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New hypertension performance measures boost 130/80 mm Hg target
PHILADELPHIA – The American Heart Association and American College of Cardiology took a big step toward facilitating widespread U.S. application of the hypertension management guideline that the societies issued in 2017 by releasing a set of performance and quality measures for adults with high blood pressure based on the 2017 guideline.
This guideline notably set a treatment target for patients diagnosed with hypertension of less than 130/80 mg/dL, and also lowered the threshold for diagnosing stage 1 hypertension to a blood pressure at or above 130/80 mm Hg, adding in a stroke about 31 million adults with hypertension to the U.S. total.
Having performance and quality measures based on the guideline is “critical, because how else would you know whether you’re having an effect on accurately diagnosing and properly controlling hypertension?” said Donald E. Casey Jr., MD, chair of the performance measures writing committee. The next step is field testing of the measures “to show they are reliable and effective,” as well as other steps to encourage widespread U.S. uptake of the performance and quality measures and the specifics of the 2017 guideline, Dr. Casey said during a presentation of the revised measures at the American Heart Association scientific sessions.
He especially highlighted the important role of Target: BP, an education, recognition, and quality improvement program run by the AHA and American Medical Association, as a tool that medical practices, health systems, and even payers and employers can use to begin to apply the new performance and quality measures (J Am Coll Cardiol. 2019 Nov 26;74[21]:2661-706) and better align with the recommendations of the 2017 high blood pressure guideline (J Am Coll Cardiol. 2018 May;71[19]:e127-248).
“We’re trying now to promote Target: BP; it’s something you can take off the shelf and get going if it’s embedded in a real-life delivery model. I think Target: BP is the secret sauce. It will be the way we’ll convince people to adopt this,” said Dr. Casey, principal and founder of IPO 4 Health, a Chicago-based health care consulting firm.
He also advised practices and health systems not to feel compelled to introduce all of the specific performance and quality measures at once. “We don’t believe everyone has the resources to do all of it at once; the point is to move toward this system of care. We understand that people don’t have the resources to get it all done” immediately, Dr. Casey said in an interview.
A report during another session at the meeting documented the potential impact that Target: BP can have on blood pressure control within a health system. The Trinity Health of New England medical group based in Springfield, Mass., a system with about 140,000 patients – including 20,000 adults diagnosed with hypertension – and served by 230 health care providers in 13 offices in western Massachusetts, began using Target: BP’s MAP improvement program in its practices in November 2018. (MAP stands for measure accurately, act rapidly, and partner with patients.) Just before the MAP program began, 72% of patients diagnosed with hypertension in the medical group were at their goal blood pressure. Less than a year later, in September 2019, the hypertension control rate had jumped to 84%, a 12 percentage point improvement in control in practices that already had been doing a relatively good job, said Daniel W. Weiswasser, MD, director of quality and clinical informatics at Trinity Health of New England. Based on this success, Trinity Health plans to next involve the remaining regions of Trinity Health of New England in Target: BP, followed by the other regions of Trinity’s national organization, which operates in 21 states with nearly 4,000 staff physicians and about half a million patients diagnosed with hypertension, Dr. Weiswasser said.
“If clinicians do the three steps of the MAP then we will see substantial drops in blood pressures. It will occur,” declared Brent M. Egan, MD, vice president for cardiovascular disease prevention of the AMA in Greenville, S.C.
The new report includes six performance measures based on the strongest guideline recommendations and designed to document adherence levels for the purposes of public reporting and pay-for-performance programs. It also includes 16 quality measures designed for local quality review purposes, with 6 process quality measures and 10 structural quality measures. The report spells out that the authors designed the performance measures for use by major national organizations such as the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance (NCQA), while the quality measures are designed to support quality improvement efforts in any care-delivery setting.
The authors said that the writing committee is sensitive to the fact that the 2019 performance measures for controlling high blood pressure developed by the NCQA for the Healthcare Effectiveness Data and Information Set and currently in use in 2019 by CMS also does not incorporate the 2017 Hypertension Clinical Practice Guidelines classification scheme. “It is well understood that these measures are already in widespread use, especially for quality-related payment programs promulgated by CMS, such as the Medicare Advantage ‘Stars’ ratings, the Medicare Shared Savings Program, and the Physician Quality Payment Program, as well as many other programs promoted by commercial health insurers. In particular, the widespread use of the 2017 Hypertension Clinical Practice Guidelines classification scheme will also help to guide decision making about when to prescribe antihypertensive medications in accordance with its current recommendations for the ACC/AHA “stages” of stage 1 and stage 2 hypertension and elevated blood pressure,” they added.
The report also says that “the writing committee was sensitive to the fact that there is currently not complete consensus among other guidelines from the American College of Physicians and the American Academy of Family Physicians, and also the European Society of Cardiology and the European Society of Hypertension. Nonetheless, despite this ongoing debate, the writing committee felt strongly that it is now time to move the U.S. health care system ahead to reflect these differing points of view and expects that widespread use of this new measure set will help to achieve this goal.” The new report revises hypertension performance measures developed by the ACC and AHA in 2011 (J Am Coll Cardiol. 2011 Jul 12;58[3]: 316-36).
In short, the performance and quality measures give all the diverse components of the U.S. health care delivery system a road map for implementing the 2017 High Blood Pressure Guideline in a format that depends on those components electing to adopt and adhere to the 2017 guideline. (Although one of the new performance measures, 1a, harmonizes with an existing and widely applied performance measure.)
“Who is the audience for this, and how will they respond? These performance measures need to be appropriated” by health systems and by performance-assessment groups. “I hope the NCQA will adopt it,” said William C. Cushman, MD, professor of preventive medicine at the University of Tennessee Health Science Center in Memphis, and chief of preventive medicine at the Memphis Veterans Affairs Medical Center. “There are some negatives to performance measures, but on balance they have done good things and led to better care.” Dr. Cushman also approved of several specific performance and quality measures included in the report. “Most of what they emphasized is good,” particularly the importance of accurate pressure measurement, he said in an interview.
“Process drives outcomes” in hypertension management, and the new performance and quality measures “have some very good process metrics,” commented Dr. Egan. “I’d encourage health systems to select two or three measures that are key to what they do and make sense in their setting rather than try to implement it all at once,” he advised, echoing what Dr. Casey had suggested. “It’s ideal to do everything, but we know that if you give physicians a long list of performance measures they just get overwhelmed. The nice thing about hypertension is that we know that process drives outcomes. In the past, we’ve had some process metrics that did not drive outcomes. Getting these processes implemented will lead to better patient outcomes and save a ton of money.”
“We have introduced the 2017 guideline recommendations throughout Target: BP, but like any quality improvement program there is a question of how does it spread,” said Gregory Wozniak, PhD, director of outcomes analytics for the AMA in Chicago. “Our goal for Target: BP is to be impacting 20 million patients by 2021.”
Dr. Casey, Dr. Weiswasser, and Dr. Wozniak had no disclosures. Dr. Cushman has received honoraria as a speaker from Arbor and Sanofi-Aventis, and travel and research support from Eli Lilly. Dr. Egan has been a consultant to and speaker on behalf of Merck and a speaker for Emcure.
SOURCE: Casey DE et al. J Am Coll Cardiol. 2019 Nov 26;74[21]: 2661-706.
PHILADELPHIA – The American Heart Association and American College of Cardiology took a big step toward facilitating widespread U.S. application of the hypertension management guideline that the societies issued in 2017 by releasing a set of performance and quality measures for adults with high blood pressure based on the 2017 guideline.
This guideline notably set a treatment target for patients diagnosed with hypertension of less than 130/80 mg/dL, and also lowered the threshold for diagnosing stage 1 hypertension to a blood pressure at or above 130/80 mm Hg, adding in a stroke about 31 million adults with hypertension to the U.S. total.
Having performance and quality measures based on the guideline is “critical, because how else would you know whether you’re having an effect on accurately diagnosing and properly controlling hypertension?” said Donald E. Casey Jr., MD, chair of the performance measures writing committee. The next step is field testing of the measures “to show they are reliable and effective,” as well as other steps to encourage widespread U.S. uptake of the performance and quality measures and the specifics of the 2017 guideline, Dr. Casey said during a presentation of the revised measures at the American Heart Association scientific sessions.
He especially highlighted the important role of Target: BP, an education, recognition, and quality improvement program run by the AHA and American Medical Association, as a tool that medical practices, health systems, and even payers and employers can use to begin to apply the new performance and quality measures (J Am Coll Cardiol. 2019 Nov 26;74[21]:2661-706) and better align with the recommendations of the 2017 high blood pressure guideline (J Am Coll Cardiol. 2018 May;71[19]:e127-248).
“We’re trying now to promote Target: BP; it’s something you can take off the shelf and get going if it’s embedded in a real-life delivery model. I think Target: BP is the secret sauce. It will be the way we’ll convince people to adopt this,” said Dr. Casey, principal and founder of IPO 4 Health, a Chicago-based health care consulting firm.
He also advised practices and health systems not to feel compelled to introduce all of the specific performance and quality measures at once. “We don’t believe everyone has the resources to do all of it at once; the point is to move toward this system of care. We understand that people don’t have the resources to get it all done” immediately, Dr. Casey said in an interview.
A report during another session at the meeting documented the potential impact that Target: BP can have on blood pressure control within a health system. The Trinity Health of New England medical group based in Springfield, Mass., a system with about 140,000 patients – including 20,000 adults diagnosed with hypertension – and served by 230 health care providers in 13 offices in western Massachusetts, began using Target: BP’s MAP improvement program in its practices in November 2018. (MAP stands for measure accurately, act rapidly, and partner with patients.) Just before the MAP program began, 72% of patients diagnosed with hypertension in the medical group were at their goal blood pressure. Less than a year later, in September 2019, the hypertension control rate had jumped to 84%, a 12 percentage point improvement in control in practices that already had been doing a relatively good job, said Daniel W. Weiswasser, MD, director of quality and clinical informatics at Trinity Health of New England. Based on this success, Trinity Health plans to next involve the remaining regions of Trinity Health of New England in Target: BP, followed by the other regions of Trinity’s national organization, which operates in 21 states with nearly 4,000 staff physicians and about half a million patients diagnosed with hypertension, Dr. Weiswasser said.
“If clinicians do the three steps of the MAP then we will see substantial drops in blood pressures. It will occur,” declared Brent M. Egan, MD, vice president for cardiovascular disease prevention of the AMA in Greenville, S.C.
The new report includes six performance measures based on the strongest guideline recommendations and designed to document adherence levels for the purposes of public reporting and pay-for-performance programs. It also includes 16 quality measures designed for local quality review purposes, with 6 process quality measures and 10 structural quality measures. The report spells out that the authors designed the performance measures for use by major national organizations such as the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance (NCQA), while the quality measures are designed to support quality improvement efforts in any care-delivery setting.
The authors said that the writing committee is sensitive to the fact that the 2019 performance measures for controlling high blood pressure developed by the NCQA for the Healthcare Effectiveness Data and Information Set and currently in use in 2019 by CMS also does not incorporate the 2017 Hypertension Clinical Practice Guidelines classification scheme. “It is well understood that these measures are already in widespread use, especially for quality-related payment programs promulgated by CMS, such as the Medicare Advantage ‘Stars’ ratings, the Medicare Shared Savings Program, and the Physician Quality Payment Program, as well as many other programs promoted by commercial health insurers. In particular, the widespread use of the 2017 Hypertension Clinical Practice Guidelines classification scheme will also help to guide decision making about when to prescribe antihypertensive medications in accordance with its current recommendations for the ACC/AHA “stages” of stage 1 and stage 2 hypertension and elevated blood pressure,” they added.
The report also says that “the writing committee was sensitive to the fact that there is currently not complete consensus among other guidelines from the American College of Physicians and the American Academy of Family Physicians, and also the European Society of Cardiology and the European Society of Hypertension. Nonetheless, despite this ongoing debate, the writing committee felt strongly that it is now time to move the U.S. health care system ahead to reflect these differing points of view and expects that widespread use of this new measure set will help to achieve this goal.” The new report revises hypertension performance measures developed by the ACC and AHA in 2011 (J Am Coll Cardiol. 2011 Jul 12;58[3]: 316-36).
In short, the performance and quality measures give all the diverse components of the U.S. health care delivery system a road map for implementing the 2017 High Blood Pressure Guideline in a format that depends on those components electing to adopt and adhere to the 2017 guideline. (Although one of the new performance measures, 1a, harmonizes with an existing and widely applied performance measure.)
“Who is the audience for this, and how will they respond? These performance measures need to be appropriated” by health systems and by performance-assessment groups. “I hope the NCQA will adopt it,” said William C. Cushman, MD, professor of preventive medicine at the University of Tennessee Health Science Center in Memphis, and chief of preventive medicine at the Memphis Veterans Affairs Medical Center. “There are some negatives to performance measures, but on balance they have done good things and led to better care.” Dr. Cushman also approved of several specific performance and quality measures included in the report. “Most of what they emphasized is good,” particularly the importance of accurate pressure measurement, he said in an interview.
“Process drives outcomes” in hypertension management, and the new performance and quality measures “have some very good process metrics,” commented Dr. Egan. “I’d encourage health systems to select two or three measures that are key to what they do and make sense in their setting rather than try to implement it all at once,” he advised, echoing what Dr. Casey had suggested. “It’s ideal to do everything, but we know that if you give physicians a long list of performance measures they just get overwhelmed. The nice thing about hypertension is that we know that process drives outcomes. In the past, we’ve had some process metrics that did not drive outcomes. Getting these processes implemented will lead to better patient outcomes and save a ton of money.”
“We have introduced the 2017 guideline recommendations throughout Target: BP, but like any quality improvement program there is a question of how does it spread,” said Gregory Wozniak, PhD, director of outcomes analytics for the AMA in Chicago. “Our goal for Target: BP is to be impacting 20 million patients by 2021.”
Dr. Casey, Dr. Weiswasser, and Dr. Wozniak had no disclosures. Dr. Cushman has received honoraria as a speaker from Arbor and Sanofi-Aventis, and travel and research support from Eli Lilly. Dr. Egan has been a consultant to and speaker on behalf of Merck and a speaker for Emcure.
SOURCE: Casey DE et al. J Am Coll Cardiol. 2019 Nov 26;74[21]: 2661-706.
PHILADELPHIA – The American Heart Association and American College of Cardiology took a big step toward facilitating widespread U.S. application of the hypertension management guideline that the societies issued in 2017 by releasing a set of performance and quality measures for adults with high blood pressure based on the 2017 guideline.
This guideline notably set a treatment target for patients diagnosed with hypertension of less than 130/80 mg/dL, and also lowered the threshold for diagnosing stage 1 hypertension to a blood pressure at or above 130/80 mm Hg, adding in a stroke about 31 million adults with hypertension to the U.S. total.
Having performance and quality measures based on the guideline is “critical, because how else would you know whether you’re having an effect on accurately diagnosing and properly controlling hypertension?” said Donald E. Casey Jr., MD, chair of the performance measures writing committee. The next step is field testing of the measures “to show they are reliable and effective,” as well as other steps to encourage widespread U.S. uptake of the performance and quality measures and the specifics of the 2017 guideline, Dr. Casey said during a presentation of the revised measures at the American Heart Association scientific sessions.
He especially highlighted the important role of Target: BP, an education, recognition, and quality improvement program run by the AHA and American Medical Association, as a tool that medical practices, health systems, and even payers and employers can use to begin to apply the new performance and quality measures (J Am Coll Cardiol. 2019 Nov 26;74[21]:2661-706) and better align with the recommendations of the 2017 high blood pressure guideline (J Am Coll Cardiol. 2018 May;71[19]:e127-248).
“We’re trying now to promote Target: BP; it’s something you can take off the shelf and get going if it’s embedded in a real-life delivery model. I think Target: BP is the secret sauce. It will be the way we’ll convince people to adopt this,” said Dr. Casey, principal and founder of IPO 4 Health, a Chicago-based health care consulting firm.
He also advised practices and health systems not to feel compelled to introduce all of the specific performance and quality measures at once. “We don’t believe everyone has the resources to do all of it at once; the point is to move toward this system of care. We understand that people don’t have the resources to get it all done” immediately, Dr. Casey said in an interview.
A report during another session at the meeting documented the potential impact that Target: BP can have on blood pressure control within a health system. The Trinity Health of New England medical group based in Springfield, Mass., a system with about 140,000 patients – including 20,000 adults diagnosed with hypertension – and served by 230 health care providers in 13 offices in western Massachusetts, began using Target: BP’s MAP improvement program in its practices in November 2018. (MAP stands for measure accurately, act rapidly, and partner with patients.) Just before the MAP program began, 72% of patients diagnosed with hypertension in the medical group were at their goal blood pressure. Less than a year later, in September 2019, the hypertension control rate had jumped to 84%, a 12 percentage point improvement in control in practices that already had been doing a relatively good job, said Daniel W. Weiswasser, MD, director of quality and clinical informatics at Trinity Health of New England. Based on this success, Trinity Health plans to next involve the remaining regions of Trinity Health of New England in Target: BP, followed by the other regions of Trinity’s national organization, which operates in 21 states with nearly 4,000 staff physicians and about half a million patients diagnosed with hypertension, Dr. Weiswasser said.
“If clinicians do the three steps of the MAP then we will see substantial drops in blood pressures. It will occur,” declared Brent M. Egan, MD, vice president for cardiovascular disease prevention of the AMA in Greenville, S.C.
The new report includes six performance measures based on the strongest guideline recommendations and designed to document adherence levels for the purposes of public reporting and pay-for-performance programs. It also includes 16 quality measures designed for local quality review purposes, with 6 process quality measures and 10 structural quality measures. The report spells out that the authors designed the performance measures for use by major national organizations such as the Centers for Medicare & Medicaid Services and the National Committee for Quality Assurance (NCQA), while the quality measures are designed to support quality improvement efforts in any care-delivery setting.
The authors said that the writing committee is sensitive to the fact that the 2019 performance measures for controlling high blood pressure developed by the NCQA for the Healthcare Effectiveness Data and Information Set and currently in use in 2019 by CMS also does not incorporate the 2017 Hypertension Clinical Practice Guidelines classification scheme. “It is well understood that these measures are already in widespread use, especially for quality-related payment programs promulgated by CMS, such as the Medicare Advantage ‘Stars’ ratings, the Medicare Shared Savings Program, and the Physician Quality Payment Program, as well as many other programs promoted by commercial health insurers. In particular, the widespread use of the 2017 Hypertension Clinical Practice Guidelines classification scheme will also help to guide decision making about when to prescribe antihypertensive medications in accordance with its current recommendations for the ACC/AHA “stages” of stage 1 and stage 2 hypertension and elevated blood pressure,” they added.
The report also says that “the writing committee was sensitive to the fact that there is currently not complete consensus among other guidelines from the American College of Physicians and the American Academy of Family Physicians, and also the European Society of Cardiology and the European Society of Hypertension. Nonetheless, despite this ongoing debate, the writing committee felt strongly that it is now time to move the U.S. health care system ahead to reflect these differing points of view and expects that widespread use of this new measure set will help to achieve this goal.” The new report revises hypertension performance measures developed by the ACC and AHA in 2011 (J Am Coll Cardiol. 2011 Jul 12;58[3]: 316-36).
In short, the performance and quality measures give all the diverse components of the U.S. health care delivery system a road map for implementing the 2017 High Blood Pressure Guideline in a format that depends on those components electing to adopt and adhere to the 2017 guideline. (Although one of the new performance measures, 1a, harmonizes with an existing and widely applied performance measure.)
“Who is the audience for this, and how will they respond? These performance measures need to be appropriated” by health systems and by performance-assessment groups. “I hope the NCQA will adopt it,” said William C. Cushman, MD, professor of preventive medicine at the University of Tennessee Health Science Center in Memphis, and chief of preventive medicine at the Memphis Veterans Affairs Medical Center. “There are some negatives to performance measures, but on balance they have done good things and led to better care.” Dr. Cushman also approved of several specific performance and quality measures included in the report. “Most of what they emphasized is good,” particularly the importance of accurate pressure measurement, he said in an interview.
“Process drives outcomes” in hypertension management, and the new performance and quality measures “have some very good process metrics,” commented Dr. Egan. “I’d encourage health systems to select two or three measures that are key to what they do and make sense in their setting rather than try to implement it all at once,” he advised, echoing what Dr. Casey had suggested. “It’s ideal to do everything, but we know that if you give physicians a long list of performance measures they just get overwhelmed. The nice thing about hypertension is that we know that process drives outcomes. In the past, we’ve had some process metrics that did not drive outcomes. Getting these processes implemented will lead to better patient outcomes and save a ton of money.”
“We have introduced the 2017 guideline recommendations throughout Target: BP, but like any quality improvement program there is a question of how does it spread,” said Gregory Wozniak, PhD, director of outcomes analytics for the AMA in Chicago. “Our goal for Target: BP is to be impacting 20 million patients by 2021.”
Dr. Casey, Dr. Weiswasser, and Dr. Wozniak had no disclosures. Dr. Cushman has received honoraria as a speaker from Arbor and Sanofi-Aventis, and travel and research support from Eli Lilly. Dr. Egan has been a consultant to and speaker on behalf of Merck and a speaker for Emcure.
SOURCE: Casey DE et al. J Am Coll Cardiol. 2019 Nov 26;74[21]: 2661-706.
REPORTING FROM AHA 2019
SZC passes extension test for hyperkalemia
Treatment with sodium zirconium cyclosilicate (SZC) led to lasting improvement of hyperkalemia, according to results from an 11-month open-label extension study of the HARMONIZE randomized clinical trial.
SZC selectively binds potassium ions in the colon, reducing absorption and promoting excretion. In the original study, 248 patients with mild hyperkalemia were randomized to SZC or placebo. Within 48 hours, the drug returned potassium to normal and maintained those levels out to 4 weeks.
In the extension study, 123 patients with measured potassium levels of 3.5-6.2 mmol/L, 48 of whom had previously been assigned to placebo, received a 5- to 10-g dose of SZC once per day for up to 337 days. Median daily dose was 10 g, with a dose range of 2.5-15 g (Am J Nephrol. 2019;50[6]:473-480).
Just under 65% of patients completed the 11 months of the open-label extension study, with 88.3% of those achieving the primary endpoint of mean serum potassium levels of 5.1 mmol/L or lower, according to Simon D. Roger, MD, a nephrologist based in Gosford, Australia, and colleagues.
Most patients (83) were taking renin–angiotensin–aldosterone system inhibitors at baseline of the extension study; 78.3% continued a stable dose throughout the open-label phase, 8.4% increased the dose, and 3.6% discontinued.
Two-thirds of patients reported adverse events, most commonly gastrointestinal disorders (18.7%). Constipation was the most frequent (5.7%), followed by nausea, vomiting, and diarrhea (3.3% each).
Adverse events that occurred in 5% or more of participants included hypertension (12.2%), urinary tract infection (8.9%), and peripheral edema (8.1%). Hypertension severity was either mild (46.7%) or moderate (53.3%), and only one case was believed to be associated with the study medication. Thirteen percent of participants reported a total of 17 SMQ edema events. Eleven of the 16 patients had baseline risk factors for edema, leading the authors to conclude that causality between SZC and edema could not be established.
Serious adverse events occurred in 19.5% of participants, and 4.9% of participants discontinued SZC as a result.
SZC is approved for the treatment of hyperkalemia in the United States and Europe. The study was funded by AstraZeneca.
SOURCE: Roger S et al. Am J Nephrol;2019:50(6):473-80.
Treatment with sodium zirconium cyclosilicate (SZC) led to lasting improvement of hyperkalemia, according to results from an 11-month open-label extension study of the HARMONIZE randomized clinical trial.
SZC selectively binds potassium ions in the colon, reducing absorption and promoting excretion. In the original study, 248 patients with mild hyperkalemia were randomized to SZC or placebo. Within 48 hours, the drug returned potassium to normal and maintained those levels out to 4 weeks.
In the extension study, 123 patients with measured potassium levels of 3.5-6.2 mmol/L, 48 of whom had previously been assigned to placebo, received a 5- to 10-g dose of SZC once per day for up to 337 days. Median daily dose was 10 g, with a dose range of 2.5-15 g (Am J Nephrol. 2019;50[6]:473-480).
Just under 65% of patients completed the 11 months of the open-label extension study, with 88.3% of those achieving the primary endpoint of mean serum potassium levels of 5.1 mmol/L or lower, according to Simon D. Roger, MD, a nephrologist based in Gosford, Australia, and colleagues.
Most patients (83) were taking renin–angiotensin–aldosterone system inhibitors at baseline of the extension study; 78.3% continued a stable dose throughout the open-label phase, 8.4% increased the dose, and 3.6% discontinued.
Two-thirds of patients reported adverse events, most commonly gastrointestinal disorders (18.7%). Constipation was the most frequent (5.7%), followed by nausea, vomiting, and diarrhea (3.3% each).
Adverse events that occurred in 5% or more of participants included hypertension (12.2%), urinary tract infection (8.9%), and peripheral edema (8.1%). Hypertension severity was either mild (46.7%) or moderate (53.3%), and only one case was believed to be associated with the study medication. Thirteen percent of participants reported a total of 17 SMQ edema events. Eleven of the 16 patients had baseline risk factors for edema, leading the authors to conclude that causality between SZC and edema could not be established.
Serious adverse events occurred in 19.5% of participants, and 4.9% of participants discontinued SZC as a result.
SZC is approved for the treatment of hyperkalemia in the United States and Europe. The study was funded by AstraZeneca.
SOURCE: Roger S et al. Am J Nephrol;2019:50(6):473-80.
Treatment with sodium zirconium cyclosilicate (SZC) led to lasting improvement of hyperkalemia, according to results from an 11-month open-label extension study of the HARMONIZE randomized clinical trial.
SZC selectively binds potassium ions in the colon, reducing absorption and promoting excretion. In the original study, 248 patients with mild hyperkalemia were randomized to SZC or placebo. Within 48 hours, the drug returned potassium to normal and maintained those levels out to 4 weeks.
In the extension study, 123 patients with measured potassium levels of 3.5-6.2 mmol/L, 48 of whom had previously been assigned to placebo, received a 5- to 10-g dose of SZC once per day for up to 337 days. Median daily dose was 10 g, with a dose range of 2.5-15 g (Am J Nephrol. 2019;50[6]:473-480).
Just under 65% of patients completed the 11 months of the open-label extension study, with 88.3% of those achieving the primary endpoint of mean serum potassium levels of 5.1 mmol/L or lower, according to Simon D. Roger, MD, a nephrologist based in Gosford, Australia, and colleagues.
Most patients (83) were taking renin–angiotensin–aldosterone system inhibitors at baseline of the extension study; 78.3% continued a stable dose throughout the open-label phase, 8.4% increased the dose, and 3.6% discontinued.
Two-thirds of patients reported adverse events, most commonly gastrointestinal disorders (18.7%). Constipation was the most frequent (5.7%), followed by nausea, vomiting, and diarrhea (3.3% each).
Adverse events that occurred in 5% or more of participants included hypertension (12.2%), urinary tract infection (8.9%), and peripheral edema (8.1%). Hypertension severity was either mild (46.7%) or moderate (53.3%), and only one case was believed to be associated with the study medication. Thirteen percent of participants reported a total of 17 SMQ edema events. Eleven of the 16 patients had baseline risk factors for edema, leading the authors to conclude that causality between SZC and edema could not be established.
Serious adverse events occurred in 19.5% of participants, and 4.9% of participants discontinued SZC as a result.
SZC is approved for the treatment of hyperkalemia in the United States and Europe. The study was funded by AstraZeneca.
SOURCE: Roger S et al. Am J Nephrol;2019:50(6):473-80.
FROM AMERICAN JOURNAL OF NEPHROLOGY
ASH releases guidelines on managing cardiopulmonary and kidney disease in SCD
ORLANDO – It is good practice to consult with a pulmonary hypertension (PH) expert before referring a patient with sickle cell disease (SCD) for right-heart catheterization or PH evaluation, according to new American Society of Hematology guidelines for the screening and management of cardiopulmonary and kidney disease in patients with SCD.
That “Good Practice” recommendation is one of several included in the evidence-based guidelines published Dec. 10 in Blood Advances and highlighted during a Special Education Session at the annual ASH meeting.
The guidelines provide 10 main recommendations intended to “support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD,” wrote Robert I. Liem, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago and colleagues.
The recommendations, agreed upon by a multidisciplinary guideline panel, relate to screening, diagnosis, and management of PH, pulmonary arterial hypertension (PAH), hypertension, proteinuria and chronic kidney disease, and venous thromboembolism (VTE). Most are “conditional,” as opposed to “strong,” because of a paucity of direct, high-quality outcomes data, and they are accompanied by the Good Practice Statements, descriptive remarks and caveats based on the available data, as well as suggestions for future research.
At the special ASH session, Ankit A. Desai, MD, highlighted some of the recommendations and discussed considerations for their practical application.
The Good Practice Statement on consulting a specialist before referring a patient for PH relates specifically to Recommendations 2a and 2b on the management of abnormal echocardiography, explained Dr. Desai of Indiana University, Indianapolis.
For asymptomatic children and adults with SCD and an isolated peak tricuspid regurgitant jet velocity (TRJV) of at least 2.5-2.9 m/s on echocardiography, the panel recommends against right-heart catheterization (Recommendation 2a, conditional), he said.
For children and adults with SCD and a peak TRJV of at least 2.5 m/s who also have a reduced 6-minute walk distance (6MWD) and/or elevated N-terminal proB-type natriuretic peptide (NT-proBNP), the panel supports right-heart catheterization (Recommendation 2b, conditional).
Dr. Desai noted that the 2.5 m/s threshold was found to be suboptimal when used as the sole criteria for right-heart catheterization. Using that threshold alone is associated with “moderate to large” harms, such as starting inappropriate PH-specific therapies and/or performing unnecessary right-heart catheterization. However, when used in combination with 6MWD, the predictive capacity improved significantly, and the risk for potential harm was low, he explained.
Another Good Practice Statement included in the guidelines, and relevant to these recommendations on managing abnormal echocardiography, addresses the importance of basing decisions about the need for right-heart catheterization on echocardiograms obtained at steady state rather than during acute illness, such as during hospitalization for pain or acute chest syndrome.
This is in part because of technical factors, Dr. Desai said.
“We know that repeating [echocardiography] is something that should be considered in patients because ... results vary – sometimes quite a bit – from study to study,” he said.
As for the cutoff values for 6MWD and NT-proBNP, “a decent amount of literature” suggests that less than 333 m and less than 160 pg/ml, respectively, are good thresholds, he said.
“Importantly, this should all be taken in the context of good clinical judgment ... along with discussion with a PH expert,” he added.
The full guidelines are available, along with additional ASH guidelines on immune thrombocytopenia and prevention of venous thromboembolism in surgical hospitalized patients, at the ASH publications website.
Of note, the SCD guidelines on cardiopulmonary disease and kidney disease are one of five sets of SCD guidelines that have been in development; these are the first of those to be published. The remaining four sets of guidelines will address pain, cerebrovascular complications, transfusion, and hematopoietic stem cell transplant. All will be published in Blood Advances, and according to Dr. Liem, the transfusion medicine guidelines have been accepted and should be published in January 2020, followed by those for cerebrovascular complications. Publication of the pain and transplant guidelines are anticipated later in 2020.
Dr. Liem and Dr. Desai reported having no conflicts of interest.
ORLANDO – It is good practice to consult with a pulmonary hypertension (PH) expert before referring a patient with sickle cell disease (SCD) for right-heart catheterization or PH evaluation, according to new American Society of Hematology guidelines for the screening and management of cardiopulmonary and kidney disease in patients with SCD.
That “Good Practice” recommendation is one of several included in the evidence-based guidelines published Dec. 10 in Blood Advances and highlighted during a Special Education Session at the annual ASH meeting.
The guidelines provide 10 main recommendations intended to “support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD,” wrote Robert I. Liem, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago and colleagues.
The recommendations, agreed upon by a multidisciplinary guideline panel, relate to screening, diagnosis, and management of PH, pulmonary arterial hypertension (PAH), hypertension, proteinuria and chronic kidney disease, and venous thromboembolism (VTE). Most are “conditional,” as opposed to “strong,” because of a paucity of direct, high-quality outcomes data, and they are accompanied by the Good Practice Statements, descriptive remarks and caveats based on the available data, as well as suggestions for future research.
At the special ASH session, Ankit A. Desai, MD, highlighted some of the recommendations and discussed considerations for their practical application.
The Good Practice Statement on consulting a specialist before referring a patient for PH relates specifically to Recommendations 2a and 2b on the management of abnormal echocardiography, explained Dr. Desai of Indiana University, Indianapolis.
For asymptomatic children and adults with SCD and an isolated peak tricuspid regurgitant jet velocity (TRJV) of at least 2.5-2.9 m/s on echocardiography, the panel recommends against right-heart catheterization (Recommendation 2a, conditional), he said.
For children and adults with SCD and a peak TRJV of at least 2.5 m/s who also have a reduced 6-minute walk distance (6MWD) and/or elevated N-terminal proB-type natriuretic peptide (NT-proBNP), the panel supports right-heart catheterization (Recommendation 2b, conditional).
Dr. Desai noted that the 2.5 m/s threshold was found to be suboptimal when used as the sole criteria for right-heart catheterization. Using that threshold alone is associated with “moderate to large” harms, such as starting inappropriate PH-specific therapies and/or performing unnecessary right-heart catheterization. However, when used in combination with 6MWD, the predictive capacity improved significantly, and the risk for potential harm was low, he explained.
Another Good Practice Statement included in the guidelines, and relevant to these recommendations on managing abnormal echocardiography, addresses the importance of basing decisions about the need for right-heart catheterization on echocardiograms obtained at steady state rather than during acute illness, such as during hospitalization for pain or acute chest syndrome.
This is in part because of technical factors, Dr. Desai said.
“We know that repeating [echocardiography] is something that should be considered in patients because ... results vary – sometimes quite a bit – from study to study,” he said.
As for the cutoff values for 6MWD and NT-proBNP, “a decent amount of literature” suggests that less than 333 m and less than 160 pg/ml, respectively, are good thresholds, he said.
“Importantly, this should all be taken in the context of good clinical judgment ... along with discussion with a PH expert,” he added.
The full guidelines are available, along with additional ASH guidelines on immune thrombocytopenia and prevention of venous thromboembolism in surgical hospitalized patients, at the ASH publications website.
Of note, the SCD guidelines on cardiopulmonary disease and kidney disease are one of five sets of SCD guidelines that have been in development; these are the first of those to be published. The remaining four sets of guidelines will address pain, cerebrovascular complications, transfusion, and hematopoietic stem cell transplant. All will be published in Blood Advances, and according to Dr. Liem, the transfusion medicine guidelines have been accepted and should be published in January 2020, followed by those for cerebrovascular complications. Publication of the pain and transplant guidelines are anticipated later in 2020.
Dr. Liem and Dr. Desai reported having no conflicts of interest.
ORLANDO – It is good practice to consult with a pulmonary hypertension (PH) expert before referring a patient with sickle cell disease (SCD) for right-heart catheterization or PH evaluation, according to new American Society of Hematology guidelines for the screening and management of cardiopulmonary and kidney disease in patients with SCD.
That “Good Practice” recommendation is one of several included in the evidence-based guidelines published Dec. 10 in Blood Advances and highlighted during a Special Education Session at the annual ASH meeting.
The guidelines provide 10 main recommendations intended to “support patients, clinicians, and other health care professionals in their decisions about screening, diagnosis, and management of cardiopulmonary and renal complications of SCD,” wrote Robert I. Liem, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago and colleagues.
The recommendations, agreed upon by a multidisciplinary guideline panel, relate to screening, diagnosis, and management of PH, pulmonary arterial hypertension (PAH), hypertension, proteinuria and chronic kidney disease, and venous thromboembolism (VTE). Most are “conditional,” as opposed to “strong,” because of a paucity of direct, high-quality outcomes data, and they are accompanied by the Good Practice Statements, descriptive remarks and caveats based on the available data, as well as suggestions for future research.
At the special ASH session, Ankit A. Desai, MD, highlighted some of the recommendations and discussed considerations for their practical application.
The Good Practice Statement on consulting a specialist before referring a patient for PH relates specifically to Recommendations 2a and 2b on the management of abnormal echocardiography, explained Dr. Desai of Indiana University, Indianapolis.
For asymptomatic children and adults with SCD and an isolated peak tricuspid regurgitant jet velocity (TRJV) of at least 2.5-2.9 m/s on echocardiography, the panel recommends against right-heart catheterization (Recommendation 2a, conditional), he said.
For children and adults with SCD and a peak TRJV of at least 2.5 m/s who also have a reduced 6-minute walk distance (6MWD) and/or elevated N-terminal proB-type natriuretic peptide (NT-proBNP), the panel supports right-heart catheterization (Recommendation 2b, conditional).
Dr. Desai noted that the 2.5 m/s threshold was found to be suboptimal when used as the sole criteria for right-heart catheterization. Using that threshold alone is associated with “moderate to large” harms, such as starting inappropriate PH-specific therapies and/or performing unnecessary right-heart catheterization. However, when used in combination with 6MWD, the predictive capacity improved significantly, and the risk for potential harm was low, he explained.
Another Good Practice Statement included in the guidelines, and relevant to these recommendations on managing abnormal echocardiography, addresses the importance of basing decisions about the need for right-heart catheterization on echocardiograms obtained at steady state rather than during acute illness, such as during hospitalization for pain or acute chest syndrome.
This is in part because of technical factors, Dr. Desai said.
“We know that repeating [echocardiography] is something that should be considered in patients because ... results vary – sometimes quite a bit – from study to study,” he said.
As for the cutoff values for 6MWD and NT-proBNP, “a decent amount of literature” suggests that less than 333 m and less than 160 pg/ml, respectively, are good thresholds, he said.
“Importantly, this should all be taken in the context of good clinical judgment ... along with discussion with a PH expert,” he added.
The full guidelines are available, along with additional ASH guidelines on immune thrombocytopenia and prevention of venous thromboembolism in surgical hospitalized patients, at the ASH publications website.
Of note, the SCD guidelines on cardiopulmonary disease and kidney disease are one of five sets of SCD guidelines that have been in development; these are the first of those to be published. The remaining four sets of guidelines will address pain, cerebrovascular complications, transfusion, and hematopoietic stem cell transplant. All will be published in Blood Advances, and according to Dr. Liem, the transfusion medicine guidelines have been accepted and should be published in January 2020, followed by those for cerebrovascular complications. Publication of the pain and transplant guidelines are anticipated later in 2020.
Dr. Liem and Dr. Desai reported having no conflicts of interest.
EXPERT ANALYSIS FROM ASH 2019
Intensive BP control reduced dementia but increased brain atrophy and hurt cognition
SAN DIEGO – Intensive blood pressure control over 4 years reduced the overall risk of all-cause dementia by 17%, compared with standard care, but in subanalyses of the Systolic Blood Pressure Intervention Trial (SPRINT) it was also associated with significant decreases in cognitive function and total brain volume, researchers said at the Clinical Trials on Alzheimer’s Disease conference.
Whether these between-group differences were clinically meaningful was the topic of some debate, but they were enough to prompt Mary Sano, PhD, to strongly state her reservations.
“The cardiovascular effects of SPRINT were impressive, but I am concerned about minimizing the potentially negative effect on cognition,” said Dr. Sano, professor of psychiatry and director of the Alzheimer’s Disease Research Center at the Icahn School of Medicine at Mount Sinai, New York. “Do I really want to treat a healthy, nonimpaired patient like this if I have to warn them that their cognition might actually get worse? We just cannot minimize this risk. There is very strong evidence that [intensive treatment of blood pressure] might be a step backward in cognition. Would you lower your own blood pressure at a risk of losing some points on your cognition?”
The subanalyses were conducted as part of the SPRINT Memory and Cognition In Decreased Hypertension (SPRINT MIND) substudy, which looked at cardiovascular and mortality outcomes in 9,361 subjects whose hypertension was managed intensively or by standard care (target systolic blood pressure less than 120 mm Hg vs. less than 140 mm Hg). The trial was stopped early because of a 25% reduction in the primary composite cardiovascular disease endpoint and a 27% reduction in all-cause mortality in the intensive-treatment group.
SPRINT MIND examined the risks of incident probable dementia, mild cognitive impairment (MCI), and a composite outcome of both. Intensive control reduced the risk of MCI by 19% and the combined outcome by 15%.
At the conference, SPRINT MIND investigators presented three long-term subanalyses with a median intervention and follow-up time of about 4 years.
Sarah Gaussoin of Wake Forest University, Winston-Salem, N.C., presented unpublished data detailing the effects of intensive control on several dementia subtypes: nonamnestic single domain, nonamnestic multidomain, amnestic single domain, and amnestic multidomain. There were 640 subjects in this analysis.
After a median of 3.3 years of intervention and 5 years of follow-up, there were no differences in the rate of incident probable dementia between the single- and multidomain nonamnestic groups. “We did see a strong 22% decreased risk in single-domain versus multidomain amnestic MCI, however,” she said.
Nicholas Pajewski, PhD, also of Wake Forest University, discussed more detailed cognitive outcomes in SPRINT MIND among 2,900 subjects who had a full battery of cognitive testing at every assessment over 5 years. The outcomes included memory deficit and processing speed.
Dr. Pajewski reported finding no significant difference between the groups in the rates of memory decline in either outcome. But there was a greater rate of decline in processing speed in the intensively treated group, he added. The difference was small but statistically significant.
The difference was largely driven by results of a single cognitive test – the Trail Making Test Part A. “It corresponded to about a 1.25-second increase over 4 years,” in processing speed on this test, Dr. Pajewski said.
There were no between-group differences in any of the other domains explored, including language, executive function, global cognitive function, or the Montreal Cognitive Assessment.
“Obviously, these results are perplexing,” given the overall positive results of SPRINT MIND, he said. “Intensive blood pressure control is a beneficial thing, and we expected to see an effect on memory, or a blunting of decline, and instead we saw some small decrements going the other way. This led us to speculate about what’s going on.”
The trial relied on a narrow definition of MCI that might have affected the outcomes. There was also a very broad range of ages in the study, ranging from 53 to 86 years. More importantly, he said, the original SPRINT study didn’t collect cognitive data at baseline, so there was no way to know how many subjects already might have had MCI when they entered the trial.
Ilya Nasrallah, MD, PhD, of the University of Pennsylvania, Philadelphia, presented MRI data on white-matter lesions, hippocampal volume fractional anisotropy in the cingulum, and cerebral blood flow. The median time between scans was 4 years, with a median treatment time of 3.4 years.
The standard-care group showed a significantly greater increase in white-matter lesion volume at the follow-up scan than did the intensive-treatment group (1.45 cm3 vs. 0.92 cm3). But the intensively treated group had significantly more brain atrophy, losing a median of 30.6 cm3, compared with a loss of 26.9 cm3 in the standard-treatment group.
“It was a very small difference amounting to less than 1% of the total brain volume, but it was still statistically significant,” Dr. Nasrallah said.
Loss of gray-matter volume drove about two-thirds of the difference in the intensively treated group. There was a corresponding increase in cerebrospinal fluid volume that was driven by differences in the ventricles and the subarachnoid space.
However, there were no significant differences in right, left, or total hippocampal volume. There also were no differences in cingulate bundle anisotropy or cerebral blood flow.
SPRINT was funded by the National Institutes of Health. None of the investigators reported having financial conflicts of interest.
SAN DIEGO – Intensive blood pressure control over 4 years reduced the overall risk of all-cause dementia by 17%, compared with standard care, but in subanalyses of the Systolic Blood Pressure Intervention Trial (SPRINT) it was also associated with significant decreases in cognitive function and total brain volume, researchers said at the Clinical Trials on Alzheimer’s Disease conference.
Whether these between-group differences were clinically meaningful was the topic of some debate, but they were enough to prompt Mary Sano, PhD, to strongly state her reservations.
“The cardiovascular effects of SPRINT were impressive, but I am concerned about minimizing the potentially negative effect on cognition,” said Dr. Sano, professor of psychiatry and director of the Alzheimer’s Disease Research Center at the Icahn School of Medicine at Mount Sinai, New York. “Do I really want to treat a healthy, nonimpaired patient like this if I have to warn them that their cognition might actually get worse? We just cannot minimize this risk. There is very strong evidence that [intensive treatment of blood pressure] might be a step backward in cognition. Would you lower your own blood pressure at a risk of losing some points on your cognition?”
The subanalyses were conducted as part of the SPRINT Memory and Cognition In Decreased Hypertension (SPRINT MIND) substudy, which looked at cardiovascular and mortality outcomes in 9,361 subjects whose hypertension was managed intensively or by standard care (target systolic blood pressure less than 120 mm Hg vs. less than 140 mm Hg). The trial was stopped early because of a 25% reduction in the primary composite cardiovascular disease endpoint and a 27% reduction in all-cause mortality in the intensive-treatment group.
SPRINT MIND examined the risks of incident probable dementia, mild cognitive impairment (MCI), and a composite outcome of both. Intensive control reduced the risk of MCI by 19% and the combined outcome by 15%.
At the conference, SPRINT MIND investigators presented three long-term subanalyses with a median intervention and follow-up time of about 4 years.
Sarah Gaussoin of Wake Forest University, Winston-Salem, N.C., presented unpublished data detailing the effects of intensive control on several dementia subtypes: nonamnestic single domain, nonamnestic multidomain, amnestic single domain, and amnestic multidomain. There were 640 subjects in this analysis.
After a median of 3.3 years of intervention and 5 years of follow-up, there were no differences in the rate of incident probable dementia between the single- and multidomain nonamnestic groups. “We did see a strong 22% decreased risk in single-domain versus multidomain amnestic MCI, however,” she said.
Nicholas Pajewski, PhD, also of Wake Forest University, discussed more detailed cognitive outcomes in SPRINT MIND among 2,900 subjects who had a full battery of cognitive testing at every assessment over 5 years. The outcomes included memory deficit and processing speed.
Dr. Pajewski reported finding no significant difference between the groups in the rates of memory decline in either outcome. But there was a greater rate of decline in processing speed in the intensively treated group, he added. The difference was small but statistically significant.
The difference was largely driven by results of a single cognitive test – the Trail Making Test Part A. “It corresponded to about a 1.25-second increase over 4 years,” in processing speed on this test, Dr. Pajewski said.
There were no between-group differences in any of the other domains explored, including language, executive function, global cognitive function, or the Montreal Cognitive Assessment.
“Obviously, these results are perplexing,” given the overall positive results of SPRINT MIND, he said. “Intensive blood pressure control is a beneficial thing, and we expected to see an effect on memory, or a blunting of decline, and instead we saw some small decrements going the other way. This led us to speculate about what’s going on.”
The trial relied on a narrow definition of MCI that might have affected the outcomes. There was also a very broad range of ages in the study, ranging from 53 to 86 years. More importantly, he said, the original SPRINT study didn’t collect cognitive data at baseline, so there was no way to know how many subjects already might have had MCI when they entered the trial.
Ilya Nasrallah, MD, PhD, of the University of Pennsylvania, Philadelphia, presented MRI data on white-matter lesions, hippocampal volume fractional anisotropy in the cingulum, and cerebral blood flow. The median time between scans was 4 years, with a median treatment time of 3.4 years.
The standard-care group showed a significantly greater increase in white-matter lesion volume at the follow-up scan than did the intensive-treatment group (1.45 cm3 vs. 0.92 cm3). But the intensively treated group had significantly more brain atrophy, losing a median of 30.6 cm3, compared with a loss of 26.9 cm3 in the standard-treatment group.
“It was a very small difference amounting to less than 1% of the total brain volume, but it was still statistically significant,” Dr. Nasrallah said.
Loss of gray-matter volume drove about two-thirds of the difference in the intensively treated group. There was a corresponding increase in cerebrospinal fluid volume that was driven by differences in the ventricles and the subarachnoid space.
However, there were no significant differences in right, left, or total hippocampal volume. There also were no differences in cingulate bundle anisotropy or cerebral blood flow.
SPRINT was funded by the National Institutes of Health. None of the investigators reported having financial conflicts of interest.
SAN DIEGO – Intensive blood pressure control over 4 years reduced the overall risk of all-cause dementia by 17%, compared with standard care, but in subanalyses of the Systolic Blood Pressure Intervention Trial (SPRINT) it was also associated with significant decreases in cognitive function and total brain volume, researchers said at the Clinical Trials on Alzheimer’s Disease conference.
Whether these between-group differences were clinically meaningful was the topic of some debate, but they were enough to prompt Mary Sano, PhD, to strongly state her reservations.
“The cardiovascular effects of SPRINT were impressive, but I am concerned about minimizing the potentially negative effect on cognition,” said Dr. Sano, professor of psychiatry and director of the Alzheimer’s Disease Research Center at the Icahn School of Medicine at Mount Sinai, New York. “Do I really want to treat a healthy, nonimpaired patient like this if I have to warn them that their cognition might actually get worse? We just cannot minimize this risk. There is very strong evidence that [intensive treatment of blood pressure] might be a step backward in cognition. Would you lower your own blood pressure at a risk of losing some points on your cognition?”
The subanalyses were conducted as part of the SPRINT Memory and Cognition In Decreased Hypertension (SPRINT MIND) substudy, which looked at cardiovascular and mortality outcomes in 9,361 subjects whose hypertension was managed intensively or by standard care (target systolic blood pressure less than 120 mm Hg vs. less than 140 mm Hg). The trial was stopped early because of a 25% reduction in the primary composite cardiovascular disease endpoint and a 27% reduction in all-cause mortality in the intensive-treatment group.
SPRINT MIND examined the risks of incident probable dementia, mild cognitive impairment (MCI), and a composite outcome of both. Intensive control reduced the risk of MCI by 19% and the combined outcome by 15%.
At the conference, SPRINT MIND investigators presented three long-term subanalyses with a median intervention and follow-up time of about 4 years.
Sarah Gaussoin of Wake Forest University, Winston-Salem, N.C., presented unpublished data detailing the effects of intensive control on several dementia subtypes: nonamnestic single domain, nonamnestic multidomain, amnestic single domain, and amnestic multidomain. There were 640 subjects in this analysis.
After a median of 3.3 years of intervention and 5 years of follow-up, there were no differences in the rate of incident probable dementia between the single- and multidomain nonamnestic groups. “We did see a strong 22% decreased risk in single-domain versus multidomain amnestic MCI, however,” she said.
Nicholas Pajewski, PhD, also of Wake Forest University, discussed more detailed cognitive outcomes in SPRINT MIND among 2,900 subjects who had a full battery of cognitive testing at every assessment over 5 years. The outcomes included memory deficit and processing speed.
Dr. Pajewski reported finding no significant difference between the groups in the rates of memory decline in either outcome. But there was a greater rate of decline in processing speed in the intensively treated group, he added. The difference was small but statistically significant.
The difference was largely driven by results of a single cognitive test – the Trail Making Test Part A. “It corresponded to about a 1.25-second increase over 4 years,” in processing speed on this test, Dr. Pajewski said.
There were no between-group differences in any of the other domains explored, including language, executive function, global cognitive function, or the Montreal Cognitive Assessment.
“Obviously, these results are perplexing,” given the overall positive results of SPRINT MIND, he said. “Intensive blood pressure control is a beneficial thing, and we expected to see an effect on memory, or a blunting of decline, and instead we saw some small decrements going the other way. This led us to speculate about what’s going on.”
The trial relied on a narrow definition of MCI that might have affected the outcomes. There was also a very broad range of ages in the study, ranging from 53 to 86 years. More importantly, he said, the original SPRINT study didn’t collect cognitive data at baseline, so there was no way to know how many subjects already might have had MCI when they entered the trial.
Ilya Nasrallah, MD, PhD, of the University of Pennsylvania, Philadelphia, presented MRI data on white-matter lesions, hippocampal volume fractional anisotropy in the cingulum, and cerebral blood flow. The median time between scans was 4 years, with a median treatment time of 3.4 years.
The standard-care group showed a significantly greater increase in white-matter lesion volume at the follow-up scan than did the intensive-treatment group (1.45 cm3 vs. 0.92 cm3). But the intensively treated group had significantly more brain atrophy, losing a median of 30.6 cm3, compared with a loss of 26.9 cm3 in the standard-treatment group.
“It was a very small difference amounting to less than 1% of the total brain volume, but it was still statistically significant,” Dr. Nasrallah said.
Loss of gray-matter volume drove about two-thirds of the difference in the intensively treated group. There was a corresponding increase in cerebrospinal fluid volume that was driven by differences in the ventricles and the subarachnoid space.
However, there were no significant differences in right, left, or total hippocampal volume. There also were no differences in cingulate bundle anisotropy or cerebral blood flow.
SPRINT was funded by the National Institutes of Health. None of the investigators reported having financial conflicts of interest.
REPORTING FROM CTAD 2019
Data build on cardiovascular disease risk after GDM, HDP
WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And ”
Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.
An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.
The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).
HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.
Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).
Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.
Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”
The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data
The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.
Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.
An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).
The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.
Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.
Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.
“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”
Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
Racial/ethnic disparities, postpartum care
Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.
Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).
On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.
At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.
A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).
Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.
A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).
“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”
For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.
Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.
WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And ”
Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.
An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.
The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).
HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.
Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).
Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.
Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”
The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data
The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.
Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.
An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).
The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.
Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.
Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.
“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”
Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
Racial/ethnic disparities, postpartum care
Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.
Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).
On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.
At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.
A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).
Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.
A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).
“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”
For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.
Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.
WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.
Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And ”
Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.
An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.
The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).
HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.
Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).
Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.
Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”
The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data
The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.
Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.
An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).
The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.
Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.
Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.
“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”
Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
Racial/ethnic disparities, postpartum care
Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.
Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).
On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.
At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.
A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).
Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.
A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).
“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”
For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.
Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.
REPORTING FROM THE DPSG-NA 2019
Weaknesses exposed in valsartan recall
ED visits for hypertension in month after the 2018 recall spiked 55%
PHILADELPHIA – The 2018 recall of generic forms of the antihypertensive valsartan exposed weaknesses in the recall systems for generic drugs in both the United States and Canada that caused many patients on the drug to fall through the cracks, according to a study of prescribing patterns in Ontario before and after the recall reported at the American Heart Association scientific sessions.
The results also have been published online in the journal Circulation (2019 Nov 11. doi: 10.1161/CIRCULATIONAHA.119.044494).
Cynthia Jackevicius, PharmD, of the Western University of Health Sciences in Pomona, Calif., reported that 90% of patients on recalled generic valsartan products switched to another antihypertension drug, but called the 10% for whom the study had no data “concerning.” She also said that ED visits for hypertension (HTN) in the month after the recall spiked 55%, from a rate of 0.11% to 0.17% (P = .02). While small, that increase was statistically significant, she said.
The Food and Drug Administration and Health Canada issued voluntary recalls of generic forms of valsartan in July 2018 following reports of N-nitrosodimethylamine (NDMA), a suspected carcinogen, being found in the products. Eventually, the recalls expanded to include valsartan products containing the contaminants N-nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA), as well as losartan and irbesartan products.
The Ontario study evaluated prescribing patterns and health system utilization in four different provincewide health databases and involved 55,461 patients, all of whom were on recalled generic valsartan when Health Canada issued the recall. The study also computed monthly rates of ED visits and hospitalizations for HTN, congestive heart failure, stroke/transit ischemic attack, and MI as primary diagnoses for 18 months before and 6 months after the recall. Rates of utilization for CHF and MI remained relatively flat through the study period, Dr. Jackevicius said, but rates of ED visits for stroke/TIA showed “a very small relative increase: 6% and 8% in ED visits and hospitalizations, respectively.” Respective P values were .020 and .037.
As for the nature of the ED visits after the recall, Dr. Jackevicius said the study did not tease that out. Many visits could have been for uncontrolled HTN or to get expired prescriptions refilled.
“But either way, even if it is just getting a new prescription, this isn’t the best response,” she said. We need to have a better system where patients can more easily or with less burden deal with a recall.”
Session moderator Seth S. Martin, MD, MHS, of Johns Hopkins University in Baltimore, echoed Dr. Jackevicius’s concerns about the handling of drug recalls. “Recalls are increasing,” he said. “Is this just the tip of the iceberg on the quality of generics and we’re going to see these floodgates open? Is this going to be chaos or is this more isolated to this class of medication, the ARBs? This is becoming a little concerning.”
Dr. Jackevicius made note of the recalls that followed the original valsartan recall.
“This really opened a lot of questions in terms of the quality of generic products,” she said. Drug manufacturers are putting safeguards into place to detect these potential contaminants, she said, “but a lot more work needs to be done to ensure the supply. All of these recalls and the prominence of this will be increased.”
The response to the recalls also must undergo revision, she said, citing the experiences of the United States and Canada. “There isn’t really a good system or strategy for recalls in either country,” Dr. Jackevicius said, noting that regulatory bodies notify prescribers and physicians, but “they don’t know which patients are on it.”
A better strategy would be to involve pharmacies more in the process. “The pharmacies have the lot numbers, and they will know what patients are on the recalled drug,” she said. “The pharmacists are the ones who are making the changes in the drugs, and giving them the responsibility so patients don’t have to go into the ED is important. If it’s a basic interchange of a drug, the pharmacists can do that to help raise compliance.”
Dr. Jackevicius had no relevant relationships to disclose.
SOURCE: Jackevicius J. AHA 2019. Session FS.AOS.F1.
ED visits for hypertension in month after the 2018 recall spiked 55%
ED visits for hypertension in month after the 2018 recall spiked 55%
PHILADELPHIA – The 2018 recall of generic forms of the antihypertensive valsartan exposed weaknesses in the recall systems for generic drugs in both the United States and Canada that caused many patients on the drug to fall through the cracks, according to a study of prescribing patterns in Ontario before and after the recall reported at the American Heart Association scientific sessions.
The results also have been published online in the journal Circulation (2019 Nov 11. doi: 10.1161/CIRCULATIONAHA.119.044494).
Cynthia Jackevicius, PharmD, of the Western University of Health Sciences in Pomona, Calif., reported that 90% of patients on recalled generic valsartan products switched to another antihypertension drug, but called the 10% for whom the study had no data “concerning.” She also said that ED visits for hypertension (HTN) in the month after the recall spiked 55%, from a rate of 0.11% to 0.17% (P = .02). While small, that increase was statistically significant, she said.
The Food and Drug Administration and Health Canada issued voluntary recalls of generic forms of valsartan in July 2018 following reports of N-nitrosodimethylamine (NDMA), a suspected carcinogen, being found in the products. Eventually, the recalls expanded to include valsartan products containing the contaminants N-nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA), as well as losartan and irbesartan products.
The Ontario study evaluated prescribing patterns and health system utilization in four different provincewide health databases and involved 55,461 patients, all of whom were on recalled generic valsartan when Health Canada issued the recall. The study also computed monthly rates of ED visits and hospitalizations for HTN, congestive heart failure, stroke/transit ischemic attack, and MI as primary diagnoses for 18 months before and 6 months after the recall. Rates of utilization for CHF and MI remained relatively flat through the study period, Dr. Jackevicius said, but rates of ED visits for stroke/TIA showed “a very small relative increase: 6% and 8% in ED visits and hospitalizations, respectively.” Respective P values were .020 and .037.
As for the nature of the ED visits after the recall, Dr. Jackevicius said the study did not tease that out. Many visits could have been for uncontrolled HTN or to get expired prescriptions refilled.
“But either way, even if it is just getting a new prescription, this isn’t the best response,” she said. We need to have a better system where patients can more easily or with less burden deal with a recall.”
Session moderator Seth S. Martin, MD, MHS, of Johns Hopkins University in Baltimore, echoed Dr. Jackevicius’s concerns about the handling of drug recalls. “Recalls are increasing,” he said. “Is this just the tip of the iceberg on the quality of generics and we’re going to see these floodgates open? Is this going to be chaos or is this more isolated to this class of medication, the ARBs? This is becoming a little concerning.”
Dr. Jackevicius made note of the recalls that followed the original valsartan recall.
“This really opened a lot of questions in terms of the quality of generic products,” she said. Drug manufacturers are putting safeguards into place to detect these potential contaminants, she said, “but a lot more work needs to be done to ensure the supply. All of these recalls and the prominence of this will be increased.”
The response to the recalls also must undergo revision, she said, citing the experiences of the United States and Canada. “There isn’t really a good system or strategy for recalls in either country,” Dr. Jackevicius said, noting that regulatory bodies notify prescribers and physicians, but “they don’t know which patients are on it.”
A better strategy would be to involve pharmacies more in the process. “The pharmacies have the lot numbers, and they will know what patients are on the recalled drug,” she said. “The pharmacists are the ones who are making the changes in the drugs, and giving them the responsibility so patients don’t have to go into the ED is important. If it’s a basic interchange of a drug, the pharmacists can do that to help raise compliance.”
Dr. Jackevicius had no relevant relationships to disclose.
SOURCE: Jackevicius J. AHA 2019. Session FS.AOS.F1.
PHILADELPHIA – The 2018 recall of generic forms of the antihypertensive valsartan exposed weaknesses in the recall systems for generic drugs in both the United States and Canada that caused many patients on the drug to fall through the cracks, according to a study of prescribing patterns in Ontario before and after the recall reported at the American Heart Association scientific sessions.
The results also have been published online in the journal Circulation (2019 Nov 11. doi: 10.1161/CIRCULATIONAHA.119.044494).
Cynthia Jackevicius, PharmD, of the Western University of Health Sciences in Pomona, Calif., reported that 90% of patients on recalled generic valsartan products switched to another antihypertension drug, but called the 10% for whom the study had no data “concerning.” She also said that ED visits for hypertension (HTN) in the month after the recall spiked 55%, from a rate of 0.11% to 0.17% (P = .02). While small, that increase was statistically significant, she said.
The Food and Drug Administration and Health Canada issued voluntary recalls of generic forms of valsartan in July 2018 following reports of N-nitrosodimethylamine (NDMA), a suspected carcinogen, being found in the products. Eventually, the recalls expanded to include valsartan products containing the contaminants N-nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA), as well as losartan and irbesartan products.
The Ontario study evaluated prescribing patterns and health system utilization in four different provincewide health databases and involved 55,461 patients, all of whom were on recalled generic valsartan when Health Canada issued the recall. The study also computed monthly rates of ED visits and hospitalizations for HTN, congestive heart failure, stroke/transit ischemic attack, and MI as primary diagnoses for 18 months before and 6 months after the recall. Rates of utilization for CHF and MI remained relatively flat through the study period, Dr. Jackevicius said, but rates of ED visits for stroke/TIA showed “a very small relative increase: 6% and 8% in ED visits and hospitalizations, respectively.” Respective P values were .020 and .037.
As for the nature of the ED visits after the recall, Dr. Jackevicius said the study did not tease that out. Many visits could have been for uncontrolled HTN or to get expired prescriptions refilled.
“But either way, even if it is just getting a new prescription, this isn’t the best response,” she said. We need to have a better system where patients can more easily or with less burden deal with a recall.”
Session moderator Seth S. Martin, MD, MHS, of Johns Hopkins University in Baltimore, echoed Dr. Jackevicius’s concerns about the handling of drug recalls. “Recalls are increasing,” he said. “Is this just the tip of the iceberg on the quality of generics and we’re going to see these floodgates open? Is this going to be chaos or is this more isolated to this class of medication, the ARBs? This is becoming a little concerning.”
Dr. Jackevicius made note of the recalls that followed the original valsartan recall.
“This really opened a lot of questions in terms of the quality of generic products,” she said. Drug manufacturers are putting safeguards into place to detect these potential contaminants, she said, “but a lot more work needs to be done to ensure the supply. All of these recalls and the prominence of this will be increased.”
The response to the recalls also must undergo revision, she said, citing the experiences of the United States and Canada. “There isn’t really a good system or strategy for recalls in either country,” Dr. Jackevicius said, noting that regulatory bodies notify prescribers and physicians, but “they don’t know which patients are on it.”
A better strategy would be to involve pharmacies more in the process. “The pharmacies have the lot numbers, and they will know what patients are on the recalled drug,” she said. “The pharmacists are the ones who are making the changes in the drugs, and giving them the responsibility so patients don’t have to go into the ED is important. If it’s a basic interchange of a drug, the pharmacists can do that to help raise compliance.”
Dr. Jackevicius had no relevant relationships to disclose.
SOURCE: Jackevicius J. AHA 2019. Session FS.AOS.F1.
REPORTING FROM AHA 2019
Key clinical point: Neither Canada nor the United States has a good system or strategy for recalling generic drugs.
Major finding: One in 10 patients may have discontinued therapy after the recall.
Study details: Population study of prescribing patterns and health utilization rates of 55,461 patients on valsartan before and after the July 2018 recall.
Disclosures: Dr. Jackevicius has no relevant financial relationships to report.
Source: Jackevicius C. AHA 2019. Session FS.AOS.F1.
Macitentan produces similar results in PAH-SSc and IPAH/HPAH
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
REPORTING FROM CHEST 2019
One third of CVD disease in black adults linked to hypertension
A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.
The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.
Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.
The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.
At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.
In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.
Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.
After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.
“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.
Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.
The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.
SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.
A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.
The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.
Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.
The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.
At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.
In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.
Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.
After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.
“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.
Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.
The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.
SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.
A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.
The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.
Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.
The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.
At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.
In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.
Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.
After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.
“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.
Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.
The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.
SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.
FROM JAMA CARDIOLOGY
Macitentan, tadalafil combo found effective for newly diagnosed PAH
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
REPORTING FROM CHEST 2019
Balloon pulmonary angioplasty beats riociguat in randomized CTEPH trial
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
REPORTING FROM ERS 2019