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While U.S. heart failure readmissions fall, deaths rise
DALLAS – U.S. hospitals have recently shown a consistent and disturbing disconnect between reductions in their heart failure hospital readmission rates and heart failure mortality. Readmissions have dropped while mortality has risen.
“Despite reductions in 30-day heart failure readmissions in 89% of U.S. hospitals” during 2009-2016, “30-day heart failure mortality rates increased at 73%* of these ‘successful’ hospitals” during the same period,” Ahmad A. Abdul-Aziz, MD, said at the annual scientific meeting of the Heart Failure Society of America.
These shifts in the outcomes of U.S. patients hospitalized for acute heart failure episodes are tied to the penalties that the Centers for Medicare & Medicaid Services began slapping on hospitals in 2013 for excess 30-day readmissions for heart failure patients and in 2014 for excess mortality. A problem with these two CMS programs is that the penalty on inferior readmissions performance is a lot stiffer than for excess mortality, Dr. Aziz noted: a 0.2% penalty on payments for high mortality, compared with a 3% penalty for excess readmissions, a disparity that can make hospitals focus more on the readmissions side, he suggested.
Dr. Aziz’s report isn’t the first to make this observation. Study results published earlier in 2017 used CMS Medicare data from 2008 to 2014 to show that during that period, heart failure 30-day mortality rates following hospital discharge rose by 1.3%, while 30-day readmissions fell by 2.1% (JAMA. 2017 July 18;318[3]:270-8). On the basis of these numbers, as many as 5,200 additional deaths to U.S. heart failure patients in 2014 “may be related to the Hospital Readmission Reduction Program” of CMS, Gregg C. Fonarow, MD, said during a separate talk at the meeting.
The analysis reported by Dr. Aziz included data from 3,265 U.S. hospitals for heart failure patients, and data from 1,621 hospitals that managed patients with acute MIs, another disease that the CMS has targeted for penalties based on 30-day readmissions and 30-day postdischarge mortality rates. During the 8-year period studied, heart failure 30-day readmissions fell by 2.2% while 30-day mortality rose by 1%. In contrast, among acute MI patients, readmissions fell by 3% and mortality also fell, by 2.2%, Dr. Abdul-Aziz reported.
Dr. Abdul-Aziz had no disclosures. Dr. Fonarow had been a consultant to Amgen, Janssen, Medtronic, Novartis, St. Jude, and ZS Pharma.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
*This article was updated October 5, 2017
My colleagues and I have seen in results from recent trials a changing relationship between heart failure mortality and heart failure hospitalization. In the United States in particular, where penalties exist for high rates of hospital readmissions for heart failure, we are seeing more patients treated as outpatients and we see that these “outpatient” events are associated with the same risk for subsequent mortality as we had previously seen for heart failure hospitalization.
It may be that we are keeping patients out of the hospital to avoid a financial ding, but perhaps we are keeping out patients who really should be hospitalized.
What we have begun doing in trials is to look not just at hospitalizations but also consider the incidence of other heart failure events, such as patients treated for heart failure symptoms with an intravenous diuretic in the emergency department and patients who are kept in observation rooms and are not admitted. It’s not the same as a heart failure hospitalization, but some trials are now including these other heart failure events in their primary endpoint.
Scott D. Solomon, MD, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital in Boston, made these comments as chair of the session where Dr. Aziz gave his report and in an interview. He has been a consultant to and/or received research support from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, Cytokinetics, GlaxoSmithKline, Ionis, Merck, Novartis, and Sanofi.
My colleagues and I have seen in results from recent trials a changing relationship between heart failure mortality and heart failure hospitalization. In the United States in particular, where penalties exist for high rates of hospital readmissions for heart failure, we are seeing more patients treated as outpatients and we see that these “outpatient” events are associated with the same risk for subsequent mortality as we had previously seen for heart failure hospitalization.
It may be that we are keeping patients out of the hospital to avoid a financial ding, but perhaps we are keeping out patients who really should be hospitalized.
What we have begun doing in trials is to look not just at hospitalizations but also consider the incidence of other heart failure events, such as patients treated for heart failure symptoms with an intravenous diuretic in the emergency department and patients who are kept in observation rooms and are not admitted. It’s not the same as a heart failure hospitalization, but some trials are now including these other heart failure events in their primary endpoint.
Scott D. Solomon, MD, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital in Boston, made these comments as chair of the session where Dr. Aziz gave his report and in an interview. He has been a consultant to and/or received research support from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, Cytokinetics, GlaxoSmithKline, Ionis, Merck, Novartis, and Sanofi.
My colleagues and I have seen in results from recent trials a changing relationship between heart failure mortality and heart failure hospitalization. In the United States in particular, where penalties exist for high rates of hospital readmissions for heart failure, we are seeing more patients treated as outpatients and we see that these “outpatient” events are associated with the same risk for subsequent mortality as we had previously seen for heart failure hospitalization.
It may be that we are keeping patients out of the hospital to avoid a financial ding, but perhaps we are keeping out patients who really should be hospitalized.
What we have begun doing in trials is to look not just at hospitalizations but also consider the incidence of other heart failure events, such as patients treated for heart failure symptoms with an intravenous diuretic in the emergency department and patients who are kept in observation rooms and are not admitted. It’s not the same as a heart failure hospitalization, but some trials are now including these other heart failure events in their primary endpoint.
Scott D. Solomon, MD, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital in Boston, made these comments as chair of the session where Dr. Aziz gave his report and in an interview. He has been a consultant to and/or received research support from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, Cytokinetics, GlaxoSmithKline, Ionis, Merck, Novartis, and Sanofi.
DALLAS – U.S. hospitals have recently shown a consistent and disturbing disconnect between reductions in their heart failure hospital readmission rates and heart failure mortality. Readmissions have dropped while mortality has risen.
“Despite reductions in 30-day heart failure readmissions in 89% of U.S. hospitals” during 2009-2016, “30-day heart failure mortality rates increased at 73%* of these ‘successful’ hospitals” during the same period,” Ahmad A. Abdul-Aziz, MD, said at the annual scientific meeting of the Heart Failure Society of America.
These shifts in the outcomes of U.S. patients hospitalized for acute heart failure episodes are tied to the penalties that the Centers for Medicare & Medicaid Services began slapping on hospitals in 2013 for excess 30-day readmissions for heart failure patients and in 2014 for excess mortality. A problem with these two CMS programs is that the penalty on inferior readmissions performance is a lot stiffer than for excess mortality, Dr. Aziz noted: a 0.2% penalty on payments for high mortality, compared with a 3% penalty for excess readmissions, a disparity that can make hospitals focus more on the readmissions side, he suggested.
Dr. Aziz’s report isn’t the first to make this observation. Study results published earlier in 2017 used CMS Medicare data from 2008 to 2014 to show that during that period, heart failure 30-day mortality rates following hospital discharge rose by 1.3%, while 30-day readmissions fell by 2.1% (JAMA. 2017 July 18;318[3]:270-8). On the basis of these numbers, as many as 5,200 additional deaths to U.S. heart failure patients in 2014 “may be related to the Hospital Readmission Reduction Program” of CMS, Gregg C. Fonarow, MD, said during a separate talk at the meeting.
The analysis reported by Dr. Aziz included data from 3,265 U.S. hospitals for heart failure patients, and data from 1,621 hospitals that managed patients with acute MIs, another disease that the CMS has targeted for penalties based on 30-day readmissions and 30-day postdischarge mortality rates. During the 8-year period studied, heart failure 30-day readmissions fell by 2.2% while 30-day mortality rose by 1%. In contrast, among acute MI patients, readmissions fell by 3% and mortality also fell, by 2.2%, Dr. Abdul-Aziz reported.
Dr. Abdul-Aziz had no disclosures. Dr. Fonarow had been a consultant to Amgen, Janssen, Medtronic, Novartis, St. Jude, and ZS Pharma.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
*This article was updated October 5, 2017
DALLAS – U.S. hospitals have recently shown a consistent and disturbing disconnect between reductions in their heart failure hospital readmission rates and heart failure mortality. Readmissions have dropped while mortality has risen.
“Despite reductions in 30-day heart failure readmissions in 89% of U.S. hospitals” during 2009-2016, “30-day heart failure mortality rates increased at 73%* of these ‘successful’ hospitals” during the same period,” Ahmad A. Abdul-Aziz, MD, said at the annual scientific meeting of the Heart Failure Society of America.
These shifts in the outcomes of U.S. patients hospitalized for acute heart failure episodes are tied to the penalties that the Centers for Medicare & Medicaid Services began slapping on hospitals in 2013 for excess 30-day readmissions for heart failure patients and in 2014 for excess mortality. A problem with these two CMS programs is that the penalty on inferior readmissions performance is a lot stiffer than for excess mortality, Dr. Aziz noted: a 0.2% penalty on payments for high mortality, compared with a 3% penalty for excess readmissions, a disparity that can make hospitals focus more on the readmissions side, he suggested.
Dr. Aziz’s report isn’t the first to make this observation. Study results published earlier in 2017 used CMS Medicare data from 2008 to 2014 to show that during that period, heart failure 30-day mortality rates following hospital discharge rose by 1.3%, while 30-day readmissions fell by 2.1% (JAMA. 2017 July 18;318[3]:270-8). On the basis of these numbers, as many as 5,200 additional deaths to U.S. heart failure patients in 2014 “may be related to the Hospital Readmission Reduction Program” of CMS, Gregg C. Fonarow, MD, said during a separate talk at the meeting.
The analysis reported by Dr. Aziz included data from 3,265 U.S. hospitals for heart failure patients, and data from 1,621 hospitals that managed patients with acute MIs, another disease that the CMS has targeted for penalties based on 30-day readmissions and 30-day postdischarge mortality rates. During the 8-year period studied, heart failure 30-day readmissions fell by 2.2% while 30-day mortality rose by 1%. In contrast, among acute MI patients, readmissions fell by 3% and mortality also fell, by 2.2%, Dr. Abdul-Aziz reported.
Dr. Abdul-Aziz had no disclosures. Dr. Fonarow had been a consultant to Amgen, Janssen, Medtronic, Novartis, St. Jude, and ZS Pharma.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
*This article was updated October 5, 2017
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: From 2009 to 2016, U.S. 30-day heart failure readmissions fell by 2.2% while 30-day heart failure mortality rose by 1%.
Data source: Review of Medicare data for 3,265 U.S. hospitals managing heart failure patients.
Disclosures: Dr. Abdul-Aziz had no disclosures. Dr. Fonarow had been a consultant to Amgen, Janssen, Medtronic, Novartis, St. Jude, and ZS Pharma.
Riociguat may benefit subset of PAH patients
Switching to riociguat may be an effective strategy for pulmonary arterial hypertension (PAH) patients who respond inadequately to phosphodiesterase-5 inhibitors, results from a small open-label study demonstrated.
“This study represents an important step towards determining if this new treatment strategy is an effective approach to the management of patients with PAH, although additional data from larger, randomised, controlled studies are needed to further establish the safety and efficacy of this approach,” researchers led by Marius M. Hoeper, MD, wrote in a study published online Sept. 9, 2017, in the European Respiratory Journal.
Current clinical data indicate that many patients with PAH who receive phosphodiesterase-5 inhibitors do not reach treatment goals. “For example, in the AMBITION study, 73% of patients with PAH receiving tadalafil monotherapy and 61% of those receiving tadalafil in combination with ambrisentan did not achieve a satisfactory clinical response at week 24 of the study (N Engl J Med. 2015;373:834-44),” Dr. Hoeper of the Clinic for Respiratory Medicine at Hannover Medical School Germany and his associates wrote. “Furthermore, in the SERAPHIN study, event-free survival of patients receiving [phosphodiesterase-5 inhibitors] monotherapy was approximately 50% at 3 years (N Engl J Med. 2013;369:809-18).”
For the current trial, known as RESPITE, investigators from nine countries in Europe and North America enrolled 61 PAH patients in a 24-week, open-label uncontrolled analysis to investigate the safety, feasibility, and benefit of switching them from phosphodiesterase-5 inhibitors to riociguat. The patients underwent 1-3 days free of phosphodiesterase-5 inhibitors before receiving riociguat in a maximum dose of up to 2.5 mg t.i.d. Most patients (74%) were female, and 92% were Caucasian. In all, 51 patients (84%) completed all 24 weeks of treatment, while the remaining 10 discontinued treatment, 4 of whom due to adverse events.
Additionally, 54% of the patients studied experienced an improvement in their the World Health Organization Functional Class. However, 32 patients (52%) experienced study drug–related adverse events and 10 (16%) experienced serious adverse events, two of which were related to the drug being studied. Six patients (10%) experienced clinical worsening, including death in two, though the deaths were deemed to be unrelated to the drug being studied.
“Although not mechanistically studied, the findings of RESPITE support the hypothesis that a defective [nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate] pathway might explain why some patients have no sufficient or sustained response to [phosphodiesterase-5 inhibitors] therapy,” the researchers noted. “In such patients, direct stimulation of [soluble guanylate cyclase] may be more effective than inhibition of [phosphodiesterase-5], but this hypothesis is still unproven.”
They acknowledged certain limitations of the study, including its prospective design and the relatively homogenous patient population. “Other limitations include the lack of a long-term continuation phase, and the absence of mechanistic data allowing identification of patients likely to respond or not respond to switching,” they wrote. “Two deaths were observed in this study, which might raise concerns, although neither of the deaths (one due to pneumonia and one due to subdural haematoma) was considered by the investigators to be study drug-related or due to worsening PAH. Given the lack of a control group and the rate of study withdrawals and clinical worsening events, further evaluation to clarify the safety of switching is required.”
The study was funded by Bayer AG, Berlin. Dr. Hoeper and his coauthors disclosed having financial ties to numerous pharmaceutical companies, including Bayer, which makes riociguat.
PRIMARY SOURCE: Eur Respir J. 2017 Sep 9. doi: 10.1183/13993003.02425-2016.
Switching to riociguat may be an effective strategy for pulmonary arterial hypertension (PAH) patients who respond inadequately to phosphodiesterase-5 inhibitors, results from a small open-label study demonstrated.
“This study represents an important step towards determining if this new treatment strategy is an effective approach to the management of patients with PAH, although additional data from larger, randomised, controlled studies are needed to further establish the safety and efficacy of this approach,” researchers led by Marius M. Hoeper, MD, wrote in a study published online Sept. 9, 2017, in the European Respiratory Journal.
Current clinical data indicate that many patients with PAH who receive phosphodiesterase-5 inhibitors do not reach treatment goals. “For example, in the AMBITION study, 73% of patients with PAH receiving tadalafil monotherapy and 61% of those receiving tadalafil in combination with ambrisentan did not achieve a satisfactory clinical response at week 24 of the study (N Engl J Med. 2015;373:834-44),” Dr. Hoeper of the Clinic for Respiratory Medicine at Hannover Medical School Germany and his associates wrote. “Furthermore, in the SERAPHIN study, event-free survival of patients receiving [phosphodiesterase-5 inhibitors] monotherapy was approximately 50% at 3 years (N Engl J Med. 2013;369:809-18).”
For the current trial, known as RESPITE, investigators from nine countries in Europe and North America enrolled 61 PAH patients in a 24-week, open-label uncontrolled analysis to investigate the safety, feasibility, and benefit of switching them from phosphodiesterase-5 inhibitors to riociguat. The patients underwent 1-3 days free of phosphodiesterase-5 inhibitors before receiving riociguat in a maximum dose of up to 2.5 mg t.i.d. Most patients (74%) were female, and 92% were Caucasian. In all, 51 patients (84%) completed all 24 weeks of treatment, while the remaining 10 discontinued treatment, 4 of whom due to adverse events.
Additionally, 54% of the patients studied experienced an improvement in their the World Health Organization Functional Class. However, 32 patients (52%) experienced study drug–related adverse events and 10 (16%) experienced serious adverse events, two of which were related to the drug being studied. Six patients (10%) experienced clinical worsening, including death in two, though the deaths were deemed to be unrelated to the drug being studied.
“Although not mechanistically studied, the findings of RESPITE support the hypothesis that a defective [nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate] pathway might explain why some patients have no sufficient or sustained response to [phosphodiesterase-5 inhibitors] therapy,” the researchers noted. “In such patients, direct stimulation of [soluble guanylate cyclase] may be more effective than inhibition of [phosphodiesterase-5], but this hypothesis is still unproven.”
They acknowledged certain limitations of the study, including its prospective design and the relatively homogenous patient population. “Other limitations include the lack of a long-term continuation phase, and the absence of mechanistic data allowing identification of patients likely to respond or not respond to switching,” they wrote. “Two deaths were observed in this study, which might raise concerns, although neither of the deaths (one due to pneumonia and one due to subdural haematoma) was considered by the investigators to be study drug-related or due to worsening PAH. Given the lack of a control group and the rate of study withdrawals and clinical worsening events, further evaluation to clarify the safety of switching is required.”
The study was funded by Bayer AG, Berlin. Dr. Hoeper and his coauthors disclosed having financial ties to numerous pharmaceutical companies, including Bayer, which makes riociguat.
PRIMARY SOURCE: Eur Respir J. 2017 Sep 9. doi: 10.1183/13993003.02425-2016.
Switching to riociguat may be an effective strategy for pulmonary arterial hypertension (PAH) patients who respond inadequately to phosphodiesterase-5 inhibitors, results from a small open-label study demonstrated.
“This study represents an important step towards determining if this new treatment strategy is an effective approach to the management of patients with PAH, although additional data from larger, randomised, controlled studies are needed to further establish the safety and efficacy of this approach,” researchers led by Marius M. Hoeper, MD, wrote in a study published online Sept. 9, 2017, in the European Respiratory Journal.
Current clinical data indicate that many patients with PAH who receive phosphodiesterase-5 inhibitors do not reach treatment goals. “For example, in the AMBITION study, 73% of patients with PAH receiving tadalafil monotherapy and 61% of those receiving tadalafil in combination with ambrisentan did not achieve a satisfactory clinical response at week 24 of the study (N Engl J Med. 2015;373:834-44),” Dr. Hoeper of the Clinic for Respiratory Medicine at Hannover Medical School Germany and his associates wrote. “Furthermore, in the SERAPHIN study, event-free survival of patients receiving [phosphodiesterase-5 inhibitors] monotherapy was approximately 50% at 3 years (N Engl J Med. 2013;369:809-18).”
For the current trial, known as RESPITE, investigators from nine countries in Europe and North America enrolled 61 PAH patients in a 24-week, open-label uncontrolled analysis to investigate the safety, feasibility, and benefit of switching them from phosphodiesterase-5 inhibitors to riociguat. The patients underwent 1-3 days free of phosphodiesterase-5 inhibitors before receiving riociguat in a maximum dose of up to 2.5 mg t.i.d. Most patients (74%) were female, and 92% were Caucasian. In all, 51 patients (84%) completed all 24 weeks of treatment, while the remaining 10 discontinued treatment, 4 of whom due to adverse events.
Additionally, 54% of the patients studied experienced an improvement in their the World Health Organization Functional Class. However, 32 patients (52%) experienced study drug–related adverse events and 10 (16%) experienced serious adverse events, two of which were related to the drug being studied. Six patients (10%) experienced clinical worsening, including death in two, though the deaths were deemed to be unrelated to the drug being studied.
“Although not mechanistically studied, the findings of RESPITE support the hypothesis that a defective [nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate] pathway might explain why some patients have no sufficient or sustained response to [phosphodiesterase-5 inhibitors] therapy,” the researchers noted. “In such patients, direct stimulation of [soluble guanylate cyclase] may be more effective than inhibition of [phosphodiesterase-5], but this hypothesis is still unproven.”
They acknowledged certain limitations of the study, including its prospective design and the relatively homogenous patient population. “Other limitations include the lack of a long-term continuation phase, and the absence of mechanistic data allowing identification of patients likely to respond or not respond to switching,” they wrote. “Two deaths were observed in this study, which might raise concerns, although neither of the deaths (one due to pneumonia and one due to subdural haematoma) was considered by the investigators to be study drug-related or due to worsening PAH. Given the lack of a control group and the rate of study withdrawals and clinical worsening events, further evaluation to clarify the safety of switching is required.”
The study was funded by Bayer AG, Berlin. Dr. Hoeper and his coauthors disclosed having financial ties to numerous pharmaceutical companies, including Bayer, which makes riociguat.
PRIMARY SOURCE: Eur Respir J. 2017 Sep 9. doi: 10.1183/13993003.02425-2016.
FROM THE EUROPEAN RESPIRATORY JOURNAL
Key clinical point: Selected patients with pulmonary artery hypertension (PAH) may benefit from switching from phosphodiesterase-5 inhibitors to riociguat.
Major finding: Among patients who completed all 24 weeks of treatment with riociguat, their mean 6-minute walking distance had increased by a mean of 31 meters, and their N-terminal pro b-type natriuretic peptide level decreased by a mean of 347 pg/mL.
Study details: A multicenter, open-label trial of 61 patients with PAH.
Disclosures: The study was funded by Bayer AG, Berlin. Dr. Hoeper and his coauthors disclosed having financial ties to numerous pharmaceutical companies, including Bayer, which makes riociguat.
Source: Marius M. Hoeper, et al. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphdiesterase-5 inhibitors. Eur Resp J. 2017 Sep 09. doi: 10.1183/13993003.02425-2016.
Hepatitis C falls as barrier to heart transplantation
DALLAS – The heart transplant team at Vanderbilt University has successfully placed hearts from deceased, hepatitis C virus–positive patients into recipients, and then eradicated the subsequent infection that appeared in most recipients using a standard regimen.
So far, five of nine heart transplant recipients who developed a posttransplant hepatitis C virus (HCV) infection had the infection eradicated using one of the highly effective HCV drug regimens, and an additional three patients from the series are nearing their 12th week without detectable virus following treatment that marks a sustained response, Kelly H. Schlendorf, MD, said at the annual scientific meeting of the Heart Failure Society of America. The ninth patient died after developing a pulmonary embolism during the 7th week on antiviral therapy.
The recipients have been patients in a marginal clinical state and facing a long projected wait on the heart-recipient queue of the United Network for Organ Sharing (UNOS), Dr. Schlendorf said in an interview.
These have been “patients with a morbidity and mortality risk from waiting that can be mitigated by expanding the donor pool.” She gave an example of a patient with a left ventricular assist device that required replacement by either a second device or transplant, “so getting the transplant quickly was a good thing,” said Dr. Schlendorf, a cardiologist at Vanderbilt in Nashville.
Based on her analysis of UNOS data, “upwards of 100” and perhaps as many as 300 additional donor hearts could be available annually for U.S. transplants if the organs weren’t excluded because of HCV infection.
The Vanderbilt team has so far approached 15 patients in their program wait-listed for hearts about the possibility of accepting an HCV-positive organ, and all 15 have given their consent, she said. “We spend a lot of time talking with patients and their caregivers about the risks and benefits and possible complications.”
The 13 recipients, starting in September 2016, included 12 patients who were HCV naive and 1 patient with a history of HCV exposure. All 13 received the program’s standard three-drug regimen for immunosuppression.
During close surveillance, 9 of the 13 developed an infection. Patients with genotype 1 HCV received 12 weeks of treatment with ledipasvir plus sofosbuvir. Those infected with genotype 3 received 12-24 weeks of treatment with sofosbuvir plus velpatasvir. Treatment with these direct-acting antivirals meant that patients had to adjust the time when they took their proton-pump inhibitors, and they needed to stop treatment with diltiazem and statins while on the antivirals.
“In the era of direct-acting antivirals, HCV-positive donors may provide a safe and effective way to expand the donor pool and reduce wait-list times,” Dr. Schlendorf said. She noted that in recent years an increased number of potential organ donors have been HCV positive. She also cautioned that so far follow-up has been relatively brief, with no patient yet followed as long as 1 year after transplant.
The direct-acting HCV antivirals are expensive, and some payers established clinical criteria that patients must meet to qualify for coverage of these regimens. “We have not encountered difficulties getting insurers to pay,” Dr. Schlendorf said. Despite the antivirals’ cost there are significant cost savings from fewer days in the ICU waiting for heart transplantation and a reduced need for mechanical support as a bridge to transplant, she noted.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
DALLAS – The heart transplant team at Vanderbilt University has successfully placed hearts from deceased, hepatitis C virus–positive patients into recipients, and then eradicated the subsequent infection that appeared in most recipients using a standard regimen.
So far, five of nine heart transplant recipients who developed a posttransplant hepatitis C virus (HCV) infection had the infection eradicated using one of the highly effective HCV drug regimens, and an additional three patients from the series are nearing their 12th week without detectable virus following treatment that marks a sustained response, Kelly H. Schlendorf, MD, said at the annual scientific meeting of the Heart Failure Society of America. The ninth patient died after developing a pulmonary embolism during the 7th week on antiviral therapy.
The recipients have been patients in a marginal clinical state and facing a long projected wait on the heart-recipient queue of the United Network for Organ Sharing (UNOS), Dr. Schlendorf said in an interview.
These have been “patients with a morbidity and mortality risk from waiting that can be mitigated by expanding the donor pool.” She gave an example of a patient with a left ventricular assist device that required replacement by either a second device or transplant, “so getting the transplant quickly was a good thing,” said Dr. Schlendorf, a cardiologist at Vanderbilt in Nashville.
Based on her analysis of UNOS data, “upwards of 100” and perhaps as many as 300 additional donor hearts could be available annually for U.S. transplants if the organs weren’t excluded because of HCV infection.
The Vanderbilt team has so far approached 15 patients in their program wait-listed for hearts about the possibility of accepting an HCV-positive organ, and all 15 have given their consent, she said. “We spend a lot of time talking with patients and their caregivers about the risks and benefits and possible complications.”
The 13 recipients, starting in September 2016, included 12 patients who were HCV naive and 1 patient with a history of HCV exposure. All 13 received the program’s standard three-drug regimen for immunosuppression.
During close surveillance, 9 of the 13 developed an infection. Patients with genotype 1 HCV received 12 weeks of treatment with ledipasvir plus sofosbuvir. Those infected with genotype 3 received 12-24 weeks of treatment with sofosbuvir plus velpatasvir. Treatment with these direct-acting antivirals meant that patients had to adjust the time when they took their proton-pump inhibitors, and they needed to stop treatment with diltiazem and statins while on the antivirals.
“In the era of direct-acting antivirals, HCV-positive donors may provide a safe and effective way to expand the donor pool and reduce wait-list times,” Dr. Schlendorf said. She noted that in recent years an increased number of potential organ donors have been HCV positive. She also cautioned that so far follow-up has been relatively brief, with no patient yet followed as long as 1 year after transplant.
The direct-acting HCV antivirals are expensive, and some payers established clinical criteria that patients must meet to qualify for coverage of these regimens. “We have not encountered difficulties getting insurers to pay,” Dr. Schlendorf said. Despite the antivirals’ cost there are significant cost savings from fewer days in the ICU waiting for heart transplantation and a reduced need for mechanical support as a bridge to transplant, she noted.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
DALLAS – The heart transplant team at Vanderbilt University has successfully placed hearts from deceased, hepatitis C virus–positive patients into recipients, and then eradicated the subsequent infection that appeared in most recipients using a standard regimen.
So far, five of nine heart transplant recipients who developed a posttransplant hepatitis C virus (HCV) infection had the infection eradicated using one of the highly effective HCV drug regimens, and an additional three patients from the series are nearing their 12th week without detectable virus following treatment that marks a sustained response, Kelly H. Schlendorf, MD, said at the annual scientific meeting of the Heart Failure Society of America. The ninth patient died after developing a pulmonary embolism during the 7th week on antiviral therapy.
The recipients have been patients in a marginal clinical state and facing a long projected wait on the heart-recipient queue of the United Network for Organ Sharing (UNOS), Dr. Schlendorf said in an interview.
These have been “patients with a morbidity and mortality risk from waiting that can be mitigated by expanding the donor pool.” She gave an example of a patient with a left ventricular assist device that required replacement by either a second device or transplant, “so getting the transplant quickly was a good thing,” said Dr. Schlendorf, a cardiologist at Vanderbilt in Nashville.
Based on her analysis of UNOS data, “upwards of 100” and perhaps as many as 300 additional donor hearts could be available annually for U.S. transplants if the organs weren’t excluded because of HCV infection.
The Vanderbilt team has so far approached 15 patients in their program wait-listed for hearts about the possibility of accepting an HCV-positive organ, and all 15 have given their consent, she said. “We spend a lot of time talking with patients and their caregivers about the risks and benefits and possible complications.”
The 13 recipients, starting in September 2016, included 12 patients who were HCV naive and 1 patient with a history of HCV exposure. All 13 received the program’s standard three-drug regimen for immunosuppression.
During close surveillance, 9 of the 13 developed an infection. Patients with genotype 1 HCV received 12 weeks of treatment with ledipasvir plus sofosbuvir. Those infected with genotype 3 received 12-24 weeks of treatment with sofosbuvir plus velpatasvir. Treatment with these direct-acting antivirals meant that patients had to adjust the time when they took their proton-pump inhibitors, and they needed to stop treatment with diltiazem and statins while on the antivirals.
“In the era of direct-acting antivirals, HCV-positive donors may provide a safe and effective way to expand the donor pool and reduce wait-list times,” Dr. Schlendorf said. She noted that in recent years an increased number of potential organ donors have been HCV positive. She also cautioned that so far follow-up has been relatively brief, with no patient yet followed as long as 1 year after transplant.
The direct-acting HCV antivirals are expensive, and some payers established clinical criteria that patients must meet to qualify for coverage of these regimens. “We have not encountered difficulties getting insurers to pay,” Dr. Schlendorf said. Despite the antivirals’ cost there are significant cost savings from fewer days in the ICU waiting for heart transplantation and a reduced need for mechanical support as a bridge to transplant, she noted.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Eight of nine patients who developed HCV infection had it eradicated by a direct-acting antiviral regimen.
Data source: A series of 13 patients treated at one U.S. center.
Disclosures: Dr. Schlendorf had no disclosures.
Metabolically healthy obese still at elevated cardiovascular risk
Obese individuals with no metabolic abnormalities, such as dyslipidemia, high blood pressure, or high blood sugar levels, still have a higher risk of cardiovascular disease than do metabolically healthy people of normal weight, new data suggests.
“Our study robustly challenges the assertion that MHO [metabolically healthy obese] is a benign condition and adds to the evidence base that MHO is a high-risk state for future CVD events,” wrote Rishi Caleyachetty, MD, of the University of Birmingham, England, and his coauthors online (J Am Coll Cardiol. 2017, Sep 11. doi. 10.1016/j.jacc.2017.07.763).
Dr. Caleyachetty and his associates reported findings from a population-based study using the electronic health records of nearly 3.5 million individuals aged 18 years or older who were free of cardiovascular disease at baseline.
Overall, 15% of the population were classified as being metabolically healthy obese, meaning that they had a body mass index (BMI) of at least 30 kg/m2 with no sign of diabetes, hypertension, or hyperlipidemia, and 26% were overweight with no metabolic abnormalities. Despite their lack of metabolic disease, these obese individuals still had a significant 49% higher risk of coronary heart disease, 7% higher risk of cerebrovascular disease, and 96% higher risk of heart failure, compared with normal-weight individuals with no metabolic disease, after researchers adjusted for age, sex, smoking status, and social deprivation.
Individuals who were overweight but metabolically healthy had a 30% increased risk of ischemic heart disease, 11% increased risk of heart failure, and the same risk of cerebrovascular disease as normal-weight, healthy individuals.
They also saw an increasing risk of ischemic heart disease, cerebrovascular disease, heart failure, and peripheral vascular disease with each additional metabolic abnormality, even among underweight and normal-weight individuals, and suggested that a focus on screening overweight and obese individuals only could miss metabolic abnormalities in many patients.
Overweight and obese individuals without metabolic disease had a significantly lower risk of peripheral vascular disease, compared with healthy normal-weight individuals. The authors said this was a surprising finding but suggested cigarette smoking could be a confounding factor, as this is associated with both peripheral vascular disease and lower BMI.
“In sensitivity analyses restricted to individuals who were obese with no metabolic abnormalities and reported never smoking cigarettes, risk for PVD [peripheral vascular disease] was increased, compared [with] normal-weight individuals with no metabolic abnormalities,” Dr. Caleyachetty and his coinvestigators wrote.
Over the mean follow-up of 5.4 years, 5.6% of initially metabolically healthy obese individuals developed diabetes, 11.5% developed hyperlipidemia and 10.5% developed hypertension. In contrast, among the metabolically healthy overweight individuals at baseline, 1.9% developed diabetes, 9.4% developed hyperlipidemia, and 7.2% developed hypertension.
While the analysis adjusted for sex, the authors did note that women who were overweight or obese but metabolically healthy had stronger positive associations than did males with cerebrovascular disease and heart failure.
“Clinicians need to be aware that individuals who would otherwise be considered nonobese, based on a normal BMI, can have metabolic abnormalities, and therefore also be at high risk for CVD events,” the investigators concluded.
No conflicts of interest were declared.
Recently, studies have consistently placed metabolically healthy obese individuals between metabolically healthy lean and metabolically unhealthy obese individuals in terms of cardiovascular disease risk, occult cardiac dysfunction, and type 2 diabetes. Thus, either metabolic dysfunction or elevated body mass index appears to increases CVD risk factors.
Often, one or two metabolic risk factors in normal weight individuals are dismissed as unimportant because they are of healthy weight; however, these data suggest that the normal-weight group is at similar risk, compared with overweight, and at times, obese individuals, when metabolic abnormalities are present. The study not only definitively counters the concept of metabolically benign obesity but also demonstrates great risk to normal weight individuals if metabolic dysfunction is present. Thus, we would suggest an increased need for screening in the normal-weight population.
Jennifer W. Bea, PhD, is from the Collaboratory for Metabolic Disease Prevention and Treatment in Tucson, Ariz., and Nancy K. Sweitzer, MD, is chief of the division of cardiology at the Sarver Heart Center. These comments are taken from an accompanying editorial (J Am Coll Cardiol. 2017 Sep 19;70:1438-40. doi. org/10.1016/j.jacc.2017.07.742). No conflicts of interest were declared.
Recently, studies have consistently placed metabolically healthy obese individuals between metabolically healthy lean and metabolically unhealthy obese individuals in terms of cardiovascular disease risk, occult cardiac dysfunction, and type 2 diabetes. Thus, either metabolic dysfunction or elevated body mass index appears to increases CVD risk factors.
Often, one or two metabolic risk factors in normal weight individuals are dismissed as unimportant because they are of healthy weight; however, these data suggest that the normal-weight group is at similar risk, compared with overweight, and at times, obese individuals, when metabolic abnormalities are present. The study not only definitively counters the concept of metabolically benign obesity but also demonstrates great risk to normal weight individuals if metabolic dysfunction is present. Thus, we would suggest an increased need for screening in the normal-weight population.
Jennifer W. Bea, PhD, is from the Collaboratory for Metabolic Disease Prevention and Treatment in Tucson, Ariz., and Nancy K. Sweitzer, MD, is chief of the division of cardiology at the Sarver Heart Center. These comments are taken from an accompanying editorial (J Am Coll Cardiol. 2017 Sep 19;70:1438-40. doi. org/10.1016/j.jacc.2017.07.742). No conflicts of interest were declared.
Recently, studies have consistently placed metabolically healthy obese individuals between metabolically healthy lean and metabolically unhealthy obese individuals in terms of cardiovascular disease risk, occult cardiac dysfunction, and type 2 diabetes. Thus, either metabolic dysfunction or elevated body mass index appears to increases CVD risk factors.
Often, one or two metabolic risk factors in normal weight individuals are dismissed as unimportant because they are of healthy weight; however, these data suggest that the normal-weight group is at similar risk, compared with overweight, and at times, obese individuals, when metabolic abnormalities are present. The study not only definitively counters the concept of metabolically benign obesity but also demonstrates great risk to normal weight individuals if metabolic dysfunction is present. Thus, we would suggest an increased need for screening in the normal-weight population.
Jennifer W. Bea, PhD, is from the Collaboratory for Metabolic Disease Prevention and Treatment in Tucson, Ariz., and Nancy K. Sweitzer, MD, is chief of the division of cardiology at the Sarver Heart Center. These comments are taken from an accompanying editorial (J Am Coll Cardiol. 2017 Sep 19;70:1438-40. doi. org/10.1016/j.jacc.2017.07.742). No conflicts of interest were declared.
Obese individuals with no metabolic abnormalities, such as dyslipidemia, high blood pressure, or high blood sugar levels, still have a higher risk of cardiovascular disease than do metabolically healthy people of normal weight, new data suggests.
“Our study robustly challenges the assertion that MHO [metabolically healthy obese] is a benign condition and adds to the evidence base that MHO is a high-risk state for future CVD events,” wrote Rishi Caleyachetty, MD, of the University of Birmingham, England, and his coauthors online (J Am Coll Cardiol. 2017, Sep 11. doi. 10.1016/j.jacc.2017.07.763).
Dr. Caleyachetty and his associates reported findings from a population-based study using the electronic health records of nearly 3.5 million individuals aged 18 years or older who were free of cardiovascular disease at baseline.
Overall, 15% of the population were classified as being metabolically healthy obese, meaning that they had a body mass index (BMI) of at least 30 kg/m2 with no sign of diabetes, hypertension, or hyperlipidemia, and 26% were overweight with no metabolic abnormalities. Despite their lack of metabolic disease, these obese individuals still had a significant 49% higher risk of coronary heart disease, 7% higher risk of cerebrovascular disease, and 96% higher risk of heart failure, compared with normal-weight individuals with no metabolic disease, after researchers adjusted for age, sex, smoking status, and social deprivation.
Individuals who were overweight but metabolically healthy had a 30% increased risk of ischemic heart disease, 11% increased risk of heart failure, and the same risk of cerebrovascular disease as normal-weight, healthy individuals.
They also saw an increasing risk of ischemic heart disease, cerebrovascular disease, heart failure, and peripheral vascular disease with each additional metabolic abnormality, even among underweight and normal-weight individuals, and suggested that a focus on screening overweight and obese individuals only could miss metabolic abnormalities in many patients.
Overweight and obese individuals without metabolic disease had a significantly lower risk of peripheral vascular disease, compared with healthy normal-weight individuals. The authors said this was a surprising finding but suggested cigarette smoking could be a confounding factor, as this is associated with both peripheral vascular disease and lower BMI.
“In sensitivity analyses restricted to individuals who were obese with no metabolic abnormalities and reported never smoking cigarettes, risk for PVD [peripheral vascular disease] was increased, compared [with] normal-weight individuals with no metabolic abnormalities,” Dr. Caleyachetty and his coinvestigators wrote.
Over the mean follow-up of 5.4 years, 5.6% of initially metabolically healthy obese individuals developed diabetes, 11.5% developed hyperlipidemia and 10.5% developed hypertension. In contrast, among the metabolically healthy overweight individuals at baseline, 1.9% developed diabetes, 9.4% developed hyperlipidemia, and 7.2% developed hypertension.
While the analysis adjusted for sex, the authors did note that women who were overweight or obese but metabolically healthy had stronger positive associations than did males with cerebrovascular disease and heart failure.
“Clinicians need to be aware that individuals who would otherwise be considered nonobese, based on a normal BMI, can have metabolic abnormalities, and therefore also be at high risk for CVD events,” the investigators concluded.
No conflicts of interest were declared.
Obese individuals with no metabolic abnormalities, such as dyslipidemia, high blood pressure, or high blood sugar levels, still have a higher risk of cardiovascular disease than do metabolically healthy people of normal weight, new data suggests.
“Our study robustly challenges the assertion that MHO [metabolically healthy obese] is a benign condition and adds to the evidence base that MHO is a high-risk state for future CVD events,” wrote Rishi Caleyachetty, MD, of the University of Birmingham, England, and his coauthors online (J Am Coll Cardiol. 2017, Sep 11. doi. 10.1016/j.jacc.2017.07.763).
Dr. Caleyachetty and his associates reported findings from a population-based study using the electronic health records of nearly 3.5 million individuals aged 18 years or older who were free of cardiovascular disease at baseline.
Overall, 15% of the population were classified as being metabolically healthy obese, meaning that they had a body mass index (BMI) of at least 30 kg/m2 with no sign of diabetes, hypertension, or hyperlipidemia, and 26% were overweight with no metabolic abnormalities. Despite their lack of metabolic disease, these obese individuals still had a significant 49% higher risk of coronary heart disease, 7% higher risk of cerebrovascular disease, and 96% higher risk of heart failure, compared with normal-weight individuals with no metabolic disease, after researchers adjusted for age, sex, smoking status, and social deprivation.
Individuals who were overweight but metabolically healthy had a 30% increased risk of ischemic heart disease, 11% increased risk of heart failure, and the same risk of cerebrovascular disease as normal-weight, healthy individuals.
They also saw an increasing risk of ischemic heart disease, cerebrovascular disease, heart failure, and peripheral vascular disease with each additional metabolic abnormality, even among underweight and normal-weight individuals, and suggested that a focus on screening overweight and obese individuals only could miss metabolic abnormalities in many patients.
Overweight and obese individuals without metabolic disease had a significantly lower risk of peripheral vascular disease, compared with healthy normal-weight individuals. The authors said this was a surprising finding but suggested cigarette smoking could be a confounding factor, as this is associated with both peripheral vascular disease and lower BMI.
“In sensitivity analyses restricted to individuals who were obese with no metabolic abnormalities and reported never smoking cigarettes, risk for PVD [peripheral vascular disease] was increased, compared [with] normal-weight individuals with no metabolic abnormalities,” Dr. Caleyachetty and his coinvestigators wrote.
Over the mean follow-up of 5.4 years, 5.6% of initially metabolically healthy obese individuals developed diabetes, 11.5% developed hyperlipidemia and 10.5% developed hypertension. In contrast, among the metabolically healthy overweight individuals at baseline, 1.9% developed diabetes, 9.4% developed hyperlipidemia, and 7.2% developed hypertension.
While the analysis adjusted for sex, the authors did note that women who were overweight or obese but metabolically healthy had stronger positive associations than did males with cerebrovascular disease and heart failure.
“Clinicians need to be aware that individuals who would otherwise be considered nonobese, based on a normal BMI, can have metabolic abnormalities, and therefore also be at high risk for CVD events,” the investigators concluded.
No conflicts of interest were declared.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Obese individuals without any sign of metabolic disease, such as hypertension or dyslipidemia, still have a greater risk of cardiovascular disease than do normal weight individuals.
Major finding: Metabolically healthy obese individuals have a 49% higher risk of coronary heart disease and 96% higher risk of heart failure than metabolically healthy normal weight individuals.
Data source: Population-based electronic health record study of 3.5 million people.
Disclosures: No conflicts of interest were declared.
Ivabradine cut mortality in HFrEF patients not on beta-blocker
BARCELONA – The time is right for a placebo-controlled, randomized trial of ivabradine in patients with heart failure with reduced ejection fraction who are unwilling or unable to take a beta-blocker as recommended in the guidelines, John G.F. Cleland, MD, asserted at the annual congress of the European Society of Cardiology.
He cited as the rationale for such a study a new post-hoc analysis of data from the SHIFT trial showing that ivabradine (Corlanor) significantly reduced both cardiovascular and all-cause mortality, as well as hospitalizations for heart failure, in the subset of study participants who weren’t on beta-blocker therapy.
“I think there would be ethical equipoise,” he added. “If patients are unwilling or unable to take a beta-blocker, or their cardiologist feels it’s not in their best interest, then I certainly think a placebo-controlled trial would not only be appropriate, but there’s also an onus on the cardiology community to do such a trial.”
Ivabradine slows heart rate by a unique mechanism that doesn’t involve blockade of adrenergic receptors. In the SHIFT trial (Lancet. 2010 Sep 11;376[9744]:875-85), more than 6,500 patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate greater than 70 bpm were randomized to ivabradine or placebo on top of guideline-directed medical therapy for heart failure. During a median 23 months of follow-up, heart failure hospitalizations were significantly reduced by 26% in the ivabradine group, although cardiovascular deaths were not significantly affected.
As a result of the SHIFT findings, the drug was approved with an indication for use only in combination with a beta-blocker in patients with HFrEF whose on-treatment heart rate exceeds 70 bpm. Ivabradine is not currently recommended as an alternative to beta-blocker therapy. However, in real-world clinical practice a large number of heart failure patients are not managed with a beta-blocker, the cardiologist noted.
His post-hoc analysis focused on the 685 SHIFT participants who were not on a beta-blocker at randomization. During follow-up, there were 93 deaths among patients who were on placebo and only 71 in those randomized to ivabradine, for a statistically significant 30% reduction in all-cause mortality. Cardiovascular mortality was reduced to a similar extent. These hazard ratios remained similar after adjusting for differences in heart rate and other clinical characteristics.
“Beta-blockers are a highly effective therapy for heart failure with reduced ejection fraction, but the mechanism of benefit remains uncertain. It might simply be due to heart rate reduction. And I would point out that we have no evidence of a dose response for beta-blockers: It may well be that you get most of the effect of a beta-blocker with the lowest dose. Titrating to the full dose of a beta-blocker might only be helpful in that it lowers your heart rate. I would argue that 6.25 mg/day of carvedilol plus ivabradine might be as good as 50 mg twice daily of carvedilol but with much higher patient acceptability. We don’t know,” said Dr. Cleland.
“This is an interesting, hypothesis-generating analysis, and we need confirmation now that ivabradine reduces mortality in heart failure patients who are unwilling or unable to take a beta-blocker,” he concluded.
The SHIFT trial was sponsored by Servier. Dr. Cleland reported serving as a consultant to and receiving research funding from that company and others.
BARCELONA – The time is right for a placebo-controlled, randomized trial of ivabradine in patients with heart failure with reduced ejection fraction who are unwilling or unable to take a beta-blocker as recommended in the guidelines, John G.F. Cleland, MD, asserted at the annual congress of the European Society of Cardiology.
He cited as the rationale for such a study a new post-hoc analysis of data from the SHIFT trial showing that ivabradine (Corlanor) significantly reduced both cardiovascular and all-cause mortality, as well as hospitalizations for heart failure, in the subset of study participants who weren’t on beta-blocker therapy.
“I think there would be ethical equipoise,” he added. “If patients are unwilling or unable to take a beta-blocker, or their cardiologist feels it’s not in their best interest, then I certainly think a placebo-controlled trial would not only be appropriate, but there’s also an onus on the cardiology community to do such a trial.”
Ivabradine slows heart rate by a unique mechanism that doesn’t involve blockade of adrenergic receptors. In the SHIFT trial (Lancet. 2010 Sep 11;376[9744]:875-85), more than 6,500 patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate greater than 70 bpm were randomized to ivabradine or placebo on top of guideline-directed medical therapy for heart failure. During a median 23 months of follow-up, heart failure hospitalizations were significantly reduced by 26% in the ivabradine group, although cardiovascular deaths were not significantly affected.
As a result of the SHIFT findings, the drug was approved with an indication for use only in combination with a beta-blocker in patients with HFrEF whose on-treatment heart rate exceeds 70 bpm. Ivabradine is not currently recommended as an alternative to beta-blocker therapy. However, in real-world clinical practice a large number of heart failure patients are not managed with a beta-blocker, the cardiologist noted.
His post-hoc analysis focused on the 685 SHIFT participants who were not on a beta-blocker at randomization. During follow-up, there were 93 deaths among patients who were on placebo and only 71 in those randomized to ivabradine, for a statistically significant 30% reduction in all-cause mortality. Cardiovascular mortality was reduced to a similar extent. These hazard ratios remained similar after adjusting for differences in heart rate and other clinical characteristics.
“Beta-blockers are a highly effective therapy for heart failure with reduced ejection fraction, but the mechanism of benefit remains uncertain. It might simply be due to heart rate reduction. And I would point out that we have no evidence of a dose response for beta-blockers: It may well be that you get most of the effect of a beta-blocker with the lowest dose. Titrating to the full dose of a beta-blocker might only be helpful in that it lowers your heart rate. I would argue that 6.25 mg/day of carvedilol plus ivabradine might be as good as 50 mg twice daily of carvedilol but with much higher patient acceptability. We don’t know,” said Dr. Cleland.
“This is an interesting, hypothesis-generating analysis, and we need confirmation now that ivabradine reduces mortality in heart failure patients who are unwilling or unable to take a beta-blocker,” he concluded.
The SHIFT trial was sponsored by Servier. Dr. Cleland reported serving as a consultant to and receiving research funding from that company and others.
BARCELONA – The time is right for a placebo-controlled, randomized trial of ivabradine in patients with heart failure with reduced ejection fraction who are unwilling or unable to take a beta-blocker as recommended in the guidelines, John G.F. Cleland, MD, asserted at the annual congress of the European Society of Cardiology.
He cited as the rationale for such a study a new post-hoc analysis of data from the SHIFT trial showing that ivabradine (Corlanor) significantly reduced both cardiovascular and all-cause mortality, as well as hospitalizations for heart failure, in the subset of study participants who weren’t on beta-blocker therapy.
“I think there would be ethical equipoise,” he added. “If patients are unwilling or unable to take a beta-blocker, or their cardiologist feels it’s not in their best interest, then I certainly think a placebo-controlled trial would not only be appropriate, but there’s also an onus on the cardiology community to do such a trial.”
Ivabradine slows heart rate by a unique mechanism that doesn’t involve blockade of adrenergic receptors. In the SHIFT trial (Lancet. 2010 Sep 11;376[9744]:875-85), more than 6,500 patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate greater than 70 bpm were randomized to ivabradine or placebo on top of guideline-directed medical therapy for heart failure. During a median 23 months of follow-up, heart failure hospitalizations were significantly reduced by 26% in the ivabradine group, although cardiovascular deaths were not significantly affected.
As a result of the SHIFT findings, the drug was approved with an indication for use only in combination with a beta-blocker in patients with HFrEF whose on-treatment heart rate exceeds 70 bpm. Ivabradine is not currently recommended as an alternative to beta-blocker therapy. However, in real-world clinical practice a large number of heart failure patients are not managed with a beta-blocker, the cardiologist noted.
His post-hoc analysis focused on the 685 SHIFT participants who were not on a beta-blocker at randomization. During follow-up, there were 93 deaths among patients who were on placebo and only 71 in those randomized to ivabradine, for a statistically significant 30% reduction in all-cause mortality. Cardiovascular mortality was reduced to a similar extent. These hazard ratios remained similar after adjusting for differences in heart rate and other clinical characteristics.
“Beta-blockers are a highly effective therapy for heart failure with reduced ejection fraction, but the mechanism of benefit remains uncertain. It might simply be due to heart rate reduction. And I would point out that we have no evidence of a dose response for beta-blockers: It may well be that you get most of the effect of a beta-blocker with the lowest dose. Titrating to the full dose of a beta-blocker might only be helpful in that it lowers your heart rate. I would argue that 6.25 mg/day of carvedilol plus ivabradine might be as good as 50 mg twice daily of carvedilol but with much higher patient acceptability. We don’t know,” said Dr. Cleland.
“This is an interesting, hypothesis-generating analysis, and we need confirmation now that ivabradine reduces mortality in heart failure patients who are unwilling or unable to take a beta-blocker,” he concluded.
The SHIFT trial was sponsored by Servier. Dr. Cleland reported serving as a consultant to and receiving research funding from that company and others.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: All-cause mortality was reduced by 30%, compared with placebo, in ivabradine-treated patients with heart failure with reduced ejection fraction who were not on a beta-blocker.
Data source: A post-hoc analysis of the 685 patients in a much larger randomized, placebo-controlled clinical trial of ivabradine in patients with heart failure with reduced ejection fraction.
Disclosures: The SHIFT trial was funded by Servier. The presenter reported serving as a consultant to and recipient of research grants from that and other companies.
Preventive upstream therapy prevents progression of atrial fib
BARCELONA – Aggressive treatment of known risk factors for atrial fibrillation resulted in improved 1-year maintenance of sinus rhythm in patients with recent-onset atrial fibrillation and heart failure in the randomized multicenter RACE 3 trial, Isabelle C. van Gelder, MD, reported at the annual congress of the European Society of Cardiology.
“We now screen for AF, making it possible to catch patients early. That’s what we’ve learned from this trial: if we start treating patients after their first episode of AF and aggressively reduce risk factors for AF, it may help the sinus rhythm. I think that’s an important message: do not wait too long, start treatment early,” said Dr. van Gelder, professor of cardiology at the University of Groningen, the Netherlands.
She calls the interventional strategy tested in RACE 3 “risk factor-driven upstream therapy.” The four-pronged strategy consisted of statin therapy, a mineralcorticoid receptor antagonist, an ACE inhibitor and/or an angiotensin receptor blocker, and a 9- to 11-week supervised cardiac rehabilitation program emphasizing lifestyle modification through physical training and dietary changes supported by professional counseling to promote adherence.
“These are interventions designed to improve the atrial substrate,” Dr. van Gelder explained.
RACE 3 (Routine versus Aggressive Upstream Rhythm Control for Prevention of Early Atrial Fibrillation in Heart Failure 3) was a multicenter, randomized, nonblinded clinical trial including 245 patients with, on average, a 3-month history of AF, a 2-month history of persistent AF, and a 2-month history of mild to moderate heart failure, either with preserved or reduced ejection fraction. All participants received guideline-directed rhythm control and heart failure therapies. In addition, half of participants were randomized to the upstream intervention. Three weeks after enrollment, all patients underwent electrical cardioversion.
The primary outcome was maintenance of sinus rhythm at 1 year as determined by 7-day Holter monitoring analyzed in blinded fashion at a central laboratory. The rate was 75% in the upstream intervention group, significantly better than the 63% in controls. This represented a 76% greater likelihood of sinus rhythm at 1 year in the upstream intervention group. They also showed significant reductions in systolic and diastolic blood pressure, N-terminal pro-brain natriuretic peptide, and LDL cholesterol, compared with controls. However, at 1 year, the two groups didn’t differ significantly in body mass index or left atrial volume. The lack of impact on left atrial volume was disappointing, Dr. van Gelder said.
“The remodeling process starts long before the first episode of AF, although we don’t know exactly when. Although we intended to intervene early in the remodeling process, I think we weren’t that early,” according to the cardiologist.
Discussant Josep Brugada, MD, applauded the Dutch investigators for opening the door to evidence-based preventive upstream therapy for AF, which he declared is vital given the worsening AF epidemic.
“In recent years enormous efforts have been put into treating symptoms of AF, but clearly we have failed to control the epidemic of AF in our societies, probably because we’ve been aiming only at treating symptoms, not treating the causes,” observed Dr. Brugada of the University of Barcelona.
He added, however, that the RACE 3 intervention didn’t go far enough.
“It’s a bit of a disappointment that there is no change in BMI seen after 1 year. Zero. That probably means the rehabilitation program wasn’t strong enough. Yet, the study results are positive, so if we used physical training in a stronger way to get a reduction in body weight and BMI, probably the outcome would be even greater,” he said.
To be maximally effective, an upstream intervention for AF should also address two other important risk factors for the arrhythmia: heavy alcohol drinking and obstructive sleep apnea, the electrophysiologist added.
The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. Dr. van Gelder reported having no relevant financial interests.
Dr. van Gelder discussed the RACE 3 trial and results in a video interview.
BARCELONA – Aggressive treatment of known risk factors for atrial fibrillation resulted in improved 1-year maintenance of sinus rhythm in patients with recent-onset atrial fibrillation and heart failure in the randomized multicenter RACE 3 trial, Isabelle C. van Gelder, MD, reported at the annual congress of the European Society of Cardiology.
“We now screen for AF, making it possible to catch patients early. That’s what we’ve learned from this trial: if we start treating patients after their first episode of AF and aggressively reduce risk factors for AF, it may help the sinus rhythm. I think that’s an important message: do not wait too long, start treatment early,” said Dr. van Gelder, professor of cardiology at the University of Groningen, the Netherlands.
She calls the interventional strategy tested in RACE 3 “risk factor-driven upstream therapy.” The four-pronged strategy consisted of statin therapy, a mineralcorticoid receptor antagonist, an ACE inhibitor and/or an angiotensin receptor blocker, and a 9- to 11-week supervised cardiac rehabilitation program emphasizing lifestyle modification through physical training and dietary changes supported by professional counseling to promote adherence.
“These are interventions designed to improve the atrial substrate,” Dr. van Gelder explained.
RACE 3 (Routine versus Aggressive Upstream Rhythm Control for Prevention of Early Atrial Fibrillation in Heart Failure 3) was a multicenter, randomized, nonblinded clinical trial including 245 patients with, on average, a 3-month history of AF, a 2-month history of persistent AF, and a 2-month history of mild to moderate heart failure, either with preserved or reduced ejection fraction. All participants received guideline-directed rhythm control and heart failure therapies. In addition, half of participants were randomized to the upstream intervention. Three weeks after enrollment, all patients underwent electrical cardioversion.
The primary outcome was maintenance of sinus rhythm at 1 year as determined by 7-day Holter monitoring analyzed in blinded fashion at a central laboratory. The rate was 75% in the upstream intervention group, significantly better than the 63% in controls. This represented a 76% greater likelihood of sinus rhythm at 1 year in the upstream intervention group. They also showed significant reductions in systolic and diastolic blood pressure, N-terminal pro-brain natriuretic peptide, and LDL cholesterol, compared with controls. However, at 1 year, the two groups didn’t differ significantly in body mass index or left atrial volume. The lack of impact on left atrial volume was disappointing, Dr. van Gelder said.
“The remodeling process starts long before the first episode of AF, although we don’t know exactly when. Although we intended to intervene early in the remodeling process, I think we weren’t that early,” according to the cardiologist.
Discussant Josep Brugada, MD, applauded the Dutch investigators for opening the door to evidence-based preventive upstream therapy for AF, which he declared is vital given the worsening AF epidemic.
“In recent years enormous efforts have been put into treating symptoms of AF, but clearly we have failed to control the epidemic of AF in our societies, probably because we’ve been aiming only at treating symptoms, not treating the causes,” observed Dr. Brugada of the University of Barcelona.
He added, however, that the RACE 3 intervention didn’t go far enough.
“It’s a bit of a disappointment that there is no change in BMI seen after 1 year. Zero. That probably means the rehabilitation program wasn’t strong enough. Yet, the study results are positive, so if we used physical training in a stronger way to get a reduction in body weight and BMI, probably the outcome would be even greater,” he said.
To be maximally effective, an upstream intervention for AF should also address two other important risk factors for the arrhythmia: heavy alcohol drinking and obstructive sleep apnea, the electrophysiologist added.
The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. Dr. van Gelder reported having no relevant financial interests.
Dr. van Gelder discussed the RACE 3 trial and results in a video interview.
BARCELONA – Aggressive treatment of known risk factors for atrial fibrillation resulted in improved 1-year maintenance of sinus rhythm in patients with recent-onset atrial fibrillation and heart failure in the randomized multicenter RACE 3 trial, Isabelle C. van Gelder, MD, reported at the annual congress of the European Society of Cardiology.
“We now screen for AF, making it possible to catch patients early. That’s what we’ve learned from this trial: if we start treating patients after their first episode of AF and aggressively reduce risk factors for AF, it may help the sinus rhythm. I think that’s an important message: do not wait too long, start treatment early,” said Dr. van Gelder, professor of cardiology at the University of Groningen, the Netherlands.
She calls the interventional strategy tested in RACE 3 “risk factor-driven upstream therapy.” The four-pronged strategy consisted of statin therapy, a mineralcorticoid receptor antagonist, an ACE inhibitor and/or an angiotensin receptor blocker, and a 9- to 11-week supervised cardiac rehabilitation program emphasizing lifestyle modification through physical training and dietary changes supported by professional counseling to promote adherence.
“These are interventions designed to improve the atrial substrate,” Dr. van Gelder explained.
RACE 3 (Routine versus Aggressive Upstream Rhythm Control for Prevention of Early Atrial Fibrillation in Heart Failure 3) was a multicenter, randomized, nonblinded clinical trial including 245 patients with, on average, a 3-month history of AF, a 2-month history of persistent AF, and a 2-month history of mild to moderate heart failure, either with preserved or reduced ejection fraction. All participants received guideline-directed rhythm control and heart failure therapies. In addition, half of participants were randomized to the upstream intervention. Three weeks after enrollment, all patients underwent electrical cardioversion.
The primary outcome was maintenance of sinus rhythm at 1 year as determined by 7-day Holter monitoring analyzed in blinded fashion at a central laboratory. The rate was 75% in the upstream intervention group, significantly better than the 63% in controls. This represented a 76% greater likelihood of sinus rhythm at 1 year in the upstream intervention group. They also showed significant reductions in systolic and diastolic blood pressure, N-terminal pro-brain natriuretic peptide, and LDL cholesterol, compared with controls. However, at 1 year, the two groups didn’t differ significantly in body mass index or left atrial volume. The lack of impact on left atrial volume was disappointing, Dr. van Gelder said.
“The remodeling process starts long before the first episode of AF, although we don’t know exactly when. Although we intended to intervene early in the remodeling process, I think we weren’t that early,” according to the cardiologist.
Discussant Josep Brugada, MD, applauded the Dutch investigators for opening the door to evidence-based preventive upstream therapy for AF, which he declared is vital given the worsening AF epidemic.
“In recent years enormous efforts have been put into treating symptoms of AF, but clearly we have failed to control the epidemic of AF in our societies, probably because we’ve been aiming only at treating symptoms, not treating the causes,” observed Dr. Brugada of the University of Barcelona.
He added, however, that the RACE 3 intervention didn’t go far enough.
“It’s a bit of a disappointment that there is no change in BMI seen after 1 year. Zero. That probably means the rehabilitation program wasn’t strong enough. Yet, the study results are positive, so if we used physical training in a stronger way to get a reduction in body weight and BMI, probably the outcome would be even greater,” he said.
To be maximally effective, an upstream intervention for AF should also address two other important risk factors for the arrhythmia: heavy alcohol drinking and obstructive sleep apnea, the electrophysiologist added.
The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. Dr. van Gelder reported having no relevant financial interests.
Dr. van Gelder discussed the RACE 3 trial and results in a video interview.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: At 1 year, 75% of patients with baseline persistent atrial fibrillation who received a four-pronged program of upstream risk factor modification were in sinus rhythm, compared with 63% of controls.
Data source: RACE 3 was a multicenter, randomized, nonblinded clinical trial including 245 patients with a recent history of persistent atrial fibrillation and heart failure.
Disclosures: The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. The presenter reported having no relevant financial interests.
Big risk of serious falls after first episode of syncope
BARCELONA – Patients have an exorbitant 80% increased risk of hospitalization for falls resulting in fracture or head injury in the first year after discharge following a first-ever episode of syncope, according to a Danish national cohort study. One in five patients who sustained a fall resulting in hospitalization experienced a hip fracture, according to Anna-Karin Nume, MD, of the University of Copenhagen.
In this interview at the annual congress of the European Society of Cardiology, Dr. Nume highlights findings from her study, which included 125,763 Danish adults with first-time syncope.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BARCELONA – Patients have an exorbitant 80% increased risk of hospitalization for falls resulting in fracture or head injury in the first year after discharge following a first-ever episode of syncope, according to a Danish national cohort study. One in five patients who sustained a fall resulting in hospitalization experienced a hip fracture, according to Anna-Karin Nume, MD, of the University of Copenhagen.
In this interview at the annual congress of the European Society of Cardiology, Dr. Nume highlights findings from her study, which included 125,763 Danish adults with first-time syncope.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BARCELONA – Patients have an exorbitant 80% increased risk of hospitalization for falls resulting in fracture or head injury in the first year after discharge following a first-ever episode of syncope, according to a Danish national cohort study. One in five patients who sustained a fall resulting in hospitalization experienced a hip fracture, according to Anna-Karin Nume, MD, of the University of Copenhagen.
In this interview at the annual congress of the European Society of Cardiology, Dr. Nume highlights findings from her study, which included 125,763 Danish adults with first-time syncope.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ESC CONGRESS 2017
Despite global decline, rheumatic heart disease persists in poorest regions
Global mortality due to rheumatic heart disease fell by about 48% during a recent 25-year-period, but some of the poorest areas of the world were left behind, according to a report in the New England Journal of Medicine.
Those regions included Oceania, South Asia, and central sub-Saharan Africa, where rheumatic heart disease remains endemic, wrote David A. Watkins, MD, MPH, of the University of Washington, Seattle, and his coinvestigators. “We estimate that 10 persons per 1,000 population living in South Asia and central sub-Saharan Africa and 15 persons per 1,000 population in Oceania were living with rheumatic heart disease in the year 2015,” they wrote. “Improvements in the measurement of the burden of rheumatic heart disease will assist in planning for its control and will help identify countries where further investments are needed.”
To better define the problem, Dr. Watkins and his associates analyzed epidemiologic studies of rheumatic heart disease from 1990 through 2015. They used the Cause of Death Ensemble model, which estimates mortality more reliably than older methods, and DisMod-MR (version 2.1), which sums epidemiologic data from multiple sources and corrects for gaps and inconsistencies (N Engl J Med. 2017;377:713-22).
Worldwide, about 319,400 individuals died of rheumatic heart disease in 2015, the researchers reported. Age-adjusted death rates fell by about 48% (95% confidence interval, 45%-51%), from 9.2 deaths per 100,000 population in 1990 to 4.8 deaths per 100,000 population in 2015. But this global trend masked striking regional disparities. In 1990, 77% of deaths from rheumatic heart disease occurred in endemic areas of Africa, South Asia, Oceania, and the Caribbean; by 2015, 82% of deaths occurred in endemic regions. Oceania, South Asia, and central sub-Saharan Africa had the highest death rates and were the only regions where the 95% confidence intervals for 1990 and 2015 overlapped, the investigators noted.
In 2015, age-standardized death rates exceeded 10 deaths per 100,000 population in the Solomon Islands, Pakistan, Papua New Guinea, Kiribati, Vanuatu, Fiji, India, Federated States of Micronesia, Marshall Islands, Central African Republic, and Lesotho, they reported. Estimated fatalities were highest in India (119,100 deaths), China (72,600), and Pakistan (18,900). They estimated that in 2015, there were 33.2 million cases of rheumatic heart disease and 10.5 million associated disability-adjusted life-years globally.
The study excluded “borderline” or subclinical rheumatic heart disease, which is detected by echocardiography and whose management remains unclear. “Better data for low-income and middle-income countries are needed to guide policies for the control of rheumatic heart disease,” the investigators wrote. They recommended studying death certificate misclassifications, disease prevalence among adults, and longitudinal trends in nonfatal outcomes and excess mortality.
Funders of the study included the Bill and Melinda Gates Foundation and the Medtronic Foundation. Dr. Watkins disclosed grants from the Medtronic Foundation during the conduct of the study and grants from the Bill and Melinda Gates Foundation outside the submitted work.
Rheumatic heart disease ranks as one of the most serious cardiovascular scourges of the past century. As a result of improvements in living conditions and the introduction of penicillin, the disease was almost eradicated in the developed world by the 1980s. However, it remains a force to be reckoned with in the developing world, as demonstrated by an assessment from the 2015 Global Burden of Disease study (GBD 2015), painstakingly performed by Dr. Watkins and his colleagues.
Several key messages emerge from this important study. It confirms the marked global heterogeneity of the burden of rheumatic heart disease, with near-zero prevalence in developed countries sharply contrasting with substantial prevalence and mortality in developing areas. In addition, however, the study documents the scarcity of accurately measured data in many locations, especially in areas with the highest prevalence (such as sub-Saharan Africa).
Although the “headline news” of a global decline in the prevalence of rheumatic heart disease described by Watkins et al. may give cause for optimism, the burden remains great for those parts of the world least able to afford it. Without sustained re-engagement of clinicians, researchers, funders, and public health bodies, the menace of rheumatic heart disease is unlikely to be eliminated in the near future. Rheumatic heart disease remains a problematic iceberg, yet undissolved, in warm tropical waters.
Eloi Marijon, MD, PhD, and Xavier Jouven, MD, PhD, are at European Georges Pompidou Hospital, Paris. David S. Celermajer, PhD, is at Sydney (Australia) Medical School. They reported having no conflicts of interest. Their editorial accompanied the report by Dr. Watkins and his colleagues (N Engl J Med. 2017;377:780-1).
Rheumatic heart disease ranks as one of the most serious cardiovascular scourges of the past century. As a result of improvements in living conditions and the introduction of penicillin, the disease was almost eradicated in the developed world by the 1980s. However, it remains a force to be reckoned with in the developing world, as demonstrated by an assessment from the 2015 Global Burden of Disease study (GBD 2015), painstakingly performed by Dr. Watkins and his colleagues.
Several key messages emerge from this important study. It confirms the marked global heterogeneity of the burden of rheumatic heart disease, with near-zero prevalence in developed countries sharply contrasting with substantial prevalence and mortality in developing areas. In addition, however, the study documents the scarcity of accurately measured data in many locations, especially in areas with the highest prevalence (such as sub-Saharan Africa).
Although the “headline news” of a global decline in the prevalence of rheumatic heart disease described by Watkins et al. may give cause for optimism, the burden remains great for those parts of the world least able to afford it. Without sustained re-engagement of clinicians, researchers, funders, and public health bodies, the menace of rheumatic heart disease is unlikely to be eliminated in the near future. Rheumatic heart disease remains a problematic iceberg, yet undissolved, in warm tropical waters.
Eloi Marijon, MD, PhD, and Xavier Jouven, MD, PhD, are at European Georges Pompidou Hospital, Paris. David S. Celermajer, PhD, is at Sydney (Australia) Medical School. They reported having no conflicts of interest. Their editorial accompanied the report by Dr. Watkins and his colleagues (N Engl J Med. 2017;377:780-1).
Rheumatic heart disease ranks as one of the most serious cardiovascular scourges of the past century. As a result of improvements in living conditions and the introduction of penicillin, the disease was almost eradicated in the developed world by the 1980s. However, it remains a force to be reckoned with in the developing world, as demonstrated by an assessment from the 2015 Global Burden of Disease study (GBD 2015), painstakingly performed by Dr. Watkins and his colleagues.
Several key messages emerge from this important study. It confirms the marked global heterogeneity of the burden of rheumatic heart disease, with near-zero prevalence in developed countries sharply contrasting with substantial prevalence and mortality in developing areas. In addition, however, the study documents the scarcity of accurately measured data in many locations, especially in areas with the highest prevalence (such as sub-Saharan Africa).
Although the “headline news” of a global decline in the prevalence of rheumatic heart disease described by Watkins et al. may give cause for optimism, the burden remains great for those parts of the world least able to afford it. Without sustained re-engagement of clinicians, researchers, funders, and public health bodies, the menace of rheumatic heart disease is unlikely to be eliminated in the near future. Rheumatic heart disease remains a problematic iceberg, yet undissolved, in warm tropical waters.
Eloi Marijon, MD, PhD, and Xavier Jouven, MD, PhD, are at European Georges Pompidou Hospital, Paris. David S. Celermajer, PhD, is at Sydney (Australia) Medical School. They reported having no conflicts of interest. Their editorial accompanied the report by Dr. Watkins and his colleagues (N Engl J Med. 2017;377:780-1).
Global mortality due to rheumatic heart disease fell by about 48% during a recent 25-year-period, but some of the poorest areas of the world were left behind, according to a report in the New England Journal of Medicine.
Those regions included Oceania, South Asia, and central sub-Saharan Africa, where rheumatic heart disease remains endemic, wrote David A. Watkins, MD, MPH, of the University of Washington, Seattle, and his coinvestigators. “We estimate that 10 persons per 1,000 population living in South Asia and central sub-Saharan Africa and 15 persons per 1,000 population in Oceania were living with rheumatic heart disease in the year 2015,” they wrote. “Improvements in the measurement of the burden of rheumatic heart disease will assist in planning for its control and will help identify countries where further investments are needed.”
To better define the problem, Dr. Watkins and his associates analyzed epidemiologic studies of rheumatic heart disease from 1990 through 2015. They used the Cause of Death Ensemble model, which estimates mortality more reliably than older methods, and DisMod-MR (version 2.1), which sums epidemiologic data from multiple sources and corrects for gaps and inconsistencies (N Engl J Med. 2017;377:713-22).
Worldwide, about 319,400 individuals died of rheumatic heart disease in 2015, the researchers reported. Age-adjusted death rates fell by about 48% (95% confidence interval, 45%-51%), from 9.2 deaths per 100,000 population in 1990 to 4.8 deaths per 100,000 population in 2015. But this global trend masked striking regional disparities. In 1990, 77% of deaths from rheumatic heart disease occurred in endemic areas of Africa, South Asia, Oceania, and the Caribbean; by 2015, 82% of deaths occurred in endemic regions. Oceania, South Asia, and central sub-Saharan Africa had the highest death rates and were the only regions where the 95% confidence intervals for 1990 and 2015 overlapped, the investigators noted.
In 2015, age-standardized death rates exceeded 10 deaths per 100,000 population in the Solomon Islands, Pakistan, Papua New Guinea, Kiribati, Vanuatu, Fiji, India, Federated States of Micronesia, Marshall Islands, Central African Republic, and Lesotho, they reported. Estimated fatalities were highest in India (119,100 deaths), China (72,600), and Pakistan (18,900). They estimated that in 2015, there were 33.2 million cases of rheumatic heart disease and 10.5 million associated disability-adjusted life-years globally.
The study excluded “borderline” or subclinical rheumatic heart disease, which is detected by echocardiography and whose management remains unclear. “Better data for low-income and middle-income countries are needed to guide policies for the control of rheumatic heart disease,” the investigators wrote. They recommended studying death certificate misclassifications, disease prevalence among adults, and longitudinal trends in nonfatal outcomes and excess mortality.
Funders of the study included the Bill and Melinda Gates Foundation and the Medtronic Foundation. Dr. Watkins disclosed grants from the Medtronic Foundation during the conduct of the study and grants from the Bill and Melinda Gates Foundation outside the submitted work.
Global mortality due to rheumatic heart disease fell by about 48% during a recent 25-year-period, but some of the poorest areas of the world were left behind, according to a report in the New England Journal of Medicine.
Those regions included Oceania, South Asia, and central sub-Saharan Africa, where rheumatic heart disease remains endemic, wrote David A. Watkins, MD, MPH, of the University of Washington, Seattle, and his coinvestigators. “We estimate that 10 persons per 1,000 population living in South Asia and central sub-Saharan Africa and 15 persons per 1,000 population in Oceania were living with rheumatic heart disease in the year 2015,” they wrote. “Improvements in the measurement of the burden of rheumatic heart disease will assist in planning for its control and will help identify countries where further investments are needed.”
To better define the problem, Dr. Watkins and his associates analyzed epidemiologic studies of rheumatic heart disease from 1990 through 2015. They used the Cause of Death Ensemble model, which estimates mortality more reliably than older methods, and DisMod-MR (version 2.1), which sums epidemiologic data from multiple sources and corrects for gaps and inconsistencies (N Engl J Med. 2017;377:713-22).
Worldwide, about 319,400 individuals died of rheumatic heart disease in 2015, the researchers reported. Age-adjusted death rates fell by about 48% (95% confidence interval, 45%-51%), from 9.2 deaths per 100,000 population in 1990 to 4.8 deaths per 100,000 population in 2015. But this global trend masked striking regional disparities. In 1990, 77% of deaths from rheumatic heart disease occurred in endemic areas of Africa, South Asia, Oceania, and the Caribbean; by 2015, 82% of deaths occurred in endemic regions. Oceania, South Asia, and central sub-Saharan Africa had the highest death rates and were the only regions where the 95% confidence intervals for 1990 and 2015 overlapped, the investigators noted.
In 2015, age-standardized death rates exceeded 10 deaths per 100,000 population in the Solomon Islands, Pakistan, Papua New Guinea, Kiribati, Vanuatu, Fiji, India, Federated States of Micronesia, Marshall Islands, Central African Republic, and Lesotho, they reported. Estimated fatalities were highest in India (119,100 deaths), China (72,600), and Pakistan (18,900). They estimated that in 2015, there were 33.2 million cases of rheumatic heart disease and 10.5 million associated disability-adjusted life-years globally.
The study excluded “borderline” or subclinical rheumatic heart disease, which is detected by echocardiography and whose management remains unclear. “Better data for low-income and middle-income countries are needed to guide policies for the control of rheumatic heart disease,” the investigators wrote. They recommended studying death certificate misclassifications, disease prevalence among adults, and longitudinal trends in nonfatal outcomes and excess mortality.
Funders of the study included the Bill and Melinda Gates Foundation and the Medtronic Foundation. Dr. Watkins disclosed grants from the Medtronic Foundation during the conduct of the study and grants from the Bill and Melinda Gates Foundation outside the submitted work.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Globally, age-adjusted death rates fell by about 48% between 1990 and 2015. Oceania, South Asia, and central sub-Saharan Africa had the highest death rates in 2015, and were the only regions where the 95% confidence intervals overlapped with those for 1990.
Data source: A systematic review and analysis of morbidity and mortality data from 1990 through 2015.
Disclosures: Funders included the Bill and Melinda Gates Foundation and the Medtronic Foundation. Dr. Watkins disclosed grants from the Medtronic Foundation during the conduct of the study and grants from the Bill and Melinda Gates Foundation outside the submitted work.
First trial of TAVR vs. SAVR in low-risk patients
PARIS – Five-year hemodynamic results of the first randomized trial of transcatheter versus surgical aortic valve replacement in low-surgical-risk patients with severe aortic stenosis showed continued superior valve performance in the TAVR group, Lars Sondergaard, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“The durability results are very encouraging. We can’t see that the TAVR patients are doing worse. So I think this is setting the scene to try to move forward in patients at low risk and also in younger patients,” declared Dr. Sondergaard, professor of cardiology at the University of Copenhagen.
He presented an update from the Nordic Aortic Valve Intervention (NOTION) trial, a prospective, multicenter, randomized, all-comers clinical trial in which 280 patients with symptomatic severe aortic stenosis at low surgical risk were assigned to surgical aortic valve replacement (SAVR) or to TAVR with the self-expanding CoreValve. Their mean age was 79 years, with an average Society of Thoracic Surgeons projected risk of mortality score of 3%. Eighty-two percent of participants had an STS score below 4%. Roughly 40% of TAVR patients got the first-generation CoreValve in the 26-mm size, 40% received the 29-mm version, and the rest got the 31-mm CoreValve.
Among patients in the lowest-surgical-risk and youngest subgroup – those aged 70-75 with a Society of Thoracic Surgeons risk score below 4% – the composite primary endpoint rate at 4 years was 15.6% with TAVR compared with 27.2% with SAVR. However, only 62 NOTION participants fell into this category, so the between-group difference, while sizable, didn’t achieve statistical significance, according to Dr. Sondergaard.
There was a trade-off between the two valve replacement strategies with regard to procedural complications. The rate of new-onset atrial fibrillation was far higher in the SAVR group: 59.4% at 1 year and 60.2% at 4 years of follow-up, compared with 21.2% and 24.5% at 1 and 4 years, respectively, in the TAVR group.
On the other hand, 38% of the TAVR patients got a new pacemaker within the first year of follow-up, compared with only 2.4% in the SAVR group. At 4 years, 43.7% of the TAVR group had a pacemaker, versus 9% of the SAVR group.
Turning to the hemodynamic data, the cardiologist noted that the effective orifice area in the TAVR group went from 0.71 cm2 at baseline to 1.66 at 1 year and remained steady thereafter at 1.67 cm2 through 5 years. The TAVR group’s mean gradient improved from 45.4 mm Hg at baseline to 8.6 mm Hg at 1 year and 7.9 mm Hg at 5 years. These outcomes were significantly better than in the SAVR group, where the effective orifice area went from 0.74 cm2 at baseline to 1.32 at 1 year and 1.24 cm2 at 5 years, while the mean gradient fell from 44.9 mm Hg to 12.5 at 1 year and 13.6 mm Hg at 5 years.
Moderate hemodynamic structural valve deterioration was significantly more common in the SAVR group: 20.7% at 5 years, compared with 2.9% in the TAVR patients. The opposite was true with regard to moderate paravalvular leak, which occurred in 20.9% of the TAVI group but only 1.5% of SAVR patients.
Late complications were rare following either procedure. There were no cases of valve thrombosis through 5 years. The incidence of endocarditis at 5 years was 4.3% in the TAVR patients and similar at 5.9% in the SAVR group.
Discussant Samer Mansour, MD, of the University of Montreal, remarked that the rate of new pacemaker implantation following TAVR seemed extraordinarily high.
“This was early days,” Dr. Sondergaard explained. “We had a lower threshold for putting in a pacemaker and we put the valves in a little deeper.”
About half of new pacemaker recipients didn’t use the device after the first year, he added. Also, neither getting a new pacemaker nor moderate paravalvular leak was associated with increased mortality in the TAVR group.
Dr. Mansour observed that subtle but real differences in mortality probably wouldn’t show up in a 280-patient trial. Dr. Sondergaard concurred.
“We designed the NOTION trial in 2008-2009. Knowing what we know now, we should have had a larger study, but at that time TAVR volume wasn’t that big and it wasn’t realistic as a Nordic trial to include 1,000 patients. This was the best we could do,” he said.
Follow-up in the NOTION study will continue out to 10 years.
The study is funded by Medtronic. Dr. Sondergaard reported serving as a consultant to and receiving research grant support from the company.
PARIS – Five-year hemodynamic results of the first randomized trial of transcatheter versus surgical aortic valve replacement in low-surgical-risk patients with severe aortic stenosis showed continued superior valve performance in the TAVR group, Lars Sondergaard, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“The durability results are very encouraging. We can’t see that the TAVR patients are doing worse. So I think this is setting the scene to try to move forward in patients at low risk and also in younger patients,” declared Dr. Sondergaard, professor of cardiology at the University of Copenhagen.
He presented an update from the Nordic Aortic Valve Intervention (NOTION) trial, a prospective, multicenter, randomized, all-comers clinical trial in which 280 patients with symptomatic severe aortic stenosis at low surgical risk were assigned to surgical aortic valve replacement (SAVR) or to TAVR with the self-expanding CoreValve. Their mean age was 79 years, with an average Society of Thoracic Surgeons projected risk of mortality score of 3%. Eighty-two percent of participants had an STS score below 4%. Roughly 40% of TAVR patients got the first-generation CoreValve in the 26-mm size, 40% received the 29-mm version, and the rest got the 31-mm CoreValve.
Among patients in the lowest-surgical-risk and youngest subgroup – those aged 70-75 with a Society of Thoracic Surgeons risk score below 4% – the composite primary endpoint rate at 4 years was 15.6% with TAVR compared with 27.2% with SAVR. However, only 62 NOTION participants fell into this category, so the between-group difference, while sizable, didn’t achieve statistical significance, according to Dr. Sondergaard.
There was a trade-off between the two valve replacement strategies with regard to procedural complications. The rate of new-onset atrial fibrillation was far higher in the SAVR group: 59.4% at 1 year and 60.2% at 4 years of follow-up, compared with 21.2% and 24.5% at 1 and 4 years, respectively, in the TAVR group.
On the other hand, 38% of the TAVR patients got a new pacemaker within the first year of follow-up, compared with only 2.4% in the SAVR group. At 4 years, 43.7% of the TAVR group had a pacemaker, versus 9% of the SAVR group.
Turning to the hemodynamic data, the cardiologist noted that the effective orifice area in the TAVR group went from 0.71 cm2 at baseline to 1.66 at 1 year and remained steady thereafter at 1.67 cm2 through 5 years. The TAVR group’s mean gradient improved from 45.4 mm Hg at baseline to 8.6 mm Hg at 1 year and 7.9 mm Hg at 5 years. These outcomes were significantly better than in the SAVR group, where the effective orifice area went from 0.74 cm2 at baseline to 1.32 at 1 year and 1.24 cm2 at 5 years, while the mean gradient fell from 44.9 mm Hg to 12.5 at 1 year and 13.6 mm Hg at 5 years.
Moderate hemodynamic structural valve deterioration was significantly more common in the SAVR group: 20.7% at 5 years, compared with 2.9% in the TAVR patients. The opposite was true with regard to moderate paravalvular leak, which occurred in 20.9% of the TAVI group but only 1.5% of SAVR patients.
Late complications were rare following either procedure. There were no cases of valve thrombosis through 5 years. The incidence of endocarditis at 5 years was 4.3% in the TAVR patients and similar at 5.9% in the SAVR group.
Discussant Samer Mansour, MD, of the University of Montreal, remarked that the rate of new pacemaker implantation following TAVR seemed extraordinarily high.
“This was early days,” Dr. Sondergaard explained. “We had a lower threshold for putting in a pacemaker and we put the valves in a little deeper.”
About half of new pacemaker recipients didn’t use the device after the first year, he added. Also, neither getting a new pacemaker nor moderate paravalvular leak was associated with increased mortality in the TAVR group.
Dr. Mansour observed that subtle but real differences in mortality probably wouldn’t show up in a 280-patient trial. Dr. Sondergaard concurred.
“We designed the NOTION trial in 2008-2009. Knowing what we know now, we should have had a larger study, but at that time TAVR volume wasn’t that big and it wasn’t realistic as a Nordic trial to include 1,000 patients. This was the best we could do,” he said.
Follow-up in the NOTION study will continue out to 10 years.
The study is funded by Medtronic. Dr. Sondergaard reported serving as a consultant to and receiving research grant support from the company.
PARIS – Five-year hemodynamic results of the first randomized trial of transcatheter versus surgical aortic valve replacement in low-surgical-risk patients with severe aortic stenosis showed continued superior valve performance in the TAVR group, Lars Sondergaard, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“The durability results are very encouraging. We can’t see that the TAVR patients are doing worse. So I think this is setting the scene to try to move forward in patients at low risk and also in younger patients,” declared Dr. Sondergaard, professor of cardiology at the University of Copenhagen.
He presented an update from the Nordic Aortic Valve Intervention (NOTION) trial, a prospective, multicenter, randomized, all-comers clinical trial in which 280 patients with symptomatic severe aortic stenosis at low surgical risk were assigned to surgical aortic valve replacement (SAVR) or to TAVR with the self-expanding CoreValve. Their mean age was 79 years, with an average Society of Thoracic Surgeons projected risk of mortality score of 3%. Eighty-two percent of participants had an STS score below 4%. Roughly 40% of TAVR patients got the first-generation CoreValve in the 26-mm size, 40% received the 29-mm version, and the rest got the 31-mm CoreValve.
Among patients in the lowest-surgical-risk and youngest subgroup – those aged 70-75 with a Society of Thoracic Surgeons risk score below 4% – the composite primary endpoint rate at 4 years was 15.6% with TAVR compared with 27.2% with SAVR. However, only 62 NOTION participants fell into this category, so the between-group difference, while sizable, didn’t achieve statistical significance, according to Dr. Sondergaard.
There was a trade-off between the two valve replacement strategies with regard to procedural complications. The rate of new-onset atrial fibrillation was far higher in the SAVR group: 59.4% at 1 year and 60.2% at 4 years of follow-up, compared with 21.2% and 24.5% at 1 and 4 years, respectively, in the TAVR group.
On the other hand, 38% of the TAVR patients got a new pacemaker within the first year of follow-up, compared with only 2.4% in the SAVR group. At 4 years, 43.7% of the TAVR group had a pacemaker, versus 9% of the SAVR group.
Turning to the hemodynamic data, the cardiologist noted that the effective orifice area in the TAVR group went from 0.71 cm2 at baseline to 1.66 at 1 year and remained steady thereafter at 1.67 cm2 through 5 years. The TAVR group’s mean gradient improved from 45.4 mm Hg at baseline to 8.6 mm Hg at 1 year and 7.9 mm Hg at 5 years. These outcomes were significantly better than in the SAVR group, where the effective orifice area went from 0.74 cm2 at baseline to 1.32 at 1 year and 1.24 cm2 at 5 years, while the mean gradient fell from 44.9 mm Hg to 12.5 at 1 year and 13.6 mm Hg at 5 years.
Moderate hemodynamic structural valve deterioration was significantly more common in the SAVR group: 20.7% at 5 years, compared with 2.9% in the TAVR patients. The opposite was true with regard to moderate paravalvular leak, which occurred in 20.9% of the TAVI group but only 1.5% of SAVR patients.
Late complications were rare following either procedure. There were no cases of valve thrombosis through 5 years. The incidence of endocarditis at 5 years was 4.3% in the TAVR patients and similar at 5.9% in the SAVR group.
Discussant Samer Mansour, MD, of the University of Montreal, remarked that the rate of new pacemaker implantation following TAVR seemed extraordinarily high.
“This was early days,” Dr. Sondergaard explained. “We had a lower threshold for putting in a pacemaker and we put the valves in a little deeper.”
About half of new pacemaker recipients didn’t use the device after the first year, he added. Also, neither getting a new pacemaker nor moderate paravalvular leak was associated with increased mortality in the TAVR group.
Dr. Mansour observed that subtle but real differences in mortality probably wouldn’t show up in a 280-patient trial. Dr. Sondergaard concurred.
“We designed the NOTION trial in 2008-2009. Knowing what we know now, we should have had a larger study, but at that time TAVR volume wasn’t that big and it wasn’t realistic as a Nordic trial to include 1,000 patients. This was the best we could do,” he said.
Follow-up in the NOTION study will continue out to 10 years.
The study is funded by Medtronic. Dr. Sondergaard reported serving as a consultant to and receiving research grant support from the company.
AT EuroPCR
Key clinical point:
Major finding: At 4 years of follow-up, the composite endpoint of all-cause mortality, MI, or stroke occurred in 29% of low-surgical-risk patients with severe aortic stenosis who were randomized to transcatheter aortic valve replacement (TAVR) and 30% of those who underwent surgical valve replacement.
Data source: NOTION, a prospective multicenter randomized trial in which 280 Nordic patients with symptomatic severe aortic stenosis at low surgical risk were assigned to surgical aortic valve replacement (SAVR) or to TAVR with the self-expanding CoreValve.
Disclosures: The study is funded by Medtronic. The presenter reported serving as a consultant to and receiving research grant support from the company.
FDA approves first spironolactone oral suspension
The Food and Drug Administration has approved CaroSpir, the first oral suspension form of spironolactone, the aldosterone antagonist that was first approved in 1960, according to an announcement from CMP Pharma.
CaroSpir is intended for the treatment of New York Heart Association class III-IV heart failure and reduced ejection fraction, usually in combination with other treatments. CaroSpir is also indicated as an add-on medication for the treatment of hypertension, and for the treatment of edema in cirrhotic patients who have not adequately responded to fluid and sodium restriction.
“CaroSpir provides a stable, ready to use, and consistent liquid treatment option for adult patients. Up until now, these patients have been prescribed a pharmacy-compounded liquid form of spironolactone. The dosing inconsistencies of compounded liquids have long been a persistent challenge for physicians,” Gerald Sakowski, CEO at CMP Pharma, said in the press release.
Find the full press release on the CMP Pharma website.
The Food and Drug Administration has approved CaroSpir, the first oral suspension form of spironolactone, the aldosterone antagonist that was first approved in 1960, according to an announcement from CMP Pharma.
CaroSpir is intended for the treatment of New York Heart Association class III-IV heart failure and reduced ejection fraction, usually in combination with other treatments. CaroSpir is also indicated as an add-on medication for the treatment of hypertension, and for the treatment of edema in cirrhotic patients who have not adequately responded to fluid and sodium restriction.
“CaroSpir provides a stable, ready to use, and consistent liquid treatment option for adult patients. Up until now, these patients have been prescribed a pharmacy-compounded liquid form of spironolactone. The dosing inconsistencies of compounded liquids have long been a persistent challenge for physicians,” Gerald Sakowski, CEO at CMP Pharma, said in the press release.
Find the full press release on the CMP Pharma website.
The Food and Drug Administration has approved CaroSpir, the first oral suspension form of spironolactone, the aldosterone antagonist that was first approved in 1960, according to an announcement from CMP Pharma.
CaroSpir is intended for the treatment of New York Heart Association class III-IV heart failure and reduced ejection fraction, usually in combination with other treatments. CaroSpir is also indicated as an add-on medication for the treatment of hypertension, and for the treatment of edema in cirrhotic patients who have not adequately responded to fluid and sodium restriction.
“CaroSpir provides a stable, ready to use, and consistent liquid treatment option for adult patients. Up until now, these patients have been prescribed a pharmacy-compounded liquid form of spironolactone. The dosing inconsistencies of compounded liquids have long been a persistent challenge for physicians,” Gerald Sakowski, CEO at CMP Pharma, said in the press release.
Find the full press release on the CMP Pharma website.