MDedge Emergency Medicine

Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

WhiteHouse.gov

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

gtwachtman@mdedge.com

Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

WhiteHouse.gov

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

gtwachtman@mdedge.com

Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

WhiteHouse.gov

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

gtwachtman@mdedge.com

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.

“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.

Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.

In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.

The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.

A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.

“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
 

Aiming at different targets

To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.

Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.

A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.

An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).

Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.

In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).

Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.

The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.
 

Avoiding one in four events

Assessing the French participants in the TST trial showed that targeting LDL below 70 mg/dL for more than 5 years avoided more than one in four subsequent major cardiovascular events among adults who experienced a recent ischemic stroke or TIA.

Furthermore, more intense LDL lowering also avoided more than one in four recurrent cerebral infarctions or urgent carotid revascularizations following a TIA, as well as one in four recurrent cerebral infarctions or hemorrhages (all strokes), compared with the higher LDL target.

“This was obtained without increasing the risk of intracranial hemorrhage with a number needed to treat of 30,” the researchers noted. “In the context of all randomized clinical trials with statin and other lipid-lowering drugs, there is no reason to think that Asian patients do not benefit from statin treatment and from a lower target LDL cholesterol,” the researchers added.

Therefore, they plan to continue assessing the 742 Korean participants until they reach a median of 5 years of follow-up.

Clinically validating results

“My feeling is that these data are highly supportive of a practice that many of us have been using for years without this level of evidence,” Mitchell S.V. Elkind, MD, said when asked to comment on the study.

Prior secondary analyses of studies, including research into patients with intracranial atherosclerosis, demonstrated benefit from treating to this lower LDL cholesterol target. “These studies were suggestive enough that many of us were treating patients aggressively with statins,” added Dr. Elkind, professor of neurology and epidemiology and chief of the division of neurology clinical outcomes research and population sciences at Columbia University in New York.

“But this really confirms that [fact] with clinical trial evidence,” said Dr. Elkind, “and I think will be very useful to us as clinicians.”

The results could be used to counsel patients about the potential benefits of statin therapy or to motivate primary care providers to treat patients more aggressively, said Dr. Elkind, who will begin his term as president of the American Heart Association/American Stroke Association in July.

This study was supported by a grant from the French Ministry of Health and from SOS-Attaque Cérébrale Association, with unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites and from Pfizer for South Korean sites.

Dr. Amarenco receives research grant support and consulting fees from Pfizer, Merck, and AstraZeneca. Elkind had has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SOURCE: Amarenko P et al. ISC 2020. Late-breaking abstract 9.

LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.

“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.

Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.

In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.

The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.

A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.

“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
 

Aiming at different targets

To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.

Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.

A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.

An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).

Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.

In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).

Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.

The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.
 

Avoiding one in four events

Assessing the French participants in the TST trial showed that targeting LDL below 70 mg/dL for more than 5 years avoided more than one in four subsequent major cardiovascular events among adults who experienced a recent ischemic stroke or TIA.

Furthermore, more intense LDL lowering also avoided more than one in four recurrent cerebral infarctions or urgent carotid revascularizations following a TIA, as well as one in four recurrent cerebral infarctions or hemorrhages (all strokes), compared with the higher LDL target.

“This was obtained without increasing the risk of intracranial hemorrhage with a number needed to treat of 30,” the researchers noted. “In the context of all randomized clinical trials with statin and other lipid-lowering drugs, there is no reason to think that Asian patients do not benefit from statin treatment and from a lower target LDL cholesterol,” the researchers added.

Therefore, they plan to continue assessing the 742 Korean participants until they reach a median of 5 years of follow-up.

Clinically validating results

“My feeling is that these data are highly supportive of a practice that many of us have been using for years without this level of evidence,” Mitchell S.V. Elkind, MD, said when asked to comment on the study.

Prior secondary analyses of studies, including research into patients with intracranial atherosclerosis, demonstrated benefit from treating to this lower LDL cholesterol target. “These studies were suggestive enough that many of us were treating patients aggressively with statins,” added Dr. Elkind, professor of neurology and epidemiology and chief of the division of neurology clinical outcomes research and population sciences at Columbia University in New York.

“But this really confirms that [fact] with clinical trial evidence,” said Dr. Elkind, “and I think will be very useful to us as clinicians.”

The results could be used to counsel patients about the potential benefits of statin therapy or to motivate primary care providers to treat patients more aggressively, said Dr. Elkind, who will begin his term as president of the American Heart Association/American Stroke Association in July.

This study was supported by a grant from the French Ministry of Health and from SOS-Attaque Cérébrale Association, with unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites and from Pfizer for South Korean sites.

Dr. Amarenco receives research grant support and consulting fees from Pfizer, Merck, and AstraZeneca. Elkind had has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SOURCE: Amarenko P et al. ISC 2020. Late-breaking abstract 9.

LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.

“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.

Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.

In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.

The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.

A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.

“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
 

Aiming at different targets

To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.

Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.

A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.

An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).

Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.

In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).

Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.

The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.
 

Avoiding one in four events

Assessing the French participants in the TST trial showed that targeting LDL below 70 mg/dL for more than 5 years avoided more than one in four subsequent major cardiovascular events among adults who experienced a recent ischemic stroke or TIA.

Furthermore, more intense LDL lowering also avoided more than one in four recurrent cerebral infarctions or urgent carotid revascularizations following a TIA, as well as one in four recurrent cerebral infarctions or hemorrhages (all strokes), compared with the higher LDL target.

“This was obtained without increasing the risk of intracranial hemorrhage with a number needed to treat of 30,” the researchers noted. “In the context of all randomized clinical trials with statin and other lipid-lowering drugs, there is no reason to think that Asian patients do not benefit from statin treatment and from a lower target LDL cholesterol,” the researchers added.

Therefore, they plan to continue assessing the 742 Korean participants until they reach a median of 5 years of follow-up.

Clinically validating results

“My feeling is that these data are highly supportive of a practice that many of us have been using for years without this level of evidence,” Mitchell S.V. Elkind, MD, said when asked to comment on the study.

Prior secondary analyses of studies, including research into patients with intracranial atherosclerosis, demonstrated benefit from treating to this lower LDL cholesterol target. “These studies were suggestive enough that many of us were treating patients aggressively with statins,” added Dr. Elkind, professor of neurology and epidemiology and chief of the division of neurology clinical outcomes research and population sciences at Columbia University in New York.

“But this really confirms that [fact] with clinical trial evidence,” said Dr. Elkind, “and I think will be very useful to us as clinicians.”

The results could be used to counsel patients about the potential benefits of statin therapy or to motivate primary care providers to treat patients more aggressively, said Dr. Elkind, who will begin his term as president of the American Heart Association/American Stroke Association in July.

This study was supported by a grant from the French Ministry of Health and from SOS-Attaque Cérébrale Association, with unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites and from Pfizer for South Korean sites.

Dr. Amarenco receives research grant support and consulting fees from Pfizer, Merck, and AstraZeneca. Elkind had has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SOURCE: Amarenko P et al. ISC 2020. Late-breaking abstract 9.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects hair follicles, with predilection for intertriginous sites. The prevalence of HS ranges from 0.1% to 2%, with HS significantly affecting the quality of life for patients, with both physical and emotional consequences.

Guidelines from the U.S. and Canadian Hidradenitis Suppurativa Foundations provide a summary of management and treatment for patients.
 

Grading

Hurley staging is recommended to determine therapies. Stage I is classified by recurrent nodules and abscesses with minimal scars. Stage II is classified by one or a limited number of sinuses and/or scarring within a body region. Stage III is classified by multiple or extensive sinuses and/or scarring. The Dermatology Life Quality Index and pain visual analog scale scores can be used in addition to the Hurley staging for management.

Diagnostic testing/comorbidities screening

There is limited evidence for microbiological testing for HS because skin flora is the main bacteria cultured. Patients should be screened for smoking use, diabetes, metabolic syndrome, depression/anxiety, follicular occlusion tetrad, and squamous cell carcinoma. Some studies have suggested an association between the severity of HS and smoking; therefore, smoking cessation is recommended. Patients should also be counseled on weight loss.

Zinc supplementation (90 mg daily) may be helpful. However, there is insufficient evidence for recommendations to avoid diary, brewer’s yeast, friction, deodorant, depilation, or shaving. There is also insufficient data to support vitamin D supplementation.
 

Topical/intralesional therapies

Expert opinion supports the use of chlorhexidine, benzoyl peroxide, or zinc pyrithione. A keratolytic and antiseptic cream such as resorcinol 15% cream may be used but can cause contact dermatitis. Topical clindamycin may decrease pustules formation, but it can increase resistance to Staphylococcus aureus. Triamcinolone intravlesional injections may decrease inflamed HS lesions in the short term.

Systemic antibiotics

Systemic antibiotics have been used for decades to treat HS. Tetracyclines for a 12-week course or long-term maintenance can be used in mild to moderate HS. Clindamycin and rifampin combination can be used as second-line therapy for mild to moderate HS. Moxifloxacin, metronidazole, and rifampin combination can also be considered second-line treatment for moderate to severe disease. Dapsone can be used in patients with Hurley stage I or II for maintenance therapy. Ertapenem IV can be used as a rescue or as bridge therapy for severe disease.

The duration of antibiotics and frequency of use depends on each patient and resistance.

Hormonal agents and retinoids

Although androgens may influence HS, evidence for hormonal agents is limited. Hormonal agents, such as ethinyl estradiol and spironolactone, can be considered for females with mild to moderate HS. Retinoids may be considered as a second- or third-line agent, especially in patients with severe acne and HS.

Immunosuppressants and biologics

Immunosuppressants such as methotrexate and azathioprine provide limited benefit; therefore, they are not recommended. Colchicine with minocycline may provide slight benefit in refractory mild to moderate HS. Cyclosporine may be considered in recalcitrant, severe HS. Systemic corticosteroids can be used short term for acute flares or long term for severe HS.

Biologic therapy is becoming more common and the choice of therapy for moderate to severe HS. Adalimumab is currently the only Food and Drug Administration–approved tumor necrosis factor–inhibitor treatment for HS. Other biologics – including infliximab, anakinra, and ustekinumab – may be effective for HS, but optimal dosing needs to be determined.
 

Pain management

While there are no studies about pain in HS, acute pain management should include topical analgesics and oral nonsteroidal anti-inflammatory drugs. Anticonvulsants such as pregabalin or gabapentin may help with neuropathic pain, and opioids can be considered if there is no improvement with first-line agents.

Surgical management

Recurrent nodules and tunnels can be deroofed or excised. Acute abscesses may be relieved by incision and drainage. Extensive lesions may require wide local scalpel excision, carbon dioxide laser excision, or electrosurgical excision. Surgery alone does not affect the biology of HS; therefore, surgical interventions should be reserved for disease that is not managed by medical therapy.

The bottom line

HS is a chronic inflammatory condition with complex medical management and surgical treatment options. Hurley staging I-III can be used to grade severity and determine therapy. Management of pain, tobacco cessation, weight loss, and mental health are important aspects of HS. Zinc supplementation (90 mg daily) may be helpful. Experts opinion supports the use of chlorhexidine, benzoyl peroxide or zinc pyrithione.

Acute lesions may be managed with short-term oral or intralesional corticosteroids, as well as deroofing or incision and drainage. Moderate-to-severe HS may be managed with systemic antibiotics or biologics and surgical therapy. Adalimumab is the only FDA-approved biologic for treatment of HS.

Dr. Chuong is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

References

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019 Jul;81(1):76-90.

Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication form the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.

NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.

Mitchel L. Zoler/MDedge News

Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.

The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.

The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.

It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.

While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.

The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).

The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.

mzoler@mdedge.com

NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.

Mitchel L. Zoler/MDedge News

Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.

The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.

The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.

It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.

While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.

The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).

The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.

mzoler@mdedge.com

NATIONAL HARBOR, MD. – Researchers have created an artificial intelligence algorithm that can evaluate a 10-second ECG recording of a person in normal sinus rhythm and tell with a sensitivity and specificity of almost 80% whether or not that person ever had atrial fibrillation episodes some time in the past or will have a first arrhythmia episode in the near future.

Mitchel L. Zoler/MDedge News

Although this algorithm – derived from and then validated with a dataset of nearly 650,000 ECG recordings from more than 180,000 patients – still needs prospective validation, it offers the prospect for a potential revolution in screening for atrial fibrillation (AFib), Paul A. Friedman, MD, cautioned at the annual International AF Symposium. If initial clinical findings are confirmed, it would show that a 10-second, 12-lead ECG recording can provide the same screening scope as what otherwise takes weeks of ambulatory ECG recording with a Holter monitor or an implanted device, explained Dr. Friedman, professor of medicine and chair of the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

This finding “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” Dr. Friedman and his associates noted in the published report of their study (Lancet. 2019 Sep 7;394[10201]:861-7). “We’re still working to define the window of ECG” recording time that provides the optimal assessment for a history of asymptomatic AFib, but the “possibilities this opens are huge,” Dr. Friedman said in his talk at the symposium. This work sprang from the premise that “subtle signatures” in a brief, apparently normal sinus rhythm ECG tracing can harbor reliable clues about AFib history or an imminent episode.

The 2019 report by Dr. Friedman and associates documented that in the validation phase of their study, the trained artificial intelligence (AI) program identified patients with a history of AFib or an impending arrhythmia event from a single, 10-second ECG that to the naked eye seemed to show normal sinus rhythm with a sensitivity of 79.0%, a specificity of 79.5%, and an accuracy of 79.4%. It also showed an area under a receiver operating characteristic curve of 0.87, meaning that screening for AFib by this method compared favorably with the area-under-the-curve (AUC) results tallied by several widely accepted screening tools, including Pap smears for cervical cancer (AUC of 0.70), mammograms for breast cancer (AUC of 0.85), and CHA2DS2-VASc scoring for estimating stroke risk in AFib patients (AUC of 0.57-0.72), Dr. Friedman said.

The researchers developed the AI algorithm with more than 450,000 10-second ECG tracings collected from roughly 126,000 patients who underwent at least one ECG recording as part of their routine care at the Mayo Clinic during 1993-2017. The goal was for the program to find and validate recurring characteristics in the ECG that consistently linked with a history of or an impending AFib episode and that did not appear in ECG recordings from people without any AFib history. The program this effort produced then underwent further adjustment with the use of more than 64,340 ECGs from an additional 18,116 patients, and then the final product underwent validation testing with a further 130,802 ECGs collected from an additional 36,280 people, the study phase that resulted in the reported sensitivity and specificity estimates.

It’s currently unclear to Dr. Friedman and associates what specific features the program uses to classify patients. It’s an important question, but if the results are reproducible and reliable, this uncertainty shouldn’t slow clinical adoption, he said in an interview.

While “this particular algorithm needs prospective vetting,” a similar algorithm developed by Dr. Friedman and the same research team that uses a 10-second ECG to identify patients with a left ventricular ejection fraction of 35% or less is further advanced in development, and a device that uses this algorithm will soon receive Food and Drug Administration review under a fast track designation that the agency approved in late 2019.

The researchers developed this algorithm for estimating left ventricular function using a strategy similar to their development of a tool for diagnosing AFib (Nat Med. 2019 Jan 7;25[1]:70-4), and results from 100 patients prospectively studied with this approach to ECG analysis and reported at the American Heart Association scientific sessions in November 2019 showed that the algorithm identified substantial left ventricular dysfunction with an AUC of 0.906 (Circulation. 2019 Nov 19;140[suppl 1]:A13447). The same team of investigators has developed an AI algorithm that can calculate a person’s physiologic age based on the ECG recording (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]: 10.1161/CIRCEP.119.007284).

The study received no commercial funding, and Dr. Friedman and coauthors had no relevant disclosures. The Mayo Clinic has licensed a related artificial intelligence algorithm to EKO, and Dr. Friedman may benefit financially from this arrangement.

mzoler@mdedge.com

LOS ANGELES – Endovascular therapy significantly improved functional outcomes and reduced mortality at 90 days, compared with standard thrombolysis alone, new evidence from a large, prospective registry study suggests.

Participants who received both interventions were almost five times more likely to be able to walk independently at 90 days compared with those who received thrombolysis alone.

Despite multiple trials supporting the potential benefits of endovascular therapy for anterior stroke, little prospective research addresses outcomes associated with an ischemic stroke caused by a posterior basilar artery occlusion (BAO).

“Basilar artery occlusion is the ‘orphan’ of the large vessel occlusions,” Raul Gomes Nogueira, MD, PhD, said here at a late-breaking abstract session at the International Stroke Conference sponsored by the American Heart Association.

“They account for about 5% of the large vessel occlusions – but have the most dismal prognosis.” Severe disability and mortality rates associated with BAO, for example, reach an estimated 68% to 78%, he said.

The results, from the EVT for Acute Basilar Artery Occlusion Study (BASILAR), were also simultaneously published in JAMA Neurology.

Prior studies in this patient population are generally single-center, retrospective studies and “the numbers tend to be small,” said Nogueira, who is affiliated with the Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine in Atlanta, Georgia.

Nogueira and colleagues studied 829 consecutive adults who presented with an acute, symptomatic BAO. They examined a nationwide prospective registry study of people with radiologically confirmed BAO in 47 comprehensive stroke centers across 15 provinces in China.

The median age was 65 years and 74% were men. A total 182 participants received thrombolysis therapy within 6 hours of estimated BAO onset. The 647 people in the dual intervention group also received endovascular therapy within 24 hours.

Standard medical treatment included intravenous rt-PA or urokinase, antiplatelet drugs and systematic anticoagulation alone or in combination. Endovascular therapy included mechanical thrombectomy with stent retrievers and/or thromboaspiration, balloon angioplasty, stenting, intra-arterial thrombolysis, or a combination of these interventions.

Interestingly, participants were not randomly assigned, in part because of the favorable outcomes associated with endovascular therapy. “The high number of patients who received [the dual intervention] may suggest the existence of a lack of equipoise among participating centers,” the researchers note.

Key Efficacy Endpoints

A significantly higher proportion of people in the dual treatment group achieved the primary outcome, functional improvement at 90 days, at 32%, compared with 9.3% in the thrombolysis-only group. This endpoint was defined as a modified Rankin Scale (mRS) score of 3 or less, which reflects an ability to walk independently. The difference was statistically significant (P < .001).

The absolute difference between groups was 22.7% (95% confidence interval, 17.1%-28.2%) with an adjusted odds ratio of 4.70 (95% CI, 2.53-8.75; P < .001) in favor of dual intervention.

The number needed to treat for one additional patient to be able to walk unassisted was 4.4.

Other outcomes, including differences in National Institutes of Health Stroke Scale scores from baseline to 5 to 7 days or discharge, as well as propensity score matching and subgroup analyses, likewise supported the superiority of using both interventions.
 

Safety Outcomes

Nogueira and colleagues also assessed safety. They found that symptomatic intracerebral hemorrhage (ICH) occurred in 45 patients, or 7.1% of the endovascular treatment group. In contrast, only one patient, or 0.5%, of the standard medical treatment alone cohort experienced an ICH. This difference was statistically significant (P < .001).

Mortality at 90 days was significantly lower in the endovascular therapy plus medical therapy group, 46.2%, compared with 71.4% in the standard medical treatment alone group (P < .001).

The absolute difference in mortality was 25.2% (95% CI, 17.6%-2.8%) favoring dual treatment, with an adjusted odds ratio of 2.93 (95% CI, 1.95-4.40; P < .001).

Rates of other serious adverse events during the 90-day follow-up period were similar in the two study groups, Nogueira said.

He acknowledged that the nonrandomized design was a limitation of the registry study, adding that “sometimes in life it’s important to acknowledge the best of what can be done. It’s very hard when you have access to thrombectomy to randomize people.”

However, other researchers have attempted or are enrolling people with BAO into trials that randomly assign them to endovascular therapy and standard medical treatment or medical treatment alone.

The BEST trial in China, for example, randomly assigned 131 patients to these groups but was stopped early in September 2017. “The BEST trial was terminated prematurely because of loss of equipoise that led to a high crossover rate and drop in valid recruitment,” the current researchers note.

“The other two trials…are facing the challenge of whether they will achieve their inclusion target,” they add, “because a growing number of stroke centers are unwilling to randomize patients to standard medical treatment alone after the many positive results of trials for endovascular treatment in patients with anterior-circulation stroke.”

The BAOCHE trial from China, for example, is ongoing with approximately 110 patients enrolled so far.

Investigators for the Basilar Artery International Cooperation Study (BASICS) in the Netherlands just completed enrollment of their 300th and final patient in December 2019.

“We are hopeful BASICS trial will shed additional light,” Nogueira said. The results are expected to be presented at the European Stroke Organization Conference in Vienna in May 2020.
 

More Guidance From MRI?

“With the advent of the stent retrievers and successful recanalization, we know there can be better outcomes for patients. And we know the morbidity and mortality of the basilar artery occlusions are so poor that we tend to want to be aggressive in these cases,” session comoderator Shlee S. Song, MD, director of the Comprehensive Stroke Center and associate professor of neurology at Cedars-Sinai Medical Center in Los Angeles, California, told Medscape Medical News when asked to comment on the study.

“I agree that we’ve lost equipoise in this cohort – that we really cannot do a randomized trial anymore. You know if you don’t do anything, 90% of the time there will be a poor outcome,” she added.

This is an important study for showing how BAO patients fare after endovascular treatment, Song said.

One unanswered question from the study is if any of the centers in China used magnetic resonance imaging to help determine the most appropriate candidates for endovascular treatment of these posterior circulation strokes, which is a common practice in the United States, she said.

The study was supported by the National Science Fund for Distinguished Young Scholars, Chongqing Major Disease Prevention and Control Technology Research Project, Army Medical University Clinical Medical Research Talent Training Program, and Major Clinical Innovation Technology Project of the Second Affiliated Hospital of the Army Military Medical University. Sing had no relevant disclosures. Nogueira’s financial disclosures include working as a consultant for Stryker Neurovascular; as a principal investigator on the Imperative trial and the PROST trial; as a steering committee member for Biogen for the CHARM trial; as an advisory board member for Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals and Brainomix; and as an advisory board member with stock options for Viz.ai, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte Pharmaceuticals, and Cerebrotech.

This article first appeared on Medscape.com.

SOURCE: Nogueira RG et al. ISC 2020. Late-breaking abstract 17.

LOS ANGELES – Endovascular therapy significantly improved functional outcomes and reduced mortality at 90 days, compared with standard thrombolysis alone, new evidence from a large, prospective registry study suggests.

Participants who received both interventions were almost five times more likely to be able to walk independently at 90 days compared with those who received thrombolysis alone.

Despite multiple trials supporting the potential benefits of endovascular therapy for anterior stroke, little prospective research addresses outcomes associated with an ischemic stroke caused by a posterior basilar artery occlusion (BAO).

“Basilar artery occlusion is the ‘orphan’ of the large vessel occlusions,” Raul Gomes Nogueira, MD, PhD, said here at a late-breaking abstract session at the International Stroke Conference sponsored by the American Heart Association.

“They account for about 5% of the large vessel occlusions – but have the most dismal prognosis.” Severe disability and mortality rates associated with BAO, for example, reach an estimated 68% to 78%, he said.

The results, from the EVT for Acute Basilar Artery Occlusion Study (BASILAR), were also simultaneously published in JAMA Neurology.

Prior studies in this patient population are generally single-center, retrospective studies and “the numbers tend to be small,” said Nogueira, who is affiliated with the Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine in Atlanta, Georgia.

Nogueira and colleagues studied 829 consecutive adults who presented with an acute, symptomatic BAO. They examined a nationwide prospective registry study of people with radiologically confirmed BAO in 47 comprehensive stroke centers across 15 provinces in China.

The median age was 65 years and 74% were men. A total 182 participants received thrombolysis therapy within 6 hours of estimated BAO onset. The 647 people in the dual intervention group also received endovascular therapy within 24 hours.

Standard medical treatment included intravenous rt-PA or urokinase, antiplatelet drugs and systematic anticoagulation alone or in combination. Endovascular therapy included mechanical thrombectomy with stent retrievers and/or thromboaspiration, balloon angioplasty, stenting, intra-arterial thrombolysis, or a combination of these interventions.

Interestingly, participants were not randomly assigned, in part because of the favorable outcomes associated with endovascular therapy. “The high number of patients who received [the dual intervention] may suggest the existence of a lack of equipoise among participating centers,” the researchers note.

Key Efficacy Endpoints

A significantly higher proportion of people in the dual treatment group achieved the primary outcome, functional improvement at 90 days, at 32%, compared with 9.3% in the thrombolysis-only group. This endpoint was defined as a modified Rankin Scale (mRS) score of 3 or less, which reflects an ability to walk independently. The difference was statistically significant (P < .001).

The absolute difference between groups was 22.7% (95% confidence interval, 17.1%-28.2%) with an adjusted odds ratio of 4.70 (95% CI, 2.53-8.75; P < .001) in favor of dual intervention.

The number needed to treat for one additional patient to be able to walk unassisted was 4.4.

Other outcomes, including differences in National Institutes of Health Stroke Scale scores from baseline to 5 to 7 days or discharge, as well as propensity score matching and subgroup analyses, likewise supported the superiority of using both interventions.
 

Safety Outcomes

Nogueira and colleagues also assessed safety. They found that symptomatic intracerebral hemorrhage (ICH) occurred in 45 patients, or 7.1% of the endovascular treatment group. In contrast, only one patient, or 0.5%, of the standard medical treatment alone cohort experienced an ICH. This difference was statistically significant (P < .001).

Mortality at 90 days was significantly lower in the endovascular therapy plus medical therapy group, 46.2%, compared with 71.4% in the standard medical treatment alone group (P < .001).

The absolute difference in mortality was 25.2% (95% CI, 17.6%-2.8%) favoring dual treatment, with an adjusted odds ratio of 2.93 (95% CI, 1.95-4.40; P < .001).

Rates of other serious adverse events during the 90-day follow-up period were similar in the two study groups, Nogueira said.

He acknowledged that the nonrandomized design was a limitation of the registry study, adding that “sometimes in life it’s important to acknowledge the best of what can be done. It’s very hard when you have access to thrombectomy to randomize people.”

However, other researchers have attempted or are enrolling people with BAO into trials that randomly assign them to endovascular therapy and standard medical treatment or medical treatment alone.

The BEST trial in China, for example, randomly assigned 131 patients to these groups but was stopped early in September 2017. “The BEST trial was terminated prematurely because of loss of equipoise that led to a high crossover rate and drop in valid recruitment,” the current researchers note.

“The other two trials…are facing the challenge of whether they will achieve their inclusion target,” they add, “because a growing number of stroke centers are unwilling to randomize patients to standard medical treatment alone after the many positive results of trials for endovascular treatment in patients with anterior-circulation stroke.”

The BAOCHE trial from China, for example, is ongoing with approximately 110 patients enrolled so far.

Investigators for the Basilar Artery International Cooperation Study (BASICS) in the Netherlands just completed enrollment of their 300th and final patient in December 2019.

“We are hopeful BASICS trial will shed additional light,” Nogueira said. The results are expected to be presented at the European Stroke Organization Conference in Vienna in May 2020.
 

More Guidance From MRI?

“With the advent of the stent retrievers and successful recanalization, we know there can be better outcomes for patients. And we know the morbidity and mortality of the basilar artery occlusions are so poor that we tend to want to be aggressive in these cases,” session comoderator Shlee S. Song, MD, director of the Comprehensive Stroke Center and associate professor of neurology at Cedars-Sinai Medical Center in Los Angeles, California, told Medscape Medical News when asked to comment on the study.

“I agree that we’ve lost equipoise in this cohort – that we really cannot do a randomized trial anymore. You know if you don’t do anything, 90% of the time there will be a poor outcome,” she added.

This is an important study for showing how BAO patients fare after endovascular treatment, Song said.

One unanswered question from the study is if any of the centers in China used magnetic resonance imaging to help determine the most appropriate candidates for endovascular treatment of these posterior circulation strokes, which is a common practice in the United States, she said.

The study was supported by the National Science Fund for Distinguished Young Scholars, Chongqing Major Disease Prevention and Control Technology Research Project, Army Medical University Clinical Medical Research Talent Training Program, and Major Clinical Innovation Technology Project of the Second Affiliated Hospital of the Army Military Medical University. Sing had no relevant disclosures. Nogueira’s financial disclosures include working as a consultant for Stryker Neurovascular; as a principal investigator on the Imperative trial and the PROST trial; as a steering committee member for Biogen for the CHARM trial; as an advisory board member for Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals and Brainomix; and as an advisory board member with stock options for Viz.ai, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte Pharmaceuticals, and Cerebrotech.

This article first appeared on Medscape.com.

SOURCE: Nogueira RG et al. ISC 2020. Late-breaking abstract 17.

LOS ANGELES – Endovascular therapy significantly improved functional outcomes and reduced mortality at 90 days, compared with standard thrombolysis alone, new evidence from a large, prospective registry study suggests.

Participants who received both interventions were almost five times more likely to be able to walk independently at 90 days compared with those who received thrombolysis alone.

Despite multiple trials supporting the potential benefits of endovascular therapy for anterior stroke, little prospective research addresses outcomes associated with an ischemic stroke caused by a posterior basilar artery occlusion (BAO).

“Basilar artery occlusion is the ‘orphan’ of the large vessel occlusions,” Raul Gomes Nogueira, MD, PhD, said here at a late-breaking abstract session at the International Stroke Conference sponsored by the American Heart Association.

“They account for about 5% of the large vessel occlusions – but have the most dismal prognosis.” Severe disability and mortality rates associated with BAO, for example, reach an estimated 68% to 78%, he said.

The results, from the EVT for Acute Basilar Artery Occlusion Study (BASILAR), were also simultaneously published in JAMA Neurology.

Prior studies in this patient population are generally single-center, retrospective studies and “the numbers tend to be small,” said Nogueira, who is affiliated with the Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine in Atlanta, Georgia.

Nogueira and colleagues studied 829 consecutive adults who presented with an acute, symptomatic BAO. They examined a nationwide prospective registry study of people with radiologically confirmed BAO in 47 comprehensive stroke centers across 15 provinces in China.

The median age was 65 years and 74% were men. A total 182 participants received thrombolysis therapy within 6 hours of estimated BAO onset. The 647 people in the dual intervention group also received endovascular therapy within 24 hours.

Standard medical treatment included intravenous rt-PA or urokinase, antiplatelet drugs and systematic anticoagulation alone or in combination. Endovascular therapy included mechanical thrombectomy with stent retrievers and/or thromboaspiration, balloon angioplasty, stenting, intra-arterial thrombolysis, or a combination of these interventions.

Interestingly, participants were not randomly assigned, in part because of the favorable outcomes associated with endovascular therapy. “The high number of patients who received [the dual intervention] may suggest the existence of a lack of equipoise among participating centers,” the researchers note.

Key Efficacy Endpoints

A significantly higher proportion of people in the dual treatment group achieved the primary outcome, functional improvement at 90 days, at 32%, compared with 9.3% in the thrombolysis-only group. This endpoint was defined as a modified Rankin Scale (mRS) score of 3 or less, which reflects an ability to walk independently. The difference was statistically significant (P < .001).

The absolute difference between groups was 22.7% (95% confidence interval, 17.1%-28.2%) with an adjusted odds ratio of 4.70 (95% CI, 2.53-8.75; P < .001) in favor of dual intervention.

The number needed to treat for one additional patient to be able to walk unassisted was 4.4.

Other outcomes, including differences in National Institutes of Health Stroke Scale scores from baseline to 5 to 7 days or discharge, as well as propensity score matching and subgroup analyses, likewise supported the superiority of using both interventions.
 

Safety Outcomes

Nogueira and colleagues also assessed safety. They found that symptomatic intracerebral hemorrhage (ICH) occurred in 45 patients, or 7.1% of the endovascular treatment group. In contrast, only one patient, or 0.5%, of the standard medical treatment alone cohort experienced an ICH. This difference was statistically significant (P < .001).

Mortality at 90 days was significantly lower in the endovascular therapy plus medical therapy group, 46.2%, compared with 71.4% in the standard medical treatment alone group (P < .001).

The absolute difference in mortality was 25.2% (95% CI, 17.6%-2.8%) favoring dual treatment, with an adjusted odds ratio of 2.93 (95% CI, 1.95-4.40; P < .001).

Rates of other serious adverse events during the 90-day follow-up period were similar in the two study groups, Nogueira said.

He acknowledged that the nonrandomized design was a limitation of the registry study, adding that “sometimes in life it’s important to acknowledge the best of what can be done. It’s very hard when you have access to thrombectomy to randomize people.”

However, other researchers have attempted or are enrolling people with BAO into trials that randomly assign them to endovascular therapy and standard medical treatment or medical treatment alone.

The BEST trial in China, for example, randomly assigned 131 patients to these groups but was stopped early in September 2017. “The BEST trial was terminated prematurely because of loss of equipoise that led to a high crossover rate and drop in valid recruitment,” the current researchers note.

“The other two trials…are facing the challenge of whether they will achieve their inclusion target,” they add, “because a growing number of stroke centers are unwilling to randomize patients to standard medical treatment alone after the many positive results of trials for endovascular treatment in patients with anterior-circulation stroke.”

The BAOCHE trial from China, for example, is ongoing with approximately 110 patients enrolled so far.

Investigators for the Basilar Artery International Cooperation Study (BASICS) in the Netherlands just completed enrollment of their 300th and final patient in December 2019.

“We are hopeful BASICS trial will shed additional light,” Nogueira said. The results are expected to be presented at the European Stroke Organization Conference in Vienna in May 2020.
 

More Guidance From MRI?

“With the advent of the stent retrievers and successful recanalization, we know there can be better outcomes for patients. And we know the morbidity and mortality of the basilar artery occlusions are so poor that we tend to want to be aggressive in these cases,” session comoderator Shlee S. Song, MD, director of the Comprehensive Stroke Center and associate professor of neurology at Cedars-Sinai Medical Center in Los Angeles, California, told Medscape Medical News when asked to comment on the study.

“I agree that we’ve lost equipoise in this cohort – that we really cannot do a randomized trial anymore. You know if you don’t do anything, 90% of the time there will be a poor outcome,” she added.

This is an important study for showing how BAO patients fare after endovascular treatment, Song said.

One unanswered question from the study is if any of the centers in China used magnetic resonance imaging to help determine the most appropriate candidates for endovascular treatment of these posterior circulation strokes, which is a common practice in the United States, she said.

The study was supported by the National Science Fund for Distinguished Young Scholars, Chongqing Major Disease Prevention and Control Technology Research Project, Army Medical University Clinical Medical Research Talent Training Program, and Major Clinical Innovation Technology Project of the Second Affiliated Hospital of the Army Military Medical University. Sing had no relevant disclosures. Nogueira’s financial disclosures include working as a consultant for Stryker Neurovascular; as a principal investigator on the Imperative trial and the PROST trial; as a steering committee member for Biogen for the CHARM trial; as an advisory board member for Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals and Brainomix; and as an advisory board member with stock options for Viz.ai, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte Pharmaceuticals, and Cerebrotech.

This article first appeared on Medscape.com.

SOURCE: Nogueira RG et al. ISC 2020. Late-breaking abstract 17.

It’s past time to call the novel coronavirus, COVID-19, a pandemic and “time to push people to prepare, and guide their prep,” according to risk communication experts.

Courtesy NIAID-RML

Medical messaging about containing or stopping the spread of the virus is doing more harm than good, write Peter Sandman, PhD, and Jody Lanard, MD, both based in New York City, in a recent blog post.

“We are near-certain that the desperate-sounding last-ditch containment messaging of recent days is contributing to a massive global misperception,” they warn.

“The most crucial (and overdue) risk communication task … is to help people visualize their communities when ‘keeping it out’ – containment – is no longer relevant.”

That message is embraced by several experts who spoke to Medscape Medical News.

“I’m jealous of what [they] have written: It is so clear, so correct, and so practical,” said David Fisman, MD, MPH, professor of epidemiology at the University of Toronto, Canada. “I think WHO [World Health Organization] is shying away from the P word,” he continued, referring to the organization’s continuing decision not to call the outbreak a pandemic.

“I fully support exactly what [Sandman and Lanard] are saying,” said Michael Osterholm, PhD, MPH, professor of environmental health sciences and director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota in Minneapolis.

Health care professionals should now be advising people how to prepare – yet this is the most neglected message, Sandman and Lanard write. “Hardly any officials are telling civil society and the general public how to get ready for this pandemic.”

Effective communication should inform people of what to expect now, they continue: “[T]he end of most quarantines, travel restrictions, contact tracing, and other measures designed to keep ‘them’ from infecting ‘us,’ and the switch to measures like canceling mass events designed to keep us from infecting each other.”

Among the new messages that should be delivered are things like:

• Stockpiling nonperishable food and prescription meds.
• Considering care of sick family members.
• Cross-training work personnel so one person’s absence won’t derail an organization’s ability to function.

“We hope that governments and healthcare institutions are using this time wisely,” Sandman and Lanard continue. “We know that ordinary citizens are not being asked to do so. In most countries … ordinary citizens have not been asked to prepare. Instead, they have been led to expect that their governments will keep the virus from their doors.”

This article first appeared on Medscape.com.

It’s past time to call the novel coronavirus, COVID-19, a pandemic and “time to push people to prepare, and guide their prep,” according to risk communication experts.

Courtesy NIAID-RML

Medical messaging about containing or stopping the spread of the virus is doing more harm than good, write Peter Sandman, PhD, and Jody Lanard, MD, both based in New York City, in a recent blog post.

“We are near-certain that the desperate-sounding last-ditch containment messaging of recent days is contributing to a massive global misperception,” they warn.

“The most crucial (and overdue) risk communication task … is to help people visualize their communities when ‘keeping it out’ – containment – is no longer relevant.”

That message is embraced by several experts who spoke to Medscape Medical News.

“I’m jealous of what [they] have written: It is so clear, so correct, and so practical,” said David Fisman, MD, MPH, professor of epidemiology at the University of Toronto, Canada. “I think WHO [World Health Organization] is shying away from the P word,” he continued, referring to the organization’s continuing decision not to call the outbreak a pandemic.

“I fully support exactly what [Sandman and Lanard] are saying,” said Michael Osterholm, PhD, MPH, professor of environmental health sciences and director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota in Minneapolis.

Health care professionals should now be advising people how to prepare – yet this is the most neglected message, Sandman and Lanard write. “Hardly any officials are telling civil society and the general public how to get ready for this pandemic.”

Effective communication should inform people of what to expect now, they continue: “[T]he end of most quarantines, travel restrictions, contact tracing, and other measures designed to keep ‘them’ from infecting ‘us,’ and the switch to measures like canceling mass events designed to keep us from infecting each other.”

Among the new messages that should be delivered are things like:

• Stockpiling nonperishable food and prescription meds.
• Considering care of sick family members.
• Cross-training work personnel so one person’s absence won’t derail an organization’s ability to function.

“We hope that governments and healthcare institutions are using this time wisely,” Sandman and Lanard continue. “We know that ordinary citizens are not being asked to do so. In most countries … ordinary citizens have not been asked to prepare. Instead, they have been led to expect that their governments will keep the virus from their doors.”

This article first appeared on Medscape.com.

It’s past time to call the novel coronavirus, COVID-19, a pandemic and “time to push people to prepare, and guide their prep,” according to risk communication experts.

Courtesy NIAID-RML

Medical messaging about containing or stopping the spread of the virus is doing more harm than good, write Peter Sandman, PhD, and Jody Lanard, MD, both based in New York City, in a recent blog post.

“We are near-certain that the desperate-sounding last-ditch containment messaging of recent days is contributing to a massive global misperception,” they warn.

“The most crucial (and overdue) risk communication task … is to help people visualize their communities when ‘keeping it out’ – containment – is no longer relevant.”

That message is embraced by several experts who spoke to Medscape Medical News.

“I’m jealous of what [they] have written: It is so clear, so correct, and so practical,” said David Fisman, MD, MPH, professor of epidemiology at the University of Toronto, Canada. “I think WHO [World Health Organization] is shying away from the P word,” he continued, referring to the organization’s continuing decision not to call the outbreak a pandemic.

“I fully support exactly what [Sandman and Lanard] are saying,” said Michael Osterholm, PhD, MPH, professor of environmental health sciences and director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota in Minneapolis.

Health care professionals should now be advising people how to prepare – yet this is the most neglected message, Sandman and Lanard write. “Hardly any officials are telling civil society and the general public how to get ready for this pandemic.”

Effective communication should inform people of what to expect now, they continue: “[T]he end of most quarantines, travel restrictions, contact tracing, and other measures designed to keep ‘them’ from infecting ‘us,’ and the switch to measures like canceling mass events designed to keep us from infecting each other.”

Among the new messages that should be delivered are things like:

• Stockpiling nonperishable food and prescription meds.
• Considering care of sick family members.
• Cross-training work personnel so one person’s absence won’t derail an organization’s ability to function.

“We hope that governments and healthcare institutions are using this time wisely,” Sandman and Lanard continue. “We know that ordinary citizens are not being asked to do so. In most countries … ordinary citizens have not been asked to prepare. Instead, they have been led to expect that their governments will keep the virus from their doors.”

This article first appeared on Medscape.com.

Bempedoic acid, the first agent in a new class of drugs that reduce LDL cholesterol, received Food and Drug Administration approval on Feb. 21 for treating selected hypercholesterolemic patients and is a welcome addition to the medicine cabinet, say lipid experts.

MDedge News

However, it is a tertiary option at least until results from a 14,000 patient clinical-outcome trial of bempedoic acid come out, likely in 2022, they agreed.

“I’m excited to have a new tool in the toolkit for treating high-risk patients, but I will always reach first for the drugs proven to reduce clinical outcomes,” said Erin D. Michos, MD, director of Women’s Cardiovascular Health and associate director of Preventive Cardiology at Johns Hopkins Medicine in Baltimore. That sentiment, shared by other experts, should for the time being relegate bempedoic acid (Nexletol) to a backup role behind statins, ezetimibe, and the PCSK9 inhibitor antibodies that are all now on the U.S. market and all buttressed with evidence of their ability to cut cardiovascular disease death and other CVD outcomes from large outcome studies.

The existing evidence base for bempedoic acid rests primarily two multicenter, randomized, placebo-controlled clinical trials of bempedoic acid in patients with LDL levels above 70 mg/dL while on maximally tolerated lipid-lowering therapy. In CLEAR Harmony, results showed that treatment with bempedoic acid cut LDL-cholesterol levels by an average of 18% more compared with placebo (N Engl J Med 2019;380:1022-32). In CLEAR Wisdom, bempedoic acid reduced LDL cholesterol levels by 17% (JAMA. 2019;322[18]:1780-8).

While those two trials proved the drug’s ability to lower levels of LDL cholesterol, they lacked the power to address whether this effect cut the incidence of CVD events, a question that the CLEAR Outcomes trial aims to answer.

“I believe in the lipid hypothesis, but the main thing we need to see is whether bempedoic acid leads to a meaningful reduction in CVD events. The window for bempedoic acid will remain narrow until we see the outcomes results,” Dr. Michos said in an interview.

Bempedoic acid is a prodrug that’s activated in liver and targets the same cholesterol synthesis pathway as statins by inhibition of ATP-citrate lyase, an enzyme that’s upstream of HMG-CoA reductase, thereby enhancing LDL cholesterol clearance via up-regulation of LDL receptors

.

Combined treatment with bempedoic acid and ezetimibe “may be successful in avoiding [using] a PCSK9 inhibitor in some patients, and in particular patients with HeFH or those who are statin intolerant.” But like his colleagues, Dr. Eckel agreed that, for the moment, ezetimibe has an edge over bempedoic acid because of its more extensive evidence base. “If the combination of bempedoic acid and ezetimibe is not needed, the decision [of which one of these to use] needs to depend on the outcome trial results for ezetimibe,” he said. Other factors clinicians could apply if faced with choosing between these two agents include the significant reduction in high-sensitivity C-reactive protein that bempedoic acid produces; the downside that bempedoic acid can cause in some patients an early and persistent rise in serum uric acid levels that can trigger gout flares in patients with a history of gout or at risk for gout; and cost, he said.

Cost is the room-dwelling elephant that colors many decisions about which lipid-lowering drug to use for patients, with options running the price gamut from the generic and uniformly affordable statins and ezetimibe, to the notoriously pricey PCSK9 inhibitors that remain for many patients either prohibitively expensive or hard to get covered by some insurers. Bempedoic acid seems on track to fall somewhere between these two poles, although staff members from Esperion, the company that developed and will market bempedoic acid as Nexletol starting on March 30, declared in a conference call on Feb. 24 that “cost will not be an issue,” for indicated patients prescribed the drug. Company representatives cited a program of coupons, discounts, and rebates they have planned that they anticipate will allow patients who meet the labeled indications to have an out-of-pocket cost for bempedoic acid of “as low as” $10 for a 90-pill supply. They also noted their goal of getting bempedoic acid onto the lowest tier of the Medicare formulary.

How these steps actually play out in the fun house of U.S. prescription drug pricing and preauthorizations remains to be seen. “Out-of-pocket costs are not the real drivers” of drug access, noted Dr. Robinson. “Insurers will likely start with restricted access and prior authorization requirements, just as they did with ezetimibe when it was on patent and prior to having the results from a CVD outcomes trial.” For the time being, bempedoic acid can generally be seen as “expensive ezetimibe,” summed up Dr. Robinson.

Despite that somewhat dismissive characterization, experts are intrigued by the possibility of combining two moderately potent, oral, and safe lipid-lowering drugs in selected patients as a potential alternative to the still financially challenging PCSK9 inhibitors. Combining bempedoic acid and ezetimibe “has a lot of appeal,” said Dr. Michos. “Even though preauthorization has gotten better, it’s still a challenge to get a PCSK9 inhibitor approved.”

Much of her enthusiasm stems from a study reported last year that randomized 301 patients to treatment with bempedoic acid, ezetimibe, or both. The results showed that combined treatment has a similar safety profile to treatment with either drug alone, and produced a cut in LDL cholesterol that was roughly additive for the reductions produced by each drug by itself: Ezetimibe alone cut LDL by about 23%, bempedoic acid alone by about 17%, and the two dosed together once daily resulted in an average 36% drop (Eur J Prev Cardiol. 2019 Jul 29. doi: 10.1177/2047487319864671). The results showed that, “in patients requiring intensive LDL cholesterol lowering, who cannot afford PCSK9 inhibitors, or have statin intolerance, bempedoic acid and ezetimibe are stronger together and can serve as an alternative approach for lipid management in ASCVD prevention,” wrote Dr. Michos and a coauthor in a commentary that appeared with the study results (Eur J Prev Cardiol. 2019 Jul 29. doi: 10.1177/2047487319864672).

The concept of combined bempedoic acid and ezetimibe treatment is so appealing that the bempedoic acid manufacturer, Esperion, has already developed a single-pill formulation of the two drugs that received FDA marketing approval on February 26. A company statement said that marketing of this combined formulation, Nexlizet, will start in July 2020.

Although interest in bempedoic acid seems running high for patients included in the new FDA indication, Dr. Michos and others see possibly greater potential for what would now be off-label use for primary prevention in high-risk patients without HeFH, patients who generally don’t qualify for insurance coverage of a PCSK9 inhibitor.

“Use in primary prevention in [non-HeFH] patients with insufficient lowering of LDL cholesterol wouldn’t surprise me,” but a big concern will be out-of-pocket cost when off-label use precludes insurance coverage or discount eligibility, noted Dr. Eckel. An Esperion spokesperson said that the undiscounted, wholesale acquisition cost for bempedoic acid is expected to be roughly $10/pill, or about $300 for a 30-day supply, positioning it more or less midway between generic statins and ezetimibe and the list price for a PCSk9 inhibitor of roughly $500/month.

“I’m most excited about bempedoic acid in the off-label space, for patients who can’t get approved for a PCSK9 inhibitor, for treating patients with subclinical ASCVD, or really high-risk patients with multiple risk factors including diabetes,” especially when these patients are intolerant of a high-intensity statin regimen, said Dr. Michos. “I have a clinic full of patients” who can’t take their full, indicated dosage of a high-intensity statin, and when those patients also can’t get on treatment with a PCSK9 inhibitor then bempedoic acid will be an important part of their alternative regimen, she explained.

Dr. Michos had no disclosures. Dr. Robinson has received research funding from Esperion and from several other companies, and she has been a consultant to Amgen, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, and Sanofi. Dr. Eckel has received honoraria from Kowa, Merck, Novo Nordisk, and Sanofi/Regeneron.

This article was updated 2/27/20.

mzoler@mdedge.com

Bempedoic acid, the first agent in a new class of drugs that reduce LDL cholesterol, received Food and Drug Administration approval on Feb. 21 for treating selected hypercholesterolemic patients and is a welcome addition to the medicine cabinet, say lipid experts.

MDedge News

However, it is a tertiary option at least until results from a 14,000 patient clinical-outcome trial of bempedoic acid come out, likely in 2022, they agreed.

“I’m excited to have a new tool in the toolkit for treating high-risk patients, but I will always reach first for the drugs proven to reduce clinical outcomes,” said Erin D. Michos, MD, director of Women’s Cardiovascular Health and associate director of Preventive Cardiology at Johns Hopkins Medicine in Baltimore. That sentiment, shared by other experts, should for the time being relegate bempedoic acid (Nexletol) to a backup role behind statins, ezetimibe, and the PCSK9 inhibitor antibodies that are all now on the U.S. market and all buttressed with evidence of their ability to cut cardiovascular disease death and other CVD outcomes from large outcome studies.

The existing evidence base for bempedoic acid rests primarily two multicenter, randomized, placebo-controlled clinical trials of bempedoic acid in patients with LDL levels above 70 mg/dL while on maximally tolerated lipid-lowering therapy. In CLEAR Harmony, results showed that treatment with bempedoic acid cut LDL-cholesterol levels by an average of 18% more compared with placebo (N Engl J Med 2019;380:1022-32). In CLEAR Wisdom, bempedoic acid reduced LDL cholesterol levels by 17% (JAMA. 2019;322[18]:1780-8).

While those two trials proved the drug’s ability to lower levels of LDL cholesterol, they lacked the power to address whether this effect cut the incidence of CVD events, a question that the CLEAR Outcomes trial aims to answer.

“I believe in the lipid hypothesis, but the main thing we need to see is whether bempedoic acid leads to a meaningful reduction in CVD events. The window for bempedoic acid will remain narrow until we see the outcomes results,” Dr. Michos said in an interview.

Bempedoic acid is a prodrug that’s activated in liver and targets the same cholesterol synthesis pathway as statins by inhibition of ATP-citrate lyase, an enzyme that’s upstream of HMG-CoA reductase, thereby enhancing LDL cholesterol clearance via up-regulation of LDL receptors

.

Combined treatment with bempedoic acid and ezetimibe “may be successful in avoiding [using] a PCSK9 inhibitor in some patients, and in particular patients with HeFH or those who are statin intolerant.” But like his colleagues, Dr. Eckel agreed that, for the moment, ezetimibe has an edge over bempedoic acid because of its more extensive evidence base. “If the combination of bempedoic acid and ezetimibe is not needed, the decision [of which one of these to use] needs to depend on the outcome trial results for ezetimibe,” he said. Other factors clinicians could apply if faced with choosing between these two agents include the significant reduction in high-sensitivity C-reactive protein that bempedoic acid produces; the downside that bempedoic acid can cause in some patients an early and persistent rise in serum uric acid levels that can trigger gout flares in patients with a history of gout or at risk for gout; and cost, he said.

Cost is the room-dwelling elephant that colors many decisions about which lipid-lowering drug to use for patients, with options running the price gamut from the generic and uniformly affordable statins and ezetimibe, to the notoriously pricey PCSK9 inhibitors that remain for many patients either prohibitively expensive or hard to get covered by some insurers. Bempedoic acid seems on track to fall somewhere between these two poles, although staff members from Esperion, the company that developed and will market bempedoic acid as Nexletol starting on March 30, declared in a conference call on Feb. 24 that “cost will not be an issue,” for indicated patients prescribed the drug. Company representatives cited a program of coupons, discounts, and rebates they have planned that they anticipate will allow patients who meet the labeled indications to have an out-of-pocket cost for bempedoic acid of “as low as” $10 for a 90-pill supply. They also noted their goal of getting bempedoic acid onto the lowest tier of the Medicare formulary.

How these steps actually play out in the fun house of U.S. prescription drug pricing and preauthorizations remains to be seen. “Out-of-pocket costs are not the real drivers” of drug access, noted Dr. Robinson. “Insurers will likely start with restricted access and prior authorization requirements, just as they did with ezetimibe when it was on patent and prior to having the results from a CVD outcomes trial.” For the time being, bempedoic acid can generally be seen as “expensive ezetimibe,” summed up Dr. Robinson.

Despite that somewhat dismissive characterization, experts are intrigued by the possibility of combining two moderately potent, oral, and safe lipid-lowering drugs in selected patients as a potential alternative to the still financially challenging PCSK9 inhibitors. Combining bempedoic acid and ezetimibe “has a lot of appeal,” said Dr. Michos. “Even though preauthorization has gotten better, it’s still a challenge to get a PCSK9 inhibitor approved.”

Much of her enthusiasm stems from a study reported last year that randomized 301 patients to treatment with bempedoic acid, ezetimibe, or both. The results showed that combined treatment has a similar safety profile to treatment with either drug alone, and produced a cut in LDL cholesterol that was roughly additive for the reductions produced by each drug by itself: Ezetimibe alone cut LDL by about 23%, bempedoic acid alone by about 17%, and the two dosed together once daily resulted in an average 36% drop (Eur J Prev Cardiol. 2019 Jul 29. doi: 10.1177/2047487319864671). The results showed that, “in patients requiring intensive LDL cholesterol lowering, who cannot afford PCSK9 inhibitors, or have statin intolerance, bempedoic acid and ezetimibe are stronger together and can serve as an alternative approach for lipid management in ASCVD prevention,” wrote Dr. Michos and a coauthor in a commentary that appeared with the study results (Eur J Prev Cardiol. 2019 Jul 29. doi: 10.1177/2047487319864672).

The concept of combined bempedoic acid and ezetimibe treatment is so appealing that the bempedoic acid manufacturer, Esperion, has already developed a single-pill formulation of the two drugs that received FDA marketing approval on February 26. A company statement said that marketing of this combined formulation, Nexlizet, will start in July 2020.

Although interest in bempedoic acid seems running high for patients included in the new FDA indication, Dr. Michos and others see possibly greater potential for what would now be off-label use for primary prevention in high-risk patients without HeFH, patients who generally don’t qualify for insurance coverage of a PCSK9 inhibitor.

“Use in primary prevention in [non-HeFH] patients with insufficient lowering of LDL cholesterol wouldn’t surprise me,” but a big concern will be out-of-pocket cost when off-label use precludes insurance coverage or discount eligibility, noted Dr. Eckel. An Esperion spokesperson said that the undiscounted, wholesale acquisition cost for bempedoic acid is expected to be roughly $10/pill, or about $300 for a 30-day supply, positioning it more or less midway between generic statins and ezetimibe and the list price for a PCSk9 inhibitor of roughly $500/month.

“I’m most excited about bempedoic acid in the off-label space, for patients who can’t get approved for a PCSK9 inhibitor, for treating patients with subclinical ASCVD, or really high-risk patients with multiple risk factors including diabetes,” especially when these patients are intolerant of a high-intensity statin regimen, said Dr. Michos. “I have a clinic full of patients” who can’t take their full, indicated dosage of a high-intensity statin, and when those patients also can’t get on treatment with a PCSK9 inhibitor then bempedoic acid will be an important part of their alternative regimen, she explained.

Dr. Michos had no disclosures. Dr. Robinson has received research funding from Esperion and from several other companies, and she has been a consultant to Amgen, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, and Sanofi. Dr. Eckel has received honoraria from Kowa, Merck, Novo Nordisk, and Sanofi/Regeneron.

This article was updated 2/27/20.

mzoler@mdedge.com

Bempedoic acid, the first agent in a new class of drugs that reduce LDL cholesterol, received Food and Drug Administration approval on Feb. 21 for treating selected hypercholesterolemic patients and is a welcome addition to the medicine cabinet, say lipid experts.

MDedge News

However, it is a tertiary option at least until results from a 14,000 patient clinical-outcome trial of bempedoic acid come out, likely in 2022, they agreed.

“I’m excited to have a new tool in the toolkit for treating high-risk patients, but I will always reach first for the drugs proven to reduce clinical outcomes,” said Erin D. Michos, MD, director of Women’s Cardiovascular Health and associate director of Preventive Cardiology at Johns Hopkins Medicine in Baltimore. That sentiment, shared by other experts, should for the time being relegate bempedoic acid (Nexletol) to a backup role behind statins, ezetimibe, and the PCSK9 inhibitor antibodies that are all now on the U.S. market and all buttressed with evidence of their ability to cut cardiovascular disease death and other CVD outcomes from large outcome studies.

The existing evidence base for bempedoic acid rests primarily two multicenter, randomized, placebo-controlled clinical trials of bempedoic acid in patients with LDL levels above 70 mg/dL while on maximally tolerated lipid-lowering therapy. In CLEAR Harmony, results showed that treatment with bempedoic acid cut LDL-cholesterol levels by an average of 18% more compared with placebo (N Engl J Med 2019;380:1022-32). In CLEAR Wisdom, bempedoic acid reduced LDL cholesterol levels by 17% (JAMA. 2019;322[18]:1780-8).

While those two trials proved the drug’s ability to lower levels of LDL cholesterol, they lacked the power to address whether this effect cut the incidence of CVD events, a question that the CLEAR Outcomes trial aims to answer.

“I believe in the lipid hypothesis, but the main thing we need to see is whether bempedoic acid leads to a meaningful reduction in CVD events. The window for bempedoic acid will remain narrow until we see the outcomes results,” Dr. Michos said in an interview.

Bempedoic acid is a prodrug that’s activated in liver and targets the same cholesterol synthesis pathway as statins by inhibition of ATP-citrate lyase, an enzyme that’s upstream of HMG-CoA reductase, thereby enhancing LDL cholesterol clearance via up-regulation of LDL receptors

.

Combined treatment with bempedoic acid and ezetimibe “may be successful in avoiding [using] a PCSK9 inhibitor in some patients, and in particular patients with HeFH or those who are statin intolerant.” But like his colleagues, Dr. Eckel agreed that, for the moment, ezetimibe has an edge over bempedoic acid because of its more extensive evidence base. “If the combination of bempedoic acid and ezetimibe is not needed, the decision [of which one of these to use] needs to depend on the outcome trial results for ezetimibe,” he said. Other factors clinicians could apply if faced with choosing between these two agents include the significant reduction in high-sensitivity C-reactive protein that bempedoic acid produces; the downside that bempedoic acid can cause in some patients an early and persistent rise in serum uric acid levels that can trigger gout flares in patients with a history of gout or at risk for gout; and cost, he said.

Cost is the room-dwelling elephant that colors many decisions about which lipid-lowering drug to use for patients, with options running the price gamut from the generic and uniformly affordable statins and ezetimibe, to the notoriously pricey PCSK9 inhibitors that remain for many patients either prohibitively expensive or hard to get covered by some insurers. Bempedoic acid seems on track to fall somewhere between these two poles, although staff members from Esperion, the company that developed and will market bempedoic acid as Nexletol starting on March 30, declared in a conference call on Feb. 24 that “cost will not be an issue,” for indicated patients prescribed the drug. Company representatives cited a program of coupons, discounts, and rebates they have planned that they anticipate will allow patients who meet the labeled indications to have an out-of-pocket cost for bempedoic acid of “as low as” $10 for a 90-pill supply. They also noted their goal of getting bempedoic acid onto the lowest tier of the Medicare formulary.

How these steps actually play out in the fun house of U.S. prescription drug pricing and preauthorizations remains to be seen. “Out-of-pocket costs are not the real drivers” of drug access, noted Dr. Robinson. “Insurers will likely start with restricted access and prior authorization requirements, just as they did with ezetimibe when it was on patent and prior to having the results from a CVD outcomes trial.” For the time being, bempedoic acid can generally be seen as “expensive ezetimibe,” summed up Dr. Robinson.

Despite that somewhat dismissive characterization, experts are intrigued by the possibility of combining two moderately potent, oral, and safe lipid-lowering drugs in selected patients as a potential alternative to the still financially challenging PCSK9 inhibitors. Combining bempedoic acid and ezetimibe “has a lot of appeal,” said Dr. Michos. “Even though preauthorization has gotten better, it’s still a challenge to get a PCSK9 inhibitor approved.”

Much of her enthusiasm stems from a study reported last year that randomized 301 patients to treatment with bempedoic acid, ezetimibe, or both. The results showed that combined treatment has a similar safety profile to treatment with either drug alone, and produced a cut in LDL cholesterol that was roughly additive for the reductions produced by each drug by itself: Ezetimibe alone cut LDL by about 23%, bempedoic acid alone by about 17%, and the two dosed together once daily resulted in an average 36% drop (Eur J Prev Cardiol. 2019 Jul 29. doi: 10.1177/2047487319864671). The results showed that, “in patients requiring intensive LDL cholesterol lowering, who cannot afford PCSK9 inhibitors, or have statin intolerance, bempedoic acid and ezetimibe are stronger together and can serve as an alternative approach for lipid management in ASCVD prevention,” wrote Dr. Michos and a coauthor in a commentary that appeared with the study results (Eur J Prev Cardiol. 2019 Jul 29. doi: 10.1177/2047487319864672).

The concept of combined bempedoic acid and ezetimibe treatment is so appealing that the bempedoic acid manufacturer, Esperion, has already developed a single-pill formulation of the two drugs that received FDA marketing approval on February 26. A company statement said that marketing of this combined formulation, Nexlizet, will start in July 2020.

Although interest in bempedoic acid seems running high for patients included in the new FDA indication, Dr. Michos and others see possibly greater potential for what would now be off-label use for primary prevention in high-risk patients without HeFH, patients who generally don’t qualify for insurance coverage of a PCSK9 inhibitor.

“Use in primary prevention in [non-HeFH] patients with insufficient lowering of LDL cholesterol wouldn’t surprise me,” but a big concern will be out-of-pocket cost when off-label use precludes insurance coverage or discount eligibility, noted Dr. Eckel. An Esperion spokesperson said that the undiscounted, wholesale acquisition cost for bempedoic acid is expected to be roughly $10/pill, or about $300 for a 30-day supply, positioning it more or less midway between generic statins and ezetimibe and the list price for a PCSk9 inhibitor of roughly $500/month.

“I’m most excited about bempedoic acid in the off-label space, for patients who can’t get approved for a PCSK9 inhibitor, for treating patients with subclinical ASCVD, or really high-risk patients with multiple risk factors including diabetes,” especially when these patients are intolerant of a high-intensity statin regimen, said Dr. Michos. “I have a clinic full of patients” who can’t take their full, indicated dosage of a high-intensity statin, and when those patients also can’t get on treatment with a PCSK9 inhibitor then bempedoic acid will be an important part of their alternative regimen, she explained.

Dr. Michos had no disclosures. Dr. Robinson has received research funding from Esperion and from several other companies, and she has been a consultant to Amgen, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, and Sanofi. Dr. Eckel has received honoraria from Kowa, Merck, Novo Nordisk, and Sanofi/Regeneron.

This article was updated 2/27/20.

mzoler@mdedge.com

Women who had gestational diabetes mellitus had an increased risk for later type 2 diabetes if they carried certain genetic risk factors for the disease, according to a new analysis in BMJ Open Diabetes Research & Care of data from two independent populations.

A higher genetic risk score (GRS) had a modest association with developing type 2 diabetes, but a healthier diet may mitigate this risk, as Mengying Li, PhD, and her colleagues found for participants in the Nurses’ Health Study and members of the Danish National Birth Cohort who developed gestational diabetes mellitus (GDM).

Of 1,884 white women with a history of GDM in the Nurses’ Health Study II (NHSII), 446 (23.7%) went on to develop type 2 diabetes, and of the 550 women who had GDM in the Danish National Birth Cohort (DNBC), 155 (28.2%) developed the disease. The researchers calculated a GRS for type 2 diabetes for the full cohort. Genome-wide association studies completed in European populations were used to identify 59 single-nucleotide polymorphisms (SNPs) associated with the disease.

Dr. Li, an epidemiologist and postdoctoral researcher at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md., and her coauthors found that women whose GRS was in the highest quartile had a relative risk of 1.19 for type 2 diabetes. The relative risks for the three lower quartiles were 1.25, 0.97, and 1.00, respectively (P value for trend = .02). For each increase of five risk alleles in the GRS, NHSII participants had a 7% increased risk for type 2 diabetes, and DNBC participants saw a 9% increased risk.

Comparing these findings with other studies looking at genetic risk and type 2 diabetes in the general population, Dr. Li and her coauthors noted that the increase in relative risk for type 2 disease with increase in GRS was actually slightly weaker in the GDM cohort they studied. “The smaller effect size among women with GDM likely reflects an already higher baseline genetic risk for [type 2 diabetes] than the general population, as we have demonstrated,” they explained.

Though 11 individual SNPs had a significant individual association with the risk for type 2 diabetes initially, that association disappeared after correction for a false-discovery rate. Dr. Li and her coinvestigators conducted a sensitivity analysis that included only 42 SNPs that were later definitively associated with type 2 disease and they saw essentially unchanged results.

The researchers also investigated how dietary quality affected the GRS–type 2 diabetes association by dichotomizing self-reported diet quality in both cohorts into healthier diet quality and less healthy diet quality. They found a tighter association between GRS and type 2 diabetes for women with diet quality below the median, whereas women with higher diet quality did not have such a strong association between GRS and type 2 disease. The researchers wrote that there was “suggestive evidence that a healthful diet might mitigate the excessive risk of T2D [type 2 diabetes] related to greater genetic susceptibility, which supports public health efforts of encouraging a healthful diet” for diabetes prevention in this high-risk population.

Patients in the NHSII were followed for a mean 21.3 years, and those in the DNBC were followed for a mean 12.7 years. Mean age at index pregnancy was 30.5 years for the NHSII cohort and 31.7 for the DNBC cohort. In the NHSII cohort, just 8.4% of participants reported smoking before pregnancy, compared with 26.4% of those in the DNBC cohort. The NHSII cohort participants, wrote Dr. Li and her coauthors, “were also less likely to have a family history of diabetes, less likely to smoke, and be leaner than women in the DNBC.”

Dr. Li and her coauthors noted that, “despite being the largest genetic study by far on [type 2 diabetes] among women with GDM, our study may not be sufficiently powered to examine the associations of individual T2D SNPs in relation to the risk of developing T2D.” Another limitation was that for the Danish cohort, information about diet was drawn from a one-time questionnaire administered between 9 and 16 years after the index pregnancy, so full data about dietary quality over time was not available. Also of note is that the study included only white participants, limiting generalizability to women of color. The authors called for expanding this research into more racially diverse populations.

The study was supported by the National Institutes of Health. The authors reported that they had no conflicts of interest.

SOURCE: Li M et al. BMJ Open Diab Res Care. 2020 Feb 13. doi: 10.1136/bmjdrc-2019-000850.

Women who had gestational diabetes mellitus had an increased risk for later type 2 diabetes if they carried certain genetic risk factors for the disease, according to a new analysis in BMJ Open Diabetes Research & Care of data from two independent populations.

A higher genetic risk score (GRS) had a modest association with developing type 2 diabetes, but a healthier diet may mitigate this risk, as Mengying Li, PhD, and her colleagues found for participants in the Nurses’ Health Study and members of the Danish National Birth Cohort who developed gestational diabetes mellitus (GDM).

Of 1,884 white women with a history of GDM in the Nurses’ Health Study II (NHSII), 446 (23.7%) went on to develop type 2 diabetes, and of the 550 women who had GDM in the Danish National Birth Cohort (DNBC), 155 (28.2%) developed the disease. The researchers calculated a GRS for type 2 diabetes for the full cohort. Genome-wide association studies completed in European populations were used to identify 59 single-nucleotide polymorphisms (SNPs) associated with the disease.

Dr. Li, an epidemiologist and postdoctoral researcher at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md., and her coauthors found that women whose GRS was in the highest quartile had a relative risk of 1.19 for type 2 diabetes. The relative risks for the three lower quartiles were 1.25, 0.97, and 1.00, respectively (P value for trend = .02). For each increase of five risk alleles in the GRS, NHSII participants had a 7% increased risk for type 2 diabetes, and DNBC participants saw a 9% increased risk.

Comparing these findings with other studies looking at genetic risk and type 2 diabetes in the general population, Dr. Li and her coauthors noted that the increase in relative risk for type 2 disease with increase in GRS was actually slightly weaker in the GDM cohort they studied. “The smaller effect size among women with GDM likely reflects an already higher baseline genetic risk for [type 2 diabetes] than the general population, as we have demonstrated,” they explained.

Though 11 individual SNPs had a significant individual association with the risk for type 2 diabetes initially, that association disappeared after correction for a false-discovery rate. Dr. Li and her coinvestigators conducted a sensitivity analysis that included only 42 SNPs that were later definitively associated with type 2 disease and they saw essentially unchanged results.

The researchers also investigated how dietary quality affected the GRS–type 2 diabetes association by dichotomizing self-reported diet quality in both cohorts into healthier diet quality and less healthy diet quality. They found a tighter association between GRS and type 2 diabetes for women with diet quality below the median, whereas women with higher diet quality did not have such a strong association between GRS and type 2 disease. The researchers wrote that there was “suggestive evidence that a healthful diet might mitigate the excessive risk of T2D [type 2 diabetes] related to greater genetic susceptibility, which supports public health efforts of encouraging a healthful diet” for diabetes prevention in this high-risk population.

Patients in the NHSII were followed for a mean 21.3 years, and those in the DNBC were followed for a mean 12.7 years. Mean age at index pregnancy was 30.5 years for the NHSII cohort and 31.7 for the DNBC cohort. In the NHSII cohort, just 8.4% of participants reported smoking before pregnancy, compared with 26.4% of those in the DNBC cohort. The NHSII cohort participants, wrote Dr. Li and her coauthors, “were also less likely to have a family history of diabetes, less likely to smoke, and be leaner than women in the DNBC.”

Dr. Li and her coauthors noted that, “despite being the largest genetic study by far on [type 2 diabetes] among women with GDM, our study may not be sufficiently powered to examine the associations of individual T2D SNPs in relation to the risk of developing T2D.” Another limitation was that for the Danish cohort, information about diet was drawn from a one-time questionnaire administered between 9 and 16 years after the index pregnancy, so full data about dietary quality over time was not available. Also of note is that the study included only white participants, limiting generalizability to women of color. The authors called for expanding this research into more racially diverse populations.

The study was supported by the National Institutes of Health. The authors reported that they had no conflicts of interest.

SOURCE: Li M et al. BMJ Open Diab Res Care. 2020 Feb 13. doi: 10.1136/bmjdrc-2019-000850.

Women who had gestational diabetes mellitus had an increased risk for later type 2 diabetes if they carried certain genetic risk factors for the disease, according to a new analysis in BMJ Open Diabetes Research & Care of data from two independent populations.

A higher genetic risk score (GRS) had a modest association with developing type 2 diabetes, but a healthier diet may mitigate this risk, as Mengying Li, PhD, and her colleagues found for participants in the Nurses’ Health Study and members of the Danish National Birth Cohort who developed gestational diabetes mellitus (GDM).

Of 1,884 white women with a history of GDM in the Nurses’ Health Study II (NHSII), 446 (23.7%) went on to develop type 2 diabetes, and of the 550 women who had GDM in the Danish National Birth Cohort (DNBC), 155 (28.2%) developed the disease. The researchers calculated a GRS for type 2 diabetes for the full cohort. Genome-wide association studies completed in European populations were used to identify 59 single-nucleotide polymorphisms (SNPs) associated with the disease.

Dr. Li, an epidemiologist and postdoctoral researcher at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md., and her coauthors found that women whose GRS was in the highest quartile had a relative risk of 1.19 for type 2 diabetes. The relative risks for the three lower quartiles were 1.25, 0.97, and 1.00, respectively (P value for trend = .02). For each increase of five risk alleles in the GRS, NHSII participants had a 7% increased risk for type 2 diabetes, and DNBC participants saw a 9% increased risk.

Comparing these findings with other studies looking at genetic risk and type 2 diabetes in the general population, Dr. Li and her coauthors noted that the increase in relative risk for type 2 disease with increase in GRS was actually slightly weaker in the GDM cohort they studied. “The smaller effect size among women with GDM likely reflects an already higher baseline genetic risk for [type 2 diabetes] than the general population, as we have demonstrated,” they explained.

Though 11 individual SNPs had a significant individual association with the risk for type 2 diabetes initially, that association disappeared after correction for a false-discovery rate. Dr. Li and her coinvestigators conducted a sensitivity analysis that included only 42 SNPs that were later definitively associated with type 2 disease and they saw essentially unchanged results.

The researchers also investigated how dietary quality affected the GRS–type 2 diabetes association by dichotomizing self-reported diet quality in both cohorts into healthier diet quality and less healthy diet quality. They found a tighter association between GRS and type 2 diabetes for women with diet quality below the median, whereas women with higher diet quality did not have such a strong association between GRS and type 2 disease. The researchers wrote that there was “suggestive evidence that a healthful diet might mitigate the excessive risk of T2D [type 2 diabetes] related to greater genetic susceptibility, which supports public health efforts of encouraging a healthful diet” for diabetes prevention in this high-risk population.

Patients in the NHSII were followed for a mean 21.3 years, and those in the DNBC were followed for a mean 12.7 years. Mean age at index pregnancy was 30.5 years for the NHSII cohort and 31.7 for the DNBC cohort. In the NHSII cohort, just 8.4% of participants reported smoking before pregnancy, compared with 26.4% of those in the DNBC cohort. The NHSII cohort participants, wrote Dr. Li and her coauthors, “were also less likely to have a family history of diabetes, less likely to smoke, and be leaner than women in the DNBC.”

Dr. Li and her coauthors noted that, “despite being the largest genetic study by far on [type 2 diabetes] among women with GDM, our study may not be sufficiently powered to examine the associations of individual T2D SNPs in relation to the risk of developing T2D.” Another limitation was that for the Danish cohort, information about diet was drawn from a one-time questionnaire administered between 9 and 16 years after the index pregnancy, so full data about dietary quality over time was not available. Also of note is that the study included only white participants, limiting generalizability to women of color. The authors called for expanding this research into more racially diverse populations.

The study was supported by the National Institutes of Health. The authors reported that they had no conflicts of interest.

SOURCE: Li M et al. BMJ Open Diab Res Care. 2020 Feb 13. doi: 10.1136/bmjdrc-2019-000850.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.