Patrice Wendling

CHICAGO – The global practice of giving oxygen to patients having a heart attack may cause more harm than good, results from the AVOID study showed.

Patients who were not hypoxic and received oxygen for ST-segment elevation MI (STEMI) had larger myocardial infarct size, as measured during the first 3 days of hospitalization using cardiac enzymes.

The oxygen arm had a statistically significant 25% increase in creatine kinase, compared with the no-oxygen arm, whether measured as geometric mean peak (1,948 U/L vs. 1,543 U/L) or median peak (2,073 U/L vs. 1,727 U/L), Dr. Stub said.

Cardiac troponin I levels were nonsignificantly higher with oxygen therapy (geometric mean peak, 57.4 mcg/L vs. 48 mcg/L; median peak, 65.7 mcg/L vs. 62.1 mcg/L).

When the preferred treatment approach cardiac magnetic resonance imaging was applied in about a third of patients at 6 months’ follow-up, the median infarct size remained significantly larger, at 20.3 g, in those given oxygen therapy, than in those who did not receive such therapy, whose median infarct size was 13.1 g, Dr. Dion Stub said at the American Heart Association scientific sessions.

“The primary endpoint of infarct size was significantly less without oxygen. That’s an astounding finding and really one that I think will cause many cardiologists to take note and perhaps step back,” said invited discussant Dr. Karl Kern, the Gordon A. Ewy Distinguished Endowed Chair of Cardiovascular Medicine, University of Arizona, Tucson.

“On the other hand, it’s important to realize that is a surrogate endpoint. That is not a mortality or outcome endpoint and the way that this was measured with biomarkers was admirable, but perhaps not today the most accurate. What is accurate was cardiac MR scanning, and the data held up at 6 months as well,” he added.

Although the study was not powered for clinical outcomes, patients receiving oxygen, compared with no oxygen, also had significantly more recurrent MI, at 5.5% and 0.9%, respectively, and major arrhythmia, at 40.4% and 31.4%, at discharge.

Survival at discharge was similar with oxygen versus no oxygen (1.8% vs. 4.5%), Dr. Stub, an interventional cardiologist at St. Paul’s Hospital, Vancouver, B.C., and a researcher at the Baker IDI Heart & Diabetes Institute, Melbourne, reported. .

Oxygen therapy has been used for more than a century in the initial treatment of patients with suspected MI, although there is limited evidence suggesting such therapy is beneficial in patients without hypoxia. A growing body of evidence, however, suggests that even 15 minutes of oxygen can reduce coronary blood flow, increase the production of oxygen-free radicals, and disturb microcirculation, all of which can contribute to reperfusion injury during MI, he said.

The 638 Australian patients in the AVOID (Air Versus Oxygen in ST-Elevation Myocardial Infarction) study were randomized, before hospitalization, by paramedics to oxygen administered via face mask at a flow rate of 8 L/min until patients were stabilized on the ward or to no oxygen, unless oxygen saturation fell below 94%.

Dr. Kern and others pointed out that the oxygen level provided to study participants exceeds the 2-4 L typically given to MI patients in the United States, particularly those who are nonhypoxic.

All parties agreed there is an urgent need for an adequately powered randomized trial to evaluate the effectiveness of oxygen therapy in MI, a conclusion also reached by a recent Cochrane review of the topic (Cochrane Syst. Rev. 2013 August;8:CD007160).

[email protected]

CHICAGO – The global practice of giving oxygen to patients having a heart attack may cause more harm than good, results from the AVOID study showed.

Patients who were not hypoxic and received oxygen for ST-segment elevation MI (STEMI) had larger myocardial infarct size, as measured during the first 3 days of hospitalization using cardiac enzymes.

The oxygen arm had a statistically significant 25% increase in creatine kinase, compared with the no-oxygen arm, whether measured as geometric mean peak (1,948 U/L vs. 1,543 U/L) or median peak (2,073 U/L vs. 1,727 U/L), Dr. Stub said.

Cardiac troponin I levels were nonsignificantly higher with oxygen therapy (geometric mean peak, 57.4 mcg/L vs. 48 mcg/L; median peak, 65.7 mcg/L vs. 62.1 mcg/L).

When the preferred treatment approach cardiac magnetic resonance imaging was applied in about a third of patients at 6 months’ follow-up, the median infarct size remained significantly larger, at 20.3 g, in those given oxygen therapy, than in those who did not receive such therapy, whose median infarct size was 13.1 g, Dr. Dion Stub said at the American Heart Association scientific sessions.

“The primary endpoint of infarct size was significantly less without oxygen. That’s an astounding finding and really one that I think will cause many cardiologists to take note and perhaps step back,” said invited discussant Dr. Karl Kern, the Gordon A. Ewy Distinguished Endowed Chair of Cardiovascular Medicine, University of Arizona, Tucson.

“On the other hand, it’s important to realize that is a surrogate endpoint. That is not a mortality or outcome endpoint and the way that this was measured with biomarkers was admirable, but perhaps not today the most accurate. What is accurate was cardiac MR scanning, and the data held up at 6 months as well,” he added.

Although the study was not powered for clinical outcomes, patients receiving oxygen, compared with no oxygen, also had significantly more recurrent MI, at 5.5% and 0.9%, respectively, and major arrhythmia, at 40.4% and 31.4%, at discharge.

Survival at discharge was similar with oxygen versus no oxygen (1.8% vs. 4.5%), Dr. Stub, an interventional cardiologist at St. Paul’s Hospital, Vancouver, B.C., and a researcher at the Baker IDI Heart & Diabetes Institute, Melbourne, reported. .

Oxygen therapy has been used for more than a century in the initial treatment of patients with suspected MI, although there is limited evidence suggesting such therapy is beneficial in patients without hypoxia. A growing body of evidence, however, suggests that even 15 minutes of oxygen can reduce coronary blood flow, increase the production of oxygen-free radicals, and disturb microcirculation, all of which can contribute to reperfusion injury during MI, he said.

The 638 Australian patients in the AVOID (Air Versus Oxygen in ST-Elevation Myocardial Infarction) study were randomized, before hospitalization, by paramedics to oxygen administered via face mask at a flow rate of 8 L/min until patients were stabilized on the ward or to no oxygen, unless oxygen saturation fell below 94%.

Dr. Kern and others pointed out that the oxygen level provided to study participants exceeds the 2-4 L typically given to MI patients in the United States, particularly those who are nonhypoxic.

All parties agreed there is an urgent need for an adequately powered randomized trial to evaluate the effectiveness of oxygen therapy in MI, a conclusion also reached by a recent Cochrane review of the topic (Cochrane Syst. Rev. 2013 August;8:CD007160).

[email protected]

CHICAGO – The global practice of giving oxygen to patients having a heart attack may cause more harm than good, results from the AVOID study showed.

Patients who were not hypoxic and received oxygen for ST-segment elevation MI (STEMI) had larger myocardial infarct size, as measured during the first 3 days of hospitalization using cardiac enzymes.

The oxygen arm had a statistically significant 25% increase in creatine kinase, compared with the no-oxygen arm, whether measured as geometric mean peak (1,948 U/L vs. 1,543 U/L) or median peak (2,073 U/L vs. 1,727 U/L), Dr. Stub said.

Cardiac troponin I levels were nonsignificantly higher with oxygen therapy (geometric mean peak, 57.4 mcg/L vs. 48 mcg/L; median peak, 65.7 mcg/L vs. 62.1 mcg/L).

When the preferred treatment approach cardiac magnetic resonance imaging was applied in about a third of patients at 6 months’ follow-up, the median infarct size remained significantly larger, at 20.3 g, in those given oxygen therapy, than in those who did not receive such therapy, whose median infarct size was 13.1 g, Dr. Dion Stub said at the American Heart Association scientific sessions.

“The primary endpoint of infarct size was significantly less without oxygen. That’s an astounding finding and really one that I think will cause many cardiologists to take note and perhaps step back,” said invited discussant Dr. Karl Kern, the Gordon A. Ewy Distinguished Endowed Chair of Cardiovascular Medicine, University of Arizona, Tucson.

“On the other hand, it’s important to realize that is a surrogate endpoint. That is not a mortality or outcome endpoint and the way that this was measured with biomarkers was admirable, but perhaps not today the most accurate. What is accurate was cardiac MR scanning, and the data held up at 6 months as well,” he added.

Although the study was not powered for clinical outcomes, patients receiving oxygen, compared with no oxygen, also had significantly more recurrent MI, at 5.5% and 0.9%, respectively, and major arrhythmia, at 40.4% and 31.4%, at discharge.

Survival at discharge was similar with oxygen versus no oxygen (1.8% vs. 4.5%), Dr. Stub, an interventional cardiologist at St. Paul’s Hospital, Vancouver, B.C., and a researcher at the Baker IDI Heart & Diabetes Institute, Melbourne, reported. .

Oxygen therapy has been used for more than a century in the initial treatment of patients with suspected MI, although there is limited evidence suggesting such therapy is beneficial in patients without hypoxia. A growing body of evidence, however, suggests that even 15 minutes of oxygen can reduce coronary blood flow, increase the production of oxygen-free radicals, and disturb microcirculation, all of which can contribute to reperfusion injury during MI, he said.

The 638 Australian patients in the AVOID (Air Versus Oxygen in ST-Elevation Myocardial Infarction) study were randomized, before hospitalization, by paramedics to oxygen administered via face mask at a flow rate of 8 L/min until patients were stabilized on the ward or to no oxygen, unless oxygen saturation fell below 94%.

Dr. Kern and others pointed out that the oxygen level provided to study participants exceeds the 2-4 L typically given to MI patients in the United States, particularly those who are nonhypoxic.

All parties agreed there is an urgent need for an adequately powered randomized trial to evaluate the effectiveness of oxygen therapy in MI, a conclusion also reached by a recent Cochrane review of the topic (Cochrane Syst. Rev. 2013 August;8:CD007160).

[email protected]

CHICAGO – Optimal guideline-directed medical therapy appears more important than routine coronary CT screening in preventing death and cardiac events in patients with diabetes at high risk for asymptomatic coronary artery disease, the FACTOR-64 trial suggests.

At an average follow-up of 4 years, routine coronary computed tomography angiography (CCTA) failed to significantly reduce the primary composite endpoint of all-cause mortality, nonfatal myocardial infarction, or hospitalization for unstable angina, compared with medical management in the intent-to-treat analysis (6.2% vs. 7.6%, respectively; hazard ratio, 0.80; P = .38).

Event rates were also similar between groups in the as-treated analysis (5.6% vs. 7.9%; HR, 0.69; P = .16), study author Dr. Joseph Brent Muhlestein reported at the American Heart Association scientific sessions.

These findings do not support CCTA screening in this population,” he said.

CCTA screening, however, did reveal coronary artery disease in 70% of patients, prompting a recommendation for additional diagnostics and/or more aggressive management of risk factors. This resulted in modest but significant improvements in lipid subfractions and blood pressure levels in the CCTA group and coronary revascularization procedures in 5.8%, Dr. Muhlestein, with the Intermountain Heart Institute in Murray, Utah, said.

FACTOR-64 randomized 900 patients with type 1 or 2 diabetes for at least 3-5 years and without CAD symptoms to 64-slice CCTA screening or standard guideline-based optimal diabetes care including a target hemoglobin A_1c level of less than 7.0%, LDL cholesterol level below 100 mg/dL, and systolic BP less than 130 mm Hg. Based on CCTA findings, recommendations were made for standard or aggressive therapy (HbA_1c below 6.0%, LDL cholesterol under 70 mg/dL, HDL cholesterol greater than 50 mg/dL in women or above 40 mg/dL in men, triglycerides below 150 mg/dL, and systolic BP under 120 mm Hg) or aggressive therapy with invasive angiography. All patients were recruited from the Intermountain Healthcare system in Utah. Their mean age was 61 years.

The secondary composite endpoint of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina was similar between the CCTA and control groups analyzed by intention to treat (4.6% vs. 5.1%, respectively; HR, 0.89; P = .70) and as-treated (4.1% vs. 5.6%; HR, 0.72; P = .30), according to the results, published online simultaneously (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15825]).

Continued on next page >>

The overall annual event rates in both the control and intervention groups were low, at less than 2% per year. This may be attributed to the excellent medical management received by all patients, as evidenced by baseline levels near or exceeding system targets for HbA_1c, LDL cholesterol, and systolic BP, Dr. Muhlestein said.

In an accompanying editorial (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15958]), Dr. Raymond Gibbons of the Mayo Clinic in Rochester, Minn., agreed that the findings are likely explained by the excellent baseline medical therapy.

“The data in this study suggest that Intermountain Healthcare has set a new published standard for what is achievable in patients with diabetes with respect to blood pressure control and lipid-lowering therapy and that, when therapy is applied this effectively, patients with diabetes are no longer at high risk for major cardiovascular events,” Dr. Gibbons wrote.

Invited discussant Dr. Pamela Douglas, professor of medicine at Duke University in Durham, N.C., said the key message is that the study was tested in a highly managed population, but that nationally less than 10% of diabetes patients are at goal for cardiovascular protection.

Dr. Douglas said CCTA screening may still have a limited role in asymptomatic patients if used to help patients adhere to treatment strategies that can improve outcomes. “This may be a bit roundabout, but that’s the one time,” she added.

Dr. Douglas also called for improved risk-prediction tools to identify even higher-risk individuals, observing that events were not confined to those with obstructive disease.

“We need to be looking for nonobstructive disease, which was in fact the hypothesis of this trial,” she said. “So perhaps we need to look beyond ischemia, beyond atherosclerosis to vulnerable plaque ... and cell targets.”

During the roundtable discussion of the study, panelists suggested that a coronary calcium score could play a role in identifying these higher-risk patients, and that telling a patient they have a calcium score of 800 may also get even the most stubborn diabetes patient to actually take their medications.

The study was supported by the Intermountain Research and Medical Foundation, Intermountain Heart Institute, and grants from Toshiba and Bracco. The study authors reported having no financial disclosures. Dr. Gibbons reported serving as a consultant for Lantheus Medical Imaging. Dr. Douglas reported no conflicts.

CHICAGO – Optimal guideline-directed medical therapy appears more important than routine coronary CT screening in preventing death and cardiac events in patients with diabetes at high risk for asymptomatic coronary artery disease, the FACTOR-64 trial suggests.

At an average follow-up of 4 years, routine coronary computed tomography angiography (CCTA) failed to significantly reduce the primary composite endpoint of all-cause mortality, nonfatal myocardial infarction, or hospitalization for unstable angina, compared with medical management in the intent-to-treat analysis (6.2% vs. 7.6%, respectively; hazard ratio, 0.80; P = .38).

Event rates were also similar between groups in the as-treated analysis (5.6% vs. 7.9%; HR, 0.69; P = .16), study author Dr. Joseph Brent Muhlestein reported at the American Heart Association scientific sessions.

These findings do not support CCTA screening in this population,” he said.

CCTA screening, however, did reveal coronary artery disease in 70% of patients, prompting a recommendation for additional diagnostics and/or more aggressive management of risk factors. This resulted in modest but significant improvements in lipid subfractions and blood pressure levels in the CCTA group and coronary revascularization procedures in 5.8%, Dr. Muhlestein, with the Intermountain Heart Institute in Murray, Utah, said.

FACTOR-64 randomized 900 patients with type 1 or 2 diabetes for at least 3-5 years and without CAD symptoms to 64-slice CCTA screening or standard guideline-based optimal diabetes care including a target hemoglobin A_1c level of less than 7.0%, LDL cholesterol level below 100 mg/dL, and systolic BP less than 130 mm Hg. Based on CCTA findings, recommendations were made for standard or aggressive therapy (HbA_1c below 6.0%, LDL cholesterol under 70 mg/dL, HDL cholesterol greater than 50 mg/dL in women or above 40 mg/dL in men, triglycerides below 150 mg/dL, and systolic BP under 120 mm Hg) or aggressive therapy with invasive angiography. All patients were recruited from the Intermountain Healthcare system in Utah. Their mean age was 61 years.

The secondary composite endpoint of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina was similar between the CCTA and control groups analyzed by intention to treat (4.6% vs. 5.1%, respectively; HR, 0.89; P = .70) and as-treated (4.1% vs. 5.6%; HR, 0.72; P = .30), according to the results, published online simultaneously (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15825]).

Continued on next page >>

The overall annual event rates in both the control and intervention groups were low, at less than 2% per year. This may be attributed to the excellent medical management received by all patients, as evidenced by baseline levels near or exceeding system targets for HbA_1c, LDL cholesterol, and systolic BP, Dr. Muhlestein said.

In an accompanying editorial (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15958]), Dr. Raymond Gibbons of the Mayo Clinic in Rochester, Minn., agreed that the findings are likely explained by the excellent baseline medical therapy.

“The data in this study suggest that Intermountain Healthcare has set a new published standard for what is achievable in patients with diabetes with respect to blood pressure control and lipid-lowering therapy and that, when therapy is applied this effectively, patients with diabetes are no longer at high risk for major cardiovascular events,” Dr. Gibbons wrote.

Invited discussant Dr. Pamela Douglas, professor of medicine at Duke University in Durham, N.C., said the key message is that the study was tested in a highly managed population, but that nationally less than 10% of diabetes patients are at goal for cardiovascular protection.

Dr. Douglas said CCTA screening may still have a limited role in asymptomatic patients if used to help patients adhere to treatment strategies that can improve outcomes. “This may be a bit roundabout, but that’s the one time,” she added.

Dr. Douglas also called for improved risk-prediction tools to identify even higher-risk individuals, observing that events were not confined to those with obstructive disease.

“We need to be looking for nonobstructive disease, which was in fact the hypothesis of this trial,” she said. “So perhaps we need to look beyond ischemia, beyond atherosclerosis to vulnerable plaque ... and cell targets.”

During the roundtable discussion of the study, panelists suggested that a coronary calcium score could play a role in identifying these higher-risk patients, and that telling a patient they have a calcium score of 800 may also get even the most stubborn diabetes patient to actually take their medications.

The study was supported by the Intermountain Research and Medical Foundation, Intermountain Heart Institute, and grants from Toshiba and Bracco. The study authors reported having no financial disclosures. Dr. Gibbons reported serving as a consultant for Lantheus Medical Imaging. Dr. Douglas reported no conflicts.

CHICAGO – Optimal guideline-directed medical therapy appears more important than routine coronary CT screening in preventing death and cardiac events in patients with diabetes at high risk for asymptomatic coronary artery disease, the FACTOR-64 trial suggests.

At an average follow-up of 4 years, routine coronary computed tomography angiography (CCTA) failed to significantly reduce the primary composite endpoint of all-cause mortality, nonfatal myocardial infarction, or hospitalization for unstable angina, compared with medical management in the intent-to-treat analysis (6.2% vs. 7.6%, respectively; hazard ratio, 0.80; P = .38).

Event rates were also similar between groups in the as-treated analysis (5.6% vs. 7.9%; HR, 0.69; P = .16), study author Dr. Joseph Brent Muhlestein reported at the American Heart Association scientific sessions.

These findings do not support CCTA screening in this population,” he said.

CCTA screening, however, did reveal coronary artery disease in 70% of patients, prompting a recommendation for additional diagnostics and/or more aggressive management of risk factors. This resulted in modest but significant improvements in lipid subfractions and blood pressure levels in the CCTA group and coronary revascularization procedures in 5.8%, Dr. Muhlestein, with the Intermountain Heart Institute in Murray, Utah, said.

FACTOR-64 randomized 900 patients with type 1 or 2 diabetes for at least 3-5 years and without CAD symptoms to 64-slice CCTA screening or standard guideline-based optimal diabetes care including a target hemoglobin A_1c level of less than 7.0%, LDL cholesterol level below 100 mg/dL, and systolic BP less than 130 mm Hg. Based on CCTA findings, recommendations were made for standard or aggressive therapy (HbA_1c below 6.0%, LDL cholesterol under 70 mg/dL, HDL cholesterol greater than 50 mg/dL in women or above 40 mg/dL in men, triglycerides below 150 mg/dL, and systolic BP under 120 mm Hg) or aggressive therapy with invasive angiography. All patients were recruited from the Intermountain Healthcare system in Utah. Their mean age was 61 years.

The secondary composite endpoint of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina was similar between the CCTA and control groups analyzed by intention to treat (4.6% vs. 5.1%, respectively; HR, 0.89; P = .70) and as-treated (4.1% vs. 5.6%; HR, 0.72; P = .30), according to the results, published online simultaneously (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15825]).

Continued on next page >>

The overall annual event rates in both the control and intervention groups were low, at less than 2% per year. This may be attributed to the excellent medical management received by all patients, as evidenced by baseline levels near or exceeding system targets for HbA_1c, LDL cholesterol, and systolic BP, Dr. Muhlestein said.

In an accompanying editorial (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15958]), Dr. Raymond Gibbons of the Mayo Clinic in Rochester, Minn., agreed that the findings are likely explained by the excellent baseline medical therapy.

“The data in this study suggest that Intermountain Healthcare has set a new published standard for what is achievable in patients with diabetes with respect to blood pressure control and lipid-lowering therapy and that, when therapy is applied this effectively, patients with diabetes are no longer at high risk for major cardiovascular events,” Dr. Gibbons wrote.

Invited discussant Dr. Pamela Douglas, professor of medicine at Duke University in Durham, N.C., said the key message is that the study was tested in a highly managed population, but that nationally less than 10% of diabetes patients are at goal for cardiovascular protection.

Dr. Douglas said CCTA screening may still have a limited role in asymptomatic patients if used to help patients adhere to treatment strategies that can improve outcomes. “This may be a bit roundabout, but that’s the one time,” she added.

Dr. Douglas also called for improved risk-prediction tools to identify even higher-risk individuals, observing that events were not confined to those with obstructive disease.

“We need to be looking for nonobstructive disease, which was in fact the hypothesis of this trial,” she said. “So perhaps we need to look beyond ischemia, beyond atherosclerosis to vulnerable plaque ... and cell targets.”

During the roundtable discussion of the study, panelists suggested that a coronary calcium score could play a role in identifying these higher-risk patients, and that telling a patient they have a calcium score of 800 may also get even the most stubborn diabetes patient to actually take their medications.

The study was supported by the Intermountain Research and Medical Foundation, Intermountain Heart Institute, and grants from Toshiba and Bracco. The study authors reported having no financial disclosures. Dr. Gibbons reported serving as a consultant for Lantheus Medical Imaging. Dr. Douglas reported no conflicts.

CHICAGO – Optimal guideline-directed medical therapy appears more important than routine coronary CT screening in preventing death and cardiac events in patients with diabetes at high risk for asymptomatic coronary artery disease, the FACTOR-64 trial suggests.

At an average follow-up of 4 years, routine coronary computed tomography angiography (CCTA) failed to significantly reduce the primary composite endpoint of all-cause mortality, nonfatal myocardial infarction, or hospitalization for unstable angina, compared with medical management in the intent-to-treat analysis (6.2% vs. 7.6%, respectively; hazard ratio, 0.80; P = .38).

Event rates were also similar between groups in the as-treated analysis (5.6% vs. 7.9%; HR, 0.69; P = .16), study author Dr. Joseph Brent Muhlestein reported at the American Heart Association scientific sessions.

Robert Lodge/Frontline Medical News

These findings do not support CCTA screening in this population,” he said.

CCTA screening, however, did reveal coronary artery disease in 70% of patients, prompting a recommendation for additional diagnostics and/or more aggressive management of risk factors. This resulted in modest but significant improvements in lipid subfractions and blood pressure levels in the CCTA group and coronary revascularization procedures in 5.8%, Dr. Muhlestein, with the Intermountain Heart Institute in Murray, Utah, said.

FACTOR-64 randomized 900 patients with type 1 or 2 diabetes for at least 3-5 years and without CAD symptoms to 64-slice CCTA screening or standard guideline-based optimal diabetes care including a target hemoglobin A_1c level of less than 7.0%, LDL cholesterol level below 100 mg/dL, and systolic BP less than 130 mm Hg. Based on CCTA findings, recommendations were made for standard or aggressive therapy (HbA_1c below 6.0%, LDL cholesterol under 70 mg/dL, HDL cholesterol greater than 50 mg/dL in women or above 40 mg/dL in men, triglycerides below 150 mg/dL, and systolic BP under 120 mm Hg) or aggressive therapy with invasive angiography. All patients were recruited from the Intermountain Healthcare system in Utah. Their mean age was 61 years.

The secondary composite endpoint of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina was similar between the CCTA and control groups analyzed by intention to treat (4.6% vs. 5.1%, respectively; HR, 0.89; P = .70) and as-treated (4.1% vs. 5.6%; HR, 0.72; P = .30), according to the results, published online simultaneously (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15825]).

The overall annual event rates in both the control and intervention groups were low, at less than 2% per year. This may be attributed to the excellent medical management received by all patients, as evidenced by baseline levels near or exceeding system targets for HbA_1c, LDL cholesterol, and systolic BP, Dr. Muhlestein said.

In an accompanying editorial (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15958]), Dr. Raymond Gibbons of the Mayo Clinic in Rochester, Minn., agreed that the findings are likely explained by the excellent baseline medical therapy.

“The data in this study suggest that Intermountain Healthcare has set a new published standard for what is achievable in patients with diabetes with respect to blood pressure control and lipid-lowering therapy and that, when therapy is applied this effectively, patients with diabetes are no longer at high risk for major cardiovascular events,” Dr. Gibbons wrote.

Invited discussant Dr. Pamela Douglas, professor of medicine at Duke University in Durham, N.C., said the key message is that the study was tested in a highly managed population, but that nationally less than 10% of diabetes patients are at goal for cardiovascular protection.

Dr. Douglas said CCTA screening may still have a limited role in asymptomatic patients if used to help patients adhere to treatment strategies that can improve outcomes. “This may be a bit roundabout, but that’s the one time,” she added.

Dr. Douglas also called for improved risk-prediction tools to identify even higher-risk individuals, observing that events were not confined to those with obstructive disease.

“We need to be looking for nonobstructive disease, which was in fact the hypothesis of this trial,” she said. “So perhaps we need to look beyond ischemia, beyond atherosclerosis to vulnerable plaque ... and cell targets.”

During the roundtable discussion of the study, panelists suggested that a coronary calcium score could play a role in identifying these higher-risk patients, and that telling a patient they have a calcium score of 800 may also get even the most stubborn diabetes patient to actually take their medications.

The study was supported by the Intermountain Research and Medical Foundation, Intermountain Heart Institute, and grants from Toshiba and Bracco. The study authors reported having no financial disclosures. Dr. Gibbons reported serving as a consultant for Lantheus Medical Imaging. Dr. Douglas reported no conflicts.

[email protected]

CHICAGO – Optimal guideline-directed medical therapy appears more important than routine coronary CT screening in preventing death and cardiac events in patients with diabetes at high risk for asymptomatic coronary artery disease, the FACTOR-64 trial suggests.

At an average follow-up of 4 years, routine coronary computed tomography angiography (CCTA) failed to significantly reduce the primary composite endpoint of all-cause mortality, nonfatal myocardial infarction, or hospitalization for unstable angina, compared with medical management in the intent-to-treat analysis (6.2% vs. 7.6%, respectively; hazard ratio, 0.80; P = .38).

Event rates were also similar between groups in the as-treated analysis (5.6% vs. 7.9%; HR, 0.69; P = .16), study author Dr. Joseph Brent Muhlestein reported at the American Heart Association scientific sessions.

Robert Lodge/Frontline Medical News

These findings do not support CCTA screening in this population,” he said.

CCTA screening, however, did reveal coronary artery disease in 70% of patients, prompting a recommendation for additional diagnostics and/or more aggressive management of risk factors. This resulted in modest but significant improvements in lipid subfractions and blood pressure levels in the CCTA group and coronary revascularization procedures in 5.8%, Dr. Muhlestein, with the Intermountain Heart Institute in Murray, Utah, said.

FACTOR-64 randomized 900 patients with type 1 or 2 diabetes for at least 3-5 years and without CAD symptoms to 64-slice CCTA screening or standard guideline-based optimal diabetes care including a target hemoglobin A_1c level of less than 7.0%, LDL cholesterol level below 100 mg/dL, and systolic BP less than 130 mm Hg. Based on CCTA findings, recommendations were made for standard or aggressive therapy (HbA_1c below 6.0%, LDL cholesterol under 70 mg/dL, HDL cholesterol greater than 50 mg/dL in women or above 40 mg/dL in men, triglycerides below 150 mg/dL, and systolic BP under 120 mm Hg) or aggressive therapy with invasive angiography. All patients were recruited from the Intermountain Healthcare system in Utah. Their mean age was 61 years.

The secondary composite endpoint of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina was similar between the CCTA and control groups analyzed by intention to treat (4.6% vs. 5.1%, respectively; HR, 0.89; P = .70) and as-treated (4.1% vs. 5.6%; HR, 0.72; P = .30), according to the results, published online simultaneously (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15825]).

The overall annual event rates in both the control and intervention groups were low, at less than 2% per year. This may be attributed to the excellent medical management received by all patients, as evidenced by baseline levels near or exceeding system targets for HbA_1c, LDL cholesterol, and systolic BP, Dr. Muhlestein said.

In an accompanying editorial (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15958]), Dr. Raymond Gibbons of the Mayo Clinic in Rochester, Minn., agreed that the findings are likely explained by the excellent baseline medical therapy.

“The data in this study suggest that Intermountain Healthcare has set a new published standard for what is achievable in patients with diabetes with respect to blood pressure control and lipid-lowering therapy and that, when therapy is applied this effectively, patients with diabetes are no longer at high risk for major cardiovascular events,” Dr. Gibbons wrote.

Invited discussant Dr. Pamela Douglas, professor of medicine at Duke University in Durham, N.C., said the key message is that the study was tested in a highly managed population, but that nationally less than 10% of diabetes patients are at goal for cardiovascular protection.

Dr. Douglas said CCTA screening may still have a limited role in asymptomatic patients if used to help patients adhere to treatment strategies that can improve outcomes. “This may be a bit roundabout, but that’s the one time,” she added.

Dr. Douglas also called for improved risk-prediction tools to identify even higher-risk individuals, observing that events were not confined to those with obstructive disease.

“We need to be looking for nonobstructive disease, which was in fact the hypothesis of this trial,” she said. “So perhaps we need to look beyond ischemia, beyond atherosclerosis to vulnerable plaque ... and cell targets.”

During the roundtable discussion of the study, panelists suggested that a coronary calcium score could play a role in identifying these higher-risk patients, and that telling a patient they have a calcium score of 800 may also get even the most stubborn diabetes patient to actually take their medications.

The study was supported by the Intermountain Research and Medical Foundation, Intermountain Heart Institute, and grants from Toshiba and Bracco. The study authors reported having no financial disclosures. Dr. Gibbons reported serving as a consultant for Lantheus Medical Imaging. Dr. Douglas reported no conflicts.

[email protected]

CHICAGO – Optimal guideline-directed medical therapy appears more important than routine coronary CT screening in preventing death and cardiac events in patients with diabetes at high risk for asymptomatic coronary artery disease, the FACTOR-64 trial suggests.

At an average follow-up of 4 years, routine coronary computed tomography angiography (CCTA) failed to significantly reduce the primary composite endpoint of all-cause mortality, nonfatal myocardial infarction, or hospitalization for unstable angina, compared with medical management in the intent-to-treat analysis (6.2% vs. 7.6%, respectively; hazard ratio, 0.80; P = .38).

Event rates were also similar between groups in the as-treated analysis (5.6% vs. 7.9%; HR, 0.69; P = .16), study author Dr. Joseph Brent Muhlestein reported at the American Heart Association scientific sessions.

Robert Lodge/Frontline Medical News

These findings do not support CCTA screening in this population,” he said.

CCTA screening, however, did reveal coronary artery disease in 70% of patients, prompting a recommendation for additional diagnostics and/or more aggressive management of risk factors. This resulted in modest but significant improvements in lipid subfractions and blood pressure levels in the CCTA group and coronary revascularization procedures in 5.8%, Dr. Muhlestein, with the Intermountain Heart Institute in Murray, Utah, said.

FACTOR-64 randomized 900 patients with type 1 or 2 diabetes for at least 3-5 years and without CAD symptoms to 64-slice CCTA screening or standard guideline-based optimal diabetes care including a target hemoglobin A_1c level of less than 7.0%, LDL cholesterol level below 100 mg/dL, and systolic BP less than 130 mm Hg. Based on CCTA findings, recommendations were made for standard or aggressive therapy (HbA_1c below 6.0%, LDL cholesterol under 70 mg/dL, HDL cholesterol greater than 50 mg/dL in women or above 40 mg/dL in men, triglycerides below 150 mg/dL, and systolic BP under 120 mm Hg) or aggressive therapy with invasive angiography. All patients were recruited from the Intermountain Healthcare system in Utah. Their mean age was 61 years.

The secondary composite endpoint of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina was similar between the CCTA and control groups analyzed by intention to treat (4.6% vs. 5.1%, respectively; HR, 0.89; P = .70) and as-treated (4.1% vs. 5.6%; HR, 0.72; P = .30), according to the results, published online simultaneously (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15825]).

The overall annual event rates in both the control and intervention groups were low, at less than 2% per year. This may be attributed to the excellent medical management received by all patients, as evidenced by baseline levels near or exceeding system targets for HbA_1c, LDL cholesterol, and systolic BP, Dr. Muhlestein said.

In an accompanying editorial (JAMA 2014 Nov. 17 [doi: 10.1001/jama.2014.15958]), Dr. Raymond Gibbons of the Mayo Clinic in Rochester, Minn., agreed that the findings are likely explained by the excellent baseline medical therapy.

“The data in this study suggest that Intermountain Healthcare has set a new published standard for what is achievable in patients with diabetes with respect to blood pressure control and lipid-lowering therapy and that, when therapy is applied this effectively, patients with diabetes are no longer at high risk for major cardiovascular events,” Dr. Gibbons wrote.

Invited discussant Dr. Pamela Douglas, professor of medicine at Duke University in Durham, N.C., said the key message is that the study was tested in a highly managed population, but that nationally less than 10% of diabetes patients are at goal for cardiovascular protection.

Dr. Douglas said CCTA screening may still have a limited role in asymptomatic patients if used to help patients adhere to treatment strategies that can improve outcomes. “This may be a bit roundabout, but that’s the one time,” she added.

Dr. Douglas also called for improved risk-prediction tools to identify even higher-risk individuals, observing that events were not confined to those with obstructive disease.

“We need to be looking for nonobstructive disease, which was in fact the hypothesis of this trial,” she said. “So perhaps we need to look beyond ischemia, beyond atherosclerosis to vulnerable plaque ... and cell targets.”

During the roundtable discussion of the study, panelists suggested that a coronary calcium score could play a role in identifying these higher-risk patients, and that telling a patient they have a calcium score of 800 may also get even the most stubborn diabetes patient to actually take their medications.

The study was supported by the Intermountain Research and Medical Foundation, Intermountain Heart Institute, and grants from Toshiba and Bracco. The study authors reported having no financial disclosures. Dr. Gibbons reported serving as a consultant for Lantheus Medical Imaging. Dr. Douglas reported no conflicts.

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EDINBURGH – It’s 4 o’clock in the afternoon on a long Mohs surgery day, and you’ve got another patient with innumerable stages plus reconstructions to do.

Performing a fatigue check that gives nursing and biomedical staff the opportunity to admit they’re too tired may be the best next step to prevent wrong-site surgery, Dr. Colin Fleming, president of the British Society for Dermatological Surgery (BSDS), posited at the 15th World Congress on Cancers of the Skin.

@Skynesher/iStockphoto.com

“When we introduced this, it gave great power to the staff, whom we as doctors were asking to work hard on our behalf,” he said. “It’s been a really valuable tool in increasing safety at the end of a long operating day.”

The fatigue check is separate from the oft-recommended preprocedural surgical pause. Though helpful, research has shown that the surgical pause failed to prevent wrong-site surgery in 10% to a third of cases, said Dr. Fleming, a consultant dermatologist and Mohs surgeon at Ninewells Hospital, Dundee, Scotland.

A study on the usefulness of proposed methods for correct biopsy site identification in cutaneous surgery with the Delphi consensus method was recently published (JAMA Dermatol. 2014;150:550-8), but “I’m not convinced it really tells us anything,” he remarked.

Dr. Fleming suggested coupling the surgical pause with a site check, and he emphasized the value of good quality preoperative photographs of the index lesion. Today’s ubiquitous “selfie” may even have a role, as patients themselves often misidentify the biopsy site.

In addition, dermatology departments should have a protocol incorporating a variety of safety features, he said.

However, only 54% of surgeons said they have a written protocol in place to identify the correct surgical site, based on data from a recent survey of BSDS members conducted by Dr. Fleming and his colleagues.

More than a half of respondents (60/114) acknowledged it was “sometimes” difficult to locate the surgical site, with 47 respondents saying it was difficult to locate the surgical site in 1%-10% of cases and 13 admitting it was difficult to do so in 10%-25% of cases.

The face, scalp, and back were reported as the most challenging areas in which to locate the exact surgical site, Dr. Fleming said at the meeting, sponsored by the Skin Cancer Foundation.

When asked what steps they take in their local written protocols to avoid wrong site surgery, 82 respondents said they check with the patient, 66 use drawings/templates with the site marked, 50 use a mirror or photographs, and 39 respondents double-check with a colleague.

Overall, slightly less than 40% of respondents recalled having no patient in the past 5 years who underwent wrong-site surgery. Approximately 28% had 1 wrong-site surgery patient, 28% had 2-3 patients, 3% had 4-5 patients, and 1% had more than 10 such patients.

“Wrong-site surgery in U.K. dermatology departments is infrequent,” Dr. Fleming concluded, adding that only a small proportion led to formal complaints or a medicolegal case.

The response rate to the web-based survey was 37.5% (115/306 members); 32 respondents were Mohs surgeons, 75 were non-Mohs surgeons, 68 worked at a teaching hospital, and 110 had a regular surgical list of between 500 and 2,000 procedures per year that they were responsible for or did themselves.

[email protected]

EDINBURGH – It’s 4 o’clock in the afternoon on a long Mohs surgery day, and you’ve got another patient with innumerable stages plus reconstructions to do.

Performing a fatigue check that gives nursing and biomedical staff the opportunity to admit they’re too tired may be the best next step to prevent wrong-site surgery, Dr. Colin Fleming, president of the British Society for Dermatological Surgery (BSDS), posited at the 15th World Congress on Cancers of the Skin.

@Skynesher/iStockphoto.com

“When we introduced this, it gave great power to the staff, whom we as doctors were asking to work hard on our behalf,” he said. “It’s been a really valuable tool in increasing safety at the end of a long operating day.”

The fatigue check is separate from the oft-recommended preprocedural surgical pause. Though helpful, research has shown that the surgical pause failed to prevent wrong-site surgery in 10% to a third of cases, said Dr. Fleming, a consultant dermatologist and Mohs surgeon at Ninewells Hospital, Dundee, Scotland.

A study on the usefulness of proposed methods for correct biopsy site identification in cutaneous surgery with the Delphi consensus method was recently published (JAMA Dermatol. 2014;150:550-8), but “I’m not convinced it really tells us anything,” he remarked.

Dr. Fleming suggested coupling the surgical pause with a site check, and he emphasized the value of good quality preoperative photographs of the index lesion. Today’s ubiquitous “selfie” may even have a role, as patients themselves often misidentify the biopsy site.

In addition, dermatology departments should have a protocol incorporating a variety of safety features, he said.

However, only 54% of surgeons said they have a written protocol in place to identify the correct surgical site, based on data from a recent survey of BSDS members conducted by Dr. Fleming and his colleagues.

More than a half of respondents (60/114) acknowledged it was “sometimes” difficult to locate the surgical site, with 47 respondents saying it was difficult to locate the surgical site in 1%-10% of cases and 13 admitting it was difficult to do so in 10%-25% of cases.

The face, scalp, and back were reported as the most challenging areas in which to locate the exact surgical site, Dr. Fleming said at the meeting, sponsored by the Skin Cancer Foundation.

When asked what steps they take in their local written protocols to avoid wrong site surgery, 82 respondents said they check with the patient, 66 use drawings/templates with the site marked, 50 use a mirror or photographs, and 39 respondents double-check with a colleague.

Overall, slightly less than 40% of respondents recalled having no patient in the past 5 years who underwent wrong-site surgery. Approximately 28% had 1 wrong-site surgery patient, 28% had 2-3 patients, 3% had 4-5 patients, and 1% had more than 10 such patients.

“Wrong-site surgery in U.K. dermatology departments is infrequent,” Dr. Fleming concluded, adding that only a small proportion led to formal complaints or a medicolegal case.

The response rate to the web-based survey was 37.5% (115/306 members); 32 respondents were Mohs surgeons, 75 were non-Mohs surgeons, 68 worked at a teaching hospital, and 110 had a regular surgical list of between 500 and 2,000 procedures per year that they were responsible for or did themselves.

[email protected]

EDINBURGH – It’s 4 o’clock in the afternoon on a long Mohs surgery day, and you’ve got another patient with innumerable stages plus reconstructions to do.

Performing a fatigue check that gives nursing and biomedical staff the opportunity to admit they’re too tired may be the best next step to prevent wrong-site surgery, Dr. Colin Fleming, president of the British Society for Dermatological Surgery (BSDS), posited at the 15th World Congress on Cancers of the Skin.

@Skynesher/iStockphoto.com

“When we introduced this, it gave great power to the staff, whom we as doctors were asking to work hard on our behalf,” he said. “It’s been a really valuable tool in increasing safety at the end of a long operating day.”

The fatigue check is separate from the oft-recommended preprocedural surgical pause. Though helpful, research has shown that the surgical pause failed to prevent wrong-site surgery in 10% to a third of cases, said Dr. Fleming, a consultant dermatologist and Mohs surgeon at Ninewells Hospital, Dundee, Scotland.

A study on the usefulness of proposed methods for correct biopsy site identification in cutaneous surgery with the Delphi consensus method was recently published (JAMA Dermatol. 2014;150:550-8), but “I’m not convinced it really tells us anything,” he remarked.

Dr. Fleming suggested coupling the surgical pause with a site check, and he emphasized the value of good quality preoperative photographs of the index lesion. Today’s ubiquitous “selfie” may even have a role, as patients themselves often misidentify the biopsy site.

In addition, dermatology departments should have a protocol incorporating a variety of safety features, he said.

However, only 54% of surgeons said they have a written protocol in place to identify the correct surgical site, based on data from a recent survey of BSDS members conducted by Dr. Fleming and his colleagues.

More than a half of respondents (60/114) acknowledged it was “sometimes” difficult to locate the surgical site, with 47 respondents saying it was difficult to locate the surgical site in 1%-10% of cases and 13 admitting it was difficult to do so in 10%-25% of cases.

The face, scalp, and back were reported as the most challenging areas in which to locate the exact surgical site, Dr. Fleming said at the meeting, sponsored by the Skin Cancer Foundation.

When asked what steps they take in their local written protocols to avoid wrong site surgery, 82 respondents said they check with the patient, 66 use drawings/templates with the site marked, 50 use a mirror or photographs, and 39 respondents double-check with a colleague.

Overall, slightly less than 40% of respondents recalled having no patient in the past 5 years who underwent wrong-site surgery. Approximately 28% had 1 wrong-site surgery patient, 28% had 2-3 patients, 3% had 4-5 patients, and 1% had more than 10 such patients.

“Wrong-site surgery in U.K. dermatology departments is infrequent,” Dr. Fleming concluded, adding that only a small proportion led to formal complaints or a medicolegal case.

The response rate to the web-based survey was 37.5% (115/306 members); 32 respondents were Mohs surgeons, 75 were non-Mohs surgeons, 68 worked at a teaching hospital, and 110 had a regular surgical list of between 500 and 2,000 procedures per year that they were responsible for or did themselves.

[email protected]

CHICAGO– Daily low-dose aspirin did not prevent atherosclerotic events in high-risk, elderly Japanese patients in the Japanese Primary Prevention Project.

After a median follow-up of 5 years, the composite primary outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction occurred in 2.77% of patients with hypertension, dyslipidemia, or diabetes on aspirin and 2.96% of those not on aspirin, a nonsignificant difference.

Subgroup analyses did not identify significant differences between study groups, Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.The study was stopped prematurely because the number of primary events was insufficient for the study to reach statistical power.

Daily low-dose aspirin, compared with no aspirin, however, significantly reduced the rate of nonfatal myocardial infarction (0.30% vs. 0.58%; HR, 0.53; P = .02) and transient ischemic attack (0.26% vs. 0.49%; HR, 0.57; P = .04).

However, these benefits must be weighed against an 85% increased risk of serious extracranial hemorrhage in patients on daily aspirin (0.86% vs. 0.51%; HR, 1.85, P = .004), Dr. Shimada of Shin-Oyama City Hospital, Tochigi, Japan, said.

Prespecified gastrointestinal adverse events, including stomach/abdominal pain, gastroduodenal ulcer, reflux esophagitis, and gastrointestinal hemorrhage, were also increased in patients on aspirin, according to results of the late-breaking study, simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

Invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India in Delhi said the negative results do not spell the “end of the road” for aspirin in primary prevention, but emphasize the need to use an individualized, stepwise risk-benefit approach to aspirin therapy.

“The benefit is very unlikely in very low-risk populations such as those with less than 1% [cardiovascular] events per year,” he said. “There would be a role in special groups such as younger populations, lower-income countries, but these are not evaluated well.”

During the discussion following the study presentation, panelists raised concerns about the development of polypills, most of which are for secondary prevention but typically contain aspirin. Other panelists said the study provides a sobering reminder of the risks faced by patients who put themselves on a daily aspirin regimen without consulting a physician.

The Japanese Primary Prevention Project (JPPP) evenly randomized 14,658 patients, aged at least 60 years, with hypertension, dyslipidemia, or diabetes to enteric aspirin 100 mg or no aspirin. A total of 194 patients were excluded because of protocol violations, study withdrawal, or failing to meet inclusion criteria, leaving 7,220 patients in the aspirin group and 7,244 in the no-aspirin group for the modified intention-to-treat population.

In addition to the lower-than-expected total event rate in both the aspirin and no-aspirin groups (193 vs. 207), the use of statins in both arms could have contributed to the negative results, Dr. Shimada reported. Aspirin adherence also fell from 89% in year 1 to only 76% in year 5, while aspirin use in the no-aspirin group increased from 1.5% to 9.8%.

Further analyses are planned to determine whether aspirin is beneficial in select subgroups or in the prevention of cancer.

Dr. J. Michael Gaziano of Brigham and Women’s Hospital in Boston commented in an accompanying JAMA editorial (doi:10.1001/jama.2014.16047) that information from three ongoing primary prevention aspirin trials in patients at higher-than-average risk “will prove helpful for clinical decision making involving the role of aspirin for primary prevention.”

Those trials include the ASCEND study of aspirin 100 mg with or without omega-3 fatty acids in patients at least 40 years old with diabetes, the ARRIVE trial in middle-aged and older patients at moderate risk of cardiovascular disease, and the ASPREE study in the elderly older than 65 years.

JPPP was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainihon-Sumitomo, and serving as a consultant/advisory board member for Omron. Dr. Prabhakaran reported no relevant financial disclosures. Dr. Gaziano reported serving on the executive committee of the ARRIVE trial and as a consultant for and receiving speaking honoraria from Bayer.

[email protected]

CHICAGO– Daily low-dose aspirin did not prevent atherosclerotic events in high-risk, elderly Japanese patients in the Japanese Primary Prevention Project.

After a median follow-up of 5 years, the composite primary outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction occurred in 2.77% of patients with hypertension, dyslipidemia, or diabetes on aspirin and 2.96% of those not on aspirin, a nonsignificant difference.

Subgroup analyses did not identify significant differences between study groups, Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.The study was stopped prematurely because the number of primary events was insufficient for the study to reach statistical power.

Daily low-dose aspirin, compared with no aspirin, however, significantly reduced the rate of nonfatal myocardial infarction (0.30% vs. 0.58%; HR, 0.53; P = .02) and transient ischemic attack (0.26% vs. 0.49%; HR, 0.57; P = .04).

However, these benefits must be weighed against an 85% increased risk of serious extracranial hemorrhage in patients on daily aspirin (0.86% vs. 0.51%; HR, 1.85, P = .004), Dr. Shimada of Shin-Oyama City Hospital, Tochigi, Japan, said.

Prespecified gastrointestinal adverse events, including stomach/abdominal pain, gastroduodenal ulcer, reflux esophagitis, and gastrointestinal hemorrhage, were also increased in patients on aspirin, according to results of the late-breaking study, simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

Invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India in Delhi said the negative results do not spell the “end of the road” for aspirin in primary prevention, but emphasize the need to use an individualized, stepwise risk-benefit approach to aspirin therapy.

“The benefit is very unlikely in very low-risk populations such as those with less than 1% [cardiovascular] events per year,” he said. “There would be a role in special groups such as younger populations, lower-income countries, but these are not evaluated well.”

During the discussion following the study presentation, panelists raised concerns about the development of polypills, most of which are for secondary prevention but typically contain aspirin. Other panelists said the study provides a sobering reminder of the risks faced by patients who put themselves on a daily aspirin regimen without consulting a physician.

The Japanese Primary Prevention Project (JPPP) evenly randomized 14,658 patients, aged at least 60 years, with hypertension, dyslipidemia, or diabetes to enteric aspirin 100 mg or no aspirin. A total of 194 patients were excluded because of protocol violations, study withdrawal, or failing to meet inclusion criteria, leaving 7,220 patients in the aspirin group and 7,244 in the no-aspirin group for the modified intention-to-treat population.

In addition to the lower-than-expected total event rate in both the aspirin and no-aspirin groups (193 vs. 207), the use of statins in both arms could have contributed to the negative results, Dr. Shimada reported. Aspirin adherence also fell from 89% in year 1 to only 76% in year 5, while aspirin use in the no-aspirin group increased from 1.5% to 9.8%.

Further analyses are planned to determine whether aspirin is beneficial in select subgroups or in the prevention of cancer.

Dr. J. Michael Gaziano of Brigham and Women’s Hospital in Boston commented in an accompanying JAMA editorial (doi:10.1001/jama.2014.16047) that information from three ongoing primary prevention aspirin trials in patients at higher-than-average risk “will prove helpful for clinical decision making involving the role of aspirin for primary prevention.”

Those trials include the ASCEND study of aspirin 100 mg with or without omega-3 fatty acids in patients at least 40 years old with diabetes, the ARRIVE trial in middle-aged and older patients at moderate risk of cardiovascular disease, and the ASPREE study in the elderly older than 65 years.

JPPP was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainihon-Sumitomo, and serving as a consultant/advisory board member for Omron. Dr. Prabhakaran reported no relevant financial disclosures. Dr. Gaziano reported serving on the executive committee of the ARRIVE trial and as a consultant for and receiving speaking honoraria from Bayer.

[email protected]

CHICAGO– Daily low-dose aspirin did not prevent atherosclerotic events in high-risk, elderly Japanese patients in the Japanese Primary Prevention Project.

After a median follow-up of 5 years, the composite primary outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction occurred in 2.77% of patients with hypertension, dyslipidemia, or diabetes on aspirin and 2.96% of those not on aspirin, a nonsignificant difference.

Subgroup analyses did not identify significant differences between study groups, Dr. Kazuyuki Shimada reported at the American Heart Association scientific sessions.The study was stopped prematurely because the number of primary events was insufficient for the study to reach statistical power.

Daily low-dose aspirin, compared with no aspirin, however, significantly reduced the rate of nonfatal myocardial infarction (0.30% vs. 0.58%; HR, 0.53; P = .02) and transient ischemic attack (0.26% vs. 0.49%; HR, 0.57; P = .04).

However, these benefits must be weighed against an 85% increased risk of serious extracranial hemorrhage in patients on daily aspirin (0.86% vs. 0.51%; HR, 1.85, P = .004), Dr. Shimada of Shin-Oyama City Hospital, Tochigi, Japan, said.

Prespecified gastrointestinal adverse events, including stomach/abdominal pain, gastroduodenal ulcer, reflux esophagitis, and gastrointestinal hemorrhage, were also increased in patients on aspirin, according to results of the late-breaking study, simultaneously published online in JAMA (doi:10.1001/jama.2014.15690).

Invited discussant Dr. Dorairaj Prabhakaran of the Public Health Foundation of India in Delhi said the negative results do not spell the “end of the road” for aspirin in primary prevention, but emphasize the need to use an individualized, stepwise risk-benefit approach to aspirin therapy.

“The benefit is very unlikely in very low-risk populations such as those with less than 1% [cardiovascular] events per year,” he said. “There would be a role in special groups such as younger populations, lower-income countries, but these are not evaluated well.”

During the discussion following the study presentation, panelists raised concerns about the development of polypills, most of which are for secondary prevention but typically contain aspirin. Other panelists said the study provides a sobering reminder of the risks faced by patients who put themselves on a daily aspirin regimen without consulting a physician.

The Japanese Primary Prevention Project (JPPP) evenly randomized 14,658 patients, aged at least 60 years, with hypertension, dyslipidemia, or diabetes to enteric aspirin 100 mg or no aspirin. A total of 194 patients were excluded because of protocol violations, study withdrawal, or failing to meet inclusion criteria, leaving 7,220 patients in the aspirin group and 7,244 in the no-aspirin group for the modified intention-to-treat population.

In addition to the lower-than-expected total event rate in both the aspirin and no-aspirin groups (193 vs. 207), the use of statins in both arms could have contributed to the negative results, Dr. Shimada reported. Aspirin adherence also fell from 89% in year 1 to only 76% in year 5, while aspirin use in the no-aspirin group increased from 1.5% to 9.8%.

Further analyses are planned to determine whether aspirin is beneficial in select subgroups or in the prevention of cancer.

Dr. J. Michael Gaziano of Brigham and Women’s Hospital in Boston commented in an accompanying JAMA editorial (doi:10.1001/jama.2014.16047) that information from three ongoing primary prevention aspirin trials in patients at higher-than-average risk “will prove helpful for clinical decision making involving the role of aspirin for primary prevention.”

Those trials include the ASCEND study of aspirin 100 mg with or without omega-3 fatty acids in patients at least 40 years old with diabetes, the ARRIVE trial in middle-aged and older patients at moderate risk of cardiovascular disease, and the ASPREE study in the elderly older than 65 years.

JPPP was sponsored by the Japanese Ministry of Health, Labor, and Welfare, and the Waksman Foundation of Japan. Bayer Yakuhin provided the aspirin. Dr. Shimada reported honorarium from MSD, Shionogi, Takeda, Daiichi-Sankyo, and Dainihon-Sumitomo, and serving as a consultant/advisory board member for Omron. Dr. Prabhakaran reported no relevant financial disclosures. Dr. Gaziano reported serving on the executive committee of the ARRIVE trial and as a consultant for and receiving speaking honoraria from Bayer.

[email protected]

CHICAGO – Nivolumab monotherapy resulted in a median overall survival of 8.2 months and a 1-year survival rate of 41% in advanced, heavily pretreated squamous cell non–small cell lung cancer in a phase II study.

Advanced, treatment-refractory squamous cell non–small cell lung cancer (NSCLC) is an area of high unmet need with no effective therapeutic options and this cohort was “truly” treatment refractory, study author Dr. Suresh Ramalingam said at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.

Patrice Wendling/Frontline Medical News

Of the 117 patients, 65% had received at least three prior systemic regimens, 61% had progressive disease as their best response to the most recent therapy, and 76% came into the study within 3 months of completing their most recent therapy.

The patients had stage IIIB/IV disease and were given nivolumab 3 mg/kg IV every 2 weeks until progressive disease or unacceptable toxicity. Their median age was 65 years (range 37-87 years).

The study’s primary end point of objective response rate by independent radiology review was 15% (17/117 patients), including eight confirmed partial responses in patients with rapid progression on prior therapy, Dr. Ramalingam, director of medical oncology and the lung cancer program, Winship Cancer Institute of Emory University, Atlanta, said.

The median duration of response has not been reached and 76% of responses are ongoing. In all, 24% of patients received subsequent therapy, excluding subsequent immunotherapy.

Median progression-free survival (PFS) was 2 months and the 1-year PFS rate was 20%, he said.

An exploratory biomarker analysis of 76 evaluable samples showed nivolumab was clinically active in patients whose tumors were positive as well as negative for programmed death-ligand 1 expression.

Dr. Ramalingam highlighted a 73-year-old former smoker with stage IIIB disease and active brain metastasis at study entry who had stable disease after treatment with nivolumab that was ongoing at 68 weeks including a response in his brain lesions, despite having no prior central nervous system-directed therapy, and failing prior radiotherapy and three prior systemic regimens (cisplatin[Platinol]/gemcitabine [Gemzar], docetaxel [Taxotere], and vinorelbine [Navelbine]).

Overall, nivolumab was well tolerated, as shown by the fact that 85% of patients received at least 90% of their planned dose intensity, he said.

The safety profile was consistent with prior nivolumab studies, with 12% of patients discontinuing treatment because of toxicity. Two treatment-related deaths (one hypoxic pneumonia and one ischemic stroke) occurred in patients with multiple comorbidities and concurrent progressive disease.

A poster also presented at the meeting (Ab. 170, Gettinger, S.N., et al.) showed an objective response rate of 17% among 54 treatment-refractory patients given second-line or later nivolumab 1 mg/kg, 3 mg/kg, or 10 mg/kg every 2 weeks for squamous cell NSCLC, among other solid tumors. The median PFS was 3.8 months, 1-year PFS 27%, median overall survival 9.2 months, and 1-year overall survival 41%.

A phase III trial is also ongoing comparing overall survival of nivolumab vs. docetaxel in advanced squamous cell NSCLC after failure of prior platinum-based chemotherapy, Dr. Ramalingam said.

[email protected]

CHICAGO – Nivolumab monotherapy resulted in a median overall survival of 8.2 months and a 1-year survival rate of 41% in advanced, heavily pretreated squamous cell non–small cell lung cancer in a phase II study.

Advanced, treatment-refractory squamous cell non–small cell lung cancer (NSCLC) is an area of high unmet need with no effective therapeutic options and this cohort was “truly” treatment refractory, study author Dr. Suresh Ramalingam said at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.

Patrice Wendling/Frontline Medical News

Of the 117 patients, 65% had received at least three prior systemic regimens, 61% had progressive disease as their best response to the most recent therapy, and 76% came into the study within 3 months of completing their most recent therapy.

The patients had stage IIIB/IV disease and were given nivolumab 3 mg/kg IV every 2 weeks until progressive disease or unacceptable toxicity. Their median age was 65 years (range 37-87 years).

The study’s primary end point of objective response rate by independent radiology review was 15% (17/117 patients), including eight confirmed partial responses in patients with rapid progression on prior therapy, Dr. Ramalingam, director of medical oncology and the lung cancer program, Winship Cancer Institute of Emory University, Atlanta, said.

The median duration of response has not been reached and 76% of responses are ongoing. In all, 24% of patients received subsequent therapy, excluding subsequent immunotherapy.

Median progression-free survival (PFS) was 2 months and the 1-year PFS rate was 20%, he said.

An exploratory biomarker analysis of 76 evaluable samples showed nivolumab was clinically active in patients whose tumors were positive as well as negative for programmed death-ligand 1 expression.

Dr. Ramalingam highlighted a 73-year-old former smoker with stage IIIB disease and active brain metastasis at study entry who had stable disease after treatment with nivolumab that was ongoing at 68 weeks including a response in his brain lesions, despite having no prior central nervous system-directed therapy, and failing prior radiotherapy and three prior systemic regimens (cisplatin[Platinol]/gemcitabine [Gemzar], docetaxel [Taxotere], and vinorelbine [Navelbine]).

Overall, nivolumab was well tolerated, as shown by the fact that 85% of patients received at least 90% of their planned dose intensity, he said.

The safety profile was consistent with prior nivolumab studies, with 12% of patients discontinuing treatment because of toxicity. Two treatment-related deaths (one hypoxic pneumonia and one ischemic stroke) occurred in patients with multiple comorbidities and concurrent progressive disease.

A poster also presented at the meeting (Ab. 170, Gettinger, S.N., et al.) showed an objective response rate of 17% among 54 treatment-refractory patients given second-line or later nivolumab 1 mg/kg, 3 mg/kg, or 10 mg/kg every 2 weeks for squamous cell NSCLC, among other solid tumors. The median PFS was 3.8 months, 1-year PFS 27%, median overall survival 9.2 months, and 1-year overall survival 41%.

A phase III trial is also ongoing comparing overall survival of nivolumab vs. docetaxel in advanced squamous cell NSCLC after failure of prior platinum-based chemotherapy, Dr. Ramalingam said.

[email protected]

CHICAGO – Nivolumab monotherapy resulted in a median overall survival of 8.2 months and a 1-year survival rate of 41% in advanced, heavily pretreated squamous cell non–small cell lung cancer in a phase II study.

Advanced, treatment-refractory squamous cell non–small cell lung cancer (NSCLC) is an area of high unmet need with no effective therapeutic options and this cohort was “truly” treatment refractory, study author Dr. Suresh Ramalingam said at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology.

Patrice Wendling/Frontline Medical News

Of the 117 patients, 65% had received at least three prior systemic regimens, 61% had progressive disease as their best response to the most recent therapy, and 76% came into the study within 3 months of completing their most recent therapy.

The patients had stage IIIB/IV disease and were given nivolumab 3 mg/kg IV every 2 weeks until progressive disease or unacceptable toxicity. Their median age was 65 years (range 37-87 years).

The study’s primary end point of objective response rate by independent radiology review was 15% (17/117 patients), including eight confirmed partial responses in patients with rapid progression on prior therapy, Dr. Ramalingam, director of medical oncology and the lung cancer program, Winship Cancer Institute of Emory University, Atlanta, said.

The median duration of response has not been reached and 76% of responses are ongoing. In all, 24% of patients received subsequent therapy, excluding subsequent immunotherapy.

Median progression-free survival (PFS) was 2 months and the 1-year PFS rate was 20%, he said.

An exploratory biomarker analysis of 76 evaluable samples showed nivolumab was clinically active in patients whose tumors were positive as well as negative for programmed death-ligand 1 expression.

Dr. Ramalingam highlighted a 73-year-old former smoker with stage IIIB disease and active brain metastasis at study entry who had stable disease after treatment with nivolumab that was ongoing at 68 weeks including a response in his brain lesions, despite having no prior central nervous system-directed therapy, and failing prior radiotherapy and three prior systemic regimens (cisplatin[Platinol]/gemcitabine [Gemzar], docetaxel [Taxotere], and vinorelbine [Navelbine]).

Overall, nivolumab was well tolerated, as shown by the fact that 85% of patients received at least 90% of their planned dose intensity, he said.

The safety profile was consistent with prior nivolumab studies, with 12% of patients discontinuing treatment because of toxicity. Two treatment-related deaths (one hypoxic pneumonia and one ischemic stroke) occurred in patients with multiple comorbidities and concurrent progressive disease.

A poster also presented at the meeting (Ab. 170, Gettinger, S.N., et al.) showed an objective response rate of 17% among 54 treatment-refractory patients given second-line or later nivolumab 1 mg/kg, 3 mg/kg, or 10 mg/kg every 2 weeks for squamous cell NSCLC, among other solid tumors. The median PFS was 3.8 months, 1-year PFS 27%, median overall survival 9.2 months, and 1-year overall survival 41%.

A phase III trial is also ongoing comparing overall survival of nivolumab vs. docetaxel in advanced squamous cell NSCLC after failure of prior platinum-based chemotherapy, Dr. Ramalingam said.

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CHICAGO – Biopsies performed in patients ultimately not diagnosed with lung cancer accounted for 43% of the $38.3 million spent in lung cancer diagnostic costs in a Medicare analysis.

“We need to develop more precise risk stratification tools to better identify patients who require referrals for lung biopsy. This has the potential to reduce costs and improve patient outcomes,” study author Tasneem Lokhandwala, Ph.D., said during a press briefing at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. To estimate the use of diagnostic tests in lung cancer diagnosis and detection as well as the costs incurred by Medicare patients, Dr. Lokhandwala and her associates used a random 5% sample of Medicare patients from Jan. 1, 2009 through Dec. 31, 2011.

In all, 8,979 patients, aged 65-74 years, were identified with an abnormal computed tomography scan from July 1, 2009 through Dec. 31, 2010. Their mean age was 69.3 years, 43.6% were male, and 86.5% white.

The date of the patient’s abnormal CT scan was defined as the index date. Patients diagnosed with any cancer, pneumonia, atelectasis, or tuberculosis in the 6-month preindex period were excluded.

During the 12-month follow-up period, 14% of patients were diagnosed with lung cancer, with a median time to diagnosis from the abnormal chest CT of 11 days.

Diagnostic tests used were chest x-rays for 54.4%, chest CT scans for 33%, chest positron emission tomography scans for 0.5%, and lung biopsy for 19.4%, Dr. Lokhandwala, a data analyst at Xcenda, Palm Harbor, Fla., reported.

Importantly, the National Comprehensive Cancer Network guidelines call for low-dose chest CT followed by a PET scan to identify patients for biopsy.

In terms of financial costs, the average total cost of the diagnostic work-up was $7,567 for patients diagnosed with lung cancer and $3,558 for those without a lung cancer diagnosis.

For both groups, these costs rose dramatically with the use of biopsy to $8,341 and $22,127, respectively, Dr. Lokhandwala said.

Of the 1,744 patients who underwent a biopsy, 19.3% experienced a biopsy-related adverse event. An adverse event increased the average cost of a biopsy fourfold from $8,869 to $37,745, she said.

“Apart from the financial costs and the adverse events associated with tests and biopsies, there was also likely tremendous stress for those patients who ultimately were not found to have lung cancer,” press briefing moderator Dr. Laurie E. Gaspar, professor and chair of radiation oncology at the University of Colorado at Denver, Aurora, said.

Dr. Gaspar agreed that the data highlight the need to better identify patients with lung cancer through the use of better imaging tests, follow-up CT or PET scans, or liquid biopsies.

[email protected]

CHICAGO – Biopsies performed in patients ultimately not diagnosed with lung cancer accounted for 43% of the $38.3 million spent in lung cancer diagnostic costs in a Medicare analysis.

“We need to develop more precise risk stratification tools to better identify patients who require referrals for lung biopsy. This has the potential to reduce costs and improve patient outcomes,” study author Tasneem Lokhandwala, Ph.D., said during a press briefing at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. To estimate the use of diagnostic tests in lung cancer diagnosis and detection as well as the costs incurred by Medicare patients, Dr. Lokhandwala and her associates used a random 5% sample of Medicare patients from Jan. 1, 2009 through Dec. 31, 2011.

In all, 8,979 patients, aged 65-74 years, were identified with an abnormal computed tomography scan from July 1, 2009 through Dec. 31, 2010. Their mean age was 69.3 years, 43.6% were male, and 86.5% white.

The date of the patient’s abnormal CT scan was defined as the index date. Patients diagnosed with any cancer, pneumonia, atelectasis, or tuberculosis in the 6-month preindex period were excluded.

During the 12-month follow-up period, 14% of patients were diagnosed with lung cancer, with a median time to diagnosis from the abnormal chest CT of 11 days.

Diagnostic tests used were chest x-rays for 54.4%, chest CT scans for 33%, chest positron emission tomography scans for 0.5%, and lung biopsy for 19.4%, Dr. Lokhandwala, a data analyst at Xcenda, Palm Harbor, Fla., reported.

Importantly, the National Comprehensive Cancer Network guidelines call for low-dose chest CT followed by a PET scan to identify patients for biopsy.

In terms of financial costs, the average total cost of the diagnostic work-up was $7,567 for patients diagnosed with lung cancer and $3,558 for those without a lung cancer diagnosis.

For both groups, these costs rose dramatically with the use of biopsy to $8,341 and $22,127, respectively, Dr. Lokhandwala said.

Of the 1,744 patients who underwent a biopsy, 19.3% experienced a biopsy-related adverse event. An adverse event increased the average cost of a biopsy fourfold from $8,869 to $37,745, she said.

“Apart from the financial costs and the adverse events associated with tests and biopsies, there was also likely tremendous stress for those patients who ultimately were not found to have lung cancer,” press briefing moderator Dr. Laurie E. Gaspar, professor and chair of radiation oncology at the University of Colorado at Denver, Aurora, said.

Dr. Gaspar agreed that the data highlight the need to better identify patients with lung cancer through the use of better imaging tests, follow-up CT or PET scans, or liquid biopsies.

[email protected]

CHICAGO – Biopsies performed in patients ultimately not diagnosed with lung cancer accounted for 43% of the $38.3 million spent in lung cancer diagnostic costs in a Medicare analysis.

“We need to develop more precise risk stratification tools to better identify patients who require referrals for lung biopsy. This has the potential to reduce costs and improve patient outcomes,” study author Tasneem Lokhandwala, Ph.D., said during a press briefing at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. To estimate the use of diagnostic tests in lung cancer diagnosis and detection as well as the costs incurred by Medicare patients, Dr. Lokhandwala and her associates used a random 5% sample of Medicare patients from Jan. 1, 2009 through Dec. 31, 2011.

In all, 8,979 patients, aged 65-74 years, were identified with an abnormal computed tomography scan from July 1, 2009 through Dec. 31, 2010. Their mean age was 69.3 years, 43.6% were male, and 86.5% white.

The date of the patient’s abnormal CT scan was defined as the index date. Patients diagnosed with any cancer, pneumonia, atelectasis, or tuberculosis in the 6-month preindex period were excluded.

During the 12-month follow-up period, 14% of patients were diagnosed with lung cancer, with a median time to diagnosis from the abnormal chest CT of 11 days.

Diagnostic tests used were chest x-rays for 54.4%, chest CT scans for 33%, chest positron emission tomography scans for 0.5%, and lung biopsy for 19.4%, Dr. Lokhandwala, a data analyst at Xcenda, Palm Harbor, Fla., reported.

Importantly, the National Comprehensive Cancer Network guidelines call for low-dose chest CT followed by a PET scan to identify patients for biopsy.

In terms of financial costs, the average total cost of the diagnostic work-up was $7,567 for patients diagnosed with lung cancer and $3,558 for those without a lung cancer diagnosis.

For both groups, these costs rose dramatically with the use of biopsy to $8,341 and $22,127, respectively, Dr. Lokhandwala said.

Of the 1,744 patients who underwent a biopsy, 19.3% experienced a biopsy-related adverse event. An adverse event increased the average cost of a biopsy fourfold from $8,869 to $37,745, she said.

“Apart from the financial costs and the adverse events associated with tests and biopsies, there was also likely tremendous stress for those patients who ultimately were not found to have lung cancer,” press briefing moderator Dr. Laurie E. Gaspar, professor and chair of radiation oncology at the University of Colorado at Denver, Aurora, said.

Dr. Gaspar agreed that the data highlight the need to better identify patients with lung cancer through the use of better imaging tests, follow-up CT or PET scans, or liquid biopsies.

[email protected]