AHA Scientific Sessions 2014

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).

pwendling@frontlinemedcom.com

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).

pwendling@frontlinemedcom.com

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).

pwendling@frontlinemedcom.com

CHICAGO – Two new types of drug-eluting, biodegradable polymer stents weren’t inferior to current drug-eluting stents, and they possibly may have caused fewer stent thrombosis episodes.

But do the new stents reduce the risk of long-term stent thrombosis? How will their ease of use affect choice of stents? And how should long-term coronary events that aren’t related to the stents themselves shape approaches to secondary prevention?

In an interview at the American Heart Association scientific sessions, Dr. Robert Harrington shared his perspectives on these questions and connected the stent studies’ results with new findings in prevention research.

The two studies of the new stents were not large enough, nor were patients followed long enough, to prove an advantage in stent thrombosis rates in a definitive way. But the lead investigator in the everolimus-eluting Synergy stent study described the stent as more flexible and deliverable than current coronary stents.

Those usability features may make that stent an attractive option for interventional cardiologists even if clinical outcomes are not significantly improved, Dr. Harrington noted.

“These technical features, such as improved deliverability, are things that will resonate with the interventional community,” he said. “It offers another option for complex cases, and that appeals greatly to interventional cardiologists who are looking for technical solutions,” said Dr. Harrington, professor and chairman of medicine at Stanford (Calif.) University.

Dr. Harrington said that he had no disclosures regarding the studied stents, but he has received grants from several drug companies that market drugs used during and after patients undergo percutaneous coronary interventions.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

CHICAGO – Two new types of drug-eluting, biodegradable polymer stents weren’t inferior to current drug-eluting stents, and they possibly may have caused fewer stent thrombosis episodes.

But do the new stents reduce the risk of long-term stent thrombosis? How will their ease of use affect choice of stents? And how should long-term coronary events that aren’t related to the stents themselves shape approaches to secondary prevention?

In an interview at the American Heart Association scientific sessions, Dr. Robert Harrington shared his perspectives on these questions and connected the stent studies’ results with new findings in prevention research.

The two studies of the new stents were not large enough, nor were patients followed long enough, to prove an advantage in stent thrombosis rates in a definitive way. But the lead investigator in the everolimus-eluting Synergy stent study described the stent as more flexible and deliverable than current coronary stents.

Those usability features may make that stent an attractive option for interventional cardiologists even if clinical outcomes are not significantly improved, Dr. Harrington noted.

“These technical features, such as improved deliverability, are things that will resonate with the interventional community,” he said. “It offers another option for complex cases, and that appeals greatly to interventional cardiologists who are looking for technical solutions,” said Dr. Harrington, professor and chairman of medicine at Stanford (Calif.) University.

Dr. Harrington said that he had no disclosures regarding the studied stents, but he has received grants from several drug companies that market drugs used during and after patients undergo percutaneous coronary interventions.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

CHICAGO – Two new types of drug-eluting, biodegradable polymer stents weren’t inferior to current drug-eluting stents, and they possibly may have caused fewer stent thrombosis episodes.

But do the new stents reduce the risk of long-term stent thrombosis? How will their ease of use affect choice of stents? And how should long-term coronary events that aren’t related to the stents themselves shape approaches to secondary prevention?

In an interview at the American Heart Association scientific sessions, Dr. Robert Harrington shared his perspectives on these questions and connected the stent studies’ results with new findings in prevention research.

The two studies of the new stents were not large enough, nor were patients followed long enough, to prove an advantage in stent thrombosis rates in a definitive way. But the lead investigator in the everolimus-eluting Synergy stent study described the stent as more flexible and deliverable than current coronary stents.

Those usability features may make that stent an attractive option for interventional cardiologists even if clinical outcomes are not significantly improved, Dr. Harrington noted.

“These technical features, such as improved deliverability, are things that will resonate with the interventional community,” he said. “It offers another option for complex cases, and that appeals greatly to interventional cardiologists who are looking for technical solutions,” said Dr. Harrington, professor and chairman of medicine at Stanford (Calif.) University.

Dr. Harrington said that he had no disclosures regarding the studied stents, but he has received grants from several drug companies that market drugs used during and after patients undergo percutaneous coronary interventions.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

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.

pwendling@frontlinemedcom.com

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.

pwendling@frontlinemedcom.com

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.

pwendling@frontlinemedcom.com

CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.

In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.

One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”

Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.

Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.

While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.

“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.

He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.

“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.

Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).

For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.

Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”

He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.

“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.

CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.

In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.

One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”

Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.

Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.

While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.

“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.

He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.

“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.

Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).

For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.

Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”

He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.

“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.

CHICAGO – The next time the U.S. hypertension management guideline gets revised, possibly within another couple of years, it may abandon the current approach of focusing primarily on a person’s blood pressure numbers and center instead on assessing a patient’s overall cardiovascular risk and using that status to guide the need for antihypertensive treatment and how aggressively it is applied.

In short, what some preventive cardiologists see coming down the pike is a blood pressure management guideline that follows the same path carved by the cholesterol management guideline issued by the American College of Cardiology and American Heart Association in 2013 (Circulation 2014 [doi: 10.1161/01.cir.0000437738.63853.7a]) that linked use of lipid-lowering treatment with a statin mostly to a patient’s atherosclerotic cardiovascular disease (ASCVD) risk rather than to their level of LDL cholesterol.

One example of the evidence driving this revisionist approach to thinking about hypertension definition came in a report at the American Heart Association Scientific Sessions that showed “a blood pressure treatment strategy focused just on blood pressure leaves substantial CVD risk unaddressed,” said Dr. Kunal N. Karmali, a cardiologist at Northwestern University, Chicago. “Multivariate risk estimation may help identify types of individuals who are likely to benefit from risk-reducing therapy across the spectrum of blood pressure.”

Dr. Karmali and his associates ran their analysis using data from two well-defined U.S. population data bases that included long-term follow-up, the Atherosclerosis Risk in Communities study and the Framingham Offspring Study, which together provided data for 18,898 people. The researchers categorized these people by their baseline systolic blood pressures into six groups, from below 120 mm Hg to 160 mm Hg and above, and calculated each person’s risk for an incident ASCVD event according to their baseline ASCVD risk score using the risk calculator that accompanied release of the 2013 cholesterol management guidelines. By subtracting the baseline risk–derived prediction of the CVD event rate from the actual number of events during follow-up, Dr. Karmali’s group came up with an estimate of the level of “excess” risk for people within each 10 mm Hg blood pressure stratum.

Ten-year follow-up of the two cohorts identified 739 ASCVD events, of which more than 500 were “excess;” the people in the two cohorts had substantially more ASCVD events than would have been predicted by their risk factors alone. These excess events occurred at all levels of blood pressure. The 6,656 people with baseline systolic blood pressures of 120-139 mm Hg, 35% of the people included in the study, had 45% of the excess events, Dr. Karmali reported.

While people with blood pressures of 120-139 mm Hg would generally not be candidates for antihypertensive treatment based on the existing U.S. guideline (JAMA 2014;311[5]:507-20), a sizable majority, 73%, had high baseline ASCVD risk levels, with predicted 10-year CVD rates of 7.5% or greater.

“An implication of this finding is to think beyond just blood pressure,” Dr. Karmali said. “You need to consider multiple risk factors and use overall risk assessment to inform your management decisions. Looking at just the single risk factor of blood pressure doesn’t capture the true benefits of treatment and weigh that against the risks from treatment,” he said in an interview.

He gave the example of an otherwise healthy woman aged 40 years with a systolic blood pressure of 142 mm Hg, who clearly has a different 10-year risk level than a man aged 70 years who has diabetes and smokes and also has a systolic pressure of 142 mm Hg.

“For cholesterol, we now direct our interventions at people who are at the highest risk, but for blood pressure we still focus on just the single number. Multivariate risk assessment would allow us to direct the interventions at the people who are more likely to benefit,” Dr. Kamali said.

Other recent analyses have also supported this approach, he noted. For example, a metaanalysis published in August used data from nearly 52,000 people collected in 11 studies to show that blood pressure–lowering treatment had a very similar impact on reducing future cardiovascular disease events regardless of a person’s baseline cardiovascular risk level (Lancet 2014;384:591-8).

For middle-aged adults and older people, “I think we would become much more efficient in our selection of people with modestly elevated blood pressure [who need drug treatment] by considering their global risk,” said Dr. Donald M. Lloyd-Jones, professor and chairman of preventive medicine at Northwestern University, and a collaborator on Dr. Karmali’s study.

Another advantage of a risk-based approach to blood pressure management over a number-based approach is that “putting blood pressure into the global context of risk makes me think about global risk management, and that is where clinicians need to move,” Dr. Lloyd-Jones said in an interview. “It’s not just, ‘get a number, treat it, and you’re done.’ You need to also think about statin treatment.”

He acknowledged the need for some caution in this approach, such as recognizing that blood pressure must be carefully reduced in, for example, people with a systolic pressure of 120-129 mm Hg so that blood pressure is not reduced to a dangerously low level (unlike cholesterol, which so far has not shown been shown to cause problems when reduced to very low levels). He also noted that a young adult with a fairly high systolic pressure of, say, 160 mm Hg should receive antihypertensive treatment even if the person has an otherwise low ASCVD risk. But in general a risk-based approach should provide better patient care, he said.

“If this is where new hypertension management guidelines go it would be a significant change,” Dr. Lloyd-Jones acknowledged, “but I think it would help patients. I think this approach merits real consideration” by the panel that will soon create the next revision to the U.S. hypertension management guideline.

Treatment with losartan instead of more conventional atenolol yielded no significant difference in aortic-root dilation in children and young adults with Marfan’s syndrome over 3 years, according to a new study published in the New England Journal of Medicine and presented simultaneously at the American Heart Association’s Scientific Sessions.

In a randomized trial, researchers identified 608 children and young adults with Marfan’s syndrome and randomized them to treatment with either losartan (267) or atenolol (268) for 3 years. The participants were between the ages of 6 months and 25 years, had been diagnosed with Marfan’s syndrome according to the original Ghent criteria, and possessed a z score of 3.0 for maximum aortic-root diameter indexed to body surface area. The baseline subgroups were predefined as aortic-root z score being less than 4.5 vs. at or greater than 4.5, young adult vs. child, and previous use of beta-blocker (yes vs. no).

The results indicate that the baseline-adjusted annual rate of change in the aortic-root z score did not differ substantially between the losartan and atenolol groups: –0.107 ± 0.013 and –0.139 ± 0.013 standard deviation units, respectively (P = .08). Both data groups were significantly less than 0, however, indicating that both treatments were effective in decreasing aortic-root z scores. Younger patients in both groups experienced greater decreases in aortic-root z scores, but one was not significantly more than the other (P = .002 and P < .001 for losartan and atenolol, respectively).

“We did not find the expected advantage of angiotensin-receptor blockade therapy over beta-blocker therapy,” wrote the authors, led by Dr. Ronald V. Lacro of Boston Children’s Hospital’s Department of Cardiology (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1404731]).

There were “small but significant differences favoring atenolol in the average annual change in the absolute diameter and z score for the aortic annulus, but there were no significant differences in the diameter or z score for the ascending aorta,” according to the investigators.

“This finding was unexpected, without a clear physiological explanation,” wrote Dr. Lacro and his associates.

The study was supported by a grant from the National Institute of Health’s National Heart, Lung, and Blood Institute. The authors reported no other financial conflicts of interest.

dchitnis@frontlinemedcom.com

Treatment with losartan instead of more conventional atenolol yielded no significant difference in aortic-root dilation in children and young adults with Marfan’s syndrome over 3 years, according to a new study published in the New England Journal of Medicine and presented simultaneously at the American Heart Association’s Scientific Sessions.

In a randomized trial, researchers identified 608 children and young adults with Marfan’s syndrome and randomized them to treatment with either losartan (267) or atenolol (268) for 3 years. The participants were between the ages of 6 months and 25 years, had been diagnosed with Marfan’s syndrome according to the original Ghent criteria, and possessed a z score of 3.0 for maximum aortic-root diameter indexed to body surface area. The baseline subgroups were predefined as aortic-root z score being less than 4.5 vs. at or greater than 4.5, young adult vs. child, and previous use of beta-blocker (yes vs. no).

The results indicate that the baseline-adjusted annual rate of change in the aortic-root z score did not differ substantially between the losartan and atenolol groups: –0.107 ± 0.013 and –0.139 ± 0.013 standard deviation units, respectively (P = .08). Both data groups were significantly less than 0, however, indicating that both treatments were effective in decreasing aortic-root z scores. Younger patients in both groups experienced greater decreases in aortic-root z scores, but one was not significantly more than the other (P = .002 and P < .001 for losartan and atenolol, respectively).

“We did not find the expected advantage of angiotensin-receptor blockade therapy over beta-blocker therapy,” wrote the authors, led by Dr. Ronald V. Lacro of Boston Children’s Hospital’s Department of Cardiology (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1404731]).

There were “small but significant differences favoring atenolol in the average annual change in the absolute diameter and z score for the aortic annulus, but there were no significant differences in the diameter or z score for the ascending aorta,” according to the investigators.

“This finding was unexpected, without a clear physiological explanation,” wrote Dr. Lacro and his associates.

The study was supported by a grant from the National Institute of Health’s National Heart, Lung, and Blood Institute. The authors reported no other financial conflicts of interest.

dchitnis@frontlinemedcom.com

Treatment with losartan instead of more conventional atenolol yielded no significant difference in aortic-root dilation in children and young adults with Marfan’s syndrome over 3 years, according to a new study published in the New England Journal of Medicine and presented simultaneously at the American Heart Association’s Scientific Sessions.

In a randomized trial, researchers identified 608 children and young adults with Marfan’s syndrome and randomized them to treatment with either losartan (267) or atenolol (268) for 3 years. The participants were between the ages of 6 months and 25 years, had been diagnosed with Marfan’s syndrome according to the original Ghent criteria, and possessed a z score of 3.0 for maximum aortic-root diameter indexed to body surface area. The baseline subgroups were predefined as aortic-root z score being less than 4.5 vs. at or greater than 4.5, young adult vs. child, and previous use of beta-blocker (yes vs. no).

The results indicate that the baseline-adjusted annual rate of change in the aortic-root z score did not differ substantially between the losartan and atenolol groups: –0.107 ± 0.013 and –0.139 ± 0.013 standard deviation units, respectively (P = .08). Both data groups were significantly less than 0, however, indicating that both treatments were effective in decreasing aortic-root z scores. Younger patients in both groups experienced greater decreases in aortic-root z scores, but one was not significantly more than the other (P = .002 and P < .001 for losartan and atenolol, respectively).

“We did not find the expected advantage of angiotensin-receptor blockade therapy over beta-blocker therapy,” wrote the authors, led by Dr. Ronald V. Lacro of Boston Children’s Hospital’s Department of Cardiology (N. Engl. J. Med. 2014 [doi:10.1056/NEJMoa1404731]).

There were “small but significant differences favoring atenolol in the average annual change in the absolute diameter and z score for the aortic annulus, but there were no significant differences in the diameter or z score for the ascending aorta,” according to the investigators.

“This finding was unexpected, without a clear physiological explanation,” wrote Dr. Lacro and his associates.

The study was supported by a grant from the National Institute of Health’s National Heart, Lung, and Blood Institute. The authors reported no other financial conflicts of interest.

dchitnis@frontlinemedcom.com

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.

pwendling@frontlinemedcom.com

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.

pwendling@frontlinemedcom.com

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.

pwendling@frontlinemedcom.com