AHA Scientific Sessions 2015

ORLANDO – Results from the SPRINT hypertension trial are “truly practice changing,” by “giving us definitive clinical-trial evidence that an additional 15-18 mm Hg lowering of systolic blood pressure, aiming for a target of less than 120 mm Hg, translates into” a significantly reduced composite cardiovascular-event endpoint as well as significantly reduced all-cause death, Dr. Gregg C. Fonarow said in an interview at the American Heart Association scientific sessions.

The significant, 27% relative reduction in all-cause mortality in SPRINT in patients targeted to a systolic blood pressure of less than 120 mm Hg was especially notable because an all-cause mortality benefit is not typically seen with other interventions, and because it “ultimately demonstrates that the benefits clearly outweigh the potential risks,” said Dr. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

Dr. Fonarow acknowledged that results from SPRINT showed a more aggressive regimen also produced higher rates of certain important adverse effects, such as acute kidney injury. But the large incremental benefit in total mortality during the greater than 3 years of average follow-up showed the overwhelming net benefit from more aggressive antihypertensive treatment.

Less clear is whether the SPRINT results say anything about initiating antihypertensive treatment in a patients who resemble those enrolled in the trial and have an untreated systolic blood pressure of 130-139 mm Hg. While people like these could enter SPRINT, they constituted just under 10% of the enrolled population.

“The vast majority of patients in the trial met the conventional clinical definition of hypertension, with a systolic blood pressure of 140 mm Hg or greater and already on some treatment, and treating them to a systolic pressure of less than 120 mm Hg, usually by adding just one antihypertensive drug, translated into substantial clinical benefit,” Dr. Fonarow concluded. He also noted that a large subgroup, about 28% of enrolled patients, were at least 75 years old, and in these patients the more aggressive regimen was as safe and effective as in the entire study. “We have a spectacular result” for elderly patients, he said.

Dr. Fonarow had no disclosures.

[email protected]

On Twitter @mitchelzoler

ORLANDO – Results from the SPRINT hypertension trial are “truly practice changing,” by “giving us definitive clinical-trial evidence that an additional 15-18 mm Hg lowering of systolic blood pressure, aiming for a target of less than 120 mm Hg, translates into” a significantly reduced composite cardiovascular-event endpoint as well as significantly reduced all-cause death, Dr. Gregg C. Fonarow said in an interview at the American Heart Association scientific sessions.

The significant, 27% relative reduction in all-cause mortality in SPRINT in patients targeted to a systolic blood pressure of less than 120 mm Hg was especially notable because an all-cause mortality benefit is not typically seen with other interventions, and because it “ultimately demonstrates that the benefits clearly outweigh the potential risks,” said Dr. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

Dr. Fonarow acknowledged that results from SPRINT showed a more aggressive regimen also produced higher rates of certain important adverse effects, such as acute kidney injury. But the large incremental benefit in total mortality during the greater than 3 years of average follow-up showed the overwhelming net benefit from more aggressive antihypertensive treatment.

Less clear is whether the SPRINT results say anything about initiating antihypertensive treatment in a patients who resemble those enrolled in the trial and have an untreated systolic blood pressure of 130-139 mm Hg. While people like these could enter SPRINT, they constituted just under 10% of the enrolled population.

“The vast majority of patients in the trial met the conventional clinical definition of hypertension, with a systolic blood pressure of 140 mm Hg or greater and already on some treatment, and treating them to a systolic pressure of less than 120 mm Hg, usually by adding just one antihypertensive drug, translated into substantial clinical benefit,” Dr. Fonarow concluded. He also noted that a large subgroup, about 28% of enrolled patients, were at least 75 years old, and in these patients the more aggressive regimen was as safe and effective as in the entire study. “We have a spectacular result” for elderly patients, he said.

Dr. Fonarow had no disclosures.

[email protected]

On Twitter @mitchelzoler

ORLANDO – Results from the SPRINT hypertension trial are “truly practice changing,” by “giving us definitive clinical-trial evidence that an additional 15-18 mm Hg lowering of systolic blood pressure, aiming for a target of less than 120 mm Hg, translates into” a significantly reduced composite cardiovascular-event endpoint as well as significantly reduced all-cause death, Dr. Gregg C. Fonarow said in an interview at the American Heart Association scientific sessions.

The significant, 27% relative reduction in all-cause mortality in SPRINT in patients targeted to a systolic blood pressure of less than 120 mm Hg was especially notable because an all-cause mortality benefit is not typically seen with other interventions, and because it “ultimately demonstrates that the benefits clearly outweigh the potential risks,” said Dr. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

Dr. Fonarow acknowledged that results from SPRINT showed a more aggressive regimen also produced higher rates of certain important adverse effects, such as acute kidney injury. But the large incremental benefit in total mortality during the greater than 3 years of average follow-up showed the overwhelming net benefit from more aggressive antihypertensive treatment.

Less clear is whether the SPRINT results say anything about initiating antihypertensive treatment in a patients who resemble those enrolled in the trial and have an untreated systolic blood pressure of 130-139 mm Hg. While people like these could enter SPRINT, they constituted just under 10% of the enrolled population.

“The vast majority of patients in the trial met the conventional clinical definition of hypertension, with a systolic blood pressure of 140 mm Hg or greater and already on some treatment, and treating them to a systolic pressure of less than 120 mm Hg, usually by adding just one antihypertensive drug, translated into substantial clinical benefit,” Dr. Fonarow concluded. He also noted that a large subgroup, about 28% of enrolled patients, were at least 75 years old, and in these patients the more aggressive regimen was as safe and effective as in the entire study. “We have a spectacular result” for elderly patients, he said.

Dr. Fonarow had no disclosures.

[email protected]

On Twitter @mitchelzoler

ORLANDO – Concomitant treatment with candesartan protects against the early decline in left ventricular ejection fraction associated with adjunct therapy for early breast cancer.

That was the key finding in the PRADA trial (PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy), the largest study to date looking at prevention of cardiac dysfunction in a breast cancer population.

Another important finding in PRADA was that unlike the angiotensin receptor blocker candesartan (Atacand), metoprolol, a beta blocker, didn’t prevent the early drop in LVEF commonly seen in breast cancer patients treated with anthracyclines and trastuzumab (Herceptin), even though both classes of heart medications are cornerstones of the treatment of ischemic and hypertensive cardiomyopathy, Dr. Geeta Gulati reported at the American Heart Association scientific sessions.

Although the cardiotoxicity of certain breast cancer treatments is widely recognized and has spawned the emerging field of cardio-oncology, the literature in this area is weak. Indeed, a recent meta-analysis identified only four published randomized studies evaluating the possible cardioprotective role for beta blockers and angiotensin antagonists in patients undergoing anthracycline-based chemotherapy (Postgrad Med J doi:10.1136/ postgradmedj-2015-133535). None of the studies was double-blind, all relied upon echocardiographic assessment of changes in LVEF rather than gold-standard cardiac MRI, and the study sizes were small -- just 18-45 breast cancer patients.

Most problematic of all, the studies employed a variety of different definitions of cardiotoxicity, noted Dr. Gulati of Akershus University Hospital in Lorenskog, Norway.

In contrast, PRADA was a double-blind, placebo-controlled, 2 by 2 factorial design, single-center trial, which included 120 patients with early breast cancer. Participants were randomized to candesartan at a starting dose of 8 mg and target dose of 32 mg/day, metoprolol starting at 25 mg with a target of 100 mg/day, or placebo after breast cancer surgery but before the start of anthracycline-containing chemotherapy.

The primary endpoint was change in LVEF from baseline to completion of adjuvant therapy, a period as short as 10 weeks and as long as 64 weeks depending upon whether a woman also underwent courses of trastuzumab, taxanes, and/or radiation therapy.

The overall decline in LVEF was 2.6% in the placebo group and 0.6% in the candesartan group, a significant difference. Metoprolol didn’t put a dent in the LVEF decline.

“Observational studies show early reduction in LVEF is associated with increased risk of developing heart failure later. So if a sustained, long-term effect of angiotensin inhibition can be confirmed in larger multicenter trials, preventive therapy may be indicated as standard care for breast cancer patients,” Dr. Gulati said.

Discussant Dr. Bonnie Ky of the University of Pennsylvania, Philadelphia, called PRADA an important study that moves the field of cardio-oncology forward, yet it’s also a trial that raises more questions than it answers.

PRADA certainly addresses a major problem: “The incidence of heart failure and cardiomyopathy increases over time in breast cancer patients exposed to anthracyclines and trastuzumab. Because patients are living longer because of cancer chemotherapy, their risk of dying of cardiovascular disease actually exceeds that of recurrent cancer in the long term,” she observed.

The study has three major limitations that prevent its findings being implemented in routine clinical practice at this time, Dr. Ky said. One is its relatively small size, even though it’s far bigger than any previous study. Another limitation is that this was an extremely low-cardiovascular-risk patient cohort: the baseline prevalence of diabetes was only 1.5%, fewer than 7% of patients had hypertension, and the baseline LVEF was 63%. That may be why no one developed a substantial decrement in LVEF or actual heart failure.

And since the incidence of cardiomyopathy following breast cancer therapy is known to climb over time, reaching a cumulative 12% at 6 years followup in trastuzumab-treated patients and 20% in those who receive both anthracyclines and trastuzumab (J Natl Cancer Inst. 2012 Sep 5;104(17):1293-305), the lack of extended followup time in PRADA is a significant shortcoming, she added.

The important questions raised by PRADA, Dr. Ky continued, include whether carvedilol or another beta blocker would have generated a positive result where metoprolol failed. Also, should the target population for prevention of cardiotoxicity be more narrowly focused on those at higher baseline cardiovascular risk? And bearing in mind that change in LVEF is a surrogate endpoint, what might be a more clinically meaningful and valid outcome measure? What’s the effect of carvedilol and other cardioprotective medications on cardiac biomarkers in breast cancer patients? And the most important questions of all, she said: What would be the effects of longer followup time and extended therapy?

“This study highlights for us in the field of cardio-oncology the critical need to develop a robust consensus definition of cardiotoxicity and a methodology to identify high cardiovascular risk patients,” she concluded.

PRADA was funded primarily by the University of Oslo and the Norwegian Cancer Society. Dr. Gulati reported having no financial conflicts of interest. Dr. Ky reported receiving a research grant from Pfizer and serving as a consultant to Bristol Myers Squibb.

[email protected]

ORLANDO – Concomitant treatment with candesartan protects against the early decline in left ventricular ejection fraction associated with adjunct therapy for early breast cancer.

That was the key finding in the PRADA trial (PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy), the largest study to date looking at prevention of cardiac dysfunction in a breast cancer population.

Another important finding in PRADA was that unlike the angiotensin receptor blocker candesartan (Atacand), metoprolol, a beta blocker, didn’t prevent the early drop in LVEF commonly seen in breast cancer patients treated with anthracyclines and trastuzumab (Herceptin), even though both classes of heart medications are cornerstones of the treatment of ischemic and hypertensive cardiomyopathy, Dr. Geeta Gulati reported at the American Heart Association scientific sessions.

Although the cardiotoxicity of certain breast cancer treatments is widely recognized and has spawned the emerging field of cardio-oncology, the literature in this area is weak. Indeed, a recent meta-analysis identified only four published randomized studies evaluating the possible cardioprotective role for beta blockers and angiotensin antagonists in patients undergoing anthracycline-based chemotherapy (Postgrad Med J doi:10.1136/ postgradmedj-2015-133535). None of the studies was double-blind, all relied upon echocardiographic assessment of changes in LVEF rather than gold-standard cardiac MRI, and the study sizes were small -- just 18-45 breast cancer patients.

Most problematic of all, the studies employed a variety of different definitions of cardiotoxicity, noted Dr. Gulati of Akershus University Hospital in Lorenskog, Norway.

In contrast, PRADA was a double-blind, placebo-controlled, 2 by 2 factorial design, single-center trial, which included 120 patients with early breast cancer. Participants were randomized to candesartan at a starting dose of 8 mg and target dose of 32 mg/day, metoprolol starting at 25 mg with a target of 100 mg/day, or placebo after breast cancer surgery but before the start of anthracycline-containing chemotherapy.

The primary endpoint was change in LVEF from baseline to completion of adjuvant therapy, a period as short as 10 weeks and as long as 64 weeks depending upon whether a woman also underwent courses of trastuzumab, taxanes, and/or radiation therapy.

The overall decline in LVEF was 2.6% in the placebo group and 0.6% in the candesartan group, a significant difference. Metoprolol didn’t put a dent in the LVEF decline.

“Observational studies show early reduction in LVEF is associated with increased risk of developing heart failure later. So if a sustained, long-term effect of angiotensin inhibition can be confirmed in larger multicenter trials, preventive therapy may be indicated as standard care for breast cancer patients,” Dr. Gulati said.

Discussant Dr. Bonnie Ky of the University of Pennsylvania, Philadelphia, called PRADA an important study that moves the field of cardio-oncology forward, yet it’s also a trial that raises more questions than it answers.

PRADA certainly addresses a major problem: “The incidence of heart failure and cardiomyopathy increases over time in breast cancer patients exposed to anthracyclines and trastuzumab. Because patients are living longer because of cancer chemotherapy, their risk of dying of cardiovascular disease actually exceeds that of recurrent cancer in the long term,” she observed.

The study has three major limitations that prevent its findings being implemented in routine clinical practice at this time, Dr. Ky said. One is its relatively small size, even though it’s far bigger than any previous study. Another limitation is that this was an extremely low-cardiovascular-risk patient cohort: the baseline prevalence of diabetes was only 1.5%, fewer than 7% of patients had hypertension, and the baseline LVEF was 63%. That may be why no one developed a substantial decrement in LVEF or actual heart failure.

And since the incidence of cardiomyopathy following breast cancer therapy is known to climb over time, reaching a cumulative 12% at 6 years followup in trastuzumab-treated patients and 20% in those who receive both anthracyclines and trastuzumab (J Natl Cancer Inst. 2012 Sep 5;104(17):1293-305), the lack of extended followup time in PRADA is a significant shortcoming, she added.

The important questions raised by PRADA, Dr. Ky continued, include whether carvedilol or another beta blocker would have generated a positive result where metoprolol failed. Also, should the target population for prevention of cardiotoxicity be more narrowly focused on those at higher baseline cardiovascular risk? And bearing in mind that change in LVEF is a surrogate endpoint, what might be a more clinically meaningful and valid outcome measure? What’s the effect of carvedilol and other cardioprotective medications on cardiac biomarkers in breast cancer patients? And the most important questions of all, she said: What would be the effects of longer followup time and extended therapy?

“This study highlights for us in the field of cardio-oncology the critical need to develop a robust consensus definition of cardiotoxicity and a methodology to identify high cardiovascular risk patients,” she concluded.

PRADA was funded primarily by the University of Oslo and the Norwegian Cancer Society. Dr. Gulati reported having no financial conflicts of interest. Dr. Ky reported receiving a research grant from Pfizer and serving as a consultant to Bristol Myers Squibb.

[email protected]

ORLANDO – Concomitant treatment with candesartan protects against the early decline in left ventricular ejection fraction associated with adjunct therapy for early breast cancer.

That was the key finding in the PRADA trial (PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy), the largest study to date looking at prevention of cardiac dysfunction in a breast cancer population.

Another important finding in PRADA was that unlike the angiotensin receptor blocker candesartan (Atacand), metoprolol, a beta blocker, didn’t prevent the early drop in LVEF commonly seen in breast cancer patients treated with anthracyclines and trastuzumab (Herceptin), even though both classes of heart medications are cornerstones of the treatment of ischemic and hypertensive cardiomyopathy, Dr. Geeta Gulati reported at the American Heart Association scientific sessions.

Although the cardiotoxicity of certain breast cancer treatments is widely recognized and has spawned the emerging field of cardio-oncology, the literature in this area is weak. Indeed, a recent meta-analysis identified only four published randomized studies evaluating the possible cardioprotective role for beta blockers and angiotensin antagonists in patients undergoing anthracycline-based chemotherapy (Postgrad Med J doi:10.1136/ postgradmedj-2015-133535). None of the studies was double-blind, all relied upon echocardiographic assessment of changes in LVEF rather than gold-standard cardiac MRI, and the study sizes were small -- just 18-45 breast cancer patients.

Most problematic of all, the studies employed a variety of different definitions of cardiotoxicity, noted Dr. Gulati of Akershus University Hospital in Lorenskog, Norway.

In contrast, PRADA was a double-blind, placebo-controlled, 2 by 2 factorial design, single-center trial, which included 120 patients with early breast cancer. Participants were randomized to candesartan at a starting dose of 8 mg and target dose of 32 mg/day, metoprolol starting at 25 mg with a target of 100 mg/day, or placebo after breast cancer surgery but before the start of anthracycline-containing chemotherapy.

The primary endpoint was change in LVEF from baseline to completion of adjuvant therapy, a period as short as 10 weeks and as long as 64 weeks depending upon whether a woman also underwent courses of trastuzumab, taxanes, and/or radiation therapy.

The overall decline in LVEF was 2.6% in the placebo group and 0.6% in the candesartan group, a significant difference. Metoprolol didn’t put a dent in the LVEF decline.

“Observational studies show early reduction in LVEF is associated with increased risk of developing heart failure later. So if a sustained, long-term effect of angiotensin inhibition can be confirmed in larger multicenter trials, preventive therapy may be indicated as standard care for breast cancer patients,” Dr. Gulati said.

Discussant Dr. Bonnie Ky of the University of Pennsylvania, Philadelphia, called PRADA an important study that moves the field of cardio-oncology forward, yet it’s also a trial that raises more questions than it answers.

PRADA certainly addresses a major problem: “The incidence of heart failure and cardiomyopathy increases over time in breast cancer patients exposed to anthracyclines and trastuzumab. Because patients are living longer because of cancer chemotherapy, their risk of dying of cardiovascular disease actually exceeds that of recurrent cancer in the long term,” she observed.

The study has three major limitations that prevent its findings being implemented in routine clinical practice at this time, Dr. Ky said. One is its relatively small size, even though it’s far bigger than any previous study. Another limitation is that this was an extremely low-cardiovascular-risk patient cohort: the baseline prevalence of diabetes was only 1.5%, fewer than 7% of patients had hypertension, and the baseline LVEF was 63%. That may be why no one developed a substantial decrement in LVEF or actual heart failure.

And since the incidence of cardiomyopathy following breast cancer therapy is known to climb over time, reaching a cumulative 12% at 6 years followup in trastuzumab-treated patients and 20% in those who receive both anthracyclines and trastuzumab (J Natl Cancer Inst. 2012 Sep 5;104(17):1293-305), the lack of extended followup time in PRADA is a significant shortcoming, she added.

The important questions raised by PRADA, Dr. Ky continued, include whether carvedilol or another beta blocker would have generated a positive result where metoprolol failed. Also, should the target population for prevention of cardiotoxicity be more narrowly focused on those at higher baseline cardiovascular risk? And bearing in mind that change in LVEF is a surrogate endpoint, what might be a more clinically meaningful and valid outcome measure? What’s the effect of carvedilol and other cardioprotective medications on cardiac biomarkers in breast cancer patients? And the most important questions of all, she said: What would be the effects of longer followup time and extended therapy?

“This study highlights for us in the field of cardio-oncology the critical need to develop a robust consensus definition of cardiotoxicity and a methodology to identify high cardiovascular risk patients,” she concluded.

PRADA was funded primarily by the University of Oslo and the Norwegian Cancer Society. Dr. Gulati reported having no financial conflicts of interest. Dr. Ky reported receiving a research grant from Pfizer and serving as a consultant to Bristol Myers Squibb.

[email protected]

ORLANDO – Interrupting prolonged sitting with brief bouts of light-intensity activity throughout the workday resulted in an impressive drop in blood pressure in overweight sedentary men and women with type 2 diabetes, Bronwyn Kingwell, Ph.D., said in a video interview at the American Heart Association scientific sessions.

A total of 24 such individuals were randomized in crossover fashion to a 3-day study conducted under controlled conditions in a physiology lab. On one day participants did what they usually do: They sat at their desks for an 8-hour workday. On another day they rose from their desks every 30 minutes for 3 minutes of walking down the hall at a 2-mph pace. And on yet another day they stood up every 30 minutes and did 3 minutes of simple resistance activities at their desks: half squats, knee raises, calf stretches.

Blood pressure was measured eight times per day, and plasma norepinephrine as a measure of sympathetic activity was measured nine times. At the end of the light walking day, subjects’ blood pressure was on average 14/8 mm Hg lower than on the uninterrupted sitting day. On the simple resistance activity day, it was 16/10 mm Hg lower.

“This is quite an impressive reduction, and more than we might have anticipated. It’s similar to the type of reduction you might see with single-drug antihypertensive therapy. And I thought it was interesting that two-thirds of subjects were already taking antihypertensive drugs,” observed Dr. Kingwell, head of metabolic and vascular physiology at the Baker IDI Heart and Diabetes Institute in Melbourne.

“I think the new thing here is that even with these very small bouts of activity – just 3 minutes – we’re getting this reduction that’s sustained throughout the day, provided you break it up every 30 minutes,” she said. “We’ve seen an increase in sitting behavior in most industrialized countries, particularly over the last 10 years, and we also see low adherence to structured exercise programs. The approach examined in this simple study may represent a practical strategy which could contribute to blood pressure reduction in a group that is at high risk.”

ORLANDO – Interrupting prolonged sitting with brief bouts of light-intensity activity throughout the workday resulted in an impressive drop in blood pressure in overweight sedentary men and women with type 2 diabetes, Bronwyn Kingwell, Ph.D., said in a video interview at the American Heart Association scientific sessions.

A total of 24 such individuals were randomized in crossover fashion to a 3-day study conducted under controlled conditions in a physiology lab. On one day participants did what they usually do: They sat at their desks for an 8-hour workday. On another day they rose from their desks every 30 minutes for 3 minutes of walking down the hall at a 2-mph pace. And on yet another day they stood up every 30 minutes and did 3 minutes of simple resistance activities at their desks: half squats, knee raises, calf stretches.

Blood pressure was measured eight times per day, and plasma norepinephrine as a measure of sympathetic activity was measured nine times. At the end of the light walking day, subjects’ blood pressure was on average 14/8 mm Hg lower than on the uninterrupted sitting day. On the simple resistance activity day, it was 16/10 mm Hg lower.

“This is quite an impressive reduction, and more than we might have anticipated. It’s similar to the type of reduction you might see with single-drug antihypertensive therapy. And I thought it was interesting that two-thirds of subjects were already taking antihypertensive drugs,” observed Dr. Kingwell, head of metabolic and vascular physiology at the Baker IDI Heart and Diabetes Institute in Melbourne.

“I think the new thing here is that even with these very small bouts of activity – just 3 minutes – we’re getting this reduction that’s sustained throughout the day, provided you break it up every 30 minutes,” she said. “We’ve seen an increase in sitting behavior in most industrialized countries, particularly over the last 10 years, and we also see low adherence to structured exercise programs. The approach examined in this simple study may represent a practical strategy which could contribute to blood pressure reduction in a group that is at high risk.”

ORLANDO – Interrupting prolonged sitting with brief bouts of light-intensity activity throughout the workday resulted in an impressive drop in blood pressure in overweight sedentary men and women with type 2 diabetes, Bronwyn Kingwell, Ph.D., said in a video interview at the American Heart Association scientific sessions.

A total of 24 such individuals were randomized in crossover fashion to a 3-day study conducted under controlled conditions in a physiology lab. On one day participants did what they usually do: They sat at their desks for an 8-hour workday. On another day they rose from their desks every 30 minutes for 3 minutes of walking down the hall at a 2-mph pace. And on yet another day they stood up every 30 minutes and did 3 minutes of simple resistance activities at their desks: half squats, knee raises, calf stretches.

Blood pressure was measured eight times per day, and plasma norepinephrine as a measure of sympathetic activity was measured nine times. At the end of the light walking day, subjects’ blood pressure was on average 14/8 mm Hg lower than on the uninterrupted sitting day. On the simple resistance activity day, it was 16/10 mm Hg lower.

“This is quite an impressive reduction, and more than we might have anticipated. It’s similar to the type of reduction you might see with single-drug antihypertensive therapy. And I thought it was interesting that two-thirds of subjects were already taking antihypertensive drugs,” observed Dr. Kingwell, head of metabolic and vascular physiology at the Baker IDI Heart and Diabetes Institute in Melbourne.

“I think the new thing here is that even with these very small bouts of activity – just 3 minutes – we’re getting this reduction that’s sustained throughout the day, provided you break it up every 30 minutes,” she said. “We’ve seen an increase in sitting behavior in most industrialized countries, particularly over the last 10 years, and we also see low adherence to structured exercise programs. The approach examined in this simple study may represent a practical strategy which could contribute to blood pressure reduction in a group that is at high risk.”

ORLANDO – College football linemen develop adverse cardiac structural and functional changes over the course of their freshman season that are not seen in teammates who play at other positions, Dr. Jeffrey Lin said in an interview at the American Heart Association scientific sessions.

He followed 30 Harvard University linemen and 57 players at other football positions through their 3-month fall freshman season by means of serial blood pressure measurements and 2-D echocardiography, including speckle tracking. During the course of that season, 90% of the linemen developed prehypertension or hypertension, 30% showed clear echocardiographic evidence of concentric left ventricular hypertrophy, and as a group they also developed a relative decrease in systolic function, with a reduction from baseline in global longitudinal strain by speckle tracking.

It’s concerning because these 18-year-old linemen are going to expose themselves to another 3 years of the stresses of year-round intensive training along with three more seasons of university-level football, noted Dr. Lin, a cardiac imaging fellow at Columbia University in New York.

These cardiac changes were not seen in non-linemen. They developed adaptive cardiac structural remodeling with eccentric hypertrophy and an increase in global longitudinal strain, which is characteristic of what’s been called the “athlete’s heart,” according to Dr. Lin.

Watch the video to learn what he thinks may be going on.

[email protected]

ORLANDO – College football linemen develop adverse cardiac structural and functional changes over the course of their freshman season that are not seen in teammates who play at other positions, Dr. Jeffrey Lin said in an interview at the American Heart Association scientific sessions.

He followed 30 Harvard University linemen and 57 players at other football positions through their 3-month fall freshman season by means of serial blood pressure measurements and 2-D echocardiography, including speckle tracking. During the course of that season, 90% of the linemen developed prehypertension or hypertension, 30% showed clear echocardiographic evidence of concentric left ventricular hypertrophy, and as a group they also developed a relative decrease in systolic function, with a reduction from baseline in global longitudinal strain by speckle tracking.

It’s concerning because these 18-year-old linemen are going to expose themselves to another 3 years of the stresses of year-round intensive training along with three more seasons of university-level football, noted Dr. Lin, a cardiac imaging fellow at Columbia University in New York.

These cardiac changes were not seen in non-linemen. They developed adaptive cardiac structural remodeling with eccentric hypertrophy and an increase in global longitudinal strain, which is characteristic of what’s been called the “athlete’s heart,” according to Dr. Lin.

Watch the video to learn what he thinks may be going on.

[email protected]

ORLANDO – College football linemen develop adverse cardiac structural and functional changes over the course of their freshman season that are not seen in teammates who play at other positions, Dr. Jeffrey Lin said in an interview at the American Heart Association scientific sessions.

He followed 30 Harvard University linemen and 57 players at other football positions through their 3-month fall freshman season by means of serial blood pressure measurements and 2-D echocardiography, including speckle tracking. During the course of that season, 90% of the linemen developed prehypertension or hypertension, 30% showed clear echocardiographic evidence of concentric left ventricular hypertrophy, and as a group they also developed a relative decrease in systolic function, with a reduction from baseline in global longitudinal strain by speckle tracking.

It’s concerning because these 18-year-old linemen are going to expose themselves to another 3 years of the stresses of year-round intensive training along with three more seasons of university-level football, noted Dr. Lin, a cardiac imaging fellow at Columbia University in New York.

These cardiac changes were not seen in non-linemen. They developed adaptive cardiac structural remodeling with eccentric hypertrophy and an increase in global longitudinal strain, which is characteristic of what’s been called the “athlete’s heart,” according to Dr. Lin.

Watch the video to learn what he thinks may be going on.

[email protected]

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.

ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.

When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.

The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:

“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.

“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.

Mitchel L. Zoler/Frontline Medical News

“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.

Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).

ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.

In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.

SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.

“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.

Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:

• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.

• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.

• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.

Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”

“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.

For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.

SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”

SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.

ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.

When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.

The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:

“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.

“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.

Mitchel L. Zoler/Frontline Medical News

“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.

Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).

ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.

In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.

SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.

“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.

Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:

• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.

• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.

• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.

Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”

“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.

For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.

SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”

SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.

ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.

When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.

The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:

“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.

“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.

Mitchel L. Zoler/Frontline Medical News

“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.

Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).

ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.

In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.

SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.

“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.

Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:

• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.

• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.

• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.

Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”

“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.

For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.

SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”

SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.

ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.

When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.

The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:

“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.

“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.

Mitchel L. Zoler/Frontline Medical News

“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.

Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).

ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.

In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.

SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.

“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.

Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:

• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.

• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.

• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.

Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”

“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.

For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.

SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”

SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.

[email protected]

On Twitter @mitchelzoler

ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.

When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.

The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:

“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.

“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.

Mitchel L. Zoler/Frontline Medical News

“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.

Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).

ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.

In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.

SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.

“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.

Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:

• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.

• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.

• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.

Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”

“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.

For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.

SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”

SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.

[email protected]

On Twitter @mitchelzoler

ORLANDO – Results from the SPRINT hypertension trial had been highly anticipated ever since the study stopped early in August and the sponsoring National Heart, Lung, and Blood Institute released the top-line positive result in September that treating systolic blood pressure to a target of less than 120 mm Hg led to statistically significant drops in a composite of cardiovascular endpoints as well as in all-cause death, compared with the standard target of less than 140 mm Hg.

When the much fuller report on the results finally came out in a special session at the American Heart Association scientific sessions as well as in a simultaneous publication (N Engl J Med. 2015 Nov 9. doi: 10.1056/NEJMoa1511939), the data left attendees buzzing and debating what the results will mean for revised hypertension guidelines and for clinical practice.

The most prominent reactions were accolades for the trial, starting with the independent discussants that the AHA invited to comment at the session, an outpouring of praise reminiscent of that showered on a hit movie:

“A major coup. Thank you, NHLBI,” declared Dr. Marc A. Pfeffer, professor of medicine at Harvard and a cardiologist at Brigham and Women’s Hospital in Boston.

“Thank you for this groundbreaking study,” said Dr. Clive Rosendorff, professor and cardiologist at Mount Sinai Hospital in New York.

Mitchel L. Zoler/Frontline Medical News

“A remarkable trial. The most important blood pressure study in the last 40 years,” gushed Dr. Daniel W. Jones, professor of medicine at the University of Mississippi, Oxford, and director of clinical and population sciences at the Mississippi Center for Obesity Research, Jackson.

Following the huzzahs came a more substantive discussion among meeting attendees of what results from the 9,361-patient Systolic Blood Pressure Intervention Trial will mean for revised blood pressure goals in U.S. guidelines, what it might mean for defining who has hypertension, and how it might influence practice. Perhaps the most pressing issue for the AHA and American College of Cardiology panel that began work on a new revision of hypertension treatment guidelines earlier this year is how to reconcile the SPRINT results with finding from prior studies, especially the 2010 report of results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (N Engl J Med. 2010;362[17]:1575-85.).

ACCORD, at half the size of SPRINT with 4,733 patients, had a very similar design as SPRINT but included only patients with diabetes while SPRINT excluded patients with diabetes. ACCORD failed to show a significant difference in its primary composite outcome after an average of 4.7 years between patients randomized to a hypertension treatment target of less than 140 mm Hg or less than 120 mm Hg, the same goals as in SPRINT. ACCORD did show a statistically significant 41% relative risk reduction for stroke, also in contrast to SPRINT, which showed a much less robust and nonsignificant 11% relative risk reduction in stroke.

In his commentary on SPRINT, Dr. Jones offered several possible explanations for the divergent results, including a possible inherent difference in vascular physiology between patients with diabetes and those with normal glycemic control; the younger patients enrolled in ACCORD (patients averaged 62 years old in ACCORD and 68 years old in SPRINT, and 28% of patients in SPRINT were at least 75 years old); the use of hydrochlorothiazide as the predominant diuretic in ACCORD versus predominant use of chlorthalidone in SPRINT; and the multiple interventions simultaneously tested in ACCORD, which also randomized patients into two arms with respect to glycemic control and into two arms of different lipid-controlling treatment.

SPRINT’s results “need to be assessed in the context of ACCORD,” commented Dr. Salim Yusuf in an interview. “I think the real result is somewhere in between the results of SPRINT and ACCORD” in terms of the appropriate systolic blood pressure target. What we need is a balanced perspective that takes all the trials. SPRINT was a very good trial, but like all studies it should be interpreted in the context of all the other related studies, not in isolation,” said Dr. Yusuf, professor and director of the Population Health Research Institute of McMaster University in Hamilton, Ont.

“Understandably, when something like SPRINT comes out there is a lot of enthusiasm. The first reaction is always ‘Wow!’ For patients who meet SPRINT’s enrollment criteria I think we will treat to a target of less than 120 mm Hg. But the guideline writers need to discuss SPRINT and balance it,” he said.

Despite his regard for SPRINT, Dr. Yusuf cited several additional concerns he has about the trial:

• Its early stoppage (SPRINT had originally been designed to run 5-6 years, but it was halted after an average treatment duration of just over 3 years). “When you stop a trial early there is always an upward bias. The apparent treatment effect gets inflated,” he said.

• The increased rate of acute kidney injury among patients randomized to the more aggressive treatment arm, a 4.1% rate, compared with a 2.5% rate in the control patients randomized to treatment to a goal of systolic pressure less than 140 mm Hg, a statistically significant difference.

• The “highly selected, high-risk” patients enrolled into SPRINT. “You can’t extrapolate the results to the average patient,” Dr. Yusuf said.

Some of these concerns and cautions were shared by Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco, although overall he called the SPRINT results “very exciting.”

“Superficially, SPRINT seems to say treat everyone to a blood pressure of less than 120 mm Hg, but that’s not the case. The patients in SPRINT were primarily very well established patients with hypertension. I’d be concerned about an elderly patient with cardiovascular disease and a blood pressure of 130 mm Hg. If you reduce that to less than 120 mm Hg the diastolic pressure may also fall and that’s important for coronary perfusion.” He also cited the absence so far of a subanalysis of what happened to patients with preexisting renal disease and the lack of data on the outcomes of patients whose systolic pressure fell to levels well below 120 mm Hg.

For others, however, the overall, statistically significant 27% reduction in overall mortality was a reassuring indicator of the safety of the aggressive treatment regimen used in SPRINT. “If there was a meaningful worsening of renal function that harmed patients, you would not see a reduction in all-cause mortality,” commented Dr. Gregg C. Fonarow, professor and associate chief of cardiology at the University of California, Los Angeles.

“We have had so many trials that couldn’t dream of producing a reduction in all-cause mortality. Here we have a trial with a robust, clinically meaningful reduction in all-cause mortality that ultimately demonstrates the benefits outweigh the risks,” he said in an interview.

SPRINT “is a phenomenal breakthrough. It’s data we’ve been awaiting for 20-plus years, to now know that a lower blood pressure target is safe and absolutely essential, and where the benefits outweigh the risks,” Dr. Fonarow said. “Now implementation becomes critical. The SPRINT results are truly practice changing.”

SPRINT received no commercial support. The study received antihypertensive drugs from Arbor and Takeda at no charge for a small percentage of enrolled patients. Dr. Pfeffer has been a consultant to more than 20 companies. Dr. Rosendorff has been a consultant to McNeil and received research funding from Eisai. Dr. Yusuf has received honoraria and research grants from Sanofi-Aventis, Bristol-Myers Squibb, Pfizer, Boehringer-Ingelheim, Bayer, and Astra Zeneca. Dr. Jones, Dr. Deedwania, and Dr. Fonarow had no disclosures.

[email protected]

On Twitter @mitchelzoler

Continuous chest compressions during CPR failed to improve survival or neurologic function compared with standard chest compressions that are briefly interrupted for ventilation, based on findings in the first large randomized trial to compare the two strategies for out-of-hospital, nontraumatic cardiac arrest.

In a presentation at the American Heart Association scientific sessions, simultaneously published online Nov. 9 in the New England Journal of Medicine, Dr. Graham Nichol and his associates analyzed data from the Resuscitation Outcomes Consortium, a network of clinical centers and EMS agencies that have expertise in conducting research on out-of-hospital cardiac arrest.

Data were analyzed for 23,711 adults treated by 114 EMS agencies affiliated with eight clinical centers across the United States and Canada. These agencies were grouped into 47 clusters that were randomly assigned to perform CPR using either continuous chest compressions (100 per minute) with asynchronous positive-pressure ventilations (10 per minute) or standard chest compressions interrupted for ventilations (at a rate of 30 compressions per two ventilations) at every response to an out-of-hospital cardiac arrest. Twice per year, each cluster crossed over to the other resuscitation strategy, said Dr. Nichol of the University of Washington–Harborview Center for Prehospital Emergency Care and Clinical Trial Center in Seattle.

A total of 12,653 patients were assigned to continuous chest compressions (the intervention group) and 11,058 to interrupted chest compressions (the control group). The primary outcome – the rate of survival to hospital discharge – was 9.0% in the intervention group and 9.7% in the control group, a nonsignificant difference. Similarly, the rate of survival with favorable neurologic function did not differ significantly, at 7.0% and 7.7%, respectively, the investigators said (N Engl J Med. 2015 Nov 9. doi:10.1056/NEJMoa1509139).

The reason for these unexpected findings is not yet known. It is plausible that continuous chest compressions really don’t improve outcomes and that the previous positive results were actually due to improvements in the CPR process, such as more consistent rate and depth of compressions; concurrent improvements in the system of care; or Hawthorne effects, in which CPR providers altered their behavior during the studies because they were aware they were being observed.

However, it is also possible that three important limitations of this trial unduly influenced the results.

First, the per-protocol analysis, which used an automated algorithm to assess adherence to the compression assignments, could not classify many patients as having received either continuous or interrupted chest compressions. Second, the quality of postresuscitation care, which certainly influences outcomes, was not monitored. And third, actual oxygenation levels were not measured, nor were minutes of ventilation delivered. Thus, “we do not know whether there were important differences in oxygenation or ventilation between the two treatment strategies,” he said.

Continuous chest compressions during CPR failed to improve survival or neurologic function compared with standard chest compressions that are briefly interrupted for ventilation, based on findings in the first large randomized trial to compare the two strategies for out-of-hospital, nontraumatic cardiac arrest.

In a presentation at the American Heart Association scientific sessions, simultaneously published online Nov. 9 in the New England Journal of Medicine, Dr. Graham Nichol and his associates analyzed data from the Resuscitation Outcomes Consortium, a network of clinical centers and EMS agencies that have expertise in conducting research on out-of-hospital cardiac arrest.

Data were analyzed for 23,711 adults treated by 114 EMS agencies affiliated with eight clinical centers across the United States and Canada. These agencies were grouped into 47 clusters that were randomly assigned to perform CPR using either continuous chest compressions (100 per minute) with asynchronous positive-pressure ventilations (10 per minute) or standard chest compressions interrupted for ventilations (at a rate of 30 compressions per two ventilations) at every response to an out-of-hospital cardiac arrest. Twice per year, each cluster crossed over to the other resuscitation strategy, said Dr. Nichol of the University of Washington–Harborview Center for Prehospital Emergency Care and Clinical Trial Center in Seattle.

A total of 12,653 patients were assigned to continuous chest compressions (the intervention group) and 11,058 to interrupted chest compressions (the control group). The primary outcome – the rate of survival to hospital discharge – was 9.0% in the intervention group and 9.7% in the control group, a nonsignificant difference. Similarly, the rate of survival with favorable neurologic function did not differ significantly, at 7.0% and 7.7%, respectively, the investigators said (N Engl J Med. 2015 Nov 9. doi:10.1056/NEJMoa1509139).

The reason for these unexpected findings is not yet known. It is plausible that continuous chest compressions really don’t improve outcomes and that the previous positive results were actually due to improvements in the CPR process, such as more consistent rate and depth of compressions; concurrent improvements in the system of care; or Hawthorne effects, in which CPR providers altered their behavior during the studies because they were aware they were being observed.

However, it is also possible that three important limitations of this trial unduly influenced the results.

First, the per-protocol analysis, which used an automated algorithm to assess adherence to the compression assignments, could not classify many patients as having received either continuous or interrupted chest compressions. Second, the quality of postresuscitation care, which certainly influences outcomes, was not monitored. And third, actual oxygenation levels were not measured, nor were minutes of ventilation delivered. Thus, “we do not know whether there were important differences in oxygenation or ventilation between the two treatment strategies,” he said.

Continuous chest compressions during CPR failed to improve survival or neurologic function compared with standard chest compressions that are briefly interrupted for ventilation, based on findings in the first large randomized trial to compare the two strategies for out-of-hospital, nontraumatic cardiac arrest.

In a presentation at the American Heart Association scientific sessions, simultaneously published online Nov. 9 in the New England Journal of Medicine, Dr. Graham Nichol and his associates analyzed data from the Resuscitation Outcomes Consortium, a network of clinical centers and EMS agencies that have expertise in conducting research on out-of-hospital cardiac arrest.

Data were analyzed for 23,711 adults treated by 114 EMS agencies affiliated with eight clinical centers across the United States and Canada. These agencies were grouped into 47 clusters that were randomly assigned to perform CPR using either continuous chest compressions (100 per minute) with asynchronous positive-pressure ventilations (10 per minute) or standard chest compressions interrupted for ventilations (at a rate of 30 compressions per two ventilations) at every response to an out-of-hospital cardiac arrest. Twice per year, each cluster crossed over to the other resuscitation strategy, said Dr. Nichol of the University of Washington–Harborview Center for Prehospital Emergency Care and Clinical Trial Center in Seattle.

A total of 12,653 patients were assigned to continuous chest compressions (the intervention group) and 11,058 to interrupted chest compressions (the control group). The primary outcome – the rate of survival to hospital discharge – was 9.0% in the intervention group and 9.7% in the control group, a nonsignificant difference. Similarly, the rate of survival with favorable neurologic function did not differ significantly, at 7.0% and 7.7%, respectively, the investigators said (N Engl J Med. 2015 Nov 9. doi:10.1056/NEJMoa1509139).

The reason for these unexpected findings is not yet known. It is plausible that continuous chest compressions really don’t improve outcomes and that the previous positive results were actually due to improvements in the CPR process, such as more consistent rate and depth of compressions; concurrent improvements in the system of care; or Hawthorne effects, in which CPR providers altered their behavior during the studies because they were aware they were being observed.

However, it is also possible that three important limitations of this trial unduly influenced the results.

First, the per-protocol analysis, which used an automated algorithm to assess adherence to the compression assignments, could not classify many patients as having received either continuous or interrupted chest compressions. Second, the quality of postresuscitation care, which certainly influences outcomes, was not monitored. And third, actual oxygenation levels were not measured, nor were minutes of ventilation delivered. Thus, “we do not know whether there were important differences in oxygenation or ventilation between the two treatment strategies,” he said.