Federal Practitioner

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

Low-dose erlotinib is a valid treatment option for elderly and frail patients with non–small cell lung cancer (NSCLC), according to researchers.

They conducted a phase 2 trial to investigate whether one-third of the maximum tolerated dose of erlotinib could maintain sufficient plasma concentration of the drug while avoiding the adverse effects of higher doses. The results were published in JAMA Oncology.

Erlotinib and other epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in elderly patients with EGFR-positive NSCLC, according to study author Shingo Miyamoto, MD, of Japanese Red Cross Medical Center in Tokyo, and colleagues.

“With the increasing number of elderly patients with cancer, many of whom also have significant comorbidities, there is a considerable value in investigating whether EGFR-TKIs are effective for the frail population,” the authors wrote. They also noted that it is “difficult to identify the appropriate dose of molecular-targeted drugs.”

With this in mind, Dr. Miyamoto and colleagues conducted a single-arm, phase 2 trial of low-dose erlotinib in 80 chemotherapy-naive frail or elderly patients with EGFR-positive NSCLC. Frailty was defined by age and the Charlson Comorbidity Index. The patients’ median age was 80 years (range, 49-90 years).

Patients received erlotinib at 50 mg per day, which is one-third of the established maximum tolerated dose, for 4 weeks. Then, they were evaluated with radiologic imaging. Treatment continued until disease progression or unacceptable adverse events. Dosing was modified by treatment response or by adverse events.
 

Results

At last follow-up, 7 of the 80 patients were still receiving low-dose erlotinib. Reasons for discontinuation were disease progression (n = 60), patient request (n = 6), adverse events (n = 4), and death (n = 3).

The overall response rate was 60%, and the disease control rate was 90%. The researchers measured plasma erlotinib concentration in 48 patients and found it did not correlate with response.

The median progression-free survival was 9.3 months, and the median overall survival was 26.2 months.

Ten patients had erlotinib temporarily suspended because of adverse events. Five patients had their dose reduced to 25 mg because of adverse events, including oral mucositis, paronychia, erythema multiforme, diarrhea, and anorexia.

Two patients discontinued treatment because of adverse events. One patient had a cutaneous ulcer and bone infection. The other had oral mucositis.

Dr. Miyamoto and colleagues concluded that, “low-dose erlotinib was associated with efficacy and safety in frail patients with EGFR mutation–positive lung cancer. More research on the dosing strategy of target-based drugs is warranted, especially in frail patients in the real-world setting.”
 

Less is more

Sometimes, less can be more, said Mellar P. Davis, MD, an oncologist and section head of the palliative care department at Geisinger Medical System in Danville, Penn., who was not involved in this study.

“Why do patients benefit from small doses? It may be that there are fewer drug interruptions over time and patients are able to stay on schedule,” Dr. Davis said. “It may also be that erlotinib clearance is reduced in the elderly and comorbid patient. The reduced dose may, in fact, be the ‘therapeutic’ dose in this special population.”

Plasma levels were frequently in therapeutic ranges in this study, but patients who had subtherapeutic plasma levels also responded to therapy, Dr. Davis pointed out. The lower dose was shown to maintain sufficient concentrations of the treatment while reducing adverse effects.

However, Dr. Davis noted, this was not a randomized trial. “It is always a risk hedging bets on single-arm trials,” he said. “Randomized trials often prove phase 2 single-arm trials wrong.”

He added that quality-of-life measures are absent from the study. Erlotinib is a palliative drug with side effects, Dr. Davis noted.

“Control of cancer and cancer regression should improve symptoms and quality of life when balanced against treatment toxicity,” he said. “In this study, I would have thought that symptom improvement, performance score, and quality of life would have been the primary outcome or the co-primary outcome with disease control.”

Should a randomized, controlled trial of low-dose erlotinib be conducted in the frail/elderly population? “If one believes trials should be quantitatively based, the answer would be no,” Dr. Davis said. “Responses may be the same, and it would be expensive to prove that low-dose erlotinib is the same as standard doses when comparing survival.”

However, if one is interested in quality of life, particularly in this growing population, a trial that incorporated quality-of-life measures would make more sense, according to Dr. Davis. “For if one can achieve less toxicity and treat more patients and get the same duration of clinical benefit, then less will be more,” he concluded.

Dr. Davis reported having no conflicts of interest. Study authors disclosed relationships with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, and many other companies. Erlotinib is manufactured for OSI Pharmaceuticals, an affiliate of Astellas Pharma, and distributed by Genentech, a member of the Roche Group.

The study was supported by the Japan Agency for Medical Research and Development.

SOURCE: Miyamoto S et al. JAMA Oncol. 2020 May 14; e201250. doi: 10.1001/jamaoncol.2020.1250.

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

Catherine Hackett/MDedge News

John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

Catherine Hackett/MDedge News

John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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

A new nationwide U.S. observational study suggests that ACE inhibitors may protect against severe illness in older people with COVID-19, prompting the start of a randomized clinical trial to test the strategy.

In addition, a new meta-analysis of all the available data on the use of ACE inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19–infected patients has concluded that these drugs are not associated with more severe disease and do not increase susceptibility to infection.

The observational study, which was published on the MedRxiv preprint server on May 19 and has not yet been peer reviewed, was conducted by the health insurance company United Heath Group and by Yale University, New Haven, Conn.

The investigators analyzed data from 10,000 patients from across the United States who had tested positive for COVID-19, who were enrolled in Medicare Advantage insurance plans or were commercially insured, and who had received a prescription for one or more antihypertensive medications.

Results showed that the use of ACE inhibitors was associated with an almost 40% lower risk for COVID-19 hospitalization for older people enrolled in Medicare Advantage plans. No such benefit was seen in the younger commercially insured patients or in either group with ARBs.

Courtesy Yale University

At a telephone media briefing on the study, senior investigator Harlan M. Krumholz, MD, said: “We don’t believe this is enough info to change practice, but we do think this is an interesting and intriguing result.

“These findings merit a clinical trial to formally test whether ACE inhibitors – which are cheap, widely available, and well-tolerated drugs – can reduce hospitalization of patients infected with COVID-19,” added Dr. Krumholz, professor of medicine at Yale and director of the Yale New Haven Hospital Center for Outcomes Research.

A pragmatic clinical trial is now being planned. In this trial, 10,000 older people who test positive for COVID-19 will be randomly assigned to receive either a low dose of an ACE inhibitor or placebo. It is hoped that recruitment for the trial will begin in June of 2020. It is open to all eligible Americans who are older than 50 years, who test negative for COVID-19, and who are not taking medications for hypertension. Prospective patients can sign up at a dedicated website.

The randomized trial, also conducted by United Health Group and Yale, is said to be “one of the first virtual COVID-19 clinical trials to be launched at scale.”

For the observational study, the researchers identified 2,263 people who were receiving medication for hypertension and who tested positive for COVID-19. Of these, approximately two-thirds were older, Medicare Advantage enrollees; one-third were younger, commercially insured individuals.

In a propensity score–matched analysis, the investigators matched 441 patients who were taking ACE inhibitors to 441 patients who were taking other antihypertensive agents; and 412 patients who were receiving an ARB to 412 patients who were receiving other antihypertensive agents.

Results showed that during a median of 30 days after testing positive, 12.7% of the cohort were hospitalized for COVID-19. In propensity score–matched analyses, neither ACE inhibitors (hazard ratio [HR], 0.77; P = .18) nor ARBs (HR, 0.88; P =.48) were significantly associated with risk for hospitalization.

However, in analyses stratified by the insurance group, ACE inhibitors (but not ARBs) were associated with a significant lower risk for hospitalization among the Medicare group (HR, 0.61; P = .02) but not among the commercially insured group (HR, 2.14; P = .12).

A second study examined outcomes of 7,933 individuals with hypertension who were hospitalized with COVID-19 (92% of these patients were Medicare Advantage enrollees). Of these, 14.2% died, 59.5% survived to discharge, and 26.3% underwent ongoing hospitalization. In propensity score–matched analyses, use of neither an ACE inhibitor (HR, 0.97; P = .74) nor an ARB (HR, 1.15; P = .15) was associated with risk of in-hospital mortality.

The researchers said their findings are consistent with prior evidence from randomized clinical trials suggesting a reduced risk for pneumonia with ACE inhibitors that is not observed with ARBs.

They also cited some preclinical evidence that they said suggests a possible protective role for ACE inhibitors in COVID-19: that ACE inhibitors, but not ARBs, are associated with the upregulation of ACE2 receptors, which modulate the local interactions of the renin-angiotensin-aldosterone system in the lung tissue.

“The presence of ACE2 receptors, therefore, exerts a protective effect against the development of acute lung injury in infections with SARS coronaviruses, which lead to dysregulation of these mechanisms and endothelial damage,” they added. “Further, our observations do not support theoretical concerns of adverse outcomes due to enhanced virulence of SARS coronaviruses due to overexpression of ACE2 receptors in cell cultures – an indirect binding site for these viruses.”

The authors also noted that their findings have “important implications” for four ongoing randomized trials of ACE inhibitors/ARBs in COVID-19, “as none of them align with the observations of our study.”

They pointed out that of the four ongoing trials, three are testing the use of ACE inhibitors or ARBs in the treatment of hospitalized COVID-19 patients, and one is testing the use of a 10-day course of ARBs after a positive SARS-CoV-2 test to prevent hospitalization.
 

Experts cautious

However, two cardiovascular experts who were asked to comment on this latest study were not overly optimistic about the data.

Michael A. Weber, MD, professor of medicine at the State University of New York, Brooklyn, said: “This report adds to the growing number of observational studies that show varying effects of ACE inhibitors and ARBs in increasing or decreasing hospitalizations for COVID-19 and the likelihood of in-hospital mortality. Overall, this new report differs from others in the remarkable effects of insurance coverage: In particular, for ACE inhibitors, there was a 40% reduction in fatal events in Medicare patients but a twofold increase in patients using commercial insurance – albeit the test for heterogeneity when comparing the two groups did not quite reach statistical significance.

“In essence, these authors are saying that ACE inhibitors are highly protective in patients aged 65 or older but bordering on harmful in patients aged below 65. I agree that it’s worthwhile to check this finding in a prospective trial ... but this hypothesis does seem to be a reach.”

Dr. Weber noted that both ACE inhibitors and ARBs increase the level of the ACE2 enzyme to which the COVID-19 virus binds in the lungs.

“The ACE inhibitors do so by inhibiting the enzyme’s action and thus stimulate further enzyme production; the ARBs block the effects of angiotensin II, which results in high angiotensin II levels that also upregulate ACE2 production,” he said. “Perhaps the ACE inhibitors, by binding to the ACE enzyme, can in some way interfere with the enzyme’s uptake of the COVID virus and thus provide some measure of clinical protection. This is possible, but why would this effect be apparent only in older people?”

Catherine Hackett/MDedge News

John McMurray, MD, professor of medical cardiology at the University of Glasgow, Scotland, added: “This looks like a subgroup of a subgroup type analysis based on small numbers of events – I think there were only 77 hospitalizations among the 722 patients treated with an ACE inhibitor, and the Medicare Advantage subgroup was only 581 of those 722 patients.

“The hazard ratio had wide 95% CI [confidence interval] and a modest P value,” Dr. McMurray added. “So yes, interesting and hypothesis-generating, but not definitive.”
 

New meta-analysis

The new meta-analysis of all data so far available on ACE inhibitor and ARB use for patients with COVID-19 was published online in Annals of Internal Medicine on May 15.

The analysis is a living, systematic review with ongoing literature surveillance and critical appraisal, which will be updated as new data become available. It included 14 observational studies.

The authors, led by Katherine M. Mackey, MD, VA Portland Health Care System, Oregon, concluded: “High-certainty evidence suggests that ACE-inhibitor or ARB use is not associated with more severe COVID-19 disease, and moderate certainty evidence suggested no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.”

In an accompanying editorial, William G. Kussmaul III, MD, Drexel University, Philadelphia, said that initial fears that these drugs may be harmful for patients with COVID-19 now seem to have been unfounded.

“We now have reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers,” he wrote.
 

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

The drastic drop in admissions for acute myocardial infarctions (AMI) during the COVID-19 pandemic in Italy has seen a parallel rise in MI fatality rates in those who do present to hospitals, according to a new report. This gives credence to suggestions that people have avoided hospitals during the pandemic despite life-threatening emergencies.

Salvatore De Rosa, MD, PhD, and colleagues reported their results in the European Heart Journal.

“These data return a frightening picture of about half of AMI patients not reaching out to the hospital at all, which will probably significantly increase mortality for AMI and bring with it a number of patients with post-MI heart failure, despite the fact that acute coronary syndrome management protocols were promptly implemented,” Dr. De Rosa, of Magna Graecia University in Catanzaro, Italy, and associates wrote.
 

Hospitalizations down

The study counted AMIs at 54 hospital coronary care units nationwide for the week of March 12-19, 2020, at the height of the coronavirus outbreak in northern Italy, and compared that with an equivalent week in 2019. The researchers reported 319 AMIs during the week in 2020, compared with 618 in the equivalent 2019 week, a 48% reduction (P < .001). Although the outbreak was worst in northern Italy, the decline in admissions occurred throughout the country.

An analysis of subtype determined the decline in the incidence of ST-segment elevation MI lagged significantly behind that of non-STEMI. STEMI declined from 268 in 2019 to 197 in 2020, a 27% reduction, while hospitalizations for non-STEMI went from 350 to 122, a 65% reduction.

The researchers also found substantial reductions in hospitalizations for heart failure, by 47%, and atrial fibrillation, by 53%. Incidentally, the mean age of atrial fibrillation patients was considerably younger in 2020: 64.6 vs. 70 years.
 

Death, complications up

AMI patients who managed to get to the hospital during the pandemic also had worse outcomes. Mortality for STEMI cases more than tripled, to 14% during the outbreak, compared with 4% in 2019 (P < .001) and complication rates increased by 80% to 19% (P = .025). Twenty-one STEMI patients were positive for COVID-19 and more than a quarter (29%) died, which was more than two and a half times the 12% death rate in non–COVID-19 STEMI patients.

Analysis of the STEMI group also found that the care gap for women with heart disease worsened significantly during the pandemic, as they comprised 20.3% of cases this year, compared with 25.4% before the pandemic. Also, the reduction in admissions for STEMI during the pandemic was statistically significant at 41% for women, but not for men at 18%.

Non-STEMI patients fared better overall than STEMI patients, but their outcomes also worsened during the pandemic. Non-STEMI patients were significantly less likely to have percutaneous coronary intervention during the pandemic than previously; the rate declined by 13%, from 77% to 66%. The non-STEMI mortality rate nearly doubled, although not statistically significantly, from 1.7% to 3.3%, whereas complication rates actually more than doubled, from 5.1% to 10.7%, a significant difference. Twelve (9.8%) of the non-STEMI patients were COVID-19 positive, but none died.
 

Trend extends beyond borders

Dr. De Rosa and colleagues noted that their findings are in line with studies that reported similar declines for STEMI interventions in the United States and Spain during the pandemic (J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.011; REC Interv Cardiol. 2020. doi: 10.24875/RECIC.M20000120).

Additionally, a group at Kaiser Permanente in Northern California also reported a 50% decline in the incidence of AMI hospitalizations during the pandemic (N Engl J Med. 2020 May 19. doi: 10.1056/NEJMc2015630). Likewise, a study of aortic dissections in New York reported a sharp decline in procedures during the pandemic in the city, from 13 to 3 a month (J Am Coll Cardiol. 2020 May 15. doi: 10.1016/j.jacc.2020.05.022)

The researchers in Italy didn’t aim to determine the reasons for the decline in AMI hospitalizations, but Dr. De Rosa and colleagues speculated on the following explanations: Fear of contagion in response to media reports, concentration of resources to address COVID-19 may have engendered a sense to defer less urgent care among patients and health care systems, and a true reduction in acute cardiovascular disease because people under stay-at-home orders had low physical stress.

“The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, in interpreting the results of the Italian study.

That could be a result of a mixed message from the media about accessing health care during the pandemic. “What it suggests to a lot of us is that the media has transmitted this notion that hospitals are busy taking care of COVID-19 patients, but we never said don’t come to hospital if you’re having a heart attack,” Dr. Gulati said. “I think we created some sort of fear that patients if they didn’t have COVID-19 they didn’t want to bother physicians.”

Dr. Gulati, whose practice focuses on women with CVD, said the study’s findings that interventions in women dropped more precipitously than men were concerning. “We know already that women don’t do as well after a heart attack, compared to men, and now we see it worsen it even further when women aren’t presenting,” she said. “We’re worried that this is going to increase the gap.”

Dr. DeRosa and colleagues have no relevant financial relationships to disclose.

SOURCE: De Rosa S et al. Euro Heart J. 2020 May 15. doi: 10.1093/eurheartj/ehaa409.

The drastic drop in admissions for acute myocardial infarctions (AMI) during the COVID-19 pandemic in Italy has seen a parallel rise in MI fatality rates in those who do present to hospitals, according to a new report. This gives credence to suggestions that people have avoided hospitals during the pandemic despite life-threatening emergencies.

Salvatore De Rosa, MD, PhD, and colleagues reported their results in the European Heart Journal.

“These data return a frightening picture of about half of AMI patients not reaching out to the hospital at all, which will probably significantly increase mortality for AMI and bring with it a number of patients with post-MI heart failure, despite the fact that acute coronary syndrome management protocols were promptly implemented,” Dr. De Rosa, of Magna Graecia University in Catanzaro, Italy, and associates wrote.
 

Hospitalizations down

The study counted AMIs at 54 hospital coronary care units nationwide for the week of March 12-19, 2020, at the height of the coronavirus outbreak in northern Italy, and compared that with an equivalent week in 2019. The researchers reported 319 AMIs during the week in 2020, compared with 618 in the equivalent 2019 week, a 48% reduction (P < .001). Although the outbreak was worst in northern Italy, the decline in admissions occurred throughout the country.

An analysis of subtype determined the decline in the incidence of ST-segment elevation MI lagged significantly behind that of non-STEMI. STEMI declined from 268 in 2019 to 197 in 2020, a 27% reduction, while hospitalizations for non-STEMI went from 350 to 122, a 65% reduction.

The researchers also found substantial reductions in hospitalizations for heart failure, by 47%, and atrial fibrillation, by 53%. Incidentally, the mean age of atrial fibrillation patients was considerably younger in 2020: 64.6 vs. 70 years.
 

Death, complications up

AMI patients who managed to get to the hospital during the pandemic also had worse outcomes. Mortality for STEMI cases more than tripled, to 14% during the outbreak, compared with 4% in 2019 (P < .001) and complication rates increased by 80% to 19% (P = .025). Twenty-one STEMI patients were positive for COVID-19 and more than a quarter (29%) died, which was more than two and a half times the 12% death rate in non–COVID-19 STEMI patients.

Analysis of the STEMI group also found that the care gap for women with heart disease worsened significantly during the pandemic, as they comprised 20.3% of cases this year, compared with 25.4% before the pandemic. Also, the reduction in admissions for STEMI during the pandemic was statistically significant at 41% for women, but not for men at 18%.

Non-STEMI patients fared better overall than STEMI patients, but their outcomes also worsened during the pandemic. Non-STEMI patients were significantly less likely to have percutaneous coronary intervention during the pandemic than previously; the rate declined by 13%, from 77% to 66%. The non-STEMI mortality rate nearly doubled, although not statistically significantly, from 1.7% to 3.3%, whereas complication rates actually more than doubled, from 5.1% to 10.7%, a significant difference. Twelve (9.8%) of the non-STEMI patients were COVID-19 positive, but none died.
 

Trend extends beyond borders

Dr. De Rosa and colleagues noted that their findings are in line with studies that reported similar declines for STEMI interventions in the United States and Spain during the pandemic (J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.011; REC Interv Cardiol. 2020. doi: 10.24875/RECIC.M20000120).

Additionally, a group at Kaiser Permanente in Northern California also reported a 50% decline in the incidence of AMI hospitalizations during the pandemic (N Engl J Med. 2020 May 19. doi: 10.1056/NEJMc2015630). Likewise, a study of aortic dissections in New York reported a sharp decline in procedures during the pandemic in the city, from 13 to 3 a month (J Am Coll Cardiol. 2020 May 15. doi: 10.1016/j.jacc.2020.05.022)

The researchers in Italy didn’t aim to determine the reasons for the decline in AMI hospitalizations, but Dr. De Rosa and colleagues speculated on the following explanations: Fear of contagion in response to media reports, concentration of resources to address COVID-19 may have engendered a sense to defer less urgent care among patients and health care systems, and a true reduction in acute cardiovascular disease because people under stay-at-home orders had low physical stress.

“The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, in interpreting the results of the Italian study.

That could be a result of a mixed message from the media about accessing health care during the pandemic. “What it suggests to a lot of us is that the media has transmitted this notion that hospitals are busy taking care of COVID-19 patients, but we never said don’t come to hospital if you’re having a heart attack,” Dr. Gulati said. “I think we created some sort of fear that patients if they didn’t have COVID-19 they didn’t want to bother physicians.”

Dr. Gulati, whose practice focuses on women with CVD, said the study’s findings that interventions in women dropped more precipitously than men were concerning. “We know already that women don’t do as well after a heart attack, compared to men, and now we see it worsen it even further when women aren’t presenting,” she said. “We’re worried that this is going to increase the gap.”

Dr. DeRosa and colleagues have no relevant financial relationships to disclose.

SOURCE: De Rosa S et al. Euro Heart J. 2020 May 15. doi: 10.1093/eurheartj/ehaa409.

The drastic drop in admissions for acute myocardial infarctions (AMI) during the COVID-19 pandemic in Italy has seen a parallel rise in MI fatality rates in those who do present to hospitals, according to a new report. This gives credence to suggestions that people have avoided hospitals during the pandemic despite life-threatening emergencies.

Salvatore De Rosa, MD, PhD, and colleagues reported their results in the European Heart Journal.

“These data return a frightening picture of about half of AMI patients not reaching out to the hospital at all, which will probably significantly increase mortality for AMI and bring with it a number of patients with post-MI heart failure, despite the fact that acute coronary syndrome management protocols were promptly implemented,” Dr. De Rosa, of Magna Graecia University in Catanzaro, Italy, and associates wrote.
 

Hospitalizations down

The study counted AMIs at 54 hospital coronary care units nationwide for the week of March 12-19, 2020, at the height of the coronavirus outbreak in northern Italy, and compared that with an equivalent week in 2019. The researchers reported 319 AMIs during the week in 2020, compared with 618 in the equivalent 2019 week, a 48% reduction (P < .001). Although the outbreak was worst in northern Italy, the decline in admissions occurred throughout the country.

An analysis of subtype determined the decline in the incidence of ST-segment elevation MI lagged significantly behind that of non-STEMI. STEMI declined from 268 in 2019 to 197 in 2020, a 27% reduction, while hospitalizations for non-STEMI went from 350 to 122, a 65% reduction.

The researchers also found substantial reductions in hospitalizations for heart failure, by 47%, and atrial fibrillation, by 53%. Incidentally, the mean age of atrial fibrillation patients was considerably younger in 2020: 64.6 vs. 70 years.
 

Death, complications up

AMI patients who managed to get to the hospital during the pandemic also had worse outcomes. Mortality for STEMI cases more than tripled, to 14% during the outbreak, compared with 4% in 2019 (P < .001) and complication rates increased by 80% to 19% (P = .025). Twenty-one STEMI patients were positive for COVID-19 and more than a quarter (29%) died, which was more than two and a half times the 12% death rate in non–COVID-19 STEMI patients.

Analysis of the STEMI group also found that the care gap for women with heart disease worsened significantly during the pandemic, as they comprised 20.3% of cases this year, compared with 25.4% before the pandemic. Also, the reduction in admissions for STEMI during the pandemic was statistically significant at 41% for women, but not for men at 18%.

Non-STEMI patients fared better overall than STEMI patients, but their outcomes also worsened during the pandemic. Non-STEMI patients were significantly less likely to have percutaneous coronary intervention during the pandemic than previously; the rate declined by 13%, from 77% to 66%. The non-STEMI mortality rate nearly doubled, although not statistically significantly, from 1.7% to 3.3%, whereas complication rates actually more than doubled, from 5.1% to 10.7%, a significant difference. Twelve (9.8%) of the non-STEMI patients were COVID-19 positive, but none died.
 

Trend extends beyond borders

Dr. De Rosa and colleagues noted that their findings are in line with studies that reported similar declines for STEMI interventions in the United States and Spain during the pandemic (J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.011; REC Interv Cardiol. 2020. doi: 10.24875/RECIC.M20000120).

Additionally, a group at Kaiser Permanente in Northern California also reported a 50% decline in the incidence of AMI hospitalizations during the pandemic (N Engl J Med. 2020 May 19. doi: 10.1056/NEJMc2015630). Likewise, a study of aortic dissections in New York reported a sharp decline in procedures during the pandemic in the city, from 13 to 3 a month (J Am Coll Cardiol. 2020 May 15. doi: 10.1016/j.jacc.2020.05.022)

The researchers in Italy didn’t aim to determine the reasons for the decline in AMI hospitalizations, but Dr. De Rosa and colleagues speculated on the following explanations: Fear of contagion in response to media reports, concentration of resources to address COVID-19 may have engendered a sense to defer less urgent care among patients and health care systems, and a true reduction in acute cardiovascular disease because people under stay-at-home orders had low physical stress.

“The concern is fewer MIs most likely means people are dying at home or presenting later as this study suggests,” said Martha Gulati, MD, chief of cardiology at the University of Arizona, Phoenix, in interpreting the results of the Italian study.

That could be a result of a mixed message from the media about accessing health care during the pandemic. “What it suggests to a lot of us is that the media has transmitted this notion that hospitals are busy taking care of COVID-19 patients, but we never said don’t come to hospital if you’re having a heart attack,” Dr. Gulati said. “I think we created some sort of fear that patients if they didn’t have COVID-19 they didn’t want to bother physicians.”

Dr. Gulati, whose practice focuses on women with CVD, said the study’s findings that interventions in women dropped more precipitously than men were concerning. “We know already that women don’t do as well after a heart attack, compared to men, and now we see it worsen it even further when women aren’t presenting,” she said. “We’re worried that this is going to increase the gap.”

Dr. DeRosa and colleagues have no relevant financial relationships to disclose.

SOURCE: De Rosa S et al. Euro Heart J. 2020 May 15. doi: 10.1093/eurheartj/ehaa409.

Higher cardiovascular risk burden, as measured by the Framingham General Cardiovascular Risk Score (FGCRS), is associated with neurodegenerative signs in the brain and may predict cognitive decline over time.

“In the absence of effective treatments for dementia, we need to monitor and control cardiovascular risk burden as a way to maintain patient’s cognitive health as they age,” said Weili Xu, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China, in a press release.

“Given the progressive increase in the number of dementia cases worldwide, our findings have both clinical and public health relevance.”

Dr. Xu and first author Ruixue Song, MSc, also from Tianjin Medical University, published their findings online ahead of print May 18 in the Journal of the American College of Cardiology.

The World Health Organization projects that up to 82 million people will have dementia by 2050. Given the lack of effective treatments for dementia, identifying modifiable risk factors for cognitive decline and aggressively managing them is an increasingly appealing strategy.
 

Assessing cardiovascular risk and cognition

The researchers followed 1,588 dementia-free participants from the Rush Memory and Aging Project for 21 years (median, 5.8 years). FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Mean age of the studied population was 79.5 years, 75.8% of participants were female, and mean Framingham score was 15.6 (range, 4 to 28).

Annual evaluations included assessment of episodic memory (memory of everyday events), semantic memory (long-term memory), working memory (short-term memory), visuospatial ability (capacity to identify visual and spatial relationships among objects), and perceptual speed (ability to accurately and completely compare letters, numbers, objects, pictures, or patterns) using 19 tests to derive a composite score.

A subsample (n = 378) of participants underwent MRI, and structural total and regional brain volumes were estimated.

Linear regression was used to estimate beta-coefficients for the relationship between cardiovascular risk burden at baseline and longitudinally. If the beta-coefficient is negative, the interpretation is that for every 1-unit increase in the predictor variable (FGCRS), the outcome variable (cognitive function) will decrease by the beta-coefficient value.

At baseline, higher FGCRS was related to small but consistent (although not usually statistically significant) decreases in hippocampal volume, gray matter, and total brain volume.

Considered longitudinally, participants in the highest-risk tertile of FGCRS experienced faster decline in global cognition (beta = −0.019), episodic memory (beta = −0.023), working memory (beta = −0.021), and perceptual speed (beta = −0.027) during follow-up (P < .05 for all) than those in the lowest-risk tertile.

The declines in semantic memory (beta = –0.012) and visuospatial ability (beta = –0.010) did not reach statistical significance.

Bringing dementia prevention into the exam room early

Commenting on the research, Costantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said the study has immediate clinical usefulness.

“The link between the cardiovascular risk factors and dementia is well known, but in your doctor’s office, that link is not seen. If your GP or cardiologist sees you with high blood pressure, he’s not immediately going to think about the risk of dementia 20 years later,” said Dr. Iadecola.

“What this study does is it directly links a simple score that’s commonly used to assess cardiovascular risk to dementia risk, which can be used to counsel patients and, hopefully, reduce the risk of both cardiovascular disease and cognitive disorders.”

Dr. Iadecola wrote an editorial together with Neal S. Parikh, MD, MS, also from Weill Cornell Medicine, that accompanied the findings of the trial.

Even neurologists sometimes fail to make the connection between vascular risk and dementia, he said. “They think that by making a stroke patient move their hand better, they’re treating them, but 30% of stroke patients get dementia 6 or 8 months later and they’re missing this link between cerebrovascular pathology and dementia.

Dr. Iadecola is one of 26 experts who authored the recent Berlin Manifesto, an effort led by Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in Ontario, Canada, to raise awareness of the link between cardiovascular and brain health.

Dr. Hachinski coined the term “brain attack” and devised the Hachinski Ischemic Score that remains the standard for identifying a vascular component of cognitive impairment.

The current study has some strengths and limitations, noted Dr. Iadecola. The average age of participants was 80 years, which is appropriate given the high risk for cognitive decline at this age, but the generalizability of the study may be limited given that most participants were white women.

Going forward, he said, rigorous studies are needed to confirm these findings and to determine how to best prevent dementia through treatment of individual cardiovascular risk factors.

Dr. Xu has received grants from nonindustry entities, including the Swedish Research Council and the National Natural Science Foundation of China. The study was funded by the European Union’s Horizon 320230 research and innovation program. Dr. Iadecola is a member of the scientific advisory board for Broadview Ventures.

This article appeared on Medscape.com.

Higher cardiovascular risk burden, as measured by the Framingham General Cardiovascular Risk Score (FGCRS), is associated with neurodegenerative signs in the brain and may predict cognitive decline over time.

“In the absence of effective treatments for dementia, we need to monitor and control cardiovascular risk burden as a way to maintain patient’s cognitive health as they age,” said Weili Xu, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China, in a press release.

“Given the progressive increase in the number of dementia cases worldwide, our findings have both clinical and public health relevance.”

Dr. Xu and first author Ruixue Song, MSc, also from Tianjin Medical University, published their findings online ahead of print May 18 in the Journal of the American College of Cardiology.

The World Health Organization projects that up to 82 million people will have dementia by 2050. Given the lack of effective treatments for dementia, identifying modifiable risk factors for cognitive decline and aggressively managing them is an increasingly appealing strategy.
 

Assessing cardiovascular risk and cognition

The researchers followed 1,588 dementia-free participants from the Rush Memory and Aging Project for 21 years (median, 5.8 years). FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Mean age of the studied population was 79.5 years, 75.8% of participants were female, and mean Framingham score was 15.6 (range, 4 to 28).

Annual evaluations included assessment of episodic memory (memory of everyday events), semantic memory (long-term memory), working memory (short-term memory), visuospatial ability (capacity to identify visual and spatial relationships among objects), and perceptual speed (ability to accurately and completely compare letters, numbers, objects, pictures, or patterns) using 19 tests to derive a composite score.

A subsample (n = 378) of participants underwent MRI, and structural total and regional brain volumes were estimated.

Linear regression was used to estimate beta-coefficients for the relationship between cardiovascular risk burden at baseline and longitudinally. If the beta-coefficient is negative, the interpretation is that for every 1-unit increase in the predictor variable (FGCRS), the outcome variable (cognitive function) will decrease by the beta-coefficient value.

At baseline, higher FGCRS was related to small but consistent (although not usually statistically significant) decreases in hippocampal volume, gray matter, and total brain volume.

Considered longitudinally, participants in the highest-risk tertile of FGCRS experienced faster decline in global cognition (beta = −0.019), episodic memory (beta = −0.023), working memory (beta = −0.021), and perceptual speed (beta = −0.027) during follow-up (P < .05 for all) than those in the lowest-risk tertile.

The declines in semantic memory (beta = –0.012) and visuospatial ability (beta = –0.010) did not reach statistical significance.

Bringing dementia prevention into the exam room early

Commenting on the research, Costantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said the study has immediate clinical usefulness.

“The link between the cardiovascular risk factors and dementia is well known, but in your doctor’s office, that link is not seen. If your GP or cardiologist sees you with high blood pressure, he’s not immediately going to think about the risk of dementia 20 years later,” said Dr. Iadecola.

“What this study does is it directly links a simple score that’s commonly used to assess cardiovascular risk to dementia risk, which can be used to counsel patients and, hopefully, reduce the risk of both cardiovascular disease and cognitive disorders.”

Dr. Iadecola wrote an editorial together with Neal S. Parikh, MD, MS, also from Weill Cornell Medicine, that accompanied the findings of the trial.

Even neurologists sometimes fail to make the connection between vascular risk and dementia, he said. “They think that by making a stroke patient move their hand better, they’re treating them, but 30% of stroke patients get dementia 6 or 8 months later and they’re missing this link between cerebrovascular pathology and dementia.

Dr. Iadecola is one of 26 experts who authored the recent Berlin Manifesto, an effort led by Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in Ontario, Canada, to raise awareness of the link between cardiovascular and brain health.

Dr. Hachinski coined the term “brain attack” and devised the Hachinski Ischemic Score that remains the standard for identifying a vascular component of cognitive impairment.

The current study has some strengths and limitations, noted Dr. Iadecola. The average age of participants was 80 years, which is appropriate given the high risk for cognitive decline at this age, but the generalizability of the study may be limited given that most participants were white women.

Going forward, he said, rigorous studies are needed to confirm these findings and to determine how to best prevent dementia through treatment of individual cardiovascular risk factors.

Dr. Xu has received grants from nonindustry entities, including the Swedish Research Council and the National Natural Science Foundation of China. The study was funded by the European Union’s Horizon 320230 research and innovation program. Dr. Iadecola is a member of the scientific advisory board for Broadview Ventures.

This article appeared on Medscape.com.

Higher cardiovascular risk burden, as measured by the Framingham General Cardiovascular Risk Score (FGCRS), is associated with neurodegenerative signs in the brain and may predict cognitive decline over time.

“In the absence of effective treatments for dementia, we need to monitor and control cardiovascular risk burden as a way to maintain patient’s cognitive health as they age,” said Weili Xu, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China, in a press release.

“Given the progressive increase in the number of dementia cases worldwide, our findings have both clinical and public health relevance.”

Dr. Xu and first author Ruixue Song, MSc, also from Tianjin Medical University, published their findings online ahead of print May 18 in the Journal of the American College of Cardiology.

The World Health Organization projects that up to 82 million people will have dementia by 2050. Given the lack of effective treatments for dementia, identifying modifiable risk factors for cognitive decline and aggressively managing them is an increasingly appealing strategy.
 

Assessing cardiovascular risk and cognition

The researchers followed 1,588 dementia-free participants from the Rush Memory and Aging Project for 21 years (median, 5.8 years). FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Mean age of the studied population was 79.5 years, 75.8% of participants were female, and mean Framingham score was 15.6 (range, 4 to 28).

Annual evaluations included assessment of episodic memory (memory of everyday events), semantic memory (long-term memory), working memory (short-term memory), visuospatial ability (capacity to identify visual and spatial relationships among objects), and perceptual speed (ability to accurately and completely compare letters, numbers, objects, pictures, or patterns) using 19 tests to derive a composite score.

A subsample (n = 378) of participants underwent MRI, and structural total and regional brain volumes were estimated.

Linear regression was used to estimate beta-coefficients for the relationship between cardiovascular risk burden at baseline and longitudinally. If the beta-coefficient is negative, the interpretation is that for every 1-unit increase in the predictor variable (FGCRS), the outcome variable (cognitive function) will decrease by the beta-coefficient value.

At baseline, higher FGCRS was related to small but consistent (although not usually statistically significant) decreases in hippocampal volume, gray matter, and total brain volume.

Considered longitudinally, participants in the highest-risk tertile of FGCRS experienced faster decline in global cognition (beta = −0.019), episodic memory (beta = −0.023), working memory (beta = −0.021), and perceptual speed (beta = −0.027) during follow-up (P < .05 for all) than those in the lowest-risk tertile.

The declines in semantic memory (beta = –0.012) and visuospatial ability (beta = –0.010) did not reach statistical significance.

Bringing dementia prevention into the exam room early

Commenting on the research, Costantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said the study has immediate clinical usefulness.

“The link between the cardiovascular risk factors and dementia is well known, but in your doctor’s office, that link is not seen. If your GP or cardiologist sees you with high blood pressure, he’s not immediately going to think about the risk of dementia 20 years later,” said Dr. Iadecola.

“What this study does is it directly links a simple score that’s commonly used to assess cardiovascular risk to dementia risk, which can be used to counsel patients and, hopefully, reduce the risk of both cardiovascular disease and cognitive disorders.”

Dr. Iadecola wrote an editorial together with Neal S. Parikh, MD, MS, also from Weill Cornell Medicine, that accompanied the findings of the trial.

Even neurologists sometimes fail to make the connection between vascular risk and dementia, he said. “They think that by making a stroke patient move their hand better, they’re treating them, but 30% of stroke patients get dementia 6 or 8 months later and they’re missing this link between cerebrovascular pathology and dementia.

Dr. Iadecola is one of 26 experts who authored the recent Berlin Manifesto, an effort led by Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in Ontario, Canada, to raise awareness of the link between cardiovascular and brain health.

Dr. Hachinski coined the term “brain attack” and devised the Hachinski Ischemic Score that remains the standard for identifying a vascular component of cognitive impairment.

The current study has some strengths and limitations, noted Dr. Iadecola. The average age of participants was 80 years, which is appropriate given the high risk for cognitive decline at this age, but the generalizability of the study may be limited given that most participants were white women.

Going forward, he said, rigorous studies are needed to confirm these findings and to determine how to best prevent dementia through treatment of individual cardiovascular risk factors.

Dr. Xu has received grants from nonindustry entities, including the Swedish Research Council and the National Natural Science Foundation of China. The study was funded by the European Union’s Horizon 320230 research and innovation program. Dr. Iadecola is a member of the scientific advisory board for Broadview Ventures.

This article appeared on Medscape.com.

Coronavirus disease of 2019 (COVID-19) may lead to subacute thyroiditis in some patients, which is suspected to have viral or postviral origin, especially with upper respiratory tract infections, according to a case study in the Journal of Clinical Endocrinology & Metabolism.

Alessandro Brancatella, a PhD student at the University Hospital Pisa (Italy), and colleagues described the case of an 18-year-old woman who was tested Feb. 21 for SARS-CoV-2 infection after her father was hospitalized because of COVID-19. Her results were positive for the virus, and not long after, she developed mild symptoms. By March 13 and again on March 14, test swabs for SARS-CoV-2 were both negative.

On March 17, she presented with fever, fatigue, palpitations, and neck pain that radiated to her jaw. Testing and physical examination pointed to subacute thyroiditis, and she was soon diagnosed and treated with prednisone. Her neck pain and fever disappeared within 2 days, and the remaining symptoms went away within a week.

The authors noted that the woman’s thyroid had been evaluated before she tested positive for SARS-CoV-2, and at that time, thyroid disease was ruled out. They also pointed out that, although the exact etiology for subacute thyroiditis is unknown, “it is common opinion that the disease is due to a viral infection or to a post-viral inflammatory reaction in genetically predisposed subjects.” They cited examples of viruses with suspected causal associations, including mumps, Epstein-Barr virus, and HIV, and they suggested that, based on the timing of the woman’s subacute thyroiditis and the normal results of her thyroid evaluation before developing COVID-19, SARS-CoV-2 be added to that list.

“To our knowledge, this is the first case of [subacute thyroiditis] related to SARS-CoV-2,” they concluded. “We therefore believe that physicians should be alerted about the possibility of this additional clinical manifestation related to SARS-CoV-2 infection.”

One author reported funding from the University of Pisa.

[email protected]

SOURCE: Brancatella A et al. J Clin Endocrinol Metab. 2020 May 21. doi: 10.1210/clinem/dgaa276.

Coronavirus disease of 2019 (COVID-19) may lead to subacute thyroiditis in some patients, which is suspected to have viral or postviral origin, especially with upper respiratory tract infections, according to a case study in the Journal of Clinical Endocrinology & Metabolism.

Alessandro Brancatella, a PhD student at the University Hospital Pisa (Italy), and colleagues described the case of an 18-year-old woman who was tested Feb. 21 for SARS-CoV-2 infection after her father was hospitalized because of COVID-19. Her results were positive for the virus, and not long after, she developed mild symptoms. By March 13 and again on March 14, test swabs for SARS-CoV-2 were both negative.

On March 17, she presented with fever, fatigue, palpitations, and neck pain that radiated to her jaw. Testing and physical examination pointed to subacute thyroiditis, and she was soon diagnosed and treated with prednisone. Her neck pain and fever disappeared within 2 days, and the remaining symptoms went away within a week.

The authors noted that the woman’s thyroid had been evaluated before she tested positive for SARS-CoV-2, and at that time, thyroid disease was ruled out. They also pointed out that, although the exact etiology for subacute thyroiditis is unknown, “it is common opinion that the disease is due to a viral infection or to a post-viral inflammatory reaction in genetically predisposed subjects.” They cited examples of viruses with suspected causal associations, including mumps, Epstein-Barr virus, and HIV, and they suggested that, based on the timing of the woman’s subacute thyroiditis and the normal results of her thyroid evaluation before developing COVID-19, SARS-CoV-2 be added to that list.

“To our knowledge, this is the first case of [subacute thyroiditis] related to SARS-CoV-2,” they concluded. “We therefore believe that physicians should be alerted about the possibility of this additional clinical manifestation related to SARS-CoV-2 infection.”

One author reported funding from the University of Pisa.

[email protected]

SOURCE: Brancatella A et al. J Clin Endocrinol Metab. 2020 May 21. doi: 10.1210/clinem/dgaa276.

Coronavirus disease of 2019 (COVID-19) may lead to subacute thyroiditis in some patients, which is suspected to have viral or postviral origin, especially with upper respiratory tract infections, according to a case study in the Journal of Clinical Endocrinology & Metabolism.

Alessandro Brancatella, a PhD student at the University Hospital Pisa (Italy), and colleagues described the case of an 18-year-old woman who was tested Feb. 21 for SARS-CoV-2 infection after her father was hospitalized because of COVID-19. Her results were positive for the virus, and not long after, she developed mild symptoms. By March 13 and again on March 14, test swabs for SARS-CoV-2 were both negative.

On March 17, she presented with fever, fatigue, palpitations, and neck pain that radiated to her jaw. Testing and physical examination pointed to subacute thyroiditis, and she was soon diagnosed and treated with prednisone. Her neck pain and fever disappeared within 2 days, and the remaining symptoms went away within a week.

The authors noted that the woman’s thyroid had been evaluated before she tested positive for SARS-CoV-2, and at that time, thyroid disease was ruled out. They also pointed out that, although the exact etiology for subacute thyroiditis is unknown, “it is common opinion that the disease is due to a viral infection or to a post-viral inflammatory reaction in genetically predisposed subjects.” They cited examples of viruses with suspected causal associations, including mumps, Epstein-Barr virus, and HIV, and they suggested that, based on the timing of the woman’s subacute thyroiditis and the normal results of her thyroid evaluation before developing COVID-19, SARS-CoV-2 be added to that list.

“To our knowledge, this is the first case of [subacute thyroiditis] related to SARS-CoV-2,” they concluded. “We therefore believe that physicians should be alerted about the possibility of this additional clinical manifestation related to SARS-CoV-2 infection.”

One author reported funding from the University of Pisa.

[email protected]

SOURCE: Brancatella A et al. J Clin Endocrinol Metab. 2020 May 21. doi: 10.1210/clinem/dgaa276.