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CANTOS sings of novel strategy for cardiovascular, cancer prevention
BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.
“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.
CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.
Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.
At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.
Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.
“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.
A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.
“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.
Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”
“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.
Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.
Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.
“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.
An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.
“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.
Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.
He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.
“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.
For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.
“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.
Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.
Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.
He reported serving as a consultant to Novartis.
BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.
“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.
CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.
Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.
At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.
Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.
“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.
A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.
“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.
Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”
“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.
Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.
Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.
“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.
An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.
“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.
Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.
He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.
“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.
For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.
“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.
Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.
Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.
He reported serving as a consultant to Novartis.
BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.
“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.
CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.
Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.
At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.
Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.
“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.
A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.
“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.
Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”
“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.
Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.
Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.
“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.
An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.
“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.
Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.
He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.
“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.
For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.
“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.
Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.
Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.
He reported serving as a consultant to Novartis.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Canakinumab reduced the risk of recurrent cardiovascular events in a very-high-risk population by 15%, compared with placebo, while cutting incident lung cancer by 67% in a major clinical trial.
Data source: CANTOS was a phase III, randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all with a previous MI and chronically high systemic inflammation.
Disclosures: The study was sponsored by Novartis. The presenter reported serving as a consultant to the company.
Sneak Peek: The Hospital Leader blog - Aug. 2017 “A Conversation with Dr. Eric Howell”
Quality improvement became a foundational theme for SHM early in the growth of hospitalists. It’s not a coincidence that many of our leaders, such as Bob Wachter, Win Whitcomb, Greg Maynard, and Mark Williams are QI leaders as well. As hospitalists, we were and are best positioned to impact quality in the hospital.
Eric Howell, MD, of Johns Hopkins Bayview Medical Center in Baltimore serves as the senior physician advisor for SHM’s Center for Quality Improvement, while Jenna Goldstein runs the day-to-day aspects at SHM headquarters. A few months ago, Dr. Howell and I discussed how he started in QI, the role of SHM’s Center, and how hospitalists can receive effective QI training. The following Q&A is edited for conciseness and clarity.
You’ve been a leader in QI for many years; how did you get started in QI?
I trained as an electrical engineer before I went to medical school, which helped me when I went to residency.
When I was a chief at Hopkins Bayview in 1999, there were a number of systems-related issues, including throughput from the emergency department. I became involved with QI because I looked at these systems, thinking they could be better if I used the lens of an engineer. The hospital was very interested in reducing costs, and the physicians, including myself, were interested in making things safer. I was successful because I didn’t just focus on QI but on both sides of the value equation. In the early 2000s, I started to do more and more re-engineering and system improvement projects, and I found them very rewarding. As I showed some success, I was asked to do more.
What you are describing is hands-on training, learning by doing. It seems a lot of your QI training was hands on, as opposed to structured coursework. Was there formal training or is getting your hands dirty in a project the best way to start learning QI?
There is no replacement for actually doing it.
My training was in leadership, which is an integral part of QI. It’s pretty hard to get people to change for quality if you can’t lead them through that change. Initially, I did a lot of work to improve my leadership potential. As faculty, we taught teaching skills, which is a part of leadership. I spent time teaching residents best practices. That’s why I became involved early on with SHM’s Leadership Academy from its start in 2005. I also read a lot of books and still read often to improve my weaknesses. I have my own physicians go through Lean Six Sigma training and get their green belt or black belt.
That said, there is no substitute for doing it and, as they say, “bruising your knuckles” in QI.
Read the full post at hospitalleader.org.
Also on The Hospital Leader…
- From SXSW to SHM: Our Tour to Promote Value Conversations Between Doctors & Patients by Chris Moriates, MD
- It’s Time for a Buzz Cut by Tracy Cardin, ACNP-NC, SFHM
- The Essentials of QI Leadership: A Conversation with Dr. Eric Howell, Part 2 by Jordan Messler, MD, SFHM
Quality improvement became a foundational theme for SHM early in the growth of hospitalists. It’s not a coincidence that many of our leaders, such as Bob Wachter, Win Whitcomb, Greg Maynard, and Mark Williams are QI leaders as well. As hospitalists, we were and are best positioned to impact quality in the hospital.
Eric Howell, MD, of Johns Hopkins Bayview Medical Center in Baltimore serves as the senior physician advisor for SHM’s Center for Quality Improvement, while Jenna Goldstein runs the day-to-day aspects at SHM headquarters. A few months ago, Dr. Howell and I discussed how he started in QI, the role of SHM’s Center, and how hospitalists can receive effective QI training. The following Q&A is edited for conciseness and clarity.
You’ve been a leader in QI for many years; how did you get started in QI?
I trained as an electrical engineer before I went to medical school, which helped me when I went to residency.
When I was a chief at Hopkins Bayview in 1999, there were a number of systems-related issues, including throughput from the emergency department. I became involved with QI because I looked at these systems, thinking they could be better if I used the lens of an engineer. The hospital was very interested in reducing costs, and the physicians, including myself, were interested in making things safer. I was successful because I didn’t just focus on QI but on both sides of the value equation. In the early 2000s, I started to do more and more re-engineering and system improvement projects, and I found them very rewarding. As I showed some success, I was asked to do more.
What you are describing is hands-on training, learning by doing. It seems a lot of your QI training was hands on, as opposed to structured coursework. Was there formal training or is getting your hands dirty in a project the best way to start learning QI?
There is no replacement for actually doing it.
My training was in leadership, which is an integral part of QI. It’s pretty hard to get people to change for quality if you can’t lead them through that change. Initially, I did a lot of work to improve my leadership potential. As faculty, we taught teaching skills, which is a part of leadership. I spent time teaching residents best practices. That’s why I became involved early on with SHM’s Leadership Academy from its start in 2005. I also read a lot of books and still read often to improve my weaknesses. I have my own physicians go through Lean Six Sigma training and get their green belt or black belt.
That said, there is no substitute for doing it and, as they say, “bruising your knuckles” in QI.
Read the full post at hospitalleader.org.
Also on The Hospital Leader…
- From SXSW to SHM: Our Tour to Promote Value Conversations Between Doctors & Patients by Chris Moriates, MD
- It’s Time for a Buzz Cut by Tracy Cardin, ACNP-NC, SFHM
- The Essentials of QI Leadership: A Conversation with Dr. Eric Howell, Part 2 by Jordan Messler, MD, SFHM
Quality improvement became a foundational theme for SHM early in the growth of hospitalists. It’s not a coincidence that many of our leaders, such as Bob Wachter, Win Whitcomb, Greg Maynard, and Mark Williams are QI leaders as well. As hospitalists, we were and are best positioned to impact quality in the hospital.
Eric Howell, MD, of Johns Hopkins Bayview Medical Center in Baltimore serves as the senior physician advisor for SHM’s Center for Quality Improvement, while Jenna Goldstein runs the day-to-day aspects at SHM headquarters. A few months ago, Dr. Howell and I discussed how he started in QI, the role of SHM’s Center, and how hospitalists can receive effective QI training. The following Q&A is edited for conciseness and clarity.
You’ve been a leader in QI for many years; how did you get started in QI?
I trained as an electrical engineer before I went to medical school, which helped me when I went to residency.
When I was a chief at Hopkins Bayview in 1999, there were a number of systems-related issues, including throughput from the emergency department. I became involved with QI because I looked at these systems, thinking they could be better if I used the lens of an engineer. The hospital was very interested in reducing costs, and the physicians, including myself, were interested in making things safer. I was successful because I didn’t just focus on QI but on both sides of the value equation. In the early 2000s, I started to do more and more re-engineering and system improvement projects, and I found them very rewarding. As I showed some success, I was asked to do more.
What you are describing is hands-on training, learning by doing. It seems a lot of your QI training was hands on, as opposed to structured coursework. Was there formal training or is getting your hands dirty in a project the best way to start learning QI?
There is no replacement for actually doing it.
My training was in leadership, which is an integral part of QI. It’s pretty hard to get people to change for quality if you can’t lead them through that change. Initially, I did a lot of work to improve my leadership potential. As faculty, we taught teaching skills, which is a part of leadership. I spent time teaching residents best practices. That’s why I became involved early on with SHM’s Leadership Academy from its start in 2005. I also read a lot of books and still read often to improve my weaknesses. I have my own physicians go through Lean Six Sigma training and get their green belt or black belt.
That said, there is no substitute for doing it and, as they say, “bruising your knuckles” in QI.
Read the full post at hospitalleader.org.
Also on The Hospital Leader…
- From SXSW to SHM: Our Tour to Promote Value Conversations Between Doctors & Patients by Chris Moriates, MD
- It’s Time for a Buzz Cut by Tracy Cardin, ACNP-NC, SFHM
- The Essentials of QI Leadership: A Conversation with Dr. Eric Howell, Part 2 by Jordan Messler, MD, SFHM
Forgo supplemental oxygen in adequately perfused patients with acute MI, study suggests
Supplemental oxygen did not prevent mortality or rehospitalization among patients with suspected myocardial infarction whose oxygen saturation on room air exceeded 90%, investigators reported.
Rates of all-cause mortality at 1 year were 5% among patients who received supplemental oxygen through an open face mask (6 liters per minute for 6-12 hours) and 5.1% among patients who breathed room air, said Robin Hofmann, MD, of Karolinska Institutet, Stockholm, and his associates. In addition, rehospitalization for MI occurred in 3.8% of patients who received supplemental oxygen and 3.3% of those breathed room air. The findings of the randomized registry-based trial of 6,629 patients were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
Guidelines recommend oxygen supplementation in MI, and the practice has persisted for more than a century, but adequately powered trials of hard clinical endpoints are lacking. Above-normal oxygen saturation can potentially worsen reperfusion injury by causing coronary vasoconstriction and increasing production of reactive oxygen species, the researchers noted.
Notably, the Australian Air Versus Oxygen in Myocardial Infarction (AVOID) trial found that oxygen supplementation was associated with larger infarct sizes in patients with ST-segment elevation myocardial infarction, and a recent Cochrane report did not support routine oxygen supplementation for MI.
The current trial enrolled patients aged 30 years and older who had chest pain or shortness of breath lasting less than 6 hours, an oxygen saturation of at least 90% on pulse oximetry, and either electrocardiographic evidence of ischemia or elevated cardiac troponin T or I levels (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMoa1706222).
Oxygen therapy lasted a median of 11.6 hours, after which median oxygen saturation levels were 99% in the intervention group and 97% in the control group.
A total of 62 patients (2%) who received oxygen developed hypoxemia, as did 254 patients (8%) who breathed room air. Median highest troponin levels during hospitalization were 946.5 ng per L and 983.0 ng per L, respectively. A total of 166 (5%) patients in the oxygen group and 168 (5.1%) control patients died from any cause by a year after treatment (hazard ratio, 0.97; P = .8). Likewise, supplemental oxygen did not prevent rehospitalization with MI within 1 year (HR, 1.13; P = .3).
“Because power for evaluation of the primary endpoint was lower than anticipated, we cannot completely rule out a small beneficial or detrimental effect of oxygen on mortality,” the researchers wrote. But clinical differences were unlikely, based on the superimposable time-to-event curves through 12 months, the consistent results across subgroups, and the neutral findings on secondary clinical endpoints, they added.
The Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research funded the study. Dr. Hofmann disclosed research grants from these entities.
The study by Hofmann and coworkers provides definitive evidence for a lack of benefit of supplemental oxygen therapy in patients with acute myocardial infarction who have normal oxygen saturation. Although the mechanisms underlying physiological and biochemical adaptation to myocardial ischemia are complex, the answer to the question is straightforward, and its implications for coronary care are indisputable: Supplemental oxygen provides no benefit to patients with acute coronary syndromes who do not have hypoxemia. It is clearly time for clinical practice to change to reflect this definitive evidence.
Joseph Loscalzo, MD, PhD, is in the department of medicine, Brigham and Women’s Hospital, Boston. He is an editor-at-large for the New England Journal of Medicine. He had no other disclosures. These comments are from his accompanying editorial (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMe1709250).
The study by Hofmann and coworkers provides definitive evidence for a lack of benefit of supplemental oxygen therapy in patients with acute myocardial infarction who have normal oxygen saturation. Although the mechanisms underlying physiological and biochemical adaptation to myocardial ischemia are complex, the answer to the question is straightforward, and its implications for coronary care are indisputable: Supplemental oxygen provides no benefit to patients with acute coronary syndromes who do not have hypoxemia. It is clearly time for clinical practice to change to reflect this definitive evidence.
Joseph Loscalzo, MD, PhD, is in the department of medicine, Brigham and Women’s Hospital, Boston. He is an editor-at-large for the New England Journal of Medicine. He had no other disclosures. These comments are from his accompanying editorial (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMe1709250).
The study by Hofmann and coworkers provides definitive evidence for a lack of benefit of supplemental oxygen therapy in patients with acute myocardial infarction who have normal oxygen saturation. Although the mechanisms underlying physiological and biochemical adaptation to myocardial ischemia are complex, the answer to the question is straightforward, and its implications for coronary care are indisputable: Supplemental oxygen provides no benefit to patients with acute coronary syndromes who do not have hypoxemia. It is clearly time for clinical practice to change to reflect this definitive evidence.
Joseph Loscalzo, MD, PhD, is in the department of medicine, Brigham and Women’s Hospital, Boston. He is an editor-at-large for the New England Journal of Medicine. He had no other disclosures. These comments are from his accompanying editorial (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMe1709250).
Supplemental oxygen did not prevent mortality or rehospitalization among patients with suspected myocardial infarction whose oxygen saturation on room air exceeded 90%, investigators reported.
Rates of all-cause mortality at 1 year were 5% among patients who received supplemental oxygen through an open face mask (6 liters per minute for 6-12 hours) and 5.1% among patients who breathed room air, said Robin Hofmann, MD, of Karolinska Institutet, Stockholm, and his associates. In addition, rehospitalization for MI occurred in 3.8% of patients who received supplemental oxygen and 3.3% of those breathed room air. The findings of the randomized registry-based trial of 6,629 patients were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
Guidelines recommend oxygen supplementation in MI, and the practice has persisted for more than a century, but adequately powered trials of hard clinical endpoints are lacking. Above-normal oxygen saturation can potentially worsen reperfusion injury by causing coronary vasoconstriction and increasing production of reactive oxygen species, the researchers noted.
Notably, the Australian Air Versus Oxygen in Myocardial Infarction (AVOID) trial found that oxygen supplementation was associated with larger infarct sizes in patients with ST-segment elevation myocardial infarction, and a recent Cochrane report did not support routine oxygen supplementation for MI.
The current trial enrolled patients aged 30 years and older who had chest pain or shortness of breath lasting less than 6 hours, an oxygen saturation of at least 90% on pulse oximetry, and either electrocardiographic evidence of ischemia or elevated cardiac troponin T or I levels (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMoa1706222).
Oxygen therapy lasted a median of 11.6 hours, after which median oxygen saturation levels were 99% in the intervention group and 97% in the control group.
A total of 62 patients (2%) who received oxygen developed hypoxemia, as did 254 patients (8%) who breathed room air. Median highest troponin levels during hospitalization were 946.5 ng per L and 983.0 ng per L, respectively. A total of 166 (5%) patients in the oxygen group and 168 (5.1%) control patients died from any cause by a year after treatment (hazard ratio, 0.97; P = .8). Likewise, supplemental oxygen did not prevent rehospitalization with MI within 1 year (HR, 1.13; P = .3).
“Because power for evaluation of the primary endpoint was lower than anticipated, we cannot completely rule out a small beneficial or detrimental effect of oxygen on mortality,” the researchers wrote. But clinical differences were unlikely, based on the superimposable time-to-event curves through 12 months, the consistent results across subgroups, and the neutral findings on secondary clinical endpoints, they added.
The Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research funded the study. Dr. Hofmann disclosed research grants from these entities.
Supplemental oxygen did not prevent mortality or rehospitalization among patients with suspected myocardial infarction whose oxygen saturation on room air exceeded 90%, investigators reported.
Rates of all-cause mortality at 1 year were 5% among patients who received supplemental oxygen through an open face mask (6 liters per minute for 6-12 hours) and 5.1% among patients who breathed room air, said Robin Hofmann, MD, of Karolinska Institutet, Stockholm, and his associates. In addition, rehospitalization for MI occurred in 3.8% of patients who received supplemental oxygen and 3.3% of those breathed room air. The findings of the randomized registry-based trial of 6,629 patients were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
Guidelines recommend oxygen supplementation in MI, and the practice has persisted for more than a century, but adequately powered trials of hard clinical endpoints are lacking. Above-normal oxygen saturation can potentially worsen reperfusion injury by causing coronary vasoconstriction and increasing production of reactive oxygen species, the researchers noted.
Notably, the Australian Air Versus Oxygen in Myocardial Infarction (AVOID) trial found that oxygen supplementation was associated with larger infarct sizes in patients with ST-segment elevation myocardial infarction, and a recent Cochrane report did not support routine oxygen supplementation for MI.
The current trial enrolled patients aged 30 years and older who had chest pain or shortness of breath lasting less than 6 hours, an oxygen saturation of at least 90% on pulse oximetry, and either electrocardiographic evidence of ischemia or elevated cardiac troponin T or I levels (N Engl J Med. 2017 Aug 28. doi: 10.1056/NEJMoa1706222).
Oxygen therapy lasted a median of 11.6 hours, after which median oxygen saturation levels were 99% in the intervention group and 97% in the control group.
A total of 62 patients (2%) who received oxygen developed hypoxemia, as did 254 patients (8%) who breathed room air. Median highest troponin levels during hospitalization were 946.5 ng per L and 983.0 ng per L, respectively. A total of 166 (5%) patients in the oxygen group and 168 (5.1%) control patients died from any cause by a year after treatment (hazard ratio, 0.97; P = .8). Likewise, supplemental oxygen did not prevent rehospitalization with MI within 1 year (HR, 1.13; P = .3).
“Because power for evaluation of the primary endpoint was lower than anticipated, we cannot completely rule out a small beneficial or detrimental effect of oxygen on mortality,” the researchers wrote. But clinical differences were unlikely, based on the superimposable time-to-event curves through 12 months, the consistent results across subgroups, and the neutral findings on secondary clinical endpoints, they added.
The Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research funded the study. Dr. Hofmann disclosed research grants from these entities.
FROM THE ESC CONGRESS 2017
Key clinical point: Supplemental oxygen did not benefit patients with suspected myocardial infarction who did not have hypoxemia.
Major finding: At 1 year, rates of all-cause mortality were 5% among patients who received supplemental oxygen and 5.1% among those who received no oxygen.
Data source: A registry-based, randomized clinical trial of 6,629 patients with suspected myocardial infarction without hypoxemia.
Disclosures: The Swedish Research Council, the Swedish Heart-Lung Foundation, and the Swedish Foundation for Strategic Research funded the study. Dr. Hofmann disclosed research grants from these entities.
Therapy shows promise for PUPs with severe hemophilia A
A fourth-generation recombinant factor VIII (FVIII) therapy has demonstrated “convincing” efficacy and tolerability as well as low immunogenicity in previously untreated patients (PUPs) with severe hemophilia A, according to researchers.
The therapy, simoctocog alfa, is a B-domain-deleted recombinant FVIII product derived from a human cell line.
In the NuProtect study (also known as GENA-05), researchers are evaluating simoctocog alfa in PUPs with severe hemophilia A.
Interim results from this study were recently published in Haemophilia. The research is sponsored by Octapharma, makers of simoctocog alfa.
Thus far, NuProtect has enrolled 110 PUPs who will receive simoctocog alfa for up to 100 exposure days (EDs).
The Haemophilia article describes interim results for 66 PUPs treated for at least 20 EDs, the time by which most inhibitors arise. The patients’ median age at first treatment was 13 months (range, 3 months to 135 months).
The patients received simoctocog alfa for standard prophylaxis, surgical prophylaxis, or on-demand treatment.
Forty-five (68.2%) patients received standard prophylaxis, 13 (19.7%) received only on-demand treatment, 8 (12.1%) were initially treated on-demand but later received prophylaxis, and 13 (19.7%) patients received surgical prophylaxis (for 14 procedures).
The median number of EDs was 43.0 (range, 4-120).
Results
The primary objective of this study is to assess the immunogenicity of simoctocog alfa by determining inhibitor activity using the Nijmegen-modified Bethesda assay at a central laboratory.
After a median of 11.5 EDs (range, 6-24), 8 patients had developed high-titer anti-FVIII inhibitors, and 5 patients had developed low-titer inhibitors, 4 of them transient.
The cumulative incidence of all inhibitors was 20.8%—12.8% for high-titer and 8.4% for low-titer inhibitors.
For patients who received prophylaxis, the median annual bleeding rate, during inhibitor-free periods, was 2.40 for all bleeds and 0 for spontaneous bleeds.
When simoctocog alfa was used on-demand, 92.4% of bleeds were controlled with 1 or 2 infusions. In addition, simoctocog alfa was said to demonstrate “excellent” or “good” efficacy in 89% of surgical procedures.
Three patients experienced adverse events (other than inhibitor development) that were considered related to simoctocog alfa.
One patient developed a mild fever. Another had a mild allergic reaction after 3 consecutive infusions of simoctocog alfa (but not after subsequent infusions).
The third patient developed a rash that was described as mild but considered serious due to hospitalization. This patient continued treatment and completed the study. 
A fourth-generation recombinant factor VIII (FVIII) therapy has demonstrated “convincing” efficacy and tolerability as well as low immunogenicity in previously untreated patients (PUPs) with severe hemophilia A, according to researchers.
The therapy, simoctocog alfa, is a B-domain-deleted recombinant FVIII product derived from a human cell line.
In the NuProtect study (also known as GENA-05), researchers are evaluating simoctocog alfa in PUPs with severe hemophilia A.
Interim results from this study were recently published in Haemophilia. The research is sponsored by Octapharma, makers of simoctocog alfa.
Thus far, NuProtect has enrolled 110 PUPs who will receive simoctocog alfa for up to 100 exposure days (EDs).
The Haemophilia article describes interim results for 66 PUPs treated for at least 20 EDs, the time by which most inhibitors arise. The patients’ median age at first treatment was 13 months (range, 3 months to 135 months).
The patients received simoctocog alfa for standard prophylaxis, surgical prophylaxis, or on-demand treatment.
Forty-five (68.2%) patients received standard prophylaxis, 13 (19.7%) received only on-demand treatment, 8 (12.1%) were initially treated on-demand but later received prophylaxis, and 13 (19.7%) patients received surgical prophylaxis (for 14 procedures).
The median number of EDs was 43.0 (range, 4-120).
Results
The primary objective of this study is to assess the immunogenicity of simoctocog alfa by determining inhibitor activity using the Nijmegen-modified Bethesda assay at a central laboratory.
After a median of 11.5 EDs (range, 6-24), 8 patients had developed high-titer anti-FVIII inhibitors, and 5 patients had developed low-titer inhibitors, 4 of them transient.
The cumulative incidence of all inhibitors was 20.8%—12.8% for high-titer and 8.4% for low-titer inhibitors.
For patients who received prophylaxis, the median annual bleeding rate, during inhibitor-free periods, was 2.40 for all bleeds and 0 for spontaneous bleeds.
When simoctocog alfa was used on-demand, 92.4% of bleeds were controlled with 1 or 2 infusions. In addition, simoctocog alfa was said to demonstrate “excellent” or “good” efficacy in 89% of surgical procedures.
Three patients experienced adverse events (other than inhibitor development) that were considered related to simoctocog alfa.
One patient developed a mild fever. Another had a mild allergic reaction after 3 consecutive infusions of simoctocog alfa (but not after subsequent infusions).
The third patient developed a rash that was described as mild but considered serious due to hospitalization. This patient continued treatment and completed the study.
A fourth-generation recombinant factor VIII (FVIII) therapy has demonstrated “convincing” efficacy and tolerability as well as low immunogenicity in previously untreated patients (PUPs) with severe hemophilia A, according to researchers.
The therapy, simoctocog alfa, is a B-domain-deleted recombinant FVIII product derived from a human cell line.
In the NuProtect study (also known as GENA-05), researchers are evaluating simoctocog alfa in PUPs with severe hemophilia A.
Interim results from this study were recently published in Haemophilia. The research is sponsored by Octapharma, makers of simoctocog alfa.
Thus far, NuProtect has enrolled 110 PUPs who will receive simoctocog alfa for up to 100 exposure days (EDs).
The Haemophilia article describes interim results for 66 PUPs treated for at least 20 EDs, the time by which most inhibitors arise. The patients’ median age at first treatment was 13 months (range, 3 months to 135 months).
The patients received simoctocog alfa for standard prophylaxis, surgical prophylaxis, or on-demand treatment.
Forty-five (68.2%) patients received standard prophylaxis, 13 (19.7%) received only on-demand treatment, 8 (12.1%) were initially treated on-demand but later received prophylaxis, and 13 (19.7%) patients received surgical prophylaxis (for 14 procedures).
The median number of EDs was 43.0 (range, 4-120).
Results
The primary objective of this study is to assess the immunogenicity of simoctocog alfa by determining inhibitor activity using the Nijmegen-modified Bethesda assay at a central laboratory.
After a median of 11.5 EDs (range, 6-24), 8 patients had developed high-titer anti-FVIII inhibitors, and 5 patients had developed low-titer inhibitors, 4 of them transient.
The cumulative incidence of all inhibitors was 20.8%—12.8% for high-titer and 8.4% for low-titer inhibitors.
For patients who received prophylaxis, the median annual bleeding rate, during inhibitor-free periods, was 2.40 for all bleeds and 0 for spontaneous bleeds.
When simoctocog alfa was used on-demand, 92.4% of bleeds were controlled with 1 or 2 infusions. In addition, simoctocog alfa was said to demonstrate “excellent” or “good” efficacy in 89% of surgical procedures.
Three patients experienced adverse events (other than inhibitor development) that were considered related to simoctocog alfa.
One patient developed a mild fever. Another had a mild allergic reaction after 3 consecutive infusions of simoctocog alfa (but not after subsequent infusions).
The third patient developed a rash that was described as mild but considered serious due to hospitalization. This patient continued treatment and completed the study.
Reimmunization appears safe in children with history of adverse events
(AEFI), but there are not enough data to make firm conclusions about severe AEFIs, according to a systematic review of studies that were published in English and French between 1982 and 2016 and were made available to Medline via PubMed, Embase, and the Cochrane library.
Apnea was found to be of concern only in children under the age of 1 year and usually found only in lower birth weight babies and those with ongoing hospitalization for complications related to prematurity, the investigators said. A 10-g increase in birth weight was associated with a 6% reduction in risk of apnea recurrence (odds ratio, 0.94; 95% CI, 0.89-1.00), and odds of recurrence were 23 times higher in infants hospitalized for complications related to prematurity (OR, 23; 95% CI, 2-272).
Some of the studies also evaluated for injection site reactions, Henoch-Schönlein purpura, or other AEFI, Dr. Zafack and her coauthors continued. Injection site reactions varied depending on vaccine and number of doses, but all children recovered within 19 days of immunization. Only one child in one study had a recurrence of Henoch-Schönlein purpura. Vomiting, persistent crying, decreased appetite, and drowsiness recurred in 15%, 24%, 25%, and 35% of the reimmunized patients, respectively, across all the studies.
“In a context of vaccine hesitancy and growing concerns regarding vaccine safety, evaluating the risk of recurrence of all AEFIs should become part of the standard evaluation of vaccine safety,” the researchers wrote. “Reimmunization appears to be safe for patients with mild to moderate AEFIs. However, the data are insufficient to draw firm conclusions regarding the safety of reimmunization after a severe AEFI.”
In this study, “it appears that the risk of recurrence of serious AEFIs (anaphylaxis, seizures, or apnea in term infants) was low (less than 1%). For minor to moderate AEFIs (fever, extensive limb swelling, oculorespiratory syndrome, allergic-like events, sleepiness, thrombocytopenia, decreased appetite, vomiting, or persistent crying), the risk of recurrence ranged from 4% to 48%,” the investigators concluded.
The study was funded by the Canadian Immunization Research Network, which is sponsored by the Public Health Agency of Canada and the Canadian Institutes of Health Research. Dr. Zafack reported no financial disclosures. Some of her coauthors reported financial support from GlaxoSmithKline and Pfizer.
There are few experiences more challenging for a pediatrician than trying to convince a parent to continue vaccinating his or her child after witnessing a seemingly related adverse event following immunization (AEFI). The question they want answered is, Will it happen again?
Zafack et al. have sought to answer that question by providing previously lacking estimates of the risk of recurrence. By consolidating the data available in a range of literature, they showed that the risk of a serious AEFI is less than 1%. More accurate risk assessments also are available for mild to moderate AEFI for many vaccines.
The Zafack et al. article also reinforces what vaccinologists and pediatricians have known for many years: Vaccines are incredibly safe. Vaccines are administered to millions of children every year, and the list of known adverse events still is very short. The researchers reaffirm the overwhelming value and safety of vaccines that protect infants and children from complications and death resulting from infectious diseases.
Even though this article does not address AEFI risk for all vaccines, it is impressively comprehensive and will be a useful reference for practicing pediatricians everywhere for years to come.
Sean T. O’Leary, MD, MPH , is an associate professor in the division of infectious diseases in the department of pediatrics at the University of Colorado at Denver, Aurora. Yvonne A. Maldonado, MD , is chief of the division of pediatric infectious diseases and a professor of pediatrics at Stanford (Calif.) University. She serves on a Data Safety Monitoring Board for a Pfizer vaccine trial. Both authors are members of the American Academy of Pediatrics committee on infectious disease and subcommittee on vaccine policy and vaccine hesitancy. These comments were published in an editorial accompanying the Zafack et al. article in Pediatrics (2017. doi: 10.1542/peds.2017-1760 ).
There are few experiences more challenging for a pediatrician than trying to convince a parent to continue vaccinating his or her child after witnessing a seemingly related adverse event following immunization (AEFI). The question they want answered is, Will it happen again?
Zafack et al. have sought to answer that question by providing previously lacking estimates of the risk of recurrence. By consolidating the data available in a range of literature, they showed that the risk of a serious AEFI is less than 1%. More accurate risk assessments also are available for mild to moderate AEFI for many vaccines.
The Zafack et al. article also reinforces what vaccinologists and pediatricians have known for many years: Vaccines are incredibly safe. Vaccines are administered to millions of children every year, and the list of known adverse events still is very short. The researchers reaffirm the overwhelming value and safety of vaccines that protect infants and children from complications and death resulting from infectious diseases.
Even though this article does not address AEFI risk for all vaccines, it is impressively comprehensive and will be a useful reference for practicing pediatricians everywhere for years to come.
Sean T. O’Leary, MD, MPH , is an associate professor in the division of infectious diseases in the department of pediatrics at the University of Colorado at Denver, Aurora. Yvonne A. Maldonado, MD , is chief of the division of pediatric infectious diseases and a professor of pediatrics at Stanford (Calif.) University. She serves on a Data Safety Monitoring Board for a Pfizer vaccine trial. Both authors are members of the American Academy of Pediatrics committee on infectious disease and subcommittee on vaccine policy and vaccine hesitancy. These comments were published in an editorial accompanying the Zafack et al. article in Pediatrics (2017. doi: 10.1542/peds.2017-1760 ).
There are few experiences more challenging for a pediatrician than trying to convince a parent to continue vaccinating his or her child after witnessing a seemingly related adverse event following immunization (AEFI). The question they want answered is, Will it happen again?
Zafack et al. have sought to answer that question by providing previously lacking estimates of the risk of recurrence. By consolidating the data available in a range of literature, they showed that the risk of a serious AEFI is less than 1%. More accurate risk assessments also are available for mild to moderate AEFI for many vaccines.
The Zafack et al. article also reinforces what vaccinologists and pediatricians have known for many years: Vaccines are incredibly safe. Vaccines are administered to millions of children every year, and the list of known adverse events still is very short. The researchers reaffirm the overwhelming value and safety of vaccines that protect infants and children from complications and death resulting from infectious diseases.
Even though this article does not address AEFI risk for all vaccines, it is impressively comprehensive and will be a useful reference for practicing pediatricians everywhere for years to come.
Sean T. O’Leary, MD, MPH , is an associate professor in the division of infectious diseases in the department of pediatrics at the University of Colorado at Denver, Aurora. Yvonne A. Maldonado, MD , is chief of the division of pediatric infectious diseases and a professor of pediatrics at Stanford (Calif.) University. She serves on a Data Safety Monitoring Board for a Pfizer vaccine trial. Both authors are members of the American Academy of Pediatrics committee on infectious disease and subcommittee on vaccine policy and vaccine hesitancy. These comments were published in an editorial accompanying the Zafack et al. article in Pediatrics (2017. doi: 10.1542/peds.2017-1760 ).
(AEFI), but there are not enough data to make firm conclusions about severe AEFIs, according to a systematic review of studies that were published in English and French between 1982 and 2016 and were made available to Medline via PubMed, Embase, and the Cochrane library.
Apnea was found to be of concern only in children under the age of 1 year and usually found only in lower birth weight babies and those with ongoing hospitalization for complications related to prematurity, the investigators said. A 10-g increase in birth weight was associated with a 6% reduction in risk of apnea recurrence (odds ratio, 0.94; 95% CI, 0.89-1.00), and odds of recurrence were 23 times higher in infants hospitalized for complications related to prematurity (OR, 23; 95% CI, 2-272).
Some of the studies also evaluated for injection site reactions, Henoch-Schönlein purpura, or other AEFI, Dr. Zafack and her coauthors continued. Injection site reactions varied depending on vaccine and number of doses, but all children recovered within 19 days of immunization. Only one child in one study had a recurrence of Henoch-Schönlein purpura. Vomiting, persistent crying, decreased appetite, and drowsiness recurred in 15%, 24%, 25%, and 35% of the reimmunized patients, respectively, across all the studies.
“In a context of vaccine hesitancy and growing concerns regarding vaccine safety, evaluating the risk of recurrence of all AEFIs should become part of the standard evaluation of vaccine safety,” the researchers wrote. “Reimmunization appears to be safe for patients with mild to moderate AEFIs. However, the data are insufficient to draw firm conclusions regarding the safety of reimmunization after a severe AEFI.”
In this study, “it appears that the risk of recurrence of serious AEFIs (anaphylaxis, seizures, or apnea in term infants) was low (less than 1%). For minor to moderate AEFIs (fever, extensive limb swelling, oculorespiratory syndrome, allergic-like events, sleepiness, thrombocytopenia, decreased appetite, vomiting, or persistent crying), the risk of recurrence ranged from 4% to 48%,” the investigators concluded.
The study was funded by the Canadian Immunization Research Network, which is sponsored by the Public Health Agency of Canada and the Canadian Institutes of Health Research. Dr. Zafack reported no financial disclosures. Some of her coauthors reported financial support from GlaxoSmithKline and Pfizer.
(AEFI), but there are not enough data to make firm conclusions about severe AEFIs, according to a systematic review of studies that were published in English and French between 1982 and 2016 and were made available to Medline via PubMed, Embase, and the Cochrane library.
Apnea was found to be of concern only in children under the age of 1 year and usually found only in lower birth weight babies and those with ongoing hospitalization for complications related to prematurity, the investigators said. A 10-g increase in birth weight was associated with a 6% reduction in risk of apnea recurrence (odds ratio, 0.94; 95% CI, 0.89-1.00), and odds of recurrence were 23 times higher in infants hospitalized for complications related to prematurity (OR, 23; 95% CI, 2-272).
Some of the studies also evaluated for injection site reactions, Henoch-Schönlein purpura, or other AEFI, Dr. Zafack and her coauthors continued. Injection site reactions varied depending on vaccine and number of doses, but all children recovered within 19 days of immunization. Only one child in one study had a recurrence of Henoch-Schönlein purpura. Vomiting, persistent crying, decreased appetite, and drowsiness recurred in 15%, 24%, 25%, and 35% of the reimmunized patients, respectively, across all the studies.
“In a context of vaccine hesitancy and growing concerns regarding vaccine safety, evaluating the risk of recurrence of all AEFIs should become part of the standard evaluation of vaccine safety,” the researchers wrote. “Reimmunization appears to be safe for patients with mild to moderate AEFIs. However, the data are insufficient to draw firm conclusions regarding the safety of reimmunization after a severe AEFI.”
In this study, “it appears that the risk of recurrence of serious AEFIs (anaphylaxis, seizures, or apnea in term infants) was low (less than 1%). For minor to moderate AEFIs (fever, extensive limb swelling, oculorespiratory syndrome, allergic-like events, sleepiness, thrombocytopenia, decreased appetite, vomiting, or persistent crying), the risk of recurrence ranged from 4% to 48%,” the investigators concluded.
The study was funded by the Canadian Immunization Research Network, which is sponsored by the Public Health Agency of Canada and the Canadian Institutes of Health Research. Dr. Zafack reported no financial disclosures. Some of her coauthors reported financial support from GlaxoSmithKline and Pfizer.
FROM PEDIATRICS
Key clinical point: Reimmunization appears to be safe for patients with mild to moderate adverse events following immunization.
Major finding: The risk of a serious AEFI is less than 1%. More accurate risk assessments also are available for mild to moderate AEFI.
Data source: A systematic review of 29 studies assessing the risks of AEFI.
Disclosures: The study was funded by the Canadian Immunization Research Network, which is sponsored by the Public Health Agency of Canada and the Canadian Institutes of Health Research. Dr. Zafack reported no financial disclosures. Some of her coauthors reported financial support from GlaxoSmithKline and Pfizer.
Rapid AMI rule out
Clinical Question: Can a single high-sensitivity cardiac troponin-T (hs-cTnT) reliably rule-out acute myocardial infarction (AMI) to safely enable earlier discharge?
Background: Current practice includes serial measures of hs-cTnT to rule out AMI.
Study Design: A meta-analysis of 11 prospective cohorts at various international locations
Setting: Patients presenting to emergency departments with chest pain.
Synopsis: Of 9,241, a total of 2,825 patients were classified as low risk with a single negative hs-cTnT and nonischemic EKG. The primary outcome was AMI during initial hospitalization. Of low-risk patients, 14 (0.5%) had AMI. Pooled estimated sensitivity was 98.7% and pooled negative predictive value was 99.3%. For the secondary outcome of 30-day major adverse cardiac events, pooled sensitivity was 98%. Limitations include a small number of studies, high statistical heterogeneity, variation in troponin assays, and variable prevalence of AMI across studies.
Bottom Line: A single negative hs-cTnT and nonischemic EKG after three hours of chest pain can reliably rule out AMI. Further research is, however, required to validate the unequivocal use of this early rule out strategy.
Citation: Pickering J, Than M, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin t measurement below the limit of detection: A collaborative meta-analysis. Ann Intern Med. 2017 May 16;166(10):715-24.
Dr. Dogra is clinical instructor of medicine in the University of Kentucky division of hospital medicine.
Clinical Question: Can a single high-sensitivity cardiac troponin-T (hs-cTnT) reliably rule-out acute myocardial infarction (AMI) to safely enable earlier discharge?
Background: Current practice includes serial measures of hs-cTnT to rule out AMI.
Study Design: A meta-analysis of 11 prospective cohorts at various international locations
Setting: Patients presenting to emergency departments with chest pain.
Synopsis: Of 9,241, a total of 2,825 patients were classified as low risk with a single negative hs-cTnT and nonischemic EKG. The primary outcome was AMI during initial hospitalization. Of low-risk patients, 14 (0.5%) had AMI. Pooled estimated sensitivity was 98.7% and pooled negative predictive value was 99.3%. For the secondary outcome of 30-day major adverse cardiac events, pooled sensitivity was 98%. Limitations include a small number of studies, high statistical heterogeneity, variation in troponin assays, and variable prevalence of AMI across studies.
Bottom Line: A single negative hs-cTnT and nonischemic EKG after three hours of chest pain can reliably rule out AMI. Further research is, however, required to validate the unequivocal use of this early rule out strategy.
Citation: Pickering J, Than M, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin t measurement below the limit of detection: A collaborative meta-analysis. Ann Intern Med. 2017 May 16;166(10):715-24.
Dr. Dogra is clinical instructor of medicine in the University of Kentucky division of hospital medicine.
Clinical Question: Can a single high-sensitivity cardiac troponin-T (hs-cTnT) reliably rule-out acute myocardial infarction (AMI) to safely enable earlier discharge?
Background: Current practice includes serial measures of hs-cTnT to rule out AMI.
Study Design: A meta-analysis of 11 prospective cohorts at various international locations
Setting: Patients presenting to emergency departments with chest pain.
Synopsis: Of 9,241, a total of 2,825 patients were classified as low risk with a single negative hs-cTnT and nonischemic EKG. The primary outcome was AMI during initial hospitalization. Of low-risk patients, 14 (0.5%) had AMI. Pooled estimated sensitivity was 98.7% and pooled negative predictive value was 99.3%. For the secondary outcome of 30-day major adverse cardiac events, pooled sensitivity was 98%. Limitations include a small number of studies, high statistical heterogeneity, variation in troponin assays, and variable prevalence of AMI across studies.
Bottom Line: A single negative hs-cTnT and nonischemic EKG after three hours of chest pain can reliably rule out AMI. Further research is, however, required to validate the unequivocal use of this early rule out strategy.
Citation: Pickering J, Than M, Cullen L, et al. Rapid rule-out of acute myocardial infarction with a single high-sensitivity cardiac troponin t measurement below the limit of detection: A collaborative meta-analysis. Ann Intern Med. 2017 May 16;166(10):715-24.
Dr. Dogra is clinical instructor of medicine in the University of Kentucky division of hospital medicine.
Study finds bivalirudin efficacy for PCI no better than heparin
A large study of more than 6,000 heart patients in Sweden has found that patients having percutaneous coronary intervention who received bivalirudin did not have lower rates of deleterious outcomes – death, heart attack, or major bleeding – than did patients who received heparin monotherapy, a contrast to previous trials that found that bivalirudin had a lower bleeding risk than heparin alone after PCI.
The findings were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
The study sought to explain the conflicting findings of previous trials investigating the efficacy of bivalirudin vs. heparin monotherapy. The VALIDATE-SWEDEHEART trial evaluated 6,006 patients who had PCI from June 2014 to September 2016, 90.3% via radial-artery access. This trial differed from previous studies because it was conducted after radial-artery access was routine and potent P2Y12 inhibitors were available, and earlier trials did not compare bivalirudin to heparin monotherapy, said David Erlinge, MD, PhD, of Lund (Sweden) University, and 38 coauthors (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1706443).
The Swedish investigators evaluated the primary endpoint – the composite of any-cause death, MI or major bleeding – during 180 days of follow-up. Among the study patients, 3,005 had ST-segment elevation MI (STEMI) and 3,001 non-STEMI (NSTEMI). All had undergone urgent PCI and most were also on P2Y inhibitors. The P2Y12 inhibitors used were ticagrelor in 5,697 patients (94.9%), prasugrel in 125 (2.1%) and cangrelor in 21 (0.3%).
Study patients with STEMI were permitted to receive up to 5,000 U of intravenous unfractionated heparin before arrival in the catheterization laboratory, and both STEMI and non-STEMI patients who had not received heparin previously could receive up to 3,000 U of intra-arterial heparin before angiography. All patients received aspirin pretreatment, and 62% received potent P2Y12 inhibitors at least one hour before PCI.
After angiography, but before PCI, patients were randomized 1:1 to receive in an open-label fashion either intravenous bivalirudin (The Medicines Company), or intra-arterial unfractionated heparin (LEO Pharma). Bivalirudin was administered as a bolus of 0.75 mg/kg of body weight followed by an infusion of 1.7 mg/kg per hour.
Research nurses contacted patients by phone 7 and 180 days after PCI. Baseline characteristics were similar between the bivalirudin and heparin groups. For example, around 31% of both groups had hyperlipidemia, and 15.2% of the bivalirudin group and 14.2% of the heparin group had a previous PCI.
“The rate of the primary endpoint did not differ significantly between the treatment groups at 30 days after PCI,” Dr. Erlinge and his coauthors noted. At 30 days, 7.2% of the bivalirudin patients and 8% of the heparin group had one of the primary endpoint outcomes, a nonsignificant difference. At 180 days, 12.3% of the bivalirudin group and 12.8% of those receiving heparin had one of the primary endpoint outcomes, also a nonsignificant difference.
Specific outcomes in the bivalirudin vs. heparin patients, respectively, at 180 days were: MI, 2% vs. 2.4%; major bleeding, 8.6% in both groups; stent thrombosis, 0.4% vs. 0.7%; and death from any cause, 2.9% vs. 2.8%, all nonsignificant differences.
“Results were consistent between patients with STEMI and those with NSTEMI and across all other prespecified subgroups,” the researchers wrote. They noted that women in the bivalirudin group had a lower, although not statistically significant, primary endpoint rate than did women in the heparin group.
In this trial, the high rate of radial-artery access and the low use of glycoprotein IIb/IIIa inhibitors may explain the low bleeding rates, the researchers said.
Among the study limitations were that patients excluded from the trial were at higher risk for a primary endpoint than those enrolled, the open-label design may have biased participating physicians in identifying outcomes, the telephone call-based follow-up may have been inherently unreliable, and the fact that most patients received a small dose of heparin before randomization may have reconciled any differences between the two drugs.
Coauthors Stefan James, MD, and Ollie Ostlund, MD, disclosed receiving grants from Astra Zeneca, and The Medicines Company. Dr. Erlinge and other coauthors had no financial relationships relevant to the work.
After considering the findings of the VALIDATE-SWEDEHEART trial, Gregg W. Stone, MD, said in an accompanying editorial, “there is no definitive answer to the question of whether to use bivalirudin or heparin during PCI.”
Dr. Stone, of New York–Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, noted four potential flaws in the study findings. One, the 30-day interval may be a better for evaluating procedural anticoagulation than 180 days – and at 30 days the Swedish study showed “a nonsignificant trend in favor of bivalirudin.” Two, the composite primary endpoint could bias outcomes because individual measures could essentially cancel each other out. Three, differences between treatment groups could have been further minimized because 91% of patients who received bivalirudin also received a substantial dose of heparin before and during PCI. Finally, Dr. Stone said, the study was underpowered to examine the individual components of outcomes.
The data comparing outcomes in STEMI and NSTEMI patients did not show separate results for death, bleeding, and stent thrombosis. Dr. Stone pointed to a meta-analysis of six randomized trials of 14,095 patients with STEMI, showing that bivalirudin had lower rates of major bleeding and 30-day death but higher rates of stent thrombosis than heparin, and that mortality was lower regardless of the use of femoral artery or radial-artery access or other procedural factors. By contrast, previous trials did show similar rates of death, MI, and stent thrombosis between both treatment groups, although lower bleeding rates were seen with bivalirudin.
More definitive answers may lie in investigators from the large-scale randomized trials comparing the anticoagulant agents, including the Swedish authors, combining their data on more than 36,000 patients into a single database, as they have agreed to do, Dr. Stone said. That “should provide robust evidence to guide decisions regarding anticoagulation among patients with STEMI and NSTEMI,” he concluded.
Dr. Stone had no relevant financial relationships to disclose. He made his comments in an invited editorial in the New England Journal of Medicine (doi: 10.1056/NEJMe1709247).
After considering the findings of the VALIDATE-SWEDEHEART trial, Gregg W. Stone, MD, said in an accompanying editorial, “there is no definitive answer to the question of whether to use bivalirudin or heparin during PCI.”
Dr. Stone, of New York–Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, noted four potential flaws in the study findings. One, the 30-day interval may be a better for evaluating procedural anticoagulation than 180 days – and at 30 days the Swedish study showed “a nonsignificant trend in favor of bivalirudin.” Two, the composite primary endpoint could bias outcomes because individual measures could essentially cancel each other out. Three, differences between treatment groups could have been further minimized because 91% of patients who received bivalirudin also received a substantial dose of heparin before and during PCI. Finally, Dr. Stone said, the study was underpowered to examine the individual components of outcomes.
The data comparing outcomes in STEMI and NSTEMI patients did not show separate results for death, bleeding, and stent thrombosis. Dr. Stone pointed to a meta-analysis of six randomized trials of 14,095 patients with STEMI, showing that bivalirudin had lower rates of major bleeding and 30-day death but higher rates of stent thrombosis than heparin, and that mortality was lower regardless of the use of femoral artery or radial-artery access or other procedural factors. By contrast, previous trials did show similar rates of death, MI, and stent thrombosis between both treatment groups, although lower bleeding rates were seen with bivalirudin.
More definitive answers may lie in investigators from the large-scale randomized trials comparing the anticoagulant agents, including the Swedish authors, combining their data on more than 36,000 patients into a single database, as they have agreed to do, Dr. Stone said. That “should provide robust evidence to guide decisions regarding anticoagulation among patients with STEMI and NSTEMI,” he concluded.
Dr. Stone had no relevant financial relationships to disclose. He made his comments in an invited editorial in the New England Journal of Medicine (doi: 10.1056/NEJMe1709247).
After considering the findings of the VALIDATE-SWEDEHEART trial, Gregg W. Stone, MD, said in an accompanying editorial, “there is no definitive answer to the question of whether to use bivalirudin or heparin during PCI.”
Dr. Stone, of New York–Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, noted four potential flaws in the study findings. One, the 30-day interval may be a better for evaluating procedural anticoagulation than 180 days – and at 30 days the Swedish study showed “a nonsignificant trend in favor of bivalirudin.” Two, the composite primary endpoint could bias outcomes because individual measures could essentially cancel each other out. Three, differences between treatment groups could have been further minimized because 91% of patients who received bivalirudin also received a substantial dose of heparin before and during PCI. Finally, Dr. Stone said, the study was underpowered to examine the individual components of outcomes.
The data comparing outcomes in STEMI and NSTEMI patients did not show separate results for death, bleeding, and stent thrombosis. Dr. Stone pointed to a meta-analysis of six randomized trials of 14,095 patients with STEMI, showing that bivalirudin had lower rates of major bleeding and 30-day death but higher rates of stent thrombosis than heparin, and that mortality was lower regardless of the use of femoral artery or radial-artery access or other procedural factors. By contrast, previous trials did show similar rates of death, MI, and stent thrombosis between both treatment groups, although lower bleeding rates were seen with bivalirudin.
More definitive answers may lie in investigators from the large-scale randomized trials comparing the anticoagulant agents, including the Swedish authors, combining their data on more than 36,000 patients into a single database, as they have agreed to do, Dr. Stone said. That “should provide robust evidence to guide decisions regarding anticoagulation among patients with STEMI and NSTEMI,” he concluded.
Dr. Stone had no relevant financial relationships to disclose. He made his comments in an invited editorial in the New England Journal of Medicine (doi: 10.1056/NEJMe1709247).
A large study of more than 6,000 heart patients in Sweden has found that patients having percutaneous coronary intervention who received bivalirudin did not have lower rates of deleterious outcomes – death, heart attack, or major bleeding – than did patients who received heparin monotherapy, a contrast to previous trials that found that bivalirudin had a lower bleeding risk than heparin alone after PCI.
The findings were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
The study sought to explain the conflicting findings of previous trials investigating the efficacy of bivalirudin vs. heparin monotherapy. The VALIDATE-SWEDEHEART trial evaluated 6,006 patients who had PCI from June 2014 to September 2016, 90.3% via radial-artery access. This trial differed from previous studies because it was conducted after radial-artery access was routine and potent P2Y12 inhibitors were available, and earlier trials did not compare bivalirudin to heparin monotherapy, said David Erlinge, MD, PhD, of Lund (Sweden) University, and 38 coauthors (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1706443).
The Swedish investigators evaluated the primary endpoint – the composite of any-cause death, MI or major bleeding – during 180 days of follow-up. Among the study patients, 3,005 had ST-segment elevation MI (STEMI) and 3,001 non-STEMI (NSTEMI). All had undergone urgent PCI and most were also on P2Y inhibitors. The P2Y12 inhibitors used were ticagrelor in 5,697 patients (94.9%), prasugrel in 125 (2.1%) and cangrelor in 21 (0.3%).
Study patients with STEMI were permitted to receive up to 5,000 U of intravenous unfractionated heparin before arrival in the catheterization laboratory, and both STEMI and non-STEMI patients who had not received heparin previously could receive up to 3,000 U of intra-arterial heparin before angiography. All patients received aspirin pretreatment, and 62% received potent P2Y12 inhibitors at least one hour before PCI.
After angiography, but before PCI, patients were randomized 1:1 to receive in an open-label fashion either intravenous bivalirudin (The Medicines Company), or intra-arterial unfractionated heparin (LEO Pharma). Bivalirudin was administered as a bolus of 0.75 mg/kg of body weight followed by an infusion of 1.7 mg/kg per hour.
Research nurses contacted patients by phone 7 and 180 days after PCI. Baseline characteristics were similar between the bivalirudin and heparin groups. For example, around 31% of both groups had hyperlipidemia, and 15.2% of the bivalirudin group and 14.2% of the heparin group had a previous PCI.
“The rate of the primary endpoint did not differ significantly between the treatment groups at 30 days after PCI,” Dr. Erlinge and his coauthors noted. At 30 days, 7.2% of the bivalirudin patients and 8% of the heparin group had one of the primary endpoint outcomes, a nonsignificant difference. At 180 days, 12.3% of the bivalirudin group and 12.8% of those receiving heparin had one of the primary endpoint outcomes, also a nonsignificant difference.
Specific outcomes in the bivalirudin vs. heparin patients, respectively, at 180 days were: MI, 2% vs. 2.4%; major bleeding, 8.6% in both groups; stent thrombosis, 0.4% vs. 0.7%; and death from any cause, 2.9% vs. 2.8%, all nonsignificant differences.
“Results were consistent between patients with STEMI and those with NSTEMI and across all other prespecified subgroups,” the researchers wrote. They noted that women in the bivalirudin group had a lower, although not statistically significant, primary endpoint rate than did women in the heparin group.
In this trial, the high rate of radial-artery access and the low use of glycoprotein IIb/IIIa inhibitors may explain the low bleeding rates, the researchers said.
Among the study limitations were that patients excluded from the trial were at higher risk for a primary endpoint than those enrolled, the open-label design may have biased participating physicians in identifying outcomes, the telephone call-based follow-up may have been inherently unreliable, and the fact that most patients received a small dose of heparin before randomization may have reconciled any differences between the two drugs.
Coauthors Stefan James, MD, and Ollie Ostlund, MD, disclosed receiving grants from Astra Zeneca, and The Medicines Company. Dr. Erlinge and other coauthors had no financial relationships relevant to the work.
A large study of more than 6,000 heart patients in Sweden has found that patients having percutaneous coronary intervention who received bivalirudin did not have lower rates of deleterious outcomes – death, heart attack, or major bleeding – than did patients who received heparin monotherapy, a contrast to previous trials that found that bivalirudin had a lower bleeding risk than heparin alone after PCI.
The findings were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.
The study sought to explain the conflicting findings of previous trials investigating the efficacy of bivalirudin vs. heparin monotherapy. The VALIDATE-SWEDEHEART trial evaluated 6,006 patients who had PCI from June 2014 to September 2016, 90.3% via radial-artery access. This trial differed from previous studies because it was conducted after radial-artery access was routine and potent P2Y12 inhibitors were available, and earlier trials did not compare bivalirudin to heparin monotherapy, said David Erlinge, MD, PhD, of Lund (Sweden) University, and 38 coauthors (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1706443).
The Swedish investigators evaluated the primary endpoint – the composite of any-cause death, MI or major bleeding – during 180 days of follow-up. Among the study patients, 3,005 had ST-segment elevation MI (STEMI) and 3,001 non-STEMI (NSTEMI). All had undergone urgent PCI and most were also on P2Y inhibitors. The P2Y12 inhibitors used were ticagrelor in 5,697 patients (94.9%), prasugrel in 125 (2.1%) and cangrelor in 21 (0.3%).
Study patients with STEMI were permitted to receive up to 5,000 U of intravenous unfractionated heparin before arrival in the catheterization laboratory, and both STEMI and non-STEMI patients who had not received heparin previously could receive up to 3,000 U of intra-arterial heparin before angiography. All patients received aspirin pretreatment, and 62% received potent P2Y12 inhibitors at least one hour before PCI.
After angiography, but before PCI, patients were randomized 1:1 to receive in an open-label fashion either intravenous bivalirudin (The Medicines Company), or intra-arterial unfractionated heparin (LEO Pharma). Bivalirudin was administered as a bolus of 0.75 mg/kg of body weight followed by an infusion of 1.7 mg/kg per hour.
Research nurses contacted patients by phone 7 and 180 days after PCI. Baseline characteristics were similar between the bivalirudin and heparin groups. For example, around 31% of both groups had hyperlipidemia, and 15.2% of the bivalirudin group and 14.2% of the heparin group had a previous PCI.
“The rate of the primary endpoint did not differ significantly between the treatment groups at 30 days after PCI,” Dr. Erlinge and his coauthors noted. At 30 days, 7.2% of the bivalirudin patients and 8% of the heparin group had one of the primary endpoint outcomes, a nonsignificant difference. At 180 days, 12.3% of the bivalirudin group and 12.8% of those receiving heparin had one of the primary endpoint outcomes, also a nonsignificant difference.
Specific outcomes in the bivalirudin vs. heparin patients, respectively, at 180 days were: MI, 2% vs. 2.4%; major bleeding, 8.6% in both groups; stent thrombosis, 0.4% vs. 0.7%; and death from any cause, 2.9% vs. 2.8%, all nonsignificant differences.
“Results were consistent between patients with STEMI and those with NSTEMI and across all other prespecified subgroups,” the researchers wrote. They noted that women in the bivalirudin group had a lower, although not statistically significant, primary endpoint rate than did women in the heparin group.
In this trial, the high rate of radial-artery access and the low use of glycoprotein IIb/IIIa inhibitors may explain the low bleeding rates, the researchers said.
Among the study limitations were that patients excluded from the trial were at higher risk for a primary endpoint than those enrolled, the open-label design may have biased participating physicians in identifying outcomes, the telephone call-based follow-up may have been inherently unreliable, and the fact that most patients received a small dose of heparin before randomization may have reconciled any differences between the two drugs.
Coauthors Stefan James, MD, and Ollie Ostlund, MD, disclosed receiving grants from Astra Zeneca, and The Medicines Company. Dr. Erlinge and other coauthors had no financial relationships relevant to the work.
FROM THE ESC CONGRESS 2017
Key clinical point: The rates of composite death, MI, or major bleeding for patients having PCI for MI were similar regardless of whether they received bivalirudin or heparin monotherapy.
Major finding: At 180 days, 12.3% of the bivalirudin patients and 12.8% of the heparin patients had one of the primary endpoint outcomes.
Data source: VALIDATE-SWEDEHEART, a registry-based, multicenter, randomized, controlled, open-label clinical trial of 6,006 patients who had PCI between June 2014 and September 2016.
Disclosure: Coauthors Stefan James, MD, and Ollie Ostlund, MD, disclosed receiving grants from AstraZeneca, and The Medicines Company. Dr. Erlinge and other coauthors had no financial relationships relevant to the work.
VIDEO: Inflammation’s role in atherosclerosis confirmed in CANTOS
BARCELONA – The results of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) mark the validation of many years of research on inflammation for Peter Libby, MD, Mallinckrodt Professor of Medicine, Harvard Medical School, Boston.
The CANTOS investigator said that, although some trials, most notably JUPITER, have linked reduced markers of inflammation with reduced cardiovascular events, none have been able to separate the effects of lowering LDL cholesterol from those of lowering the inflammatory marker interleukin-1B.
But using the monoclonal antibody canakinumab to target only interleukin-1B in CANTOS reduced the composite endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death by 15% at the highest dosage tested, compared with placebo, while lowering high-sensitivity C-reactive protein by 39 percentage points.
Dr. Libby has been studying interleukin-1B since the 1980s. “Now, today, for the first time, in a rigorous trial, we can show that an anti-inflammatory agent that is neutral for lipids (that doesn’t lower LDL) can provide a benefit for our patients, and that’s a real step forward,” Dr. Libby said in a video interview at the annual congress of the European Society of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Importantly, a dividend of the investigation was that “we found a decrease in fatal cancers, particularly lung cancer. So this again opens the door toward a whole new therapeutic window in patients not just in the cardiovascular space, but also in oncology. So it’s a doubly exciting day for us.”
CANTOS was presented at the meeting by Paul Ridker, MD, also of Harvard Medical School; the results were also published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
BARCELONA – The results of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) mark the validation of many years of research on inflammation for Peter Libby, MD, Mallinckrodt Professor of Medicine, Harvard Medical School, Boston.
The CANTOS investigator said that, although some trials, most notably JUPITER, have linked reduced markers of inflammation with reduced cardiovascular events, none have been able to separate the effects of lowering LDL cholesterol from those of lowering the inflammatory marker interleukin-1B.
But using the monoclonal antibody canakinumab to target only interleukin-1B in CANTOS reduced the composite endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death by 15% at the highest dosage tested, compared with placebo, while lowering high-sensitivity C-reactive protein by 39 percentage points.
Dr. Libby has been studying interleukin-1B since the 1980s. “Now, today, for the first time, in a rigorous trial, we can show that an anti-inflammatory agent that is neutral for lipids (that doesn’t lower LDL) can provide a benefit for our patients, and that’s a real step forward,” Dr. Libby said in a video interview at the annual congress of the European Society of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Importantly, a dividend of the investigation was that “we found a decrease in fatal cancers, particularly lung cancer. So this again opens the door toward a whole new therapeutic window in patients not just in the cardiovascular space, but also in oncology. So it’s a doubly exciting day for us.”
CANTOS was presented at the meeting by Paul Ridker, MD, also of Harvard Medical School; the results were also published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
BARCELONA – The results of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) mark the validation of many years of research on inflammation for Peter Libby, MD, Mallinckrodt Professor of Medicine, Harvard Medical School, Boston.
The CANTOS investigator said that, although some trials, most notably JUPITER, have linked reduced markers of inflammation with reduced cardiovascular events, none have been able to separate the effects of lowering LDL cholesterol from those of lowering the inflammatory marker interleukin-1B.
But using the monoclonal antibody canakinumab to target only interleukin-1B in CANTOS reduced the composite endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death by 15% at the highest dosage tested, compared with placebo, while lowering high-sensitivity C-reactive protein by 39 percentage points.
Dr. Libby has been studying interleukin-1B since the 1980s. “Now, today, for the first time, in a rigorous trial, we can show that an anti-inflammatory agent that is neutral for lipids (that doesn’t lower LDL) can provide a benefit for our patients, and that’s a real step forward,” Dr. Libby said in a video interview at the annual congress of the European Society of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Importantly, a dividend of the investigation was that “we found a decrease in fatal cancers, particularly lung cancer. So this again opens the door toward a whole new therapeutic window in patients not just in the cardiovascular space, but also in oncology. So it’s a doubly exciting day for us.”
CANTOS was presented at the meeting by Paul Ridker, MD, also of Harvard Medical School; the results were also published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
AT THE ESC CONGRESS 2017
Make the Diagnosis - August 2017
Trichofolliculoma
Trichofolliculoma is a rare, benign skin lesion that was first described in 1944. While the etiology is largely known, it is considered to be a hamartoma with follicular differentiation that results when the pluripotent skin cells cease to differentiate into the hair follicle. The lesion lacks specific predilection for gender or race but most commonly occurs on the face of adults. Clinically, trichofolliculoma presents as a solitary, skin-colored papule or nodule. It may contain a central sebum-producing pore or have a tuft of white hair protruding from the central pore, although neither of these manifestations are mandatory. Trichofolliculomas generally are asymptomatic and are not associated with any systemic or other cutaneous diseases. Therefore, no treatment is required. However, surgical excision or curettage and electrodesiccation may be performed for cosmetic reasons.
Definitive diagnosis of trichofolliculoma requires a biopsy. The histopathology shows a primary cystic structure within the dermis that may or may not be connected to the epidermis. There are multiple abnormal secondary follicles that radiate from the primary cystic structure, and the entire apparatus is surrounded by a well-circumscribed dense connective tissue. Immunohistochemical studies have revealed that trichofolliculoma is characterized by activated, aberrant cytokeratin-15 (CK15)–positive follicle stem cells that show outer root sheath differentiation while attempting to make hair. This results in disorder of the normal hair cycle.
The clinical differential diagnosis for trichofolliculoma includes dermal nevus, basal cell carcinoma, and pilar sheath acanthoma. These cutaneous entities may be ruled out by histopathology.
The histopathology of basal cell carcinoma consists of tumors of basaloid cells with little cytoplasm and hyperchromatic nuclei. There is palisading around the periphery of the tumor with stromal retraction that leads to a clefting appearance, as well as mucinous change in the stroma.
The histopathology of dermal nevus reveals small nests of melanocytes within the upper dermis that commonly localize around the pilosebaceous units. There is variability in pigmentation and cellularity of the melanocytes, and there is no junctional component.
The histopathology of pilar sheath acanthoma shows dermal proliferation of lobules comprising benign squamous epithelium that arrange themselves around small cystic spaces. The lobules themselves are surrounded by eosinophilic basement membrane.
The case and photo were submitted by Victoria Billero, MS; Adam Wulkan, MD; and Caroline Winslow, MD, all of the department of dermatology, University of Miami (Fla.).
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
Trichofolliculoma
Trichofolliculoma is a rare, benign skin lesion that was first described in 1944. While the etiology is largely known, it is considered to be a hamartoma with follicular differentiation that results when the pluripotent skin cells cease to differentiate into the hair follicle. The lesion lacks specific predilection for gender or race but most commonly occurs on the face of adults. Clinically, trichofolliculoma presents as a solitary, skin-colored papule or nodule. It may contain a central sebum-producing pore or have a tuft of white hair protruding from the central pore, although neither of these manifestations are mandatory. Trichofolliculomas generally are asymptomatic and are not associated with any systemic or other cutaneous diseases. Therefore, no treatment is required. However, surgical excision or curettage and electrodesiccation may be performed for cosmetic reasons.
Definitive diagnosis of trichofolliculoma requires a biopsy. The histopathology shows a primary cystic structure within the dermis that may or may not be connected to the epidermis. There are multiple abnormal secondary follicles that radiate from the primary cystic structure, and the entire apparatus is surrounded by a well-circumscribed dense connective tissue. Immunohistochemical studies have revealed that trichofolliculoma is characterized by activated, aberrant cytokeratin-15 (CK15)–positive follicle stem cells that show outer root sheath differentiation while attempting to make hair. This results in disorder of the normal hair cycle.
The clinical differential diagnosis for trichofolliculoma includes dermal nevus, basal cell carcinoma, and pilar sheath acanthoma. These cutaneous entities may be ruled out by histopathology.
The histopathology of basal cell carcinoma consists of tumors of basaloid cells with little cytoplasm and hyperchromatic nuclei. There is palisading around the periphery of the tumor with stromal retraction that leads to a clefting appearance, as well as mucinous change in the stroma.
The histopathology of dermal nevus reveals small nests of melanocytes within the upper dermis that commonly localize around the pilosebaceous units. There is variability in pigmentation and cellularity of the melanocytes, and there is no junctional component.
The histopathology of pilar sheath acanthoma shows dermal proliferation of lobules comprising benign squamous epithelium that arrange themselves around small cystic spaces. The lobules themselves are surrounded by eosinophilic basement membrane.
The case and photo were submitted by Victoria Billero, MS; Adam Wulkan, MD; and Caroline Winslow, MD, all of the department of dermatology, University of Miami (Fla.).
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
Trichofolliculoma
Trichofolliculoma is a rare, benign skin lesion that was first described in 1944. While the etiology is largely known, it is considered to be a hamartoma with follicular differentiation that results when the pluripotent skin cells cease to differentiate into the hair follicle. The lesion lacks specific predilection for gender or race but most commonly occurs on the face of adults. Clinically, trichofolliculoma presents as a solitary, skin-colored papule or nodule. It may contain a central sebum-producing pore or have a tuft of white hair protruding from the central pore, although neither of these manifestations are mandatory. Trichofolliculomas generally are asymptomatic and are not associated with any systemic or other cutaneous diseases. Therefore, no treatment is required. However, surgical excision or curettage and electrodesiccation may be performed for cosmetic reasons.
Definitive diagnosis of trichofolliculoma requires a biopsy. The histopathology shows a primary cystic structure within the dermis that may or may not be connected to the epidermis. There are multiple abnormal secondary follicles that radiate from the primary cystic structure, and the entire apparatus is surrounded by a well-circumscribed dense connective tissue. Immunohistochemical studies have revealed that trichofolliculoma is characterized by activated, aberrant cytokeratin-15 (CK15)–positive follicle stem cells that show outer root sheath differentiation while attempting to make hair. This results in disorder of the normal hair cycle.
The clinical differential diagnosis for trichofolliculoma includes dermal nevus, basal cell carcinoma, and pilar sheath acanthoma. These cutaneous entities may be ruled out by histopathology.
The histopathology of basal cell carcinoma consists of tumors of basaloid cells with little cytoplasm and hyperchromatic nuclei. There is palisading around the periphery of the tumor with stromal retraction that leads to a clefting appearance, as well as mucinous change in the stroma.
The histopathology of dermal nevus reveals small nests of melanocytes within the upper dermis that commonly localize around the pilosebaceous units. There is variability in pigmentation and cellularity of the melanocytes, and there is no junctional component.
The histopathology of pilar sheath acanthoma shows dermal proliferation of lobules comprising benign squamous epithelium that arrange themselves around small cystic spaces. The lobules themselves are surrounded by eosinophilic basement membrane.
The case and photo were submitted by Victoria Billero, MS; Adam Wulkan, MD; and Caroline Winslow, MD, all of the department of dermatology, University of Miami (Fla.).
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].
A 67-year-old white female with no significant past medical history presented as a first-time patient to clinic for a full skin check. An incidental finding of a solitary, asymptomatic, non-tender 8 mm flesh-colored papule with a tuft of long white hair protruding through a central pore was observed on her right lateral forehead that had been present for longer than 10 years.
Orsiro coronary DES outperforms Xience
BARCELONA – A new model of drug-eluting coronary stent outperformed the reigning benchmark Xience stent in a head-to-head, pivotal comparison with 1,334 patients.
The results “advance a new standard for drug eluting stents,” David E. Kandzari, MD, said at the annual congress of the European Society of Cardiology. The trial tested the Orsiro stent, which features very thin, 60-micron-thick cobalt chromium struts, a bioresorbable polymer, and sirolimus as the antiproliferative drug that’s released during the first 90 days of stent placement.
“To our knowledge, this is the only trial that has demonstrated superiority [of a new stent] to the Xience drug-eluting stent in a large, randomized trial. This is a landmark in interventional cardiology that raises the bar for future comparisons” of drug eluting coronary stents, Dr. Kandzari said in an interview.
The study’s primary endpoint of target lesion failure after 12 months of follow-up – a rate that combined the incidence of cardiovascular death, target-vessel related MI, and ischemia-driven target-lesion revascularization – stood at 6.2% for the 884 patients treated with the Orsiro stent and 9.6% of the 450 randomized to treatment with the Xience stent, which has struts that are 81 microns wide, and a durable polymer that releases everolimus as the antiproliferative drug.
The difference in the primary endpoint was driven primarily by a 3.6% absolute difference in the rate of target-vessel related MIs, a statistically significant difference, plus the Orsiro-treated patients showed numerically smaller rates of cardiac death and ischemia-driven target lesion revascularization, although the between-group differences for each of these two endpoints were not statistically significant. The Orsiro stent also showed a significantly reduced rate of late stent thrombosis, occurring during day 31 through 1 year, a 0.1% rate in the Orsiro-treated patients and a 0.9% rate in those who received Xience stents.
“These are remarkable results,” said Michael Haude, MD, an interventional cardiologist at Lukas Hospital in Neuss, Germany, and a cochair of the session in which Dr. Kandzari gave his report.
These results from the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions (BIOFLOW-V) trial will be the centerpiece of an application for U.S. marketing approval for the Orsiro stent, Dr. Kandzari said. The BIOFLOW-V trial enrolled patients at 90 centers in 13 countries including the United States.
Concurrently with his report, the results were published online (Lancet. 2017 Aug 26. doi: 10.1016/S0140-6736[17]32249-3).
The potential advantage of a thinner-strut drug eluting stent showed up during the initial treatment phase, with a procedural success rate of 94% using the Orsiro stent and 90% with the Xience stent. This difference in procedural success seemed largely the result of an increased rate of periprocedural MIs, a difference that might be explained by the difference in strut thickness, said Dr. Kandzari, of Piedmont Heart Institute, Atlanta. Based on this success, designers of future drug-eluting stents may focus on thinner-strut models, he suggested.
An additional analysis that Dr. Kandzari reported combined results from two prior randomized comparisons of the Orsiro and Xience stents, creating a pooled analysis with 2,208 patients. This Bayesian analysis calculated a 100% probability of noninferiority of the Orsiro stent compared with the Xience stent, and a 97% probability of superiority. This 97% probability of superiority fell just short of the 97.5% threshold for establishing superiority that Dr. Kandzari and his associates had prespecified for this analysis.
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On Twitter @mitchelzoler
BARCELONA – A new model of drug-eluting coronary stent outperformed the reigning benchmark Xience stent in a head-to-head, pivotal comparison with 1,334 patients.
The results “advance a new standard for drug eluting stents,” David E. Kandzari, MD, said at the annual congress of the European Society of Cardiology. The trial tested the Orsiro stent, which features very thin, 60-micron-thick cobalt chromium struts, a bioresorbable polymer, and sirolimus as the antiproliferative drug that’s released during the first 90 days of stent placement.
“To our knowledge, this is the only trial that has demonstrated superiority [of a new stent] to the Xience drug-eluting stent in a large, randomized trial. This is a landmark in interventional cardiology that raises the bar for future comparisons” of drug eluting coronary stents, Dr. Kandzari said in an interview.
The study’s primary endpoint of target lesion failure after 12 months of follow-up – a rate that combined the incidence of cardiovascular death, target-vessel related MI, and ischemia-driven target-lesion revascularization – stood at 6.2% for the 884 patients treated with the Orsiro stent and 9.6% of the 450 randomized to treatment with the Xience stent, which has struts that are 81 microns wide, and a durable polymer that releases everolimus as the antiproliferative drug.
The difference in the primary endpoint was driven primarily by a 3.6% absolute difference in the rate of target-vessel related MIs, a statistically significant difference, plus the Orsiro-treated patients showed numerically smaller rates of cardiac death and ischemia-driven target lesion revascularization, although the between-group differences for each of these two endpoints were not statistically significant. The Orsiro stent also showed a significantly reduced rate of late stent thrombosis, occurring during day 31 through 1 year, a 0.1% rate in the Orsiro-treated patients and a 0.9% rate in those who received Xience stents.
“These are remarkable results,” said Michael Haude, MD, an interventional cardiologist at Lukas Hospital in Neuss, Germany, and a cochair of the session in which Dr. Kandzari gave his report.
These results from the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions (BIOFLOW-V) trial will be the centerpiece of an application for U.S. marketing approval for the Orsiro stent, Dr. Kandzari said. The BIOFLOW-V trial enrolled patients at 90 centers in 13 countries including the United States.
Concurrently with his report, the results were published online (Lancet. 2017 Aug 26. doi: 10.1016/S0140-6736[17]32249-3).
The potential advantage of a thinner-strut drug eluting stent showed up during the initial treatment phase, with a procedural success rate of 94% using the Orsiro stent and 90% with the Xience stent. This difference in procedural success seemed largely the result of an increased rate of periprocedural MIs, a difference that might be explained by the difference in strut thickness, said Dr. Kandzari, of Piedmont Heart Institute, Atlanta. Based on this success, designers of future drug-eluting stents may focus on thinner-strut models, he suggested.
An additional analysis that Dr. Kandzari reported combined results from two prior randomized comparisons of the Orsiro and Xience stents, creating a pooled analysis with 2,208 patients. This Bayesian analysis calculated a 100% probability of noninferiority of the Orsiro stent compared with the Xience stent, and a 97% probability of superiority. This 97% probability of superiority fell just short of the 97.5% threshold for establishing superiority that Dr. Kandzari and his associates had prespecified for this analysis.
[email protected]
On Twitter @mitchelzoler
BARCELONA – A new model of drug-eluting coronary stent outperformed the reigning benchmark Xience stent in a head-to-head, pivotal comparison with 1,334 patients.
The results “advance a new standard for drug eluting stents,” David E. Kandzari, MD, said at the annual congress of the European Society of Cardiology. The trial tested the Orsiro stent, which features very thin, 60-micron-thick cobalt chromium struts, a bioresorbable polymer, and sirolimus as the antiproliferative drug that’s released during the first 90 days of stent placement.
“To our knowledge, this is the only trial that has demonstrated superiority [of a new stent] to the Xience drug-eluting stent in a large, randomized trial. This is a landmark in interventional cardiology that raises the bar for future comparisons” of drug eluting coronary stents, Dr. Kandzari said in an interview.
The study’s primary endpoint of target lesion failure after 12 months of follow-up – a rate that combined the incidence of cardiovascular death, target-vessel related MI, and ischemia-driven target-lesion revascularization – stood at 6.2% for the 884 patients treated with the Orsiro stent and 9.6% of the 450 randomized to treatment with the Xience stent, which has struts that are 81 microns wide, and a durable polymer that releases everolimus as the antiproliferative drug.
The difference in the primary endpoint was driven primarily by a 3.6% absolute difference in the rate of target-vessel related MIs, a statistically significant difference, plus the Orsiro-treated patients showed numerically smaller rates of cardiac death and ischemia-driven target lesion revascularization, although the between-group differences for each of these two endpoints were not statistically significant. The Orsiro stent also showed a significantly reduced rate of late stent thrombosis, occurring during day 31 through 1 year, a 0.1% rate in the Orsiro-treated patients and a 0.9% rate in those who received Xience stents.
“These are remarkable results,” said Michael Haude, MD, an interventional cardiologist at Lukas Hospital in Neuss, Germany, and a cochair of the session in which Dr. Kandzari gave his report.
These results from the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions (BIOFLOW-V) trial will be the centerpiece of an application for U.S. marketing approval for the Orsiro stent, Dr. Kandzari said. The BIOFLOW-V trial enrolled patients at 90 centers in 13 countries including the United States.
Concurrently with his report, the results were published online (Lancet. 2017 Aug 26. doi: 10.1016/S0140-6736[17]32249-3).
The potential advantage of a thinner-strut drug eluting stent showed up during the initial treatment phase, with a procedural success rate of 94% using the Orsiro stent and 90% with the Xience stent. This difference in procedural success seemed largely the result of an increased rate of periprocedural MIs, a difference that might be explained by the difference in strut thickness, said Dr. Kandzari, of Piedmont Heart Institute, Atlanta. Based on this success, designers of future drug-eluting stents may focus on thinner-strut models, he suggested.
An additional analysis that Dr. Kandzari reported combined results from two prior randomized comparisons of the Orsiro and Xience stents, creating a pooled analysis with 2,208 patients. This Bayesian analysis calculated a 100% probability of noninferiority of the Orsiro stent compared with the Xience stent, and a 97% probability of superiority. This 97% probability of superiority fell just short of the 97.5% threshold for establishing superiority that Dr. Kandzari and his associates had prespecified for this analysis.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The target-lesion failure rate after 12 months was 6.2% with the Orsiro stent and 9.6% with the Xience stent.
Data source: BIOFLOW-V, a multicenter, randomized trial with 1,334 patients.
Disclosures: BIOFLOW-V was sponsored by Biotronik, the company that markets the Orsiro stent. Dr. Kandzari has been a consultant to and/or has received research funding from Biotronik, Boston Scientific, Medtronic, Micell Technologies, Abbott Vascular, St. Jude, Medinol, and OrbusNeich. Dr. Haude has been a consultant to and has received honoraria from Biotronik and from several other device and drug companies.