13% of children lacked coverage when interviewed, and in Texas, that number was almost 17%.

Nine states had lower rates of uninsured than the national average of 17.5%: Illinois, Massachusetts, Michigan, New Jersey, New York, Ohio, Pennsylvania, Washington, and Wisconsin.

For more information, go to www.cdc.gov/nchs

WASHINGTON — Direct-to-consumer genetic tests are deceptively marketed and often give misleading results that are of little or no practical use, said the U.S. Government Accountability Office in a report at a hearing of the House Energy and Commerce Committee's Subcommittee on Oversight and Investigations.

Subcommittee chairman Rep. Bart Stupak (D-Mich.) called on the three genetic testing companies in attendance to stop marketing their products to consumers until the Food and Drug Administration or National Institutes of Health can establish standards for how the testing should be conducted and how the results should be shared with consumers.

Currently, the tests are being sold without FDA approval. But Dr. Jeffrey Shuren, director of the FDA's Center for Devices and Radiological Health, said that the agency has been trying to assess how to regulate the products. A genetic test is subject to FDA oversight if it is a medical device being used in the diagnosis of disease or to cure, mitigate, treat, or prevent disease.

The agency has basically hung back on enforcing the rule of the law on the direct-to-consumer (DTC) tests but now is clamping down, said Dr. Shuren. In May, the FDA told Pathway Genomics Inc. that it had to get approval for its genetic health report, which it was going to sell at Walgreens stores. Pathway is no longer marketing directly to consumers.

Pathway's agreement with Walgreens “lit a fire” at the FDA, said Dr. Shuren. “We thought at this point, it's time to take action,” he said.

In June, the FDA sent similar warnings to 4 other companies: Knome Inc., Navigenics Inc., deCODE genetics, and 23andMe, and, on July 19, the agency warned 15 more companies.

The Government Accountability Office (GAO) investigated companies selling DTC tests in 2006 but was asked by the subcommittee to revisit the market in the wake of reports that companies were more “reputable.” The agency bought 10 tests each from four companies—23andMe, deCODE genetics, Pathway Genomics, and Navigenics—using five volunteer DNA donors.

Each volunteer used his or her own information when submitting one test, and submitted fictitious information for the second test. Each kit cost between $300 and $1,000.

All five donors received conflicting results. A total of 68% of the time, the donors received a different prediction for the same disease being tested, according to Gregory Kutz, managing director of the GAO's Forensic Audit and Special Investigations Unit. In one case, a donor with a pacemaker implanted for 13 years to treat atrial fibrillation was told he was at a lower risk for developing the condition.

“These results show that these tests aren't ready for prime time,” said Mr. Kutz. And yet, the market for the tests is at about $1 billion a year and is growing some 20%–30% a year, he said.

The GAO also made undercover calls to 15 companies, including the 4 from which the agency bought test kits, asking about test reliability, privacy policies, and to inquire about supplements that some of the testing firms were selling. Four of the companies claimed that “a consumer's DNA could be used to create personalized supplements that would cure diseases,” said the GAO in its report.

Representatives from 23andMe, Navigenics, and Pathway Genomics all defended their products at the hearing, but added that they agreed that more regulation of the industry was needed.

WASHINGTON — Direct-to-consumer genetic tests are deceptively marketed and often give misleading results that are of little or no practical use, said the U.S. Government Accountability Office in a report at a hearing of the House Energy and Commerce Committee's Subcommittee on Oversight and Investigations.

Subcommittee chairman Rep. Bart Stupak (D-Mich.) called on the three genetic testing companies in attendance to stop marketing their products to consumers until the Food and Drug Administration or National Institutes of Health can establish standards for how the testing should be conducted and how the results should be shared with consumers.

Currently, the tests are being sold without FDA approval. But Dr. Jeffrey Shuren, director of the FDA's Center for Devices and Radiological Health, said that the agency has been trying to assess how to regulate the products. A genetic test is subject to FDA oversight if it is a medical device being used in the diagnosis of disease or to cure, mitigate, treat, or prevent disease.

The agency has basically hung back on enforcing the rule of the law on the direct-to-consumer (DTC) tests but now is clamping down, said Dr. Shuren. In May, the FDA told Pathway Genomics Inc. that it had to get approval for its genetic health report, which it was going to sell at Walgreens stores. Pathway is no longer marketing directly to consumers.

Pathway's agreement with Walgreens “lit a fire” at the FDA, said Dr. Shuren. “We thought at this point, it's time to take action,” he said.

In June, the FDA sent similar warnings to 4 other companies: Knome Inc., Navigenics Inc., deCODE genetics, and 23andMe, and, on July 19, the agency warned 15 more companies.

The Government Accountability Office (GAO) investigated companies selling DTC tests in 2006 but was asked by the subcommittee to revisit the market in the wake of reports that companies were more “reputable.” The agency bought 10 tests each from four companies—23andMe, deCODE genetics, Pathway Genomics, and Navigenics—using five volunteer DNA donors.

Each volunteer used his or her own information when submitting one test, and submitted fictitious information for the second test. Each kit cost between $300 and $1,000.

All five donors received conflicting results. A total of 68% of the time, the donors received a different prediction for the same disease being tested, according to Gregory Kutz, managing director of the GAO's Forensic Audit and Special Investigations Unit. In one case, a donor with a pacemaker implanted for 13 years to treat atrial fibrillation was told he was at a lower risk for developing the condition.

“These results show that these tests aren't ready for prime time,” said Mr. Kutz. And yet, the market for the tests is at about $1 billion a year and is growing some 20%–30% a year, he said.

The GAO also made undercover calls to 15 companies, including the 4 from which the agency bought test kits, asking about test reliability, privacy policies, and to inquire about supplements that some of the testing firms were selling. Four of the companies claimed that “a consumer's DNA could be used to create personalized supplements that would cure diseases,” said the GAO in its report.

Representatives from 23andMe, Navigenics, and Pathway Genomics all defended their products at the hearing, but added that they agreed that more regulation of the industry was needed.

WASHINGTON — Direct-to-consumer genetic tests are deceptively marketed and often give misleading results that are of little or no practical use, said the U.S. Government Accountability Office in a report at a hearing of the House Energy and Commerce Committee's Subcommittee on Oversight and Investigations.

Subcommittee chairman Rep. Bart Stupak (D-Mich.) called on the three genetic testing companies in attendance to stop marketing their products to consumers until the Food and Drug Administration or National Institutes of Health can establish standards for how the testing should be conducted and how the results should be shared with consumers.

Currently, the tests are being sold without FDA approval. But Dr. Jeffrey Shuren, director of the FDA's Center for Devices and Radiological Health, said that the agency has been trying to assess how to regulate the products. A genetic test is subject to FDA oversight if it is a medical device being used in the diagnosis of disease or to cure, mitigate, treat, or prevent disease.

The agency has basically hung back on enforcing the rule of the law on the direct-to-consumer (DTC) tests but now is clamping down, said Dr. Shuren. In May, the FDA told Pathway Genomics Inc. that it had to get approval for its genetic health report, which it was going to sell at Walgreens stores. Pathway is no longer marketing directly to consumers.

Pathway's agreement with Walgreens “lit a fire” at the FDA, said Dr. Shuren. “We thought at this point, it's time to take action,” he said.

In June, the FDA sent similar warnings to 4 other companies: Knome Inc., Navigenics Inc., deCODE genetics, and 23andMe, and, on July 19, the agency warned 15 more companies.

The Government Accountability Office (GAO) investigated companies selling DTC tests in 2006 but was asked by the subcommittee to revisit the market in the wake of reports that companies were more “reputable.” The agency bought 10 tests each from four companies—23andMe, deCODE genetics, Pathway Genomics, and Navigenics—using five volunteer DNA donors.

Each volunteer used his or her own information when submitting one test, and submitted fictitious information for the second test. Each kit cost between $300 and $1,000.

All five donors received conflicting results. A total of 68% of the time, the donors received a different prediction for the same disease being tested, according to Gregory Kutz, managing director of the GAO's Forensic Audit and Special Investigations Unit. In one case, a donor with a pacemaker implanted for 13 years to treat atrial fibrillation was told he was at a lower risk for developing the condition.

“These results show that these tests aren't ready for prime time,” said Mr. Kutz. And yet, the market for the tests is at about $1 billion a year and is growing some 20%–30% a year, he said.

The GAO also made undercover calls to 15 companies, including the 4 from which the agency bought test kits, asking about test reliability, privacy policies, and to inquire about supplements that some of the testing firms were selling. Four of the companies claimed that “a consumer's DNA could be used to create personalized supplements that would cure diseases,” said the GAO in its report.

Representatives from 23andMe, Navigenics, and Pathway Genomics all defended their products at the hearing, but added that they agreed that more regulation of the industry was needed.

COLLEGE PARK, MD. — The Food and Drug Administration's Cardiovascular and Renal Drugs Advisory Committee voted 7-1 to recommend approval of the platelet inhibitor ticagrelor to treat non–ST elevation myocardial infarction and ST-elevation myocardial infarction in patients intended to receive primary coronary intervention or who would be managed medically.

The panel did not directly address other indications being sought by ticagrelor's maker, AstraZeneca, including its use in unstable angina and after a coronary artery bypass graft (CABG). But in an interview after the meeting, FDA official Robert Temple said that the panel had basically covered all the populations that would be considered under the rubric of acute coronary syndrome (ACS). As the agency weighs approval, it will decide whether to grant specific indications, said Dr. Temple, who is head of the office reviewing ticagrelor (Brilinta).

According to the company, ticagrelor is the first reversibly binding oral adenosine diphosphate receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP.

FDA committee member Mori J. Krantz was the lone panelist who voted against approval. He said that he was concerned about data from PLATO (A Study of Platelet Inhibition and Patient Outcomes), a pivotal study showing that patients in the United States did not fare as well as those in overseas sites. “That it went in the opposite direction is a little discomforting,” said Dr. Krantz of the University of Colorado, Denver.

Committee chairman Sanjay Kaul voted in favor of approval, but said, “I am concerned, however, about the data going in the wrong direction in the United States.” He urged the FDA to require a postapproval study that would include a substantial number of Americans and look in particular at unstable angina.

The FDA generally follows its panels' advice.

The PLATO data were first presented at the European Society of Cardiology in 2009 and published online in the New England Journal of Medicine in August 2009. The randomized, double-blind trial compared ticagrelor with clopidogrel in all-comer ACS patients. The study enrolled 18,624 patients at 862 centers in 43 countries.

AstraZeneca said that PLATO proved that ticagrelor was superior to clopidogrel, with a 16% reduction in relative risk for the primary composite end point of cardiovascular death, myocardial infarction, or stroke. The company claimed there was no difference in major bleeding as defined by the trial, but acknowledged that there was a slightly higher number of patients with intracranial hemorrhage, including fatal hemorrhage.

The FDA reviewers said that they also found a higher rate of bleeding after CABG. But the main concern—and the primary reason for the panel meeting—was why there were more cardiovascular events in Americans. AstraZeneca said that a post hoc analysis determined that Americans were taking higher doses of aspirin, which led to more heart attacks, strokes, and deaths.

After lengthy debate, the committee said the difference could not be attributed to chance alone or to the aspirin dosages. Differences in clinical practice in the United States were the more likely explanation, said several panelists.

Members of FDA advisory panels have been cleared of conflicts related to the topic under discussion.

The agency is due to make a decision on the application for approval by Sept. 18.

COLLEGE PARK, MD. — The Food and Drug Administration's Cardiovascular and Renal Drugs Advisory Committee voted 7-1 to recommend approval of the platelet inhibitor ticagrelor to treat non–ST elevation myocardial infarction and ST-elevation myocardial infarction in patients intended to receive primary coronary intervention or who would be managed medically.

The panel did not directly address other indications being sought by ticagrelor's maker, AstraZeneca, including its use in unstable angina and after a coronary artery bypass graft (CABG). But in an interview after the meeting, FDA official Robert Temple said that the panel had basically covered all the populations that would be considered under the rubric of acute coronary syndrome (ACS). As the agency weighs approval, it will decide whether to grant specific indications, said Dr. Temple, who is head of the office reviewing ticagrelor (Brilinta).

According to the company, ticagrelor is the first reversibly binding oral adenosine diphosphate receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP.

FDA committee member Mori J. Krantz was the lone panelist who voted against approval. He said that he was concerned about data from PLATO (A Study of Platelet Inhibition and Patient Outcomes), a pivotal study showing that patients in the United States did not fare as well as those in overseas sites. “That it went in the opposite direction is a little discomforting,” said Dr. Krantz of the University of Colorado, Denver.

Committee chairman Sanjay Kaul voted in favor of approval, but said, “I am concerned, however, about the data going in the wrong direction in the United States.” He urged the FDA to require a postapproval study that would include a substantial number of Americans and look in particular at unstable angina.

The FDA generally follows its panels' advice.

The PLATO data were first presented at the European Society of Cardiology in 2009 and published online in the New England Journal of Medicine in August 2009. The randomized, double-blind trial compared ticagrelor with clopidogrel in all-comer ACS patients. The study enrolled 18,624 patients at 862 centers in 43 countries.

AstraZeneca said that PLATO proved that ticagrelor was superior to clopidogrel, with a 16% reduction in relative risk for the primary composite end point of cardiovascular death, myocardial infarction, or stroke. The company claimed there was no difference in major bleeding as defined by the trial, but acknowledged that there was a slightly higher number of patients with intracranial hemorrhage, including fatal hemorrhage.

The FDA reviewers said that they also found a higher rate of bleeding after CABG. But the main concern—and the primary reason for the panel meeting—was why there were more cardiovascular events in Americans. AstraZeneca said that a post hoc analysis determined that Americans were taking higher doses of aspirin, which led to more heart attacks, strokes, and deaths.

After lengthy debate, the committee said the difference could not be attributed to chance alone or to the aspirin dosages. Differences in clinical practice in the United States were the more likely explanation, said several panelists.

Members of FDA advisory panels have been cleared of conflicts related to the topic under discussion.

The agency is due to make a decision on the application for approval by Sept. 18.

COLLEGE PARK, MD. — The Food and Drug Administration's Cardiovascular and Renal Drugs Advisory Committee voted 7-1 to recommend approval of the platelet inhibitor ticagrelor to treat non–ST elevation myocardial infarction and ST-elevation myocardial infarction in patients intended to receive primary coronary intervention or who would be managed medically.

The panel did not directly address other indications being sought by ticagrelor's maker, AstraZeneca, including its use in unstable angina and after a coronary artery bypass graft (CABG). But in an interview after the meeting, FDA official Robert Temple said that the panel had basically covered all the populations that would be considered under the rubric of acute coronary syndrome (ACS). As the agency weighs approval, it will decide whether to grant specific indications, said Dr. Temple, who is head of the office reviewing ticagrelor (Brilinta).

According to the company, ticagrelor is the first reversibly binding oral adenosine diphosphate receptor antagonist. It selectively inhibits P2Y12, a key target receptor for ADP.

FDA committee member Mori J. Krantz was the lone panelist who voted against approval. He said that he was concerned about data from PLATO (A Study of Platelet Inhibition and Patient Outcomes), a pivotal study showing that patients in the United States did not fare as well as those in overseas sites. “That it went in the opposite direction is a little discomforting,” said Dr. Krantz of the University of Colorado, Denver.

Committee chairman Sanjay Kaul voted in favor of approval, but said, “I am concerned, however, about the data going in the wrong direction in the United States.” He urged the FDA to require a postapproval study that would include a substantial number of Americans and look in particular at unstable angina.

The FDA generally follows its panels' advice.

The PLATO data were first presented at the European Society of Cardiology in 2009 and published online in the New England Journal of Medicine in August 2009. The randomized, double-blind trial compared ticagrelor with clopidogrel in all-comer ACS patients. The study enrolled 18,624 patients at 862 centers in 43 countries.

AstraZeneca said that PLATO proved that ticagrelor was superior to clopidogrel, with a 16% reduction in relative risk for the primary composite end point of cardiovascular death, myocardial infarction, or stroke. The company claimed there was no difference in major bleeding as defined by the trial, but acknowledged that there was a slightly higher number of patients with intracranial hemorrhage, including fatal hemorrhage.

The FDA reviewers said that they also found a higher rate of bleeding after CABG. But the main concern—and the primary reason for the panel meeting—was why there were more cardiovascular events in Americans. AstraZeneca said that a post hoc analysis determined that Americans were taking higher doses of aspirin, which led to more heart attacks, strokes, and deaths.

After lengthy debate, the committee said the difference could not be attributed to chance alone or to the aspirin dosages. Differences in clinical practice in the United States were the more likely explanation, said several panelists.

Members of FDA advisory panels have been cleared of conflicts related to the topic under discussion.

The agency is due to make a decision on the application for approval by Sept. 18.