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Malpractice: Communication and compensation program helps to minimize lawsuits
Communication and resolution programs at four Massachusetts medical centers helped resolve adverse medical events without increasing lawsuits or leading to excessive payouts to patients, according to Michelle M. Mello, PhD, and her colleagues.
They evaluated a communication and resolution program (CRP) model known as CARe (Communication, Apology, and Resolution) implemented at Beth Israel Deaconess Medical Center in Boston and Baystate Medical Center in Springfield, Mass., and at two of each center’s community hospitals. As part of the CARe model, hospital staff and insurers communicate with patients when adverse events occur, investigate and explain what happened, and, when appropriate, apologize and offer compensation.
Of 989 total events studied, 929 (90%) entered the program because an adverse event that allegedly exceeded the severity threshold was reported and 60 (6%) entered CARe because a prelitigation notice or claim was received, said Dr. Mello, professor of law and health research and policy at Stanford (Calif.) University.
Few events that entered the CARe process met the criteria for compensation. The standard of care was violated in 26% of cases where a determination could be reached. No determination could be reached in 59 cases, 9 cases were pending at the close of data collection, and 5 were referred directly to the insurer. Of the 241 cases involving standard-of-care violations, 55% were potentially eligible for compensation because they involved significant harm. After further review, monetary compensation was offered in 43 cases and paid in 40 cases by August 2016, with $75,000 as the median payment (Health Aff. 2017 Oct 2;36[10]:1795-1803).
As of August 2016, 5% of the 929 adverse events led to claims or lawsuits. Insurers deemed 14 of the 47 events that ultimately resulted in legal action ineligible for compensation because of a lack of negligence or lack of harm. They deemed 22 of the cases compensable, offered compensation in all of them, and had settled 20 by August 2016.
During the CARe process, patient safety improvements were frequently identified and improvements made, the investigators said. Of 132 cases in which review progressed far enough for patient safety questions to have been answered, 41% of the incidents gave rise to a safety improvement action. Actions included sharing investigation findings with clinical staff members, clinical staff educational efforts, policy changes, safety alerts sent to staff members, input into the quality improvement system for further analysis, new process flow diagrams, and human factor engineering analysis, among others.
Investigators also surveyed clinicians on their satisfaction with the CARe program. Of 162 clinicians (124 physicians), nearly 40% were either not very or not at all familiar with the program. More than two-thirds (69%) of those who felt well informed about the program gave strongly positive ratings and 10% gave a negative rating to the program. The most commonly suggested improvement to CARe was to improve communication with clinicians.
[email protected]
On Twitter @legal_med
Communication and resolution programs at four Massachusetts medical centers helped resolve adverse medical events without increasing lawsuits or leading to excessive payouts to patients, according to Michelle M. Mello, PhD, and her colleagues.
They evaluated a communication and resolution program (CRP) model known as CARe (Communication, Apology, and Resolution) implemented at Beth Israel Deaconess Medical Center in Boston and Baystate Medical Center in Springfield, Mass., and at two of each center’s community hospitals. As part of the CARe model, hospital staff and insurers communicate with patients when adverse events occur, investigate and explain what happened, and, when appropriate, apologize and offer compensation.
Of 989 total events studied, 929 (90%) entered the program because an adverse event that allegedly exceeded the severity threshold was reported and 60 (6%) entered CARe because a prelitigation notice or claim was received, said Dr. Mello, professor of law and health research and policy at Stanford (Calif.) University.
Few events that entered the CARe process met the criteria for compensation. The standard of care was violated in 26% of cases where a determination could be reached. No determination could be reached in 59 cases, 9 cases were pending at the close of data collection, and 5 were referred directly to the insurer. Of the 241 cases involving standard-of-care violations, 55% were potentially eligible for compensation because they involved significant harm. After further review, monetary compensation was offered in 43 cases and paid in 40 cases by August 2016, with $75,000 as the median payment (Health Aff. 2017 Oct 2;36[10]:1795-1803).
As of August 2016, 5% of the 929 adverse events led to claims or lawsuits. Insurers deemed 14 of the 47 events that ultimately resulted in legal action ineligible for compensation because of a lack of negligence or lack of harm. They deemed 22 of the cases compensable, offered compensation in all of them, and had settled 20 by August 2016.
During the CARe process, patient safety improvements were frequently identified and improvements made, the investigators said. Of 132 cases in which review progressed far enough for patient safety questions to have been answered, 41% of the incidents gave rise to a safety improvement action. Actions included sharing investigation findings with clinical staff members, clinical staff educational efforts, policy changes, safety alerts sent to staff members, input into the quality improvement system for further analysis, new process flow diagrams, and human factor engineering analysis, among others.
Investigators also surveyed clinicians on their satisfaction with the CARe program. Of 162 clinicians (124 physicians), nearly 40% were either not very or not at all familiar with the program. More than two-thirds (69%) of those who felt well informed about the program gave strongly positive ratings and 10% gave a negative rating to the program. The most commonly suggested improvement to CARe was to improve communication with clinicians.
[email protected]
On Twitter @legal_med
Communication and resolution programs at four Massachusetts medical centers helped resolve adverse medical events without increasing lawsuits or leading to excessive payouts to patients, according to Michelle M. Mello, PhD, and her colleagues.
They evaluated a communication and resolution program (CRP) model known as CARe (Communication, Apology, and Resolution) implemented at Beth Israel Deaconess Medical Center in Boston and Baystate Medical Center in Springfield, Mass., and at two of each center’s community hospitals. As part of the CARe model, hospital staff and insurers communicate with patients when adverse events occur, investigate and explain what happened, and, when appropriate, apologize and offer compensation.
Of 989 total events studied, 929 (90%) entered the program because an adverse event that allegedly exceeded the severity threshold was reported and 60 (6%) entered CARe because a prelitigation notice or claim was received, said Dr. Mello, professor of law and health research and policy at Stanford (Calif.) University.
Few events that entered the CARe process met the criteria for compensation. The standard of care was violated in 26% of cases where a determination could be reached. No determination could be reached in 59 cases, 9 cases were pending at the close of data collection, and 5 were referred directly to the insurer. Of the 241 cases involving standard-of-care violations, 55% were potentially eligible for compensation because they involved significant harm. After further review, monetary compensation was offered in 43 cases and paid in 40 cases by August 2016, with $75,000 as the median payment (Health Aff. 2017 Oct 2;36[10]:1795-1803).
As of August 2016, 5% of the 929 adverse events led to claims or lawsuits. Insurers deemed 14 of the 47 events that ultimately resulted in legal action ineligible for compensation because of a lack of negligence or lack of harm. They deemed 22 of the cases compensable, offered compensation in all of them, and had settled 20 by August 2016.
During the CARe process, patient safety improvements were frequently identified and improvements made, the investigators said. Of 132 cases in which review progressed far enough for patient safety questions to have been answered, 41% of the incidents gave rise to a safety improvement action. Actions included sharing investigation findings with clinical staff members, clinical staff educational efforts, policy changes, safety alerts sent to staff members, input into the quality improvement system for further analysis, new process flow diagrams, and human factor engineering analysis, among others.
Investigators also surveyed clinicians on their satisfaction with the CARe program. Of 162 clinicians (124 physicians), nearly 40% were either not very or not at all familiar with the program. More than two-thirds (69%) of those who felt well informed about the program gave strongly positive ratings and 10% gave a negative rating to the program. The most commonly suggested improvement to CARe was to improve communication with clinicians.
[email protected]
On Twitter @legal_med
FROM HEALTH AFFAIRS
Key clinical point:
Major finding: Out of 989 events, monetary compensation was paid in 40 cases, with a $75,000 median payment.
Data source: Review of 989 adverse events at four Massachusetts hospitals.
Disclosures: The project was funded by Baystate Health Insurance Company, Blue Cross Blue Shield of Massachusetts, CRICO RMF, Coverys, Harvard Pilgrim Health Care, Massachusetts Medical Society, and Tufts Health Plan. The authors listed no relevant conflicts of interest.
Trump order allows end-around ACA rules
An executive order signed by President Donald J. Trump aims to expand health care coverage options, primarily for small businesses.
The order includes three key provisions.
First, it allows small businesses to band together to buy insurance collectively for their workers and allows plans to be sold across state lines, in theory extending the buying power that comes with a larger base of employees to smaller businesses.
Employers participating in association health plans “cannot exclude any employee from joining the plan and cannot develop premiums based on health condition,” according to a White House statement on the executive order.
Second, the executive order allows broader use of limited duration health insurance – short-term policies that are not intended to be comprehensive offerings and are not subject to Affordable Care Act coverage requirements.
These plans “typically feature broad provider networks and high coverage limits,” according to the White House statement. The plans are geared toward “people between jobs, people in counties with only a single insurer offering exchange plans, people with limited coverage networks, and people who missed the open enrollment period but still want insurance,” according to the executive order.
Association health plans and the short-term, limited duration insurance will not need to fully cover the ACA’s essential health benefits package; instead, they are intended to be alternatives to “expensive, mandate-laden [ACA] insurance,” according to the executive order.
Third, the order directs the secretaries of Health & Human Services, Treasury, and Labor to “explore how they can allow more businesses to use tax-free health reimbursement arrangements, or HRAs, to compensate their employees for their health care expenses,” according to the White House statement.
HRAs allow employers to cover select items, such as copayments, deductibles, and other items, that are not covered by the insurance plan offered to employees.
“With these actions, we are moving toward lower costs and more options in the health care market and taking crucial steps toward saving the American people from the nightmare of Obamacare,” President Trump said, adding that the White House will continue to put pressure on Congress to finish repeal and replace activities. He also said that Congress will be pursuing block grants, presumably for Medicaid, which he said he had the votes to accomplish.
The action taken today by the White House is already receiving pushback.
The American College of Physicians “has said repeatedly that any attempts by Congress to ‘repeal and replace’ the ACA must first do no harm to patients,” Susan Thompson Hingle, MD, chair of the American College of Physicians Board of Regents, said in a statement. “This executive order utterly fails that test.”
Under the association health plans “small employers would be allowed to purchase health plans that do not meet the ACA’s requirement to provide essential health benefits,” Dr. Hingle noted. “This means that plans would no longer have to cover medical patients needs; plans could choose not to cover pregnancy, maternity, and newborn care, or even chemotherapy. This would also mean that the ACA’s prohibition on annual and lifetime limits on coverage would no longer apply to any service an employer decides is not essential. These changes would be devastating for patients who need access to the ‘nonessential’ services, leaving them with potentially millions of dollars in out-of-pocket costs despite being insured.”
Association health plans also could further destabilize the individual market if healthy workers – who currently may have purchased coverage on the individual market – shifted to less comprehensive association health plans, leaving even fewer healthy individuals in the individual market. “Insurers will be forced to either leave the markets in droves or charge much higher premiums.”
The rules may not be able to provide the relief that President Trump has promised, according to Julius Hobson, a Washington-based health care lobbyist
“The changes that he is talking about are going to require departments and agencies to promulgate rules. They just simply can’t do that by fiat,” Mr. Hobson said in an interview. “I am not sure that we will see an immediate impact on the executive order. ... When you get down to the nitty-gritty of implementation, we could be a bit away from seeing anything that actually has impact.”
An executive order signed by President Donald J. Trump aims to expand health care coverage options, primarily for small businesses.
The order includes three key provisions.
First, it allows small businesses to band together to buy insurance collectively for their workers and allows plans to be sold across state lines, in theory extending the buying power that comes with a larger base of employees to smaller businesses.
Employers participating in association health plans “cannot exclude any employee from joining the plan and cannot develop premiums based on health condition,” according to a White House statement on the executive order.
Second, the executive order allows broader use of limited duration health insurance – short-term policies that are not intended to be comprehensive offerings and are not subject to Affordable Care Act coverage requirements.
These plans “typically feature broad provider networks and high coverage limits,” according to the White House statement. The plans are geared toward “people between jobs, people in counties with only a single insurer offering exchange plans, people with limited coverage networks, and people who missed the open enrollment period but still want insurance,” according to the executive order.
Association health plans and the short-term, limited duration insurance will not need to fully cover the ACA’s essential health benefits package; instead, they are intended to be alternatives to “expensive, mandate-laden [ACA] insurance,” according to the executive order.
Third, the order directs the secretaries of Health & Human Services, Treasury, and Labor to “explore how they can allow more businesses to use tax-free health reimbursement arrangements, or HRAs, to compensate their employees for their health care expenses,” according to the White House statement.
HRAs allow employers to cover select items, such as copayments, deductibles, and other items, that are not covered by the insurance plan offered to employees.
“With these actions, we are moving toward lower costs and more options in the health care market and taking crucial steps toward saving the American people from the nightmare of Obamacare,” President Trump said, adding that the White House will continue to put pressure on Congress to finish repeal and replace activities. He also said that Congress will be pursuing block grants, presumably for Medicaid, which he said he had the votes to accomplish.
The action taken today by the White House is already receiving pushback.
The American College of Physicians “has said repeatedly that any attempts by Congress to ‘repeal and replace’ the ACA must first do no harm to patients,” Susan Thompson Hingle, MD, chair of the American College of Physicians Board of Regents, said in a statement. “This executive order utterly fails that test.”
Under the association health plans “small employers would be allowed to purchase health plans that do not meet the ACA’s requirement to provide essential health benefits,” Dr. Hingle noted. “This means that plans would no longer have to cover medical patients needs; plans could choose not to cover pregnancy, maternity, and newborn care, or even chemotherapy. This would also mean that the ACA’s prohibition on annual and lifetime limits on coverage would no longer apply to any service an employer decides is not essential. These changes would be devastating for patients who need access to the ‘nonessential’ services, leaving them with potentially millions of dollars in out-of-pocket costs despite being insured.”
Association health plans also could further destabilize the individual market if healthy workers – who currently may have purchased coverage on the individual market – shifted to less comprehensive association health plans, leaving even fewer healthy individuals in the individual market. “Insurers will be forced to either leave the markets in droves or charge much higher premiums.”
The rules may not be able to provide the relief that President Trump has promised, according to Julius Hobson, a Washington-based health care lobbyist
“The changes that he is talking about are going to require departments and agencies to promulgate rules. They just simply can’t do that by fiat,” Mr. Hobson said in an interview. “I am not sure that we will see an immediate impact on the executive order. ... When you get down to the nitty-gritty of implementation, we could be a bit away from seeing anything that actually has impact.”
An executive order signed by President Donald J. Trump aims to expand health care coverage options, primarily for small businesses.
The order includes three key provisions.
First, it allows small businesses to band together to buy insurance collectively for their workers and allows plans to be sold across state lines, in theory extending the buying power that comes with a larger base of employees to smaller businesses.
Employers participating in association health plans “cannot exclude any employee from joining the plan and cannot develop premiums based on health condition,” according to a White House statement on the executive order.
Second, the executive order allows broader use of limited duration health insurance – short-term policies that are not intended to be comprehensive offerings and are not subject to Affordable Care Act coverage requirements.
These plans “typically feature broad provider networks and high coverage limits,” according to the White House statement. The plans are geared toward “people between jobs, people in counties with only a single insurer offering exchange plans, people with limited coverage networks, and people who missed the open enrollment period but still want insurance,” according to the executive order.
Association health plans and the short-term, limited duration insurance will not need to fully cover the ACA’s essential health benefits package; instead, they are intended to be alternatives to “expensive, mandate-laden [ACA] insurance,” according to the executive order.
Third, the order directs the secretaries of Health & Human Services, Treasury, and Labor to “explore how they can allow more businesses to use tax-free health reimbursement arrangements, or HRAs, to compensate their employees for their health care expenses,” according to the White House statement.
HRAs allow employers to cover select items, such as copayments, deductibles, and other items, that are not covered by the insurance plan offered to employees.
“With these actions, we are moving toward lower costs and more options in the health care market and taking crucial steps toward saving the American people from the nightmare of Obamacare,” President Trump said, adding that the White House will continue to put pressure on Congress to finish repeal and replace activities. He also said that Congress will be pursuing block grants, presumably for Medicaid, which he said he had the votes to accomplish.
The action taken today by the White House is already receiving pushback.
The American College of Physicians “has said repeatedly that any attempts by Congress to ‘repeal and replace’ the ACA must first do no harm to patients,” Susan Thompson Hingle, MD, chair of the American College of Physicians Board of Regents, said in a statement. “This executive order utterly fails that test.”
Under the association health plans “small employers would be allowed to purchase health plans that do not meet the ACA’s requirement to provide essential health benefits,” Dr. Hingle noted. “This means that plans would no longer have to cover medical patients needs; plans could choose not to cover pregnancy, maternity, and newborn care, or even chemotherapy. This would also mean that the ACA’s prohibition on annual and lifetime limits on coverage would no longer apply to any service an employer decides is not essential. These changes would be devastating for patients who need access to the ‘nonessential’ services, leaving them with potentially millions of dollars in out-of-pocket costs despite being insured.”
Association health plans also could further destabilize the individual market if healthy workers – who currently may have purchased coverage on the individual market – shifted to less comprehensive association health plans, leaving even fewer healthy individuals in the individual market. “Insurers will be forced to either leave the markets in droves or charge much higher premiums.”
The rules may not be able to provide the relief that President Trump has promised, according to Julius Hobson, a Washington-based health care lobbyist
“The changes that he is talking about are going to require departments and agencies to promulgate rules. They just simply can’t do that by fiat,” Mr. Hobson said in an interview. “I am not sure that we will see an immediate impact on the executive order. ... When you get down to the nitty-gritty of implementation, we could be a bit away from seeing anything that actually has impact.”
MedPAC calls for MIPS repeal
WASHINGTON – In a rare display of a near-immediate consensus, the Medicare Payment Advisory Commission agreed that the Merit-Based Incentive Payment System track of the new Quality Payment Program should be scrapped, although commission members are not yet ready to endorse a replacement plan.
MedPAC staff presented its idea of “repeal and replace” less then 10 months into the first reporting year, with staff member David V. Glass noting during an Oct. 6 meeting that “MIPS will not achieve the goal of identifying and rewarding high-value clinicians.”
“Our most basic concern is that measures used in MIPS have not been proven to be associated with high-value care,” Mr. Glass said. “Many of the MIPS quality measures are process measures, assessing only the care a provider delivers within their four walls.”
MedPAC staff proposed a replacement option affecting all clinicians who are not a part of an advanced Alternative Payment Model program. Under their proposal, Medicare would withhold 2% of each clinician’s Medicare payments. Clinicians could earn back that 2% by joining a large reporting entity (either as part of a formal business structure or something like a virtual group); they could elect to join an advanced APM, earning back the 2% and possibly bonus payments; or they could do nothing and lose the 2%.
Measurements in the proposed value program would be similar to those employed by advanced APMs in that they would be focused on population-based measures assessing clinical quality, patient experience, and value. Potential measures would address avoidable admissions/emergency department visits, mortality, readmissions, ability to obtain care, ability to communicate with clinicians, spending per beneficiary, resource use, and rates of low-value care use. Measures would be calculated based on claims.
MedPAC commissioners were nearly unanimous in their agreement to the idea of repealing MIPS but were not ready to sign off on the proposed replacement.
“I’m really concerned about the burden on physicians, and I’m concerned about some of the outlandish potential rewards for groups under MIPS that can really dissuade them from investing and moving into APMs,” commission member Paul B. Ginsburg, PhD, senior fellow in economic studies at the Brookings Institution said.
“I think we really have to get rid of MIPS and either replace it with this system, which I think has a lot of merit, or just get rid of it,” said commission member Jack Hoadley, PhD, of Georgetown University in Washington, suggesting MIPS would be “even worse” than the old Sustainable Growth Rate formula over time. It is “clear to me that MIPS is not going to ... get us toward high-value care, it is not going to make clinicians’ lives better, it is not going to make patients’ lives better, and there is a lot of money at stake.”
Commission member Dana Gelb Safran, ScD, chief performance measurement and improvement officer at Blue Cross Blue Shield of Massachusetts said she did not believe that there would be any value being gained in return for the money given to clinicians who participate in MIPS.
Not everyone was on board with the proposed replacement.
“I am very much in favor of repealing MIPS, but I don’t get the sense that we’ve gotten the replacement model quite right yet” because the proposed system does not do enough to get physicians into advanced APMs, commission member Craig Samitt, MD, chief clinical officer at Anthem, said. “So if a replacement is a voluntary model that would allow us to keep practicing health care the way we’ve been practicing, then that replacement is not a good replacement.”
The American Medical Association declined to evaluate the proposal that was laid forth by staff.
“The AMA welcomes ideas on how to improve Medicare physician payment policies,” AMA President David O. Barbe said in a statement. “We understand that MedPAC’s proposals are a work in progress, so it’s too early to render any judgment.”
Dr. Barbe noted that the AMA recommends that physicians participate in MIPS, even if it is at the lowest level simply to avoid any penalty and continue investing in the infrastructure to participate. The AMA, AGA, and other medical societies also are asking CMS to allow those who are exempt from MIPS participation to be able to opt into the program.
The American Medical Group Association (AMGA), a trade organization representing multispecialty medical groups, however, has criticized the move by CMS to increase the number of clinicians who are exempt from MIPS.
Under the proposed expansion – which would approximately double the number of clinicians who are MIPS exempt – “MIPS no longer provides really any incentive to get to value and in fact it’s a disincentive,” said Chet Speed, AMGA vice president of public policy. “That is one of the realities that MedPAC was dealing with.”
Mr. Speed emphasized that AMGA has not altered its policy on MIPS, which it wants to see enacted for all and has offered its own resources to help with the transition, but “if AMGA were to entertain a new position on MIPS, I think we probably would go with a more simple route, which is to just get rid of MIPS and repurpose the revenues that were in MIPS to APMs. ... We have not agreed upon that policy but that has been discussed internally.”
He added that “AMGA’s membership does look at MIPS as a tool that has really devolved from a value mechanism to a compliance exercise and nothing more.”
As to whether health care provider associations would come together and support the repeal of MIPS, Mr. Speed was hesitant to predict that, even though many have reservations about it, noting that it could be because the broadening of exclusions, which the AMA and most other associations support, effectively remove a lot of their membership from having to participate anyway, leaving the bigger groups such as Mayo, the Cleveland Clinic and Intermountain Healthcare to fight over a much smaller pot of bonus payments, significantly limiting the returns on investments made to be ready for the MIPS transition.
WASHINGTON – In a rare display of a near-immediate consensus, the Medicare Payment Advisory Commission agreed that the Merit-Based Incentive Payment System track of the new Quality Payment Program should be scrapped, although commission members are not yet ready to endorse a replacement plan.
MedPAC staff presented its idea of “repeal and replace” less then 10 months into the first reporting year, with staff member David V. Glass noting during an Oct. 6 meeting that “MIPS will not achieve the goal of identifying and rewarding high-value clinicians.”
“Our most basic concern is that measures used in MIPS have not been proven to be associated with high-value care,” Mr. Glass said. “Many of the MIPS quality measures are process measures, assessing only the care a provider delivers within their four walls.”
MedPAC staff proposed a replacement option affecting all clinicians who are not a part of an advanced Alternative Payment Model program. Under their proposal, Medicare would withhold 2% of each clinician’s Medicare payments. Clinicians could earn back that 2% by joining a large reporting entity (either as part of a formal business structure or something like a virtual group); they could elect to join an advanced APM, earning back the 2% and possibly bonus payments; or they could do nothing and lose the 2%.
Measurements in the proposed value program would be similar to those employed by advanced APMs in that they would be focused on population-based measures assessing clinical quality, patient experience, and value. Potential measures would address avoidable admissions/emergency department visits, mortality, readmissions, ability to obtain care, ability to communicate with clinicians, spending per beneficiary, resource use, and rates of low-value care use. Measures would be calculated based on claims.
MedPAC commissioners were nearly unanimous in their agreement to the idea of repealing MIPS but were not ready to sign off on the proposed replacement.
“I’m really concerned about the burden on physicians, and I’m concerned about some of the outlandish potential rewards for groups under MIPS that can really dissuade them from investing and moving into APMs,” commission member Paul B. Ginsburg, PhD, senior fellow in economic studies at the Brookings Institution said.
“I think we really have to get rid of MIPS and either replace it with this system, which I think has a lot of merit, or just get rid of it,” said commission member Jack Hoadley, PhD, of Georgetown University in Washington, suggesting MIPS would be “even worse” than the old Sustainable Growth Rate formula over time. It is “clear to me that MIPS is not going to ... get us toward high-value care, it is not going to make clinicians’ lives better, it is not going to make patients’ lives better, and there is a lot of money at stake.”
Commission member Dana Gelb Safran, ScD, chief performance measurement and improvement officer at Blue Cross Blue Shield of Massachusetts said she did not believe that there would be any value being gained in return for the money given to clinicians who participate in MIPS.
Not everyone was on board with the proposed replacement.
“I am very much in favor of repealing MIPS, but I don’t get the sense that we’ve gotten the replacement model quite right yet” because the proposed system does not do enough to get physicians into advanced APMs, commission member Craig Samitt, MD, chief clinical officer at Anthem, said. “So if a replacement is a voluntary model that would allow us to keep practicing health care the way we’ve been practicing, then that replacement is not a good replacement.”
The American Medical Association declined to evaluate the proposal that was laid forth by staff.
“The AMA welcomes ideas on how to improve Medicare physician payment policies,” AMA President David O. Barbe said in a statement. “We understand that MedPAC’s proposals are a work in progress, so it’s too early to render any judgment.”
Dr. Barbe noted that the AMA recommends that physicians participate in MIPS, even if it is at the lowest level simply to avoid any penalty and continue investing in the infrastructure to participate. The AMA, AGA, and other medical societies also are asking CMS to allow those who are exempt from MIPS participation to be able to opt into the program.
The American Medical Group Association (AMGA), a trade organization representing multispecialty medical groups, however, has criticized the move by CMS to increase the number of clinicians who are exempt from MIPS.
Under the proposed expansion – which would approximately double the number of clinicians who are MIPS exempt – “MIPS no longer provides really any incentive to get to value and in fact it’s a disincentive,” said Chet Speed, AMGA vice president of public policy. “That is one of the realities that MedPAC was dealing with.”
Mr. Speed emphasized that AMGA has not altered its policy on MIPS, which it wants to see enacted for all and has offered its own resources to help with the transition, but “if AMGA were to entertain a new position on MIPS, I think we probably would go with a more simple route, which is to just get rid of MIPS and repurpose the revenues that were in MIPS to APMs. ... We have not agreed upon that policy but that has been discussed internally.”
He added that “AMGA’s membership does look at MIPS as a tool that has really devolved from a value mechanism to a compliance exercise and nothing more.”
As to whether health care provider associations would come together and support the repeal of MIPS, Mr. Speed was hesitant to predict that, even though many have reservations about it, noting that it could be because the broadening of exclusions, which the AMA and most other associations support, effectively remove a lot of their membership from having to participate anyway, leaving the bigger groups such as Mayo, the Cleveland Clinic and Intermountain Healthcare to fight over a much smaller pot of bonus payments, significantly limiting the returns on investments made to be ready for the MIPS transition.
WASHINGTON – In a rare display of a near-immediate consensus, the Medicare Payment Advisory Commission agreed that the Merit-Based Incentive Payment System track of the new Quality Payment Program should be scrapped, although commission members are not yet ready to endorse a replacement plan.
MedPAC staff presented its idea of “repeal and replace” less then 10 months into the first reporting year, with staff member David V. Glass noting during an Oct. 6 meeting that “MIPS will not achieve the goal of identifying and rewarding high-value clinicians.”
“Our most basic concern is that measures used in MIPS have not been proven to be associated with high-value care,” Mr. Glass said. “Many of the MIPS quality measures are process measures, assessing only the care a provider delivers within their four walls.”
MedPAC staff proposed a replacement option affecting all clinicians who are not a part of an advanced Alternative Payment Model program. Under their proposal, Medicare would withhold 2% of each clinician’s Medicare payments. Clinicians could earn back that 2% by joining a large reporting entity (either as part of a formal business structure or something like a virtual group); they could elect to join an advanced APM, earning back the 2% and possibly bonus payments; or they could do nothing and lose the 2%.
Measurements in the proposed value program would be similar to those employed by advanced APMs in that they would be focused on population-based measures assessing clinical quality, patient experience, and value. Potential measures would address avoidable admissions/emergency department visits, mortality, readmissions, ability to obtain care, ability to communicate with clinicians, spending per beneficiary, resource use, and rates of low-value care use. Measures would be calculated based on claims.
MedPAC commissioners were nearly unanimous in their agreement to the idea of repealing MIPS but were not ready to sign off on the proposed replacement.
“I’m really concerned about the burden on physicians, and I’m concerned about some of the outlandish potential rewards for groups under MIPS that can really dissuade them from investing and moving into APMs,” commission member Paul B. Ginsburg, PhD, senior fellow in economic studies at the Brookings Institution said.
“I think we really have to get rid of MIPS and either replace it with this system, which I think has a lot of merit, or just get rid of it,” said commission member Jack Hoadley, PhD, of Georgetown University in Washington, suggesting MIPS would be “even worse” than the old Sustainable Growth Rate formula over time. It is “clear to me that MIPS is not going to ... get us toward high-value care, it is not going to make clinicians’ lives better, it is not going to make patients’ lives better, and there is a lot of money at stake.”
Commission member Dana Gelb Safran, ScD, chief performance measurement and improvement officer at Blue Cross Blue Shield of Massachusetts said she did not believe that there would be any value being gained in return for the money given to clinicians who participate in MIPS.
Not everyone was on board with the proposed replacement.
“I am very much in favor of repealing MIPS, but I don’t get the sense that we’ve gotten the replacement model quite right yet” because the proposed system does not do enough to get physicians into advanced APMs, commission member Craig Samitt, MD, chief clinical officer at Anthem, said. “So if a replacement is a voluntary model that would allow us to keep practicing health care the way we’ve been practicing, then that replacement is not a good replacement.”
The American Medical Association declined to evaluate the proposal that was laid forth by staff.
“The AMA welcomes ideas on how to improve Medicare physician payment policies,” AMA President David O. Barbe said in a statement. “We understand that MedPAC’s proposals are a work in progress, so it’s too early to render any judgment.”
Dr. Barbe noted that the AMA recommends that physicians participate in MIPS, even if it is at the lowest level simply to avoid any penalty and continue investing in the infrastructure to participate. The AMA, AGA, and other medical societies also are asking CMS to allow those who are exempt from MIPS participation to be able to opt into the program.
The American Medical Group Association (AMGA), a trade organization representing multispecialty medical groups, however, has criticized the move by CMS to increase the number of clinicians who are exempt from MIPS.
Under the proposed expansion – which would approximately double the number of clinicians who are MIPS exempt – “MIPS no longer provides really any incentive to get to value and in fact it’s a disincentive,” said Chet Speed, AMGA vice president of public policy. “That is one of the realities that MedPAC was dealing with.”
Mr. Speed emphasized that AMGA has not altered its policy on MIPS, which it wants to see enacted for all and has offered its own resources to help with the transition, but “if AMGA were to entertain a new position on MIPS, I think we probably would go with a more simple route, which is to just get rid of MIPS and repurpose the revenues that were in MIPS to APMs. ... We have not agreed upon that policy but that has been discussed internally.”
He added that “AMGA’s membership does look at MIPS as a tool that has really devolved from a value mechanism to a compliance exercise and nothing more.”
As to whether health care provider associations would come together and support the repeal of MIPS, Mr. Speed was hesitant to predict that, even though many have reservations about it, noting that it could be because the broadening of exclusions, which the AMA and most other associations support, effectively remove a lot of their membership from having to participate anyway, leaving the bigger groups such as Mayo, the Cleveland Clinic and Intermountain Healthcare to fight over a much smaller pot of bonus payments, significantly limiting the returns on investments made to be ready for the MIPS transition.
AT A MEDPAC MEETING
VIDEO: Intermittent furosemide during acute HFpEF favors kidneys
DALLAS – Patients with heart failure with preserved ejection fraction who were hospitalized for acute decompensation had a significantly smaller rise in serum creatinine when treated with intermittent, bolus doses of furosemide, compared with patients who received a continuous furosemide infusion in a single-center, randomized trial with 90 patients.
Intermittent furosemide also resulted in many fewer episodes of worsening renal function. In the trial, 12% of patients who received bolus furosemide doses developed worsening renal function during hospitalization compared with 36% of patients treated with a continuous furosemide infusion, Kavita Sharma, MD, said at the annual scientific meeting of the Heart Failure Society of America.
While acknowledging that this finding is preliminary because it was made in a relatively small, single-center study, “I’d be cautious about continuous infusion” in acute decompensated patients with heart failure with preserved ejection fraction (HFpEF); “bolus is preferred,” Dr. Sharma said in a video interview.
Results from the prior Diuretic Optimization Strategies Evaluation (DOSE) trial, published in 2011, had shown no significant difference in renal function in hospitalized heart failure patients randomized to receive either bolus or continuous furosemide, but that study largely enrolled patients with heart failure with reduced ejection fraction (HFrEF) (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“When patients with HFpEF are hospitalized with acute heart failure there is a high rate of kidney injury, that often results in slowing diuresis leading to longer hospital stays. With adjustment for changes in blood pressure and volume of diuresis we saw a fourfold increase in worsening renal failure [with continuous infusion], so you should think twice before using continuous dosing,” said Dr. Sharma, a heart failure cardiologist at Johns Hopkins Medicine in Baltimore.
She presented results from Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction (ROPA-DOP), which randomized 90 hospitalized heart failure patients with a left ventricular ejection fraction of at least 50% and an estimated glomerular filtration rate of more than 15 mL/min/1.73 m2. The enrolled patients averaged 66 years old, 61% were women, their average body mass index was 41 kg/m2, and their average estimated glomerular filtration rate was 58 mL/min/1.73 m2.
The study’s primary endpoint was percent change in creatinine during hospitalization, which rose by an average 5% in the patients who received intermittent bolus furosemide and by an average 16% in patient who received a continuous infusion, a statistically significant difference. In a regression analysis that controlled for between-group differences in patient’s age, sex, race, body mass index, smoking status, changes in systolic blood pressure, heart rate, fluid balance after 72 hours, and other variables, patients treated with continuous furosemide infusion averaged an 11% greater increase in serum creatinine, Dr. Sharma reported. After similar adjustments, the secondary endpoint rate of worsening renal function was more than four times more likely to occur in the patients on continuous infusion compared with those who received intermittent bolus treatment, she said.
A second aspect of the ROPA-DOP trial randomized the same patients to received either low dose (3 mcg/kg per min) dopamine or placebo during hospitalization. The results showed that low-dose dopamine had no significant impact on either change in creatinine levels or on the incidence of worsening renal function compared with placebo, though dopamine treatment did link with a nonsignificant trend toward somewhat greater diuresis. These results were consistent with prior findings in the Renal Optimization Strategies Evaluation (ROSE) trial (JAMA. 2013 Nov 18;310[23]:2533-43), which used a mixed population of patients with HFpEF or HFrEF but predominantly patients with HFrEF, Dr. Sharma noted.
“It was a neutral finding [for dopamine in ROPA-DOP], and while there was no harm from dopamine there was clearly no benefit,” she said. It is possible that HFpEF patients with right ventricular dysfunction secondary to pulmonary hypertension might benefit from low-dose dopamine, but this needs further study, Dr. Sharma said.
[email protected]
On Twitter @mitchelzoler
In the Diuretic Optimization Strategies Evaluation (DOSE) trial, we enrolled heart failure patients with a mix of reduced ejection fraction and preserved ejection fraction. The DOSE results showed no relationship between ejection fraction and the response to furosemide treatment by intermittent bolus or by continuous infusion in patients hospitalized with acute decompensated heart failure. The results also showed that continuous infusion was no better than intermittent bolus treatment, and following our report in 2011 (N Engl J Med. 2011 Mar 3;364[9]:797-805), many centers that had previously relied on continuous furosemide switched to use of bolus doses primarily because continuous infusion is much less convenient.
But it is important to keep in mind that trial results focus on averages and populations of patients. Anecdotally, we see some acute heart failure patients who seem to respond better to continuous infusion, and so some clinicians switch patients who do not respond well to bolus treatment to continuous infusion. In DOSE, we only tested the efficacy of the initial strategy; we have no evidence on whether or not changing the dosing strategy helps patients who do not respond adequately to an initial strategy of intermittent bolus doses.
G. Michael Felker, MD , professor of medicine at Duke University, Durham, N.C., made these comments in an interview. He has been a consultant to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, MyoKardia, Novartis, Stealth, and Trevena.
In the Diuretic Optimization Strategies Evaluation (DOSE) trial, we enrolled heart failure patients with a mix of reduced ejection fraction and preserved ejection fraction. The DOSE results showed no relationship between ejection fraction and the response to furosemide treatment by intermittent bolus or by continuous infusion in patients hospitalized with acute decompensated heart failure. The results also showed that continuous infusion was no better than intermittent bolus treatment, and following our report in 2011 (N Engl J Med. 2011 Mar 3;364[9]:797-805), many centers that had previously relied on continuous furosemide switched to use of bolus doses primarily because continuous infusion is much less convenient.
But it is important to keep in mind that trial results focus on averages and populations of patients. Anecdotally, we see some acute heart failure patients who seem to respond better to continuous infusion, and so some clinicians switch patients who do not respond well to bolus treatment to continuous infusion. In DOSE, we only tested the efficacy of the initial strategy; we have no evidence on whether or not changing the dosing strategy helps patients who do not respond adequately to an initial strategy of intermittent bolus doses.
G. Michael Felker, MD , professor of medicine at Duke University, Durham, N.C., made these comments in an interview. He has been a consultant to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, MyoKardia, Novartis, Stealth, and Trevena.
In the Diuretic Optimization Strategies Evaluation (DOSE) trial, we enrolled heart failure patients with a mix of reduced ejection fraction and preserved ejection fraction. The DOSE results showed no relationship between ejection fraction and the response to furosemide treatment by intermittent bolus or by continuous infusion in patients hospitalized with acute decompensated heart failure. The results also showed that continuous infusion was no better than intermittent bolus treatment, and following our report in 2011 (N Engl J Med. 2011 Mar 3;364[9]:797-805), many centers that had previously relied on continuous furosemide switched to use of bolus doses primarily because continuous infusion is much less convenient.
But it is important to keep in mind that trial results focus on averages and populations of patients. Anecdotally, we see some acute heart failure patients who seem to respond better to continuous infusion, and so some clinicians switch patients who do not respond well to bolus treatment to continuous infusion. In DOSE, we only tested the efficacy of the initial strategy; we have no evidence on whether or not changing the dosing strategy helps patients who do not respond adequately to an initial strategy of intermittent bolus doses.
G. Michael Felker, MD , professor of medicine at Duke University, Durham, N.C., made these comments in an interview. He has been a consultant to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, MyoKardia, Novartis, Stealth, and Trevena.
DALLAS – Patients with heart failure with preserved ejection fraction who were hospitalized for acute decompensation had a significantly smaller rise in serum creatinine when treated with intermittent, bolus doses of furosemide, compared with patients who received a continuous furosemide infusion in a single-center, randomized trial with 90 patients.
Intermittent furosemide also resulted in many fewer episodes of worsening renal function. In the trial, 12% of patients who received bolus furosemide doses developed worsening renal function during hospitalization compared with 36% of patients treated with a continuous furosemide infusion, Kavita Sharma, MD, said at the annual scientific meeting of the Heart Failure Society of America.
While acknowledging that this finding is preliminary because it was made in a relatively small, single-center study, “I’d be cautious about continuous infusion” in acute decompensated patients with heart failure with preserved ejection fraction (HFpEF); “bolus is preferred,” Dr. Sharma said in a video interview.
Results from the prior Diuretic Optimization Strategies Evaluation (DOSE) trial, published in 2011, had shown no significant difference in renal function in hospitalized heart failure patients randomized to receive either bolus or continuous furosemide, but that study largely enrolled patients with heart failure with reduced ejection fraction (HFrEF) (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“When patients with HFpEF are hospitalized with acute heart failure there is a high rate of kidney injury, that often results in slowing diuresis leading to longer hospital stays. With adjustment for changes in blood pressure and volume of diuresis we saw a fourfold increase in worsening renal failure [with continuous infusion], so you should think twice before using continuous dosing,” said Dr. Sharma, a heart failure cardiologist at Johns Hopkins Medicine in Baltimore.
She presented results from Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction (ROPA-DOP), which randomized 90 hospitalized heart failure patients with a left ventricular ejection fraction of at least 50% and an estimated glomerular filtration rate of more than 15 mL/min/1.73 m2. The enrolled patients averaged 66 years old, 61% were women, their average body mass index was 41 kg/m2, and their average estimated glomerular filtration rate was 58 mL/min/1.73 m2.
The study’s primary endpoint was percent change in creatinine during hospitalization, which rose by an average 5% in the patients who received intermittent bolus furosemide and by an average 16% in patient who received a continuous infusion, a statistically significant difference. In a regression analysis that controlled for between-group differences in patient’s age, sex, race, body mass index, smoking status, changes in systolic blood pressure, heart rate, fluid balance after 72 hours, and other variables, patients treated with continuous furosemide infusion averaged an 11% greater increase in serum creatinine, Dr. Sharma reported. After similar adjustments, the secondary endpoint rate of worsening renal function was more than four times more likely to occur in the patients on continuous infusion compared with those who received intermittent bolus treatment, she said.
A second aspect of the ROPA-DOP trial randomized the same patients to received either low dose (3 mcg/kg per min) dopamine or placebo during hospitalization. The results showed that low-dose dopamine had no significant impact on either change in creatinine levels or on the incidence of worsening renal function compared with placebo, though dopamine treatment did link with a nonsignificant trend toward somewhat greater diuresis. These results were consistent with prior findings in the Renal Optimization Strategies Evaluation (ROSE) trial (JAMA. 2013 Nov 18;310[23]:2533-43), which used a mixed population of patients with HFpEF or HFrEF but predominantly patients with HFrEF, Dr. Sharma noted.
“It was a neutral finding [for dopamine in ROPA-DOP], and while there was no harm from dopamine there was clearly no benefit,” she said. It is possible that HFpEF patients with right ventricular dysfunction secondary to pulmonary hypertension might benefit from low-dose dopamine, but this needs further study, Dr. Sharma said.
[email protected]
On Twitter @mitchelzoler
DALLAS – Patients with heart failure with preserved ejection fraction who were hospitalized for acute decompensation had a significantly smaller rise in serum creatinine when treated with intermittent, bolus doses of furosemide, compared with patients who received a continuous furosemide infusion in a single-center, randomized trial with 90 patients.
Intermittent furosemide also resulted in many fewer episodes of worsening renal function. In the trial, 12% of patients who received bolus furosemide doses developed worsening renal function during hospitalization compared with 36% of patients treated with a continuous furosemide infusion, Kavita Sharma, MD, said at the annual scientific meeting of the Heart Failure Society of America.
While acknowledging that this finding is preliminary because it was made in a relatively small, single-center study, “I’d be cautious about continuous infusion” in acute decompensated patients with heart failure with preserved ejection fraction (HFpEF); “bolus is preferred,” Dr. Sharma said in a video interview.
Results from the prior Diuretic Optimization Strategies Evaluation (DOSE) trial, published in 2011, had shown no significant difference in renal function in hospitalized heart failure patients randomized to receive either bolus or continuous furosemide, but that study largely enrolled patients with heart failure with reduced ejection fraction (HFrEF) (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“When patients with HFpEF are hospitalized with acute heart failure there is a high rate of kidney injury, that often results in slowing diuresis leading to longer hospital stays. With adjustment for changes in blood pressure and volume of diuresis we saw a fourfold increase in worsening renal failure [with continuous infusion], so you should think twice before using continuous dosing,” said Dr. Sharma, a heart failure cardiologist at Johns Hopkins Medicine in Baltimore.
She presented results from Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction (ROPA-DOP), which randomized 90 hospitalized heart failure patients with a left ventricular ejection fraction of at least 50% and an estimated glomerular filtration rate of more than 15 mL/min/1.73 m2. The enrolled patients averaged 66 years old, 61% were women, their average body mass index was 41 kg/m2, and their average estimated glomerular filtration rate was 58 mL/min/1.73 m2.
The study’s primary endpoint was percent change in creatinine during hospitalization, which rose by an average 5% in the patients who received intermittent bolus furosemide and by an average 16% in patient who received a continuous infusion, a statistically significant difference. In a regression analysis that controlled for between-group differences in patient’s age, sex, race, body mass index, smoking status, changes in systolic blood pressure, heart rate, fluid balance after 72 hours, and other variables, patients treated with continuous furosemide infusion averaged an 11% greater increase in serum creatinine, Dr. Sharma reported. After similar adjustments, the secondary endpoint rate of worsening renal function was more than four times more likely to occur in the patients on continuous infusion compared with those who received intermittent bolus treatment, she said.
A second aspect of the ROPA-DOP trial randomized the same patients to received either low dose (3 mcg/kg per min) dopamine or placebo during hospitalization. The results showed that low-dose dopamine had no significant impact on either change in creatinine levels or on the incidence of worsening renal function compared with placebo, though dopamine treatment did link with a nonsignificant trend toward somewhat greater diuresis. These results were consistent with prior findings in the Renal Optimization Strategies Evaluation (ROSE) trial (JAMA. 2013 Nov 18;310[23]:2533-43), which used a mixed population of patients with HFpEF or HFrEF but predominantly patients with HFrEF, Dr. Sharma noted.
“It was a neutral finding [for dopamine in ROPA-DOP], and while there was no harm from dopamine there was clearly no benefit,” she said. It is possible that HFpEF patients with right ventricular dysfunction secondary to pulmonary hypertension might benefit from low-dose dopamine, but this needs further study, Dr. Sharma said.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Serum creatinine rose by an average 5% with intermittent bolus furosemide and by 16% with continuous infusion.
Data source: ROPA-DOP, a single-center randomized trial with 90 patients.
Disclosures: Dr. Sharma had no disclosures.
Phrenic nerve stimulator shows heart failure benefits
DALLAS– Heart failure patients with central sleep apnea who received treatment with a transvenous phrenic nerve–stimulating device showed dramatic improvement in their global self-assessment, compared with control patients, in a subgroup analysis of 80 patients enrolled in the device’s pivotal trial.
Among 35 patients with heart failure enrolled in the remedē System pivotal trial and treated for 6 months with phrenic nerve stimulation, 57% reported that they had “markedly” or “moderately” improved, compared with a 9% rate for this self-rating among 44 control heart failure patients in the trial, a statistically significant difference, Lee R. Goldberg, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Further analysis focused on echocardiographic examinations after 12 months in 23 of the heart failure patients who entered the study with a left ventricular ejection fraction of 45% or less and received 12 months of phrenic nerve stimulation. The average LVEF rose in these patients from 30% at baseline to 35%, a statistically significant difference, and left ventricular end systolic volume fell by an average of almost 11 mL from baseline, a difference just short of statistical significance, findings Dr. Goldberg called “a little exciting.”
“It is very encouraging to see some evidence for ventricular remodeling,” commented Lynne W. Stevenson, MD, professor of medicine and a heart failure specialist at Vanderbilt University in Nashville, Tenn.
The FDA approved the use of this device for the treatment of moderate to severe central sleep apnea on Oct. 6. “I think we would use it” in heart failure patients with intolerable symptoms from central sleep apnea, Dr. Goldberg said in an interview during the meeting.
“There is a tight connection between sleep-disordered breathing, sleep apnea, heart failure, and cardiovascular disease, and we have been pretty aggressive in trying to treat the sleep apnea. Even if phrenic nerve stimulation just improves patients’ quality of life and is neutral for other outcomes,” it would be reasonable to offer it to patients, he said. “But many of us think there is a bigger connection that results in a therapeutic benefit [to heart failure patients] by treating their central sleep apnea.”
The pivotal trial enrolled a total of 151 patients with central sleep apnea at 31 centers in Germany, Poland, and the United States who were selected based on having an apnea-hypopnea index of at least 20 events per hour. All participants received a transvenous phrenic nerve–stimulator implant, and then randomization assigned 73 patients to have the device turned on for the first 6 months while 78 device recipients had their devices left off to serve as controls. The study’s primary efficacy endpoint was the percentage of patients having at least a 50% cut in their apnea-hypopnea index, which happened in 51% of evaluable patients in the active treatment arm and in 11% of the evaluable controls. The primary results were published last year (Lancet. 2016 Sep 3;388[10048]974-82).
“We hope this treatment will have the collateral effect of improving cardiovascular disease outcomes, but we don’t know that yet. The initial target will be patients with apnea-hypopnea episodes that affect their quality of life,” Dr. Goldberg said.
The apparent safety of this approach for treating central sleep apnea may relate to its mechanism of action, he suggested. The mortality-boosting effect of adaptive servo-ventilation may correlate with the positive pressure it creates in a patient’s chest that perhaps causes myocardial stress or hemodynamic problems. In contrast, phrenic nerve stimulation produces diaphragm motion that mimics normal breathing and creates negative chest pressure. “A lot of hypothesis generation needs to happen to better understand the underlying physiology,” Dr. Goldberg conceded.
At the end of the 6-month period that compared active treatment with control, the heart failure subgroup also showed statistically significant benefits from treatment for several sleep metrics, including apnea-hypopnea index, the central apnea index, and oxygen desaturation, and also for daytime sleepiness measured on the Epworth Sleepiness Scale. After 12 months on active treatment, patients also showed a significant improvement over baseline in their score on the Minnesota Living With Heart Failure Questionnaire, Dr. Goldberg reported.
The trial was sponsored by Respicardia, the company developing the remedē System. Dr. Goldberg has been a consultant to and has received research funding from Respicardia. Dr. Stevenson had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
DALLAS– Heart failure patients with central sleep apnea who received treatment with a transvenous phrenic nerve–stimulating device showed dramatic improvement in their global self-assessment, compared with control patients, in a subgroup analysis of 80 patients enrolled in the device’s pivotal trial.
Among 35 patients with heart failure enrolled in the remedē System pivotal trial and treated for 6 months with phrenic nerve stimulation, 57% reported that they had “markedly” or “moderately” improved, compared with a 9% rate for this self-rating among 44 control heart failure patients in the trial, a statistically significant difference, Lee R. Goldberg, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Further analysis focused on echocardiographic examinations after 12 months in 23 of the heart failure patients who entered the study with a left ventricular ejection fraction of 45% or less and received 12 months of phrenic nerve stimulation. The average LVEF rose in these patients from 30% at baseline to 35%, a statistically significant difference, and left ventricular end systolic volume fell by an average of almost 11 mL from baseline, a difference just short of statistical significance, findings Dr. Goldberg called “a little exciting.”
“It is very encouraging to see some evidence for ventricular remodeling,” commented Lynne W. Stevenson, MD, professor of medicine and a heart failure specialist at Vanderbilt University in Nashville, Tenn.
The FDA approved the use of this device for the treatment of moderate to severe central sleep apnea on Oct. 6. “I think we would use it” in heart failure patients with intolerable symptoms from central sleep apnea, Dr. Goldberg said in an interview during the meeting.
“There is a tight connection between sleep-disordered breathing, sleep apnea, heart failure, and cardiovascular disease, and we have been pretty aggressive in trying to treat the sleep apnea. Even if phrenic nerve stimulation just improves patients’ quality of life and is neutral for other outcomes,” it would be reasonable to offer it to patients, he said. “But many of us think there is a bigger connection that results in a therapeutic benefit [to heart failure patients] by treating their central sleep apnea.”
The pivotal trial enrolled a total of 151 patients with central sleep apnea at 31 centers in Germany, Poland, and the United States who were selected based on having an apnea-hypopnea index of at least 20 events per hour. All participants received a transvenous phrenic nerve–stimulator implant, and then randomization assigned 73 patients to have the device turned on for the first 6 months while 78 device recipients had their devices left off to serve as controls. The study’s primary efficacy endpoint was the percentage of patients having at least a 50% cut in their apnea-hypopnea index, which happened in 51% of evaluable patients in the active treatment arm and in 11% of the evaluable controls. The primary results were published last year (Lancet. 2016 Sep 3;388[10048]974-82).
“We hope this treatment will have the collateral effect of improving cardiovascular disease outcomes, but we don’t know that yet. The initial target will be patients with apnea-hypopnea episodes that affect their quality of life,” Dr. Goldberg said.
The apparent safety of this approach for treating central sleep apnea may relate to its mechanism of action, he suggested. The mortality-boosting effect of adaptive servo-ventilation may correlate with the positive pressure it creates in a patient’s chest that perhaps causes myocardial stress or hemodynamic problems. In contrast, phrenic nerve stimulation produces diaphragm motion that mimics normal breathing and creates negative chest pressure. “A lot of hypothesis generation needs to happen to better understand the underlying physiology,” Dr. Goldberg conceded.
At the end of the 6-month period that compared active treatment with control, the heart failure subgroup also showed statistically significant benefits from treatment for several sleep metrics, including apnea-hypopnea index, the central apnea index, and oxygen desaturation, and also for daytime sleepiness measured on the Epworth Sleepiness Scale. After 12 months on active treatment, patients also showed a significant improvement over baseline in their score on the Minnesota Living With Heart Failure Questionnaire, Dr. Goldberg reported.
The trial was sponsored by Respicardia, the company developing the remedē System. Dr. Goldberg has been a consultant to and has received research funding from Respicardia. Dr. Stevenson had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
DALLAS– Heart failure patients with central sleep apnea who received treatment with a transvenous phrenic nerve–stimulating device showed dramatic improvement in their global self-assessment, compared with control patients, in a subgroup analysis of 80 patients enrolled in the device’s pivotal trial.
Among 35 patients with heart failure enrolled in the remedē System pivotal trial and treated for 6 months with phrenic nerve stimulation, 57% reported that they had “markedly” or “moderately” improved, compared with a 9% rate for this self-rating among 44 control heart failure patients in the trial, a statistically significant difference, Lee R. Goldberg, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Further analysis focused on echocardiographic examinations after 12 months in 23 of the heart failure patients who entered the study with a left ventricular ejection fraction of 45% or less and received 12 months of phrenic nerve stimulation. The average LVEF rose in these patients from 30% at baseline to 35%, a statistically significant difference, and left ventricular end systolic volume fell by an average of almost 11 mL from baseline, a difference just short of statistical significance, findings Dr. Goldberg called “a little exciting.”
“It is very encouraging to see some evidence for ventricular remodeling,” commented Lynne W. Stevenson, MD, professor of medicine and a heart failure specialist at Vanderbilt University in Nashville, Tenn.
The FDA approved the use of this device for the treatment of moderate to severe central sleep apnea on Oct. 6. “I think we would use it” in heart failure patients with intolerable symptoms from central sleep apnea, Dr. Goldberg said in an interview during the meeting.
“There is a tight connection between sleep-disordered breathing, sleep apnea, heart failure, and cardiovascular disease, and we have been pretty aggressive in trying to treat the sleep apnea. Even if phrenic nerve stimulation just improves patients’ quality of life and is neutral for other outcomes,” it would be reasonable to offer it to patients, he said. “But many of us think there is a bigger connection that results in a therapeutic benefit [to heart failure patients] by treating their central sleep apnea.”
The pivotal trial enrolled a total of 151 patients with central sleep apnea at 31 centers in Germany, Poland, and the United States who were selected based on having an apnea-hypopnea index of at least 20 events per hour. All participants received a transvenous phrenic nerve–stimulator implant, and then randomization assigned 73 patients to have the device turned on for the first 6 months while 78 device recipients had their devices left off to serve as controls. The study’s primary efficacy endpoint was the percentage of patients having at least a 50% cut in their apnea-hypopnea index, which happened in 51% of evaluable patients in the active treatment arm and in 11% of the evaluable controls. The primary results were published last year (Lancet. 2016 Sep 3;388[10048]974-82).
“We hope this treatment will have the collateral effect of improving cardiovascular disease outcomes, but we don’t know that yet. The initial target will be patients with apnea-hypopnea episodes that affect their quality of life,” Dr. Goldberg said.
The apparent safety of this approach for treating central sleep apnea may relate to its mechanism of action, he suggested. The mortality-boosting effect of adaptive servo-ventilation may correlate with the positive pressure it creates in a patient’s chest that perhaps causes myocardial stress or hemodynamic problems. In contrast, phrenic nerve stimulation produces diaphragm motion that mimics normal breathing and creates negative chest pressure. “A lot of hypothesis generation needs to happen to better understand the underlying physiology,” Dr. Goldberg conceded.
At the end of the 6-month period that compared active treatment with control, the heart failure subgroup also showed statistically significant benefits from treatment for several sleep metrics, including apnea-hypopnea index, the central apnea index, and oxygen desaturation, and also for daytime sleepiness measured on the Epworth Sleepiness Scale. After 12 months on active treatment, patients also showed a significant improvement over baseline in their score on the Minnesota Living With Heart Failure Questionnaire, Dr. Goldberg reported.
The trial was sponsored by Respicardia, the company developing the remedē System. Dr. Goldberg has been a consultant to and has received research funding from Respicardia. Dr. Stevenson had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Patient-reported global assessment improved markedly or moderately in 57% of treated patients and in 9% of controls.
Data source: Subgroup analysis of the remedē System pivotal trial.
Disclosures: The trial was sponsored by Respicardia, the company developing the remedē System. Dr. Goldberg has been a consultant to and has received research funding from Respicardia. Dr. Stevenson had no relevant disclosures.
Cardio-oncology booms but awareness lags
Cardio-oncology is expanding, fed by a steadily increasing population of cancer survivors at elevated risk for a range of cardiovascular diseases and complications because of the anticancer treatments they received. Cardio-oncology’s quick growth has also been driven by the rapidly expanding universe of cancer treatments with direct or indirect adverse effects on a diverse range of cardiovascular functions.
During the past year, the field’s rapid evolution has featured the first formal diagnostic and care standards in two iterations: A position paper on the cardiovascular toxicities of cancer treatment from the European Society of Cardiology (ESC), released in August 2016 (Eur Heart J. 2016 Sept 21;37[36]:2766-801); and a guideline for preventing and monitoring cardiac dysfunction in adult cancer survivors, issued last December by the American Society of Clinical Oncology (ASCO) and endorsed by the American Heart Association (J Clin Oncol. 2017 March 10;35[8]:893-913), but notably not endorsed by the American College of Cardiology, despite having an ACC representative on the guideline panel. In 2015, the ACC started a Cardio-Oncology Section, one of 20 special-interest sections it maintains, and by mid-2017 the section had some 500 members.
“I’ve had recent conversations with cardiologists who said ‘I’m not sure what cardio-oncology is,’ ” said Tomas G. Neilan, MD, director of the cardio-oncology program at Massachusetts General Hospital in Boston.
More than just heart failure
A few decades ago, in the primordial days of cardio-oncology, the concept of cardiovascular damage during cancer therapy focused entirely on myocardial damage caused by anthracyclines and chest radiation, a concern that eventually expanded to include trastuzumab (Herceptin) and other agents that target the human epidermal growth factor receptor 2 (HER2). These treatments cause significantly reduced left ventricular ejection fractions and heart failure in a significant minority of treated patients. Patients who receive combined treatment with an anthracycline and trastuzumab are at the highest risk for developing heart failure with reduced ejection fraction, but even among patients treated with this combination, fewer than 5% develop outright heart failure.
While this parochial view of cardio-oncology has recently shifted, it remains true that myocardial damage from a relatively large cumulative anthracycline dose, or from radiation, causes some of the most extreme cases of cardiovascular adverse effects and remains an ongoing problem as these treatments stay front line for selected cancer patients.
But some of the recent burgeoning of cardio-oncology has followed the recognition that many other drugs and drug classes can cause a spectrum of adverse cardiovascular effects.
“There has been a significant focus on heart failure and cardiomyopathy due to anthracyclines and HER2-targeted therapies. I think the field will continue to evolve over the next 5 years to focus on other cardiovascular complications, including arrhythmias and vascular disease,” observed Michael Fradley, MD, director of cardio-oncology at Moffitt Cancer Center in Tampa. “In addition, there will be an increased focus on targeted drugs and immunotherapies,” agents that Dr. Fradley said “have many unique cardiovascular complications. We need additional guidelines regarding the management of a variety of cardiotoxicities as well as long-term monitoring strategies.”
In a review article Dr. Moslehi published toward the end of 2016, he fleshed out the wider scope of adverse cardiovascular effects from cancer therapies, noting that the vascular endothelial growth factor (VEGF) signaling pathway inhibitors, drugs such as bevacizumab (Avastin) and aflibercept (Zaltrap), have been documented to cause hypertension, arterial thromboembolic events, and cardiomyopathy; and that tyrosine kinase inhibitors have been shown to cause vascular events, QT interval prolongation, and cerebral and peripheral vascular events (N Engl J Med. 2016 Oct 13;375[15]:1457-67).
In his own recent review, Dr. Fradley highlighted adverse cardiovascular effects from additional anticancer drug classes, including proteasome inhibitors, which can trigger hypertension and cardiomyopathy; immunomodulators, implicated in causing both venous and arterial thromboembolism; and the immune checkpoint inhibitors, linked with myocarditis, arrhythmias, hypotension, and myocardial ischemia (Eur Heart J. 2016 Sept 21;37[36]:2740-2). A similarly broad spectrum of adverse cardiovascular effects linked with a wide range of anticancer treatments also appeared in the ESC 2016 position paper on cancer treatments.
But while the range of cancer treatments that can have some impact on the cardiovascular system is strikingly large, experts uniformly caution that far from every patient treated for cancer needs an immediate cardiology consult and work-up, especially when the cancers appear in young adults.
“We’re not quite at the point where every cancer patient needs to be seen by a cardiologist or cardio-oncologist,” Dr. Fradley noted in an interview.
“If a patient develops hypertension while on treatment I refer them to a PCP or cardiologist. I don’t treat hypertension myself. But if a patient is ‘normal’ they don’t need a cardiology assessment up front. It’s impossible to refer all patients, especially younger patients, with current resources. There are too many patients who receive cardiotoxic therapies to refer everyone. I involve the cardiologist once there is evidence of damage,”she explained.
Cardio-oncology centers or community practice?
The rise of cardio-oncology, especially over the last decade or so, has given rise to a new academic niche, the cardio-oncology clinic. Starting from almost no programs a few years ago, by 2016 one tally put the total number of U.S. self-designated cardio-oncology centers at about 40 (Heart Fail Clin. 2017 April;13[2]:347-55), and that number undoubtedly grew even more during the year since. While these programs promote and advance the nascent subspecialty of cardio-oncology, and provide a foundation for development of formalized training programs, many experts see a clear hierarchy of risk that distinguishes the patients who should ideally be managed at these focused, multidisciplinary programs from the lower-risk patients who probably do fine under the care of just their oncologist or their oncologist in collaboration with a community cardiologist or primary care physician.
“The cardio-oncology community recognizes that it is nice to have programs at academic centers but it’s more important to deliver this care in the community,” said Dr. Lenihan. “Many cancer patients have no prior history of cardiovascular disease. These low-risk patients don’t necessarily need a cardio-oncologist. They may need to have their blood pressure managed more effectively or receive other preventive care, but that can certainly be done locally. There are low-risk patients who don’t need to go to a major center.” Dr. Lenihan and other cardio-oncologists see the majority of cancer patients as low risk when it comes to cardiovascular complications.
But it’s different when patients receive an anthracycline or an anthracycline plus trastuzumab. “This high-risk population is best seen at a cardio-oncology center.” Dr. Lenihan also included in this high-risk subgroup patients treated with mediastinal radiation, an option often used during the 1980s-2000s.
“Any time a patient receives treatment with the potential to cause a cardiovascular effect, which is pretty much any drug that now comes out, you need an accurate baseline assessment. But that doesn’t mean you need do anything different; you still treat the patient’s cancer. A thorough baseline assessment is a necessity, but it does not need to be done at a cardio-oncology center,” Dr. Lenihan said in an interview.
“For the vast majority of patients, care can be at community hospitals, similar to the delivery of the vast majority of oncology care. Some patients need referral to tertiary cardiology centers for advanced heart failure or to undergo advanced procedures, but that is a very small percentage of patients,” said Ana Barac, MD, director of the cardio-oncology program at the MedStar Heart Institute in Washington, and chair of the ACC’s Cardio-Oncology Section.
“Patients receiving more novel or unusual therapies, and those participating in trials” are appropriate for centers, while community care by a cardiologist and oncologist should suffice for more routine patients, said Dr. Fradley.
“Cardio-oncology centers are good for patients with type I damage from anthracycline treatment, especially patients who already had underlying heart disease,” said Michael S. Ewer, MD, a cardiologist and professor of medicine at MD Anderson Cancer Center in Houston. Specialist centers are also for patients with cardiovascular risk factors: older age, diabetes, preexisting coronary artery disease, and patients who receive cardiotoxic type I therapy (J Clin Oncol. 2005 May;23[13]:2900-2). Also, patients with a significant, immediate cardiac reaction to treatment, and those with an unexpected cardiac reaction, Dr. Ewer said.
A somewhat more expansive view of the typical cardio-oncology patient came from Dr. Neilan, based on the patients he sees at his program in Boston. Dr. Neilan estimated that roughly 60%-70% of his patients first present while they undergo active cancer treatment, with another 20% coming to the program as cancer survivors, and a small percentage of patients showing up for cardiology assessments and treatments without a cancer history. Among those with a cancer history, he guessed that perhaps 10%-20% were treated with an anthracycline, at least 10% received trastuzumab, and about 10% received radiation treatment. “I also see a lot of patients with complications from treatment” with tyrosine kinase inhibitors, VEGF inhibitors, and immunotherapies. “I don’t see a lot of patients for cardiovascular disease assessment before they start cancer therapy,” Dr. Neilan added.
Cardio-oncology heads toward a new cardiology subspecialty
These views of how cardio-oncology is practiced in the real world raise a question about the role of the growing roster of U.S. cardio-oncology programs. If most cancer patients can have their cardiology needs taken care of in the community, how do all the academic programs fit in? The answer seems to be that they model successful oncology and cardiology collaborations, provide a training ground for physicians from both specialties to learn how to collaborate, and serve as the home for research that broadens the field’s evidence base and moves knowledge forward.
“Education and partnerships with oncology teams is the key,” said Dr. Barac. “Our traditional subspecialty training focused on ‘treating cancer’ and ‘treating cardiovascular disease.’ Learning about and seeing effective partnerships during training” is the best model to foster cardiology and oncology partnerships among early-career physicians, she suggested.
“What is the spectrum of knowledge required to be proficient in cardio-oncology, and how do we enhance training at the resident or fellowship level? How do we get [all cardiology] trainees exposed to this knowledge?” wondered Dr. Lenihan, who viewed cardio-oncology programs as a way to meet these needs. “Cardio-oncology is not an established subspecialty. A goal is to establish training requirements and expand training opportunities. And the whole field needs to contribute to clinical research. We need cardio-oncologists to share their experience and improve our level of research.”
ASCO’s cardiac dysfunction practice guideline, first released last December and formally published in March, is likely helping to further entrench cardio-oncology as a new subspecialty. The guideline was “a remarkable step forward,” said Dr. Barac. In addition to establishing a U.S. standard of care for preventing and monitoring cardiac dysfunction in cancer patients, “I use it as a guide for creation of referral pathways with my oncology colleagues, as well as in education of cardiovascular and oncology trainees,” she said in an interview.
Though produced primarily through ASCO’s leadership, the target audience for the guideline seems to be as much cardiologists as it is oncologists. Dissemination of the guideline to cardiologists snagged when it failed to appear in the cardiology literature. That wasn’t the original plan, said guideline participants.
“Before we started, it was agreed that both ASCO and the ACC would publish it. We had a [letter] signed by the president of the ACC saying the ACC would publish it,” recalled Dr. Lenihan, a guideline coauthor. “After all the details were settled, the ACC bailed. They said that they had changed their organizational structure and that they wouldn’t publish the guideline even though they had agreed to.” Not having the guideline appear simultaneously in the cardiology literature “hinders getting the message to the cardiology community,” he said, a sentiment echoed by other cardio-oncologists.
“I served as the ACC representative on the guideline, and the lack of ACC endorsement was the unfortunate consequence of approval and publication timing that coincided with restructuring of the ACC committees,” said Dr. Barac. “It absolutely does not reflect a lack of interest from the ACC.” As an example of the College’s commitment example, she cited an ACC 1.5-day educational course on cardiovascular care of oncology patients held for the first time in February 2017 and scheduled for a second edition next February.
Publication of the guideline in a cardiology journal “would indeed help dissemination among U.S. cardiologists,” agreed Pamela S. Douglas, MD, professor of medicine at Duke University in Durham, N.C., and another of the several cardiologists who served on the ASCO guideline’s panel.
Further advancing awareness of patients with cardio-oncology issues, what Dr. Moslehi has called “an emerging epidemic,” seems the most fundamental of the goals currently advanced by many active in this field.
One step to grow the subspecialty that he and his associates at Vanderbilt have taken is to start this year a formally recognized fellowship program in cardio-oncology; an initial class of three cardiologists started in the program this summer. The Vanderbilt group also plans to launch a website before the end of 2017 that will include an oncology-drug database that compiles all available information on each agent’s cardiovascular effects. The planned website will aggregate links to all existing cardio-oncology programs.
“We will absolutely see the field grow,” said Dr. Swain. “It has only sprung up in the past 10 or so years. It is now getting recognition, people are being trained in cardio-oncology, and it will grow as a subspecialty. It’s very exciting, and it’s better for patients.”
“A cardiologist with no cancer patients or survivors in their practice is unheard of; many cardiologists just don’t realize that,” Dr. Lenihan said. At least 10%-15% of the U.S. population in their 60s or older has a cancer history, he noted. The common mindset among cardiologists has been that cancer patients and survivors are not among their patients.
“It’s unlikely that a busy cardiology practice has no cancer survivors or active cancer patients,” Dr. Douglas suggested. When this happens, a likely explanations is that the cardiologist simply failed to elicit a completely comprehensive history from the practice’s patient roster. And even a cardiology practice today that includes no cancer patients or survivors will likely see some turning up soon, she predicted, because so many are receiving cardiovascular-toxic therapies and then surviving longer than ever before.
“What oncologists and cardiologists want to do is to optimize oncologic outcomes but with an acceptable adverse event profile. The cardio-oncologist helps push that envelope. The goal is not to eliminate cardiac events at the expense of oncologic outcomes, but to shift the balance to fewer and less severe cardiac events without unduly compromising oncologic outcomes,” explained Dr. Ewer. Cardio-oncology grapples with one of the core challenges of medicine, how to balance the potential risks from treatment against its potential benefits, he observed.
Dr. Neilan has been a consultant to Ariad and Takeda. Dr. Lenihan has been a consultant to Janssen and Roche and has received research funding from Takeda. Dr. Moslehi has been a consultant to Acceleron, Ariad, Bristol-Myers Squibb, Incyte, Pfizer, Takeda/Millennium, Verastem and Vertex. Dr. Ewer, Dr. Fradley, and Dr. Barac had no relevant disclosures. Dr. Swain has been a consultant to Genentech and Roche. Dr. Douglas has been a consultant to CardioDx, Interleukin Genetics, and Omicia, and has an ownership interest in CardioDx.
[email protected]
On Twitter @mitchelzoler
Cardio-oncology is expanding, fed by a steadily increasing population of cancer survivors at elevated risk for a range of cardiovascular diseases and complications because of the anticancer treatments they received. Cardio-oncology’s quick growth has also been driven by the rapidly expanding universe of cancer treatments with direct or indirect adverse effects on a diverse range of cardiovascular functions.
During the past year, the field’s rapid evolution has featured the first formal diagnostic and care standards in two iterations: A position paper on the cardiovascular toxicities of cancer treatment from the European Society of Cardiology (ESC), released in August 2016 (Eur Heart J. 2016 Sept 21;37[36]:2766-801); and a guideline for preventing and monitoring cardiac dysfunction in adult cancer survivors, issued last December by the American Society of Clinical Oncology (ASCO) and endorsed by the American Heart Association (J Clin Oncol. 2017 March 10;35[8]:893-913), but notably not endorsed by the American College of Cardiology, despite having an ACC representative on the guideline panel. In 2015, the ACC started a Cardio-Oncology Section, one of 20 special-interest sections it maintains, and by mid-2017 the section had some 500 members.
“I’ve had recent conversations with cardiologists who said ‘I’m not sure what cardio-oncology is,’ ” said Tomas G. Neilan, MD, director of the cardio-oncology program at Massachusetts General Hospital in Boston.
More than just heart failure
A few decades ago, in the primordial days of cardio-oncology, the concept of cardiovascular damage during cancer therapy focused entirely on myocardial damage caused by anthracyclines and chest radiation, a concern that eventually expanded to include trastuzumab (Herceptin) and other agents that target the human epidermal growth factor receptor 2 (HER2). These treatments cause significantly reduced left ventricular ejection fractions and heart failure in a significant minority of treated patients. Patients who receive combined treatment with an anthracycline and trastuzumab are at the highest risk for developing heart failure with reduced ejection fraction, but even among patients treated with this combination, fewer than 5% develop outright heart failure.
While this parochial view of cardio-oncology has recently shifted, it remains true that myocardial damage from a relatively large cumulative anthracycline dose, or from radiation, causes some of the most extreme cases of cardiovascular adverse effects and remains an ongoing problem as these treatments stay front line for selected cancer patients.
But some of the recent burgeoning of cardio-oncology has followed the recognition that many other drugs and drug classes can cause a spectrum of adverse cardiovascular effects.
“There has been a significant focus on heart failure and cardiomyopathy due to anthracyclines and HER2-targeted therapies. I think the field will continue to evolve over the next 5 years to focus on other cardiovascular complications, including arrhythmias and vascular disease,” observed Michael Fradley, MD, director of cardio-oncology at Moffitt Cancer Center in Tampa. “In addition, there will be an increased focus on targeted drugs and immunotherapies,” agents that Dr. Fradley said “have many unique cardiovascular complications. We need additional guidelines regarding the management of a variety of cardiotoxicities as well as long-term monitoring strategies.”
In a review article Dr. Moslehi published toward the end of 2016, he fleshed out the wider scope of adverse cardiovascular effects from cancer therapies, noting that the vascular endothelial growth factor (VEGF) signaling pathway inhibitors, drugs such as bevacizumab (Avastin) and aflibercept (Zaltrap), have been documented to cause hypertension, arterial thromboembolic events, and cardiomyopathy; and that tyrosine kinase inhibitors have been shown to cause vascular events, QT interval prolongation, and cerebral and peripheral vascular events (N Engl J Med. 2016 Oct 13;375[15]:1457-67).
In his own recent review, Dr. Fradley highlighted adverse cardiovascular effects from additional anticancer drug classes, including proteasome inhibitors, which can trigger hypertension and cardiomyopathy; immunomodulators, implicated in causing both venous and arterial thromboembolism; and the immune checkpoint inhibitors, linked with myocarditis, arrhythmias, hypotension, and myocardial ischemia (Eur Heart J. 2016 Sept 21;37[36]:2740-2). A similarly broad spectrum of adverse cardiovascular effects linked with a wide range of anticancer treatments also appeared in the ESC 2016 position paper on cancer treatments.
But while the range of cancer treatments that can have some impact on the cardiovascular system is strikingly large, experts uniformly caution that far from every patient treated for cancer needs an immediate cardiology consult and work-up, especially when the cancers appear in young adults.
“We’re not quite at the point where every cancer patient needs to be seen by a cardiologist or cardio-oncologist,” Dr. Fradley noted in an interview.
“If a patient develops hypertension while on treatment I refer them to a PCP or cardiologist. I don’t treat hypertension myself. But if a patient is ‘normal’ they don’t need a cardiology assessment up front. It’s impossible to refer all patients, especially younger patients, with current resources. There are too many patients who receive cardiotoxic therapies to refer everyone. I involve the cardiologist once there is evidence of damage,”she explained.
Cardio-oncology centers or community practice?
The rise of cardio-oncology, especially over the last decade or so, has given rise to a new academic niche, the cardio-oncology clinic. Starting from almost no programs a few years ago, by 2016 one tally put the total number of U.S. self-designated cardio-oncology centers at about 40 (Heart Fail Clin. 2017 April;13[2]:347-55), and that number undoubtedly grew even more during the year since. While these programs promote and advance the nascent subspecialty of cardio-oncology, and provide a foundation for development of formalized training programs, many experts see a clear hierarchy of risk that distinguishes the patients who should ideally be managed at these focused, multidisciplinary programs from the lower-risk patients who probably do fine under the care of just their oncologist or their oncologist in collaboration with a community cardiologist or primary care physician.
“The cardio-oncology community recognizes that it is nice to have programs at academic centers but it’s more important to deliver this care in the community,” said Dr. Lenihan. “Many cancer patients have no prior history of cardiovascular disease. These low-risk patients don’t necessarily need a cardio-oncologist. They may need to have their blood pressure managed more effectively or receive other preventive care, but that can certainly be done locally. There are low-risk patients who don’t need to go to a major center.” Dr. Lenihan and other cardio-oncologists see the majority of cancer patients as low risk when it comes to cardiovascular complications.
But it’s different when patients receive an anthracycline or an anthracycline plus trastuzumab. “This high-risk population is best seen at a cardio-oncology center.” Dr. Lenihan also included in this high-risk subgroup patients treated with mediastinal radiation, an option often used during the 1980s-2000s.
“Any time a patient receives treatment with the potential to cause a cardiovascular effect, which is pretty much any drug that now comes out, you need an accurate baseline assessment. But that doesn’t mean you need do anything different; you still treat the patient’s cancer. A thorough baseline assessment is a necessity, but it does not need to be done at a cardio-oncology center,” Dr. Lenihan said in an interview.
“For the vast majority of patients, care can be at community hospitals, similar to the delivery of the vast majority of oncology care. Some patients need referral to tertiary cardiology centers for advanced heart failure or to undergo advanced procedures, but that is a very small percentage of patients,” said Ana Barac, MD, director of the cardio-oncology program at the MedStar Heart Institute in Washington, and chair of the ACC’s Cardio-Oncology Section.
“Patients receiving more novel or unusual therapies, and those participating in trials” are appropriate for centers, while community care by a cardiologist and oncologist should suffice for more routine patients, said Dr. Fradley.
“Cardio-oncology centers are good for patients with type I damage from anthracycline treatment, especially patients who already had underlying heart disease,” said Michael S. Ewer, MD, a cardiologist and professor of medicine at MD Anderson Cancer Center in Houston. Specialist centers are also for patients with cardiovascular risk factors: older age, diabetes, preexisting coronary artery disease, and patients who receive cardiotoxic type I therapy (J Clin Oncol. 2005 May;23[13]:2900-2). Also, patients with a significant, immediate cardiac reaction to treatment, and those with an unexpected cardiac reaction, Dr. Ewer said.
A somewhat more expansive view of the typical cardio-oncology patient came from Dr. Neilan, based on the patients he sees at his program in Boston. Dr. Neilan estimated that roughly 60%-70% of his patients first present while they undergo active cancer treatment, with another 20% coming to the program as cancer survivors, and a small percentage of patients showing up for cardiology assessments and treatments without a cancer history. Among those with a cancer history, he guessed that perhaps 10%-20% were treated with an anthracycline, at least 10% received trastuzumab, and about 10% received radiation treatment. “I also see a lot of patients with complications from treatment” with tyrosine kinase inhibitors, VEGF inhibitors, and immunotherapies. “I don’t see a lot of patients for cardiovascular disease assessment before they start cancer therapy,” Dr. Neilan added.
Cardio-oncology heads toward a new cardiology subspecialty
These views of how cardio-oncology is practiced in the real world raise a question about the role of the growing roster of U.S. cardio-oncology programs. If most cancer patients can have their cardiology needs taken care of in the community, how do all the academic programs fit in? The answer seems to be that they model successful oncology and cardiology collaborations, provide a training ground for physicians from both specialties to learn how to collaborate, and serve as the home for research that broadens the field’s evidence base and moves knowledge forward.
“Education and partnerships with oncology teams is the key,” said Dr. Barac. “Our traditional subspecialty training focused on ‘treating cancer’ and ‘treating cardiovascular disease.’ Learning about and seeing effective partnerships during training” is the best model to foster cardiology and oncology partnerships among early-career physicians, she suggested.
“What is the spectrum of knowledge required to be proficient in cardio-oncology, and how do we enhance training at the resident or fellowship level? How do we get [all cardiology] trainees exposed to this knowledge?” wondered Dr. Lenihan, who viewed cardio-oncology programs as a way to meet these needs. “Cardio-oncology is not an established subspecialty. A goal is to establish training requirements and expand training opportunities. And the whole field needs to contribute to clinical research. We need cardio-oncologists to share their experience and improve our level of research.”
ASCO’s cardiac dysfunction practice guideline, first released last December and formally published in March, is likely helping to further entrench cardio-oncology as a new subspecialty. The guideline was “a remarkable step forward,” said Dr. Barac. In addition to establishing a U.S. standard of care for preventing and monitoring cardiac dysfunction in cancer patients, “I use it as a guide for creation of referral pathways with my oncology colleagues, as well as in education of cardiovascular and oncology trainees,” she said in an interview.
Though produced primarily through ASCO’s leadership, the target audience for the guideline seems to be as much cardiologists as it is oncologists. Dissemination of the guideline to cardiologists snagged when it failed to appear in the cardiology literature. That wasn’t the original plan, said guideline participants.
“Before we started, it was agreed that both ASCO and the ACC would publish it. We had a [letter] signed by the president of the ACC saying the ACC would publish it,” recalled Dr. Lenihan, a guideline coauthor. “After all the details were settled, the ACC bailed. They said that they had changed their organizational structure and that they wouldn’t publish the guideline even though they had agreed to.” Not having the guideline appear simultaneously in the cardiology literature “hinders getting the message to the cardiology community,” he said, a sentiment echoed by other cardio-oncologists.
“I served as the ACC representative on the guideline, and the lack of ACC endorsement was the unfortunate consequence of approval and publication timing that coincided with restructuring of the ACC committees,” said Dr. Barac. “It absolutely does not reflect a lack of interest from the ACC.” As an example of the College’s commitment example, she cited an ACC 1.5-day educational course on cardiovascular care of oncology patients held for the first time in February 2017 and scheduled for a second edition next February.
Publication of the guideline in a cardiology journal “would indeed help dissemination among U.S. cardiologists,” agreed Pamela S. Douglas, MD, professor of medicine at Duke University in Durham, N.C., and another of the several cardiologists who served on the ASCO guideline’s panel.
Further advancing awareness of patients with cardio-oncology issues, what Dr. Moslehi has called “an emerging epidemic,” seems the most fundamental of the goals currently advanced by many active in this field.
One step to grow the subspecialty that he and his associates at Vanderbilt have taken is to start this year a formally recognized fellowship program in cardio-oncology; an initial class of three cardiologists started in the program this summer. The Vanderbilt group also plans to launch a website before the end of 2017 that will include an oncology-drug database that compiles all available information on each agent’s cardiovascular effects. The planned website will aggregate links to all existing cardio-oncology programs.
“We will absolutely see the field grow,” said Dr. Swain. “It has only sprung up in the past 10 or so years. It is now getting recognition, people are being trained in cardio-oncology, and it will grow as a subspecialty. It’s very exciting, and it’s better for patients.”
“A cardiologist with no cancer patients or survivors in their practice is unheard of; many cardiologists just don’t realize that,” Dr. Lenihan said. At least 10%-15% of the U.S. population in their 60s or older has a cancer history, he noted. The common mindset among cardiologists has been that cancer patients and survivors are not among their patients.
“It’s unlikely that a busy cardiology practice has no cancer survivors or active cancer patients,” Dr. Douglas suggested. When this happens, a likely explanations is that the cardiologist simply failed to elicit a completely comprehensive history from the practice’s patient roster. And even a cardiology practice today that includes no cancer patients or survivors will likely see some turning up soon, she predicted, because so many are receiving cardiovascular-toxic therapies and then surviving longer than ever before.
“What oncologists and cardiologists want to do is to optimize oncologic outcomes but with an acceptable adverse event profile. The cardio-oncologist helps push that envelope. The goal is not to eliminate cardiac events at the expense of oncologic outcomes, but to shift the balance to fewer and less severe cardiac events without unduly compromising oncologic outcomes,” explained Dr. Ewer. Cardio-oncology grapples with one of the core challenges of medicine, how to balance the potential risks from treatment against its potential benefits, he observed.
Dr. Neilan has been a consultant to Ariad and Takeda. Dr. Lenihan has been a consultant to Janssen and Roche and has received research funding from Takeda. Dr. Moslehi has been a consultant to Acceleron, Ariad, Bristol-Myers Squibb, Incyte, Pfizer, Takeda/Millennium, Verastem and Vertex. Dr. Ewer, Dr. Fradley, and Dr. Barac had no relevant disclosures. Dr. Swain has been a consultant to Genentech and Roche. Dr. Douglas has been a consultant to CardioDx, Interleukin Genetics, and Omicia, and has an ownership interest in CardioDx.
[email protected]
On Twitter @mitchelzoler
Cardio-oncology is expanding, fed by a steadily increasing population of cancer survivors at elevated risk for a range of cardiovascular diseases and complications because of the anticancer treatments they received. Cardio-oncology’s quick growth has also been driven by the rapidly expanding universe of cancer treatments with direct or indirect adverse effects on a diverse range of cardiovascular functions.
During the past year, the field’s rapid evolution has featured the first formal diagnostic and care standards in two iterations: A position paper on the cardiovascular toxicities of cancer treatment from the European Society of Cardiology (ESC), released in August 2016 (Eur Heart J. 2016 Sept 21;37[36]:2766-801); and a guideline for preventing and monitoring cardiac dysfunction in adult cancer survivors, issued last December by the American Society of Clinical Oncology (ASCO) and endorsed by the American Heart Association (J Clin Oncol. 2017 March 10;35[8]:893-913), but notably not endorsed by the American College of Cardiology, despite having an ACC representative on the guideline panel. In 2015, the ACC started a Cardio-Oncology Section, one of 20 special-interest sections it maintains, and by mid-2017 the section had some 500 members.
“I’ve had recent conversations with cardiologists who said ‘I’m not sure what cardio-oncology is,’ ” said Tomas G. Neilan, MD, director of the cardio-oncology program at Massachusetts General Hospital in Boston.
More than just heart failure
A few decades ago, in the primordial days of cardio-oncology, the concept of cardiovascular damage during cancer therapy focused entirely on myocardial damage caused by anthracyclines and chest radiation, a concern that eventually expanded to include trastuzumab (Herceptin) and other agents that target the human epidermal growth factor receptor 2 (HER2). These treatments cause significantly reduced left ventricular ejection fractions and heart failure in a significant minority of treated patients. Patients who receive combined treatment with an anthracycline and trastuzumab are at the highest risk for developing heart failure with reduced ejection fraction, but even among patients treated with this combination, fewer than 5% develop outright heart failure.
While this parochial view of cardio-oncology has recently shifted, it remains true that myocardial damage from a relatively large cumulative anthracycline dose, or from radiation, causes some of the most extreme cases of cardiovascular adverse effects and remains an ongoing problem as these treatments stay front line for selected cancer patients.
But some of the recent burgeoning of cardio-oncology has followed the recognition that many other drugs and drug classes can cause a spectrum of adverse cardiovascular effects.
“There has been a significant focus on heart failure and cardiomyopathy due to anthracyclines and HER2-targeted therapies. I think the field will continue to evolve over the next 5 years to focus on other cardiovascular complications, including arrhythmias and vascular disease,” observed Michael Fradley, MD, director of cardio-oncology at Moffitt Cancer Center in Tampa. “In addition, there will be an increased focus on targeted drugs and immunotherapies,” agents that Dr. Fradley said “have many unique cardiovascular complications. We need additional guidelines regarding the management of a variety of cardiotoxicities as well as long-term monitoring strategies.”
In a review article Dr. Moslehi published toward the end of 2016, he fleshed out the wider scope of adverse cardiovascular effects from cancer therapies, noting that the vascular endothelial growth factor (VEGF) signaling pathway inhibitors, drugs such as bevacizumab (Avastin) and aflibercept (Zaltrap), have been documented to cause hypertension, arterial thromboembolic events, and cardiomyopathy; and that tyrosine kinase inhibitors have been shown to cause vascular events, QT interval prolongation, and cerebral and peripheral vascular events (N Engl J Med. 2016 Oct 13;375[15]:1457-67).
In his own recent review, Dr. Fradley highlighted adverse cardiovascular effects from additional anticancer drug classes, including proteasome inhibitors, which can trigger hypertension and cardiomyopathy; immunomodulators, implicated in causing both venous and arterial thromboembolism; and the immune checkpoint inhibitors, linked with myocarditis, arrhythmias, hypotension, and myocardial ischemia (Eur Heart J. 2016 Sept 21;37[36]:2740-2). A similarly broad spectrum of adverse cardiovascular effects linked with a wide range of anticancer treatments also appeared in the ESC 2016 position paper on cancer treatments.
But while the range of cancer treatments that can have some impact on the cardiovascular system is strikingly large, experts uniformly caution that far from every patient treated for cancer needs an immediate cardiology consult and work-up, especially when the cancers appear in young adults.
“We’re not quite at the point where every cancer patient needs to be seen by a cardiologist or cardio-oncologist,” Dr. Fradley noted in an interview.
“If a patient develops hypertension while on treatment I refer them to a PCP or cardiologist. I don’t treat hypertension myself. But if a patient is ‘normal’ they don’t need a cardiology assessment up front. It’s impossible to refer all patients, especially younger patients, with current resources. There are too many patients who receive cardiotoxic therapies to refer everyone. I involve the cardiologist once there is evidence of damage,”she explained.
Cardio-oncology centers or community practice?
The rise of cardio-oncology, especially over the last decade or so, has given rise to a new academic niche, the cardio-oncology clinic. Starting from almost no programs a few years ago, by 2016 one tally put the total number of U.S. self-designated cardio-oncology centers at about 40 (Heart Fail Clin. 2017 April;13[2]:347-55), and that number undoubtedly grew even more during the year since. While these programs promote and advance the nascent subspecialty of cardio-oncology, and provide a foundation for development of formalized training programs, many experts see a clear hierarchy of risk that distinguishes the patients who should ideally be managed at these focused, multidisciplinary programs from the lower-risk patients who probably do fine under the care of just their oncologist or their oncologist in collaboration with a community cardiologist or primary care physician.
“The cardio-oncology community recognizes that it is nice to have programs at academic centers but it’s more important to deliver this care in the community,” said Dr. Lenihan. “Many cancer patients have no prior history of cardiovascular disease. These low-risk patients don’t necessarily need a cardio-oncologist. They may need to have their blood pressure managed more effectively or receive other preventive care, but that can certainly be done locally. There are low-risk patients who don’t need to go to a major center.” Dr. Lenihan and other cardio-oncologists see the majority of cancer patients as low risk when it comes to cardiovascular complications.
But it’s different when patients receive an anthracycline or an anthracycline plus trastuzumab. “This high-risk population is best seen at a cardio-oncology center.” Dr. Lenihan also included in this high-risk subgroup patients treated with mediastinal radiation, an option often used during the 1980s-2000s.
“Any time a patient receives treatment with the potential to cause a cardiovascular effect, which is pretty much any drug that now comes out, you need an accurate baseline assessment. But that doesn’t mean you need do anything different; you still treat the patient’s cancer. A thorough baseline assessment is a necessity, but it does not need to be done at a cardio-oncology center,” Dr. Lenihan said in an interview.
“For the vast majority of patients, care can be at community hospitals, similar to the delivery of the vast majority of oncology care. Some patients need referral to tertiary cardiology centers for advanced heart failure or to undergo advanced procedures, but that is a very small percentage of patients,” said Ana Barac, MD, director of the cardio-oncology program at the MedStar Heart Institute in Washington, and chair of the ACC’s Cardio-Oncology Section.
“Patients receiving more novel or unusual therapies, and those participating in trials” are appropriate for centers, while community care by a cardiologist and oncologist should suffice for more routine patients, said Dr. Fradley.
“Cardio-oncology centers are good for patients with type I damage from anthracycline treatment, especially patients who already had underlying heart disease,” said Michael S. Ewer, MD, a cardiologist and professor of medicine at MD Anderson Cancer Center in Houston. Specialist centers are also for patients with cardiovascular risk factors: older age, diabetes, preexisting coronary artery disease, and patients who receive cardiotoxic type I therapy (J Clin Oncol. 2005 May;23[13]:2900-2). Also, patients with a significant, immediate cardiac reaction to treatment, and those with an unexpected cardiac reaction, Dr. Ewer said.
A somewhat more expansive view of the typical cardio-oncology patient came from Dr. Neilan, based on the patients he sees at his program in Boston. Dr. Neilan estimated that roughly 60%-70% of his patients first present while they undergo active cancer treatment, with another 20% coming to the program as cancer survivors, and a small percentage of patients showing up for cardiology assessments and treatments without a cancer history. Among those with a cancer history, he guessed that perhaps 10%-20% were treated with an anthracycline, at least 10% received trastuzumab, and about 10% received radiation treatment. “I also see a lot of patients with complications from treatment” with tyrosine kinase inhibitors, VEGF inhibitors, and immunotherapies. “I don’t see a lot of patients for cardiovascular disease assessment before they start cancer therapy,” Dr. Neilan added.
Cardio-oncology heads toward a new cardiology subspecialty
These views of how cardio-oncology is practiced in the real world raise a question about the role of the growing roster of U.S. cardio-oncology programs. If most cancer patients can have their cardiology needs taken care of in the community, how do all the academic programs fit in? The answer seems to be that they model successful oncology and cardiology collaborations, provide a training ground for physicians from both specialties to learn how to collaborate, and serve as the home for research that broadens the field’s evidence base and moves knowledge forward.
“Education and partnerships with oncology teams is the key,” said Dr. Barac. “Our traditional subspecialty training focused on ‘treating cancer’ and ‘treating cardiovascular disease.’ Learning about and seeing effective partnerships during training” is the best model to foster cardiology and oncology partnerships among early-career physicians, she suggested.
“What is the spectrum of knowledge required to be proficient in cardio-oncology, and how do we enhance training at the resident or fellowship level? How do we get [all cardiology] trainees exposed to this knowledge?” wondered Dr. Lenihan, who viewed cardio-oncology programs as a way to meet these needs. “Cardio-oncology is not an established subspecialty. A goal is to establish training requirements and expand training opportunities. And the whole field needs to contribute to clinical research. We need cardio-oncologists to share their experience and improve our level of research.”
ASCO’s cardiac dysfunction practice guideline, first released last December and formally published in March, is likely helping to further entrench cardio-oncology as a new subspecialty. The guideline was “a remarkable step forward,” said Dr. Barac. In addition to establishing a U.S. standard of care for preventing and monitoring cardiac dysfunction in cancer patients, “I use it as a guide for creation of referral pathways with my oncology colleagues, as well as in education of cardiovascular and oncology trainees,” she said in an interview.
Though produced primarily through ASCO’s leadership, the target audience for the guideline seems to be as much cardiologists as it is oncologists. Dissemination of the guideline to cardiologists snagged when it failed to appear in the cardiology literature. That wasn’t the original plan, said guideline participants.
“Before we started, it was agreed that both ASCO and the ACC would publish it. We had a [letter] signed by the president of the ACC saying the ACC would publish it,” recalled Dr. Lenihan, a guideline coauthor. “After all the details were settled, the ACC bailed. They said that they had changed their organizational structure and that they wouldn’t publish the guideline even though they had agreed to.” Not having the guideline appear simultaneously in the cardiology literature “hinders getting the message to the cardiology community,” he said, a sentiment echoed by other cardio-oncologists.
“I served as the ACC representative on the guideline, and the lack of ACC endorsement was the unfortunate consequence of approval and publication timing that coincided with restructuring of the ACC committees,” said Dr. Barac. “It absolutely does not reflect a lack of interest from the ACC.” As an example of the College’s commitment example, she cited an ACC 1.5-day educational course on cardiovascular care of oncology patients held for the first time in February 2017 and scheduled for a second edition next February.
Publication of the guideline in a cardiology journal “would indeed help dissemination among U.S. cardiologists,” agreed Pamela S. Douglas, MD, professor of medicine at Duke University in Durham, N.C., and another of the several cardiologists who served on the ASCO guideline’s panel.
Further advancing awareness of patients with cardio-oncology issues, what Dr. Moslehi has called “an emerging epidemic,” seems the most fundamental of the goals currently advanced by many active in this field.
One step to grow the subspecialty that he and his associates at Vanderbilt have taken is to start this year a formally recognized fellowship program in cardio-oncology; an initial class of three cardiologists started in the program this summer. The Vanderbilt group also plans to launch a website before the end of 2017 that will include an oncology-drug database that compiles all available information on each agent’s cardiovascular effects. The planned website will aggregate links to all existing cardio-oncology programs.
“We will absolutely see the field grow,” said Dr. Swain. “It has only sprung up in the past 10 or so years. It is now getting recognition, people are being trained in cardio-oncology, and it will grow as a subspecialty. It’s very exciting, and it’s better for patients.”
“A cardiologist with no cancer patients or survivors in their practice is unheard of; many cardiologists just don’t realize that,” Dr. Lenihan said. At least 10%-15% of the U.S. population in their 60s or older has a cancer history, he noted. The common mindset among cardiologists has been that cancer patients and survivors are not among their patients.
“It’s unlikely that a busy cardiology practice has no cancer survivors or active cancer patients,” Dr. Douglas suggested. When this happens, a likely explanations is that the cardiologist simply failed to elicit a completely comprehensive history from the practice’s patient roster. And even a cardiology practice today that includes no cancer patients or survivors will likely see some turning up soon, she predicted, because so many are receiving cardiovascular-toxic therapies and then surviving longer than ever before.
“What oncologists and cardiologists want to do is to optimize oncologic outcomes but with an acceptable adverse event profile. The cardio-oncologist helps push that envelope. The goal is not to eliminate cardiac events at the expense of oncologic outcomes, but to shift the balance to fewer and less severe cardiac events without unduly compromising oncologic outcomes,” explained Dr. Ewer. Cardio-oncology grapples with one of the core challenges of medicine, how to balance the potential risks from treatment against its potential benefits, he observed.
Dr. Neilan has been a consultant to Ariad and Takeda. Dr. Lenihan has been a consultant to Janssen and Roche and has received research funding from Takeda. Dr. Moslehi has been a consultant to Acceleron, Ariad, Bristol-Myers Squibb, Incyte, Pfizer, Takeda/Millennium, Verastem and Vertex. Dr. Ewer, Dr. Fradley, and Dr. Barac had no relevant disclosures. Dr. Swain has been a consultant to Genentech and Roche. Dr. Douglas has been a consultant to CardioDx, Interleukin Genetics, and Omicia, and has an ownership interest in CardioDx.
[email protected]
On Twitter @mitchelzoler
Hyperlipidemia diagnosis protects against breast cancer
BARCELONA – Women diagnosed with hyperlipidemia had a strikingly reduced risk of subsequently developing breast cancer in a big-data, case-control study, Paul R. Carter, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, those baseline hyperlipidemic women who later got breast cancer had a 40% lower risk of all-cause mortality than did matched nonhyperlipidemic controls diagnosed with the malignancy during follow-up, according to Dr. Carter, a cardiology fellow at Cambridge (England) University.
The inference isn’t that hyperlipidemia somehow protects against the most common type of cancer in women. Indeed, preclinical evidence indicates high cholesterol drives several key steps in carcinogenesis. Rather, the strong implication is that the explanation for the observed preventive effect lies in the pleotropic effects of the statin therapy routinely prescribed in accordance with guidelines once women received the diagnosis of hyperlipidemia, he continued.
“The results of this study provide the strongest justification to date for a clinical trial evaluating the protective effect of statins in patients with breast cancer, and this is what we intend to do,” according to Dr. Carter.
He presented a retrospective longitudinal study of the Algorithm for Comorbidities, Associations, Length of Stay and Mortality database, comprising more than 1.2 million patients admitted for various reasons to selected hospitals in northern England during 2000-2014. This big-data study entailed recruitment of 16,043 women aged 40 years and older who were diagnosed with hyperlipidemia during their hospital stay along with an equal number of age-matched women with normal lipid levels. None of the participants had a breast cancer diagnosis at baseline.
The all-cause mortality rate in baseline hyperlipidemic women who later developed breast cancer was 27.4%, significantly lower than the 37.4% rate in normolipidemic women with breast cancer. This translated into an adjusted 40% relative risk reduction.
All-cause mortality occurred during follow-up in 13.7% of breast cancer–free women with baseline hyperlipidemia, compared with 23.6% of nonhyperlipidemic controls without breast cancer.
In an analysis adjusted for age, ethnicity, and the top-10 causes of death in the U.K., women with baseline hyperlipidemia were 40% less likely to die during follow-up than were women without high cholesterol.
Dr. Carter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
BARCELONA – Women diagnosed with hyperlipidemia had a strikingly reduced risk of subsequently developing breast cancer in a big-data, case-control study, Paul R. Carter, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, those baseline hyperlipidemic women who later got breast cancer had a 40% lower risk of all-cause mortality than did matched nonhyperlipidemic controls diagnosed with the malignancy during follow-up, according to Dr. Carter, a cardiology fellow at Cambridge (England) University.
The inference isn’t that hyperlipidemia somehow protects against the most common type of cancer in women. Indeed, preclinical evidence indicates high cholesterol drives several key steps in carcinogenesis. Rather, the strong implication is that the explanation for the observed preventive effect lies in the pleotropic effects of the statin therapy routinely prescribed in accordance with guidelines once women received the diagnosis of hyperlipidemia, he continued.
“The results of this study provide the strongest justification to date for a clinical trial evaluating the protective effect of statins in patients with breast cancer, and this is what we intend to do,” according to Dr. Carter.
He presented a retrospective longitudinal study of the Algorithm for Comorbidities, Associations, Length of Stay and Mortality database, comprising more than 1.2 million patients admitted for various reasons to selected hospitals in northern England during 2000-2014. This big-data study entailed recruitment of 16,043 women aged 40 years and older who were diagnosed with hyperlipidemia during their hospital stay along with an equal number of age-matched women with normal lipid levels. None of the participants had a breast cancer diagnosis at baseline.
The all-cause mortality rate in baseline hyperlipidemic women who later developed breast cancer was 27.4%, significantly lower than the 37.4% rate in normolipidemic women with breast cancer. This translated into an adjusted 40% relative risk reduction.
All-cause mortality occurred during follow-up in 13.7% of breast cancer–free women with baseline hyperlipidemia, compared with 23.6% of nonhyperlipidemic controls without breast cancer.
In an analysis adjusted for age, ethnicity, and the top-10 causes of death in the U.K., women with baseline hyperlipidemia were 40% less likely to die during follow-up than were women without high cholesterol.
Dr. Carter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
BARCELONA – Women diagnosed with hyperlipidemia had a strikingly reduced risk of subsequently developing breast cancer in a big-data, case-control study, Paul R. Carter, MD, reported at the annual congress of the European Society of Cardiology.
Moreover, those baseline hyperlipidemic women who later got breast cancer had a 40% lower risk of all-cause mortality than did matched nonhyperlipidemic controls diagnosed with the malignancy during follow-up, according to Dr. Carter, a cardiology fellow at Cambridge (England) University.
The inference isn’t that hyperlipidemia somehow protects against the most common type of cancer in women. Indeed, preclinical evidence indicates high cholesterol drives several key steps in carcinogenesis. Rather, the strong implication is that the explanation for the observed preventive effect lies in the pleotropic effects of the statin therapy routinely prescribed in accordance with guidelines once women received the diagnosis of hyperlipidemia, he continued.
“The results of this study provide the strongest justification to date for a clinical trial evaluating the protective effect of statins in patients with breast cancer, and this is what we intend to do,” according to Dr. Carter.
He presented a retrospective longitudinal study of the Algorithm for Comorbidities, Associations, Length of Stay and Mortality database, comprising more than 1.2 million patients admitted for various reasons to selected hospitals in northern England during 2000-2014. This big-data study entailed recruitment of 16,043 women aged 40 years and older who were diagnosed with hyperlipidemia during their hospital stay along with an equal number of age-matched women with normal lipid levels. None of the participants had a breast cancer diagnosis at baseline.
The all-cause mortality rate in baseline hyperlipidemic women who later developed breast cancer was 27.4%, significantly lower than the 37.4% rate in normolipidemic women with breast cancer. This translated into an adjusted 40% relative risk reduction.
All-cause mortality occurred during follow-up in 13.7% of breast cancer–free women with baseline hyperlipidemia, compared with 23.6% of nonhyperlipidemic controls without breast cancer.
In an analysis adjusted for age, ethnicity, and the top-10 causes of death in the U.K., women with baseline hyperlipidemia were 40% less likely to die during follow-up than were women without high cholesterol.
Dr. Carter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The risk of subsequent development of breast cancer was one-third lower in women diagnosed with hyperlipidemia than in controls with normal lipid levels.
Data source: A retrospective longitudinal case-control study of 16,043 U.K. women aged 40 years or older when diagnosed with hyperlipidemia and an equal number of age-matched women with normal lipids.
Disclosures: The presenter reported having no financial conflicts of interest regarding his study, which was conducted free of commercial support.
Dabrafenib/trametinib bests docetaxel for advanced NSCLC in indirect comparison
CHICAGO – Compared with docetaxel in matched external controls, combination therapy with dabrafenib and trametinib was associated with significantly prolonged progression-free and overall survival in previously treated patients with metastatic non–small cell lung cancer in a phase 2 trial.
Median progression-free survival (PFS) was 9.7 months in 57 patients in an open-label, multicenter phase 2 trial that investigated dabrafenib/trametinib treatment for metastatic BRAF V600E–mutated NSCLC, compared with 4.2 months in 290 patients treated with docetaxel in the randomized phase 3 CheckMate057 trial, which compared nivolumab and docetaxel in similar patients (hazard ratio, 0.32). Overall survival in the groups was 19.2 vs. 9.3 months, respectively (HR, 0.41), Junlong Li, MD, of Analysis Group, Boston, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
Patients treated with the combination of dabrafenib and trametinib also had a significantly higher overall response rate (61% vs. 12%) and disease control rate (77% vs. 55%), Dr. Li said.
Patient-level data for the combination therapy patients and summary data for the docetaxel-treated patients were used for the current analysis. Patients and controls were matched based on age, sex, race, smoking history, performance score, tumor histology, prior regimens, prior radiotherapy, and prior maintenance therapy. The two trials used for the analysis (NCT01336634 and CheckMate 057) were comparable in design and inclusion/exclusion criteria, and both used RECIST v1.1 to evaluate response to therapy.
“In the absence of head-to-head trials ... this study contributes some comparative efficacy evidence in this area,” Dr. Li concluded.
Invited discussant, Thomas Eldridge Stinchcombe, MD, of Duke University, Durham, N.C., said that the findings are unsurprising but important in that they are confirmatory.
Dr. Li is a consultant for Novartis, which sponsored the analysis.
CHICAGO – Compared with docetaxel in matched external controls, combination therapy with dabrafenib and trametinib was associated with significantly prolonged progression-free and overall survival in previously treated patients with metastatic non–small cell lung cancer in a phase 2 trial.
Median progression-free survival (PFS) was 9.7 months in 57 patients in an open-label, multicenter phase 2 trial that investigated dabrafenib/trametinib treatment for metastatic BRAF V600E–mutated NSCLC, compared with 4.2 months in 290 patients treated with docetaxel in the randomized phase 3 CheckMate057 trial, which compared nivolumab and docetaxel in similar patients (hazard ratio, 0.32). Overall survival in the groups was 19.2 vs. 9.3 months, respectively (HR, 0.41), Junlong Li, MD, of Analysis Group, Boston, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
Patients treated with the combination of dabrafenib and trametinib also had a significantly higher overall response rate (61% vs. 12%) and disease control rate (77% vs. 55%), Dr. Li said.
Patient-level data for the combination therapy patients and summary data for the docetaxel-treated patients were used for the current analysis. Patients and controls were matched based on age, sex, race, smoking history, performance score, tumor histology, prior regimens, prior radiotherapy, and prior maintenance therapy. The two trials used for the analysis (NCT01336634 and CheckMate 057) were comparable in design and inclusion/exclusion criteria, and both used RECIST v1.1 to evaluate response to therapy.
“In the absence of head-to-head trials ... this study contributes some comparative efficacy evidence in this area,” Dr. Li concluded.
Invited discussant, Thomas Eldridge Stinchcombe, MD, of Duke University, Durham, N.C., said that the findings are unsurprising but important in that they are confirmatory.
Dr. Li is a consultant for Novartis, which sponsored the analysis.
CHICAGO – Compared with docetaxel in matched external controls, combination therapy with dabrafenib and trametinib was associated with significantly prolonged progression-free and overall survival in previously treated patients with metastatic non–small cell lung cancer in a phase 2 trial.
Median progression-free survival (PFS) was 9.7 months in 57 patients in an open-label, multicenter phase 2 trial that investigated dabrafenib/trametinib treatment for metastatic BRAF V600E–mutated NSCLC, compared with 4.2 months in 290 patients treated with docetaxel in the randomized phase 3 CheckMate057 trial, which compared nivolumab and docetaxel in similar patients (hazard ratio, 0.32). Overall survival in the groups was 19.2 vs. 9.3 months, respectively (HR, 0.41), Junlong Li, MD, of Analysis Group, Boston, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
Patients treated with the combination of dabrafenib and trametinib also had a significantly higher overall response rate (61% vs. 12%) and disease control rate (77% vs. 55%), Dr. Li said.
Patient-level data for the combination therapy patients and summary data for the docetaxel-treated patients were used for the current analysis. Patients and controls were matched based on age, sex, race, smoking history, performance score, tumor histology, prior regimens, prior radiotherapy, and prior maintenance therapy. The two trials used for the analysis (NCT01336634 and CheckMate 057) were comparable in design and inclusion/exclusion criteria, and both used RECIST v1.1 to evaluate response to therapy.
“In the absence of head-to-head trials ... this study contributes some comparative efficacy evidence in this area,” Dr. Li concluded.
Invited discussant, Thomas Eldridge Stinchcombe, MD, of Duke University, Durham, N.C., said that the findings are unsurprising but important in that they are confirmatory.
Dr. Li is a consultant for Novartis, which sponsored the analysis.
AT A SYMPOSIUM IN THORACIC ONCOLOGY
Key clinical point:
Major finding: Median PFS with dabrafenib and trametinib vs. docetaxel: 9.7 vs. 4.2 months (HR, 0.32); overall survival: 19.2 vs. 9.3 months (HR, 0.41).
Data source: An adjusted indirect comparison of data from 347 patients from two separate studies.
Disclosures: Dr. Li is a consultant for Novartis, which sponsored the analysis.
HOPE-3 wades into fray regarding optimal blood pressure targets
BARCELONA – How low to go in treating hypertension is a topic of considerable recent controversy. Now the HOPE-3 trial investigators have weighed in, reporting that optimal outcomes in their landmark randomized trial were seen with an achieved, on-treatment systolic blood pressure of 130-140 mm Hg and a diastolic blood pressure of 75-80 mm Hg, Eva M. Lonn, MD, reported at the annual congress of the European Society of Cardiology.
Those results stand in glaring contrast to the findings of the much-discussed SPRINT trial, in which hypertensive patients fared best with an on-treatment SBP driven below 120 mm Hg (N Engl J Med. 2015 Nov 26; 373:2103-16).
“Please note that lower blood pressures, both systolic and diastolic, weren’t associated with lower risk, whereas higher blood pressures considerably increased the risk for major vascular events,” she added.
HOPE-3 (the Third Heart Outcomes Prevention Evaluation) included 12,705 patients in 21 countries who did not have cardiovascular disease and were at intermediate risk, with an average age of 65 years at enrollment and a Framinhgam Risk Score of about 10%. They were randomized double-blind in a 2x2 factorial design to rosuvastatin at 10 mg per day or placebo and/or candesartan at 16 mg plus hydrochlorothiazide at 12.5 mg per day or placebo and prospectively followed for a median of 5.6 years.
The primary outcomes of HOPE-3 have been published (N Engl J Med. 2016 May 26;374[21]:2009-20 and 2021-31). This was a practice-changing trial that opened the door to broader use of statin therapy for primary prevention.
At the ESC congress in Barcelona, Dr. Lonn presented a secondary post-hoc analysis that focused on the impact of antihypertensive therapy in HOPE-3. The results shed new light on the optimal blood pressure levels for triggering initation of antihypertensive therapy, as well as defining the achieved blood pressures that resulted in the greatest reductions in major vascular events.
As this was essentially an all-comers trial of intermediate-risk patients, participants presented with a range of blood pressures at baseline. But more than 4,700 subjects had a baseline SBP of 140-159.9 mm Hg, and 833 had an SBP of 160 mm Hg or more.
The candesartan/hydrochlorothiazide regimen resulted in what Dr. Lonn termed a “moderate” net placebo-subtracted blood pressure reduction of 6/3 mm Hg. The higher the baseline blood pressure, the bigger the reduction.
In the one-third of subjects with a baseline SBP greater than 143.5 mm Hg, antihypertensive therapy resulted in a significant 27% reduction in the composite endpoint of cardiovascular death, MI, or stroke compared with placebo. Those with a baseline SBP of 150 mm Hg or more showed even greater benefit from antihypertensive therapy, with a composite event rate of 4.8% compared with 7.2% for placebo, representing a 34% relative risk reduction in which the event curves began separating at about 2 years.
In contrast, antihypertensive therapy brought no significant reduction in events in patients in the lower two tertiles of baseline SBP. And there was no association at all between baseline DBP and major cardiovascular events across the range of DBP values evaluated in HOPE-3.
But wait: Things get more interesting, according to the cardiac electrophysiologist.
“I find the association between mean in-trial blood pressure as recorded in many measurements and vascular outcomes to be the most interesting analysis. This may be a better look at the association between blood pressure and outcomes than a measurement obtained just once or twice at baseline,” she explained.
Of note, among the 6,356 subjects on candesartan/hydrochlorothiazide, those with a mean on-treatment SBP of 160 mm Hg or more had a 2.61% per year rate of the composite of cardiovascular death, MI, stroke, rescue from cardiac arrest, heart failure, or revascularization. This was more than three-fold higher than the 0.75% per year rate in patients with an on-treatment SBP of 120-139.9 mm Hg. The composite event rate was also significantly higher in those with a mean on-treatment SBP of 140-159.9 mm Hg, at 1.4% per year. The event rate in patients with an on-treatment SBP below 120 mm Hg was identical to that of patients with a value of 120-139.9 mm Hg.
Only among patients with an on-treatment DBP of 90 mm Hg or more was the composite event rate significantly greater than in those with a DBP of 70-79.9 mm Hg, who had the lowest event rate by a margin of 1.89% versus 0.75% per year.
An Australian cardiologist in the audience who has been involved in revamping hypertension treatment guidelines Down Under expressed frustration. He only recently succeeded in wrangling his fellow panelists into incorporating the SPRINT results into the draft guidelines; now HOPE-3 is sending a very different message. What gives? Could the disparate findings simply be due to play of chance? he asked.
Highly unlikely, Dr. Lonn replied.
“There were substantial differences between our trials,” she explained. “First of all, the SPRINT population was at substantially higher risk. They either had to have established cardiovascular disease – we eliminated those people – or significant renal disease – we eliminated those people, too – or age greater than 75, or a Framingham Risk Score above 15%.”
Also, the SPRINT protocol controversially called for unattended blood pressure measurement.
“This is a very pure way ot eliminating white coat hypertension, but it is different from other studies, so it is very difficult to compare SPRINT to older studies or to HOPE-3. Some other investigators have suggested that the difference between attended and unattended blood pressure is close to 10 mm Hg. So our SBP of 130 mm Hg, which had the best outcomes in HOPE-3, may be the same as about 120 mm Hg in SPRINT,” according to Dr. Lonn.
HOPE-3 was funded by the Canadian Institutes of Health Research and AstraZeneca. Dr. Lonn reported serving as a consultant to and receiving research grants from AstraZeneca, Amgen, Bayer, and Novartis.
BARCELONA – How low to go in treating hypertension is a topic of considerable recent controversy. Now the HOPE-3 trial investigators have weighed in, reporting that optimal outcomes in their landmark randomized trial were seen with an achieved, on-treatment systolic blood pressure of 130-140 mm Hg and a diastolic blood pressure of 75-80 mm Hg, Eva M. Lonn, MD, reported at the annual congress of the European Society of Cardiology.
Those results stand in glaring contrast to the findings of the much-discussed SPRINT trial, in which hypertensive patients fared best with an on-treatment SBP driven below 120 mm Hg (N Engl J Med. 2015 Nov 26; 373:2103-16).
“Please note that lower blood pressures, both systolic and diastolic, weren’t associated with lower risk, whereas higher blood pressures considerably increased the risk for major vascular events,” she added.
HOPE-3 (the Third Heart Outcomes Prevention Evaluation) included 12,705 patients in 21 countries who did not have cardiovascular disease and were at intermediate risk, with an average age of 65 years at enrollment and a Framinhgam Risk Score of about 10%. They were randomized double-blind in a 2x2 factorial design to rosuvastatin at 10 mg per day or placebo and/or candesartan at 16 mg plus hydrochlorothiazide at 12.5 mg per day or placebo and prospectively followed for a median of 5.6 years.
The primary outcomes of HOPE-3 have been published (N Engl J Med. 2016 May 26;374[21]:2009-20 and 2021-31). This was a practice-changing trial that opened the door to broader use of statin therapy for primary prevention.
At the ESC congress in Barcelona, Dr. Lonn presented a secondary post-hoc analysis that focused on the impact of antihypertensive therapy in HOPE-3. The results shed new light on the optimal blood pressure levels for triggering initation of antihypertensive therapy, as well as defining the achieved blood pressures that resulted in the greatest reductions in major vascular events.
As this was essentially an all-comers trial of intermediate-risk patients, participants presented with a range of blood pressures at baseline. But more than 4,700 subjects had a baseline SBP of 140-159.9 mm Hg, and 833 had an SBP of 160 mm Hg or more.
The candesartan/hydrochlorothiazide regimen resulted in what Dr. Lonn termed a “moderate” net placebo-subtracted blood pressure reduction of 6/3 mm Hg. The higher the baseline blood pressure, the bigger the reduction.
In the one-third of subjects with a baseline SBP greater than 143.5 mm Hg, antihypertensive therapy resulted in a significant 27% reduction in the composite endpoint of cardiovascular death, MI, or stroke compared with placebo. Those with a baseline SBP of 150 mm Hg or more showed even greater benefit from antihypertensive therapy, with a composite event rate of 4.8% compared with 7.2% for placebo, representing a 34% relative risk reduction in which the event curves began separating at about 2 years.
In contrast, antihypertensive therapy brought no significant reduction in events in patients in the lower two tertiles of baseline SBP. And there was no association at all between baseline DBP and major cardiovascular events across the range of DBP values evaluated in HOPE-3.
But wait: Things get more interesting, according to the cardiac electrophysiologist.
“I find the association between mean in-trial blood pressure as recorded in many measurements and vascular outcomes to be the most interesting analysis. This may be a better look at the association between blood pressure and outcomes than a measurement obtained just once or twice at baseline,” she explained.
Of note, among the 6,356 subjects on candesartan/hydrochlorothiazide, those with a mean on-treatment SBP of 160 mm Hg or more had a 2.61% per year rate of the composite of cardiovascular death, MI, stroke, rescue from cardiac arrest, heart failure, or revascularization. This was more than three-fold higher than the 0.75% per year rate in patients with an on-treatment SBP of 120-139.9 mm Hg. The composite event rate was also significantly higher in those with a mean on-treatment SBP of 140-159.9 mm Hg, at 1.4% per year. The event rate in patients with an on-treatment SBP below 120 mm Hg was identical to that of patients with a value of 120-139.9 mm Hg.
Only among patients with an on-treatment DBP of 90 mm Hg or more was the composite event rate significantly greater than in those with a DBP of 70-79.9 mm Hg, who had the lowest event rate by a margin of 1.89% versus 0.75% per year.
An Australian cardiologist in the audience who has been involved in revamping hypertension treatment guidelines Down Under expressed frustration. He only recently succeeded in wrangling his fellow panelists into incorporating the SPRINT results into the draft guidelines; now HOPE-3 is sending a very different message. What gives? Could the disparate findings simply be due to play of chance? he asked.
Highly unlikely, Dr. Lonn replied.
“There were substantial differences between our trials,” she explained. “First of all, the SPRINT population was at substantially higher risk. They either had to have established cardiovascular disease – we eliminated those people – or significant renal disease – we eliminated those people, too – or age greater than 75, or a Framingham Risk Score above 15%.”
Also, the SPRINT protocol controversially called for unattended blood pressure measurement.
“This is a very pure way ot eliminating white coat hypertension, but it is different from other studies, so it is very difficult to compare SPRINT to older studies or to HOPE-3. Some other investigators have suggested that the difference between attended and unattended blood pressure is close to 10 mm Hg. So our SBP of 130 mm Hg, which had the best outcomes in HOPE-3, may be the same as about 120 mm Hg in SPRINT,” according to Dr. Lonn.
HOPE-3 was funded by the Canadian Institutes of Health Research and AstraZeneca. Dr. Lonn reported serving as a consultant to and receiving research grants from AstraZeneca, Amgen, Bayer, and Novartis.
BARCELONA – How low to go in treating hypertension is a topic of considerable recent controversy. Now the HOPE-3 trial investigators have weighed in, reporting that optimal outcomes in their landmark randomized trial were seen with an achieved, on-treatment systolic blood pressure of 130-140 mm Hg and a diastolic blood pressure of 75-80 mm Hg, Eva M. Lonn, MD, reported at the annual congress of the European Society of Cardiology.
Those results stand in glaring contrast to the findings of the much-discussed SPRINT trial, in which hypertensive patients fared best with an on-treatment SBP driven below 120 mm Hg (N Engl J Med. 2015 Nov 26; 373:2103-16).
“Please note that lower blood pressures, both systolic and diastolic, weren’t associated with lower risk, whereas higher blood pressures considerably increased the risk for major vascular events,” she added.
HOPE-3 (the Third Heart Outcomes Prevention Evaluation) included 12,705 patients in 21 countries who did not have cardiovascular disease and were at intermediate risk, with an average age of 65 years at enrollment and a Framinhgam Risk Score of about 10%. They were randomized double-blind in a 2x2 factorial design to rosuvastatin at 10 mg per day or placebo and/or candesartan at 16 mg plus hydrochlorothiazide at 12.5 mg per day or placebo and prospectively followed for a median of 5.6 years.
The primary outcomes of HOPE-3 have been published (N Engl J Med. 2016 May 26;374[21]:2009-20 and 2021-31). This was a practice-changing trial that opened the door to broader use of statin therapy for primary prevention.
At the ESC congress in Barcelona, Dr. Lonn presented a secondary post-hoc analysis that focused on the impact of antihypertensive therapy in HOPE-3. The results shed new light on the optimal blood pressure levels for triggering initation of antihypertensive therapy, as well as defining the achieved blood pressures that resulted in the greatest reductions in major vascular events.
As this was essentially an all-comers trial of intermediate-risk patients, participants presented with a range of blood pressures at baseline. But more than 4,700 subjects had a baseline SBP of 140-159.9 mm Hg, and 833 had an SBP of 160 mm Hg or more.
The candesartan/hydrochlorothiazide regimen resulted in what Dr. Lonn termed a “moderate” net placebo-subtracted blood pressure reduction of 6/3 mm Hg. The higher the baseline blood pressure, the bigger the reduction.
In the one-third of subjects with a baseline SBP greater than 143.5 mm Hg, antihypertensive therapy resulted in a significant 27% reduction in the composite endpoint of cardiovascular death, MI, or stroke compared with placebo. Those with a baseline SBP of 150 mm Hg or more showed even greater benefit from antihypertensive therapy, with a composite event rate of 4.8% compared with 7.2% for placebo, representing a 34% relative risk reduction in which the event curves began separating at about 2 years.
In contrast, antihypertensive therapy brought no significant reduction in events in patients in the lower two tertiles of baseline SBP. And there was no association at all between baseline DBP and major cardiovascular events across the range of DBP values evaluated in HOPE-3.
But wait: Things get more interesting, according to the cardiac electrophysiologist.
“I find the association between mean in-trial blood pressure as recorded in many measurements and vascular outcomes to be the most interesting analysis. This may be a better look at the association between blood pressure and outcomes than a measurement obtained just once or twice at baseline,” she explained.
Of note, among the 6,356 subjects on candesartan/hydrochlorothiazide, those with a mean on-treatment SBP of 160 mm Hg or more had a 2.61% per year rate of the composite of cardiovascular death, MI, stroke, rescue from cardiac arrest, heart failure, or revascularization. This was more than three-fold higher than the 0.75% per year rate in patients with an on-treatment SBP of 120-139.9 mm Hg. The composite event rate was also significantly higher in those with a mean on-treatment SBP of 140-159.9 mm Hg, at 1.4% per year. The event rate in patients with an on-treatment SBP below 120 mm Hg was identical to that of patients with a value of 120-139.9 mm Hg.
Only among patients with an on-treatment DBP of 90 mm Hg or more was the composite event rate significantly greater than in those with a DBP of 70-79.9 mm Hg, who had the lowest event rate by a margin of 1.89% versus 0.75% per year.
An Australian cardiologist in the audience who has been involved in revamping hypertension treatment guidelines Down Under expressed frustration. He only recently succeeded in wrangling his fellow panelists into incorporating the SPRINT results into the draft guidelines; now HOPE-3 is sending a very different message. What gives? Could the disparate findings simply be due to play of chance? he asked.
Highly unlikely, Dr. Lonn replied.
“There were substantial differences between our trials,” she explained. “First of all, the SPRINT population was at substantially higher risk. They either had to have established cardiovascular disease – we eliminated those people – or significant renal disease – we eliminated those people, too – or age greater than 75, or a Framingham Risk Score above 15%.”
Also, the SPRINT protocol controversially called for unattended blood pressure measurement.
“This is a very pure way ot eliminating white coat hypertension, but it is different from other studies, so it is very difficult to compare SPRINT to older studies or to HOPE-3. Some other investigators have suggested that the difference between attended and unattended blood pressure is close to 10 mm Hg. So our SBP of 130 mm Hg, which had the best outcomes in HOPE-3, may be the same as about 120 mm Hg in SPRINT,” according to Dr. Lonn.
HOPE-3 was funded by the Canadian Institutes of Health Research and AstraZeneca. Dr. Lonn reported serving as a consultant to and receiving research grants from AstraZeneca, Amgen, Bayer, and Novartis.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The on-treatment systolic blood pressure target associated with the greatest reduction in vascular events in the HOPE-3 trial was 130-140 mm Hg.
Data source: The HOPE-3 trial was a randomized, double-blind, placebo-controlled study of 12,705 intermediate-cardiovascular-risk patients in 21 countries who were prospectively followed for a median 5.6 years.
Disclosures: HOPE-3 was funded by the Canadian Institutes of Health Research and AstraZeneca. The presenter reported serving as a consultant to and receiving research grants from AstraZeneca, Amgen, Bayer, and Novartis.
Surgical left atrial appendage closure slashes stroke risk
BARCELONA – Routine surgical closure of the left atrial appendage during open heart surgery provides long-term protection against cerebral ischemic events, according to the findings of the first-ever randomized controlled trial to address the issue.
“I think we can say, based on our study, that it would be advisable to routinely add surgical closure of the left atrial appendage to planned open heart surgery,” Jesper Park-Hansen, MD, said at the annual congress of the European Society of Cardiology.
In light of the demonstrated success of percutaneous closure of the LAA using the Watchman and other devices for stroke prevention in patients with atrial fibrillation, Dr. Park-Hansen and his coinvestigators at the University of Copenhagen organized LAACS (the Left Atrial Appendage Closure Study). The goal was to generate solid, randomized trial evidence as to whether preemptive routine surgical closure of the LAA at the time of cardiac surgery is of benefit. Some cardiac surgeons already do this routinely; many others don’t because of the lack of Level 1 supporting evidence.
LAACS included 141 patients randomized to surgical LAA closure or not at the point of first-time open heart surgery. The study population included patients with and without a history of atrial fibrillation. LAA closure was accomplished via a purse string closure with a silk string around the neck of the appendage backed up by an additional single running suture. Transesophageal echocardiography performed in 10 patients a mean of 520 days post closure showed no signs of leakage or incomplete closure.
The primary composite outcome was comprised of clinical stroke or transient ischemic attack diagnosed by a neurologist, or a silent cerebral infarct detected on MRI performed 2-4 weeks post discharge and again at least 6 months later. At a mean follow-up of 3.7 years and a maximum of 6 years, this outcome had occurred in 6.3% of the LAAC group, significantly lower than the 18.3% rate in controls. All but one patient with a cerebral ischemic event in the control group had atrial fibrillation. The risk of an event was unrelated to whether or not a patient had a history of atrial fibrillation prior to surgery or to CHA2DS2-VASc score.
Dr. Park-Hansen emphasized that he and his coinvestigators don’t consider LAACS to be the final word on routine prophylactic appendage closure.
“This is the first randomized study. We are eager to move on to another randomized study on a larger scale. That is the next step for us,” he said.
“The challenge now – and what we will be discussing with our surgeons – is to agree on a feasible safe and effective means of left atrial appendage closure. My personal opinion is the Lariat suture delivery device or some other easily reproducible method of closure could be a good way to go,” Dr. Park-Hansen added.
The research group’s cardiac surgeons already have ruled out excision and stapling because of concerns about bleeding risk and the additional cost imposed by stapling.
Discussant Volkmar Falk, MD, commented that LAACS was too small, probably severely underpowered, should have included a preoperative MRI so investigators could reliably capture perioperative silent cerebral infarcts, and the double suture purse string is “probably not the best method” to occlude the LAA.
“LAACS addresses an important question, but alas, it does not provide the answer,” declared Dr. Falk, professor and director of the department of cardiothoracic and vascular surgery at Charité Medical University in Berlin.
Dr. Park-Hansen and Dr. Falk reported having no financial conflicts of interest.
BARCELONA – Routine surgical closure of the left atrial appendage during open heart surgery provides long-term protection against cerebral ischemic events, according to the findings of the first-ever randomized controlled trial to address the issue.
“I think we can say, based on our study, that it would be advisable to routinely add surgical closure of the left atrial appendage to planned open heart surgery,” Jesper Park-Hansen, MD, said at the annual congress of the European Society of Cardiology.
In light of the demonstrated success of percutaneous closure of the LAA using the Watchman and other devices for stroke prevention in patients with atrial fibrillation, Dr. Park-Hansen and his coinvestigators at the University of Copenhagen organized LAACS (the Left Atrial Appendage Closure Study). The goal was to generate solid, randomized trial evidence as to whether preemptive routine surgical closure of the LAA at the time of cardiac surgery is of benefit. Some cardiac surgeons already do this routinely; many others don’t because of the lack of Level 1 supporting evidence.
LAACS included 141 patients randomized to surgical LAA closure or not at the point of first-time open heart surgery. The study population included patients with and without a history of atrial fibrillation. LAA closure was accomplished via a purse string closure with a silk string around the neck of the appendage backed up by an additional single running suture. Transesophageal echocardiography performed in 10 patients a mean of 520 days post closure showed no signs of leakage or incomplete closure.
The primary composite outcome was comprised of clinical stroke or transient ischemic attack diagnosed by a neurologist, or a silent cerebral infarct detected on MRI performed 2-4 weeks post discharge and again at least 6 months later. At a mean follow-up of 3.7 years and a maximum of 6 years, this outcome had occurred in 6.3% of the LAAC group, significantly lower than the 18.3% rate in controls. All but one patient with a cerebral ischemic event in the control group had atrial fibrillation. The risk of an event was unrelated to whether or not a patient had a history of atrial fibrillation prior to surgery or to CHA2DS2-VASc score.
Dr. Park-Hansen emphasized that he and his coinvestigators don’t consider LAACS to be the final word on routine prophylactic appendage closure.
“This is the first randomized study. We are eager to move on to another randomized study on a larger scale. That is the next step for us,” he said.
“The challenge now – and what we will be discussing with our surgeons – is to agree on a feasible safe and effective means of left atrial appendage closure. My personal opinion is the Lariat suture delivery device or some other easily reproducible method of closure could be a good way to go,” Dr. Park-Hansen added.
The research group’s cardiac surgeons already have ruled out excision and stapling because of concerns about bleeding risk and the additional cost imposed by stapling.
Discussant Volkmar Falk, MD, commented that LAACS was too small, probably severely underpowered, should have included a preoperative MRI so investigators could reliably capture perioperative silent cerebral infarcts, and the double suture purse string is “probably not the best method” to occlude the LAA.
“LAACS addresses an important question, but alas, it does not provide the answer,” declared Dr. Falk, professor and director of the department of cardiothoracic and vascular surgery at Charité Medical University in Berlin.
Dr. Park-Hansen and Dr. Falk reported having no financial conflicts of interest.
BARCELONA – Routine surgical closure of the left atrial appendage during open heart surgery provides long-term protection against cerebral ischemic events, according to the findings of the first-ever randomized controlled trial to address the issue.
“I think we can say, based on our study, that it would be advisable to routinely add surgical closure of the left atrial appendage to planned open heart surgery,” Jesper Park-Hansen, MD, said at the annual congress of the European Society of Cardiology.
In light of the demonstrated success of percutaneous closure of the LAA using the Watchman and other devices for stroke prevention in patients with atrial fibrillation, Dr. Park-Hansen and his coinvestigators at the University of Copenhagen organized LAACS (the Left Atrial Appendage Closure Study). The goal was to generate solid, randomized trial evidence as to whether preemptive routine surgical closure of the LAA at the time of cardiac surgery is of benefit. Some cardiac surgeons already do this routinely; many others don’t because of the lack of Level 1 supporting evidence.
LAACS included 141 patients randomized to surgical LAA closure or not at the point of first-time open heart surgery. The study population included patients with and without a history of atrial fibrillation. LAA closure was accomplished via a purse string closure with a silk string around the neck of the appendage backed up by an additional single running suture. Transesophageal echocardiography performed in 10 patients a mean of 520 days post closure showed no signs of leakage or incomplete closure.
The primary composite outcome was comprised of clinical stroke or transient ischemic attack diagnosed by a neurologist, or a silent cerebral infarct detected on MRI performed 2-4 weeks post discharge and again at least 6 months later. At a mean follow-up of 3.7 years and a maximum of 6 years, this outcome had occurred in 6.3% of the LAAC group, significantly lower than the 18.3% rate in controls. All but one patient with a cerebral ischemic event in the control group had atrial fibrillation. The risk of an event was unrelated to whether or not a patient had a history of atrial fibrillation prior to surgery or to CHA2DS2-VASc score.
Dr. Park-Hansen emphasized that he and his coinvestigators don’t consider LAACS to be the final word on routine prophylactic appendage closure.
“This is the first randomized study. We are eager to move on to another randomized study on a larger scale. That is the next step for us,” he said.
“The challenge now – and what we will be discussing with our surgeons – is to agree on a feasible safe and effective means of left atrial appendage closure. My personal opinion is the Lariat suture delivery device or some other easily reproducible method of closure could be a good way to go,” Dr. Park-Hansen added.
The research group’s cardiac surgeons already have ruled out excision and stapling because of concerns about bleeding risk and the additional cost imposed by stapling.
Discussant Volkmar Falk, MD, commented that LAACS was too small, probably severely underpowered, should have included a preoperative MRI so investigators could reliably capture perioperative silent cerebral infarcts, and the double suture purse string is “probably not the best method” to occlude the LAA.
“LAACS addresses an important question, but alas, it does not provide the answer,” declared Dr. Falk, professor and director of the department of cardiothoracic and vascular surgery at Charité Medical University in Berlin.
Dr. Park-Hansen and Dr. Falk reported having no financial conflicts of interest.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: The composite rate of clinical stroke, TIA, or silent cerebral infarct in the years following open heart surgery was threefold higher in patients randomized to no prophylactic surgical closure of the left atrial appendage, compared with patients who got appendage closure during their surgery.
Data source: A randomized trial in which 141 patients undergoing first-time open heart surgery were assigned to prophylactic surgical closure of the left atrial appendage or not.
Disclosures: The study was conducted free of commercial support. The presenter reported having no financial conflicts of interest.