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First IL-23 blocker, guselkumab, earns FDA approval for psoriasis
, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.
The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.
Results of one of the phase 3 trials, VOYAGE 1, included a significantly greater proportion of patients treated with guselkumab achieving at least a 90% improvement in the Psoriasis Area Severity Index (PASI 90) at 16 weeks, compared with placebo (73.3% vs. 2.9%). At 16 weeks, 85.1% of those treated with guselkumab achieved an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal disease), compared with 6.9% of those on placebo. Superior responses continued through 48 weeks.
In an active comparator arm of the study comparing guselkumab with the TNF blocker adalimumab (Humira), a significantly higher proportion of those treated with guselkumab achieved PASI 90 scores (76.3% vs. 47.9%) and IGA 0/1 scores (80.5% vs. 55.4%) at week 48. The results were published in March (J Am Acad Dermatol. 2017 Mar;76[3]:405-17).
Results of VOYAGE 2 comparing guselkumab with adalimumab included a PASI 90 rate of 66.1% at week 48 among adalimumab nonresponders who switched to guselkumab (J Am Acad Dermatol. 2017 Mar;76[3]:418-31).
The most common serious adverse effects associated with treatment included upper respiratory infections, headache, injection site reactions, arthralgias, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections, according to the company statement.
Phase 3 studies of guselkumab for active psoriatic arthritis and in comparison with secukinumab (Cosentyx) in patients with moderate to severe plaque psoriasis are underway, according to Janssen, which is marketing guselkumab as Tremfya.
, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.
The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.
Results of one of the phase 3 trials, VOYAGE 1, included a significantly greater proportion of patients treated with guselkumab achieving at least a 90% improvement in the Psoriasis Area Severity Index (PASI 90) at 16 weeks, compared with placebo (73.3% vs. 2.9%). At 16 weeks, 85.1% of those treated with guselkumab achieved an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal disease), compared with 6.9% of those on placebo. Superior responses continued through 48 weeks.
In an active comparator arm of the study comparing guselkumab with the TNF blocker adalimumab (Humira), a significantly higher proportion of those treated with guselkumab achieved PASI 90 scores (76.3% vs. 47.9%) and IGA 0/1 scores (80.5% vs. 55.4%) at week 48. The results were published in March (J Am Acad Dermatol. 2017 Mar;76[3]:405-17).
Results of VOYAGE 2 comparing guselkumab with adalimumab included a PASI 90 rate of 66.1% at week 48 among adalimumab nonresponders who switched to guselkumab (J Am Acad Dermatol. 2017 Mar;76[3]:418-31).
The most common serious adverse effects associated with treatment included upper respiratory infections, headache, injection site reactions, arthralgias, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections, according to the company statement.
Phase 3 studies of guselkumab for active psoriatic arthritis and in comparison with secukinumab (Cosentyx) in patients with moderate to severe plaque psoriasis are underway, according to Janssen, which is marketing guselkumab as Tremfya.
, based on three phase 3 studies of more than 2,000 adults, the manufacturer announced July 13.
The approved indication is for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, according to a press release issued by Janssen Biotech, which stated that this is the first IL-23 blocker approved for psoriasis.
Results of one of the phase 3 trials, VOYAGE 1, included a significantly greater proportion of patients treated with guselkumab achieving at least a 90% improvement in the Psoriasis Area Severity Index (PASI 90) at 16 weeks, compared with placebo (73.3% vs. 2.9%). At 16 weeks, 85.1% of those treated with guselkumab achieved an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal disease), compared with 6.9% of those on placebo. Superior responses continued through 48 weeks.
In an active comparator arm of the study comparing guselkumab with the TNF blocker adalimumab (Humira), a significantly higher proportion of those treated with guselkumab achieved PASI 90 scores (76.3% vs. 47.9%) and IGA 0/1 scores (80.5% vs. 55.4%) at week 48. The results were published in March (J Am Acad Dermatol. 2017 Mar;76[3]:405-17).
Results of VOYAGE 2 comparing guselkumab with adalimumab included a PASI 90 rate of 66.1% at week 48 among adalimumab nonresponders who switched to guselkumab (J Am Acad Dermatol. 2017 Mar;76[3]:418-31).
The most common serious adverse effects associated with treatment included upper respiratory infections, headache, injection site reactions, arthralgias, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections, according to the company statement.
Phase 3 studies of guselkumab for active psoriatic arthritis and in comparison with secukinumab (Cosentyx) in patients with moderate to severe plaque psoriasis are underway, according to Janssen, which is marketing guselkumab as Tremfya.
Report: Opioid epidemic fight must increase substantially and immediately
A concerted, multiagency, multipronged counterattack is needed to break the opioid epidemic’s grip on the nation, according to a new report from the National Academies of Sciences, Engineering, and Medicine.
The report, commissioned by the Food and Drug Administration to strengthen its own 2016 Opioids Action Plan, presents a national strategy for addressing this “urgent public health priority.”
“The ongoing opioid crisis lies at the intersection of two substantial public health challenges – reducing the burden of suffering from pain and containing the rising toll of the harms that can result from the use of opioid medications,” according to a summary of the report, “Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.”
The National Academies’ Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse spent more than a year studying the matter and developing the report. Among its recommendations is a call for investment in research to better understand pain and opioid use disorder.
“We have a specific lack of knowledge about how pain and opiate use disorder [OUD] interact – that is, why patients in pain might be more or less at risk for the development of opiate use disorder when exposed to either illicit or prescription medication,” committee member David Clark, MD, professor of anesthesia, perioperative pain medicine, and pain at Stanford (Calif.) University, said during a webinar on the report.
“This leads up to one of our first recommendations, which is to invest in research to better understand pain and opiate use disorder,” Dr. Clark said. “We want to emphasize that we need to improve our understanding of the neurobiology of pain,” which will, hopefully, provide a better foundation for the development of nonopioid treatments.
The committee also recommended that the FDA:
- Incorporate public health considerations into opioid-related regulatory decisions.
- Require additional studies along with the collection and analysis of data needed to thoroughly assess broad public health considerations.
- Ensure that public health considerations are adequately incorporated into clinical development.
- Increase transparency of regulatory decisions for opioids in light of the proposed systems approach.
“The committee believes a commitment to transparency is critical to maintain balance between preserving access to opioids when needed and mitigating opioid-related harms and to maintain public trust,” the report’s authors said. “The committee also believes aggressive use of the FDA’s currently available authorities, such as Risk Evaluation and Mitigation Strategies (REMS), safety labeling changes, and risk communications is critical to supporting the safe and effective use of opioids.”
The committee also recommended strengthening the postapproval oversight of opioids.
A full review of currently marketed and approved opioids was also recommended, as was the application of public health consideration to opioid scheduling decisions.
“The particular characteristics of opioids, we believe, require a certain amount of what we term ‘opioid exceptionalism’ from the regulator in terms of trying to consider the larger societal effects of approval and use of opioid medication,” committee member Aaron S. Kesselheim, MD, JD, of Harvard Medical School, Boston, said during the webinar. “We believe that this public health approach is both reasonable for the FDA, given the fact that it is primarily a public health agency, and can be implemented at all different levels of the development process.”
Strategies recommended by the committee for the FDA, state agencies, health professionals, and relevant private organizations, such as through public-private partnerships, include:
- Restricting the supply of opioids, with careful attention to risks and benefits of interventions aimed at reducing the supply in the community. Recommendation: Improve access to drug take-back programs.
- Improving prescribing practices. Recommendations: Establish comprehensive pain education materials and curricula for health care providers; facilitate reimbursement for comprehensive pain management; and improve the use of prescription drug monitoring program data for surveillance and intervention.
- Reducing demand. Recommendations: Evaluate the impact on patient and public education about opioids on promoting safe and effective pain management; expand treatment for opioid use disorder; improve education regarding treatment of OUD for health care providers; and remove barriers to coverage of approved medication for OUD treatment.
- Reducing harm. Recommendations: Leverage prescribers and pharmacists to help address opioid use disorder; and improve access to naloxone and safe injection equipment.
According to the report, containing the opioid epidemic and ameliorating its harmful effects on society through the development of these strategies will require “years of sustained and coordinated effort.”
Indeed, things will get worse before they get better, the committee predicted.
“Trends indicate that premature deaths associated with the use of opioids are likely to climb and that opioid overdose and other opioid-related harm will dramatically reduce quality of life for many people for years to come,” the report’s authors noted. “Access to evidence-based treatment for OUD and efforts to prevent overdose deaths and other harms should therefore be increased substantially and immediately as a public health priority.”
A concerted, multiagency, multipronged counterattack is needed to break the opioid epidemic’s grip on the nation, according to a new report from the National Academies of Sciences, Engineering, and Medicine.
The report, commissioned by the Food and Drug Administration to strengthen its own 2016 Opioids Action Plan, presents a national strategy for addressing this “urgent public health priority.”
“The ongoing opioid crisis lies at the intersection of two substantial public health challenges – reducing the burden of suffering from pain and containing the rising toll of the harms that can result from the use of opioid medications,” according to a summary of the report, “Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.”
The National Academies’ Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse spent more than a year studying the matter and developing the report. Among its recommendations is a call for investment in research to better understand pain and opioid use disorder.
“We have a specific lack of knowledge about how pain and opiate use disorder [OUD] interact – that is, why patients in pain might be more or less at risk for the development of opiate use disorder when exposed to either illicit or prescription medication,” committee member David Clark, MD, professor of anesthesia, perioperative pain medicine, and pain at Stanford (Calif.) University, said during a webinar on the report.
“This leads up to one of our first recommendations, which is to invest in research to better understand pain and opiate use disorder,” Dr. Clark said. “We want to emphasize that we need to improve our understanding of the neurobiology of pain,” which will, hopefully, provide a better foundation for the development of nonopioid treatments.
The committee also recommended that the FDA:
- Incorporate public health considerations into opioid-related regulatory decisions.
- Require additional studies along with the collection and analysis of data needed to thoroughly assess broad public health considerations.
- Ensure that public health considerations are adequately incorporated into clinical development.
- Increase transparency of regulatory decisions for opioids in light of the proposed systems approach.
“The committee believes a commitment to transparency is critical to maintain balance between preserving access to opioids when needed and mitigating opioid-related harms and to maintain public trust,” the report’s authors said. “The committee also believes aggressive use of the FDA’s currently available authorities, such as Risk Evaluation and Mitigation Strategies (REMS), safety labeling changes, and risk communications is critical to supporting the safe and effective use of opioids.”
The committee also recommended strengthening the postapproval oversight of opioids.
A full review of currently marketed and approved opioids was also recommended, as was the application of public health consideration to opioid scheduling decisions.
“The particular characteristics of opioids, we believe, require a certain amount of what we term ‘opioid exceptionalism’ from the regulator in terms of trying to consider the larger societal effects of approval and use of opioid medication,” committee member Aaron S. Kesselheim, MD, JD, of Harvard Medical School, Boston, said during the webinar. “We believe that this public health approach is both reasonable for the FDA, given the fact that it is primarily a public health agency, and can be implemented at all different levels of the development process.”
Strategies recommended by the committee for the FDA, state agencies, health professionals, and relevant private organizations, such as through public-private partnerships, include:
- Restricting the supply of opioids, with careful attention to risks and benefits of interventions aimed at reducing the supply in the community. Recommendation: Improve access to drug take-back programs.
- Improving prescribing practices. Recommendations: Establish comprehensive pain education materials and curricula for health care providers; facilitate reimbursement for comprehensive pain management; and improve the use of prescription drug monitoring program data for surveillance and intervention.
- Reducing demand. Recommendations: Evaluate the impact on patient and public education about opioids on promoting safe and effective pain management; expand treatment for opioid use disorder; improve education regarding treatment of OUD for health care providers; and remove barriers to coverage of approved medication for OUD treatment.
- Reducing harm. Recommendations: Leverage prescribers and pharmacists to help address opioid use disorder; and improve access to naloxone and safe injection equipment.
According to the report, containing the opioid epidemic and ameliorating its harmful effects on society through the development of these strategies will require “years of sustained and coordinated effort.”
Indeed, things will get worse before they get better, the committee predicted.
“Trends indicate that premature deaths associated with the use of opioids are likely to climb and that opioid overdose and other opioid-related harm will dramatically reduce quality of life for many people for years to come,” the report’s authors noted. “Access to evidence-based treatment for OUD and efforts to prevent overdose deaths and other harms should therefore be increased substantially and immediately as a public health priority.”
A concerted, multiagency, multipronged counterattack is needed to break the opioid epidemic’s grip on the nation, according to a new report from the National Academies of Sciences, Engineering, and Medicine.
The report, commissioned by the Food and Drug Administration to strengthen its own 2016 Opioids Action Plan, presents a national strategy for addressing this “urgent public health priority.”
“The ongoing opioid crisis lies at the intersection of two substantial public health challenges – reducing the burden of suffering from pain and containing the rising toll of the harms that can result from the use of opioid medications,” according to a summary of the report, “Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use.”
The National Academies’ Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse spent more than a year studying the matter and developing the report. Among its recommendations is a call for investment in research to better understand pain and opioid use disorder.
“We have a specific lack of knowledge about how pain and opiate use disorder [OUD] interact – that is, why patients in pain might be more or less at risk for the development of opiate use disorder when exposed to either illicit or prescription medication,” committee member David Clark, MD, professor of anesthesia, perioperative pain medicine, and pain at Stanford (Calif.) University, said during a webinar on the report.
“This leads up to one of our first recommendations, which is to invest in research to better understand pain and opiate use disorder,” Dr. Clark said. “We want to emphasize that we need to improve our understanding of the neurobiology of pain,” which will, hopefully, provide a better foundation for the development of nonopioid treatments.
The committee also recommended that the FDA:
- Incorporate public health considerations into opioid-related regulatory decisions.
- Require additional studies along with the collection and analysis of data needed to thoroughly assess broad public health considerations.
- Ensure that public health considerations are adequately incorporated into clinical development.
- Increase transparency of regulatory decisions for opioids in light of the proposed systems approach.
“The committee believes a commitment to transparency is critical to maintain balance between preserving access to opioids when needed and mitigating opioid-related harms and to maintain public trust,” the report’s authors said. “The committee also believes aggressive use of the FDA’s currently available authorities, such as Risk Evaluation and Mitigation Strategies (REMS), safety labeling changes, and risk communications is critical to supporting the safe and effective use of opioids.”
The committee also recommended strengthening the postapproval oversight of opioids.
A full review of currently marketed and approved opioids was also recommended, as was the application of public health consideration to opioid scheduling decisions.
“The particular characteristics of opioids, we believe, require a certain amount of what we term ‘opioid exceptionalism’ from the regulator in terms of trying to consider the larger societal effects of approval and use of opioid medication,” committee member Aaron S. Kesselheim, MD, JD, of Harvard Medical School, Boston, said during the webinar. “We believe that this public health approach is both reasonable for the FDA, given the fact that it is primarily a public health agency, and can be implemented at all different levels of the development process.”
Strategies recommended by the committee for the FDA, state agencies, health professionals, and relevant private organizations, such as through public-private partnerships, include:
- Restricting the supply of opioids, with careful attention to risks and benefits of interventions aimed at reducing the supply in the community. Recommendation: Improve access to drug take-back programs.
- Improving prescribing practices. Recommendations: Establish comprehensive pain education materials and curricula for health care providers; facilitate reimbursement for comprehensive pain management; and improve the use of prescription drug monitoring program data for surveillance and intervention.
- Reducing demand. Recommendations: Evaluate the impact on patient and public education about opioids on promoting safe and effective pain management; expand treatment for opioid use disorder; improve education regarding treatment of OUD for health care providers; and remove barriers to coverage of approved medication for OUD treatment.
- Reducing harm. Recommendations: Leverage prescribers and pharmacists to help address opioid use disorder; and improve access to naloxone and safe injection equipment.
According to the report, containing the opioid epidemic and ameliorating its harmful effects on society through the development of these strategies will require “years of sustained and coordinated effort.”
Indeed, things will get worse before they get better, the committee predicted.
“Trends indicate that premature deaths associated with the use of opioids are likely to climb and that opioid overdose and other opioid-related harm will dramatically reduce quality of life for many people for years to come,” the report’s authors noted. “Access to evidence-based treatment for OUD and efforts to prevent overdose deaths and other harms should therefore be increased substantially and immediately as a public health priority.”
Reflecting on my first 10 years
Ten years ago, I was flying back from my last job interview – I did nearly 20 – and my wife and I were stuck: Should I take a lucrative private practice gig, an academic position, or join a group? We listed the pros and cons on several condensation-soaked Southwest Air napkins and agreed to make a decision before landing. (Fortunately, it was a cross country, BWI to SAN, flight).
I don’t know if I made the right decision. I’m sure I’d have enjoyed either a cosmetic practice or walking the halls with medical students in tow. I chose to join a medical group at Kaiser Permanente, and I’ve loved it. Working here has helped me become a better dermatologist, teammate, friend, and husband. It has also allowed me to embrace digital medicine a bit earlier and with less difficulty than most. You wouldn’t be reading my “Digital Doctor” column if I hadn’t.
Digital made medicine more accessible than ever. It also made medicine more of a commodity than ever. It turned us into the highest paid data entry clerks in the world. It changed the sacrosanct doctor-patient relationship. It has also presented us with the greatest opportunity in a thousand years. An opportunity to create a new medicine, one that is patient-centric, smart, affordable, efficient, and human. I started this column to explore the digital devices we doctors have and to find ways they might improve the care we give.
I’ve been in practice for 10 years, and I’m now the chief of service for a large dermatology group, as well as physician director for Healthcare Transformation for Kaiser Permanente, San Diego. My job is to help our physicians perform at their best both at work and in life. Through research, interviews, and my own practice, I’ve learned a lot and would like to share it with you.
Starting in September, I’ll broaden the scope of this column. No longer will it be just digital. Rather, it will be about you and how you can be the best you can be. We’ll explore tools, techniques, diet, exercise, and Jedi mind tricks to make you the fastest, smartest, happiest, healthiest, funniest (results may vary) doctor you can be. It’s time to take this column, and you, to the next level – the Optimized Doctor. I can hardly wait.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente, San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Ten years ago, I was flying back from my last job interview – I did nearly 20 – and my wife and I were stuck: Should I take a lucrative private practice gig, an academic position, or join a group? We listed the pros and cons on several condensation-soaked Southwest Air napkins and agreed to make a decision before landing. (Fortunately, it was a cross country, BWI to SAN, flight).
I don’t know if I made the right decision. I’m sure I’d have enjoyed either a cosmetic practice or walking the halls with medical students in tow. I chose to join a medical group at Kaiser Permanente, and I’ve loved it. Working here has helped me become a better dermatologist, teammate, friend, and husband. It has also allowed me to embrace digital medicine a bit earlier and with less difficulty than most. You wouldn’t be reading my “Digital Doctor” column if I hadn’t.
Digital made medicine more accessible than ever. It also made medicine more of a commodity than ever. It turned us into the highest paid data entry clerks in the world. It changed the sacrosanct doctor-patient relationship. It has also presented us with the greatest opportunity in a thousand years. An opportunity to create a new medicine, one that is patient-centric, smart, affordable, efficient, and human. I started this column to explore the digital devices we doctors have and to find ways they might improve the care we give.
I’ve been in practice for 10 years, and I’m now the chief of service for a large dermatology group, as well as physician director for Healthcare Transformation for Kaiser Permanente, San Diego. My job is to help our physicians perform at their best both at work and in life. Through research, interviews, and my own practice, I’ve learned a lot and would like to share it with you.
Starting in September, I’ll broaden the scope of this column. No longer will it be just digital. Rather, it will be about you and how you can be the best you can be. We’ll explore tools, techniques, diet, exercise, and Jedi mind tricks to make you the fastest, smartest, happiest, healthiest, funniest (results may vary) doctor you can be. It’s time to take this column, and you, to the next level – the Optimized Doctor. I can hardly wait.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente, San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Ten years ago, I was flying back from my last job interview – I did nearly 20 – and my wife and I were stuck: Should I take a lucrative private practice gig, an academic position, or join a group? We listed the pros and cons on several condensation-soaked Southwest Air napkins and agreed to make a decision before landing. (Fortunately, it was a cross country, BWI to SAN, flight).
I don’t know if I made the right decision. I’m sure I’d have enjoyed either a cosmetic practice or walking the halls with medical students in tow. I chose to join a medical group at Kaiser Permanente, and I’ve loved it. Working here has helped me become a better dermatologist, teammate, friend, and husband. It has also allowed me to embrace digital medicine a bit earlier and with less difficulty than most. You wouldn’t be reading my “Digital Doctor” column if I hadn’t.
Digital made medicine more accessible than ever. It also made medicine more of a commodity than ever. It turned us into the highest paid data entry clerks in the world. It changed the sacrosanct doctor-patient relationship. It has also presented us with the greatest opportunity in a thousand years. An opportunity to create a new medicine, one that is patient-centric, smart, affordable, efficient, and human. I started this column to explore the digital devices we doctors have and to find ways they might improve the care we give.
I’ve been in practice for 10 years, and I’m now the chief of service for a large dermatology group, as well as physician director for Healthcare Transformation for Kaiser Permanente, San Diego. My job is to help our physicians perform at their best both at work and in life. Through research, interviews, and my own practice, I’ve learned a lot and would like to share it with you.
Starting in September, I’ll broaden the scope of this column. No longer will it be just digital. Rather, it will be about you and how you can be the best you can be. We’ll explore tools, techniques, diet, exercise, and Jedi mind tricks to make you the fastest, smartest, happiest, healthiest, funniest (results may vary) doctor you can be. It’s time to take this column, and you, to the next level – the Optimized Doctor. I can hardly wait.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente, San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Senate GOP tweaks health care reform proposal, but it still lacks support
in the upper chamber of Congress.
The update, released July 13, includes a number of provisions to sweeten the pot for conservatives, but it does little to address the concerns of the moderates in the party, particularly of those who are worried about cuts to the Medicaid program.
The GOP leadership also is putting an additional $45 billion into the fight against opioid addiction. Plus, the revised bill includes a provision to allow tax credits to be used to purchase plans that offer only catastrophic coverage.
What the new revision doesn’t do is alter the cuts in the Medicaid program, leaving unchanged the plan to phase out the expansion of Medicaid in 2021 and complete it by 2024; allowing state governors to choose between block grants and per capita allotments to help pay for their Medicaid populations; and allowing states to institute a work requirement for nonpregnant, nondisabled, and nonelderly individuals eligible to receive Medicaid coverage.
Despite the changes, the bill still faces an uphill climb.
Sen. Rand Paul (R-Ky.), Sen. Susan Collins (R-Maine), and Sen. Rob Portman (R-Ohio) have publicly stated that they are opposed to the bill. With only a 52-seat majority and no Democrats expected to vote in favor of the bill, Senate Majority Leader Mitch McConnell (R-Ky.) needs at least 50 votes under budget reconciliation rules to pass the bill. (Vice President Mike Pence would be the tie-breaking vote if the GOP can get to 50 votes.) There are other moderate Republican senators who have opposed previous iterations of the bill, and it remains to be seen if the current tweaks will swing their votes.
The increased funding for the opioid crisis could draw some of the opposing GOP moderates. But, as Julius Hobson, a health care lobbyist with the Washington-based firm Polsinelli, noted, there is “not enough money to deal with” the opioid crisis.
The bill also has provisions allowing insurers to offer catastrophic coverage policies with minimal coverage alongside more comprehensive policies, an effort to bring in healthy younger individuals who may not want more comprehensive coverage. But those provisions have sparked pushback from state insurance directors, America’s Health Insurance Plans, and the Blue Cross Blue Shield Association.
“I can’t see how this bill got better in terms of health care access,” added Mr. Hobson, a former lobbyist with the American Medical Association.
AMA President David Barbe, MD, said that the tweaks do not do enough.
“The revised bill does not address the key concerns of physicians and patients regarding proposed Medicaid cuts and inadequate subsidies that will result in millions of Americans losing health insurance coverage,” Dr. Barbe said in a statement.
“The additional funding to address the opioid epidemic is a positive step; however, those suffering from substance use disorder have other health care needs that are not likely to be addressed if they lose coverage through a rollback of the Medicaid expansion,” he added. “While stabilizing the individual market is an initial step, more bipartisan collaboration is needed in the months ahead to improve the delivery and financing of health care.”
in the upper chamber of Congress.
The update, released July 13, includes a number of provisions to sweeten the pot for conservatives, but it does little to address the concerns of the moderates in the party, particularly of those who are worried about cuts to the Medicaid program.
The GOP leadership also is putting an additional $45 billion into the fight against opioid addiction. Plus, the revised bill includes a provision to allow tax credits to be used to purchase plans that offer only catastrophic coverage.
What the new revision doesn’t do is alter the cuts in the Medicaid program, leaving unchanged the plan to phase out the expansion of Medicaid in 2021 and complete it by 2024; allowing state governors to choose between block grants and per capita allotments to help pay for their Medicaid populations; and allowing states to institute a work requirement for nonpregnant, nondisabled, and nonelderly individuals eligible to receive Medicaid coverage.
Despite the changes, the bill still faces an uphill climb.
Sen. Rand Paul (R-Ky.), Sen. Susan Collins (R-Maine), and Sen. Rob Portman (R-Ohio) have publicly stated that they are opposed to the bill. With only a 52-seat majority and no Democrats expected to vote in favor of the bill, Senate Majority Leader Mitch McConnell (R-Ky.) needs at least 50 votes under budget reconciliation rules to pass the bill. (Vice President Mike Pence would be the tie-breaking vote if the GOP can get to 50 votes.) There are other moderate Republican senators who have opposed previous iterations of the bill, and it remains to be seen if the current tweaks will swing their votes.
The increased funding for the opioid crisis could draw some of the opposing GOP moderates. But, as Julius Hobson, a health care lobbyist with the Washington-based firm Polsinelli, noted, there is “not enough money to deal with” the opioid crisis.
The bill also has provisions allowing insurers to offer catastrophic coverage policies with minimal coverage alongside more comprehensive policies, an effort to bring in healthy younger individuals who may not want more comprehensive coverage. But those provisions have sparked pushback from state insurance directors, America’s Health Insurance Plans, and the Blue Cross Blue Shield Association.
“I can’t see how this bill got better in terms of health care access,” added Mr. Hobson, a former lobbyist with the American Medical Association.
AMA President David Barbe, MD, said that the tweaks do not do enough.
“The revised bill does not address the key concerns of physicians and patients regarding proposed Medicaid cuts and inadequate subsidies that will result in millions of Americans losing health insurance coverage,” Dr. Barbe said in a statement.
“The additional funding to address the opioid epidemic is a positive step; however, those suffering from substance use disorder have other health care needs that are not likely to be addressed if they lose coverage through a rollback of the Medicaid expansion,” he added. “While stabilizing the individual market is an initial step, more bipartisan collaboration is needed in the months ahead to improve the delivery and financing of health care.”
in the upper chamber of Congress.
The update, released July 13, includes a number of provisions to sweeten the pot for conservatives, but it does little to address the concerns of the moderates in the party, particularly of those who are worried about cuts to the Medicaid program.
The GOP leadership also is putting an additional $45 billion into the fight against opioid addiction. Plus, the revised bill includes a provision to allow tax credits to be used to purchase plans that offer only catastrophic coverage.
What the new revision doesn’t do is alter the cuts in the Medicaid program, leaving unchanged the plan to phase out the expansion of Medicaid in 2021 and complete it by 2024; allowing state governors to choose between block grants and per capita allotments to help pay for their Medicaid populations; and allowing states to institute a work requirement for nonpregnant, nondisabled, and nonelderly individuals eligible to receive Medicaid coverage.
Despite the changes, the bill still faces an uphill climb.
Sen. Rand Paul (R-Ky.), Sen. Susan Collins (R-Maine), and Sen. Rob Portman (R-Ohio) have publicly stated that they are opposed to the bill. With only a 52-seat majority and no Democrats expected to vote in favor of the bill, Senate Majority Leader Mitch McConnell (R-Ky.) needs at least 50 votes under budget reconciliation rules to pass the bill. (Vice President Mike Pence would be the tie-breaking vote if the GOP can get to 50 votes.) There are other moderate Republican senators who have opposed previous iterations of the bill, and it remains to be seen if the current tweaks will swing their votes.
The increased funding for the opioid crisis could draw some of the opposing GOP moderates. But, as Julius Hobson, a health care lobbyist with the Washington-based firm Polsinelli, noted, there is “not enough money to deal with” the opioid crisis.
The bill also has provisions allowing insurers to offer catastrophic coverage policies with minimal coverage alongside more comprehensive policies, an effort to bring in healthy younger individuals who may not want more comprehensive coverage. But those provisions have sparked pushback from state insurance directors, America’s Health Insurance Plans, and the Blue Cross Blue Shield Association.
“I can’t see how this bill got better in terms of health care access,” added Mr. Hobson, a former lobbyist with the American Medical Association.
AMA President David Barbe, MD, said that the tweaks do not do enough.
“The revised bill does not address the key concerns of physicians and patients regarding proposed Medicaid cuts and inadequate subsidies that will result in millions of Americans losing health insurance coverage,” Dr. Barbe said in a statement.
“The additional funding to address the opioid epidemic is a positive step; however, those suffering from substance use disorder have other health care needs that are not likely to be addressed if they lose coverage through a rollback of the Medicaid expansion,” he added. “While stabilizing the individual market is an initial step, more bipartisan collaboration is needed in the months ahead to improve the delivery and financing of health care.”
Selection of strategy for high-risk early RA remission induction hinges on safety
MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.
The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.
Ms. Stouten added that, according to international guidelines, achieving clinical remission means treating patients early, as soon as possible after the diagnosis of rheumatoid arthritis is made; intensively, with a DMARD, preferably methotrexate if not contraindicated, combined with short-term glucocorticoids; and to target, meaning treatment should be targeted at achieving remission or at least low disease activity in every patient.
The CareRA trial was a prospective, randomized, multicenter trial set up to see which of three methotrexate-based, steroid-containing intensive regimens would be best for inducing remission in patients with high-risk RA. The pragmatic trial was conducted in 13 Belgian rheumatology practices recruiting 400 patients, 300 of whom were designated as high risk for progression based on factors such as their antibody status and presence of joint erosions. CareRA trial investigators defined clinical remission as less than 2.6 on the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP).
The three regimens all contained a weekly 15-mg dose of methotrexate and prednisone 30 mg or 60 mg that was then tapered weekly after the first 6-7 weeks.
In the COBRA Classic regimen, methotrexate was partnered with sulfasalazine, given as a 2-g daily dose. Prednisone was initially given at a dose of 60 mg and then taped to 5.7 mg starting at week 7.
For the COBRA Slim regimen, just methotrexate and prednisone were used, with the latter started at a dose of 30 mg and then tapered to 5 mg starting at week 6.
Lastly, the COBRA Avant-Garde regimen saw methotrexate combined with leflunomide, 10 mg daily, and the same step-down prednisone regimen as COBRA Slim.
In the first year, treatment in each group was adjusted to achieve a target of low disease activity (DAS28-CRP of 3.2 or lower), with measurements taken every 3 months. The steroid component was stepped down further after 28 weeks and stopped altogether by 34 weeks. The aim was also to reduce the number of DMARDs used, such that everyone was on DMARD monotherapy if possible. In the second year, rheumatologists could treat patients at their own discretion, with adjustments to treatment made according to DAS28-CRP at visits every 3 months.
Ms. Stouten reported that all three of the intensive induction regimens “were very effective in our high-risk population and that they showed persistently high remission rates at year 2.”
The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 65.3% for the COBRA Classic regimen, 73.5% for COBRA Slim, and 73.1% for COBRA Avant-Garde.
For inducing remission, however, she suggested that the COBRA Slim regimen might have the edge from a benefit-to-risk perspective.
A total of 60.2% of COBRA Slim patients were in remission at year 1, and 67.8% of them remained in remission throughout year 2. Also, fewer COBRA Slim patients needed biologic therapy, both overall (n = 11) and in the first year (n = 2), when compared with the other two regimens. However, in the COBRA Classic arm, 65.3% were in remission at year 1, and 54.7% of those patients maintained it throughout year 2, whereas in the COBRA Avant-Garde arm the rates were 61.3% at year 1, with 70.2% of those maintaining remission throughout year 2. A total of 18 patients in the COBRA Classic group started biologics, including 10 in the first year, compared with 15 in the COBRA Avant-Garde group, 7 of those in the first year.
“For maintaining remission, there were no statistically significant differences observed in remission rates at year 2 between treatment groups,” Ms. Stouten observed. “However, COBRA Avant-Garde had numerically better CDAI [clinical disease activity index] remission rates at year 2 [48.2% vs. 33.7% for COBRA Slim and 34.7% for COBRA Classic; P = .068].”
The total numbers of patients reporting adverse events related to treatment were lower with the COBRA Slim regimen (n = 164) than with COBRA Classic (n = 209) and COBRA Avant-Garde (n = 208). Fewer COBRA Slim patients also had to stop treatment (5 vs. 9 with COBRA Classic and 12 with COBRA Avant-Garde) or have interrupted treatment (12 vs. 17 and 19, respectively) because of adverse events.
Ms. Stouten had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).
[email protected]
On Twitter @rheumnews1
MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.
The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.
Ms. Stouten added that, according to international guidelines, achieving clinical remission means treating patients early, as soon as possible after the diagnosis of rheumatoid arthritis is made; intensively, with a DMARD, preferably methotrexate if not contraindicated, combined with short-term glucocorticoids; and to target, meaning treatment should be targeted at achieving remission or at least low disease activity in every patient.
The CareRA trial was a prospective, randomized, multicenter trial set up to see which of three methotrexate-based, steroid-containing intensive regimens would be best for inducing remission in patients with high-risk RA. The pragmatic trial was conducted in 13 Belgian rheumatology practices recruiting 400 patients, 300 of whom were designated as high risk for progression based on factors such as their antibody status and presence of joint erosions. CareRA trial investigators defined clinical remission as less than 2.6 on the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP).
The three regimens all contained a weekly 15-mg dose of methotrexate and prednisone 30 mg or 60 mg that was then tapered weekly after the first 6-7 weeks.
In the COBRA Classic regimen, methotrexate was partnered with sulfasalazine, given as a 2-g daily dose. Prednisone was initially given at a dose of 60 mg and then taped to 5.7 mg starting at week 7.
For the COBRA Slim regimen, just methotrexate and prednisone were used, with the latter started at a dose of 30 mg and then tapered to 5 mg starting at week 6.
Lastly, the COBRA Avant-Garde regimen saw methotrexate combined with leflunomide, 10 mg daily, and the same step-down prednisone regimen as COBRA Slim.
In the first year, treatment in each group was adjusted to achieve a target of low disease activity (DAS28-CRP of 3.2 or lower), with measurements taken every 3 months. The steroid component was stepped down further after 28 weeks and stopped altogether by 34 weeks. The aim was also to reduce the number of DMARDs used, such that everyone was on DMARD monotherapy if possible. In the second year, rheumatologists could treat patients at their own discretion, with adjustments to treatment made according to DAS28-CRP at visits every 3 months.
Ms. Stouten reported that all three of the intensive induction regimens “were very effective in our high-risk population and that they showed persistently high remission rates at year 2.”
The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 65.3% for the COBRA Classic regimen, 73.5% for COBRA Slim, and 73.1% for COBRA Avant-Garde.
For inducing remission, however, she suggested that the COBRA Slim regimen might have the edge from a benefit-to-risk perspective.
A total of 60.2% of COBRA Slim patients were in remission at year 1, and 67.8% of them remained in remission throughout year 2. Also, fewer COBRA Slim patients needed biologic therapy, both overall (n = 11) and in the first year (n = 2), when compared with the other two regimens. However, in the COBRA Classic arm, 65.3% were in remission at year 1, and 54.7% of those patients maintained it throughout year 2, whereas in the COBRA Avant-Garde arm the rates were 61.3% at year 1, with 70.2% of those maintaining remission throughout year 2. A total of 18 patients in the COBRA Classic group started biologics, including 10 in the first year, compared with 15 in the COBRA Avant-Garde group, 7 of those in the first year.
“For maintaining remission, there were no statistically significant differences observed in remission rates at year 2 between treatment groups,” Ms. Stouten observed. “However, COBRA Avant-Garde had numerically better CDAI [clinical disease activity index] remission rates at year 2 [48.2% vs. 33.7% for COBRA Slim and 34.7% for COBRA Classic; P = .068].”
The total numbers of patients reporting adverse events related to treatment were lower with the COBRA Slim regimen (n = 164) than with COBRA Classic (n = 209) and COBRA Avant-Garde (n = 208). Fewer COBRA Slim patients also had to stop treatment (5 vs. 9 with COBRA Classic and 12 with COBRA Avant-Garde) or have interrupted treatment (12 vs. 17 and 19, respectively) because of adverse events.
Ms. Stouten had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).
[email protected]
On Twitter @rheumnews1
MADRID – Two-year results from the Care in early RA (CareRA) trial demonstrated the sustained effectiveness of a treat-to-target approach in patients with early rheumatoid arthritis at high risk for progression.
The percentage of patients who achieved clinical remission with one of three disease-modifying antirheumatic drug (DMARD) and glucocorticoid-containing regimens ranged from 60% to 65% at 1 year, and the percentage of those patients who were able to maintain their remission at all time points in year 2 ranged from 55% to 70%, none of which were significantly different from each other.
Ms. Stouten added that, according to international guidelines, achieving clinical remission means treating patients early, as soon as possible after the diagnosis of rheumatoid arthritis is made; intensively, with a DMARD, preferably methotrexate if not contraindicated, combined with short-term glucocorticoids; and to target, meaning treatment should be targeted at achieving remission or at least low disease activity in every patient.
The CareRA trial was a prospective, randomized, multicenter trial set up to see which of three methotrexate-based, steroid-containing intensive regimens would be best for inducing remission in patients with high-risk RA. The pragmatic trial was conducted in 13 Belgian rheumatology practices recruiting 400 patients, 300 of whom were designated as high risk for progression based on factors such as their antibody status and presence of joint erosions. CareRA trial investigators defined clinical remission as less than 2.6 on the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP).
The three regimens all contained a weekly 15-mg dose of methotrexate and prednisone 30 mg or 60 mg that was then tapered weekly after the first 6-7 weeks.
In the COBRA Classic regimen, methotrexate was partnered with sulfasalazine, given as a 2-g daily dose. Prednisone was initially given at a dose of 60 mg and then taped to 5.7 mg starting at week 7.
For the COBRA Slim regimen, just methotrexate and prednisone were used, with the latter started at a dose of 30 mg and then tapered to 5 mg starting at week 6.
Lastly, the COBRA Avant-Garde regimen saw methotrexate combined with leflunomide, 10 mg daily, and the same step-down prednisone regimen as COBRA Slim.
In the first year, treatment in each group was adjusted to achieve a target of low disease activity (DAS28-CRP of 3.2 or lower), with measurements taken every 3 months. The steroid component was stepped down further after 28 weeks and stopped altogether by 34 weeks. The aim was also to reduce the number of DMARDs used, such that everyone was on DMARD monotherapy if possible. In the second year, rheumatologists could treat patients at their own discretion, with adjustments to treatment made according to DAS28-CRP at visits every 3 months.
Ms. Stouten reported that all three of the intensive induction regimens “were very effective in our high-risk population and that they showed persistently high remission rates at year 2.”
The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 65.3% for the COBRA Classic regimen, 73.5% for COBRA Slim, and 73.1% for COBRA Avant-Garde.
For inducing remission, however, she suggested that the COBRA Slim regimen might have the edge from a benefit-to-risk perspective.
A total of 60.2% of COBRA Slim patients were in remission at year 1, and 67.8% of them remained in remission throughout year 2. Also, fewer COBRA Slim patients needed biologic therapy, both overall (n = 11) and in the first year (n = 2), when compared with the other two regimens. However, in the COBRA Classic arm, 65.3% were in remission at year 1, and 54.7% of those patients maintained it throughout year 2, whereas in the COBRA Avant-Garde arm the rates were 61.3% at year 1, with 70.2% of those maintaining remission throughout year 2. A total of 18 patients in the COBRA Classic group started biologics, including 10 in the first year, compared with 15 in the COBRA Avant-Garde group, 7 of those in the first year.
“For maintaining remission, there were no statistically significant differences observed in remission rates at year 2 between treatment groups,” Ms. Stouten observed. “However, COBRA Avant-Garde had numerically better CDAI [clinical disease activity index] remission rates at year 2 [48.2% vs. 33.7% for COBRA Slim and 34.7% for COBRA Classic; P = .068].”
The total numbers of patients reporting adverse events related to treatment were lower with the COBRA Slim regimen (n = 164) than with COBRA Classic (n = 209) and COBRA Avant-Garde (n = 208). Fewer COBRA Slim patients also had to stop treatment (5 vs. 9 with COBRA Classic and 12 with COBRA Avant-Garde) or have interrupted treatment (12 vs. 17 and 19, respectively) because of adverse events.
Ms. Stouten had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).
[email protected]
On Twitter @rheumnews1
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: The percentage of patients with a DAS28-CRP of less than 2.6 at 2 years was 73.5% for the COBRA Slim regimen, 73.1% for COBRA Avant-Garde, and 65.3% for COBRA Classic.
Data source: The Care in early RA (CareRA) trial, a prospective, randomized, multicenter trial of 379 patients with treatment-naive, early rheumatoid arthritis.
Disclosures: The presenter had no personal disclosures. The study was supported by a Flemish governmental grant provided by IWT (Innovatie door Wetenschap en Technologie).
Children with HIV benefit from double dose of PCV13 vaccine
, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.
An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).
“In future studies, a larger spectrum of comorbidities should be included to determine the most cost-effective vaccination regimens particularly in low income countries,” the researchers noted.
, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.
An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).
“In future studies, a larger spectrum of comorbidities should be included to determine the most cost-effective vaccination regimens particularly in low income countries,” the researchers noted.
, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.
An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).
“In future studies, a larger spectrum of comorbidities should be included to determine the most cost-effective vaccination regimens particularly in low income countries,” the researchers noted.
FROM VACCINE
Watchman device for AF patients ineligible for oral anticoagulation gains support from 1-year registry outcomes
PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.
Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA2DS2-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.
However, the ESC guidelines were largely based on randomized trials of the Watchman versus oral anticoagulation, including PREVAIL and PROTECT-AF, showing noninferiority. The safety and efficacy of the device in warfarin-ineligible patients was less well studied at the time the guidelines were formulated. And in fact, such patients are excluded from the Food and Drug Administration’s approved indication, which is specifically for patients judged “suitable for warfarin.”
“This gap is now filled by EWOLUTION. This is a registry that’s as good as it gets. We have all the things in place that you need these days to be able to rely on the outcome data,” according to the cardiologist.
EWOLUTION is a prospective, multicenter, all-comers registry. The EWOLUTION population of AF patients on DAPT was high risk: 89% had a CHA2DS2-VASc score of 3 or more, 31% were at least 80 years old, the mean HAS-BLED score was 2.4, and oral anticoagulation was contraindicated in 84% of participants.
Eighty-seven percent of subjects underwent follow-up transesophageal echocardiography. The imaging study showed the Watchman effectively sealed the left atrial appendage in 99.2% of patients as defined by no leak greater than 5 mm. The echo exam also showed the presence of thrombus on the device at follow-up in 4% of patients, although only 1 of the 22 patients with device thrombus experienced a stroke.
“We can conclude two things from this which are in line with earlier studies. First, the rate of thrombus on the device is equal to the rate reported in the randomized controlled trials, which was also 4%, even if the patients were on warfarin for the first 45 days. And second, these thrombi are not related to stroke,” Dr. Bergmann said.
At the 1-year mark, 71% of patients had switched to a single antiplatelet agent, while 17% remained on DAPT, mainly because of comorbid coronary disease for which DAPT is indicated. Seven percent of patients were on no antithrombotic medications. The remaining 5% were transiently on warfarin or a novel oral anticoagulant.
The 1-year cumulative rate of ischemic stroke or TIA was 1.8%, with no instances of systemic embolism. Of note, there were no hemorrhagic strokes. And of the 11 cases of ischemic stroke, none were fatal and only one was disabling.
“This is a sign that comes also from the PREVAIL trial, that if you have a stroke while on left atrial appendage–closure therapy, most of the time it’s not disabling. It’s much less severe on the modified Rankin Scale than if you’re on oral anticoagulation,” said Dr. Bergmann.
The 1.4% rate of ischemic stroke at 1 year in Watchman recipients represents an 81% reduction in risk compared with the expected 7.5% rate in patients with similar CHA2DS2-VASc scores not on oral anticoagulation. This level of stroke risk reduction is similar to that seen in the pivotal ARISTOTLE trial of apixaban (Eliquis) in a high-risk AF population (Lancet. 2012 Nov 17;380[9855]:1749-58).
Major bleeding occurred in 2.5% of patients. The rate of fatal bleeding was 0.5%. To put that in perspective, the 2.5% major bleeding rate was 52% lower than would be expected based upon similar HAS-BLED scores in patients on warfarin. Still, 2.5% is unacceptably high.
“The major serious adverse event is not pericardial effusion or late device embolization, it’s major bleeding occurring during the time the patient is on DAPT, mostly within the first 3 months. So I think we have to do something about this,” he said.
One possibility worthy of formal study is 3 months of periprocedural NOAC monotherapy. “Maybe even low-dose therapy, like 75 mg of dabigatran [Pradaxa] twice daily. We have an antidote that works nicely [idarucizumab, Praxbind] so I think maybe this is the way to go,” Dr. Bergmann observed.
The ongoing EWOLUTION registry is sponsored by Boston Scientific. Dr. Bergmann is a consultant to that company as well as Bayer AG, Daiichi Sankyo, Eli Lilly, and St. Jude Medical.
PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.
Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA2DS2-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.
However, the ESC guidelines were largely based on randomized trials of the Watchman versus oral anticoagulation, including PREVAIL and PROTECT-AF, showing noninferiority. The safety and efficacy of the device in warfarin-ineligible patients was less well studied at the time the guidelines were formulated. And in fact, such patients are excluded from the Food and Drug Administration’s approved indication, which is specifically for patients judged “suitable for warfarin.”
“This gap is now filled by EWOLUTION. This is a registry that’s as good as it gets. We have all the things in place that you need these days to be able to rely on the outcome data,” according to the cardiologist.
EWOLUTION is a prospective, multicenter, all-comers registry. The EWOLUTION population of AF patients on DAPT was high risk: 89% had a CHA2DS2-VASc score of 3 or more, 31% were at least 80 years old, the mean HAS-BLED score was 2.4, and oral anticoagulation was contraindicated in 84% of participants.
Eighty-seven percent of subjects underwent follow-up transesophageal echocardiography. The imaging study showed the Watchman effectively sealed the left atrial appendage in 99.2% of patients as defined by no leak greater than 5 mm. The echo exam also showed the presence of thrombus on the device at follow-up in 4% of patients, although only 1 of the 22 patients with device thrombus experienced a stroke.
“We can conclude two things from this which are in line with earlier studies. First, the rate of thrombus on the device is equal to the rate reported in the randomized controlled trials, which was also 4%, even if the patients were on warfarin for the first 45 days. And second, these thrombi are not related to stroke,” Dr. Bergmann said.
At the 1-year mark, 71% of patients had switched to a single antiplatelet agent, while 17% remained on DAPT, mainly because of comorbid coronary disease for which DAPT is indicated. Seven percent of patients were on no antithrombotic medications. The remaining 5% were transiently on warfarin or a novel oral anticoagulant.
The 1-year cumulative rate of ischemic stroke or TIA was 1.8%, with no instances of systemic embolism. Of note, there were no hemorrhagic strokes. And of the 11 cases of ischemic stroke, none were fatal and only one was disabling.
“This is a sign that comes also from the PREVAIL trial, that if you have a stroke while on left atrial appendage–closure therapy, most of the time it’s not disabling. It’s much less severe on the modified Rankin Scale than if you’re on oral anticoagulation,” said Dr. Bergmann.
The 1.4% rate of ischemic stroke at 1 year in Watchman recipients represents an 81% reduction in risk compared with the expected 7.5% rate in patients with similar CHA2DS2-VASc scores not on oral anticoagulation. This level of stroke risk reduction is similar to that seen in the pivotal ARISTOTLE trial of apixaban (Eliquis) in a high-risk AF population (Lancet. 2012 Nov 17;380[9855]:1749-58).
Major bleeding occurred in 2.5% of patients. The rate of fatal bleeding was 0.5%. To put that in perspective, the 2.5% major bleeding rate was 52% lower than would be expected based upon similar HAS-BLED scores in patients on warfarin. Still, 2.5% is unacceptably high.
“The major serious adverse event is not pericardial effusion or late device embolization, it’s major bleeding occurring during the time the patient is on DAPT, mostly within the first 3 months. So I think we have to do something about this,” he said.
One possibility worthy of formal study is 3 months of periprocedural NOAC monotherapy. “Maybe even low-dose therapy, like 75 mg of dabigatran [Pradaxa] twice daily. We have an antidote that works nicely [idarucizumab, Praxbind] so I think maybe this is the way to go,” Dr. Bergmann observed.
The ongoing EWOLUTION registry is sponsored by Boston Scientific. Dr. Bergmann is a consultant to that company as well as Bayer AG, Daiichi Sankyo, Eli Lilly, and St. Jude Medical.
PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.
Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA2DS2-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.
However, the ESC guidelines were largely based on randomized trials of the Watchman versus oral anticoagulation, including PREVAIL and PROTECT-AF, showing noninferiority. The safety and efficacy of the device in warfarin-ineligible patients was less well studied at the time the guidelines were formulated. And in fact, such patients are excluded from the Food and Drug Administration’s approved indication, which is specifically for patients judged “suitable for warfarin.”
“This gap is now filled by EWOLUTION. This is a registry that’s as good as it gets. We have all the things in place that you need these days to be able to rely on the outcome data,” according to the cardiologist.
EWOLUTION is a prospective, multicenter, all-comers registry. The EWOLUTION population of AF patients on DAPT was high risk: 89% had a CHA2DS2-VASc score of 3 or more, 31% were at least 80 years old, the mean HAS-BLED score was 2.4, and oral anticoagulation was contraindicated in 84% of participants.
Eighty-seven percent of subjects underwent follow-up transesophageal echocardiography. The imaging study showed the Watchman effectively sealed the left atrial appendage in 99.2% of patients as defined by no leak greater than 5 mm. The echo exam also showed the presence of thrombus on the device at follow-up in 4% of patients, although only 1 of the 22 patients with device thrombus experienced a stroke.
“We can conclude two things from this which are in line with earlier studies. First, the rate of thrombus on the device is equal to the rate reported in the randomized controlled trials, which was also 4%, even if the patients were on warfarin for the first 45 days. And second, these thrombi are not related to stroke,” Dr. Bergmann said.
At the 1-year mark, 71% of patients had switched to a single antiplatelet agent, while 17% remained on DAPT, mainly because of comorbid coronary disease for which DAPT is indicated. Seven percent of patients were on no antithrombotic medications. The remaining 5% were transiently on warfarin or a novel oral anticoagulant.
The 1-year cumulative rate of ischemic stroke or TIA was 1.8%, with no instances of systemic embolism. Of note, there were no hemorrhagic strokes. And of the 11 cases of ischemic stroke, none were fatal and only one was disabling.
“This is a sign that comes also from the PREVAIL trial, that if you have a stroke while on left atrial appendage–closure therapy, most of the time it’s not disabling. It’s much less severe on the modified Rankin Scale than if you’re on oral anticoagulation,” said Dr. Bergmann.
The 1.4% rate of ischemic stroke at 1 year in Watchman recipients represents an 81% reduction in risk compared with the expected 7.5% rate in patients with similar CHA2DS2-VASc scores not on oral anticoagulation. This level of stroke risk reduction is similar to that seen in the pivotal ARISTOTLE trial of apixaban (Eliquis) in a high-risk AF population (Lancet. 2012 Nov 17;380[9855]:1749-58).
Major bleeding occurred in 2.5% of patients. The rate of fatal bleeding was 0.5%. To put that in perspective, the 2.5% major bleeding rate was 52% lower than would be expected based upon similar HAS-BLED scores in patients on warfarin. Still, 2.5% is unacceptably high.
“The major serious adverse event is not pericardial effusion or late device embolization, it’s major bleeding occurring during the time the patient is on DAPT, mostly within the first 3 months. So I think we have to do something about this,” he said.
One possibility worthy of formal study is 3 months of periprocedural NOAC monotherapy. “Maybe even low-dose therapy, like 75 mg of dabigatran [Pradaxa] twice daily. We have an antidote that works nicely [idarucizumab, Praxbind] so I think maybe this is the way to go,” Dr. Bergmann observed.
The ongoing EWOLUTION registry is sponsored by Boston Scientific. Dr. Bergmann is a consultant to that company as well as Bayer AG, Daiichi Sankyo, Eli Lilly, and St. Jude Medical.
AT EUROPCR
Key clinical point:
Major finding: Patients with AF at high stroke risk and ineligible for oral anticoagulation experienced an 81% reduction in their expected risk of ischemic stroke during their first year of LAA closure with the Watchman device backed by limited-duration dual-antiplatelet therapy
Data source: A prospective, multicenter, single-arm registry that includes 605 patients with AF who underwent left atrial appendage closure with the WATCHMAN device supported by limited-duration dual-antiplatelet therapy.
Disclosures: The ongoing EWOLUTION registry is sponsored by Boston Scientific. The presenter is a consultant to that company and several others.
Statins linked to fewer deaths, slightly higher HbA1c in T2DM
SAN DIEGO – Findings from a study of 12,725 new insulin users with type 2 diabetes mellitus (T2DM) show that those who did not take statins were slightly better able to control their blood sugar, but those who used the cholesterol-lowering drugs lived longer and had fewer cardiac events.
“It is clear that, in this high-risk population, the benefits of statins on cardiovascular outcomes outweigh the small adverse metabolic effects on glycemic control,” study lead author Uche Anyanwagu, MBBS, MSc, a graduate student and research fellow at the University of Nottingham (England), said in an interview about his data presented in a poster at the annual scientific sessions of the American Diabetes Association.
However, “there remain great concerns about statins and their modest adverse effects on glucose and insulin metabolism in increasing the risk of new-onset diabetes or worsening glycemic control, especially in higher doses and with the more potent statins,” Dr. Anyanwagu said. “Very little is known about the relationship between statin use and glycemic control in patients with established T2DM.”
The study authors retrospectively analyzed medical records of 12,725 new insulin users with T2DM from a British primary care database. “The commencement of insulin represents a group of patients with T2DM with longer disease duration and more complex needs, many of whom have other comorbid illnesses,” Dr. Anyanwagu said.
The average age of the subjects was 58.6 years (standard deviation, 13.8), and 50% were female (P less than 0.001 for both). Their average HbA1c level was 8.7 (SD, 1.8; P = .556), and 63% were obese.
The numbers of statin users and nonstatin users were 10,682 and 2,043, respectively. Researchers found that the statin users performed better in measures of all-cause mortality, nonfatal stroke, and a composite outcome measure but not in acute myocardial infarction.
In all-cause mortality, the absolute rate over 5 years was 9.5 deaths per 1,000 person years (95% confidence interval, 8.7-10.5) for statin users and 24.9 (95% CI, 21.5-28.9) for nonusers. After adjustment for age, gender, duration of insulin use, albumin, glomerular filtration rate, lipid profile, and coronary heart disease, the hazard ratio was 1.89 (95% CI, 1.51-2.37) for nonusers, compared with a reference of 1 for users. (P less than .0001).
The absolute rate for a composite outcome – encompassing measures of all-cause mortality, nonfatal acute myocardial infarction, and nonfatal stroke – was 20.7 (95% CI, 19.3-22.1) for statin users and 30.9 (95% CI , 27-35.3) for nonusers (P less than .0001).
As for HbA1c levels, at 12 months, they’d fallen by an average of 0.29% in the statin group and 0.37% in the nonuser group (P = .021). At 36 months, there was a smaller difference (–0.31% vs. –0.35%, respectively), and it wasn’t statistically significant (P = .344).
The study was funded by the University of Nottingham. (England). Dr. Anyanwagu reports no relevant disclosures.
SAN DIEGO – Findings from a study of 12,725 new insulin users with type 2 diabetes mellitus (T2DM) show that those who did not take statins were slightly better able to control their blood sugar, but those who used the cholesterol-lowering drugs lived longer and had fewer cardiac events.
“It is clear that, in this high-risk population, the benefits of statins on cardiovascular outcomes outweigh the small adverse metabolic effects on glycemic control,” study lead author Uche Anyanwagu, MBBS, MSc, a graduate student and research fellow at the University of Nottingham (England), said in an interview about his data presented in a poster at the annual scientific sessions of the American Diabetes Association.
However, “there remain great concerns about statins and their modest adverse effects on glucose and insulin metabolism in increasing the risk of new-onset diabetes or worsening glycemic control, especially in higher doses and with the more potent statins,” Dr. Anyanwagu said. “Very little is known about the relationship between statin use and glycemic control in patients with established T2DM.”
The study authors retrospectively analyzed medical records of 12,725 new insulin users with T2DM from a British primary care database. “The commencement of insulin represents a group of patients with T2DM with longer disease duration and more complex needs, many of whom have other comorbid illnesses,” Dr. Anyanwagu said.
The average age of the subjects was 58.6 years (standard deviation, 13.8), and 50% were female (P less than 0.001 for both). Their average HbA1c level was 8.7 (SD, 1.8; P = .556), and 63% were obese.
The numbers of statin users and nonstatin users were 10,682 and 2,043, respectively. Researchers found that the statin users performed better in measures of all-cause mortality, nonfatal stroke, and a composite outcome measure but not in acute myocardial infarction.
In all-cause mortality, the absolute rate over 5 years was 9.5 deaths per 1,000 person years (95% confidence interval, 8.7-10.5) for statin users and 24.9 (95% CI, 21.5-28.9) for nonusers. After adjustment for age, gender, duration of insulin use, albumin, glomerular filtration rate, lipid profile, and coronary heart disease, the hazard ratio was 1.89 (95% CI, 1.51-2.37) for nonusers, compared with a reference of 1 for users. (P less than .0001).
The absolute rate for a composite outcome – encompassing measures of all-cause mortality, nonfatal acute myocardial infarction, and nonfatal stroke – was 20.7 (95% CI, 19.3-22.1) for statin users and 30.9 (95% CI , 27-35.3) for nonusers (P less than .0001).
As for HbA1c levels, at 12 months, they’d fallen by an average of 0.29% in the statin group and 0.37% in the nonuser group (P = .021). At 36 months, there was a smaller difference (–0.31% vs. –0.35%, respectively), and it wasn’t statistically significant (P = .344).
The study was funded by the University of Nottingham. (England). Dr. Anyanwagu reports no relevant disclosures.
SAN DIEGO – Findings from a study of 12,725 new insulin users with type 2 diabetes mellitus (T2DM) show that those who did not take statins were slightly better able to control their blood sugar, but those who used the cholesterol-lowering drugs lived longer and had fewer cardiac events.
“It is clear that, in this high-risk population, the benefits of statins on cardiovascular outcomes outweigh the small adverse metabolic effects on glycemic control,” study lead author Uche Anyanwagu, MBBS, MSc, a graduate student and research fellow at the University of Nottingham (England), said in an interview about his data presented in a poster at the annual scientific sessions of the American Diabetes Association.
However, “there remain great concerns about statins and their modest adverse effects on glucose and insulin metabolism in increasing the risk of new-onset diabetes or worsening glycemic control, especially in higher doses and with the more potent statins,” Dr. Anyanwagu said. “Very little is known about the relationship between statin use and glycemic control in patients with established T2DM.”
The study authors retrospectively analyzed medical records of 12,725 new insulin users with T2DM from a British primary care database. “The commencement of insulin represents a group of patients with T2DM with longer disease duration and more complex needs, many of whom have other comorbid illnesses,” Dr. Anyanwagu said.
The average age of the subjects was 58.6 years (standard deviation, 13.8), and 50% were female (P less than 0.001 for both). Their average HbA1c level was 8.7 (SD, 1.8; P = .556), and 63% were obese.
The numbers of statin users and nonstatin users were 10,682 and 2,043, respectively. Researchers found that the statin users performed better in measures of all-cause mortality, nonfatal stroke, and a composite outcome measure but not in acute myocardial infarction.
In all-cause mortality, the absolute rate over 5 years was 9.5 deaths per 1,000 person years (95% confidence interval, 8.7-10.5) for statin users and 24.9 (95% CI, 21.5-28.9) for nonusers. After adjustment for age, gender, duration of insulin use, albumin, glomerular filtration rate, lipid profile, and coronary heart disease, the hazard ratio was 1.89 (95% CI, 1.51-2.37) for nonusers, compared with a reference of 1 for users. (P less than .0001).
The absolute rate for a composite outcome – encompassing measures of all-cause mortality, nonfatal acute myocardial infarction, and nonfatal stroke – was 20.7 (95% CI, 19.3-22.1) for statin users and 30.9 (95% CI , 27-35.3) for nonusers (P less than .0001).
As for HbA1c levels, at 12 months, they’d fallen by an average of 0.29% in the statin group and 0.37% in the nonuser group (P = .021). At 36 months, there was a smaller difference (–0.31% vs. –0.35%, respectively), and it wasn’t statistically significant (P = .344).
The study was funded by the University of Nottingham. (England). Dr. Anyanwagu reports no relevant disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: In new insulin users with T2DM, statin use appears to slightly lower the decline in HbA1c, compared with nonuse, but the drug improved all-cause mortality.
Major finding: The adjusted hazard ratio of 5-year all-cause mortality was 1.89 in nonstatin users, vs. a reference of 1 for statin users. At 12 months, HbA1c fell by an average of 0.29% in the statin group and 0.37% in the nonuser group, but the difference wasn’t statistically significant at 36 months.
Data source: A retrospective study of 10,682 stain users and 2,043 nonusers, all of whom were new insulin users, from a British primary care database.
Disclosures: The study was funded by the University of Nottingham (England).
Drug combo improves RV contractility in scleroderma-PAH
A combination of ambrisentan (Letairis) and tadalafil (Cialis) improves regional and global right ventricular contractility in patients with scleroderma-associated pulmonary arterial hypertension, according to an open-label investigation of 23 patients.
The project was a follow-up to a previous report showing that the upfront combination – tadalafil 40 mg and ambrisentan 10 mg oral once daily – improved hemodynamics, right ventricular (RV) structure and function, and functional status in treatment-naive patients after 36 weeks and “may represent a very effective therapy for this patient population” (Am J Respir Crit Care Med. 2015 Nov 1;192(9):1102-10).
At baseline, the subjects had normal left ventricular (LV) size and function, with borderline left atrial enlargement and mild LV diastolic dysfunction. Their right heart chambers were significantly dilated, with RV hypertrophy. Conventional RV function parameters – tricuspid annular systolic plane excursion (TAPSE) and fractional area change (FAC) – were impaired. RV systolic pressure (RVSP) was severely elevated. There was also a marked reduction of global RV longitudinal systolic strain (RVLSS), compared with normal values mainly because of a reduction in midventricular and apical RVLSS, with relative hyperkinesis of basal RVLSS
After 36 weeks of treatment, right heart chamber sizes were significantly reduced. There was also a decrease in RV free wall thickness, which coincided with a significant reduction in RV mass on cardiac MRI. TAPSE, FAC, and global RVLSS improved significantly, and RVSP decreased significantly. LV end-diastolic and end-systolic diameters and volumes increased significantly.
The changes “may represent transition from maladaptive RV remodeling ... to a more physiological and adaptive RV remodeling;” however, “the effects of treatment should be interpreted with caution, as this was an open-label study without a placebo or a single-drug control group,” said investigators led by Valentina Mercurio, MD, a postdoc fellow at Johns Hopkins University, Baltimore.
“It is conceivable that a heterogeneous RVLSS pattern exists in [scleroderma] patients with longitudinal hyperkinetic basal segment as the predominant vector of contraction early in the disease course. As PAH develops, the ability of the basal segment to compensate decreases, and RV failure ensues, suggesting a ‘two-hit’ hypothesis, in which a preexisting RV contractile dysfunction may predispose to further RV impairment when a second insult (PAH development) occurs,” they said.
Subjects were about 60 years old on average, and most were women. The majority shifted from World Health Organization PAH functional class 3 to 2 during the original trial. Mean 6 minute walk tests increased from 341 m to 401 m.
Gilead and United Therapeutics provided the ambrisentan and tadalafil. Dr. Mercurio reported funding from both companies and Merck. The original study was sponsored by United Therapeutics.
A combination of ambrisentan (Letairis) and tadalafil (Cialis) improves regional and global right ventricular contractility in patients with scleroderma-associated pulmonary arterial hypertension, according to an open-label investigation of 23 patients.
The project was a follow-up to a previous report showing that the upfront combination – tadalafil 40 mg and ambrisentan 10 mg oral once daily – improved hemodynamics, right ventricular (RV) structure and function, and functional status in treatment-naive patients after 36 weeks and “may represent a very effective therapy for this patient population” (Am J Respir Crit Care Med. 2015 Nov 1;192(9):1102-10).
At baseline, the subjects had normal left ventricular (LV) size and function, with borderline left atrial enlargement and mild LV diastolic dysfunction. Their right heart chambers were significantly dilated, with RV hypertrophy. Conventional RV function parameters – tricuspid annular systolic plane excursion (TAPSE) and fractional area change (FAC) – were impaired. RV systolic pressure (RVSP) was severely elevated. There was also a marked reduction of global RV longitudinal systolic strain (RVLSS), compared with normal values mainly because of a reduction in midventricular and apical RVLSS, with relative hyperkinesis of basal RVLSS
After 36 weeks of treatment, right heart chamber sizes were significantly reduced. There was also a decrease in RV free wall thickness, which coincided with a significant reduction in RV mass on cardiac MRI. TAPSE, FAC, and global RVLSS improved significantly, and RVSP decreased significantly. LV end-diastolic and end-systolic diameters and volumes increased significantly.
The changes “may represent transition from maladaptive RV remodeling ... to a more physiological and adaptive RV remodeling;” however, “the effects of treatment should be interpreted with caution, as this was an open-label study without a placebo or a single-drug control group,” said investigators led by Valentina Mercurio, MD, a postdoc fellow at Johns Hopkins University, Baltimore.
“It is conceivable that a heterogeneous RVLSS pattern exists in [scleroderma] patients with longitudinal hyperkinetic basal segment as the predominant vector of contraction early in the disease course. As PAH develops, the ability of the basal segment to compensate decreases, and RV failure ensues, suggesting a ‘two-hit’ hypothesis, in which a preexisting RV contractile dysfunction may predispose to further RV impairment when a second insult (PAH development) occurs,” they said.
Subjects were about 60 years old on average, and most were women. The majority shifted from World Health Organization PAH functional class 3 to 2 during the original trial. Mean 6 minute walk tests increased from 341 m to 401 m.
Gilead and United Therapeutics provided the ambrisentan and tadalafil. Dr. Mercurio reported funding from both companies and Merck. The original study was sponsored by United Therapeutics.
A combination of ambrisentan (Letairis) and tadalafil (Cialis) improves regional and global right ventricular contractility in patients with scleroderma-associated pulmonary arterial hypertension, according to an open-label investigation of 23 patients.
The project was a follow-up to a previous report showing that the upfront combination – tadalafil 40 mg and ambrisentan 10 mg oral once daily – improved hemodynamics, right ventricular (RV) structure and function, and functional status in treatment-naive patients after 36 weeks and “may represent a very effective therapy for this patient population” (Am J Respir Crit Care Med. 2015 Nov 1;192(9):1102-10).
At baseline, the subjects had normal left ventricular (LV) size and function, with borderline left atrial enlargement and mild LV diastolic dysfunction. Their right heart chambers were significantly dilated, with RV hypertrophy. Conventional RV function parameters – tricuspid annular systolic plane excursion (TAPSE) and fractional area change (FAC) – were impaired. RV systolic pressure (RVSP) was severely elevated. There was also a marked reduction of global RV longitudinal systolic strain (RVLSS), compared with normal values mainly because of a reduction in midventricular and apical RVLSS, with relative hyperkinesis of basal RVLSS
After 36 weeks of treatment, right heart chamber sizes were significantly reduced. There was also a decrease in RV free wall thickness, which coincided with a significant reduction in RV mass on cardiac MRI. TAPSE, FAC, and global RVLSS improved significantly, and RVSP decreased significantly. LV end-diastolic and end-systolic diameters and volumes increased significantly.
The changes “may represent transition from maladaptive RV remodeling ... to a more physiological and adaptive RV remodeling;” however, “the effects of treatment should be interpreted with caution, as this was an open-label study without a placebo or a single-drug control group,” said investigators led by Valentina Mercurio, MD, a postdoc fellow at Johns Hopkins University, Baltimore.
“It is conceivable that a heterogeneous RVLSS pattern exists in [scleroderma] patients with longitudinal hyperkinetic basal segment as the predominant vector of contraction early in the disease course. As PAH develops, the ability of the basal segment to compensate decreases, and RV failure ensues, suggesting a ‘two-hit’ hypothesis, in which a preexisting RV contractile dysfunction may predispose to further RV impairment when a second insult (PAH development) occurs,” they said.
Subjects were about 60 years old on average, and most were women. The majority shifted from World Health Organization PAH functional class 3 to 2 during the original trial. Mean 6 minute walk tests increased from 341 m to 401 m.
Gilead and United Therapeutics provided the ambrisentan and tadalafil. Dr. Mercurio reported funding from both companies and Merck. The original study was sponsored by United Therapeutics.
FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Key clinical point:
Major finding: After 36 weeks of treatment, TAPSE, FAC, and global RVLSS improved significantly, and RV systolic pressure decreased significantly.
Data source: Cardiac imaging of 23 patients.
Disclosures: Gilead and United Therapeutics provided the ambrisentan and tadalafil. The lead investigator reported funding from both companies and Merck. The original study was sponsored by United Therapeutics.
ANCA-associated vasculitis appears to increase risk of stroke, death
MADRID – Small-vessel vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCAs) appears to increase the risk of stroke and overall mortality, results of a French retrospective study suggest.
Patients with ANCA-associated vasculitis (AAV) were twice as likely as those without to experience a stroke over 7.5 years, Grégory Pugnet, MD, reported at the European Congress of Rheumatology. Their all-cause mortality was also significantly higher, with 30% of the deaths attributed to cardiovascular causes, said Dr. Pugnet of the Internal Medicine Service at Purpan Hospital in Toulouse, France.
“We think this [shows that it] is very important to monitor [these patients] and to be vigilant in our search for cardiovascular complications and cardiovascular risk factors in this population,” he said.
Dr. Pugnet and his colleagues conducted a retrospective study of 125 patients with AAV who were diagnosed in a teaching hospital between 1981 and 2015. He compared cardiovascular outcomes and mortality between this cohort and two French regional registries: the Midi-Pyrénées County Mortality and Acute Myocardial Infarction Registry and the Dijon Stroke Registry. Outcomes were the date of first acute myocardial infarction, date of first stroke, and date of death; the mean follow-up was about 90 months.
Of the 125 patients with AAV, 99 had granulomatosis with polyangiitis, and 26 had microscopic polyangiitis. Preexisting cardiovascular disease was present in 23. Patients were a mean of 61 years old. Hypertension, peripheral artery disease, and coronary artery disease were all more common among those with cardiovascular disease. These patients were also more likely to smoke.
Over the follow-up period, there were 10 acute myocardial infarctions for an incidence of 8.5 per 1,000 person-years. The MI incidence in the Midi-Pyrénées registry was 2.2 per 1,000 person-years, which was a significant difference in an unadjusted analysis. But after adjusting for age, AAV patients were not significantly more likely to experience a heart attack than were those in the registry.
There were nine strokes during the follow-up period for an incidence of 10.2 per 1,000 person-years. After adjusting for age, this was more than three times higher than the rate of 1.9 per 1,000 person-year in the Dijon Stroke Registry – a significant difference.
A total of 22 AAV patients died during the follow-up period, translating to a mortality of 22.5 per 1,000 person-years. Mortality in the stroke registry was 1.9 per 1,000 person-years. An age-adjusted analysis found that AAV patients were about 1.6 times more likely to die than were those in the Midi-Pyrénées registry.
A multivariate regression analysis identified some factors that were independently associated with the outcomes. Smoking almost quadrupled the risk of having any cardiovascular event (hazard ratio, 3.7), and having had a plasma exchange tripled it (HR, 2.9). Smoking and a history of coronary artery disease were significant risk factors for myocardial infarction (HRs of 8.8 and 10.3, respectively). Dr. Pugnet and his associates didn’t find any significant independent risk factors for stroke. Age was not independently associated with any of the outcomes.
Dr. Pugnet reported receiving travel support from AbbVie and Actelion, fees for serving on an advisory board from Grifols, and lecture fees from AbbVie.
[email protected]
On Twitter @alz_gal
MADRID – Small-vessel vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCAs) appears to increase the risk of stroke and overall mortality, results of a French retrospective study suggest.
Patients with ANCA-associated vasculitis (AAV) were twice as likely as those without to experience a stroke over 7.5 years, Grégory Pugnet, MD, reported at the European Congress of Rheumatology. Their all-cause mortality was also significantly higher, with 30% of the deaths attributed to cardiovascular causes, said Dr. Pugnet of the Internal Medicine Service at Purpan Hospital in Toulouse, France.
“We think this [shows that it] is very important to monitor [these patients] and to be vigilant in our search for cardiovascular complications and cardiovascular risk factors in this population,” he said.
Dr. Pugnet and his colleagues conducted a retrospective study of 125 patients with AAV who were diagnosed in a teaching hospital between 1981 and 2015. He compared cardiovascular outcomes and mortality between this cohort and two French regional registries: the Midi-Pyrénées County Mortality and Acute Myocardial Infarction Registry and the Dijon Stroke Registry. Outcomes were the date of first acute myocardial infarction, date of first stroke, and date of death; the mean follow-up was about 90 months.
Of the 125 patients with AAV, 99 had granulomatosis with polyangiitis, and 26 had microscopic polyangiitis. Preexisting cardiovascular disease was present in 23. Patients were a mean of 61 years old. Hypertension, peripheral artery disease, and coronary artery disease were all more common among those with cardiovascular disease. These patients were also more likely to smoke.
Over the follow-up period, there were 10 acute myocardial infarctions for an incidence of 8.5 per 1,000 person-years. The MI incidence in the Midi-Pyrénées registry was 2.2 per 1,000 person-years, which was a significant difference in an unadjusted analysis. But after adjusting for age, AAV patients were not significantly more likely to experience a heart attack than were those in the registry.
There were nine strokes during the follow-up period for an incidence of 10.2 per 1,000 person-years. After adjusting for age, this was more than three times higher than the rate of 1.9 per 1,000 person-year in the Dijon Stroke Registry – a significant difference.
A total of 22 AAV patients died during the follow-up period, translating to a mortality of 22.5 per 1,000 person-years. Mortality in the stroke registry was 1.9 per 1,000 person-years. An age-adjusted analysis found that AAV patients were about 1.6 times more likely to die than were those in the Midi-Pyrénées registry.
A multivariate regression analysis identified some factors that were independently associated with the outcomes. Smoking almost quadrupled the risk of having any cardiovascular event (hazard ratio, 3.7), and having had a plasma exchange tripled it (HR, 2.9). Smoking and a history of coronary artery disease were significant risk factors for myocardial infarction (HRs of 8.8 and 10.3, respectively). Dr. Pugnet and his associates didn’t find any significant independent risk factors for stroke. Age was not independently associated with any of the outcomes.
Dr. Pugnet reported receiving travel support from AbbVie and Actelion, fees for serving on an advisory board from Grifols, and lecture fees from AbbVie.
[email protected]
On Twitter @alz_gal
MADRID – Small-vessel vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCAs) appears to increase the risk of stroke and overall mortality, results of a French retrospective study suggest.
Patients with ANCA-associated vasculitis (AAV) were twice as likely as those without to experience a stroke over 7.5 years, Grégory Pugnet, MD, reported at the European Congress of Rheumatology. Their all-cause mortality was also significantly higher, with 30% of the deaths attributed to cardiovascular causes, said Dr. Pugnet of the Internal Medicine Service at Purpan Hospital in Toulouse, France.
“We think this [shows that it] is very important to monitor [these patients] and to be vigilant in our search for cardiovascular complications and cardiovascular risk factors in this population,” he said.
Dr. Pugnet and his colleagues conducted a retrospective study of 125 patients with AAV who were diagnosed in a teaching hospital between 1981 and 2015. He compared cardiovascular outcomes and mortality between this cohort and two French regional registries: the Midi-Pyrénées County Mortality and Acute Myocardial Infarction Registry and the Dijon Stroke Registry. Outcomes were the date of first acute myocardial infarction, date of first stroke, and date of death; the mean follow-up was about 90 months.
Of the 125 patients with AAV, 99 had granulomatosis with polyangiitis, and 26 had microscopic polyangiitis. Preexisting cardiovascular disease was present in 23. Patients were a mean of 61 years old. Hypertension, peripheral artery disease, and coronary artery disease were all more common among those with cardiovascular disease. These patients were also more likely to smoke.
Over the follow-up period, there were 10 acute myocardial infarctions for an incidence of 8.5 per 1,000 person-years. The MI incidence in the Midi-Pyrénées registry was 2.2 per 1,000 person-years, which was a significant difference in an unadjusted analysis. But after adjusting for age, AAV patients were not significantly more likely to experience a heart attack than were those in the registry.
There were nine strokes during the follow-up period for an incidence of 10.2 per 1,000 person-years. After adjusting for age, this was more than three times higher than the rate of 1.9 per 1,000 person-year in the Dijon Stroke Registry – a significant difference.
A total of 22 AAV patients died during the follow-up period, translating to a mortality of 22.5 per 1,000 person-years. Mortality in the stroke registry was 1.9 per 1,000 person-years. An age-adjusted analysis found that AAV patients were about 1.6 times more likely to die than were those in the Midi-Pyrénées registry.
A multivariate regression analysis identified some factors that were independently associated with the outcomes. Smoking almost quadrupled the risk of having any cardiovascular event (hazard ratio, 3.7), and having had a plasma exchange tripled it (HR, 2.9). Smoking and a history of coronary artery disease were significant risk factors for myocardial infarction (HRs of 8.8 and 10.3, respectively). Dr. Pugnet and his associates didn’t find any significant independent risk factors for stroke. Age was not independently associated with any of the outcomes.
Dr. Pugnet reported receiving travel support from AbbVie and Actelion, fees for serving on an advisory board from Grifols, and lecture fees from AbbVie.
[email protected]
On Twitter @alz_gal
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: AAV patients were twice as likely as those without the vasculitis to experience a stroke over 7.5 years.
Data source: A retrospective comparison of 125 AAV patients and patients from two French regional registries: the Midi-Pyrénées County Mortality and Acute Myocardial Infarction Registry and the Dijon Stroke Registry.
Disclosures: Dr. Pugnet reported receiving travel support from AbbVie and Actelion, fees for serving on an advisory board from Grifols, and lecture fees from AbbVie.