User login
Patients with an ejection fraction (EF) greater than 40% who were stabilized after recent worsening or de novo heart failure (HF) had a greater reduction in natriuretic peptides and less worsening renal function, but a higher rate of hypotension over 8 weeks with sacubitril-valsartan (Entresto) versus valsartan (Diovan) in the PARAGLIDE-HF trial.
A subgroup analysis showed evidence of a larger treatment effect among those with an EF of 60% or less, said Robert Mentz, MD, of the Duke Clinical Research Institute, Durham, N.C.
Dr. Mentz presented the findings at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) scientific sessions. The study was also published online simultaneously in the Journal of the American College of Cardiology.
“Next steps will involve further assessment of the cardiovascular and renal benefits, as well as further exploration of the symptomatic hypotension that we observed,” Dr. Mentz said in an interview.
Meanwhile, he said, “clinicians should be aware of these new data – specifically, the incremental reduction in natriuretic peptide level, compared with valsartan, and potential benefits on cardiovascular and renal events,” particularly in those with an EF greater than 40% to 60% or less.
Larger benefit for EF > 40% to < 60%
PARAGLIDE-HF was a double-blind, randomized controlled trial with 466 patients with EF greater than 40% enrolled within 30 days of a worsening HF event. The median age was 71 years, 52% were women, and 22% were Black.
The trial was a follow-up to PARAGON-HF, which had shown that, in patients with an EF of at least 45%, sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for HF or death from cardiovascular causes, compared with valsartan.
The primary endpoint for PARAGLIDE was the time-averaged proportional change in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8, as in the PIONEER-HF trial. That trial showed that among patients hospitalized for acute decompensated HF with reduced EF (< 40%), the angiotensin receptor/neprilysin inhibitor (ARNI) led to a greater reduction in NT-proBNP concentration than the angiotensin receptor blocker (ARB).
Similarly, for PARAGLIDE, the time-averaged reduction in NT-proBNP was greater with sacubitril-valsartan, with a change ratio of 0.85 (15% greater reduction).
A secondary hierarchical outcome for PARAGLIDE, using the win ratio, consisted of time to cardiovascular death, number and timing of HF hospitalizations, number and timing of urgent HF visits, and time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8.
The hierarchical outcome favored sacubitril-valsartan, but was not significant (unmatched win ratio, 1.19).
As noted, sacubitril-valsartan reduced worsening renal function, compared with valsartan (odds ratio, 0.61), but increased symptomatic hypotension (OR, 1.73).
“We will work to better characterize the hypotension events that were observed to help identify those patients at greater risk and to provide further clarity around the timing and implications of these events,” Dr. Mentz said in an interview.
The team hypothesized that such events may be prevented by optimizing volume status and background therapies commonly used to treat hypertension in these patients.
“For instance,” Dr. Mentz suggested, “calcium channel blockers like amlodipine could be dose reduced or discontinued in patients with lower baseline blood pressures to better support sacubitril/valsartan initiation and titration.”
He highlighted the subgroup analysis showing evidence of a larger treatment effect in study patients with an EF of 60% or less for the NT-proBNP change (0.78) and the hierarchical outcome (win ratio, 1.46).
“These data may influence future guidance for sacubitril-valsartan in HF with EF greater than 40%, regardless of HF chronicity [acute or chronic vs. de novo] and treatment setting [hospital vs. clinic],” Dr. Mentz concluded.
Data ‘far from conclusive’
In a comment, Sean Pinney, MD, chief of cardiology at Mount Sinai Morningside, New York, said that the study results “help expand the current evidence base supporting the use of an ARNI in patients” with an EF greater than 40% up to 60%, and “provide confidence that ARNIs help to lower natriuretic peptides.
“It comes as little surprise that not everyone was able to tolerate these medications due to intolerable side effects like dizziness or hypotension,” he said.
Nevertheless, he added, “hopefully, these trial data help strengthen clinicians’ resolve to prescribe sacubitril/valsartan to a growing population of vulnerable patients.”
In a related editorial, Hector O. Ventura, MD, of the Ochsner Clinical School–University of Queensland, New Orleans, and colleagues express several concerns about the study.
Although the trial achieved significance for the primary endpoint, the margin of benefit was less than expected and the magnitude of the NT-proBNP reduction may not have been enough to reach the threshold for clinical benefit, they wrote.
Diuretic dosing in the two groups was not reported, and between-group differences may have contributed to both the differential NT-proBNP reduction and the rates of hypotension.
Furthermore, the sacubitril-valsartan group had a higher proportion of missing NT-proBNP data, which may have biased the results.
“Clinicians who elect to use sacubitril-valsartan in this population should be mindful of the risk for hypotension and select patients carefully, while providing close ambulatory follow up to ensure stability and adherence,” they noted.
“This important trial provides some wins that support selective use of sacubitril-valsartan in HFpEF [as well as] observed losses, which too may help to define better implementation strategies in appropriately selected patients,” the editorialists concluded.
The study was funded by Novartis. Dr. Mentz and other coauthors have received fees from Novartis. Dr. Pinney, Dr. Ventura, and the other editorialists disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Patients with an ejection fraction (EF) greater than 40% who were stabilized after recent worsening or de novo heart failure (HF) had a greater reduction in natriuretic peptides and less worsening renal function, but a higher rate of hypotension over 8 weeks with sacubitril-valsartan (Entresto) versus valsartan (Diovan) in the PARAGLIDE-HF trial.
A subgroup analysis showed evidence of a larger treatment effect among those with an EF of 60% or less, said Robert Mentz, MD, of the Duke Clinical Research Institute, Durham, N.C.
Dr. Mentz presented the findings at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) scientific sessions. The study was also published online simultaneously in the Journal of the American College of Cardiology.
“Next steps will involve further assessment of the cardiovascular and renal benefits, as well as further exploration of the symptomatic hypotension that we observed,” Dr. Mentz said in an interview.
Meanwhile, he said, “clinicians should be aware of these new data – specifically, the incremental reduction in natriuretic peptide level, compared with valsartan, and potential benefits on cardiovascular and renal events,” particularly in those with an EF greater than 40% to 60% or less.
Larger benefit for EF > 40% to < 60%
PARAGLIDE-HF was a double-blind, randomized controlled trial with 466 patients with EF greater than 40% enrolled within 30 days of a worsening HF event. The median age was 71 years, 52% were women, and 22% were Black.
The trial was a follow-up to PARAGON-HF, which had shown that, in patients with an EF of at least 45%, sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for HF or death from cardiovascular causes, compared with valsartan.
The primary endpoint for PARAGLIDE was the time-averaged proportional change in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8, as in the PIONEER-HF trial. That trial showed that among patients hospitalized for acute decompensated HF with reduced EF (< 40%), the angiotensin receptor/neprilysin inhibitor (ARNI) led to a greater reduction in NT-proBNP concentration than the angiotensin receptor blocker (ARB).
Similarly, for PARAGLIDE, the time-averaged reduction in NT-proBNP was greater with sacubitril-valsartan, with a change ratio of 0.85 (15% greater reduction).
A secondary hierarchical outcome for PARAGLIDE, using the win ratio, consisted of time to cardiovascular death, number and timing of HF hospitalizations, number and timing of urgent HF visits, and time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8.
The hierarchical outcome favored sacubitril-valsartan, but was not significant (unmatched win ratio, 1.19).
As noted, sacubitril-valsartan reduced worsening renal function, compared with valsartan (odds ratio, 0.61), but increased symptomatic hypotension (OR, 1.73).
“We will work to better characterize the hypotension events that were observed to help identify those patients at greater risk and to provide further clarity around the timing and implications of these events,” Dr. Mentz said in an interview.
The team hypothesized that such events may be prevented by optimizing volume status and background therapies commonly used to treat hypertension in these patients.
“For instance,” Dr. Mentz suggested, “calcium channel blockers like amlodipine could be dose reduced or discontinued in patients with lower baseline blood pressures to better support sacubitril/valsartan initiation and titration.”
He highlighted the subgroup analysis showing evidence of a larger treatment effect in study patients with an EF of 60% or less for the NT-proBNP change (0.78) and the hierarchical outcome (win ratio, 1.46).
“These data may influence future guidance for sacubitril-valsartan in HF with EF greater than 40%, regardless of HF chronicity [acute or chronic vs. de novo] and treatment setting [hospital vs. clinic],” Dr. Mentz concluded.
Data ‘far from conclusive’
In a comment, Sean Pinney, MD, chief of cardiology at Mount Sinai Morningside, New York, said that the study results “help expand the current evidence base supporting the use of an ARNI in patients” with an EF greater than 40% up to 60%, and “provide confidence that ARNIs help to lower natriuretic peptides.
“It comes as little surprise that not everyone was able to tolerate these medications due to intolerable side effects like dizziness or hypotension,” he said.
Nevertheless, he added, “hopefully, these trial data help strengthen clinicians’ resolve to prescribe sacubitril/valsartan to a growing population of vulnerable patients.”
In a related editorial, Hector O. Ventura, MD, of the Ochsner Clinical School–University of Queensland, New Orleans, and colleagues express several concerns about the study.
Although the trial achieved significance for the primary endpoint, the margin of benefit was less than expected and the magnitude of the NT-proBNP reduction may not have been enough to reach the threshold for clinical benefit, they wrote.
Diuretic dosing in the two groups was not reported, and between-group differences may have contributed to both the differential NT-proBNP reduction and the rates of hypotension.
Furthermore, the sacubitril-valsartan group had a higher proportion of missing NT-proBNP data, which may have biased the results.
“Clinicians who elect to use sacubitril-valsartan in this population should be mindful of the risk for hypotension and select patients carefully, while providing close ambulatory follow up to ensure stability and adherence,” they noted.
“This important trial provides some wins that support selective use of sacubitril-valsartan in HFpEF [as well as] observed losses, which too may help to define better implementation strategies in appropriately selected patients,” the editorialists concluded.
The study was funded by Novartis. Dr. Mentz and other coauthors have received fees from Novartis. Dr. Pinney, Dr. Ventura, and the other editorialists disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Patients with an ejection fraction (EF) greater than 40% who were stabilized after recent worsening or de novo heart failure (HF) had a greater reduction in natriuretic peptides and less worsening renal function, but a higher rate of hypotension over 8 weeks with sacubitril-valsartan (Entresto) versus valsartan (Diovan) in the PARAGLIDE-HF trial.
A subgroup analysis showed evidence of a larger treatment effect among those with an EF of 60% or less, said Robert Mentz, MD, of the Duke Clinical Research Institute, Durham, N.C.
Dr. Mentz presented the findings at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) scientific sessions. The study was also published online simultaneously in the Journal of the American College of Cardiology.
“Next steps will involve further assessment of the cardiovascular and renal benefits, as well as further exploration of the symptomatic hypotension that we observed,” Dr. Mentz said in an interview.
Meanwhile, he said, “clinicians should be aware of these new data – specifically, the incremental reduction in natriuretic peptide level, compared with valsartan, and potential benefits on cardiovascular and renal events,” particularly in those with an EF greater than 40% to 60% or less.
Larger benefit for EF > 40% to < 60%
PARAGLIDE-HF was a double-blind, randomized controlled trial with 466 patients with EF greater than 40% enrolled within 30 days of a worsening HF event. The median age was 71 years, 52% were women, and 22% were Black.
The trial was a follow-up to PARAGON-HF, which had shown that, in patients with an EF of at least 45%, sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for HF or death from cardiovascular causes, compared with valsartan.
The primary endpoint for PARAGLIDE was the time-averaged proportional change in N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8, as in the PIONEER-HF trial. That trial showed that among patients hospitalized for acute decompensated HF with reduced EF (< 40%), the angiotensin receptor/neprilysin inhibitor (ARNI) led to a greater reduction in NT-proBNP concentration than the angiotensin receptor blocker (ARB).
Similarly, for PARAGLIDE, the time-averaged reduction in NT-proBNP was greater with sacubitril-valsartan, with a change ratio of 0.85 (15% greater reduction).
A secondary hierarchical outcome for PARAGLIDE, using the win ratio, consisted of time to cardiovascular death, number and timing of HF hospitalizations, number and timing of urgent HF visits, and time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8.
The hierarchical outcome favored sacubitril-valsartan, but was not significant (unmatched win ratio, 1.19).
As noted, sacubitril-valsartan reduced worsening renal function, compared with valsartan (odds ratio, 0.61), but increased symptomatic hypotension (OR, 1.73).
“We will work to better characterize the hypotension events that were observed to help identify those patients at greater risk and to provide further clarity around the timing and implications of these events,” Dr. Mentz said in an interview.
The team hypothesized that such events may be prevented by optimizing volume status and background therapies commonly used to treat hypertension in these patients.
“For instance,” Dr. Mentz suggested, “calcium channel blockers like amlodipine could be dose reduced or discontinued in patients with lower baseline blood pressures to better support sacubitril/valsartan initiation and titration.”
He highlighted the subgroup analysis showing evidence of a larger treatment effect in study patients with an EF of 60% or less for the NT-proBNP change (0.78) and the hierarchical outcome (win ratio, 1.46).
“These data may influence future guidance for sacubitril-valsartan in HF with EF greater than 40%, regardless of HF chronicity [acute or chronic vs. de novo] and treatment setting [hospital vs. clinic],” Dr. Mentz concluded.
Data ‘far from conclusive’
In a comment, Sean Pinney, MD, chief of cardiology at Mount Sinai Morningside, New York, said that the study results “help expand the current evidence base supporting the use of an ARNI in patients” with an EF greater than 40% up to 60%, and “provide confidence that ARNIs help to lower natriuretic peptides.
“It comes as little surprise that not everyone was able to tolerate these medications due to intolerable side effects like dizziness or hypotension,” he said.
Nevertheless, he added, “hopefully, these trial data help strengthen clinicians’ resolve to prescribe sacubitril/valsartan to a growing population of vulnerable patients.”
In a related editorial, Hector O. Ventura, MD, of the Ochsner Clinical School–University of Queensland, New Orleans, and colleagues express several concerns about the study.
Although the trial achieved significance for the primary endpoint, the margin of benefit was less than expected and the magnitude of the NT-proBNP reduction may not have been enough to reach the threshold for clinical benefit, they wrote.
Diuretic dosing in the two groups was not reported, and between-group differences may have contributed to both the differential NT-proBNP reduction and the rates of hypotension.
Furthermore, the sacubitril-valsartan group had a higher proportion of missing NT-proBNP data, which may have biased the results.
“Clinicians who elect to use sacubitril-valsartan in this population should be mindful of the risk for hypotension and select patients carefully, while providing close ambulatory follow up to ensure stability and adherence,” they noted.
“This important trial provides some wins that support selective use of sacubitril-valsartan in HFpEF [as well as] observed losses, which too may help to define better implementation strategies in appropriately selected patients,” the editorialists concluded.
The study was funded by Novartis. Dr. Mentz and other coauthors have received fees from Novartis. Dr. Pinney, Dr. Ventura, and the other editorialists disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ESC HEART FAILURE 2023
