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Despite failed primary endpoint, MI alert device has predictive value
WASHINGTON –Although an implantable device for detecting myocardial infarction missed the primary composite outcome endpoint in a controlled trial, a newly completed extended analysis associated the device with a higher positive predictive value and a lower false positive rate when compared to sham control, according to data presented at CRT 2019, sponsored by MedStar Heart & Vascular Institute.
“Among high risk patients, this system may be beneficial in the identification of both symptomatic and asymptomatic coronary events,” reported C. Michael Gibson, MD, chief of clinical research in the cardiology division at Beth Israel Deaconess Hospital, Boston.
The implantable device (AngelMed Guardian System), which received Food and Drug Administration approval in April 2018, is designed to identify MI through detection of ST-segment elevations in the absence of an elevated heart rate. When the system detects an event during continuous monitoring, it sends a signal (internal vibration and auditory signal to an external monitor) designed to tell the patient to seek medical care.
The previously published multicenter and randomized ALERTS (AngelMed for Early Recognition and Treatment of STEMI) trial that tested this device was negative for primary composite endpoint of cardiac or unexplained death, new Q-wave MI, or presentation at the emergency department (ED) more than 2 hours after symptom onset (J Am Coll Cardiol. 2019 Feb 25. pii: S0735-1097[19]30237-2). In that trial 907 patients were fitted with the device and then randomized to having the device switched on or left off.
At 7 days, a primary endpoint was reached by 3.8% of those in the device-on group versus 4.9% of those in the device-off group, which was not significantly different.
Although the primary endpoint was not met, there were promising results. For example, in those who did have an occlusive event, patients in the device-on group had better preserved left ventricular function when evaluated after the event, a result consistent with earlier presentation in the ED and earlier treatment. In fact, 85% of patients with an MI in the device-on group presented to a hospital within 2 hours, compared with just 5% of those in the device-off control group during the initial study period.
More evidence of a potential clinical role for the device has now been generated in a new extended analysis. This analysis was made possible because patients in both of the randomized groups continue to wear the device, including those in the device-off group who had their devices activated after 6 months. There are now 3 more years of data of follow-up from those initially in the device-on group and those switched from the device-off group.
“So we started the clock over with a new statistical analysis plan and new endpoints,” Dr. Gibson explained. The FDA was consulted in selecting endpoints, particularly regarding evidence that the device did not increase false-positive ED visits.
There were numerous encouraging findings. One was that 42 silent MIs, which would otherwise have been missed, were detected over the extended follow-up. Another was that the annualized false-positive rate was lower in those with an activated device (0.164/year) when compared to the original device-off group (0.678/year; P less than .001). Lastly, the positive predictive value of an alarm during the extended follow-up was higher than that of symptoms alone among the original device-off group (25.8% vs. 18.2%).
The device was found safe. The rate of system-related complications was under 4%, which Dr. Gibson said is noninferior to that associated with pacemakers.
One of the potential explanations for the failure of the device to achieve the primary endpoint in the original trial was an unexpectedly low event rate, according to Dr. Gibson.
Even before this extended analysis, the FDA had accepted the potential benefits of this device as demonstrated in the approval last year. In the labeling, the device is called “a more accurate predictor of acute coronary syndrome events when compared to patient recognized symptoms alone and demonstrates a reduced rate over time of patient presentations without ACS events.”
“About 50% of patients wait more than 3 hours after the onset of symptoms before reaching an emergency room,” observed Dr. Gibson. Emphasizing the evidence that delay is an important predictor of adverse outcomes, he suggested the alarm device might be useful in accelerating care in some high risk groups.
WASHINGTON –Although an implantable device for detecting myocardial infarction missed the primary composite outcome endpoint in a controlled trial, a newly completed extended analysis associated the device with a higher positive predictive value and a lower false positive rate when compared to sham control, according to data presented at CRT 2019, sponsored by MedStar Heart & Vascular Institute.
“Among high risk patients, this system may be beneficial in the identification of both symptomatic and asymptomatic coronary events,” reported C. Michael Gibson, MD, chief of clinical research in the cardiology division at Beth Israel Deaconess Hospital, Boston.
The implantable device (AngelMed Guardian System), which received Food and Drug Administration approval in April 2018, is designed to identify MI through detection of ST-segment elevations in the absence of an elevated heart rate. When the system detects an event during continuous monitoring, it sends a signal (internal vibration and auditory signal to an external monitor) designed to tell the patient to seek medical care.
The previously published multicenter and randomized ALERTS (AngelMed for Early Recognition and Treatment of STEMI) trial that tested this device was negative for primary composite endpoint of cardiac or unexplained death, new Q-wave MI, or presentation at the emergency department (ED) more than 2 hours after symptom onset (J Am Coll Cardiol. 2019 Feb 25. pii: S0735-1097[19]30237-2). In that trial 907 patients were fitted with the device and then randomized to having the device switched on or left off.
At 7 days, a primary endpoint was reached by 3.8% of those in the device-on group versus 4.9% of those in the device-off group, which was not significantly different.
Although the primary endpoint was not met, there were promising results. For example, in those who did have an occlusive event, patients in the device-on group had better preserved left ventricular function when evaluated after the event, a result consistent with earlier presentation in the ED and earlier treatment. In fact, 85% of patients with an MI in the device-on group presented to a hospital within 2 hours, compared with just 5% of those in the device-off control group during the initial study period.
More evidence of a potential clinical role for the device has now been generated in a new extended analysis. This analysis was made possible because patients in both of the randomized groups continue to wear the device, including those in the device-off group who had their devices activated after 6 months. There are now 3 more years of data of follow-up from those initially in the device-on group and those switched from the device-off group.
“So we started the clock over with a new statistical analysis plan and new endpoints,” Dr. Gibson explained. The FDA was consulted in selecting endpoints, particularly regarding evidence that the device did not increase false-positive ED visits.
There were numerous encouraging findings. One was that 42 silent MIs, which would otherwise have been missed, were detected over the extended follow-up. Another was that the annualized false-positive rate was lower in those with an activated device (0.164/year) when compared to the original device-off group (0.678/year; P less than .001). Lastly, the positive predictive value of an alarm during the extended follow-up was higher than that of symptoms alone among the original device-off group (25.8% vs. 18.2%).
The device was found safe. The rate of system-related complications was under 4%, which Dr. Gibson said is noninferior to that associated with pacemakers.
One of the potential explanations for the failure of the device to achieve the primary endpoint in the original trial was an unexpectedly low event rate, according to Dr. Gibson.
Even before this extended analysis, the FDA had accepted the potential benefits of this device as demonstrated in the approval last year. In the labeling, the device is called “a more accurate predictor of acute coronary syndrome events when compared to patient recognized symptoms alone and demonstrates a reduced rate over time of patient presentations without ACS events.”
“About 50% of patients wait more than 3 hours after the onset of symptoms before reaching an emergency room,” observed Dr. Gibson. Emphasizing the evidence that delay is an important predictor of adverse outcomes, he suggested the alarm device might be useful in accelerating care in some high risk groups.
WASHINGTON –Although an implantable device for detecting myocardial infarction missed the primary composite outcome endpoint in a controlled trial, a newly completed extended analysis associated the device with a higher positive predictive value and a lower false positive rate when compared to sham control, according to data presented at CRT 2019, sponsored by MedStar Heart & Vascular Institute.
“Among high risk patients, this system may be beneficial in the identification of both symptomatic and asymptomatic coronary events,” reported C. Michael Gibson, MD, chief of clinical research in the cardiology division at Beth Israel Deaconess Hospital, Boston.
The implantable device (AngelMed Guardian System), which received Food and Drug Administration approval in April 2018, is designed to identify MI through detection of ST-segment elevations in the absence of an elevated heart rate. When the system detects an event during continuous monitoring, it sends a signal (internal vibration and auditory signal to an external monitor) designed to tell the patient to seek medical care.
The previously published multicenter and randomized ALERTS (AngelMed for Early Recognition and Treatment of STEMI) trial that tested this device was negative for primary composite endpoint of cardiac or unexplained death, new Q-wave MI, or presentation at the emergency department (ED) more than 2 hours after symptom onset (J Am Coll Cardiol. 2019 Feb 25. pii: S0735-1097[19]30237-2). In that trial 907 patients were fitted with the device and then randomized to having the device switched on or left off.
At 7 days, a primary endpoint was reached by 3.8% of those in the device-on group versus 4.9% of those in the device-off group, which was not significantly different.
Although the primary endpoint was not met, there were promising results. For example, in those who did have an occlusive event, patients in the device-on group had better preserved left ventricular function when evaluated after the event, a result consistent with earlier presentation in the ED and earlier treatment. In fact, 85% of patients with an MI in the device-on group presented to a hospital within 2 hours, compared with just 5% of those in the device-off control group during the initial study period.
More evidence of a potential clinical role for the device has now been generated in a new extended analysis. This analysis was made possible because patients in both of the randomized groups continue to wear the device, including those in the device-off group who had their devices activated after 6 months. There are now 3 more years of data of follow-up from those initially in the device-on group and those switched from the device-off group.
“So we started the clock over with a new statistical analysis plan and new endpoints,” Dr. Gibson explained. The FDA was consulted in selecting endpoints, particularly regarding evidence that the device did not increase false-positive ED visits.
There were numerous encouraging findings. One was that 42 silent MIs, which would otherwise have been missed, were detected over the extended follow-up. Another was that the annualized false-positive rate was lower in those with an activated device (0.164/year) when compared to the original device-off group (0.678/year; P less than .001). Lastly, the positive predictive value of an alarm during the extended follow-up was higher than that of symptoms alone among the original device-off group (25.8% vs. 18.2%).
The device was found safe. The rate of system-related complications was under 4%, which Dr. Gibson said is noninferior to that associated with pacemakers.
One of the potential explanations for the failure of the device to achieve the primary endpoint in the original trial was an unexpectedly low event rate, according to Dr. Gibson.
Even before this extended analysis, the FDA had accepted the potential benefits of this device as demonstrated in the approval last year. In the labeling, the device is called “a more accurate predictor of acute coronary syndrome events when compared to patient recognized symptoms alone and demonstrates a reduced rate over time of patient presentations without ACS events.”
“About 50% of patients wait more than 3 hours after the onset of symptoms before reaching an emergency room,” observed Dr. Gibson. Emphasizing the evidence that delay is an important predictor of adverse outcomes, he suggested the alarm device might be useful in accelerating care in some high risk groups.
REPORTING FROM CRT 2019
Adjunctive devices for transcatheter valve replacement improve outcomes
WASHINGTON – One transcatheter device designed to prevent left ventricular outflow tract (LVOT) obstruction relevant to transcatheter mitral valve replacement (TMVR) and another designed to prevent coronary obstruction relevant to transcatheter aortic valve replacement (TAVR) performed well in feasibility studies, according to data presented in two separate late breaking clinical trial sessions at the CRT 2019, sponsored by MedStar Heart & Vascular Institute.
LVOT obstruction prevention
“The 30-day survival in subjects with an increased risk of LVOT obstruction was significantly better than that previously reported in registries,” said Jaffar M. Khan, BM BCh, of the National Heart, Lung, and Blood Institute, who addressing results with the LAMPOON device prior to TMVR,.
LAMPOON is an acronym for intentional Laceration of the Anterior Mitral valve leaflet to Prevent LVOT ObstructioN. Introduced percutaneously and guided to the valve with wires, it was designed to tear existing mitral valve leaflets to prevent them from causing life-threatening LVOT obstruction. It is used immediately prior to TMVR in patients at risk for this complication.
In a feasibility study, delivery, deployment, and retrieval of the device was achieved in all 30 patients. On the basis of the primary endpoint of LVOT gradients of less than 50 mm Hg and no emergency surgery, the procedural success was 73%. The 30-day survival was 93%.
Citing data from registries, Dr. Khan said that the expected survival in TMVR patients with LVOT obstruction caused by a native mitral valve leaflet has been less than 40%. With few existing options to prevent this complication, none of which are reliable, LAMPOON is poised to permit patients who are poor candidates or are contraindicated for TMVR to undergo this treatment, according to Dr. Khan.
“LAMPOON is feasible in all anatomies and calcium patterns,” said Dr. Khan, who noted that gradients of less than 30 mm Hg was achieved in 29 of the 30 patients. Although Dr. Khan acknowledged that this study was small and uncontrolled, and he further cautioned that current strategies for predicting mitral valve leaflet LVOT obstruction are “imprecise,” he believes larger studies of LAMPOON are warranted based on these results.
Coronary artery obstruction prevention
Dr. Khan also presented data on the BASILICA device from a second feasibility study. The device is employed immediately prior to TAVR in order to prevent large aortic valve leaflets, whether native or from an existing bioprosthetic valve, from producing coronary obstruction. BASILICA is an acronym for Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction.
This device is also introduced percutaneously and uses radiofrequency ablation to split leaflets that are considered to pose a risk for coronary obstruction. Even though Dr. Khan acknowledged that there is also a lack of precision for predicting which TAVR candidates require an intervention to prevent coronary obstruction, he cited mortality rates exceeding 40% when this complication occurs.
In the feasibility study, 30 patients, of whom 80% were female, were enrolled. In half of the cases, the target for BASILICA was a native valve. The remainder was treated for risk of coronary obstruction posed by a bioprosthetic valve. Multiple comorbidities, including a high proportion with prior stroke, made those selected for enrollment poor candidates for surgery.
The BASILICA intervention was successful in 28 of the 30 participants and in 35 of the 37 leaflets treated. At 30 days, there was one death and one disabling stroke. The overall success rate of the procedure was 93%, according to Dr. Khan.
“One hundred percent of patients were discharged from the cath lab without coronary obstruction despite the high baseline risk,” Dr. Khan said. Again, larger studies are needed to validate the safety and efficacy of this approach, but Dr. Khan believes the outcomes in this study warrant expanded clinical studies.
WASHINGTON – One transcatheter device designed to prevent left ventricular outflow tract (LVOT) obstruction relevant to transcatheter mitral valve replacement (TMVR) and another designed to prevent coronary obstruction relevant to transcatheter aortic valve replacement (TAVR) performed well in feasibility studies, according to data presented in two separate late breaking clinical trial sessions at the CRT 2019, sponsored by MedStar Heart & Vascular Institute.
LVOT obstruction prevention
“The 30-day survival in subjects with an increased risk of LVOT obstruction was significantly better than that previously reported in registries,” said Jaffar M. Khan, BM BCh, of the National Heart, Lung, and Blood Institute, who addressing results with the LAMPOON device prior to TMVR,.
LAMPOON is an acronym for intentional Laceration of the Anterior Mitral valve leaflet to Prevent LVOT ObstructioN. Introduced percutaneously and guided to the valve with wires, it was designed to tear existing mitral valve leaflets to prevent them from causing life-threatening LVOT obstruction. It is used immediately prior to TMVR in patients at risk for this complication.
In a feasibility study, delivery, deployment, and retrieval of the device was achieved in all 30 patients. On the basis of the primary endpoint of LVOT gradients of less than 50 mm Hg and no emergency surgery, the procedural success was 73%. The 30-day survival was 93%.
Citing data from registries, Dr. Khan said that the expected survival in TMVR patients with LVOT obstruction caused by a native mitral valve leaflet has been less than 40%. With few existing options to prevent this complication, none of which are reliable, LAMPOON is poised to permit patients who are poor candidates or are contraindicated for TMVR to undergo this treatment, according to Dr. Khan.
“LAMPOON is feasible in all anatomies and calcium patterns,” said Dr. Khan, who noted that gradients of less than 30 mm Hg was achieved in 29 of the 30 patients. Although Dr. Khan acknowledged that this study was small and uncontrolled, and he further cautioned that current strategies for predicting mitral valve leaflet LVOT obstruction are “imprecise,” he believes larger studies of LAMPOON are warranted based on these results.
Coronary artery obstruction prevention
Dr. Khan also presented data on the BASILICA device from a second feasibility study. The device is employed immediately prior to TAVR in order to prevent large aortic valve leaflets, whether native or from an existing bioprosthetic valve, from producing coronary obstruction. BASILICA is an acronym for Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction.
This device is also introduced percutaneously and uses radiofrequency ablation to split leaflets that are considered to pose a risk for coronary obstruction. Even though Dr. Khan acknowledged that there is also a lack of precision for predicting which TAVR candidates require an intervention to prevent coronary obstruction, he cited mortality rates exceeding 40% when this complication occurs.
In the feasibility study, 30 patients, of whom 80% were female, were enrolled. In half of the cases, the target for BASILICA was a native valve. The remainder was treated for risk of coronary obstruction posed by a bioprosthetic valve. Multiple comorbidities, including a high proportion with prior stroke, made those selected for enrollment poor candidates for surgery.
The BASILICA intervention was successful in 28 of the 30 participants and in 35 of the 37 leaflets treated. At 30 days, there was one death and one disabling stroke. The overall success rate of the procedure was 93%, according to Dr. Khan.
“One hundred percent of patients were discharged from the cath lab without coronary obstruction despite the high baseline risk,” Dr. Khan said. Again, larger studies are needed to validate the safety and efficacy of this approach, but Dr. Khan believes the outcomes in this study warrant expanded clinical studies.
WASHINGTON – One transcatheter device designed to prevent left ventricular outflow tract (LVOT) obstruction relevant to transcatheter mitral valve replacement (TMVR) and another designed to prevent coronary obstruction relevant to transcatheter aortic valve replacement (TAVR) performed well in feasibility studies, according to data presented in two separate late breaking clinical trial sessions at the CRT 2019, sponsored by MedStar Heart & Vascular Institute.
LVOT obstruction prevention
“The 30-day survival in subjects with an increased risk of LVOT obstruction was significantly better than that previously reported in registries,” said Jaffar M. Khan, BM BCh, of the National Heart, Lung, and Blood Institute, who addressing results with the LAMPOON device prior to TMVR,.
LAMPOON is an acronym for intentional Laceration of the Anterior Mitral valve leaflet to Prevent LVOT ObstructioN. Introduced percutaneously and guided to the valve with wires, it was designed to tear existing mitral valve leaflets to prevent them from causing life-threatening LVOT obstruction. It is used immediately prior to TMVR in patients at risk for this complication.
In a feasibility study, delivery, deployment, and retrieval of the device was achieved in all 30 patients. On the basis of the primary endpoint of LVOT gradients of less than 50 mm Hg and no emergency surgery, the procedural success was 73%. The 30-day survival was 93%.
Citing data from registries, Dr. Khan said that the expected survival in TMVR patients with LVOT obstruction caused by a native mitral valve leaflet has been less than 40%. With few existing options to prevent this complication, none of which are reliable, LAMPOON is poised to permit patients who are poor candidates or are contraindicated for TMVR to undergo this treatment, according to Dr. Khan.
“LAMPOON is feasible in all anatomies and calcium patterns,” said Dr. Khan, who noted that gradients of less than 30 mm Hg was achieved in 29 of the 30 patients. Although Dr. Khan acknowledged that this study was small and uncontrolled, and he further cautioned that current strategies for predicting mitral valve leaflet LVOT obstruction are “imprecise,” he believes larger studies of LAMPOON are warranted based on these results.
Coronary artery obstruction prevention
Dr. Khan also presented data on the BASILICA device from a second feasibility study. The device is employed immediately prior to TAVR in order to prevent large aortic valve leaflets, whether native or from an existing bioprosthetic valve, from producing coronary obstruction. BASILICA is an acronym for Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction.
This device is also introduced percutaneously and uses radiofrequency ablation to split leaflets that are considered to pose a risk for coronary obstruction. Even though Dr. Khan acknowledged that there is also a lack of precision for predicting which TAVR candidates require an intervention to prevent coronary obstruction, he cited mortality rates exceeding 40% when this complication occurs.
In the feasibility study, 30 patients, of whom 80% were female, were enrolled. In half of the cases, the target for BASILICA was a native valve. The remainder was treated for risk of coronary obstruction posed by a bioprosthetic valve. Multiple comorbidities, including a high proportion with prior stroke, made those selected for enrollment poor candidates for surgery.
The BASILICA intervention was successful in 28 of the 30 participants and in 35 of the 37 leaflets treated. At 30 days, there was one death and one disabling stroke. The overall success rate of the procedure was 93%, according to Dr. Khan.
“One hundred percent of patients were discharged from the cath lab without coronary obstruction despite the high baseline risk,” Dr. Khan said. Again, larger studies are needed to validate the safety and efficacy of this approach, but Dr. Khan believes the outcomes in this study warrant expanded clinical studies.
REPORTING FROM CRT 2019
High levels of estradiol in older men may be associated with young biological age
NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, suggesting that sex hormones influence the aging process.
“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.
In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.
In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.
Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.
“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.
The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.
Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.
NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, suggesting that sex hormones influence the aging process.
“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.
In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.
In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.
Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.
“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.
The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.
Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.
NEW ORLEANS – In a large community-based study that evaluated sex hormone levels in older men, suggesting that sex hormones influence the aging process.
“There was a large effect size, comparable with being 2 or 3 years younger for those with relatively high levels of estradiol, compared with those with lower levels of the hormone,” said Bu Yeap, MBBS, PhD, professor of medicine, University of Western Australia Medical School, Perth, who reported the results at the annual meeting of the Endocrine Society.
In a video interview conducted at the meeting, Dr. Yeap explained the basis of the study, which is the variety of evidence showing that decline in sex hormones correlates with higher rates of age-related disease processes. For example, increasing rates of cardiovascular disease, dementia, and mortality in men all correlate with declining levels of testosterone.
In the study, 2,913 men between the ages of 70 and 89 years and living in the community were recruited. The average age of the men was 77 years. Serum levels of testosterone, dihydrotestosterone, and estradiol were measured. Telomere length was calculated with a polymerase chain reaction test.
Serum levels of testosterone and dihydrotestosterone did not correlate with telomere length, but incremental increases in serum estradiol levels were associated with incremental increases in telomere length.
“Telomeres are both a mediator and a biomarker for biological aging,” according to Dr. Yeap, who added that the telomeres protect chromosomes from degradation. As the telomeres shorten, cell senescence is increased along with an array of age-related diseases.
The next step for researchers is to evaluate whether administering exogenous sex hormones can favorably alter telomere length. If such an effect is demonstrated, then it could provide a step toward understanding how to slow the aging process, he said.
Dr Yeap and his colleagues reported no disclosures or financial conflicts of interest.
REPORTING FROM ENDO 2019
No further amplification of signal for benefit from ultrathin stent at 3 years
WASHINGTON – In the latest analysis of data from a randomized trial comparing three different thin polymer-coated drug-eluting stents, the signal at 1 year that the thinnest device might reduce risk of target lesion revascularization has been lost at 3 years, according to an update of results from the BIO-RESORT trial presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“At 3-year follow-up, all three drug-eluting stents were associated with favorable outcomes and both very thin strut polymer-coated devices showed safety and patency similar to the thin-strut durable polymer drug-eluting stent,” reported Clemons von Birgelen, MD, PhD, professor of cardiology, University of Twente, Enschede, the Netherlands.
In order of strut thickness, the stents tested in BIO-RESORT were Orsiro (60 mcm), Synergy (74 mcm), and Resolute Integrity (90 mcm). Although the study had a noninferiority design, the potential for the biodegradable polymer coatings of the two thinner stents to provide faster healing than the durable polymer of the Resolute stent was one of the driving hypotheses of the trial (Lancet. 2016 Nov 26;388[10060]:2607-17).
Some support for this hypothesis was provided by 2-year results presented at EuroPCR 2018 last year. At that time, it was reported that the risk of target lesion revascularization between the end of year 1 and end of year 2 was significantly lower for the Orsiro stent (1.3%) than the Resolute stent (2.3%). Target lesion revascularization also was lower in the Synergy stent group (1.8%), but this rate did not differ significantly from that of the other two stents in the trial.
Now, reassessed at 3 years, the target lesion revascularization rates are 2.9%, 3.3%, and 3.8% for the Orsiro, Synergy, and Resolute stents, respectively. Although the numerical hierarchy is preserved, the differences are no longer significant.
Other outcomes, including the primary outcome of target lesion failure, show the same numerical hierarchy but, again, without differences reaching significance. For target lesion failure, these rates are 8.5%, 8.8%, and 10.0%, respectively.
The difference in the rates of stent thrombosis at 3 years was even smaller with rates of less than 1% for all three stents. A catch-up phenomenon between years 2 and 3 of follow-up largely eliminated a numerical advantage seen earlier for the Orsiro stent.
The BIO-RESORT trial randomized 3,514 patients, of whom 70% had an acute coronary syndrome. Nearly one-third had an ST-elevated myocardial infarction. Dr. von Birgelen emphasized that this was “a very complex study population.” For example, roughly 20% had severely calcified lesions. Follow-up data were available on 97% of the randomized patients at 3 years.
There are differences between these stents other than thickness and the durability of the polymer. In particular, Orsiro is coated with sirolimus, Synergy with everolimus, and Resolute with zotarolimus. While the metals of the frame also differ, the estimated time to resorption of the polymer is faster with the Synergy stent (4 months) than the Orsiro stent (24 months).
Despite the loss of a difference in target vessel revascularization in the most recent follow-up, the potential for the differences in designs and materials to influence risk of late complications, including revascularization and thrombosis, persists.
“Follow-up beyond 3 years is of interest to definitely answer the question of whether one of these drug-eluting stents might improve outcome at a later stage,” Dr. von Birgelen said.
WASHINGTON – In the latest analysis of data from a randomized trial comparing three different thin polymer-coated drug-eluting stents, the signal at 1 year that the thinnest device might reduce risk of target lesion revascularization has been lost at 3 years, according to an update of results from the BIO-RESORT trial presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“At 3-year follow-up, all three drug-eluting stents were associated with favorable outcomes and both very thin strut polymer-coated devices showed safety and patency similar to the thin-strut durable polymer drug-eluting stent,” reported Clemons von Birgelen, MD, PhD, professor of cardiology, University of Twente, Enschede, the Netherlands.
In order of strut thickness, the stents tested in BIO-RESORT were Orsiro (60 mcm), Synergy (74 mcm), and Resolute Integrity (90 mcm). Although the study had a noninferiority design, the potential for the biodegradable polymer coatings of the two thinner stents to provide faster healing than the durable polymer of the Resolute stent was one of the driving hypotheses of the trial (Lancet. 2016 Nov 26;388[10060]:2607-17).
Some support for this hypothesis was provided by 2-year results presented at EuroPCR 2018 last year. At that time, it was reported that the risk of target lesion revascularization between the end of year 1 and end of year 2 was significantly lower for the Orsiro stent (1.3%) than the Resolute stent (2.3%). Target lesion revascularization also was lower in the Synergy stent group (1.8%), but this rate did not differ significantly from that of the other two stents in the trial.
Now, reassessed at 3 years, the target lesion revascularization rates are 2.9%, 3.3%, and 3.8% for the Orsiro, Synergy, and Resolute stents, respectively. Although the numerical hierarchy is preserved, the differences are no longer significant.
Other outcomes, including the primary outcome of target lesion failure, show the same numerical hierarchy but, again, without differences reaching significance. For target lesion failure, these rates are 8.5%, 8.8%, and 10.0%, respectively.
The difference in the rates of stent thrombosis at 3 years was even smaller with rates of less than 1% for all three stents. A catch-up phenomenon between years 2 and 3 of follow-up largely eliminated a numerical advantage seen earlier for the Orsiro stent.
The BIO-RESORT trial randomized 3,514 patients, of whom 70% had an acute coronary syndrome. Nearly one-third had an ST-elevated myocardial infarction. Dr. von Birgelen emphasized that this was “a very complex study population.” For example, roughly 20% had severely calcified lesions. Follow-up data were available on 97% of the randomized patients at 3 years.
There are differences between these stents other than thickness and the durability of the polymer. In particular, Orsiro is coated with sirolimus, Synergy with everolimus, and Resolute with zotarolimus. While the metals of the frame also differ, the estimated time to resorption of the polymer is faster with the Synergy stent (4 months) than the Orsiro stent (24 months).
Despite the loss of a difference in target vessel revascularization in the most recent follow-up, the potential for the differences in designs and materials to influence risk of late complications, including revascularization and thrombosis, persists.
“Follow-up beyond 3 years is of interest to definitely answer the question of whether one of these drug-eluting stents might improve outcome at a later stage,” Dr. von Birgelen said.
WASHINGTON – In the latest analysis of data from a randomized trial comparing three different thin polymer-coated drug-eluting stents, the signal at 1 year that the thinnest device might reduce risk of target lesion revascularization has been lost at 3 years, according to an update of results from the BIO-RESORT trial presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“At 3-year follow-up, all three drug-eluting stents were associated with favorable outcomes and both very thin strut polymer-coated devices showed safety and patency similar to the thin-strut durable polymer drug-eluting stent,” reported Clemons von Birgelen, MD, PhD, professor of cardiology, University of Twente, Enschede, the Netherlands.
In order of strut thickness, the stents tested in BIO-RESORT were Orsiro (60 mcm), Synergy (74 mcm), and Resolute Integrity (90 mcm). Although the study had a noninferiority design, the potential for the biodegradable polymer coatings of the two thinner stents to provide faster healing than the durable polymer of the Resolute stent was one of the driving hypotheses of the trial (Lancet. 2016 Nov 26;388[10060]:2607-17).
Some support for this hypothesis was provided by 2-year results presented at EuroPCR 2018 last year. At that time, it was reported that the risk of target lesion revascularization between the end of year 1 and end of year 2 was significantly lower for the Orsiro stent (1.3%) than the Resolute stent (2.3%). Target lesion revascularization also was lower in the Synergy stent group (1.8%), but this rate did not differ significantly from that of the other two stents in the trial.
Now, reassessed at 3 years, the target lesion revascularization rates are 2.9%, 3.3%, and 3.8% for the Orsiro, Synergy, and Resolute stents, respectively. Although the numerical hierarchy is preserved, the differences are no longer significant.
Other outcomes, including the primary outcome of target lesion failure, show the same numerical hierarchy but, again, without differences reaching significance. For target lesion failure, these rates are 8.5%, 8.8%, and 10.0%, respectively.
The difference in the rates of stent thrombosis at 3 years was even smaller with rates of less than 1% for all three stents. A catch-up phenomenon between years 2 and 3 of follow-up largely eliminated a numerical advantage seen earlier for the Orsiro stent.
The BIO-RESORT trial randomized 3,514 patients, of whom 70% had an acute coronary syndrome. Nearly one-third had an ST-elevated myocardial infarction. Dr. von Birgelen emphasized that this was “a very complex study population.” For example, roughly 20% had severely calcified lesions. Follow-up data were available on 97% of the randomized patients at 3 years.
There are differences between these stents other than thickness and the durability of the polymer. In particular, Orsiro is coated with sirolimus, Synergy with everolimus, and Resolute with zotarolimus. While the metals of the frame also differ, the estimated time to resorption of the polymer is faster with the Synergy stent (4 months) than the Orsiro stent (24 months).
Despite the loss of a difference in target vessel revascularization in the most recent follow-up, the potential for the differences in designs and materials to influence risk of late complications, including revascularization and thrombosis, persists.
“Follow-up beyond 3 years is of interest to definitely answer the question of whether one of these drug-eluting stents might improve outcome at a later stage,” Dr. von Birgelen said.
REPORTING FROM CRT 2019
Noninfected children of HIV-positive mothers have high rates of obesity
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
REPORTING FROM ENDO 2019
30-day readmissions after STEMI with cardiogenic shock 13%
WASHINGTON – and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.
Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.
In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.
Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.
The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.
“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.
“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.
WASHINGTON – and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.
Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.
In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.
Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.
The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.
“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.
“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.
WASHINGTON – and remain in hospital for an average of 6 days, according to an analysis from the National Readmission Database presented at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
“About one in four of the readmissions was for heart failure,” reported Karan Sud, MD, a cardiology resident at the Mount Sinai St. Luke’s West Hospital, New York.
Despite gains in acute survival among STEMI patients in cardiogenic shock, little attention has been paid to the risk of readmissions, according to Dr. Sud. According to data collected from the National Readmissions Database for 2010-2014, these rates are high enough to deserve attention, he said.
“Our goal is now to develop a scoring system based on our predictive model to identify patients at the index admission who are at risk for readmission,” Dr. Sud reported. On the basis of these predictors, it might be possible to implement strategies to optimize management and improve access to care.
In the years studied, there were 94,991 patients with STEMI and cardiogenic shock captured in the National Readmissions Database, of whom 43,205 survived and were followed for readmission. Of the 5,503 readmissions within 30 days, 12% were considered unplanned.
Half of the readmissions were for noncardiovascular causes, including sepsis, respiratory failure, and major bleeding. Of those related to cardiovascular disease, about half, or nearly 25% of the total, were for heart failure.
The predictors of readmission included female sex, age older than 75 years, average length of stay longer than 10 days, and more than three comorbidities, such as diabetes or chronic kidney disease, according to Dr. Sud.
“Those sent home from the index admission were more likely than those discharged to an extended care facility to be readmitted,” he added. He also noted that lower socioeconomic status was a risk factor for readmission, a phenomenon that he attributed to access issues regarding follow-up care.
“We are now conducting a prospective study to look at readmissions at 6 months,” reported Dr. Sud, who believes that efforts to understand the risk of readmission following STEMI complicated by cardiogenic shock might uncover opportunities for better management.
REPORTING FROM CRT 2019
Sperm quality linked to some recurrent pregnancy loss
NEW ORLEANS – Couples with recurrent pregnancy loss (RPL) might benefit from seminal parameter testing, based on results from a study presented at the annual meeting of the Endocrine Society.
Sperm quality was more likely to be impaired in the 50 male partners of women with recurrent pregnancy loss than it was in a control group of 63 similar-age men, reported Anastasia P. Dimakopoulou, MBBS, a clinical research fellow at Imperial College, London.
Recurrent pregnancy loss is defined as three pregnancy losses before 20 weeks of gestation.
The reported prevalence of RPL has been estimated at less than 2% in couples attempting pregnancy. About half of those cases are considered to be idiopathic, she said.
Sperm DNA plays a role in placentation, and previous study findings have shown that men in RPL couples are more likely to have higher rates of DNA fragmentation in their sperm. Male partners are not routinely evaluated when seeking a cause for RPL, however.
In this study, 50 men from RPL couples and 63 control men were screened for factors known to affect sperm quality, such as previous testicular surgery, sexually transmitted diseases, alcohol intake, and smoking. In patients and controls, semen reactive oxidative stress, a novel biomarker of sperm function, was measured with a chemiluminescence luminol assay.
The proportion of men with abnormal sperm morphology, although modest in both groups, was significantly more common in men from RPL couples than in controls (4.5% vs. 3.4%, respectively; P less than .001). In addition, the mean reactive oxidative stress levels were four times greater in the RPL men (9.3 vs. 2.3 relative light units/sec per 106 sperm; P less than .05).
Consistent with the higher median reactive oxidative stress levels, the median DNA fragmentation index, which is likely to be linked to increased reactive oxidative stress, was more than twice as high in the RPL men, compared with the controls (16.3 vs. 7.4; P less than .0001).
In addition, the sperm volume was significantly lower in men from the RPL couples, compared with controls. The levels of morning serum testosterone also were lower in men from RPL couples, but the difference did not reach significance relative to controls.
There has been relatively little attention directed toward the male partner in the evaluation and treatment of RPL, but that should change, according to Dr. Dimakopoulou. She said data encourage a new direction of study, including the effort to look for treatable causes of RPL in the male partner.
“By pursuing drugs that stop sperm DNA damage, it may be possible to identify new therapeutic pathways for couples who experience RPL,” Dr. Dimakopoulou maintained. However, even in advance of targeted therapies, she suggested these data encourage investigation of male partners in couples with RPL. Although evidence of reactive oxidative stress may not define a cause, it broadens the scope of investigation and might have value when counseling patients.
Dr. Dimakopoulou reported no relevant financial relationships to disclose.
SOURCE: Dimakopoulou AP et al. ENDO 2019, Session OR18-5.
NEW ORLEANS – Couples with recurrent pregnancy loss (RPL) might benefit from seminal parameter testing, based on results from a study presented at the annual meeting of the Endocrine Society.
Sperm quality was more likely to be impaired in the 50 male partners of women with recurrent pregnancy loss than it was in a control group of 63 similar-age men, reported Anastasia P. Dimakopoulou, MBBS, a clinical research fellow at Imperial College, London.
Recurrent pregnancy loss is defined as three pregnancy losses before 20 weeks of gestation.
The reported prevalence of RPL has been estimated at less than 2% in couples attempting pregnancy. About half of those cases are considered to be idiopathic, she said.
Sperm DNA plays a role in placentation, and previous study findings have shown that men in RPL couples are more likely to have higher rates of DNA fragmentation in their sperm. Male partners are not routinely evaluated when seeking a cause for RPL, however.
In this study, 50 men from RPL couples and 63 control men were screened for factors known to affect sperm quality, such as previous testicular surgery, sexually transmitted diseases, alcohol intake, and smoking. In patients and controls, semen reactive oxidative stress, a novel biomarker of sperm function, was measured with a chemiluminescence luminol assay.
The proportion of men with abnormal sperm morphology, although modest in both groups, was significantly more common in men from RPL couples than in controls (4.5% vs. 3.4%, respectively; P less than .001). In addition, the mean reactive oxidative stress levels were four times greater in the RPL men (9.3 vs. 2.3 relative light units/sec per 106 sperm; P less than .05).
Consistent with the higher median reactive oxidative stress levels, the median DNA fragmentation index, which is likely to be linked to increased reactive oxidative stress, was more than twice as high in the RPL men, compared with the controls (16.3 vs. 7.4; P less than .0001).
In addition, the sperm volume was significantly lower in men from the RPL couples, compared with controls. The levels of morning serum testosterone also were lower in men from RPL couples, but the difference did not reach significance relative to controls.
There has been relatively little attention directed toward the male partner in the evaluation and treatment of RPL, but that should change, according to Dr. Dimakopoulou. She said data encourage a new direction of study, including the effort to look for treatable causes of RPL in the male partner.
“By pursuing drugs that stop sperm DNA damage, it may be possible to identify new therapeutic pathways for couples who experience RPL,” Dr. Dimakopoulou maintained. However, even in advance of targeted therapies, she suggested these data encourage investigation of male partners in couples with RPL. Although evidence of reactive oxidative stress may not define a cause, it broadens the scope of investigation and might have value when counseling patients.
Dr. Dimakopoulou reported no relevant financial relationships to disclose.
SOURCE: Dimakopoulou AP et al. ENDO 2019, Session OR18-5.
NEW ORLEANS – Couples with recurrent pregnancy loss (RPL) might benefit from seminal parameter testing, based on results from a study presented at the annual meeting of the Endocrine Society.
Sperm quality was more likely to be impaired in the 50 male partners of women with recurrent pregnancy loss than it was in a control group of 63 similar-age men, reported Anastasia P. Dimakopoulou, MBBS, a clinical research fellow at Imperial College, London.
Recurrent pregnancy loss is defined as three pregnancy losses before 20 weeks of gestation.
The reported prevalence of RPL has been estimated at less than 2% in couples attempting pregnancy. About half of those cases are considered to be idiopathic, she said.
Sperm DNA plays a role in placentation, and previous study findings have shown that men in RPL couples are more likely to have higher rates of DNA fragmentation in their sperm. Male partners are not routinely evaluated when seeking a cause for RPL, however.
In this study, 50 men from RPL couples and 63 control men were screened for factors known to affect sperm quality, such as previous testicular surgery, sexually transmitted diseases, alcohol intake, and smoking. In patients and controls, semen reactive oxidative stress, a novel biomarker of sperm function, was measured with a chemiluminescence luminol assay.
The proportion of men with abnormal sperm morphology, although modest in both groups, was significantly more common in men from RPL couples than in controls (4.5% vs. 3.4%, respectively; P less than .001). In addition, the mean reactive oxidative stress levels were four times greater in the RPL men (9.3 vs. 2.3 relative light units/sec per 106 sperm; P less than .05).
Consistent with the higher median reactive oxidative stress levels, the median DNA fragmentation index, which is likely to be linked to increased reactive oxidative stress, was more than twice as high in the RPL men, compared with the controls (16.3 vs. 7.4; P less than .0001).
In addition, the sperm volume was significantly lower in men from the RPL couples, compared with controls. The levels of morning serum testosterone also were lower in men from RPL couples, but the difference did not reach significance relative to controls.
There has been relatively little attention directed toward the male partner in the evaluation and treatment of RPL, but that should change, according to Dr. Dimakopoulou. She said data encourage a new direction of study, including the effort to look for treatable causes of RPL in the male partner.
“By pursuing drugs that stop sperm DNA damage, it may be possible to identify new therapeutic pathways for couples who experience RPL,” Dr. Dimakopoulou maintained. However, even in advance of targeted therapies, she suggested these data encourage investigation of male partners in couples with RPL. Although evidence of reactive oxidative stress may not define a cause, it broadens the scope of investigation and might have value when counseling patients.
Dr. Dimakopoulou reported no relevant financial relationships to disclose.
SOURCE: Dimakopoulou AP et al. ENDO 2019, Session OR18-5.
REPORTING FROM ENDO 2019
CPAP use associated with greater weight loss in obese patients with sleep apnea
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
REPORTING FROM ENDO 2019
First RCT with aromatase inhibitor for male hypogonadism shows promise
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
REPORTING FROM ENDO 2019
New postmenopausal osteoporosis guidelines emphasize patient priorities
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
REPORTING FROM ENDO 2019