Video

ROME – The difference between contemporary drug-eluting coronary stents and bare-metal stents is not very great, a large Norwegian coronary stent trial showed.

Today’s drug-eluting stents (DES), often called second-generation DES, largely do only what they were designed to do, compared with bare-metal stents (BMS): reduce the rate of stent restenosis and the need for target-lesion revascularization.

“The long-term benefit of contemporary DES over BMS was less that expected,” Kaare H. Bønaa, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

Results from the Norwegian Coronary Stent Trial (NORSTENT), run with 9,013 patients, showed that patients who received one or more drug-eluting stents had, during nearly 5 years of follow-up, a 5% absolute drop in target-lesion revascularizations (a 53% relative risk reduction), and a 3.3% reduction in all revascularizations (a 24% relative risk reduction), compared with patients who received bare-metal stents, said Dr. Bønaa.

The results also showed that patients who received DES had a 0.4% reduced rate of stent thrombosis (a 36% relative risk reduction), compared with patients treated with BMS during nearly 5 years of follow-up. All three differences were statistically significant.

But the NORSTENT findings also documented that the patients who received either DES or BMS had virtually identical rates of all-cause deaths and nonfatal myocardial infarctions. And, on average, the two different types of coronary stents produced identical improvements in patients’ quality of life, reported Dr. Bønaa, a professor and researcher in the Clinic for Heart Disease at St. Olav’s University Hospital in Trondheim, Norway.

The study’s primary endpoint was the combined rate of death or nonfatal MI, and so the nonsignificant difference in that outcome between the two study arms meant that, formally, the NORSTENT trial produced a neutral result. Concurrently with his report, the results appeared in an article online (New Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607991).

“The difference between the two stent types is not as great as we thought. Patients who get DES do not live longer or better” than those who receive BMS, Dr. Bønaa said. “We suggest that both contemporary DES and BMS can be recommended for contemporary revascularization. The results open up use of BMS for certain patients,” such as those scheduled for surgery or patients who cannot tolerate or afford the drugs used for dual antiplatelet therapy following coronary stent placement.

Mitchel L. Zoler/Frontline Medical News

But the designated discussant for the study, Stefan James, MD, insisted that recent-generation DES “should remain recommended over BMS,” particularly the specific DES that underwent testing in randomized trials that used hard clinical endpoints. The 2014 revascularization guidelines of the European Society of Cardiology recommend new-generation DES over BMS, he noted.

In addition, “BMS should not be specifically recommended for patients at high risk of stent thrombosis or for patients who do not tolerate dual-antiplatelet therapy,” said Dr. James, professor of cardiology at Uppsala University in Sweden.

NORSTENT ran at eight centers in Norway during 2008-2011, and enrolled patients either had acute coronary syndrome (71% of those in the study) or stable coronary disease. Patients averaged 63 years old. The trial excluded patients with prior stents or bifurcated coronary lesions. Enrolled patients received, on average, 1.7 stents. The specific stent in each class that patients received was left to the discretion of each operator, and 95% of patients in the DES arm received a second-generation device. All patients in both arms of the study received dual-antiplatelet therapy for 9 months.

The finding that DES cut the rate of revascularization procedures by 3.3%, compared with patients treated with BMS, means that, on average, clinicians would need to treat 30 patients with DES to avoid the need for one additional repeat revascularization procedure that would occur if BMS were used instead.

That number needed to treat of 30 to avoid one repeat revascularization may seem high, but the money saved that way would still counterbalance the incremental cost of a DES over a BMS, which today in Europe would be about 50-100 euros, noted one cardiologist.

If you multiply 30 procedures by 100 extra euros per stent and by an average of 1.7 stents per patient, you may spend 5,100 euros, less than the cost of a repeat revascularization procedure, commented Carlo Di Mario, MD, a professor of cardiology and an interventional cardiologist at Royal Brompton & Harefield Hospitals in London.

In a video interview, Steen D. Kristensen, MD, of Aarhus University, Denmark, discussed the NORSTENT findings and their implications.

NORSTENT received no commercial support. Dr. Bønaa and Dr. Di Mario had no disclosures. Dr. James has been a consultant to Boston Scientific and has received research support from Boston Scientific and Abbott Vascular.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – The difference between contemporary drug-eluting coronary stents and bare-metal stents is not very great, a large Norwegian coronary stent trial showed.

Today’s drug-eluting stents (DES), often called second-generation DES, largely do only what they were designed to do, compared with bare-metal stents (BMS): reduce the rate of stent restenosis and the need for target-lesion revascularization.

“The long-term benefit of contemporary DES over BMS was less that expected,” Kaare H. Bønaa, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

Results from the Norwegian Coronary Stent Trial (NORSTENT), run with 9,013 patients, showed that patients who received one or more drug-eluting stents had, during nearly 5 years of follow-up, a 5% absolute drop in target-lesion revascularizations (a 53% relative risk reduction), and a 3.3% reduction in all revascularizations (a 24% relative risk reduction), compared with patients who received bare-metal stents, said Dr. Bønaa.

The results also showed that patients who received DES had a 0.4% reduced rate of stent thrombosis (a 36% relative risk reduction), compared with patients treated with BMS during nearly 5 years of follow-up. All three differences were statistically significant.

But the NORSTENT findings also documented that the patients who received either DES or BMS had virtually identical rates of all-cause deaths and nonfatal myocardial infarctions. And, on average, the two different types of coronary stents produced identical improvements in patients’ quality of life, reported Dr. Bønaa, a professor and researcher in the Clinic for Heart Disease at St. Olav’s University Hospital in Trondheim, Norway.

The study’s primary endpoint was the combined rate of death or nonfatal MI, and so the nonsignificant difference in that outcome between the two study arms meant that, formally, the NORSTENT trial produced a neutral result. Concurrently with his report, the results appeared in an article online (New Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607991).

“The difference between the two stent types is not as great as we thought. Patients who get DES do not live longer or better” than those who receive BMS, Dr. Bønaa said. “We suggest that both contemporary DES and BMS can be recommended for contemporary revascularization. The results open up use of BMS for certain patients,” such as those scheduled for surgery or patients who cannot tolerate or afford the drugs used for dual antiplatelet therapy following coronary stent placement.

Mitchel L. Zoler/Frontline Medical News

But the designated discussant for the study, Stefan James, MD, insisted that recent-generation DES “should remain recommended over BMS,” particularly the specific DES that underwent testing in randomized trials that used hard clinical endpoints. The 2014 revascularization guidelines of the European Society of Cardiology recommend new-generation DES over BMS, he noted.

In addition, “BMS should not be specifically recommended for patients at high risk of stent thrombosis or for patients who do not tolerate dual-antiplatelet therapy,” said Dr. James, professor of cardiology at Uppsala University in Sweden.

NORSTENT ran at eight centers in Norway during 2008-2011, and enrolled patients either had acute coronary syndrome (71% of those in the study) or stable coronary disease. Patients averaged 63 years old. The trial excluded patients with prior stents or bifurcated coronary lesions. Enrolled patients received, on average, 1.7 stents. The specific stent in each class that patients received was left to the discretion of each operator, and 95% of patients in the DES arm received a second-generation device. All patients in both arms of the study received dual-antiplatelet therapy for 9 months.

The finding that DES cut the rate of revascularization procedures by 3.3%, compared with patients treated with BMS, means that, on average, clinicians would need to treat 30 patients with DES to avoid the need for one additional repeat revascularization procedure that would occur if BMS were used instead.

That number needed to treat of 30 to avoid one repeat revascularization may seem high, but the money saved that way would still counterbalance the incremental cost of a DES over a BMS, which today in Europe would be about 50-100 euros, noted one cardiologist.

If you multiply 30 procedures by 100 extra euros per stent and by an average of 1.7 stents per patient, you may spend 5,100 euros, less than the cost of a repeat revascularization procedure, commented Carlo Di Mario, MD, a professor of cardiology and an interventional cardiologist at Royal Brompton & Harefield Hospitals in London.

In a video interview, Steen D. Kristensen, MD, of Aarhus University, Denmark, discussed the NORSTENT findings and their implications.

NORSTENT received no commercial support. Dr. Bønaa and Dr. Di Mario had no disclosures. Dr. James has been a consultant to Boston Scientific and has received research support from Boston Scientific and Abbott Vascular.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – The difference between contemporary drug-eluting coronary stents and bare-metal stents is not very great, a large Norwegian coronary stent trial showed.

Today’s drug-eluting stents (DES), often called second-generation DES, largely do only what they were designed to do, compared with bare-metal stents (BMS): reduce the rate of stent restenosis and the need for target-lesion revascularization.

“The long-term benefit of contemporary DES over BMS was less that expected,” Kaare H. Bønaa, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

Results from the Norwegian Coronary Stent Trial (NORSTENT), run with 9,013 patients, showed that patients who received one or more drug-eluting stents had, during nearly 5 years of follow-up, a 5% absolute drop in target-lesion revascularizations (a 53% relative risk reduction), and a 3.3% reduction in all revascularizations (a 24% relative risk reduction), compared with patients who received bare-metal stents, said Dr. Bønaa.

The results also showed that patients who received DES had a 0.4% reduced rate of stent thrombosis (a 36% relative risk reduction), compared with patients treated with BMS during nearly 5 years of follow-up. All three differences were statistically significant.

But the NORSTENT findings also documented that the patients who received either DES or BMS had virtually identical rates of all-cause deaths and nonfatal myocardial infarctions. And, on average, the two different types of coronary stents produced identical improvements in patients’ quality of life, reported Dr. Bønaa, a professor and researcher in the Clinic for Heart Disease at St. Olav’s University Hospital in Trondheim, Norway.

The study’s primary endpoint was the combined rate of death or nonfatal MI, and so the nonsignificant difference in that outcome between the two study arms meant that, formally, the NORSTENT trial produced a neutral result. Concurrently with his report, the results appeared in an article online (New Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607991).

“The difference between the two stent types is not as great as we thought. Patients who get DES do not live longer or better” than those who receive BMS, Dr. Bønaa said. “We suggest that both contemporary DES and BMS can be recommended for contemporary revascularization. The results open up use of BMS for certain patients,” such as those scheduled for surgery or patients who cannot tolerate or afford the drugs used for dual antiplatelet therapy following coronary stent placement.

Mitchel L. Zoler/Frontline Medical News

But the designated discussant for the study, Stefan James, MD, insisted that recent-generation DES “should remain recommended over BMS,” particularly the specific DES that underwent testing in randomized trials that used hard clinical endpoints. The 2014 revascularization guidelines of the European Society of Cardiology recommend new-generation DES over BMS, he noted.

In addition, “BMS should not be specifically recommended for patients at high risk of stent thrombosis or for patients who do not tolerate dual-antiplatelet therapy,” said Dr. James, professor of cardiology at Uppsala University in Sweden.

NORSTENT ran at eight centers in Norway during 2008-2011, and enrolled patients either had acute coronary syndrome (71% of those in the study) or stable coronary disease. Patients averaged 63 years old. The trial excluded patients with prior stents or bifurcated coronary lesions. Enrolled patients received, on average, 1.7 stents. The specific stent in each class that patients received was left to the discretion of each operator, and 95% of patients in the DES arm received a second-generation device. All patients in both arms of the study received dual-antiplatelet therapy for 9 months.

The finding that DES cut the rate of revascularization procedures by 3.3%, compared with patients treated with BMS, means that, on average, clinicians would need to treat 30 patients with DES to avoid the need for one additional repeat revascularization procedure that would occur if BMS were used instead.

That number needed to treat of 30 to avoid one repeat revascularization may seem high, but the money saved that way would still counterbalance the incremental cost of a DES over a BMS, which today in Europe would be about 50-100 euros, noted one cardiologist.

If you multiply 30 procedures by 100 extra euros per stent and by an average of 1.7 stents per patient, you may spend 5,100 euros, less than the cost of a repeat revascularization procedure, commented Carlo Di Mario, MD, a professor of cardiology and an interventional cardiologist at Royal Brompton & Harefield Hospitals in London.

In a video interview, Steen D. Kristensen, MD, of Aarhus University, Denmark, discussed the NORSTENT findings and their implications.

NORSTENT received no commercial support. Dr. Bønaa and Dr. Di Mario had no disclosures. Dr. James has been a consultant to Boston Scientific and has received research support from Boston Scientific and Abbott Vascular.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

TORONTO – Antipsychotics can be safely withdrawn from many dementia patients in long-term care facilities, two new studies from Australia and Canada have determined.

When the drugs were withdrawn and supplanted with behavior-centered care in the Australian study, 80% of patients experienced no relapse of symptoms, Henry Brodaty, MD, DSc, said at the Alzheimer’s Association International Conference 2016.

“We saw no significant changes at all in agitation, aggression, delusions, or hallucinations,” Dr. Brodaty, the Scientia Professor of Ageing and Mental Health, University of New South Wales, Australia, said in an interview. “Were we surprised at this? No. Because for the majority of these patients, the medications were inappropriately prescribed.”

The 12-month Australian study is still in the process of tracking outcomes after antipsychotic withdrawal. But the Canadian study found great benefits, said Selma Didic, an improvement analyst with the Canadian Foundation for Healthcare Improvement in Ottawa. “We saw falls decrease by 20%. The incidence of verbal abuse and socially disruptive behavior actually decreased as well.”

In fact, she said, patients who discontinued the medications actually started behaving better than the comparator group that stayed on them.

The Australian experience

Dr. Brodaty discussed the HALT (Halting Antipsychotic Use in Long-Term Care) study. HALT is a single-arm, 12-month longitudinal study carried out in 23 nursing homes in New South Wales.

The study team worked with nursing leadership in each facility to identify patients who might be eligible for the program. In order to enroll, each patient’s family and general physician had to agree to a trial of deprescribing. Physicians were instructed to wean patients off the medication by decreasing the dose by half once a week. Most patients were able to stop within a couple of weeks, Dr. Brodaty said.

Getting buy-in wasn’t always easy, he noted. “Some families didn’t want to rock the boat, and some physicians were resistant,” to the idea. Overall, “Families and nurses were very, very worried” about the prospect of dropping drugs that were seen as helpful in everyday patient management.

But getting rid of the medications was just half the picture. Training nurses and care staff to intervene in problematic behaviors without resorting to drugs was just as important. A nurse-leader at each facility received training in person-centered care, and then trained the rest of the staff. This wasn’t always an easy idea to embrace, either, Dr. Brodaty said, especially since nursing staff often leads the discussion about the need for drugs to manage behavioral problems.

“Nursing staff are very task oriented, focused on dressing, bathing, eating, and toileting. They work very hard, and they don’t always have time to sit down and talk to resistant patients. It takes a much different attitude to show that you can actually save time by spending time and engaging the patient.”

He related one of his favorite illustrative stories – the milkman who caused a ruckus at bath time. “He got upset and aggressive every night when being put to bed and every morning when being given a shower. The staff spoke to his wife about it. She said that for 40 years, he was accustomed to getting up at 4 a.m. to deliver the milk. He would take a bath at night and get on his track suit and go to bed. Then at 4 a.m., he would get up and be ready to jump in the truck and go.”

When the staff started letting him shower at night and go to bed in his track suit, the milkman’s behavior improved without the need for antipsychotic medications.

“This is what we mean by ‘person-centered care,’ ” Dr. Brodaty said. “We use the ABC paradigm: Addressing the antecedent to the behavior, then the behavior, and then the consequences of the behavior.”

The intervention cohort comprised 139 patients with a mean age of 85 years; most were women. The vast majority (93%) had a diagnosis of dementia. About one-third had Alzheimer’s and one-third vascular dementia. The remainder had other diagnoses, including frontotemporal dementia, Lewy body dementia, and Parkinson’s disease. Common comorbid conditions included depression (56%) and previous stroke (36%). None of the patients had a diagnosis of psychosis.

Risperidone was the most common antipsychotic medication (85%). Other medications were olanzapine, quetiapine, and haloperidol. About 30% had come to the facility on the medication; the others had received it since admission.

Despite the national recommendation to review antipsychotic use every 12 weeks, patients had been on their current antipsychotic for an average of 2 years, and on their current dose for 1 year. In reviewing medications, Dr. Brodaty also found a “concerning” lack of informed consent. In Australia, informed consent for antipsychotic drugs can be given by a family member, but 84% of patients had no documented consent at all.

Of the original group, 125 entered the deprescribing protocol. Of these, 26 (21%) have since resumed their medications, but 79% have done well and are without a relapse of their symptoms or problematic behaviors. An ongoing medication review suggests there has been no concomitant upswing in other psychotropic medications, including benzodiazepines.

Neuropsychiatric symptoms remained stable from baseline. The mean total group score on the Neuropsychiatric Index (NPI) has not changed from its baseline of 30. The mean agitation/aggression NPI subscale has remained about 6, and the mean group score on the Cohen-Mansfield Agitation Inventory about 56. The NPI delusion subscale increased, but the change was nonsignificant, Dr. Brodaty said. The NPI hallucinations subscale decreased slightly, but again the change was nonsignificant.

“Look, we all know antipsychotics are bad for old people, and we all know they are overprescribed,” he said. “Inappropriate use of these medications is an old story, yet we’re still talking about it. Why is this? We have the knowledge now, and we have to build on this knowledge so that we can change practice.”

The Canadian experience

Ms. Didic shared a year-long quality improvement process at 24 long-term care facilities that wanted to improve antipsychotic prescribing for their dementia patients.

The program, which was sponsored by the Canadian Foundation for Healthcare Improvement, used a “train-the-trainer” approach to spread support for antipsychotic deprescribing.

The foundation deployed 15 interdisciplinary teams, which comprised 180 members, including physicians, nurses, pharmacists, recreational therapists, and “clinical champions” who took the methodology directly into participating facilities. Interactive webinars on patient-centered care and deprescribing protocols were part of the process, Ms. Didic said.

In all, 416 patients were included in the outcomes report. Within 12 months, antipsychotics were eliminated in 74 patients (18%) and in 148 (36%), the dosage was reduced.

The benefits of these changes were striking, Ms. Didic said. There were fewer falls and reductions in verbal abuse, care resistance, and socially inappropriate behaviors. These issues either remained the same or got worse in patients who did not decrease antipsychotics. Again, there was no concomitant increase in other psychotropic medications.

The results show that changing the focus from medication-first to behavior-first care is institutionally feasible, Ms. Didic said.

Staff members’ assessments of the program and its personal and institutional impact were positive:

• 91% said they instituted regular medication reviews for every resident.

• 92% said old ways of doing things were adjusted to accommodate the new type of care.

• 94% said the new person-centered care was now a standard way of working.

• 84% said the project improved their ability to lead.

• 80% said it improved their ability to communicate.

“Currently, our teams are now spreading and sharing these resources and tools, serving as advisers, and organizing clinical training and workshops,” for other Canadian nursing homes that want to adopt the strategy.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the issues surrounding antipsychotic prescribing in long-term care facilities in a video interview.

Neither Ms. Didic nor Dr. Brodaty had any financial declarations.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

TORONTO – Antipsychotics can be safely withdrawn from many dementia patients in long-term care facilities, two new studies from Australia and Canada have determined.

When the drugs were withdrawn and supplanted with behavior-centered care in the Australian study, 80% of patients experienced no relapse of symptoms, Henry Brodaty, MD, DSc, said at the Alzheimer’s Association International Conference 2016.

“We saw no significant changes at all in agitation, aggression, delusions, or hallucinations,” Dr. Brodaty, the Scientia Professor of Ageing and Mental Health, University of New South Wales, Australia, said in an interview. “Were we surprised at this? No. Because for the majority of these patients, the medications were inappropriately prescribed.”

The 12-month Australian study is still in the process of tracking outcomes after antipsychotic withdrawal. But the Canadian study found great benefits, said Selma Didic, an improvement analyst with the Canadian Foundation for Healthcare Improvement in Ottawa. “We saw falls decrease by 20%. The incidence of verbal abuse and socially disruptive behavior actually decreased as well.”

In fact, she said, patients who discontinued the medications actually started behaving better than the comparator group that stayed on them.

The Australian experience

Dr. Brodaty discussed the HALT (Halting Antipsychotic Use in Long-Term Care) study. HALT is a single-arm, 12-month longitudinal study carried out in 23 nursing homes in New South Wales.

The study team worked with nursing leadership in each facility to identify patients who might be eligible for the program. In order to enroll, each patient’s family and general physician had to agree to a trial of deprescribing. Physicians were instructed to wean patients off the medication by decreasing the dose by half once a week. Most patients were able to stop within a couple of weeks, Dr. Brodaty said.

Getting buy-in wasn’t always easy, he noted. “Some families didn’t want to rock the boat, and some physicians were resistant,” to the idea. Overall, “Families and nurses were very, very worried” about the prospect of dropping drugs that were seen as helpful in everyday patient management.

But getting rid of the medications was just half the picture. Training nurses and care staff to intervene in problematic behaviors without resorting to drugs was just as important. A nurse-leader at each facility received training in person-centered care, and then trained the rest of the staff. This wasn’t always an easy idea to embrace, either, Dr. Brodaty said, especially since nursing staff often leads the discussion about the need for drugs to manage behavioral problems.

“Nursing staff are very task oriented, focused on dressing, bathing, eating, and toileting. They work very hard, and they don’t always have time to sit down and talk to resistant patients. It takes a much different attitude to show that you can actually save time by spending time and engaging the patient.”

He related one of his favorite illustrative stories – the milkman who caused a ruckus at bath time. “He got upset and aggressive every night when being put to bed and every morning when being given a shower. The staff spoke to his wife about it. She said that for 40 years, he was accustomed to getting up at 4 a.m. to deliver the milk. He would take a bath at night and get on his track suit and go to bed. Then at 4 a.m., he would get up and be ready to jump in the truck and go.”

When the staff started letting him shower at night and go to bed in his track suit, the milkman’s behavior improved without the need for antipsychotic medications.

“This is what we mean by ‘person-centered care,’ ” Dr. Brodaty said. “We use the ABC paradigm: Addressing the antecedent to the behavior, then the behavior, and then the consequences of the behavior.”

The intervention cohort comprised 139 patients with a mean age of 85 years; most were women. The vast majority (93%) had a diagnosis of dementia. About one-third had Alzheimer’s and one-third vascular dementia. The remainder had other diagnoses, including frontotemporal dementia, Lewy body dementia, and Parkinson’s disease. Common comorbid conditions included depression (56%) and previous stroke (36%). None of the patients had a diagnosis of psychosis.

Risperidone was the most common antipsychotic medication (85%). Other medications were olanzapine, quetiapine, and haloperidol. About 30% had come to the facility on the medication; the others had received it since admission.

Despite the national recommendation to review antipsychotic use every 12 weeks, patients had been on their current antipsychotic for an average of 2 years, and on their current dose for 1 year. In reviewing medications, Dr. Brodaty also found a “concerning” lack of informed consent. In Australia, informed consent for antipsychotic drugs can be given by a family member, but 84% of patients had no documented consent at all.

Of the original group, 125 entered the deprescribing protocol. Of these, 26 (21%) have since resumed their medications, but 79% have done well and are without a relapse of their symptoms or problematic behaviors. An ongoing medication review suggests there has been no concomitant upswing in other psychotropic medications, including benzodiazepines.

Neuropsychiatric symptoms remained stable from baseline. The mean total group score on the Neuropsychiatric Index (NPI) has not changed from its baseline of 30. The mean agitation/aggression NPI subscale has remained about 6, and the mean group score on the Cohen-Mansfield Agitation Inventory about 56. The NPI delusion subscale increased, but the change was nonsignificant, Dr. Brodaty said. The NPI hallucinations subscale decreased slightly, but again the change was nonsignificant.

“Look, we all know antipsychotics are bad for old people, and we all know they are overprescribed,” he said. “Inappropriate use of these medications is an old story, yet we’re still talking about it. Why is this? We have the knowledge now, and we have to build on this knowledge so that we can change practice.”

The Canadian experience

Ms. Didic shared a year-long quality improvement process at 24 long-term care facilities that wanted to improve antipsychotic prescribing for their dementia patients.

The program, which was sponsored by the Canadian Foundation for Healthcare Improvement, used a “train-the-trainer” approach to spread support for antipsychotic deprescribing.

The foundation deployed 15 interdisciplinary teams, which comprised 180 members, including physicians, nurses, pharmacists, recreational therapists, and “clinical champions” who took the methodology directly into participating facilities. Interactive webinars on patient-centered care and deprescribing protocols were part of the process, Ms. Didic said.

In all, 416 patients were included in the outcomes report. Within 12 months, antipsychotics were eliminated in 74 patients (18%) and in 148 (36%), the dosage was reduced.

The benefits of these changes were striking, Ms. Didic said. There were fewer falls and reductions in verbal abuse, care resistance, and socially inappropriate behaviors. These issues either remained the same or got worse in patients who did not decrease antipsychotics. Again, there was no concomitant increase in other psychotropic medications.

The results show that changing the focus from medication-first to behavior-first care is institutionally feasible, Ms. Didic said.

Staff members’ assessments of the program and its personal and institutional impact were positive:

• 91% said they instituted regular medication reviews for every resident.

• 92% said old ways of doing things were adjusted to accommodate the new type of care.

• 94% said the new person-centered care was now a standard way of working.

• 84% said the project improved their ability to lead.

• 80% said it improved their ability to communicate.

“Currently, our teams are now spreading and sharing these resources and tools, serving as advisers, and organizing clinical training and workshops,” for other Canadian nursing homes that want to adopt the strategy.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the issues surrounding antipsychotic prescribing in long-term care facilities in a video interview.

Neither Ms. Didic nor Dr. Brodaty had any financial declarations.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

TORONTO – Antipsychotics can be safely withdrawn from many dementia patients in long-term care facilities, two new studies from Australia and Canada have determined.

When the drugs were withdrawn and supplanted with behavior-centered care in the Australian study, 80% of patients experienced no relapse of symptoms, Henry Brodaty, MD, DSc, said at the Alzheimer’s Association International Conference 2016.

“We saw no significant changes at all in agitation, aggression, delusions, or hallucinations,” Dr. Brodaty, the Scientia Professor of Ageing and Mental Health, University of New South Wales, Australia, said in an interview. “Were we surprised at this? No. Because for the majority of these patients, the medications were inappropriately prescribed.”

The 12-month Australian study is still in the process of tracking outcomes after antipsychotic withdrawal. But the Canadian study found great benefits, said Selma Didic, an improvement analyst with the Canadian Foundation for Healthcare Improvement in Ottawa. “We saw falls decrease by 20%. The incidence of verbal abuse and socially disruptive behavior actually decreased as well.”

In fact, she said, patients who discontinued the medications actually started behaving better than the comparator group that stayed on them.

The Australian experience

Dr. Brodaty discussed the HALT (Halting Antipsychotic Use in Long-Term Care) study. HALT is a single-arm, 12-month longitudinal study carried out in 23 nursing homes in New South Wales.

The study team worked with nursing leadership in each facility to identify patients who might be eligible for the program. In order to enroll, each patient’s family and general physician had to agree to a trial of deprescribing. Physicians were instructed to wean patients off the medication by decreasing the dose by half once a week. Most patients were able to stop within a couple of weeks, Dr. Brodaty said.

Getting buy-in wasn’t always easy, he noted. “Some families didn’t want to rock the boat, and some physicians were resistant,” to the idea. Overall, “Families and nurses were very, very worried” about the prospect of dropping drugs that were seen as helpful in everyday patient management.

But getting rid of the medications was just half the picture. Training nurses and care staff to intervene in problematic behaviors without resorting to drugs was just as important. A nurse-leader at each facility received training in person-centered care, and then trained the rest of the staff. This wasn’t always an easy idea to embrace, either, Dr. Brodaty said, especially since nursing staff often leads the discussion about the need for drugs to manage behavioral problems.

“Nursing staff are very task oriented, focused on dressing, bathing, eating, and toileting. They work very hard, and they don’t always have time to sit down and talk to resistant patients. It takes a much different attitude to show that you can actually save time by spending time and engaging the patient.”

He related one of his favorite illustrative stories – the milkman who caused a ruckus at bath time. “He got upset and aggressive every night when being put to bed and every morning when being given a shower. The staff spoke to his wife about it. She said that for 40 years, he was accustomed to getting up at 4 a.m. to deliver the milk. He would take a bath at night and get on his track suit and go to bed. Then at 4 a.m., he would get up and be ready to jump in the truck and go.”

When the staff started letting him shower at night and go to bed in his track suit, the milkman’s behavior improved without the need for antipsychotic medications.

“This is what we mean by ‘person-centered care,’ ” Dr. Brodaty said. “We use the ABC paradigm: Addressing the antecedent to the behavior, then the behavior, and then the consequences of the behavior.”

The intervention cohort comprised 139 patients with a mean age of 85 years; most were women. The vast majority (93%) had a diagnosis of dementia. About one-third had Alzheimer’s and one-third vascular dementia. The remainder had other diagnoses, including frontotemporal dementia, Lewy body dementia, and Parkinson’s disease. Common comorbid conditions included depression (56%) and previous stroke (36%). None of the patients had a diagnosis of psychosis.

Risperidone was the most common antipsychotic medication (85%). Other medications were olanzapine, quetiapine, and haloperidol. About 30% had come to the facility on the medication; the others had received it since admission.

Despite the national recommendation to review antipsychotic use every 12 weeks, patients had been on their current antipsychotic for an average of 2 years, and on their current dose for 1 year. In reviewing medications, Dr. Brodaty also found a “concerning” lack of informed consent. In Australia, informed consent for antipsychotic drugs can be given by a family member, but 84% of patients had no documented consent at all.

Of the original group, 125 entered the deprescribing protocol. Of these, 26 (21%) have since resumed their medications, but 79% have done well and are without a relapse of their symptoms or problematic behaviors. An ongoing medication review suggests there has been no concomitant upswing in other psychotropic medications, including benzodiazepines.

Neuropsychiatric symptoms remained stable from baseline. The mean total group score on the Neuropsychiatric Index (NPI) has not changed from its baseline of 30. The mean agitation/aggression NPI subscale has remained about 6, and the mean group score on the Cohen-Mansfield Agitation Inventory about 56. The NPI delusion subscale increased, but the change was nonsignificant, Dr. Brodaty said. The NPI hallucinations subscale decreased slightly, but again the change was nonsignificant.

“Look, we all know antipsychotics are bad for old people, and we all know they are overprescribed,” he said. “Inappropriate use of these medications is an old story, yet we’re still talking about it. Why is this? We have the knowledge now, and we have to build on this knowledge so that we can change practice.”

The Canadian experience

Ms. Didic shared a year-long quality improvement process at 24 long-term care facilities that wanted to improve antipsychotic prescribing for their dementia patients.

The program, which was sponsored by the Canadian Foundation for Healthcare Improvement, used a “train-the-trainer” approach to spread support for antipsychotic deprescribing.

The foundation deployed 15 interdisciplinary teams, which comprised 180 members, including physicians, nurses, pharmacists, recreational therapists, and “clinical champions” who took the methodology directly into participating facilities. Interactive webinars on patient-centered care and deprescribing protocols were part of the process, Ms. Didic said.

In all, 416 patients were included in the outcomes report. Within 12 months, antipsychotics were eliminated in 74 patients (18%) and in 148 (36%), the dosage was reduced.

The benefits of these changes were striking, Ms. Didic said. There were fewer falls and reductions in verbal abuse, care resistance, and socially inappropriate behaviors. These issues either remained the same or got worse in patients who did not decrease antipsychotics. Again, there was no concomitant increase in other psychotropic medications.

The results show that changing the focus from medication-first to behavior-first care is institutionally feasible, Ms. Didic said.

Staff members’ assessments of the program and its personal and institutional impact were positive:

• 91% said they instituted regular medication reviews for every resident.

• 92% said old ways of doing things were adjusted to accommodate the new type of care.

• 94% said the new person-centered care was now a standard way of working.

• 84% said the project improved their ability to lead.

• 80% said it improved their ability to communicate.

“Currently, our teams are now spreading and sharing these resources and tools, serving as advisers, and organizing clinical training and workshops,” for other Canadian nursing homes that want to adopt the strategy.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the issues surrounding antipsychotic prescribing in long-term care facilities in a video interview.

Neither Ms. Didic nor Dr. Brodaty had any financial declarations.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.

Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.

Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).

“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.

The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.

MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.

“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.

CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.

Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.

His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.

Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.

Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).

“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.

The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.

MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.

“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.

CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.

Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.

His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Functional, noninvasive cardiac imaging using cardiovascular MR or myocardial perfusion scintigraphy was significantly better than was a current and well regarded guideline-based approach to identifying patients with chest pain and suspected coronary artery disease who could safely avoid angiography, thereby cutting the rate of unnecessary angiography by about 75%.

Following the guideline formula adopted by the British National Institute for Health and Care Excellence (NICE) resulted in a 29% rate of unnecessary angiography compared with rates of 7.5% using cardiovascular MR (CMR) and 7.1% using myocardial perfusion scintigraphy (MPS) in a multicenter randomized trial with 1,202 patients, John P. Greenwood, MBChB, said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

This universal use of a functional, noninvasive imaging strategy to guide angiography resulted in no significant penalty of missed coronary disease or subsequent coronary events. The rate of positive angiography findings was 12% among the 240 patients managed according to the NICE guidelines, 10% among 481 patients screened by CMR, and 9% among the 481 patients screened using MPS, reported Dr. Greenwood, professor of cardiology at the University of Leeds (England). The rate of major adverse coronary events after 12 months of follow-up were 3% following the NICE protocol and 4% when screening by CMR or with MPS.

Concurrently with Dr. Greenwood’s report, the findings from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 (CE-MARC2) study appeared in an article online (JAMA. 2016 Aug 29. doi: 10.1001/jama.2016.12680).

“We showed that a functional test with CMR or MPS can reduce the rate of unnecessary coronary angiography. Cutting unnecessary angiography is really important to patients, and it may also cost effective,” he said, but cautioned that a formal cost analysis of the options tested in this study is still being run.

The NICE guidelines manage patients with chest pain that could be angina by their pretest probability of having coronary artery disease (CAD), and at the time the study was designed the NICE guidelines, issued in 2010, provided the most up-to-date expert guidance on how to triage these patients. The study enrolled patients with a pretest probability for CAD of 10%-90%; collectively their average probability was 50%. The patients participated in the study at one of six U.K. centers during November 2012 to March 2015. The average age was 56 years.

MPS is “probably the noninvasive imaging approach most commonly used worldwide to detect coronary ischemia,” Dr. Greenwood said. But he led an earlier study that showed that CMR, using a gadolinium-based tracing agent, works even better than MPS (in this study single photon emission CT) to predict a patient’s risk for major cardiac events. He said this superiority is probably because of the greater spatial resolution with CMR.

“The higher spatial resolution of CMR, about 5- to 10-fold greater that MPS, is less likely to produce false negative results,” he said in an interview. “We showed that CMR has higher diagnostic accuracy, is a better prognosticator, and is more cost effective” than MPS. Dr. Greenwood attributed the similar performance of CMR and MPS in CE-MARC2 to the study’s design, which led to fewer patients undergoing each of the two imaging methods and made CE-MARC2 underpowered to discern a difference in specificity. In his earlier study, which included 752 patients who underwent examination with both CMR and MPS, the negative predictive value of CMR was 91% compared with 79% with MPS.

CMR uses conventional MR machines, is now widely available, and is being widely used today as a first-line test in the United Kingdom and Europe, he added.

Dr. Greenwood believes that in his new study functional imaging outperformed the NICE guidelines because the pretest models used in the guidelines “tend to overestimate risk,” the factor that produces angiography overuse.

His report included two additional analyses that assessed the impact of CMR and MPS in the subgroup of patients with a high pretest probability for CAD, 61%-90%, and in the subgroup with a low pretest probability, 10%-29%. Among the patients with a high likelihood for CAD the two functional imaging methods cut the rate of unnecessary angiography by 95%, a statistically significant difference. Among those with a low likelihood functional imaging cut the rate 56%, a difference that did not reach statistical significance.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – Weekly lipoprotein apheresis in patients with highly refractory angina accompanied by high plasma lipoprotein(a) without elevated LDL cholesterol led to significantly improved myocardial blood flow in a randomized, blinded, sham-controlled clinical trial, Tina Khan, MD, reported at the annual congress of the European Society of Cardiology.

Participants also experienced clinically meaningful improvements in the secondary endpoints of quality of life, angina symptoms, exercise capacity, and atheroma burden, added Dr. Khan of Imperial College London.

Bruce Jancin/Frontline Medical News

Angina pectoris that is refractory to maximal pharmacologic, percutaneous, and surgical interventions is a major and growing problem. More than 100,000 new cases occur per year in the United States.

“We have a desperate need to develop new therapeutic options,” she said.

Lipoprotein(a), or Lp(a), is a potent independent cardiovascular risk factor. And it figures prominently in refractory angina. Indeed, 60% of the patients with refractory angina screened by Dr. Khan for her clinical trial had an isolated plasma Lp(a) level of 50 mg/dL or more, the threshold at which cardiovascular risk sharply increases. Statins have no effect on Lp(a) levels.

While a couple of observational cohort studies have suggested that reducing elevated Lp(a) in patients with cardiovascular disease is associated with a decrease in major adverse cardiovascular events, until now there have been no randomized controlled trials of apheresis as Lp(a)-lowering therapy in patients with refractory angina, according to Dr. Khan.

She presented a randomized, crossover design study in 20 patients with severe refractory angina and an Lp(a) in excess of 50 mg/dL but no elevation in LDL. They underwent 3 months of blinded weekly extracorporeal lipoprotein apheresis using a dextran sulfate filtration system or sham apheresis, followed by a month-long washout period. Participants were then crossed over to the other study arm to increase the statistical power of this small study.

The primary study endpoint was change in myocardial perfusion reserve as measured by cardiovascular magnetic resonance imaging at baseline and after 3 months of true or sham apheresis. The myocardial perfusion reserve index improved by a net of 0.63 after apheresis from a baseline of 1.45. This effect was strongly driven by a substantial increase in stress myocardial perfusion, with very little change in perfusion at rest.

Significant improvements were also recorded after apheresis in the secondary endpoints of change in carotid atheroma as reflected in total carotid wall volume, improvement on various domains of the Seattle Angina Questionnaire, physical limitations as scored on the SF-36, and exercise capacity as measured on the 6-minute walk test.

Discussant Peter Libby, MD, was effusive in his praise for Dr. Khan’s study.

Bruce Jancin/Frontline Medical News

“This is a wonderful example of how we may be able to offer new hope for patients and families with high Lp(a),” declared Dr. Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

He approved of the methodology and embraced what he called “the intriguing preliminary picture of benefit for lowering Lp(a).”

Most of all, he was pleased that Dr. Khan’s well conducted albeit small study has thrown a spotlight on Lp(a), which he characterized as a greatly underappreciated causal risk factor for a range of cardiovascular diseases.

“Lp(a) stands out like a Manhattan skyscraper as the major driver of calcific aortic stenosis, an epidemic that we see in our aging population,” he observed.

He added that topics worthy of further research with regard to Lp(a)-lowering apheresis as a treatment for refractory angina include the question of whether the mechanism of benefit involves structural changes in atherosclerosis or functional changes. And if it’s the latter, is it a matter of changes in microvascular function, macrovascular function, or a combination of the two?

Apheresis is extremely costly, inconvenient, and invasive, and there are only several dozen apheresis centers in the United States. So the future of Lp(a)-lowering to treat refractory angina, calcific aortic stenosis, and other cardiovascular conditions where elevated Lp(a) is an important player may lie in pharmacotherapy with the PCSK9 inhibitors, Dr. Libby predicted.

He cited “very promising” data showing that evolocumab (Repatha) and alirocumab (Praluent) lower Lp(a) in dose-dependent fashion. Ongoing very large clinical trials with hard clinical endpoints should eventually provide key information regarding the cardiovascular benefits of lowering Lp(a).

“We may be entering an era where we may be able to offer our patients and families – because this is often a familial problem – a non-apheresis approach to controlling what we are learning is a very important causal risk factor for atherosclerosis,” Dr. Libby said.

Patrick M. Moriarty, MD, said in a video interview that he was very intrigued by the results, and “not personally surprised.” They should stimulate interest in cardiologists to start measuring Lp(a) in their patients like those in this study, in whom the disease severity doesn’t match up with the clinical risk factors, said Dr. Moriarty of the University of Kansas, Kansas City.

Dr. Khan’s study was funded by the UK National Institute for Health Research. She reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ROME – Weekly lipoprotein apheresis in patients with highly refractory angina accompanied by high plasma lipoprotein(a) without elevated LDL cholesterol led to significantly improved myocardial blood flow in a randomized, blinded, sham-controlled clinical trial, Tina Khan, MD, reported at the annual congress of the European Society of Cardiology.

Participants also experienced clinically meaningful improvements in the secondary endpoints of quality of life, angina symptoms, exercise capacity, and atheroma burden, added Dr. Khan of Imperial College London.

Bruce Jancin/Frontline Medical News

Angina pectoris that is refractory to maximal pharmacologic, percutaneous, and surgical interventions is a major and growing problem. More than 100,000 new cases occur per year in the United States.

“We have a desperate need to develop new therapeutic options,” she said.

Lipoprotein(a), or Lp(a), is a potent independent cardiovascular risk factor. And it figures prominently in refractory angina. Indeed, 60% of the patients with refractory angina screened by Dr. Khan for her clinical trial had an isolated plasma Lp(a) level of 50 mg/dL or more, the threshold at which cardiovascular risk sharply increases. Statins have no effect on Lp(a) levels.

While a couple of observational cohort studies have suggested that reducing elevated Lp(a) in patients with cardiovascular disease is associated with a decrease in major adverse cardiovascular events, until now there have been no randomized controlled trials of apheresis as Lp(a)-lowering therapy in patients with refractory angina, according to Dr. Khan.

She presented a randomized, crossover design study in 20 patients with severe refractory angina and an Lp(a) in excess of 50 mg/dL but no elevation in LDL. They underwent 3 months of blinded weekly extracorporeal lipoprotein apheresis using a dextran sulfate filtration system or sham apheresis, followed by a month-long washout period. Participants were then crossed over to the other study arm to increase the statistical power of this small study.

The primary study endpoint was change in myocardial perfusion reserve as measured by cardiovascular magnetic resonance imaging at baseline and after 3 months of true or sham apheresis. The myocardial perfusion reserve index improved by a net of 0.63 after apheresis from a baseline of 1.45. This effect was strongly driven by a substantial increase in stress myocardial perfusion, with very little change in perfusion at rest.

Significant improvements were also recorded after apheresis in the secondary endpoints of change in carotid atheroma as reflected in total carotid wall volume, improvement on various domains of the Seattle Angina Questionnaire, physical limitations as scored on the SF-36, and exercise capacity as measured on the 6-minute walk test.

Discussant Peter Libby, MD, was effusive in his praise for Dr. Khan’s study.

Bruce Jancin/Frontline Medical News

“This is a wonderful example of how we may be able to offer new hope for patients and families with high Lp(a),” declared Dr. Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

He approved of the methodology and embraced what he called “the intriguing preliminary picture of benefit for lowering Lp(a).”

Most of all, he was pleased that Dr. Khan’s well conducted albeit small study has thrown a spotlight on Lp(a), which he characterized as a greatly underappreciated causal risk factor for a range of cardiovascular diseases.

“Lp(a) stands out like a Manhattan skyscraper as the major driver of calcific aortic stenosis, an epidemic that we see in our aging population,” he observed.

He added that topics worthy of further research with regard to Lp(a)-lowering apheresis as a treatment for refractory angina include the question of whether the mechanism of benefit involves structural changes in atherosclerosis or functional changes. And if it’s the latter, is it a matter of changes in microvascular function, macrovascular function, or a combination of the two?

Apheresis is extremely costly, inconvenient, and invasive, and there are only several dozen apheresis centers in the United States. So the future of Lp(a)-lowering to treat refractory angina, calcific aortic stenosis, and other cardiovascular conditions where elevated Lp(a) is an important player may lie in pharmacotherapy with the PCSK9 inhibitors, Dr. Libby predicted.

He cited “very promising” data showing that evolocumab (Repatha) and alirocumab (Praluent) lower Lp(a) in dose-dependent fashion. Ongoing very large clinical trials with hard clinical endpoints should eventually provide key information regarding the cardiovascular benefits of lowering Lp(a).

“We may be entering an era where we may be able to offer our patients and families – because this is often a familial problem – a non-apheresis approach to controlling what we are learning is a very important causal risk factor for atherosclerosis,” Dr. Libby said.

Patrick M. Moriarty, MD, said in a video interview that he was very intrigued by the results, and “not personally surprised.” They should stimulate interest in cardiologists to start measuring Lp(a) in their patients like those in this study, in whom the disease severity doesn’t match up with the clinical risk factors, said Dr. Moriarty of the University of Kansas, Kansas City.

Dr. Khan’s study was funded by the UK National Institute for Health Research. She reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ROME – Weekly lipoprotein apheresis in patients with highly refractory angina accompanied by high plasma lipoprotein(a) without elevated LDL cholesterol led to significantly improved myocardial blood flow in a randomized, blinded, sham-controlled clinical trial, Tina Khan, MD, reported at the annual congress of the European Society of Cardiology.

Participants also experienced clinically meaningful improvements in the secondary endpoints of quality of life, angina symptoms, exercise capacity, and atheroma burden, added Dr. Khan of Imperial College London.

Bruce Jancin/Frontline Medical News

Angina pectoris that is refractory to maximal pharmacologic, percutaneous, and surgical interventions is a major and growing problem. More than 100,000 new cases occur per year in the United States.

“We have a desperate need to develop new therapeutic options,” she said.

Lipoprotein(a), or Lp(a), is a potent independent cardiovascular risk factor. And it figures prominently in refractory angina. Indeed, 60% of the patients with refractory angina screened by Dr. Khan for her clinical trial had an isolated plasma Lp(a) level of 50 mg/dL or more, the threshold at which cardiovascular risk sharply increases. Statins have no effect on Lp(a) levels.

While a couple of observational cohort studies have suggested that reducing elevated Lp(a) in patients with cardiovascular disease is associated with a decrease in major adverse cardiovascular events, until now there have been no randomized controlled trials of apheresis as Lp(a)-lowering therapy in patients with refractory angina, according to Dr. Khan.

She presented a randomized, crossover design study in 20 patients with severe refractory angina and an Lp(a) in excess of 50 mg/dL but no elevation in LDL. They underwent 3 months of blinded weekly extracorporeal lipoprotein apheresis using a dextran sulfate filtration system or sham apheresis, followed by a month-long washout period. Participants were then crossed over to the other study arm to increase the statistical power of this small study.

The primary study endpoint was change in myocardial perfusion reserve as measured by cardiovascular magnetic resonance imaging at baseline and after 3 months of true or sham apheresis. The myocardial perfusion reserve index improved by a net of 0.63 after apheresis from a baseline of 1.45. This effect was strongly driven by a substantial increase in stress myocardial perfusion, with very little change in perfusion at rest.

Significant improvements were also recorded after apheresis in the secondary endpoints of change in carotid atheroma as reflected in total carotid wall volume, improvement on various domains of the Seattle Angina Questionnaire, physical limitations as scored on the SF-36, and exercise capacity as measured on the 6-minute walk test.

Discussant Peter Libby, MD, was effusive in his praise for Dr. Khan’s study.

Bruce Jancin/Frontline Medical News

“This is a wonderful example of how we may be able to offer new hope for patients and families with high Lp(a),” declared Dr. Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

He approved of the methodology and embraced what he called “the intriguing preliminary picture of benefit for lowering Lp(a).”

Most of all, he was pleased that Dr. Khan’s well conducted albeit small study has thrown a spotlight on Lp(a), which he characterized as a greatly underappreciated causal risk factor for a range of cardiovascular diseases.

“Lp(a) stands out like a Manhattan skyscraper as the major driver of calcific aortic stenosis, an epidemic that we see in our aging population,” he observed.

He added that topics worthy of further research with regard to Lp(a)-lowering apheresis as a treatment for refractory angina include the question of whether the mechanism of benefit involves structural changes in atherosclerosis or functional changes. And if it’s the latter, is it a matter of changes in microvascular function, macrovascular function, or a combination of the two?

Apheresis is extremely costly, inconvenient, and invasive, and there are only several dozen apheresis centers in the United States. So the future of Lp(a)-lowering to treat refractory angina, calcific aortic stenosis, and other cardiovascular conditions where elevated Lp(a) is an important player may lie in pharmacotherapy with the PCSK9 inhibitors, Dr. Libby predicted.

He cited “very promising” data showing that evolocumab (Repatha) and alirocumab (Praluent) lower Lp(a) in dose-dependent fashion. Ongoing very large clinical trials with hard clinical endpoints should eventually provide key information regarding the cardiovascular benefits of lowering Lp(a).

“We may be entering an era where we may be able to offer our patients and families – because this is often a familial problem – a non-apheresis approach to controlling what we are learning is a very important causal risk factor for atherosclerosis,” Dr. Libby said.

Patrick M. Moriarty, MD, said in a video interview that he was very intrigued by the results, and “not personally surprised.” They should stimulate interest in cardiologists to start measuring Lp(a) in their patients like those in this study, in whom the disease severity doesn’t match up with the clinical risk factors, said Dr. Moriarty of the University of Kansas, Kansas City.

Dr. Khan’s study was funded by the UK National Institute for Health Research. She reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

ROME – Treating patients with heterozygous familial hypercholesterolemia (HeFH) with PCSK9 inhibitors can reduce their need for lipoprotein apheresis and its associated costs, Patrick M. Moriarty, MD, said in a video interview at the annual congress of the European Society of Cardiology.

In the randomized, phase III ODYSSEY ESCAPE trial, HeFH patients who underwent weekly apheresis were treated with either alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, or placebo. At the end of the study, the alirocumab-treated patients had a 75% greater reduction in need for apheresis, compared with those on placebo – a statistically significant difference.

With a price tag of $50,000-$75,000 a year for lipoprotein apheresis, compared with the roughly $12,000 cost for a PCSK9 inhibitor, this represents a significant savings for patients with HeFH, which occurs in roughly 1 in 200 people worldwide, Dr. Moriarty of the University of Kansas, Kansas City, told reporter Bruce Jancin.

chackett@frontlinemedcom.com

ROME – Treating patients with heterozygous familial hypercholesterolemia (HeFH) with PCSK9 inhibitors can reduce their need for lipoprotein apheresis and its associated costs, Patrick M. Moriarty, MD, said in a video interview at the annual congress of the European Society of Cardiology.

In the randomized, phase III ODYSSEY ESCAPE trial, HeFH patients who underwent weekly apheresis were treated with either alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, or placebo. At the end of the study, the alirocumab-treated patients had a 75% greater reduction in need for apheresis, compared with those on placebo – a statistically significant difference.

With a price tag of $50,000-$75,000 a year for lipoprotein apheresis, compared with the roughly $12,000 cost for a PCSK9 inhibitor, this represents a significant savings for patients with HeFH, which occurs in roughly 1 in 200 people worldwide, Dr. Moriarty of the University of Kansas, Kansas City, told reporter Bruce Jancin.

chackett@frontlinemedcom.com

ROME – Treating patients with heterozygous familial hypercholesterolemia (HeFH) with PCSK9 inhibitors can reduce their need for lipoprotein apheresis and its associated costs, Patrick M. Moriarty, MD, said in a video interview at the annual congress of the European Society of Cardiology.

In the randomized, phase III ODYSSEY ESCAPE trial, HeFH patients who underwent weekly apheresis were treated with either alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, or placebo. At the end of the study, the alirocumab-treated patients had a 75% greater reduction in need for apheresis, compared with those on placebo – a statistically significant difference.

With a price tag of $50,000-$75,000 a year for lipoprotein apheresis, compared with the roughly $12,000 cost for a PCSK9 inhibitor, this represents a significant savings for patients with HeFH, which occurs in roughly 1 in 200 people worldwide, Dr. Moriarty of the University of Kansas, Kansas City, told reporter Bruce Jancin.

chackett@frontlinemedcom.com

ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.

During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.

“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.

The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).

Mitchel L. Zoler/Frontline Medical News

In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.

But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.

Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.

He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.

Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.

During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.

“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.

The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).

Mitchel L. Zoler/Frontline Medical News

In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.

But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.

Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.

He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.

Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – The new oral anticoagulants performed as advertised in a real-world, Danish registry of more than 40,000 patients with atrial fibrillation.

During the first year on anticoagulant treatment, patients who received a new oral anticoagulant (NOAC) had an ischemic stroke rate similar to that of patients who received the traditional oral anticoagulant, warfarin, but a significantly reduced rate of intracranial hemorrhage, Laila Stærk, MD, reported at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/Frontline Medical News

These results “reinforce what we have seen in the clinical trials, but with the strength of looking in the entire Danish population,” said Dan Atar, MD, a cardiologist and professor of medicine at the University of Oslo.

“It is enlightening and very reassuring to have these real-world, unselected, registry data. They provide reassurance about safety and efficacy” when prescribing a NOAC, Dr. Atar said in an interview.

The study reported by Dr. Stærk and her associates included 43,299 Danish patients who were recently diagnosed with nonvalvular atrial fibrillation and started on treatment with an oral anticoagulant during the period August 2011 (when the first NOAC, dabigatran, became available for routine use in Denmark) through December 2015. During this period, 42% of these patients received warfarin, 29% received dabigatran (Pradaxa), 16% received apixaban (Eliquis) and 13% received rivaroxaban (Xarelto).

Mitchel L. Zoler/Frontline Medical News

In a propensity-score type of analysis that controlled for baseline differences in clinical and demographic parameters, the results showed that the rate of ischemic stroke during the first year on treatment ranged from 2.0% to 2.5% in the four subgroups based on the anticoagulant received with no statistically-significant differences among the four subgroups. In other words, all three NOACs had efficacy profiles similar to those of warfarin, said Dr. Stærk, a cardiology researcher at Herlev and Gentofte University Hospitals in Hellerup, Denmark.

But on the safety side, all three NOACs were linked with lower rates of intracranial hemorrhages during the 1-year follow-up compared with the patients who received warfarin. In the cases of dabigatran and apixaban, the reduced intracranial hemorrhage rates were statistically significant, with a 0.6% rate among the patients on warfarin and rates that were reduced by a relative 34% for patients who received dabigatran and by a relative 20% among those on apixaban. Rivaroxaban linked with a 13% relative risk reduction in intracranial hemorrhage that was not statistically significant.

Dr. Atar said he would not make comparisons among the three NOACs based on these data, but rather interpreted the finding as showing that collectively the three NOACs assessed had comparable efficacy but better safety compared with warfarin.

He also noted that the Danish registry data document the transition that occurred during 2011 to 2015 in anticoagulant prescribing that shifted from warfarin to NOACs, with 57% of atrial fibrillation patients receiving a NOAC. In Norway, NOAC prescriptions for atrial fibrillation patients recently pulled ahead of warfarin prescription rates, Dr. Atar said. Reassuring data such as those in this report will help to further drive the shift from warfarin to NOACs, and he predicted that soon NOACs will be the anticoagulants used to treat the overwhelming majority of patients with nonvalvular atrial fibrillation.

Dr. Stærk has received research funding from Boehringer Ingelheim, the company that markets dabigatran (Pradaxa). Dr. Atar said that he has been a consultant to and has received research funding from several drug companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

ROME – “Unfounded” concerns about cardiovascular effects have contributed to underuse of varenicline for smoking cessation, Kornelia Kotseva, MD, said at the annual congress of the European Society of Cardiology.

In an exclusive video interview, Dr. Kotseva of Imperial College, London, told our reporter Bruce Jancin that meta-analyses have shown no significant difference in serious cardiovascular events between varenicline-treated patients and those on placebo, regardless of whether the patients had underlying cardiovascular disease.

Varenicline use for smoking cessation reduces the risk of cardiovascular events by 36%, she reported, more than reductions seen with either nicotine replacement therapy or bupropion.

chackett@frontlinemedcom.com

ROME – “Unfounded” concerns about cardiovascular effects have contributed to underuse of varenicline for smoking cessation, Kornelia Kotseva, MD, said at the annual congress of the European Society of Cardiology.

In an exclusive video interview, Dr. Kotseva of Imperial College, London, told our reporter Bruce Jancin that meta-analyses have shown no significant difference in serious cardiovascular events between varenicline-treated patients and those on placebo, regardless of whether the patients had underlying cardiovascular disease.

Varenicline use for smoking cessation reduces the risk of cardiovascular events by 36%, she reported, more than reductions seen with either nicotine replacement therapy or bupropion.

chackett@frontlinemedcom.com

ROME – “Unfounded” concerns about cardiovascular effects have contributed to underuse of varenicline for smoking cessation, Kornelia Kotseva, MD, said at the annual congress of the European Society of Cardiology.

In an exclusive video interview, Dr. Kotseva of Imperial College, London, told our reporter Bruce Jancin that meta-analyses have shown no significant difference in serious cardiovascular events between varenicline-treated patients and those on placebo, regardless of whether the patients had underlying cardiovascular disease.

Varenicline use for smoking cessation reduces the risk of cardiovascular events by 36%, she reported, more than reductions seen with either nicotine replacement therapy or bupropion.

chackett@frontlinemedcom.com

At the Summer Meeting of the American Academy of Dermatology, Dr. Ted Rosen provides therapeutic pearls on vitamin D for chronic idiopathic urticaria and the quadrivalent human papillomavirus vaccine as a treatment of chronic refractory common warts. Here he reviews anecdotes about successes with both and recommended amounts of vitamin D.

At the Summer Meeting of the American Academy of Dermatology, Dr. Ted Rosen provides therapeutic pearls on vitamin D for chronic idiopathic urticaria and the quadrivalent human papillomavirus vaccine as a treatment of chronic refractory common warts. Here he reviews anecdotes about successes with both and recommended amounts of vitamin D.

At the Summer Meeting of the American Academy of Dermatology, Dr. Ted Rosen provides therapeutic pearls on vitamin D for chronic idiopathic urticaria and the quadrivalent human papillomavirus vaccine as a treatment of chronic refractory common warts. Here he reviews anecdotes about successes with both and recommended amounts of vitamin D.