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Older women with ESRD face higher mortality, compared with male counterparts
LOS ANGELES – In patients with end-stage renal disease, women older than 50 years have a significantly higher mortality, compared with their male counterparts, results from an analysis of national data showed.
“The racial and ethnic disparities in the prevalence, treatment, risks, and outcomes of [hypertension] in patients with CKD [chronic kidney disease], are well recognized,” the study’s senior author, Ricardo Correa, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Whites have better control of blood pressure, compared with Hispanics or African Americans with CKD, for example. On the other hand, gender differences in the outcome of blood pressure control and mortality across the different CKD stages have been very poorly studied, with conflicting results.”
The importance of gender difference has been mostly the focus in cardiovascular diseases, he continued, with compelling data revealing a higher incidence in men than in women of similar age, and a menopause-associated increase in cardiovascular disease in women.
“Whether the same can be said for hypertension, remains to be elucidated,” said Dr. Correa, an endocrinologist who directs the diabetes and metabolism fellowship at the University of Arizona in Phoenix.
In what he said is the first study of its kind, Dr. Correa and his colleagues set out to determine if gender in the U.S. population and menopausal age affect the inpatient survival rate in hypertensive patients across different stages of CKD. They drew from the 2005-2012 National Inpatient Sample to identify 2,121,750 hospitalized hypertensive patients and compared a number of factors between men and women, including crude mortality and mortality per CKD stage, menopausal age, length of stay, and total hospital charges.
Of the 2,121,750 patients, 1,092,931 (52%) were men and 1,028,819 (48%) were women; their mean age was 65 years. Among women, 32% had stage 3 CKD, 15% had stage 4 disease, 3% had stage 5 CKD, and 54% had end-stage renal disease (ESRD). Among men, 33% had stage 3 CKD, 13% had stage 4 disease, 3% had stage 5 CKD, and 51% had ESRD. The researchers observed that in-hospital crude mortality was significantly higher for men, compared with a matched group of women at CKD stages 3 and 4 (3.09% vs. 3.29% for CDK 3; P less than .0001 and 4.05% vs. 4.36% for CDK 4; P = .0004), yet was nonsignificant among those with ESRD (4.68% vs. 4.83%; P = .45).
When the researchers factored in menopausal age, they found that women with stage 3, 4, or 5 CKD who were aged 50 years or younger had a mortality rate similar to that of men with same stage disease, whereas women older than 50 years with ESRD had a significantly higher mortality, compared with their male counterparts, especially those of Asian, African American, and Hispanic descent (P less than .001, compared with those of white, non-Hispanic descent).
“One could hypothesize that cardiac remodeling in hemodialysis women may be different than that in hemodialysis men to the extent that it affects mortality,” Dr. Correa said. “However, it is unclear if the survival benefit for dialysis men is owing to the possibility of a selection bias or not. Dialysis women may not be receiving equal access to cardiovascular procedures or surgical interventions (arteriovenous fistula, for example) or women may not be offered adequate hemodialysis to the same extent as men are. Further investigations regarding sex-based differences in dialysis treatment are required.”
He acknowledged certain limitations of the study, including its observational design. “We lacked detailed information regarding the cause of death, dialysis efficiency, types of dialysis accesses, and left ventricular hypertrophy measurements. We did not account for transitions between different hemodialysis modalities [and] we do not have information about distances or traveling time to dialysis units.”
The study’s first author was Kelvin Tran, MD. The researchers reported having no financial disclosures.
LOS ANGELES – In patients with end-stage renal disease, women older than 50 years have a significantly higher mortality, compared with their male counterparts, results from an analysis of national data showed.
“The racial and ethnic disparities in the prevalence, treatment, risks, and outcomes of [hypertension] in patients with CKD [chronic kidney disease], are well recognized,” the study’s senior author, Ricardo Correa, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Whites have better control of blood pressure, compared with Hispanics or African Americans with CKD, for example. On the other hand, gender differences in the outcome of blood pressure control and mortality across the different CKD stages have been very poorly studied, with conflicting results.”
The importance of gender difference has been mostly the focus in cardiovascular diseases, he continued, with compelling data revealing a higher incidence in men than in women of similar age, and a menopause-associated increase in cardiovascular disease in women.
“Whether the same can be said for hypertension, remains to be elucidated,” said Dr. Correa, an endocrinologist who directs the diabetes and metabolism fellowship at the University of Arizona in Phoenix.
In what he said is the first study of its kind, Dr. Correa and his colleagues set out to determine if gender in the U.S. population and menopausal age affect the inpatient survival rate in hypertensive patients across different stages of CKD. They drew from the 2005-2012 National Inpatient Sample to identify 2,121,750 hospitalized hypertensive patients and compared a number of factors between men and women, including crude mortality and mortality per CKD stage, menopausal age, length of stay, and total hospital charges.
Of the 2,121,750 patients, 1,092,931 (52%) were men and 1,028,819 (48%) were women; their mean age was 65 years. Among women, 32% had stage 3 CKD, 15% had stage 4 disease, 3% had stage 5 CKD, and 54% had end-stage renal disease (ESRD). Among men, 33% had stage 3 CKD, 13% had stage 4 disease, 3% had stage 5 CKD, and 51% had ESRD. The researchers observed that in-hospital crude mortality was significantly higher for men, compared with a matched group of women at CKD stages 3 and 4 (3.09% vs. 3.29% for CDK 3; P less than .0001 and 4.05% vs. 4.36% for CDK 4; P = .0004), yet was nonsignificant among those with ESRD (4.68% vs. 4.83%; P = .45).
When the researchers factored in menopausal age, they found that women with stage 3, 4, or 5 CKD who were aged 50 years or younger had a mortality rate similar to that of men with same stage disease, whereas women older than 50 years with ESRD had a significantly higher mortality, compared with their male counterparts, especially those of Asian, African American, and Hispanic descent (P less than .001, compared with those of white, non-Hispanic descent).
“One could hypothesize that cardiac remodeling in hemodialysis women may be different than that in hemodialysis men to the extent that it affects mortality,” Dr. Correa said. “However, it is unclear if the survival benefit for dialysis men is owing to the possibility of a selection bias or not. Dialysis women may not be receiving equal access to cardiovascular procedures or surgical interventions (arteriovenous fistula, for example) or women may not be offered adequate hemodialysis to the same extent as men are. Further investigations regarding sex-based differences in dialysis treatment are required.”
He acknowledged certain limitations of the study, including its observational design. “We lacked detailed information regarding the cause of death, dialysis efficiency, types of dialysis accesses, and left ventricular hypertrophy measurements. We did not account for transitions between different hemodialysis modalities [and] we do not have information about distances or traveling time to dialysis units.”
The study’s first author was Kelvin Tran, MD. The researchers reported having no financial disclosures.
LOS ANGELES – In patients with end-stage renal disease, women older than 50 years have a significantly higher mortality, compared with their male counterparts, results from an analysis of national data showed.
“The racial and ethnic disparities in the prevalence, treatment, risks, and outcomes of [hypertension] in patients with CKD [chronic kidney disease], are well recognized,” the study’s senior author, Ricardo Correa, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Whites have better control of blood pressure, compared with Hispanics or African Americans with CKD, for example. On the other hand, gender differences in the outcome of blood pressure control and mortality across the different CKD stages have been very poorly studied, with conflicting results.”
The importance of gender difference has been mostly the focus in cardiovascular diseases, he continued, with compelling data revealing a higher incidence in men than in women of similar age, and a menopause-associated increase in cardiovascular disease in women.
“Whether the same can be said for hypertension, remains to be elucidated,” said Dr. Correa, an endocrinologist who directs the diabetes and metabolism fellowship at the University of Arizona in Phoenix.
In what he said is the first study of its kind, Dr. Correa and his colleagues set out to determine if gender in the U.S. population and menopausal age affect the inpatient survival rate in hypertensive patients across different stages of CKD. They drew from the 2005-2012 National Inpatient Sample to identify 2,121,750 hospitalized hypertensive patients and compared a number of factors between men and women, including crude mortality and mortality per CKD stage, menopausal age, length of stay, and total hospital charges.
Of the 2,121,750 patients, 1,092,931 (52%) were men and 1,028,819 (48%) were women; their mean age was 65 years. Among women, 32% had stage 3 CKD, 15% had stage 4 disease, 3% had stage 5 CKD, and 54% had end-stage renal disease (ESRD). Among men, 33% had stage 3 CKD, 13% had stage 4 disease, 3% had stage 5 CKD, and 51% had ESRD. The researchers observed that in-hospital crude mortality was significantly higher for men, compared with a matched group of women at CKD stages 3 and 4 (3.09% vs. 3.29% for CDK 3; P less than .0001 and 4.05% vs. 4.36% for CDK 4; P = .0004), yet was nonsignificant among those with ESRD (4.68% vs. 4.83%; P = .45).
When the researchers factored in menopausal age, they found that women with stage 3, 4, or 5 CKD who were aged 50 years or younger had a mortality rate similar to that of men with same stage disease, whereas women older than 50 years with ESRD had a significantly higher mortality, compared with their male counterparts, especially those of Asian, African American, and Hispanic descent (P less than .001, compared with those of white, non-Hispanic descent).
“One could hypothesize that cardiac remodeling in hemodialysis women may be different than that in hemodialysis men to the extent that it affects mortality,” Dr. Correa said. “However, it is unclear if the survival benefit for dialysis men is owing to the possibility of a selection bias or not. Dialysis women may not be receiving equal access to cardiovascular procedures or surgical interventions (arteriovenous fistula, for example) or women may not be offered adequate hemodialysis to the same extent as men are. Further investigations regarding sex-based differences in dialysis treatment are required.”
He acknowledged certain limitations of the study, including its observational design. “We lacked detailed information regarding the cause of death, dialysis efficiency, types of dialysis accesses, and left ventricular hypertrophy measurements. We did not account for transitions between different hemodialysis modalities [and] we do not have information about distances or traveling time to dialysis units.”
The study’s first author was Kelvin Tran, MD. The researchers reported having no financial disclosures.
REPORTING FROM AACE 2019
Key clinical point: .
Major finding: Women older than 50 years with end-stage renal disease had significantly higher mortality, compared with their male counterparts, especially those of Asian, African American, and Hispanic descent (P less than .001 vs. those of white, non-Hispanic descent).
Study details: An observational study of more than 2 million hypertensive patients from the Nationwide Inpatient Sample.
Disclosures: Dr. Correa reported having no financial disclosures.
Dr. Joseph Vassalotti: Cancer risk minimal with ARBs
PHILADELPHIA – according to a senior officer of the National Kidney Foundation.
“I’ve been telling everyone not to stop on their own,” said Joseph A. Vassalotti, MD, chief medical officer for the National Kidney Foundation and associate clinical professor of medicine at Icahn School of Medicine at Mount Sinai, New York.
“The risk of cardiovascular events acutely and the long-term risk of kidney disease progression is much more concerning to me, if they self-discontinue the ARB, than the small risk of cancer,” Dr. Vassalotti said in a meet-the-professor session at the annual meeting of the American College of Physicians.
Put in perspective, the absolute risk of cancer according to the Food and Drug Administration is one new malignancy per 8,000 patients treated with 320 mg of valsartan daily – the highest ARB dose that contained N-Nitrosodimethylamine (NDMA), one of several impurities that led to the recent recalls.
Dr. Vassalotti said that so far, he’s been able to avoid switching patients from one ARB to another by working with pharmacies to get the same medication in a different generic brand not affected by the FDA recalls.
He advised caution in switching ARBs, noting a paucity of head-to-head comparative data between ARBs.
“There may be variable effects,” he said.
If switching is thought to be warranted, he said, some extra tests or visits might be needed to ensure avoidance of hyperkalemia, undertreated hypertension, or hypotension.
Dr. Vassalotti encouraged attendees to review a perspective piece in the New England Journal of Medicine (2019 Mar 13. doi: 10.1056/NEJMp1901657) describing this hypertension “hot potato” resulting from the large-scale voluntary recalls of products containing valsartan, losartan, and irbesartan due to nitrosamine contamination.
Patients may hear about recalls of hypertension drugs, but may not know what products or manufacturers are involved, leaving the burden on clinicians, pharmacies, and health care systems to respond to their concerns, said authors of that perspective piece, led by J. Brian Byrd, MD, of the University of Michigan, Ann Arbor.
“Recalls may trigger unnecessary concern among many people receiving antihypertensive therapy – and may be ignored by people who take ARBs for heart failure or chronic kidney disease,” wrote Dr. Byrd and his colleagues.
The FDA, which said it has worked with manufacturers to “swiftly” remove ARB drug products with impurity levels above acceptable limits, is now maintaining a list of other currently marketed ARB products that are being tested for impurities.
As of the latest update on April 4, the FDA listed more than 40 products with an overall nitrosamine impurity determination of “not present” and more than 300 additional products for which assessments are not yet complete.
“Essentially, we have a safe list now of ARBs that is being developed,” Dr. Vassalotti said. “So if a patient really wanted to change, I would consult that list, and consider picking one that’s been tested already on that list, and the FDA hopefully will complete testing on all the ARB drugs in the near future.”
Dr. Vassalotti is a consultant with Merck, Janssen, and the U.S. Nephrology Advisory Board.
PHILADELPHIA – according to a senior officer of the National Kidney Foundation.
“I’ve been telling everyone not to stop on their own,” said Joseph A. Vassalotti, MD, chief medical officer for the National Kidney Foundation and associate clinical professor of medicine at Icahn School of Medicine at Mount Sinai, New York.
“The risk of cardiovascular events acutely and the long-term risk of kidney disease progression is much more concerning to me, if they self-discontinue the ARB, than the small risk of cancer,” Dr. Vassalotti said in a meet-the-professor session at the annual meeting of the American College of Physicians.
Put in perspective, the absolute risk of cancer according to the Food and Drug Administration is one new malignancy per 8,000 patients treated with 320 mg of valsartan daily – the highest ARB dose that contained N-Nitrosodimethylamine (NDMA), one of several impurities that led to the recent recalls.
Dr. Vassalotti said that so far, he’s been able to avoid switching patients from one ARB to another by working with pharmacies to get the same medication in a different generic brand not affected by the FDA recalls.
He advised caution in switching ARBs, noting a paucity of head-to-head comparative data between ARBs.
“There may be variable effects,” he said.
If switching is thought to be warranted, he said, some extra tests or visits might be needed to ensure avoidance of hyperkalemia, undertreated hypertension, or hypotension.
Dr. Vassalotti encouraged attendees to review a perspective piece in the New England Journal of Medicine (2019 Mar 13. doi: 10.1056/NEJMp1901657) describing this hypertension “hot potato” resulting from the large-scale voluntary recalls of products containing valsartan, losartan, and irbesartan due to nitrosamine contamination.
Patients may hear about recalls of hypertension drugs, but may not know what products or manufacturers are involved, leaving the burden on clinicians, pharmacies, and health care systems to respond to their concerns, said authors of that perspective piece, led by J. Brian Byrd, MD, of the University of Michigan, Ann Arbor.
“Recalls may trigger unnecessary concern among many people receiving antihypertensive therapy – and may be ignored by people who take ARBs for heart failure or chronic kidney disease,” wrote Dr. Byrd and his colleagues.
The FDA, which said it has worked with manufacturers to “swiftly” remove ARB drug products with impurity levels above acceptable limits, is now maintaining a list of other currently marketed ARB products that are being tested for impurities.
As of the latest update on April 4, the FDA listed more than 40 products with an overall nitrosamine impurity determination of “not present” and more than 300 additional products for which assessments are not yet complete.
“Essentially, we have a safe list now of ARBs that is being developed,” Dr. Vassalotti said. “So if a patient really wanted to change, I would consult that list, and consider picking one that’s been tested already on that list, and the FDA hopefully will complete testing on all the ARB drugs in the near future.”
Dr. Vassalotti is a consultant with Merck, Janssen, and the U.S. Nephrology Advisory Board.
PHILADELPHIA – according to a senior officer of the National Kidney Foundation.
“I’ve been telling everyone not to stop on their own,” said Joseph A. Vassalotti, MD, chief medical officer for the National Kidney Foundation and associate clinical professor of medicine at Icahn School of Medicine at Mount Sinai, New York.
“The risk of cardiovascular events acutely and the long-term risk of kidney disease progression is much more concerning to me, if they self-discontinue the ARB, than the small risk of cancer,” Dr. Vassalotti said in a meet-the-professor session at the annual meeting of the American College of Physicians.
Put in perspective, the absolute risk of cancer according to the Food and Drug Administration is one new malignancy per 8,000 patients treated with 320 mg of valsartan daily – the highest ARB dose that contained N-Nitrosodimethylamine (NDMA), one of several impurities that led to the recent recalls.
Dr. Vassalotti said that so far, he’s been able to avoid switching patients from one ARB to another by working with pharmacies to get the same medication in a different generic brand not affected by the FDA recalls.
He advised caution in switching ARBs, noting a paucity of head-to-head comparative data between ARBs.
“There may be variable effects,” he said.
If switching is thought to be warranted, he said, some extra tests or visits might be needed to ensure avoidance of hyperkalemia, undertreated hypertension, or hypotension.
Dr. Vassalotti encouraged attendees to review a perspective piece in the New England Journal of Medicine (2019 Mar 13. doi: 10.1056/NEJMp1901657) describing this hypertension “hot potato” resulting from the large-scale voluntary recalls of products containing valsartan, losartan, and irbesartan due to nitrosamine contamination.
Patients may hear about recalls of hypertension drugs, but may not know what products or manufacturers are involved, leaving the burden on clinicians, pharmacies, and health care systems to respond to their concerns, said authors of that perspective piece, led by J. Brian Byrd, MD, of the University of Michigan, Ann Arbor.
“Recalls may trigger unnecessary concern among many people receiving antihypertensive therapy – and may be ignored by people who take ARBs for heart failure or chronic kidney disease,” wrote Dr. Byrd and his colleagues.
The FDA, which said it has worked with manufacturers to “swiftly” remove ARB drug products with impurity levels above acceptable limits, is now maintaining a list of other currently marketed ARB products that are being tested for impurities.
As of the latest update on April 4, the FDA listed more than 40 products with an overall nitrosamine impurity determination of “not present” and more than 300 additional products for which assessments are not yet complete.
“Essentially, we have a safe list now of ARBs that is being developed,” Dr. Vassalotti said. “So if a patient really wanted to change, I would consult that list, and consider picking one that’s been tested already on that list, and the FDA hopefully will complete testing on all the ARB drugs in the near future.”
Dr. Vassalotti is a consultant with Merck, Janssen, and the U.S. Nephrology Advisory Board.
FROM INTERNAL MEDICINE 2019
FDA names 40 ARBs that are free of nitrosamines
The Food and Drug Administration has identified 40 angiotensin II receptor blockers (ARBs) that do not contain the environmental contaminants, nitrosamines.
since impurities in these antihypertensive drugs were discovered last summer, according to a statement from the regulatory agency.
Among the drugs on this list are Accord Healthcare’s amlodipine and olmesartan medoxomil, Alembic Pharmaceuticals’ valsartan and hydrochlorothiazide, and Hisun Pharmaceuticals USA’s telmisartan.
Despite the FDA’s findings, the agency recommends patients continue taking the ARBs they have been prescribed until their pharmacists or physicians change their prescriptions to a safe replacement or different treatment option.
“We want to reassure patients that we strongly believe the risks, such as stroke, of abruptly discontinuing these important medications far outweighs the low risk associated with continuing the medications with these impurities,” says the statement.
The FDA noted that it is “continuing to work with manufacturers to swiftly remove medications from the market if they contain a nitrosamine impurity at levels higher than the interim acceptable intake limits,” and that this effort has resulted in shortages of valsartan products. In anticipation of more shortages, the FDA “is not objecting to temporary distribution” of specific lots of losartan containing impurities at levels exceeding the regulatory agency’s aforementioned standards.
The FDA’s scientists said that using ARBs with impurity levels above the interim acceptable intake limits over the time it should take to get impurity-free losartan to market will not result in an increased risk for cancer.
More information, including the full statement, is available on the FDA’s website.
[email protected]
The Food and Drug Administration has identified 40 angiotensin II receptor blockers (ARBs) that do not contain the environmental contaminants, nitrosamines.
since impurities in these antihypertensive drugs were discovered last summer, according to a statement from the regulatory agency.
Among the drugs on this list are Accord Healthcare’s amlodipine and olmesartan medoxomil, Alembic Pharmaceuticals’ valsartan and hydrochlorothiazide, and Hisun Pharmaceuticals USA’s telmisartan.
Despite the FDA’s findings, the agency recommends patients continue taking the ARBs they have been prescribed until their pharmacists or physicians change their prescriptions to a safe replacement or different treatment option.
“We want to reassure patients that we strongly believe the risks, such as stroke, of abruptly discontinuing these important medications far outweighs the low risk associated with continuing the medications with these impurities,” says the statement.
The FDA noted that it is “continuing to work with manufacturers to swiftly remove medications from the market if they contain a nitrosamine impurity at levels higher than the interim acceptable intake limits,” and that this effort has resulted in shortages of valsartan products. In anticipation of more shortages, the FDA “is not objecting to temporary distribution” of specific lots of losartan containing impurities at levels exceeding the regulatory agency’s aforementioned standards.
The FDA’s scientists said that using ARBs with impurity levels above the interim acceptable intake limits over the time it should take to get impurity-free losartan to market will not result in an increased risk for cancer.
More information, including the full statement, is available on the FDA’s website.
[email protected]
The Food and Drug Administration has identified 40 angiotensin II receptor blockers (ARBs) that do not contain the environmental contaminants, nitrosamines.
since impurities in these antihypertensive drugs were discovered last summer, according to a statement from the regulatory agency.
Among the drugs on this list are Accord Healthcare’s amlodipine and olmesartan medoxomil, Alembic Pharmaceuticals’ valsartan and hydrochlorothiazide, and Hisun Pharmaceuticals USA’s telmisartan.
Despite the FDA’s findings, the agency recommends patients continue taking the ARBs they have been prescribed until their pharmacists or physicians change their prescriptions to a safe replacement or different treatment option.
“We want to reassure patients that we strongly believe the risks, such as stroke, of abruptly discontinuing these important medications far outweighs the low risk associated with continuing the medications with these impurities,” says the statement.
The FDA noted that it is “continuing to work with manufacturers to swiftly remove medications from the market if they contain a nitrosamine impurity at levels higher than the interim acceptable intake limits,” and that this effort has resulted in shortages of valsartan products. In anticipation of more shortages, the FDA “is not objecting to temporary distribution” of specific lots of losartan containing impurities at levels exceeding the regulatory agency’s aforementioned standards.
The FDA’s scientists said that using ARBs with impurity levels above the interim acceptable intake limits over the time it should take to get impurity-free losartan to market will not result in an increased risk for cancer.
More information, including the full statement, is available on the FDA’s website.
[email protected]
Renal denervation reduced BP in sham-controlled trials, meta-analysis shows
although previous investigations of the procedure have had conflicting results.
Renal sympathetic denervation (RSD) was associated with statistically significant reductions in blood pressure assessed by 24-hour ambulatory, daytime ambulatory, and office measurements in the analysis of six trials including a total of 977 participants.
However, the benefit was particularly pronounced in more recent randomized trials that had few patients with isolated systolic hypertension, had highly experienced operators; used more complete techniques of radiofrequency ablation, used novel approaches such as endovascular renal denervation, and used efficacy endpoints such as clinical outcomes, according to investigator Partha Sardar, MD, of Brown University, Providence, R.I., and his colleagues.
“Altogether, the present study affirms the safety and efficacy of renal denervation for blood pressure reduction, and highlights the importance of incorporating the previously described modifications in trial design,” wrote Dr. Sardar and his coauthors. The report is in the Journal of the American College of Cardiology.
While initial trials of catheter-based denervation of renal arteries were positive, three blinded randomized, controlled trials showed no difference in blood pressure between the procedure and a sham procedure, the investigators said. Those findings led to several small, sham-controlled trials that incorporated the aforementioned changes.
For the six trials combined in the meta-analysis, reductions in 24-hour ambulatory systolic blood pressure were significantly lower for RSD, with a weighted mean difference of –3.65 mm Hg (P less than .001), Dr. Sardar and his colleagues reported.
For the earlier trials, the average reductions in 24-hour ambulatory systolic and diastolic blood pressure were 2.23 and 0.66 for RSD and sham patients, respectively.
By contrast, in the second-generation trials, those blood pressure reductions were 4.85 for RSD and 2.98 mm Hg for sham, they said in the report, adding that the reduction in daytime ambulatory systolic blood pressure with RSD was significantly greater for the second-generation studies.
The second-generation studies excluded patients with isolated systolic hypertension, based in part on observations that RSD has a more pronounced impact on blood pressure with combined systolic and diastolic hypertension, according to the authors.
Moreover, the second-generation studies required that very experienced operators perform the procedures, incorporated advanced catheter and ablation techniques, less often used modified medication regimens, and set ambulatory blood pressure as the primary end point, they added.
“These results should inform the design and powering of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with uncontrolled and resistant hypertension,” Dr. Sardar and his coauthors said.
Dr. Sardar reported no relevant financial disclosures, as did most of the coauthors. Three coauthors provided disclosures related to Regado Biosciences, Abbott Vascular, Amgen, Bristol-Myers Squibb, Lilly, Medtronic, and ReCor Medical, among others.
SOURCE: Sardar P et al. J Am Coll Cardiol. 2019;73(13):1633-42.
While questions remain about the future of renal sympathetic denervation for treatment of hypertension, the present meta-analysis provides “interesting” findings that confirm a benefit of the procedure, particularly in the more recent randomized trials, editorialists said.
“The evidence is now there to conclude that RSD does lower blood pressure in hypertensive patients,” Sverre E. Kjeldsen, MD, PhD, Fadl E.M. Fadl Elmula, MD, PhD, and Alexandre Persu, MD, PhD, wrote in their editorial. That conclusion makes sense in light of knowledge that sympathetic overactivity is a known contributor to hypertension pathogenesis.
Although the blood pressure benefits of RSD in the second-generation trials still seem “relatively modest” and equate roughly to the effect of one antihypertensive drug, the aggregate results mask a wide variation in individual patient response, with up to 30% of patients experiencing dramatic improvements after the procedure, they said.
Accordingly, one key research priority is to figure out what patient characteristics might be used to single out patients who are extreme responders to the therapy.
That kind of optimized patient selection, in tandem with technical improvements in the procedure, they said, may help break the “glass ceiling” in blood pressure reduction reported in randomized trials to date.
“Research on RSD still has good days to come, and patients may eventually benefit from this research effort,” Dr. Kjeldsen, Dr. Fadl Elmula, and Dr. Persu concluded.
Dr. Kjeldsen and Dr. Fadl Elmula are at Oslo University Hospital, Ullevaal, and the University of Oslo; Dr. Persu is at the Université Catholique de Louvain, Brussels. The comments summarize an editorial accompanying the article by Sardar et al. (J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.02.008). Dr. Kjeldsen reported disclosures related to Merck KGaA, Merck Sharp and Dohme, Sanofi, and Takeda.
While questions remain about the future of renal sympathetic denervation for treatment of hypertension, the present meta-analysis provides “interesting” findings that confirm a benefit of the procedure, particularly in the more recent randomized trials, editorialists said.
“The evidence is now there to conclude that RSD does lower blood pressure in hypertensive patients,” Sverre E. Kjeldsen, MD, PhD, Fadl E.M. Fadl Elmula, MD, PhD, and Alexandre Persu, MD, PhD, wrote in their editorial. That conclusion makes sense in light of knowledge that sympathetic overactivity is a known contributor to hypertension pathogenesis.
Although the blood pressure benefits of RSD in the second-generation trials still seem “relatively modest” and equate roughly to the effect of one antihypertensive drug, the aggregate results mask a wide variation in individual patient response, with up to 30% of patients experiencing dramatic improvements after the procedure, they said.
Accordingly, one key research priority is to figure out what patient characteristics might be used to single out patients who are extreme responders to the therapy.
That kind of optimized patient selection, in tandem with technical improvements in the procedure, they said, may help break the “glass ceiling” in blood pressure reduction reported in randomized trials to date.
“Research on RSD still has good days to come, and patients may eventually benefit from this research effort,” Dr. Kjeldsen, Dr. Fadl Elmula, and Dr. Persu concluded.
Dr. Kjeldsen and Dr. Fadl Elmula are at Oslo University Hospital, Ullevaal, and the University of Oslo; Dr. Persu is at the Université Catholique de Louvain, Brussels. The comments summarize an editorial accompanying the article by Sardar et al. (J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.02.008). Dr. Kjeldsen reported disclosures related to Merck KGaA, Merck Sharp and Dohme, Sanofi, and Takeda.
While questions remain about the future of renal sympathetic denervation for treatment of hypertension, the present meta-analysis provides “interesting” findings that confirm a benefit of the procedure, particularly in the more recent randomized trials, editorialists said.
“The evidence is now there to conclude that RSD does lower blood pressure in hypertensive patients,” Sverre E. Kjeldsen, MD, PhD, Fadl E.M. Fadl Elmula, MD, PhD, and Alexandre Persu, MD, PhD, wrote in their editorial. That conclusion makes sense in light of knowledge that sympathetic overactivity is a known contributor to hypertension pathogenesis.
Although the blood pressure benefits of RSD in the second-generation trials still seem “relatively modest” and equate roughly to the effect of one antihypertensive drug, the aggregate results mask a wide variation in individual patient response, with up to 30% of patients experiencing dramatic improvements after the procedure, they said.
Accordingly, one key research priority is to figure out what patient characteristics might be used to single out patients who are extreme responders to the therapy.
That kind of optimized patient selection, in tandem with technical improvements in the procedure, they said, may help break the “glass ceiling” in blood pressure reduction reported in randomized trials to date.
“Research on RSD still has good days to come, and patients may eventually benefit from this research effort,” Dr. Kjeldsen, Dr. Fadl Elmula, and Dr. Persu concluded.
Dr. Kjeldsen and Dr. Fadl Elmula are at Oslo University Hospital, Ullevaal, and the University of Oslo; Dr. Persu is at the Université Catholique de Louvain, Brussels. The comments summarize an editorial accompanying the article by Sardar et al. (J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.02.008). Dr. Kjeldsen reported disclosures related to Merck KGaA, Merck Sharp and Dohme, Sanofi, and Takeda.
although previous investigations of the procedure have had conflicting results.
Renal sympathetic denervation (RSD) was associated with statistically significant reductions in blood pressure assessed by 24-hour ambulatory, daytime ambulatory, and office measurements in the analysis of six trials including a total of 977 participants.
However, the benefit was particularly pronounced in more recent randomized trials that had few patients with isolated systolic hypertension, had highly experienced operators; used more complete techniques of radiofrequency ablation, used novel approaches such as endovascular renal denervation, and used efficacy endpoints such as clinical outcomes, according to investigator Partha Sardar, MD, of Brown University, Providence, R.I., and his colleagues.
“Altogether, the present study affirms the safety and efficacy of renal denervation for blood pressure reduction, and highlights the importance of incorporating the previously described modifications in trial design,” wrote Dr. Sardar and his coauthors. The report is in the Journal of the American College of Cardiology.
While initial trials of catheter-based denervation of renal arteries were positive, three blinded randomized, controlled trials showed no difference in blood pressure between the procedure and a sham procedure, the investigators said. Those findings led to several small, sham-controlled trials that incorporated the aforementioned changes.
For the six trials combined in the meta-analysis, reductions in 24-hour ambulatory systolic blood pressure were significantly lower for RSD, with a weighted mean difference of –3.65 mm Hg (P less than .001), Dr. Sardar and his colleagues reported.
For the earlier trials, the average reductions in 24-hour ambulatory systolic and diastolic blood pressure were 2.23 and 0.66 for RSD and sham patients, respectively.
By contrast, in the second-generation trials, those blood pressure reductions were 4.85 for RSD and 2.98 mm Hg for sham, they said in the report, adding that the reduction in daytime ambulatory systolic blood pressure with RSD was significantly greater for the second-generation studies.
The second-generation studies excluded patients with isolated systolic hypertension, based in part on observations that RSD has a more pronounced impact on blood pressure with combined systolic and diastolic hypertension, according to the authors.
Moreover, the second-generation studies required that very experienced operators perform the procedures, incorporated advanced catheter and ablation techniques, less often used modified medication regimens, and set ambulatory blood pressure as the primary end point, they added.
“These results should inform the design and powering of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with uncontrolled and resistant hypertension,” Dr. Sardar and his coauthors said.
Dr. Sardar reported no relevant financial disclosures, as did most of the coauthors. Three coauthors provided disclosures related to Regado Biosciences, Abbott Vascular, Amgen, Bristol-Myers Squibb, Lilly, Medtronic, and ReCor Medical, among others.
SOURCE: Sardar P et al. J Am Coll Cardiol. 2019;73(13):1633-42.
although previous investigations of the procedure have had conflicting results.
Renal sympathetic denervation (RSD) was associated with statistically significant reductions in blood pressure assessed by 24-hour ambulatory, daytime ambulatory, and office measurements in the analysis of six trials including a total of 977 participants.
However, the benefit was particularly pronounced in more recent randomized trials that had few patients with isolated systolic hypertension, had highly experienced operators; used more complete techniques of radiofrequency ablation, used novel approaches such as endovascular renal denervation, and used efficacy endpoints such as clinical outcomes, according to investigator Partha Sardar, MD, of Brown University, Providence, R.I., and his colleagues.
“Altogether, the present study affirms the safety and efficacy of renal denervation for blood pressure reduction, and highlights the importance of incorporating the previously described modifications in trial design,” wrote Dr. Sardar and his coauthors. The report is in the Journal of the American College of Cardiology.
While initial trials of catheter-based denervation of renal arteries were positive, three blinded randomized, controlled trials showed no difference in blood pressure between the procedure and a sham procedure, the investigators said. Those findings led to several small, sham-controlled trials that incorporated the aforementioned changes.
For the six trials combined in the meta-analysis, reductions in 24-hour ambulatory systolic blood pressure were significantly lower for RSD, with a weighted mean difference of –3.65 mm Hg (P less than .001), Dr. Sardar and his colleagues reported.
For the earlier trials, the average reductions in 24-hour ambulatory systolic and diastolic blood pressure were 2.23 and 0.66 for RSD and sham patients, respectively.
By contrast, in the second-generation trials, those blood pressure reductions were 4.85 for RSD and 2.98 mm Hg for sham, they said in the report, adding that the reduction in daytime ambulatory systolic blood pressure with RSD was significantly greater for the second-generation studies.
The second-generation studies excluded patients with isolated systolic hypertension, based in part on observations that RSD has a more pronounced impact on blood pressure with combined systolic and diastolic hypertension, according to the authors.
Moreover, the second-generation studies required that very experienced operators perform the procedures, incorporated advanced catheter and ablation techniques, less often used modified medication regimens, and set ambulatory blood pressure as the primary end point, they added.
“These results should inform the design and powering of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with uncontrolled and resistant hypertension,” Dr. Sardar and his coauthors said.
Dr. Sardar reported no relevant financial disclosures, as did most of the coauthors. Three coauthors provided disclosures related to Regado Biosciences, Abbott Vascular, Amgen, Bristol-Myers Squibb, Lilly, Medtronic, and ReCor Medical, among others.
SOURCE: Sardar P et al. J Am Coll Cardiol. 2019;73(13):1633-42.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Renal sympathetic denervation significantly reduced blood pressure in randomized, sham-controlled trials.
Major finding: In second-generation trials of renal sympathetic denervation for hypertension therapy, 24-hour ambulatory blood pressure reductions were 4.85 for RSD and 2.98 mm Hg for sham.
Study details: Renal sympathetic denervation for treating hypertension was tested in six randomized, sham-controlled trials of 24-hour ambulatory, daytime ambulatory, and blood pressure office measurements including a total of 977 participants.
Disclosures: Dr. Sardar reported no relevant financial disclosures, as did most of the coauthors. Three coauthors provided disclosures related to Regado Biosciences, Abbott Vascular, Amgen, Bristol-Myers Squibb, Lilly, Medtronic, and ReCor Medical, among others.
Source: Sardar P et al. J Am Coll Cardiol. 2019;73(13):1633-42.
BP control slowed brain damage in elderly hypertensives
NEW ORLEANS – Hypertensive elderly patients treated to maintain an ambulatory systolic blood pressure of 130 mm Hg had significantly slower progression of white matter lesions in their brains than did control hypertensive patients maintained at an ambulatory systolic pressure of about 145 mm Hg during 3 years of follow-up in a randomized, single-center study with 199 patients.
The results also showed similar rates of death, syncope episodes, and falls in the intensively and less rigorously treated subgroups, and the patients treated to a systolic of 130 mm Hg also had significantly fewer nonfatal cardiovascular disease events, further documenting the safety and efficacy in elderly patients of a more aggressive blood pressure goal like the one promoted in current guidelines from the American College of Cardiology and American Heart Association, William B. White, MD, said at the annual meeting of the American College of Cardiology.
The study’s findings also showed that in one measure of cognitive function, the serial reaction time task, the patients treated to a systolic pressure of 130 mm Hg had an average 23 millisecond improvement in their reaction time from baseline to their 3-year follow-up, while patients in the control group treated to a systolic pressure of 145 mm Hg had a 33 millisecond increase in their average reaction time during follow-up. This 56 millisecond between-group difference from baseline in average change in reaction time over 3 years was both statistically significant and represents a clinically meaningful difference for a measure of both processing speed and executive function, said Dr. White, professor of medicine at the University of Connecticut in Farmington. However, the participants also underwent assessment by five other clinical measures of cognitive function and in none of the other five tests did more intensive blood pressure control link with an improvement, compared with the results in control patients.
The study had two primary endpoints. One was progression of white matter hyperintensity on brain MR images, which is a measure of neuron necrosis in the brain, and this analysis showed that the growth of white matter occurred at a 40% reduced rate among 99 patients treated to an average ambulatory systolic blood pressure of 130 mm Hg, compared with the average progression among 100 controls treated to an average ambulatory systolic of 145 mm Hg. The second measure was improvement during 3 years, compared with controls, in any of six different measures of mobility, including gait speed. The results showed no significant differences between the treatment arms in any of these measures. The average progression of white matter disease among control patients after 3 years was of a magnitude that would trigger concern in a neurologist who saw these scans, said Dr. White. The researchers could already begin to see a between-group difference in the accumulation of white matter hyperintensity on the MR scans of patients at 18 months in the study, he added.
During his presentation, Dr. White suggested that the absence of discerned improvements in mobility from more aggressive blood pressure control despite the observed slowed progression of white matter disease may have resulted from the study’s relatively brief follow-up.
The INFINITY (Intensive versus Standard Ambulatory Blood Pressure Lowering to Prevent Functional Decline in the Elderly) study enrolled hypertensive patients at least 75 years old who already showed visible evidence of white matter hypertrophy on their brain MR scan at baseline but also had normal mobility and mental function (their baseline score on the mini mental state examination had to be within the normal range, with an average score of 28 among enrolled patients), and they had no history of any chronic neurological condition (Am Heart J. 2013 Mar;165[3]:258-65). The median age of enrolled patients was 80 years. They had an average of 15 years of education, indicating a study cohort with a high level of education and function, Dr. White noted. The inclusion and exclusion criteria led to a study population that was substantially older but without as much comorbidity as patients enrolled in the SPRINT MIND study (JAMA. 2019 Jan 28;321[6]:553-61), he said. The study exclusively used 24-hour ambulatory monitoring for baseline and follow-up blood pressure measurements.
The participating clinicians successfully maintained patients in each of the treatment groups at close to their goal systolic blood pressures. At 18 months, the actual average systolic pressures among patients in the two study groups were 132 mm Hg and 146 mm Hg, and at 36 months their pressures averaged 131 mm Hg and 146 mm Hg for 163 patients who remained in the study out to 36-months. Maintenance of the lower pressure generally required treatment with one additional antihypertensive medication, compared with the control patients’ treatment, Dr. White said.
The rates of total falls and falls causing injury were virtually identical in the two treatment groups. The incidence of nonfatal cardiovascular disease events over 3 years, including MI, strokes, and cardiovascular disease hospitalizations, was 4 cases in the intensively-treated patients and 17 among those treated to a higher systolic pressure, a statistically significant and unexpected difference, Dr. White reported.
This is another dataset showing that blood pressure reduction in elderly people with hypertension is safe and extremely important. Clinicians today often exclude elderly patients from aggressive blood pressure control because of an unrealized fear of causing hypotension and falls. These new data add to what’s already been reported in support of the American College of Cardiology and American Heart Association blood pressure treatment target of less than 130/80 mm Hg for noninstitutionalized, ambulatory, community-dwelling adults who are aged at least 65 years (Hypertension. 2018 June;71[6]:e13-e115). Many clinicians continue to have concerns about what this guideline says about treating older patients. These new findings support the idea that blood pressure can safely be treated to the level the guideline recommends while producing signals of beneficial changes in brain health and in cognitive function.
Providers worry a lot about the potential for harm from treatment. These findings add to the data that say clinicians can safely follow the blood pressure management guideline to benefit even very old patients.
Eileen Handberg, PhD , is a research professor of medicine and director of the Cardiovascular Clinical Trials Program at the University of Florida in Gainesville. She had no relevant disclosures. She made these comments in an interview.
This is another dataset showing that blood pressure reduction in elderly people with hypertension is safe and extremely important. Clinicians today often exclude elderly patients from aggressive blood pressure control because of an unrealized fear of causing hypotension and falls. These new data add to what’s already been reported in support of the American College of Cardiology and American Heart Association blood pressure treatment target of less than 130/80 mm Hg for noninstitutionalized, ambulatory, community-dwelling adults who are aged at least 65 years (Hypertension. 2018 June;71[6]:e13-e115). Many clinicians continue to have concerns about what this guideline says about treating older patients. These new findings support the idea that blood pressure can safely be treated to the level the guideline recommends while producing signals of beneficial changes in brain health and in cognitive function.
Providers worry a lot about the potential for harm from treatment. These findings add to the data that say clinicians can safely follow the blood pressure management guideline to benefit even very old patients.
Eileen Handberg, PhD , is a research professor of medicine and director of the Cardiovascular Clinical Trials Program at the University of Florida in Gainesville. She had no relevant disclosures. She made these comments in an interview.
This is another dataset showing that blood pressure reduction in elderly people with hypertension is safe and extremely important. Clinicians today often exclude elderly patients from aggressive blood pressure control because of an unrealized fear of causing hypotension and falls. These new data add to what’s already been reported in support of the American College of Cardiology and American Heart Association blood pressure treatment target of less than 130/80 mm Hg for noninstitutionalized, ambulatory, community-dwelling adults who are aged at least 65 years (Hypertension. 2018 June;71[6]:e13-e115). Many clinicians continue to have concerns about what this guideline says about treating older patients. These new findings support the idea that blood pressure can safely be treated to the level the guideline recommends while producing signals of beneficial changes in brain health and in cognitive function.
Providers worry a lot about the potential for harm from treatment. These findings add to the data that say clinicians can safely follow the blood pressure management guideline to benefit even very old patients.
Eileen Handberg, PhD , is a research professor of medicine and director of the Cardiovascular Clinical Trials Program at the University of Florida in Gainesville. She had no relevant disclosures. She made these comments in an interview.
NEW ORLEANS – Hypertensive elderly patients treated to maintain an ambulatory systolic blood pressure of 130 mm Hg had significantly slower progression of white matter lesions in their brains than did control hypertensive patients maintained at an ambulatory systolic pressure of about 145 mm Hg during 3 years of follow-up in a randomized, single-center study with 199 patients.
The results also showed similar rates of death, syncope episodes, and falls in the intensively and less rigorously treated subgroups, and the patients treated to a systolic of 130 mm Hg also had significantly fewer nonfatal cardiovascular disease events, further documenting the safety and efficacy in elderly patients of a more aggressive blood pressure goal like the one promoted in current guidelines from the American College of Cardiology and American Heart Association, William B. White, MD, said at the annual meeting of the American College of Cardiology.
The study’s findings also showed that in one measure of cognitive function, the serial reaction time task, the patients treated to a systolic pressure of 130 mm Hg had an average 23 millisecond improvement in their reaction time from baseline to their 3-year follow-up, while patients in the control group treated to a systolic pressure of 145 mm Hg had a 33 millisecond increase in their average reaction time during follow-up. This 56 millisecond between-group difference from baseline in average change in reaction time over 3 years was both statistically significant and represents a clinically meaningful difference for a measure of both processing speed and executive function, said Dr. White, professor of medicine at the University of Connecticut in Farmington. However, the participants also underwent assessment by five other clinical measures of cognitive function and in none of the other five tests did more intensive blood pressure control link with an improvement, compared with the results in control patients.
The study had two primary endpoints. One was progression of white matter hyperintensity on brain MR images, which is a measure of neuron necrosis in the brain, and this analysis showed that the growth of white matter occurred at a 40% reduced rate among 99 patients treated to an average ambulatory systolic blood pressure of 130 mm Hg, compared with the average progression among 100 controls treated to an average ambulatory systolic of 145 mm Hg. The second measure was improvement during 3 years, compared with controls, in any of six different measures of mobility, including gait speed. The results showed no significant differences between the treatment arms in any of these measures. The average progression of white matter disease among control patients after 3 years was of a magnitude that would trigger concern in a neurologist who saw these scans, said Dr. White. The researchers could already begin to see a between-group difference in the accumulation of white matter hyperintensity on the MR scans of patients at 18 months in the study, he added.
During his presentation, Dr. White suggested that the absence of discerned improvements in mobility from more aggressive blood pressure control despite the observed slowed progression of white matter disease may have resulted from the study’s relatively brief follow-up.
The INFINITY (Intensive versus Standard Ambulatory Blood Pressure Lowering to Prevent Functional Decline in the Elderly) study enrolled hypertensive patients at least 75 years old who already showed visible evidence of white matter hypertrophy on their brain MR scan at baseline but also had normal mobility and mental function (their baseline score on the mini mental state examination had to be within the normal range, with an average score of 28 among enrolled patients), and they had no history of any chronic neurological condition (Am Heart J. 2013 Mar;165[3]:258-65). The median age of enrolled patients was 80 years. They had an average of 15 years of education, indicating a study cohort with a high level of education and function, Dr. White noted. The inclusion and exclusion criteria led to a study population that was substantially older but without as much comorbidity as patients enrolled in the SPRINT MIND study (JAMA. 2019 Jan 28;321[6]:553-61), he said. The study exclusively used 24-hour ambulatory monitoring for baseline and follow-up blood pressure measurements.
The participating clinicians successfully maintained patients in each of the treatment groups at close to their goal systolic blood pressures. At 18 months, the actual average systolic pressures among patients in the two study groups were 132 mm Hg and 146 mm Hg, and at 36 months their pressures averaged 131 mm Hg and 146 mm Hg for 163 patients who remained in the study out to 36-months. Maintenance of the lower pressure generally required treatment with one additional antihypertensive medication, compared with the control patients’ treatment, Dr. White said.
The rates of total falls and falls causing injury were virtually identical in the two treatment groups. The incidence of nonfatal cardiovascular disease events over 3 years, including MI, strokes, and cardiovascular disease hospitalizations, was 4 cases in the intensively-treated patients and 17 among those treated to a higher systolic pressure, a statistically significant and unexpected difference, Dr. White reported.
NEW ORLEANS – Hypertensive elderly patients treated to maintain an ambulatory systolic blood pressure of 130 mm Hg had significantly slower progression of white matter lesions in their brains than did control hypertensive patients maintained at an ambulatory systolic pressure of about 145 mm Hg during 3 years of follow-up in a randomized, single-center study with 199 patients.
The results also showed similar rates of death, syncope episodes, and falls in the intensively and less rigorously treated subgroups, and the patients treated to a systolic of 130 mm Hg also had significantly fewer nonfatal cardiovascular disease events, further documenting the safety and efficacy in elderly patients of a more aggressive blood pressure goal like the one promoted in current guidelines from the American College of Cardiology and American Heart Association, William B. White, MD, said at the annual meeting of the American College of Cardiology.
The study’s findings also showed that in one measure of cognitive function, the serial reaction time task, the patients treated to a systolic pressure of 130 mm Hg had an average 23 millisecond improvement in their reaction time from baseline to their 3-year follow-up, while patients in the control group treated to a systolic pressure of 145 mm Hg had a 33 millisecond increase in their average reaction time during follow-up. This 56 millisecond between-group difference from baseline in average change in reaction time over 3 years was both statistically significant and represents a clinically meaningful difference for a measure of both processing speed and executive function, said Dr. White, professor of medicine at the University of Connecticut in Farmington. However, the participants also underwent assessment by five other clinical measures of cognitive function and in none of the other five tests did more intensive blood pressure control link with an improvement, compared with the results in control patients.
The study had two primary endpoints. One was progression of white matter hyperintensity on brain MR images, which is a measure of neuron necrosis in the brain, and this analysis showed that the growth of white matter occurred at a 40% reduced rate among 99 patients treated to an average ambulatory systolic blood pressure of 130 mm Hg, compared with the average progression among 100 controls treated to an average ambulatory systolic of 145 mm Hg. The second measure was improvement during 3 years, compared with controls, in any of six different measures of mobility, including gait speed. The results showed no significant differences between the treatment arms in any of these measures. The average progression of white matter disease among control patients after 3 years was of a magnitude that would trigger concern in a neurologist who saw these scans, said Dr. White. The researchers could already begin to see a between-group difference in the accumulation of white matter hyperintensity on the MR scans of patients at 18 months in the study, he added.
During his presentation, Dr. White suggested that the absence of discerned improvements in mobility from more aggressive blood pressure control despite the observed slowed progression of white matter disease may have resulted from the study’s relatively brief follow-up.
The INFINITY (Intensive versus Standard Ambulatory Blood Pressure Lowering to Prevent Functional Decline in the Elderly) study enrolled hypertensive patients at least 75 years old who already showed visible evidence of white matter hypertrophy on their brain MR scan at baseline but also had normal mobility and mental function (their baseline score on the mini mental state examination had to be within the normal range, with an average score of 28 among enrolled patients), and they had no history of any chronic neurological condition (Am Heart J. 2013 Mar;165[3]:258-65). The median age of enrolled patients was 80 years. They had an average of 15 years of education, indicating a study cohort with a high level of education and function, Dr. White noted. The inclusion and exclusion criteria led to a study population that was substantially older but without as much comorbidity as patients enrolled in the SPRINT MIND study (JAMA. 2019 Jan 28;321[6]:553-61), he said. The study exclusively used 24-hour ambulatory monitoring for baseline and follow-up blood pressure measurements.
The participating clinicians successfully maintained patients in each of the treatment groups at close to their goal systolic blood pressures. At 18 months, the actual average systolic pressures among patients in the two study groups were 132 mm Hg and 146 mm Hg, and at 36 months their pressures averaged 131 mm Hg and 146 mm Hg for 163 patients who remained in the study out to 36-months. Maintenance of the lower pressure generally required treatment with one additional antihypertensive medication, compared with the control patients’ treatment, Dr. White said.
The rates of total falls and falls causing injury were virtually identical in the two treatment groups. The incidence of nonfatal cardiovascular disease events over 3 years, including MI, strokes, and cardiovascular disease hospitalizations, was 4 cases in the intensively-treated patients and 17 among those treated to a higher systolic pressure, a statistically significant and unexpected difference, Dr. White reported.
REPORTING FROM ACC 19
Low-flow, low-gradient aortic stenosis with preserved LVEF: a special situation
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
SNOWMASS, COLO. – A patient who presents with symptomatic low-flow, low-gradient severe aortic stenosis, hypertension, and preserved left ventricular ejection fraction (LVEF) is often referred straightaway for consideration of aortic valve replacement. Not so fast – these patients actually constitute a special case for whom two essential questions must be answered before proceeding to that stage, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
The first question is, What happens to the patient’s symptoms upon control of the hypertension?
“Almost all of these patients with low-flow severe aortic stenosis with preserved ejection fraction are going to be hypertensive. Treat the hypertension first. If they become asymptomatic, you don’t need to intervene. The aortic stenosis wasn’t causing their symptoms. You can afford to continue to watch them,” according to Dr. Nishimura, professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.
An aortic valve area of less than 1.0 cm2 is a prerequisite for surgical or transcatheter aortic valve replacement. So the second key question is this, Does the patient have truly severe aortic stenosis (AS), or is it instead a case of pseudo-AS in which the small aortic valve area noted on echocardiography is caused by low flow secondary to a small left ventricle with a low stroke volume?
“If you increase the flow and remeasure the aortic valve area, you’ll find that a lot of these patients don’t have a really small aortic valve area of less than 1.0 cm2. You might find the aortic valve area pops up to 1.4-1.6 cm2,” he explained.
These patients with symptomatic low-flow, low-gradient severe AS with preserved LVEF are quite common.
“I don’t know why, but we’re seeing more and more of these patients. I think 10 years ago we just kind of ignored them. We thought we’d made a mistake in our calculations. But in fact if you’re very meticulous about your calculations, 30%-40% of your aortic stenosis patients fit into this category,” the cardiologist said.
Moreover, if these patients undergo aortic valve replacement when their symptoms stemmed from poorly controlled hypertension and/or pseudo-AS, they are not going to benefit from this major intervention, he added.
This issue was addressed, albeit briefly and obliquely, in the American Heart Association/ACC guidelines for management of patients with valvular heart disease, for which Dr. Nishimura served as first author and cochair of the writing committee (Circulation. 2014 Jun 10;129[23]:e521-643) as well as for the 2017 focused update of the guidelines.
The guidelines give a IIa recommendation to aortic valve replacement as “reasonable” in “symptomatic patients with low-flow/low-gradient severe AS (stage D3) with an LVEF 50% or greater, a calcified aortic valve with significantly reduced leaflet motion, and a valve area 1.0 cm2 or less only if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms and data recorded when the patient is normotensive.”
Dr. Nishimura chose the 50th annual meeting of the storied ACC Snowmass conference to elaborate upon that brief guidance. He explained that these patients with low-flow, low-gradient symptomatic “severe” AS with preserved LVEF and hypertension have two resistors in a series.
“You have a resistor at the aortic valve area but probably a greater resistor in the systemic circulation. They have high resistance at the arterial level and diastolic dysfunction due to ventricular-vascular coupling,” the cardiologist continued.
Checking for pseudo-AS in these patients is a matter of boosting their low transvalvular flow. This can be accomplished by increasing their cardiac output via monitored exercise or by pharmacologic afterload reduction.
“We’re exercising these patients in the cath lab, but you could also do it in the echocardiographic laboratory. With exercise, if cardiac output increases and the aortic valve area increases without significant change in the aortic valve mean gradient, the patient probably doesn’t have truly severe AS,” according to Dr. Nishimura.
One reason referral centers are seeing a lot more of these patients during the last decade is an influential study by Canadian investigators entitled “Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival.” Those investigators warned “this condition may often be misdiagnosed, which leads to a neglect and/or underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery” (Circulation. 2007 Jun 5;115(22):2856-64).
This report led to a great deal of interest in performing aortic valve replacement in such patients during a period when transcatheter replacement was really taking off.
When an audience member asked how commonly such patients have undergone inappropriate aortic valve replacement, Michael J. Mack, MD, took the question.
“I don’t think it’s a huge number,” said Dr. Mack, medical director of cardiovascular surgery at the Baylor Health Care System in Plano, Tex. “This is the patient group we wring our hands about most. We know they don’t do as well with aortic valve replacement as patients with high-gradient AS with a low or normal ejection fraction. We’re loathe to treat them. I think most centers are.”
REPORTING FROM ACC SNOWMASS 2019
Intensive blood pressure lowering may not reduce risk of recurrent stroke
HONOLULU – according to research presented at the International Stroke Conference sponsored by the American Heart Association.
Combined with data from previous trials, these results support a target systolic blood pressure of less than 130 mm Hg and a diastolic blood pressure of less than 80 mm Hg for secondary stroke prevention, said Kazuo Kitagawa, MD, PhD.
Lowering blood pressure reduces the risk of recurrent stroke, but investigators have not identified the best target blood pressure for this indication. The Secondary Prevention of Small Subcortical Strokes Trial (SPS3) examined the efficacy of intensive blood pressure treatment for secondary stroke prevention. The investigators randomized more than 3,000 patients with recent lacunar stroke to intensive or standard blood pressure treatment. Intensive treatment (a target systolic blood pressure of less than 130 mm Hg) conferred a nonsignificant reduction of the risk of recurrent stroke. A 2018 meta-analysis of SPS3 and two smaller randomized controlled trials also showed that intensive treatment did not significantly reduce the risk of recurrent stroke.
A new multicenter trial
Dr. Kitagawa, of Tokyo Women’s Medical University, and colleagues conducted a new trial to evaluate whether intensive blood pressure reduction significantly reduced the risk of recurrent stroke, compared with standard treatment (a systolic target of less than 140 mm Hg and a diastolic target of less than 90 mm Hg). Between 2010 and 2016, they enrolled patients with a history of stroke within the previous 3 years at 140 hospitals in Japan. Participants were randomized to standard blood pressure treatment or intensive blood pressure treatment (defined in this study as a systolic target of less than 120 mm Hg and a diastolic target of less than 80 mm Hg). The primary end point was recurrent stroke.
Both treatment regimens were based on stepwise multidrug rationing. Step 1 was an angiotensin II receptor blockade (ARB), step 2 was the addition of diuretics, step 3 was the addition of calcium channel blockers, step 4 was an increase of the ARB, step 5 was increase of the calcium channel blocker, and step 6 was the addition of spironolactone.
This trial was stopped at the end of 2016 because of slow recruitment and funding cessation. Investigators randomized 1,280 patients out of a planned 2,000. Seventeen patients were excluded from analysis. At baseline, participants’ mean age was 67 years, and mean systolic blood pressure was 145 mm Hg. The qualifying event was ischemic stroke for 85% of patients and intracerebral hemorrhage for 15%. Mean follow-up duration was 3.9 years.
Intensive treatment reduced blood pressure
At 1 year, the mean systolic blood pressure was 132.0 mm Hg in the standard-treatment group and 123.7 mm Hg in the intensive-treatment group. Mean diastolic blood pressure was 77.5 mm Hg in the standard-treatment group and 72.8 mm Hg in the intensive-treatment group. The investigators observed a significant difference in blood pressure between the groups throughout the study period.
The annual rate of stroke recurrence was 2.26% in the standard-treatment group and 1.65% in the intensive-treatment group. Intensive treatment tended to reduce stroke recurrence (hazard ratio, 0.73), but the result was not statistically significant. “The nonsignificant finding might be due to early termination or the modest difference in blood pressure level [between groups],” said Dr. Kitagawa.
Subgroup analyses did not indicate any interaction between treatment group and age, sex, qualifying event, mean systolic blood pressure at baseline, or diabetes. The rate of ischemic stroke was similar between the two groups, but the rate of intracerebral hemorrhage was lower in the intensive treatment group than in the standard treatment group. The rate of serious adverse events was similar between treatment groups.
When Dr. Kitagawa and colleagues pooled their data with those examined in the 2018 meta-analysis, they found that intensive treatment significantly reduced the risk of recurrent stroke (hazard ratio, 0.68), compared with standard treatment.
This study was sponsored by Biomedis International.
SOURCE: Kitagawa K et al. ISC 2019, Abstract LB10.
HONOLULU – according to research presented at the International Stroke Conference sponsored by the American Heart Association.
Combined with data from previous trials, these results support a target systolic blood pressure of less than 130 mm Hg and a diastolic blood pressure of less than 80 mm Hg for secondary stroke prevention, said Kazuo Kitagawa, MD, PhD.
Lowering blood pressure reduces the risk of recurrent stroke, but investigators have not identified the best target blood pressure for this indication. The Secondary Prevention of Small Subcortical Strokes Trial (SPS3) examined the efficacy of intensive blood pressure treatment for secondary stroke prevention. The investigators randomized more than 3,000 patients with recent lacunar stroke to intensive or standard blood pressure treatment. Intensive treatment (a target systolic blood pressure of less than 130 mm Hg) conferred a nonsignificant reduction of the risk of recurrent stroke. A 2018 meta-analysis of SPS3 and two smaller randomized controlled trials also showed that intensive treatment did not significantly reduce the risk of recurrent stroke.
A new multicenter trial
Dr. Kitagawa, of Tokyo Women’s Medical University, and colleagues conducted a new trial to evaluate whether intensive blood pressure reduction significantly reduced the risk of recurrent stroke, compared with standard treatment (a systolic target of less than 140 mm Hg and a diastolic target of less than 90 mm Hg). Between 2010 and 2016, they enrolled patients with a history of stroke within the previous 3 years at 140 hospitals in Japan. Participants were randomized to standard blood pressure treatment or intensive blood pressure treatment (defined in this study as a systolic target of less than 120 mm Hg and a diastolic target of less than 80 mm Hg). The primary end point was recurrent stroke.
Both treatment regimens were based on stepwise multidrug rationing. Step 1 was an angiotensin II receptor blockade (ARB), step 2 was the addition of diuretics, step 3 was the addition of calcium channel blockers, step 4 was an increase of the ARB, step 5 was increase of the calcium channel blocker, and step 6 was the addition of spironolactone.
This trial was stopped at the end of 2016 because of slow recruitment and funding cessation. Investigators randomized 1,280 patients out of a planned 2,000. Seventeen patients were excluded from analysis. At baseline, participants’ mean age was 67 years, and mean systolic blood pressure was 145 mm Hg. The qualifying event was ischemic stroke for 85% of patients and intracerebral hemorrhage for 15%. Mean follow-up duration was 3.9 years.
Intensive treatment reduced blood pressure
At 1 year, the mean systolic blood pressure was 132.0 mm Hg in the standard-treatment group and 123.7 mm Hg in the intensive-treatment group. Mean diastolic blood pressure was 77.5 mm Hg in the standard-treatment group and 72.8 mm Hg in the intensive-treatment group. The investigators observed a significant difference in blood pressure between the groups throughout the study period.
The annual rate of stroke recurrence was 2.26% in the standard-treatment group and 1.65% in the intensive-treatment group. Intensive treatment tended to reduce stroke recurrence (hazard ratio, 0.73), but the result was not statistically significant. “The nonsignificant finding might be due to early termination or the modest difference in blood pressure level [between groups],” said Dr. Kitagawa.
Subgroup analyses did not indicate any interaction between treatment group and age, sex, qualifying event, mean systolic blood pressure at baseline, or diabetes. The rate of ischemic stroke was similar between the two groups, but the rate of intracerebral hemorrhage was lower in the intensive treatment group than in the standard treatment group. The rate of serious adverse events was similar between treatment groups.
When Dr. Kitagawa and colleagues pooled their data with those examined in the 2018 meta-analysis, they found that intensive treatment significantly reduced the risk of recurrent stroke (hazard ratio, 0.68), compared with standard treatment.
This study was sponsored by Biomedis International.
SOURCE: Kitagawa K et al. ISC 2019, Abstract LB10.
HONOLULU – according to research presented at the International Stroke Conference sponsored by the American Heart Association.
Combined with data from previous trials, these results support a target systolic blood pressure of less than 130 mm Hg and a diastolic blood pressure of less than 80 mm Hg for secondary stroke prevention, said Kazuo Kitagawa, MD, PhD.
Lowering blood pressure reduces the risk of recurrent stroke, but investigators have not identified the best target blood pressure for this indication. The Secondary Prevention of Small Subcortical Strokes Trial (SPS3) examined the efficacy of intensive blood pressure treatment for secondary stroke prevention. The investigators randomized more than 3,000 patients with recent lacunar stroke to intensive or standard blood pressure treatment. Intensive treatment (a target systolic blood pressure of less than 130 mm Hg) conferred a nonsignificant reduction of the risk of recurrent stroke. A 2018 meta-analysis of SPS3 and two smaller randomized controlled trials also showed that intensive treatment did not significantly reduce the risk of recurrent stroke.
A new multicenter trial
Dr. Kitagawa, of Tokyo Women’s Medical University, and colleagues conducted a new trial to evaluate whether intensive blood pressure reduction significantly reduced the risk of recurrent stroke, compared with standard treatment (a systolic target of less than 140 mm Hg and a diastolic target of less than 90 mm Hg). Between 2010 and 2016, they enrolled patients with a history of stroke within the previous 3 years at 140 hospitals in Japan. Participants were randomized to standard blood pressure treatment or intensive blood pressure treatment (defined in this study as a systolic target of less than 120 mm Hg and a diastolic target of less than 80 mm Hg). The primary end point was recurrent stroke.
Both treatment regimens were based on stepwise multidrug rationing. Step 1 was an angiotensin II receptor blockade (ARB), step 2 was the addition of diuretics, step 3 was the addition of calcium channel blockers, step 4 was an increase of the ARB, step 5 was increase of the calcium channel blocker, and step 6 was the addition of spironolactone.
This trial was stopped at the end of 2016 because of slow recruitment and funding cessation. Investigators randomized 1,280 patients out of a planned 2,000. Seventeen patients were excluded from analysis. At baseline, participants’ mean age was 67 years, and mean systolic blood pressure was 145 mm Hg. The qualifying event was ischemic stroke for 85% of patients and intracerebral hemorrhage for 15%. Mean follow-up duration was 3.9 years.
Intensive treatment reduced blood pressure
At 1 year, the mean systolic blood pressure was 132.0 mm Hg in the standard-treatment group and 123.7 mm Hg in the intensive-treatment group. Mean diastolic blood pressure was 77.5 mm Hg in the standard-treatment group and 72.8 mm Hg in the intensive-treatment group. The investigators observed a significant difference in blood pressure between the groups throughout the study period.
The annual rate of stroke recurrence was 2.26% in the standard-treatment group and 1.65% in the intensive-treatment group. Intensive treatment tended to reduce stroke recurrence (hazard ratio, 0.73), but the result was not statistically significant. “The nonsignificant finding might be due to early termination or the modest difference in blood pressure level [between groups],” said Dr. Kitagawa.
Subgroup analyses did not indicate any interaction between treatment group and age, sex, qualifying event, mean systolic blood pressure at baseline, or diabetes. The rate of ischemic stroke was similar between the two groups, but the rate of intracerebral hemorrhage was lower in the intensive treatment group than in the standard treatment group. The rate of serious adverse events was similar between treatment groups.
When Dr. Kitagawa and colleagues pooled their data with those examined in the 2018 meta-analysis, they found that intensive treatment significantly reduced the risk of recurrent stroke (hazard ratio, 0.68), compared with standard treatment.
This study was sponsored by Biomedis International.
SOURCE: Kitagawa K et al. ISC 2019, Abstract LB10.
REPORTING FROM ISC 2019
Premature death from heart disease hits Asian subgroups hard
Among Asian American subgroups, Asian Indian, Filipino, and Vietnamese populations showed significantly higher premature death rates from ischemic heart disease, compared with other Asian subgroups, based on data from the National Center for Health Statistics for the years 2003 to 2012.
Previous studies have described death rates from cardiovascular disease in Asian subgroups, but premature death in particular has not been well studied, wrote Latha Palaniappan, MD, of the division of primary care and population health at the Stanford (Calif.) University, and her colleagues.
To examine premature mortality from cardiovascular disease in Asian subgroups, the researchers used years of potential life lost (YPLL) to measure premature mortality. “[Years of potential life lost ] compares age at death with average life expectancy to estimate the average time an individual would have lived had he/she not died prematurely from a specific disease,” they explained.
The study population included 354,256 Asian American decedents aged 25 years or older. Of that total, 59,936 died of ischemic heart disease and 28,489 died of cerebrovascular disease.
Overall, Asian men lost 779 years/100,000 people in 2003 and 574 years/100,000 in 2012. However, in 2003, Asian Indian men in particular lost 1,216 years/100,000, more than other Asian male subgroups and non-Hispanic white men.
“Use of race-specific life expectancy revealed greater heterogeneity in YPLL across all Asian subgroups,” the researchers wrote. Similarly, Asian Indian women had the highest years of potential life lost throughout the study period, with a high of 818 years/100,000 people in 2003 and 477 years/100,00 in 2012, compared with 577/100,000 and 426/100,000, respectively, among non-Hispanic white women.
All Asian male subgroups also lost more years of life to cerebrovascular disease, compared with non-Hispanic white men, and women in each Asian subgroup had a higher years of potential life lost, compared with non-Hispanic white women. Filipino men had the highest YPLL values for the period, followed by Vietnamese men, and the patterns were similar for Filipino and Vietnamese women.
Possible explanations for the high rate of premature death from ischemic heart disease in Asian Indians include greater prevalence of risk factors at younger age (including elevated apolipoprotein B100/apolipoprotein A-1 ratios), type 2 diabetes, and cardiometabolic abnormalities in people of normal weight that might go unnoticed in a clinical exam, the researchers said. In the case of cerebrovascular disease, possible risk factors for high years of potential life lost in certain subgroups include hypertension in Filipino populations, limited health literacy about stroke in Vietnamese populations, and high rates of smoking in Vietnamese men.
The study findings were limited by several factors, including the small amount of data on mortality in Asian Americans from census reports, the researchers noted. However, the use of years of potential life lost as a measure of the impact of cardiovascular disease provided a useful model of the impact of cardiovascular disease on life expectancy and total disease burden of cerebrovascular disease on Asian ethnic subgroups, they said.
“Our study also provides evidence that evaluating the Asian population together as one group underestimates the burden of [cerebrovascular disease],” they noted.
The National Institute of Minority Health and Health Disparities Research Project and the National Heart, Lung, and Blood Institute supported the study in part by grants to researchers. The researchers had no financial conflicts to disclose.
SOURCE: Iyer DG et al. J Am Heart Assoc. 2019 Mar 20. doi: 10.1161/JAHA.118.010744.
Among Asian American subgroups, Asian Indian, Filipino, and Vietnamese populations showed significantly higher premature death rates from ischemic heart disease, compared with other Asian subgroups, based on data from the National Center for Health Statistics for the years 2003 to 2012.
Previous studies have described death rates from cardiovascular disease in Asian subgroups, but premature death in particular has not been well studied, wrote Latha Palaniappan, MD, of the division of primary care and population health at the Stanford (Calif.) University, and her colleagues.
To examine premature mortality from cardiovascular disease in Asian subgroups, the researchers used years of potential life lost (YPLL) to measure premature mortality. “[Years of potential life lost ] compares age at death with average life expectancy to estimate the average time an individual would have lived had he/she not died prematurely from a specific disease,” they explained.
The study population included 354,256 Asian American decedents aged 25 years or older. Of that total, 59,936 died of ischemic heart disease and 28,489 died of cerebrovascular disease.
Overall, Asian men lost 779 years/100,000 people in 2003 and 574 years/100,000 in 2012. However, in 2003, Asian Indian men in particular lost 1,216 years/100,000, more than other Asian male subgroups and non-Hispanic white men.
“Use of race-specific life expectancy revealed greater heterogeneity in YPLL across all Asian subgroups,” the researchers wrote. Similarly, Asian Indian women had the highest years of potential life lost throughout the study period, with a high of 818 years/100,000 people in 2003 and 477 years/100,00 in 2012, compared with 577/100,000 and 426/100,000, respectively, among non-Hispanic white women.
All Asian male subgroups also lost more years of life to cerebrovascular disease, compared with non-Hispanic white men, and women in each Asian subgroup had a higher years of potential life lost, compared with non-Hispanic white women. Filipino men had the highest YPLL values for the period, followed by Vietnamese men, and the patterns were similar for Filipino and Vietnamese women.
Possible explanations for the high rate of premature death from ischemic heart disease in Asian Indians include greater prevalence of risk factors at younger age (including elevated apolipoprotein B100/apolipoprotein A-1 ratios), type 2 diabetes, and cardiometabolic abnormalities in people of normal weight that might go unnoticed in a clinical exam, the researchers said. In the case of cerebrovascular disease, possible risk factors for high years of potential life lost in certain subgroups include hypertension in Filipino populations, limited health literacy about stroke in Vietnamese populations, and high rates of smoking in Vietnamese men.
The study findings were limited by several factors, including the small amount of data on mortality in Asian Americans from census reports, the researchers noted. However, the use of years of potential life lost as a measure of the impact of cardiovascular disease provided a useful model of the impact of cardiovascular disease on life expectancy and total disease burden of cerebrovascular disease on Asian ethnic subgroups, they said.
“Our study also provides evidence that evaluating the Asian population together as one group underestimates the burden of [cerebrovascular disease],” they noted.
The National Institute of Minority Health and Health Disparities Research Project and the National Heart, Lung, and Blood Institute supported the study in part by grants to researchers. The researchers had no financial conflicts to disclose.
SOURCE: Iyer DG et al. J Am Heart Assoc. 2019 Mar 20. doi: 10.1161/JAHA.118.010744.
Among Asian American subgroups, Asian Indian, Filipino, and Vietnamese populations showed significantly higher premature death rates from ischemic heart disease, compared with other Asian subgroups, based on data from the National Center for Health Statistics for the years 2003 to 2012.
Previous studies have described death rates from cardiovascular disease in Asian subgroups, but premature death in particular has not been well studied, wrote Latha Palaniappan, MD, of the division of primary care and population health at the Stanford (Calif.) University, and her colleagues.
To examine premature mortality from cardiovascular disease in Asian subgroups, the researchers used years of potential life lost (YPLL) to measure premature mortality. “[Years of potential life lost ] compares age at death with average life expectancy to estimate the average time an individual would have lived had he/she not died prematurely from a specific disease,” they explained.
The study population included 354,256 Asian American decedents aged 25 years or older. Of that total, 59,936 died of ischemic heart disease and 28,489 died of cerebrovascular disease.
Overall, Asian men lost 779 years/100,000 people in 2003 and 574 years/100,000 in 2012. However, in 2003, Asian Indian men in particular lost 1,216 years/100,000, more than other Asian male subgroups and non-Hispanic white men.
“Use of race-specific life expectancy revealed greater heterogeneity in YPLL across all Asian subgroups,” the researchers wrote. Similarly, Asian Indian women had the highest years of potential life lost throughout the study period, with a high of 818 years/100,000 people in 2003 and 477 years/100,00 in 2012, compared with 577/100,000 and 426/100,000, respectively, among non-Hispanic white women.
All Asian male subgroups also lost more years of life to cerebrovascular disease, compared with non-Hispanic white men, and women in each Asian subgroup had a higher years of potential life lost, compared with non-Hispanic white women. Filipino men had the highest YPLL values for the period, followed by Vietnamese men, and the patterns were similar for Filipino and Vietnamese women.
Possible explanations for the high rate of premature death from ischemic heart disease in Asian Indians include greater prevalence of risk factors at younger age (including elevated apolipoprotein B100/apolipoprotein A-1 ratios), type 2 diabetes, and cardiometabolic abnormalities in people of normal weight that might go unnoticed in a clinical exam, the researchers said. In the case of cerebrovascular disease, possible risk factors for high years of potential life lost in certain subgroups include hypertension in Filipino populations, limited health literacy about stroke in Vietnamese populations, and high rates of smoking in Vietnamese men.
The study findings were limited by several factors, including the small amount of data on mortality in Asian Americans from census reports, the researchers noted. However, the use of years of potential life lost as a measure of the impact of cardiovascular disease provided a useful model of the impact of cardiovascular disease on life expectancy and total disease burden of cerebrovascular disease on Asian ethnic subgroups, they said.
“Our study also provides evidence that evaluating the Asian population together as one group underestimates the burden of [cerebrovascular disease],” they noted.
The National Institute of Minority Health and Health Disparities Research Project and the National Heart, Lung, and Blood Institute supported the study in part by grants to researchers. The researchers had no financial conflicts to disclose.
SOURCE: Iyer DG et al. J Am Heart Assoc. 2019 Mar 20. doi: 10.1161/JAHA.118.010744.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Key clinical point: Asian Indian, Filipino, and Vietnamese populations had the greatest loss of life from heart attacks and strokes among Asian population subgroups.
Major finding: Asian Indian men lost an average of 17 years of life to ischemic heart disease.
Study details: The data come from the National Center for Health Statistics Multiple Causes of Death mortality files from 2003 to 2012.
Disclosures: The National Institute of Minority Health and Health Disparities Research Project and the National Heart, Lung, and Blood Institute supported the study in part by grants to researchers. The researchers had no financial conflicts to disclose.
Source: Iyer DG et al. J Am Heart Assoc. 2019 Mar 20. doi: 10.1161/JAHA.118.010744.
Resistant hypertension hits SLE patients hard
at a tertiary care center.
A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.
The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.
at a tertiary care center.
A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.
The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.
at a tertiary care center.
A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.
The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.
FROM ARTHRITIS CARE & RESEARCH
CREOLE: Amlodipine may be preferable for lowering blood pressure in black patients
Amlodipine plus either hydrochlorothiazide or perindopril effectively reduced blood pressure better than perindopril and hydrochlorothiazide in black African patients with hypertension, based on data presented at the annual meeting of the American College of Cardiology.
“(A) long-acting dihydropyridine calcium-channel blocker (in this case, amlodipine) may be critical to more efficacious blood-pressure lowering among black patients as part of the two-drug combinations used (in Africa),” wrote lead author Dike B. Ojji, PhD, of the University of Abuja in Gwagwalada, Abuja, Nigeria, and his coauthors. “These results contrast with recommendations for black patients in the most recent U.S. guidelines” which recommend either a calcium channel blocker or a diuretic in combination with a different drug class.
The study was published simultaneously in the New England Journal of Medicine.
In the CREOLE study, Dr. Ojji and his colleagues enrolled 728 black patients, mean age 51 years and 63% of them women, in a randomized, single-blind, three-group trial across six countries in sub-Saharan Africa. All patients had uncontrolled hypertension and were assigned to one of three treatment groups: amlodipine plus hydrochlorothiazide (n = 244), amlodipine plus perindopril (n = 243), and perindopril plus hydrochlorothiazide (n = 241). Patients underwent 24-hour ambulatory blood-pressure measuring at baseline and at 6 months.
Of the 621 patients who completed the trial, those in the two groups receiving amlodipine had a larger mean reduction in systolic blood pressure after 6 months than the group receiving perindopril plus hydrochlorothiazide. Compared with the perindopril plus hydrochlorothiazide group, the amlodipine plus hydrochlorothiazide group had an additional -3.14 mm Hg reduction in systolic blood pressure from baseline (95% confidence interval, -5.90 to -0.38, P = 0.03) while the amlodipine plus perindopril group had an additional -3.00 mm Hg reduction (95% CI, -5.81 to -0.20, P = 0.04). The difference between the amlodipine plus hydrochlorothiazide group and the amlodipine plus perindopril group was -0.14 mm Hg (95% CI, -2.90 to 2.61, P = 0.92).
The limitations of the study included using nonmatching trial drugs and not adjusting the P values for the three comparisons of the primary end point, the authors wrote. It’s uncertain whether the findings can be extrapolated to black patients with diabetes or to those living outside of sub-Saharan Africa.
The study was sponsored by a grant from the GlaxoSmithKline Africa Noncommunicable Disease Open Lab. Trial drugs were donated by Aspen Pharmacare. Two authors reported receiving grants and personal fees from numerous pharmaceutical companies.
SOURCE: Ojji DB et al. NEJM. 2019 Mar 18. doi: 10.1056/NEJMoa1901113.
Amlodipine plus either hydrochlorothiazide or perindopril effectively reduced blood pressure better than perindopril and hydrochlorothiazide in black African patients with hypertension, based on data presented at the annual meeting of the American College of Cardiology.
“(A) long-acting dihydropyridine calcium-channel blocker (in this case, amlodipine) may be critical to more efficacious blood-pressure lowering among black patients as part of the two-drug combinations used (in Africa),” wrote lead author Dike B. Ojji, PhD, of the University of Abuja in Gwagwalada, Abuja, Nigeria, and his coauthors. “These results contrast with recommendations for black patients in the most recent U.S. guidelines” which recommend either a calcium channel blocker or a diuretic in combination with a different drug class.
The study was published simultaneously in the New England Journal of Medicine.
In the CREOLE study, Dr. Ojji and his colleagues enrolled 728 black patients, mean age 51 years and 63% of them women, in a randomized, single-blind, three-group trial across six countries in sub-Saharan Africa. All patients had uncontrolled hypertension and were assigned to one of three treatment groups: amlodipine plus hydrochlorothiazide (n = 244), amlodipine plus perindopril (n = 243), and perindopril plus hydrochlorothiazide (n = 241). Patients underwent 24-hour ambulatory blood-pressure measuring at baseline and at 6 months.
Of the 621 patients who completed the trial, those in the two groups receiving amlodipine had a larger mean reduction in systolic blood pressure after 6 months than the group receiving perindopril plus hydrochlorothiazide. Compared with the perindopril plus hydrochlorothiazide group, the amlodipine plus hydrochlorothiazide group had an additional -3.14 mm Hg reduction in systolic blood pressure from baseline (95% confidence interval, -5.90 to -0.38, P = 0.03) while the amlodipine plus perindopril group had an additional -3.00 mm Hg reduction (95% CI, -5.81 to -0.20, P = 0.04). The difference between the amlodipine plus hydrochlorothiazide group and the amlodipine plus perindopril group was -0.14 mm Hg (95% CI, -2.90 to 2.61, P = 0.92).
The limitations of the study included using nonmatching trial drugs and not adjusting the P values for the three comparisons of the primary end point, the authors wrote. It’s uncertain whether the findings can be extrapolated to black patients with diabetes or to those living outside of sub-Saharan Africa.
The study was sponsored by a grant from the GlaxoSmithKline Africa Noncommunicable Disease Open Lab. Trial drugs were donated by Aspen Pharmacare. Two authors reported receiving grants and personal fees from numerous pharmaceutical companies.
SOURCE: Ojji DB et al. NEJM. 2019 Mar 18. doi: 10.1056/NEJMoa1901113.
Amlodipine plus either hydrochlorothiazide or perindopril effectively reduced blood pressure better than perindopril and hydrochlorothiazide in black African patients with hypertension, based on data presented at the annual meeting of the American College of Cardiology.
“(A) long-acting dihydropyridine calcium-channel blocker (in this case, amlodipine) may be critical to more efficacious blood-pressure lowering among black patients as part of the two-drug combinations used (in Africa),” wrote lead author Dike B. Ojji, PhD, of the University of Abuja in Gwagwalada, Abuja, Nigeria, and his coauthors. “These results contrast with recommendations for black patients in the most recent U.S. guidelines” which recommend either a calcium channel blocker or a diuretic in combination with a different drug class.
The study was published simultaneously in the New England Journal of Medicine.
In the CREOLE study, Dr. Ojji and his colleagues enrolled 728 black patients, mean age 51 years and 63% of them women, in a randomized, single-blind, three-group trial across six countries in sub-Saharan Africa. All patients had uncontrolled hypertension and were assigned to one of three treatment groups: amlodipine plus hydrochlorothiazide (n = 244), amlodipine plus perindopril (n = 243), and perindopril plus hydrochlorothiazide (n = 241). Patients underwent 24-hour ambulatory blood-pressure measuring at baseline and at 6 months.
Of the 621 patients who completed the trial, those in the two groups receiving amlodipine had a larger mean reduction in systolic blood pressure after 6 months than the group receiving perindopril plus hydrochlorothiazide. Compared with the perindopril plus hydrochlorothiazide group, the amlodipine plus hydrochlorothiazide group had an additional -3.14 mm Hg reduction in systolic blood pressure from baseline (95% confidence interval, -5.90 to -0.38, P = 0.03) while the amlodipine plus perindopril group had an additional -3.00 mm Hg reduction (95% CI, -5.81 to -0.20, P = 0.04). The difference between the amlodipine plus hydrochlorothiazide group and the amlodipine plus perindopril group was -0.14 mm Hg (95% CI, -2.90 to 2.61, P = 0.92).
The limitations of the study included using nonmatching trial drugs and not adjusting the P values for the three comparisons of the primary end point, the authors wrote. It’s uncertain whether the findings can be extrapolated to black patients with diabetes or to those living outside of sub-Saharan Africa.
The study was sponsored by a grant from the GlaxoSmithKline Africa Noncommunicable Disease Open Lab. Trial drugs were donated by Aspen Pharmacare. Two authors reported receiving grants and personal fees from numerous pharmaceutical companies.
SOURCE: Ojji DB et al. NEJM. 2019 Mar 18. doi: 10.1056/NEJMoa1901113.
FROM ACC 2019