User login
Official Newspaper of the American College of Surgeons
Resorbable scaffold appears safe, effective in diabetes patients
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
An everolimus-eluting resorbable scaffold appeared to be safe and effective for percutaneous coronary intervention (PCI) in patients with diabetes and noncomplex coronary lesions, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology: Cardiovascular Interventions.
Patients with diabetes constitute an important and increasingly prevalent subgroup of PCI patients, who are at high risk of adverse clinical and angiographic outcomes such as MI, stent thrombosis, restenosis, and death. This is thought to be due to diabetic patients’ greater level of vascular inflammation and tendency toward a prothrombotic state and more complex angiographic features, said Dean J. Kereiakes, MD, of the Christ Hospital Heart and Vascular Center, Lindner Research Center, Cincinnati.
The substudy participants all received at least one resorbable scaffold in at least one target lesion. A total of 27.3% were insulin dependent and nearly 60% had HbA1c levels exceeding 7.0%. Notably, 18% of all the treated lesions in this analysis were less than 2.25 mm in diameter as assessed by quantitative coronary angiography, and approximately 60% had moderately to severely complex morphology.
The primary endpoint – the rate of target-lesion failure at 1-year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%. This rate ranged from 4.4% to 10.9% across the different trials. A sensitivity analysis confirmed that the 1-year rate of target-lesion failure was significantly lower than the prespecified performance goal.
The rates of target-lesion failure, target-vessel MI, ischemia-driven target-lesion revascularization, and scaffold thrombosis were significantly higher in diabetic patients who required insulin than in those who did not. Older patient age, insulin dependency, and small target-vessel diameter all were independent predictors of target-lesion failure at 1 year.
The overall 1-year rate of scaffold thrombosis in this study was 2.3%, which is not surprising given the study population’s risk factors. For diabetic patients with appropriately sized vessels of greater than 2.25 mm diameter, the scaffold thrombosis rate was lower (1.3%).
In addition to being underpowered to assess rare adverse events, this study was limited in that it reported outcomes at 1 year, before resorption of the device was complete. It also reflects the first-time clinical experience with a resorbable scaffold for most of the participating investigators, “and one would expect that as with all new medical procedures, results will improve over time with increased operator experience,” the coauthors wrote.
Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
Key clinical point:
Major finding: The primary endpoint – the rate of target-lesion failure at 1 year follow-up – was 8.3%, which was well below the prespecified performance goal of 12.7%.
Data source: A prespecified formal substudy of 754 patients with diabetes who participated in three clinical trials and one device registry, assessing 1-year outcomes after PCI.
Disclosures: This pooled analysis, plus all the contributing trials and the device registry, were funded by Abbott Vascular, maker of the resorbable scaffold. Dr. Kereiakes reported being a consultant to Abbott Vascular, and his associates also reported ties to the company and to other industry sources.
AAA screening showed no mortality reduction in new trial
In contrast to previous studies, screening for abdominal aortic aneurysms in older men does not appear to have a significant effect on overall mortality, according to a prospective, randomized study.
Mortality from ruptured AAA remains high in older men, which has prompted four previous large randomized trials to explore whether screening men aged 65 years and older might reduce mortality.
Writing in the October 31 online edition of JAMA Internal Medicine, the authors reported the long-term outcomes of an Australian population-based trial of screening for abdominal aortic aneurysms in 49,801 men aged 64-83 years, of whom 19 249 were invited to screening and 12,203 of those underwent screening (isrctn.org Identifier: ISRCTN16171472).
After a mean 12.8 years of follow-up, there was a non-significant 9% lower mortality in the invited screening group compared to the control group and a non-significant 8% lower mortality among men aged 65-74 years.
Overall, there were 90 deaths from ruptured AAA in the screening group and 98 in the control group (JAMA Internal Medicine 2016, October 31. DOI:10.1001/jamainternmed.2016.6633).
The prevalence of abdominal aortic aneurysms with a diameter at or above 30 mm was 6.6% in men aged 65-74, and 0.4% for those with a diameter of 55 mm or above.
While the rate of ruptured abdominal aortic aneurysms was significantly lower in the invited group compared to the control group (72 vs. 99, P = .04), the 30-day mortality after surgery for rupture was higher in the invited group compared to the control group (61.5% vs. 43.2%).
Screening had no meaningful impact on the risk of all-cause, cardiovascular, and other mortality, but men who had smoked had a higher risk of rupture and of death from a rupture than those who had never smoked, regardless of screening status.
The rate of total elective operations was significantly higher in the invited group compared to controls (536 vs. 414, P < .001), mainly in the first year after screening.
The authors calculated that to prevent one death from a ruptured abdominal aortic aneurysm in five years, 4784 men aged 64-83 years or 3290 men aged 65-74 years would need to be invited for screening.
While the strength of the study was that it was truly population-based – using the electoral roll – the authors said the lack of a benefit from screening was likely due to the relatively low rate of rupture and death from AAA, as well as a high rate of elective surgery for this condition, in the control group.
The non-significant 8% reduction in mortality observed in the study was significantly less than the 42% and 66% reductions seen in previous trials with a similar length of follow-up.
The authors suggested this may also have been related to a lower fraction of invited men participating in screening, but pointed out that the incidence of AAA in men is declining.
“The reason for the decrease in incidence and prevalence is multifactorial but is probably driven by differences in rates of smoking and cessation because the relative risk for AAA events is 3- to 6-fold higher in smokers compared with non-smokers,” they wrote.
The authors said selective screening of smokers or ex-smokers may be more effective, but pointed out that this approach would miss around one-quarter of aneurysms. However they suggested more targeted screening may yet achieve a benefit.
“The small overall benefit of population-wide screening does not mean that finding AAAs in suitable older men is not worthwhile because deaths from AAAs in men who actually attended for screening were halved by early detection and successful treatment.”
The study was supported by the National Health and Medical Research Council Project. The authors reported that they had no conflicts of interest.
These new data will not change the finding of robust reduction in AAA-related mortality from screening seen in all previous meta-analyses. However, the most recently updated meta-analyses now reveal the small reduction in all-cause mortality with screening to be statistically significant.
So although the findings of the Western Australian trial remain negative and raise some concerns about screening, their aggregation with other studies does not change the overall conclusions that screening substantially reduced AAA-related mortality and also resulted in a statistically significant reduction in all-cause mortality. Restricting screening to men who have smoked (the strongest risk factor for AAA) further lowers cost and increases efficiency.
Frank A. Lederle, MD, is from the Center for Chronic Disease Outcomes Research at the Veterans Affairs Medical Center. These comments are taken from an accompanying editorial (JAMA Internal Medicine 2016, October 31. DOI:10.1001/jamainternmed.2016.6663). No conflicts of interest were declared.
These new data will not change the finding of robust reduction in AAA-related mortality from screening seen in all previous meta-analyses. However, the most recently updated meta-analyses now reveal the small reduction in all-cause mortality with screening to be statistically significant.
So although the findings of the Western Australian trial remain negative and raise some concerns about screening, their aggregation with other studies does not change the overall conclusions that screening substantially reduced AAA-related mortality and also resulted in a statistically significant reduction in all-cause mortality. Restricting screening to men who have smoked (the strongest risk factor for AAA) further lowers cost and increases efficiency.
Frank A. Lederle, MD, is from the Center for Chronic Disease Outcomes Research at the Veterans Affairs Medical Center. These comments are taken from an accompanying editorial (JAMA Internal Medicine 2016, October 31. DOI:10.1001/jamainternmed.2016.6663). No conflicts of interest were declared.
These new data will not change the finding of robust reduction in AAA-related mortality from screening seen in all previous meta-analyses. However, the most recently updated meta-analyses now reveal the small reduction in all-cause mortality with screening to be statistically significant.
So although the findings of the Western Australian trial remain negative and raise some concerns about screening, their aggregation with other studies does not change the overall conclusions that screening substantially reduced AAA-related mortality and also resulted in a statistically significant reduction in all-cause mortality. Restricting screening to men who have smoked (the strongest risk factor for AAA) further lowers cost and increases efficiency.
Frank A. Lederle, MD, is from the Center for Chronic Disease Outcomes Research at the Veterans Affairs Medical Center. These comments are taken from an accompanying editorial (JAMA Internal Medicine 2016, October 31. DOI:10.1001/jamainternmed.2016.6663). No conflicts of interest were declared.
In contrast to previous studies, screening for abdominal aortic aneurysms in older men does not appear to have a significant effect on overall mortality, according to a prospective, randomized study.
Mortality from ruptured AAA remains high in older men, which has prompted four previous large randomized trials to explore whether screening men aged 65 years and older might reduce mortality.
Writing in the October 31 online edition of JAMA Internal Medicine, the authors reported the long-term outcomes of an Australian population-based trial of screening for abdominal aortic aneurysms in 49,801 men aged 64-83 years, of whom 19 249 were invited to screening and 12,203 of those underwent screening (isrctn.org Identifier: ISRCTN16171472).
After a mean 12.8 years of follow-up, there was a non-significant 9% lower mortality in the invited screening group compared to the control group and a non-significant 8% lower mortality among men aged 65-74 years.
Overall, there were 90 deaths from ruptured AAA in the screening group and 98 in the control group (JAMA Internal Medicine 2016, October 31. DOI:10.1001/jamainternmed.2016.6633).
The prevalence of abdominal aortic aneurysms with a diameter at or above 30 mm was 6.6% in men aged 65-74, and 0.4% for those with a diameter of 55 mm or above.
While the rate of ruptured abdominal aortic aneurysms was significantly lower in the invited group compared to the control group (72 vs. 99, P = .04), the 30-day mortality after surgery for rupture was higher in the invited group compared to the control group (61.5% vs. 43.2%).
Screening had no meaningful impact on the risk of all-cause, cardiovascular, and other mortality, but men who had smoked had a higher risk of rupture and of death from a rupture than those who had never smoked, regardless of screening status.
The rate of total elective operations was significantly higher in the invited group compared to controls (536 vs. 414, P < .001), mainly in the first year after screening.
The authors calculated that to prevent one death from a ruptured abdominal aortic aneurysm in five years, 4784 men aged 64-83 years or 3290 men aged 65-74 years would need to be invited for screening.
While the strength of the study was that it was truly population-based – using the electoral roll – the authors said the lack of a benefit from screening was likely due to the relatively low rate of rupture and death from AAA, as well as a high rate of elective surgery for this condition, in the control group.
The non-significant 8% reduction in mortality observed in the study was significantly less than the 42% and 66% reductions seen in previous trials with a similar length of follow-up.
The authors suggested this may also have been related to a lower fraction of invited men participating in screening, but pointed out that the incidence of AAA in men is declining.
“The reason for the decrease in incidence and prevalence is multifactorial but is probably driven by differences in rates of smoking and cessation because the relative risk for AAA events is 3- to 6-fold higher in smokers compared with non-smokers,” they wrote.
The authors said selective screening of smokers or ex-smokers may be more effective, but pointed out that this approach would miss around one-quarter of aneurysms. However they suggested more targeted screening may yet achieve a benefit.
“The small overall benefit of population-wide screening does not mean that finding AAAs in suitable older men is not worthwhile because deaths from AAAs in men who actually attended for screening were halved by early detection and successful treatment.”
The study was supported by the National Health and Medical Research Council Project. The authors reported that they had no conflicts of interest.
In contrast to previous studies, screening for abdominal aortic aneurysms in older men does not appear to have a significant effect on overall mortality, according to a prospective, randomized study.
Mortality from ruptured AAA remains high in older men, which has prompted four previous large randomized trials to explore whether screening men aged 65 years and older might reduce mortality.
Writing in the October 31 online edition of JAMA Internal Medicine, the authors reported the long-term outcomes of an Australian population-based trial of screening for abdominal aortic aneurysms in 49,801 men aged 64-83 years, of whom 19 249 were invited to screening and 12,203 of those underwent screening (isrctn.org Identifier: ISRCTN16171472).
After a mean 12.8 years of follow-up, there was a non-significant 9% lower mortality in the invited screening group compared to the control group and a non-significant 8% lower mortality among men aged 65-74 years.
Overall, there were 90 deaths from ruptured AAA in the screening group and 98 in the control group (JAMA Internal Medicine 2016, October 31. DOI:10.1001/jamainternmed.2016.6633).
The prevalence of abdominal aortic aneurysms with a diameter at or above 30 mm was 6.6% in men aged 65-74, and 0.4% for those with a diameter of 55 mm or above.
While the rate of ruptured abdominal aortic aneurysms was significantly lower in the invited group compared to the control group (72 vs. 99, P = .04), the 30-day mortality after surgery for rupture was higher in the invited group compared to the control group (61.5% vs. 43.2%).
Screening had no meaningful impact on the risk of all-cause, cardiovascular, and other mortality, but men who had smoked had a higher risk of rupture and of death from a rupture than those who had never smoked, regardless of screening status.
The rate of total elective operations was significantly higher in the invited group compared to controls (536 vs. 414, P < .001), mainly in the first year after screening.
The authors calculated that to prevent one death from a ruptured abdominal aortic aneurysm in five years, 4784 men aged 64-83 years or 3290 men aged 65-74 years would need to be invited for screening.
While the strength of the study was that it was truly population-based – using the electoral roll – the authors said the lack of a benefit from screening was likely due to the relatively low rate of rupture and death from AAA, as well as a high rate of elective surgery for this condition, in the control group.
The non-significant 8% reduction in mortality observed in the study was significantly less than the 42% and 66% reductions seen in previous trials with a similar length of follow-up.
The authors suggested this may also have been related to a lower fraction of invited men participating in screening, but pointed out that the incidence of AAA in men is declining.
“The reason for the decrease in incidence and prevalence is multifactorial but is probably driven by differences in rates of smoking and cessation because the relative risk for AAA events is 3- to 6-fold higher in smokers compared with non-smokers,” they wrote.
The authors said selective screening of smokers or ex-smokers may be more effective, but pointed out that this approach would miss around one-quarter of aneurysms. However they suggested more targeted screening may yet achieve a benefit.
“The small overall benefit of population-wide screening does not mean that finding AAAs in suitable older men is not worthwhile because deaths from AAAs in men who actually attended for screening were halved by early detection and successful treatment.”
The study was supported by the National Health and Medical Research Council Project. The authors reported that they had no conflicts of interest.
Key clinical point:
Major finding: Men invited to undergo screening for abdominal aortic aneurysms had a non-significant 9% lower mortality compared to a control group.
Data source: Prospective, population-based randomized controlled trial in 49,801 men aged 64-83 years.
Disclosures: The study was supported by the National Health and Medical Research Council Project. The authors reported that they had no conflicts of interest.
PCI noninferior to CABG for certain left main CAD
Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.
The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).
Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.
This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.
Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).
They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.
The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.
At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.
The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.
During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).
Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.
The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.
Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.
Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.
Dr. Stone and his associates reported ties to numerous industry sources.
The well-designed and rigorously conducted EXCEL trial’s take-home message is that most patients with left main CAD can now be managed equally well using either PCI or CABG, provided that their treatment team is as experienced as those participating in the study.
PCI may be favored in some patients because of its greater periprocedural safety, shorter hospital stay, and more rapid recovery. However, the composite rate of death, stroke, or MI after 30 days was higher with PCI (11.5% vs 7.9%). It is reassuring that these study participants will be followed for another 2 years so that longer-term events can be assessed.
Eugene Braunwald, MD, is in the Thrombolysis in Myocardial Infarction Study Group, in the cardiovascular division at Brigham and Women’s Hospital, and in the department of medicine at Harvard Medical School. He reported having no relevant financial disclosures. Dr. Braunwald made these remarks in an editorial accompanying Dr. Stone’s report (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMe1612570).
The well-designed and rigorously conducted EXCEL trial’s take-home message is that most patients with left main CAD can now be managed equally well using either PCI or CABG, provided that their treatment team is as experienced as those participating in the study.
PCI may be favored in some patients because of its greater periprocedural safety, shorter hospital stay, and more rapid recovery. However, the composite rate of death, stroke, or MI after 30 days was higher with PCI (11.5% vs 7.9%). It is reassuring that these study participants will be followed for another 2 years so that longer-term events can be assessed.
Eugene Braunwald, MD, is in the Thrombolysis in Myocardial Infarction Study Group, in the cardiovascular division at Brigham and Women’s Hospital, and in the department of medicine at Harvard Medical School. He reported having no relevant financial disclosures. Dr. Braunwald made these remarks in an editorial accompanying Dr. Stone’s report (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMe1612570).
The well-designed and rigorously conducted EXCEL trial’s take-home message is that most patients with left main CAD can now be managed equally well using either PCI or CABG, provided that their treatment team is as experienced as those participating in the study.
PCI may be favored in some patients because of its greater periprocedural safety, shorter hospital stay, and more rapid recovery. However, the composite rate of death, stroke, or MI after 30 days was higher with PCI (11.5% vs 7.9%). It is reassuring that these study participants will be followed for another 2 years so that longer-term events can be assessed.
Eugene Braunwald, MD, is in the Thrombolysis in Myocardial Infarction Study Group, in the cardiovascular division at Brigham and Women’s Hospital, and in the department of medicine at Harvard Medical School. He reported having no relevant financial disclosures. Dr. Braunwald made these remarks in an editorial accompanying Dr. Stone’s report (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMe1612570).
Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.
The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).
Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.
This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.
Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).
They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.
The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.
At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.
The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.
During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).
Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.
The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.
Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.
Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.
Dr. Stone and his associates reported ties to numerous industry sources.
Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.
The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).
Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.
This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.
Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).
They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.
The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.
At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.
The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.
During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).
Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.
The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.
Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.
Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.
Dr. Stone and his associates reported ties to numerous industry sources.
Key clinical point: PCI was found noninferior to CABG regarding the composite end point of death, stroke, or myocardial infarction in certain patients with left main CAD.
Major finding: The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (HR, 1.00) that demonstrates the noninferiority of PCI.
Data source: An international open-label randomized trial involving 1,905 patients followed for 3 years.
Disclosures: The EXCEL trial was funded by Abbott Vascular, maker of the everolimus-eluting stent used in this study. The company participated in the design of the trial and in selection and management of the treatment sites, but was not involved in managing or analyzing the data or writing the manuscript. Dr. Stone and his associates reported ties to numerous industry sources.
Surgical treatment tops medical management of prosthetic valve endocarditis
NEW ORLEANS – Over the years patients with prosthetic valve endocarditis treated at Cleveland Clinic tended to fare better with surgery compared to medical management, some clinicians noted. However, there was no data to confirm their observations.
“It was not recognized widely. A lot of our colleagues continued to believe it could be adequately treated with the right antibiotic,” Nabin K. Shrestha, MD, said at the IDWeek 2016 annual meeting on infectious diseases.
So Dr Shrestha and his colleagues conducted a retrospective cohort study to compare outcomes between 253 surgically treated adults and 77 others treated medically between April 2008 and December 2012. Survival from the time of treatment decision was the primary outcome.
The groups differed on some demographic and clinical factors. For example, the medically treated group was older, had fewer men, and more patients with mitral valves. “We might think the medical patients might be too sick for surgery, and that could certainly be true, but … they could have been too well for surgery too,” Dr. Shrestha said. To control for these differences between groups, the investigators performed a number of statistical analyses, including a propensity score adjusted model and reduced Cox proportion hazards model.
“Patients with PVE have a high hazard of death if treated medically,” Dr. Shrestha said, based on a 6.68 hazard ratio. The higher risk of death associated with medical treatment remained significant when adjusted for age, sex, and other factors. “Compared to surgical treatment, medical treatment was associated with a seven-fold higher hazard of death overall,” Dr. Shrestha said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The medical treatment group also fared worse on a number of secondary outcomes. For example, this group had a five-fold higher risk of death during hospitalization compared to the surgery group (odds ratio, 4.65); a 12-fold higher risk of death within one year (OR, 11.70); a seven-fold higher risk of subsequent surgery for infective endocarditis (OR, 6.57); and an eight-fold higher odds of surgery for the same episode of infective endocarditis at a subsequent hospitalization (OR, 8.02).
A large sample size and setting the date of management decision as time zero to avoid survival selection bias “give us confidence in our findings.” Limitations include an inability to look at some important variables because of the retrospective design.
A meeting attendee commented that surgeons often request a patient be optimized medically prior to surgery, and asked if investigators looked at time from hospitalization to the operation.
“The median date from admission to surgery was six days in our database,” said Dr. Shrestha, who is a staff physician at the Cleveland Clinic in Ohio.
“Medical treatment overall is associated with significantly poorer outcomes in patients with PVE compared with surgical treatment,” Dr. Shrestha said. “Although some patients are not candidates for surgery, a definite diagnosis of PVE should prompt a surgical evaluation in the majority of patients.”
Dr. Shrestha reported having no disclosures.
NEW ORLEANS – Over the years patients with prosthetic valve endocarditis treated at Cleveland Clinic tended to fare better with surgery compared to medical management, some clinicians noted. However, there was no data to confirm their observations.
“It was not recognized widely. A lot of our colleagues continued to believe it could be adequately treated with the right antibiotic,” Nabin K. Shrestha, MD, said at the IDWeek 2016 annual meeting on infectious diseases.
So Dr Shrestha and his colleagues conducted a retrospective cohort study to compare outcomes between 253 surgically treated adults and 77 others treated medically between April 2008 and December 2012. Survival from the time of treatment decision was the primary outcome.
The groups differed on some demographic and clinical factors. For example, the medically treated group was older, had fewer men, and more patients with mitral valves. “We might think the medical patients might be too sick for surgery, and that could certainly be true, but … they could have been too well for surgery too,” Dr. Shrestha said. To control for these differences between groups, the investigators performed a number of statistical analyses, including a propensity score adjusted model and reduced Cox proportion hazards model.
“Patients with PVE have a high hazard of death if treated medically,” Dr. Shrestha said, based on a 6.68 hazard ratio. The higher risk of death associated with medical treatment remained significant when adjusted for age, sex, and other factors. “Compared to surgical treatment, medical treatment was associated with a seven-fold higher hazard of death overall,” Dr. Shrestha said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The medical treatment group also fared worse on a number of secondary outcomes. For example, this group had a five-fold higher risk of death during hospitalization compared to the surgery group (odds ratio, 4.65); a 12-fold higher risk of death within one year (OR, 11.70); a seven-fold higher risk of subsequent surgery for infective endocarditis (OR, 6.57); and an eight-fold higher odds of surgery for the same episode of infective endocarditis at a subsequent hospitalization (OR, 8.02).
A large sample size and setting the date of management decision as time zero to avoid survival selection bias “give us confidence in our findings.” Limitations include an inability to look at some important variables because of the retrospective design.
A meeting attendee commented that surgeons often request a patient be optimized medically prior to surgery, and asked if investigators looked at time from hospitalization to the operation.
“The median date from admission to surgery was six days in our database,” said Dr. Shrestha, who is a staff physician at the Cleveland Clinic in Ohio.
“Medical treatment overall is associated with significantly poorer outcomes in patients with PVE compared with surgical treatment,” Dr. Shrestha said. “Although some patients are not candidates for surgery, a definite diagnosis of PVE should prompt a surgical evaluation in the majority of patients.”
Dr. Shrestha reported having no disclosures.
NEW ORLEANS – Over the years patients with prosthetic valve endocarditis treated at Cleveland Clinic tended to fare better with surgery compared to medical management, some clinicians noted. However, there was no data to confirm their observations.
“It was not recognized widely. A lot of our colleagues continued to believe it could be adequately treated with the right antibiotic,” Nabin K. Shrestha, MD, said at the IDWeek 2016 annual meeting on infectious diseases.
So Dr Shrestha and his colleagues conducted a retrospective cohort study to compare outcomes between 253 surgically treated adults and 77 others treated medically between April 2008 and December 2012. Survival from the time of treatment decision was the primary outcome.
The groups differed on some demographic and clinical factors. For example, the medically treated group was older, had fewer men, and more patients with mitral valves. “We might think the medical patients might be too sick for surgery, and that could certainly be true, but … they could have been too well for surgery too,” Dr. Shrestha said. To control for these differences between groups, the investigators performed a number of statistical analyses, including a propensity score adjusted model and reduced Cox proportion hazards model.
“Patients with PVE have a high hazard of death if treated medically,” Dr. Shrestha said, based on a 6.68 hazard ratio. The higher risk of death associated with medical treatment remained significant when adjusted for age, sex, and other factors. “Compared to surgical treatment, medical treatment was associated with a seven-fold higher hazard of death overall,” Dr. Shrestha said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The medical treatment group also fared worse on a number of secondary outcomes. For example, this group had a five-fold higher risk of death during hospitalization compared to the surgery group (odds ratio, 4.65); a 12-fold higher risk of death within one year (OR, 11.70); a seven-fold higher risk of subsequent surgery for infective endocarditis (OR, 6.57); and an eight-fold higher odds of surgery for the same episode of infective endocarditis at a subsequent hospitalization (OR, 8.02).
A large sample size and setting the date of management decision as time zero to avoid survival selection bias “give us confidence in our findings.” Limitations include an inability to look at some important variables because of the retrospective design.
A meeting attendee commented that surgeons often request a patient be optimized medically prior to surgery, and asked if investigators looked at time from hospitalization to the operation.
“The median date from admission to surgery was six days in our database,” said Dr. Shrestha, who is a staff physician at the Cleveland Clinic in Ohio.
“Medical treatment overall is associated with significantly poorer outcomes in patients with PVE compared with surgical treatment,” Dr. Shrestha said. “Although some patients are not candidates for surgery, a definite diagnosis of PVE should prompt a surgical evaluation in the majority of patients.”
Dr. Shrestha reported having no disclosures.
Key clinical point:
Major finding: Compared to surgery, odds of death within one year higher were almost 7 times greater with medical treatment (hazard ratio, 6.68).
Data source: Presentation at IDWeek 2016
Disclosures: Dr. Nabin K. Shrestha had no relevant disclosures.
Deep brain stimulation for early Parkinson’s disease has long-term benefit
BALTIMORE – The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.
If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.
The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.
The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.
Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.
“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.
The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.
The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.
Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.
BALTIMORE – The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.
If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.
The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.
The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.
Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.
“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.
The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.
The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.
Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.
BALTIMORE – The use of subthalamic nucleus deep brain stimulation (DBS) along with optimal drug therapy in patients with early stage Parkinson’s disease produced clinically meaningful improvements in clinician-assessed motor control that lasted at least 5 years in a prospective pilot study.
If the findings bear out a phase III trial that has been approved, DBS may become a valuable method to achieve long-term improvement in motor skills in patients with Parkinson’s disease.
The pilot trial involved 30 patients with Parkinson’s disease, aged 50-75 years, and demonstrated the safety and benefit of DBS in conjunction with optimal drug therapy (ODT) – involving drugs such as carbidopa/levodopa, pramipexole, ropinirole, and selegiline – compared with ODT alone in improving motor scores of the patients through 2 years (Parkinsonism Relat Disord. 2014. 20[7]:731-7). The latest subanalysis of the trial data took a longer look, examining the effect of DBS through 5 years.
The subanalysis involved 28 patients; 14 in the DBS plus ODT group and 14 in the ODT-only group. Both groups were predominantly male and were similar in age at baseline (about 61 years). Motor control was assessed during the periods when DBS was applied and not applied by using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III (clinician assessed) and the Hoehn and Yahr scale.
Over the 5-year period, mean UPDRS motor scores progressively worsened for the ODT group but improved for patients receiving DBS. Patients who received DBS plus ODT had improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.
“These results demonstrate that subthalamic nucleus deep brain stimulation applied in early-stage Parkinson’s disease may provide long-term, clinically meaningful improvement in motor function over standard clinical therapy,” Dr. Hacker said.
The exact mechanism of DBS is still unknown. But, there is evidence that synaptic plasticity is involved. Dr. Hacker speculated that in early Parkinson’s, the DBS intervention comes at a time of relative neuronal stability, which is then maintained.
The results of the pilot trial led to Food and Drug Administration approval of a large-scale, multicenter clinical trial. All participants will be implanted with a DBS device and will receive ODT. Some of the subjects will be randomized to receive DBS during the first 2 years, along with ODT, with the remainder receiving ODT only. In the next 2 years, all subjects will receive DBS and ODT.
Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Hacker had no disclosures.
Key clinical point:
Major finding: Patients who received DBS plus ODT had UPDRS motor score improvements relative to the ODT-only patients of 4.6 points at 1.5 years, 5.8 points at 2 years, 8.9 points at 4 years, and 10.1 points at 5 years.
Data source: Secondary analysis of a pilot, prospective, randomized, controlled, single-blind clinical trial involving 30 patients with early Parkinson’s disease.
Disclosures: Dr. Hacker had no disclosures. Funding was provided by the National Center for Advancing Translational Science, the National Institutes of Health, Medtronic, and the Michael J. Fox Foundation for Parkinson’s Research.
Anti–nerve growth factor drug has long-term OA pain benefit, but unclear safety
Treatment for a year with the human anti–nerve growth factor monoclonal antibody fulranumab provided pain relief and functional benefits to patients with moderate to severe chronic osteoarthritis knee or hip pain but continued to show signs that the biologic may contribute to rapid progression of disease in a proportion of patients who came to need joint replacement, especially when used concurrently with nonsteroidal anti-inflammatory drugs.
The findings come from the double-blind extension phase of a 12-week, phase II, placebo-controlled, double-blind, randomized study that found significant reduction in the average pain intensity score (P less than or equal to .030) for patients who took fulranumab (Pain. 2013 Oct;154[10]:1910-9). The investigators wanted to determine the long-term safety of the biologic in light of the Food and Drug Administration’s 2010 “clinical hold” on studies of anti–nerve growth factor (anti-NGF) drugs such as fulranumab after concerns emerged that the class of anti-NGF antibodies may be associated with potential treatment-emergent adverse events (TEAEs) leading to joint destruction.
The long-term safety and efficacy results in the extension phase of the study when fulranumab was given as an adjunctive therapy to standard pain therapy revealed higher rates of serious TEAEs, including joint replacement, that were associated with fulranumab. While most of those TEAEs were independently adjudicated to stem from normal progression of OA, one-fifth of the patients on fulranumab who needed joint replacement had rapid progression of OA (RPOA).
Investigators led by Panna Sanga, MD, director of clinical research at Janssen, sought to determine the effects of the anti-NGF biologic as an adjunctive therapy to standard pain therapy over a 92-week period in 401 patients who had completed the 12-week efficacy study, as well as over a 26-week posttreatment follow-up. In the current extension phase of the trial, patients continued on their randomized dose in the original trial of placebo or subcutaneous fulranumab 1 mg or 3 mg every 4 weeks or fulranumab 3 mg, 6 mg, or 10 mg every 8 weeks, but they were permitted to change their concurrent pain medications as clinically needed.
Although the study intended for patients to receive 2 years of treatment (104 weeks), the FDA’s clinical hold meant that the median duration of exposure to fulranumab in the extension study was only 365-393 days across the dosing regimens, the authors explained (Arthritis Rheumatol. 2016 Oct 16 doi: 10.1002/art.39943).
Overall, 421 (90%) of 466 intent-to-treat patients experienced at least one TEAE during both study phases, with similar incidence between those randomized to placebo (n = 69, 88%) and the fulranumab groups (n = 352, 91%).
TEAEs that occurred with a frequency of 10% or more among all fulranumab-treated patients were arthralgia (21%), OA (18%), paresthesia, and upper respiratory tract infection (13% each), while these were arthralgia (15%), OA (14%), and sinusitis (12%) among patients randomized to placebo.
A total of 109 patients (23%) reported serious TEAEs, including 13 (17%) taking placebo and 96 (25%) taking fulranumab. Serious TEAEs that were reported in 5% or more of patients in the fulranumab groups were knee arthroplasty (n = 38, 10%) and hip arthroplasty (n = 26, 7%). Overall, 81 joint replacements occurred in 71 patients (placebo: n = , 11%; fulranumab: n = 63, 89%).
An independent adjudication committee that the study sponsor, Janssen, established after the study was put on hold ruled that the majority of these joint replacements resulted from the normal progression of OA (n = 56, 79%). However, the adjudication committee determined that 15 (21%) patients in the fulranumab treatment groups had RPOA.
The study authors pointed out that the patients with RPOA regularly used NSAIDs and had a prior history of OA in the affected joint. Nevertheless, because of the small number of RPOA cases per treatment group, a drug or dose effect for RPOA could not be evaluated, they said.
“Future studies are warranted to demonstrate whether limiting the use of concomitant chronic NSAIDs and using only lower doses of fulranumab may reduce the risk of RPOA,” they wrote.
The extension study also looked at the longer-term efficacy of fulranumab. Efficacy endpoints on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales and the Patient Global Assessment (PGA) scores that looked at changes from baseline showed that in comparison with placebo, dosing regimens of fulranumab 3 mg every 4 weeks and 10 mg every 8 weeks gave “continued effective relief of the pain associated with knee and hip OA as early as week 4 and was maintained up to week 53,” the researchers reported.
These results were further corroborated by improvements in physical function on the WOMAC physical function subscale and PGA scale scores, which suggested “sustained efficacy of long-term fulranumab treatment,” they said.
All authors except one were employees of Janssen.
Treatment for a year with the human anti–nerve growth factor monoclonal antibody fulranumab provided pain relief and functional benefits to patients with moderate to severe chronic osteoarthritis knee or hip pain but continued to show signs that the biologic may contribute to rapid progression of disease in a proportion of patients who came to need joint replacement, especially when used concurrently with nonsteroidal anti-inflammatory drugs.
The findings come from the double-blind extension phase of a 12-week, phase II, placebo-controlled, double-blind, randomized study that found significant reduction in the average pain intensity score (P less than or equal to .030) for patients who took fulranumab (Pain. 2013 Oct;154[10]:1910-9). The investigators wanted to determine the long-term safety of the biologic in light of the Food and Drug Administration’s 2010 “clinical hold” on studies of anti–nerve growth factor (anti-NGF) drugs such as fulranumab after concerns emerged that the class of anti-NGF antibodies may be associated with potential treatment-emergent adverse events (TEAEs) leading to joint destruction.
The long-term safety and efficacy results in the extension phase of the study when fulranumab was given as an adjunctive therapy to standard pain therapy revealed higher rates of serious TEAEs, including joint replacement, that were associated with fulranumab. While most of those TEAEs were independently adjudicated to stem from normal progression of OA, one-fifth of the patients on fulranumab who needed joint replacement had rapid progression of OA (RPOA).
Investigators led by Panna Sanga, MD, director of clinical research at Janssen, sought to determine the effects of the anti-NGF biologic as an adjunctive therapy to standard pain therapy over a 92-week period in 401 patients who had completed the 12-week efficacy study, as well as over a 26-week posttreatment follow-up. In the current extension phase of the trial, patients continued on their randomized dose in the original trial of placebo or subcutaneous fulranumab 1 mg or 3 mg every 4 weeks or fulranumab 3 mg, 6 mg, or 10 mg every 8 weeks, but they were permitted to change their concurrent pain medications as clinically needed.
Although the study intended for patients to receive 2 years of treatment (104 weeks), the FDA’s clinical hold meant that the median duration of exposure to fulranumab in the extension study was only 365-393 days across the dosing regimens, the authors explained (Arthritis Rheumatol. 2016 Oct 16 doi: 10.1002/art.39943).
Overall, 421 (90%) of 466 intent-to-treat patients experienced at least one TEAE during both study phases, with similar incidence between those randomized to placebo (n = 69, 88%) and the fulranumab groups (n = 352, 91%).
TEAEs that occurred with a frequency of 10% or more among all fulranumab-treated patients were arthralgia (21%), OA (18%), paresthesia, and upper respiratory tract infection (13% each), while these were arthralgia (15%), OA (14%), and sinusitis (12%) among patients randomized to placebo.
A total of 109 patients (23%) reported serious TEAEs, including 13 (17%) taking placebo and 96 (25%) taking fulranumab. Serious TEAEs that were reported in 5% or more of patients in the fulranumab groups were knee arthroplasty (n = 38, 10%) and hip arthroplasty (n = 26, 7%). Overall, 81 joint replacements occurred in 71 patients (placebo: n = , 11%; fulranumab: n = 63, 89%).
An independent adjudication committee that the study sponsor, Janssen, established after the study was put on hold ruled that the majority of these joint replacements resulted from the normal progression of OA (n = 56, 79%). However, the adjudication committee determined that 15 (21%) patients in the fulranumab treatment groups had RPOA.
The study authors pointed out that the patients with RPOA regularly used NSAIDs and had a prior history of OA in the affected joint. Nevertheless, because of the small number of RPOA cases per treatment group, a drug or dose effect for RPOA could not be evaluated, they said.
“Future studies are warranted to demonstrate whether limiting the use of concomitant chronic NSAIDs and using only lower doses of fulranumab may reduce the risk of RPOA,” they wrote.
The extension study also looked at the longer-term efficacy of fulranumab. Efficacy endpoints on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales and the Patient Global Assessment (PGA) scores that looked at changes from baseline showed that in comparison with placebo, dosing regimens of fulranumab 3 mg every 4 weeks and 10 mg every 8 weeks gave “continued effective relief of the pain associated with knee and hip OA as early as week 4 and was maintained up to week 53,” the researchers reported.
These results were further corroborated by improvements in physical function on the WOMAC physical function subscale and PGA scale scores, which suggested “sustained efficacy of long-term fulranumab treatment,” they said.
All authors except one were employees of Janssen.
Treatment for a year with the human anti–nerve growth factor monoclonal antibody fulranumab provided pain relief and functional benefits to patients with moderate to severe chronic osteoarthritis knee or hip pain but continued to show signs that the biologic may contribute to rapid progression of disease in a proportion of patients who came to need joint replacement, especially when used concurrently with nonsteroidal anti-inflammatory drugs.
The findings come from the double-blind extension phase of a 12-week, phase II, placebo-controlled, double-blind, randomized study that found significant reduction in the average pain intensity score (P less than or equal to .030) for patients who took fulranumab (Pain. 2013 Oct;154[10]:1910-9). The investigators wanted to determine the long-term safety of the biologic in light of the Food and Drug Administration’s 2010 “clinical hold” on studies of anti–nerve growth factor (anti-NGF) drugs such as fulranumab after concerns emerged that the class of anti-NGF antibodies may be associated with potential treatment-emergent adverse events (TEAEs) leading to joint destruction.
The long-term safety and efficacy results in the extension phase of the study when fulranumab was given as an adjunctive therapy to standard pain therapy revealed higher rates of serious TEAEs, including joint replacement, that were associated with fulranumab. While most of those TEAEs were independently adjudicated to stem from normal progression of OA, one-fifth of the patients on fulranumab who needed joint replacement had rapid progression of OA (RPOA).
Investigators led by Panna Sanga, MD, director of clinical research at Janssen, sought to determine the effects of the anti-NGF biologic as an adjunctive therapy to standard pain therapy over a 92-week period in 401 patients who had completed the 12-week efficacy study, as well as over a 26-week posttreatment follow-up. In the current extension phase of the trial, patients continued on their randomized dose in the original trial of placebo or subcutaneous fulranumab 1 mg or 3 mg every 4 weeks or fulranumab 3 mg, 6 mg, or 10 mg every 8 weeks, but they were permitted to change their concurrent pain medications as clinically needed.
Although the study intended for patients to receive 2 years of treatment (104 weeks), the FDA’s clinical hold meant that the median duration of exposure to fulranumab in the extension study was only 365-393 days across the dosing regimens, the authors explained (Arthritis Rheumatol. 2016 Oct 16 doi: 10.1002/art.39943).
Overall, 421 (90%) of 466 intent-to-treat patients experienced at least one TEAE during both study phases, with similar incidence between those randomized to placebo (n = 69, 88%) and the fulranumab groups (n = 352, 91%).
TEAEs that occurred with a frequency of 10% or more among all fulranumab-treated patients were arthralgia (21%), OA (18%), paresthesia, and upper respiratory tract infection (13% each), while these were arthralgia (15%), OA (14%), and sinusitis (12%) among patients randomized to placebo.
A total of 109 patients (23%) reported serious TEAEs, including 13 (17%) taking placebo and 96 (25%) taking fulranumab. Serious TEAEs that were reported in 5% or more of patients in the fulranumab groups were knee arthroplasty (n = 38, 10%) and hip arthroplasty (n = 26, 7%). Overall, 81 joint replacements occurred in 71 patients (placebo: n = , 11%; fulranumab: n = 63, 89%).
An independent adjudication committee that the study sponsor, Janssen, established after the study was put on hold ruled that the majority of these joint replacements resulted from the normal progression of OA (n = 56, 79%). However, the adjudication committee determined that 15 (21%) patients in the fulranumab treatment groups had RPOA.
The study authors pointed out that the patients with RPOA regularly used NSAIDs and had a prior history of OA in the affected joint. Nevertheless, because of the small number of RPOA cases per treatment group, a drug or dose effect for RPOA could not be evaluated, they said.
“Future studies are warranted to demonstrate whether limiting the use of concomitant chronic NSAIDs and using only lower doses of fulranumab may reduce the risk of RPOA,” they wrote.
The extension study also looked at the longer-term efficacy of fulranumab. Efficacy endpoints on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales and the Patient Global Assessment (PGA) scores that looked at changes from baseline showed that in comparison with placebo, dosing regimens of fulranumab 3 mg every 4 weeks and 10 mg every 8 weeks gave “continued effective relief of the pain associated with knee and hip OA as early as week 4 and was maintained up to week 53,” the researchers reported.
These results were further corroborated by improvements in physical function on the WOMAC physical function subscale and PGA scale scores, which suggested “sustained efficacy of long-term fulranumab treatment,” they said.
All authors except one were employees of Janssen.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: A total of 81 joint replacements occurred in 71 patients (placebo: n = 8, 11%; fulranumab: n = 63, 89%).
Data source: Phase II randomized double-blind extension study of 401 patients with moderate to severe chronic OA knee or hip pain.
Disclosures: All authors except one were employees of Janssen, which funded the study.
Ezetimibe’s ACS benefit centers on high-risk, post-CABG patients
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: The absolute primary-event risk reduction was 9% in post-CABG patients and 1% in all other patients.
Data source: An exploratory, post-hoc analysis of data collected in IMPROVE-IT, a multicenter trial with 18,144 patients.
Disclosures: IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
Drug prices, not the health law, top voters’ health priorities for 2017
Until this week, when big increases in insurance premiums were unveiled for next year, the federal health law has not been a major issue in the presidential election. In fact, fixing what ails the Affordable Care Act isn’t even among voters’ top priorities for health issues for next year, according to a new poll.
The monthly October tracking poll from the Kaiser Family Foundation finds that, when voters are asked about what the next president and Congress should do about health care, issues relating to prescription drug prices and out-of-pocket spending far outrank proposals to address the shortcomings of the health law. (Kaiser Health News is an editorially independent project of the foundation.)
By contrast, fewer than a third of all voters favored proposals to repeal requirements in the health law for employers to provide health insurance to their workers or pay a fine; reduce the tax subsidies that help people pay their insurance premiums, and eliminate a tax on high-cost health plans.
Republicans (but not Democrats or independents) still overwhelmingly want to repeal the entire health law, with 60% supporting that action. But Republicans are fractured on why they don’t like the law. Asked what their main reason is for their disapproval, nearly a third (31%) said the law “gives government too big a role in the health care system,” while 27% said “the law is just one of many indications that President Obama took the country in the wrong direction.”
The poll also asked voters about adding a government-sponsored “public option” to health plans available to those purchasing insurance in the health law’s marketplaces. Both President Barack Obama and Democratic nominee Hillary Clinton have called for reconsideration of the idea, which narrowly failed to be included in the original law in 2010.
As with the health law itself, semantics matter in this debate over whether to include a government plan to compete with private plans. Even in describing the same concept, a much larger majority (70%) favored the idea of “creating a public health insurance option to compete with private health insurance plans” than favored “creating a government-administered public health insurance option to compete with private health insurance plans” (53%).
Opinions about a public option are also relatively easily swayed when voters are presented with arguments for and against the idea. For example, 21% of supporters shifted to opposition when told that doctors and hospitals might be paid less under a public option, while 13% shifted from opposition to support when told that having a public plan compete with private plans might help drive down costs.
The survey was conducted between Oct. 12 and Oct. 18 among 1,205 adults, using both land lines and cell phones. The margin of error was plus or minus 3%.
This story was produced by Kaiser Health News, a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Until this week, when big increases in insurance premiums were unveiled for next year, the federal health law has not been a major issue in the presidential election. In fact, fixing what ails the Affordable Care Act isn’t even among voters’ top priorities for health issues for next year, according to a new poll.
The monthly October tracking poll from the Kaiser Family Foundation finds that, when voters are asked about what the next president and Congress should do about health care, issues relating to prescription drug prices and out-of-pocket spending far outrank proposals to address the shortcomings of the health law. (Kaiser Health News is an editorially independent project of the foundation.)
By contrast, fewer than a third of all voters favored proposals to repeal requirements in the health law for employers to provide health insurance to their workers or pay a fine; reduce the tax subsidies that help people pay their insurance premiums, and eliminate a tax on high-cost health plans.
Republicans (but not Democrats or independents) still overwhelmingly want to repeal the entire health law, with 60% supporting that action. But Republicans are fractured on why they don’t like the law. Asked what their main reason is for their disapproval, nearly a third (31%) said the law “gives government too big a role in the health care system,” while 27% said “the law is just one of many indications that President Obama took the country in the wrong direction.”
The poll also asked voters about adding a government-sponsored “public option” to health plans available to those purchasing insurance in the health law’s marketplaces. Both President Barack Obama and Democratic nominee Hillary Clinton have called for reconsideration of the idea, which narrowly failed to be included in the original law in 2010.
As with the health law itself, semantics matter in this debate over whether to include a government plan to compete with private plans. Even in describing the same concept, a much larger majority (70%) favored the idea of “creating a public health insurance option to compete with private health insurance plans” than favored “creating a government-administered public health insurance option to compete with private health insurance plans” (53%).
Opinions about a public option are also relatively easily swayed when voters are presented with arguments for and against the idea. For example, 21% of supporters shifted to opposition when told that doctors and hospitals might be paid less under a public option, while 13% shifted from opposition to support when told that having a public plan compete with private plans might help drive down costs.
The survey was conducted between Oct. 12 and Oct. 18 among 1,205 adults, using both land lines and cell phones. The margin of error was plus or minus 3%.
This story was produced by Kaiser Health News, a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Until this week, when big increases in insurance premiums were unveiled for next year, the federal health law has not been a major issue in the presidential election. In fact, fixing what ails the Affordable Care Act isn’t even among voters’ top priorities for health issues for next year, according to a new poll.
The monthly October tracking poll from the Kaiser Family Foundation finds that, when voters are asked about what the next president and Congress should do about health care, issues relating to prescription drug prices and out-of-pocket spending far outrank proposals to address the shortcomings of the health law. (Kaiser Health News is an editorially independent project of the foundation.)
By contrast, fewer than a third of all voters favored proposals to repeal requirements in the health law for employers to provide health insurance to their workers or pay a fine; reduce the tax subsidies that help people pay their insurance premiums, and eliminate a tax on high-cost health plans.
Republicans (but not Democrats or independents) still overwhelmingly want to repeal the entire health law, with 60% supporting that action. But Republicans are fractured on why they don’t like the law. Asked what their main reason is for their disapproval, nearly a third (31%) said the law “gives government too big a role in the health care system,” while 27% said “the law is just one of many indications that President Obama took the country in the wrong direction.”
The poll also asked voters about adding a government-sponsored “public option” to health plans available to those purchasing insurance in the health law’s marketplaces. Both President Barack Obama and Democratic nominee Hillary Clinton have called for reconsideration of the idea, which narrowly failed to be included in the original law in 2010.
As with the health law itself, semantics matter in this debate over whether to include a government plan to compete with private plans. Even in describing the same concept, a much larger majority (70%) favored the idea of “creating a public health insurance option to compete with private health insurance plans” than favored “creating a government-administered public health insurance option to compete with private health insurance plans” (53%).
Opinions about a public option are also relatively easily swayed when voters are presented with arguments for and against the idea. For example, 21% of supporters shifted to opposition when told that doctors and hospitals might be paid less under a public option, while 13% shifted from opposition to support when told that having a public plan compete with private plans might help drive down costs.
The survey was conducted between Oct. 12 and Oct. 18 among 1,205 adults, using both land lines and cell phones. The margin of error was plus or minus 3%.
This story was produced by Kaiser Health News, a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Pediatric OSA improved with oral montelukast
The majority of children with obstructive sleep apnea (OSA) who took oral montelukast showed reductions in their apnea-hypopnea index (AHI) scores, in a randomized, double-blind placebo-controlled study.
Typically, OSA in children is treated by adenotonsillectomy, according to Leila Kheirandish-Gozal, MD, director of clinical sleep research at the University of Chicago, and her colleagues. Prior to this study, only one randomized controlled trial had showed that children with mild OSA “responded favorably” to the leukotriene modifier montelukast (Pediatrics. 2012 Aug 31. doi: 10.1542/peds.2012-0310).
Twenty (71%) of the children who received montelukast had fewer AHI events per hour of total sleep time at the end of the study. The average number of such events for these patients was 4.2 plus or minus 2.8 after taking the drug, compared with 9.2 plus or minus 4.1 at the beginning of the study (P less than .0001). Only two (6.9%) of the patients who took the placebo had lower AHI scores at the end of the study, with the average AHI score for the placebo group having been 8.7 plus or minus 4.9 events per hour of total sleep time. At baseline, the average score for patients in the placebo group was 8.2 plus or minus 5.0 AHI events per hour of total sleep time at baseline.
Another improvement seen by patients who received the drug was a decrease in the number of 3% reductions in arterial oxygen saturation per hour of sleep. At the beginning of the study, these patients had 7.2 plus or minus 3.1 of these events; by the end of the study, the number of these events was down to 2.8 plus or minus 1.8 (P less than .001). No significant decrease in the number of these events was seen among patients in the placebo group.
In this study, “montelukast emerges as favorably reducing the severity of OSA short term in children 2-10 years of age. These findings add to the existing evidence supporting a therapeutic role for anti-inflammatory approaches in the management of this highly prevalent condition in children, and clearly justify future studies targeting the long-term benefits of these approaches in children with OSA,” the researchers wrote.
All patients participated in overnight sleep studies following a referral to one of two sleep clinics by their primary care pediatrician or pediatric otolaryngologist, at the beginning of the study. Children who had been diagnosed with symptomatic snoring and had an AHI score of greater than 2 events per hour of total sleep time, and for whom adenotonsillectomy was contemplated, were included in the study.
Central, obstructive, mixed apneic events were counted and hypopneas were assessed. OSA was defined “as the absence of airflow with continued chest wall and abdominal movement for a duration of at least two breaths,” the investigators said. Hypopneas were defined “as a decrease in oronasal flow greater than 50% on either the thermistor or nasal pressure transducer signal. with a corresponding decrease in arterial oxygen saturation greater than 3% or arousal,” Dr. Kheirandish-Gozal and her coauthors said.
Patients were excluded from the study for a variety of reasons, including having severe OSA requiring early surgical intervention.
Adverse events included headache in two children, one from the experimental group and one from the placebo group, and nausea in two subjects from the placebo group and in one from the montelukast group.
Merck provided tablets used in this study. Dr. Kheirandish-Gozal reported grants from Merck and the National Institutes of Health during the conduct of the study. David Gozal, MD, is supported by the Herbert T. Abelson Chair in Pediatrics at the University of Chicago.
The majority of children with obstructive sleep apnea (OSA) who took oral montelukast showed reductions in their apnea-hypopnea index (AHI) scores, in a randomized, double-blind placebo-controlled study.
Typically, OSA in children is treated by adenotonsillectomy, according to Leila Kheirandish-Gozal, MD, director of clinical sleep research at the University of Chicago, and her colleagues. Prior to this study, only one randomized controlled trial had showed that children with mild OSA “responded favorably” to the leukotriene modifier montelukast (Pediatrics. 2012 Aug 31. doi: 10.1542/peds.2012-0310).
Twenty (71%) of the children who received montelukast had fewer AHI events per hour of total sleep time at the end of the study. The average number of such events for these patients was 4.2 plus or minus 2.8 after taking the drug, compared with 9.2 plus or minus 4.1 at the beginning of the study (P less than .0001). Only two (6.9%) of the patients who took the placebo had lower AHI scores at the end of the study, with the average AHI score for the placebo group having been 8.7 plus or minus 4.9 events per hour of total sleep time. At baseline, the average score for patients in the placebo group was 8.2 plus or minus 5.0 AHI events per hour of total sleep time at baseline.
Another improvement seen by patients who received the drug was a decrease in the number of 3% reductions in arterial oxygen saturation per hour of sleep. At the beginning of the study, these patients had 7.2 plus or minus 3.1 of these events; by the end of the study, the number of these events was down to 2.8 plus or minus 1.8 (P less than .001). No significant decrease in the number of these events was seen among patients in the placebo group.
In this study, “montelukast emerges as favorably reducing the severity of OSA short term in children 2-10 years of age. These findings add to the existing evidence supporting a therapeutic role for anti-inflammatory approaches in the management of this highly prevalent condition in children, and clearly justify future studies targeting the long-term benefits of these approaches in children with OSA,” the researchers wrote.
All patients participated in overnight sleep studies following a referral to one of two sleep clinics by their primary care pediatrician or pediatric otolaryngologist, at the beginning of the study. Children who had been diagnosed with symptomatic snoring and had an AHI score of greater than 2 events per hour of total sleep time, and for whom adenotonsillectomy was contemplated, were included in the study.
Central, obstructive, mixed apneic events were counted and hypopneas were assessed. OSA was defined “as the absence of airflow with continued chest wall and abdominal movement for a duration of at least two breaths,” the investigators said. Hypopneas were defined “as a decrease in oronasal flow greater than 50% on either the thermistor or nasal pressure transducer signal. with a corresponding decrease in arterial oxygen saturation greater than 3% or arousal,” Dr. Kheirandish-Gozal and her coauthors said.
Patients were excluded from the study for a variety of reasons, including having severe OSA requiring early surgical intervention.
Adverse events included headache in two children, one from the experimental group and one from the placebo group, and nausea in two subjects from the placebo group and in one from the montelukast group.
Merck provided tablets used in this study. Dr. Kheirandish-Gozal reported grants from Merck and the National Institutes of Health during the conduct of the study. David Gozal, MD, is supported by the Herbert T. Abelson Chair in Pediatrics at the University of Chicago.
The majority of children with obstructive sleep apnea (OSA) who took oral montelukast showed reductions in their apnea-hypopnea index (AHI) scores, in a randomized, double-blind placebo-controlled study.
Typically, OSA in children is treated by adenotonsillectomy, according to Leila Kheirandish-Gozal, MD, director of clinical sleep research at the University of Chicago, and her colleagues. Prior to this study, only one randomized controlled trial had showed that children with mild OSA “responded favorably” to the leukotriene modifier montelukast (Pediatrics. 2012 Aug 31. doi: 10.1542/peds.2012-0310).
Twenty (71%) of the children who received montelukast had fewer AHI events per hour of total sleep time at the end of the study. The average number of such events for these patients was 4.2 plus or minus 2.8 after taking the drug, compared with 9.2 plus or minus 4.1 at the beginning of the study (P less than .0001). Only two (6.9%) of the patients who took the placebo had lower AHI scores at the end of the study, with the average AHI score for the placebo group having been 8.7 plus or minus 4.9 events per hour of total sleep time. At baseline, the average score for patients in the placebo group was 8.2 plus or minus 5.0 AHI events per hour of total sleep time at baseline.
Another improvement seen by patients who received the drug was a decrease in the number of 3% reductions in arterial oxygen saturation per hour of sleep. At the beginning of the study, these patients had 7.2 plus or minus 3.1 of these events; by the end of the study, the number of these events was down to 2.8 plus or minus 1.8 (P less than .001). No significant decrease in the number of these events was seen among patients in the placebo group.
In this study, “montelukast emerges as favorably reducing the severity of OSA short term in children 2-10 years of age. These findings add to the existing evidence supporting a therapeutic role for anti-inflammatory approaches in the management of this highly prevalent condition in children, and clearly justify future studies targeting the long-term benefits of these approaches in children with OSA,” the researchers wrote.
All patients participated in overnight sleep studies following a referral to one of two sleep clinics by their primary care pediatrician or pediatric otolaryngologist, at the beginning of the study. Children who had been diagnosed with symptomatic snoring and had an AHI score of greater than 2 events per hour of total sleep time, and for whom adenotonsillectomy was contemplated, were included in the study.
Central, obstructive, mixed apneic events were counted and hypopneas were assessed. OSA was defined “as the absence of airflow with continued chest wall and abdominal movement for a duration of at least two breaths,” the investigators said. Hypopneas were defined “as a decrease in oronasal flow greater than 50% on either the thermistor or nasal pressure transducer signal. with a corresponding decrease in arterial oxygen saturation greater than 3% or arousal,” Dr. Kheirandish-Gozal and her coauthors said.
Patients were excluded from the study for a variety of reasons, including having severe OSA requiring early surgical intervention.
Adverse events included headache in two children, one from the experimental group and one from the placebo group, and nausea in two subjects from the placebo group and in one from the montelukast group.
Merck provided tablets used in this study. Dr. Kheirandish-Gozal reported grants from Merck and the National Institutes of Health during the conduct of the study. David Gozal, MD, is supported by the Herbert T. Abelson Chair in Pediatrics at the University of Chicago.
Key clinical point:
Major finding: 71% of patients who took montelukast had a significant reduction in AHI events per hour of total sleep time (P less than .0001).
Data source: A prospective, randomized, double-blind placebo-controlled study of 57 children with obstructive sleep apnea.
Disclosures: Merck provided tablets used in this study. Dr. Kheirandish-Gozal reported grants from Merck and the National Institutes of Health during the conduct of the study. David Gozal, MD, is supported by the Herbert T. Abelson Chair in Pediatrics at the University of Chicago.
Data point to optimal window for endoscopy in sicker patients with peptic ulcer bleeding
The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.
Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.
“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”
The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.
For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).
In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.
Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.
The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.
“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.
The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.
Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.
“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”
The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.
For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).
In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.
Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.
The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.
“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.
The timing of endoscopy may make the difference between life and death in sicker patients with peptic ulcer bleeding, according to an analysis of more than 12,000 patients treated in Denmark.
Patients who were hemodynamically stable but had a higher level of comorbidity were about half as likely to die during their hospital stay if they underwent endoscopy within 12-36 hours of presentation as compared with sooner or later, results showed (Gastrointest Endosc. 2016 Sep 10. doi: 10.1016/j.gie.2016.08.049). And hemodynamically unstable patients had a roughly one-fourth reduction in the odds of death if they underwent the procedure within 6-24 hours.
“Although caution should be applied when interpreting these data, the current recommendation of endoscopy within 0-24 hours may not be optimal for all patients,” wrote the investigators, who were led by Stig B. Laursen, PhD, department of medical gastroenterology, Odense (Denmark) University Hospital.
“Our data may suggest that in patients with major comorbidities, the first few hours of hospital admission might be best used for optimising treatment of comorbidities, which may include correction of severe anaemia, reversal of anticoagulants, and investigation for possible infection that requires rapid treatment with antibiotics,” they elaborate. “Likewise, in patients with hemodynamic instability, endoscopy between 6 and 24 hours from time of admission to hospital allows time for optimal resuscitation and initiating treatment of comorbid diseases before endoscopy. However, these data should not lead to delayed endoscopy in patients with severe hemodynamic instability not responding to intensive resuscitation.”
The investigators analyzed data from 12,601 consecutive patients with peptic ulcer bleeding admitted between January 2005 and September 2013 to Danish hospitals, where all patients had access to 24-hour endoscopy. Time to endoscopy was assessed from hospital admission, defined as arrival in the emergency department, or from symptom onset in patients who developed bleeding when already hospitalized.
For analyses, the patients were stratified by hemodynamic status (a marker for the severity of bleeding) and by American Society of Anesthesiologists score (a marker for the extent of comorbidity).
The timing of endoscopy did not significantly influence in-hospital or 30-day mortality in hemodynamically stable patients with an American Society of Anesthesiologists score of 1-2 as a whole, Dr. Laursen and his colleagues report. Subgroup analyses suggested a reduction of in-hospital mortality when it was done between 0 and 24 hours in those patients whose bleeding began outside the hospital (adjusted odds ratio, 0.48).
In contrast, analyses revealed a U-shaped association between timing and mortality for hemodynamically stable patients with an American Society of Anesthesiologists score of 3-5. For this group, in-hospital mortality was significantly lower when endoscopy was performed within 12-36 hours as compared with times outside this window (adjusted OR, 0.48), and 30-day mortality tended to be lower as well.
Similarly, timing appeared to influence outcome for hemodynamically unstable patients, having both systolic blood pressure below 100 mm Hg and heart rate above 100 beats/min. For this group, performance of endoscopy within 6-24 hours was associated with significantly lower in-hospital mortality (adjusted OR, 0.73) and also 30-day mortality (adjusted OR, 0.66). Patients’ American Society of Anesthesiologists score did not appear to play a role here.
The study’s findings may have been affected by unmeasured and unknown confounders, acknowledge the investigators, who declared that they have no competing interests related to the research.
“Although a well-powered randomized controlled trial represents the best way to account for these problems, randomizing patients with [peptic ulcer bleeding] to early versus late endoscopy will be very difficult, including from an ethical and methodological point of view,” they note.
Key clinical point:
Major finding: In-hospital mortality was lower when endoscopy was performed within 12-36 hours in hemodynamically stable patients with higher comorbidity (odds ratio, 0.48) and within 6-24 hours in hemodynamically unstable patients (OR, 0.73).
Data source: A nationwide cohort study of 12,601 consecutive patients admitted to Danish hospitals with peptic ulcer bleeding.
Disclosures: The investigators declare that they do not have any competing interests.