Rheumatology News

A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.

However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.

Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.

BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.

Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.

All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.

The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).

Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.

The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.

“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
 

Safety profile comparison

As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.

Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.

The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.

The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).

The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.

“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”

Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.

In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.

A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.

The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”

They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.

The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.

Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.

However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.

“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.

This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.

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

A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.

However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.

Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.

BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.

Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.

All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.

The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).

Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.

The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.

“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
 

Safety profile comparison

As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.

Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.

The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.

The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).

The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.

“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”

Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.

In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.

A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.

The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”

They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.

The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.

Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.

However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.

“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.

This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.

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

A combination treatment of neutralizing monoclonal antibodies bamlanivimab and etesevimab was associated with a statistically significant reduction in SARS-CoV-2 at day 11 compared with placebo among nonhospitalized patients who had mild to moderate COVID-19, new data indicate.

However, bamlanivimab alone in three different single-infusion doses showed no significant reduction in viral load, compared with placebo, according to the phase 2/3 study by Robert L. Gottlieb, MD, PhD, of the Baylor University Medical Center and the Baylor Scott & White Research Institute, both in Dallas, and colleagues.

Findings from the Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies (BLAZE-1) study were published online Jan. 21 in JAMA. The results represent findings through Oct. 6, 2020.

BLAZE-1 was funded by Eli Lilly, which makes both of the antispike neutralizing antibodies. The trial was conducted at 49 U.S. centers and included 613 outpatients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms.

Patients were randomized to one of five groups (four treatment groups and a placebo control), and researchers analyzed between-group differences.

All four treatment arms suggest a trend toward reduction in viral load, which was the primary endpoint of the trial, but only the combination showed a statistically significant reduction.

The average age of patients was 44.7 years, 54.6% were female, 42.5% were Hispanic, and 67.1% had at least one risk factor for severe COVID-19 (aged ≥55 years, body mass index of at least 30, or relevant comorbidity such as hypertension).

Among secondary outcomes, there were no consistent differences between the monotherapy groups or the combination group versus placebo for the other measures of viral load or clinical symptom scores.

The proportion of patients who had COVID-19–related hospitalizations or ED visits was 5.8% (nine events) for placebo; 1.0% (one event) for the 700-mg group; 1.9% (two events) for 2,800 mg; 2.0% (two events) for 7,000 mg; and 0.9% (one event) for combination treatment.

“Combining these two neutralizing monoclonal antibodies in clinical use may enhance viral load reduction and decrease treatment-emergent resistant variants,” the authors concluded.
 

Safety profile comparison

As for adverse events, immediate hypersensitivity reactions were reported in nine patients (six bamlanivimab, two combination treatment, and one placebo). No deaths occurred during the study.

Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups; in 0.9% (1/112) of patients in the combination group; and in 0.6% (1/156) of patients in the placebo group.

The serious adverse event in the combination group was a urinary tract infection deemed unrelated to the study drug, the authors wrote.

The two most frequently reported side effects were nausea (3.0% for the 700-mg group; 3.7% for the 2,800-mg group; 5.0% for the 7,000-mg group; 3.6% for the combination group; and 3.8% for the placebo group) and diarrhea (1.0%, 1.9%, 5.9%, 0.9%, and 4.5%, respectively).

The authors included in the study’s limitations that the primary endpoint at day 11 may have been too late to best detect treatment effects.

“All patients, including those who received placebo, demonstrated substantial viral reduction by day 11,” they noted. “An earlier time point like day 3 or day 7 could possibly have been more appropriate to measure viral load.”

Currently, only remdesivir has been approved by the Food and Drug Administration for treating COVID-19, but convalescent plasma and neutralizing monoclonal antibodies have been granted emergency-use authorization.

In an accompanying editor’s note, Preeti N. Malani, MD, with the division of infectious diseases at the University of Michigan, Ann Arbor, and associate editor of JAMA, and Robert M. Golub, MD, deputy editor of JAMA, pointed out that these results differ from an earlier interim analysis of BLAZE-1 data.

A previous publication by Peter Chen, MD, with the department of medicine at Cedars Sinai Medical Center, Los Angeles, compared the three monotherapy groups (no combination group) with placebo, and in that study the 2,800-mg dose of bamlanivimab versus placebo achieved statistical significance for reduction in viral load from baseline at day 11, whereas the other two doses did not.

The editors explain that, in the study by Dr. Chen, “Follow-up for the placebo group was incomplete at the time of the database lock on Sept. 5, 2020. In the final analysis reported in the current article, the database was locked on Oct. 6, 2020, and the longer follow-up for the placebo group, which is now complete, resulted in changes in the primary outcome among that group.”

They concluded: “The comparison of the monotherapy groups against the final results for the placebo group led to changes in the effect sizes,” and the statistical significance of the 2,800-mg group was erased.

The editors pointed out that monoclonal antibodies are likely to benefit certain patients but definitive answers regarding which patients will benefit and under what circumstances will likely take more time than clinicians have to make decisions on treatment.

Meanwhile, as this news organization reported, the United States has spent $375 million on bamlanivimab and $450 million on Regeneron’s monoclonal antibody cocktail of casirivimab plus imdevimab, with the promise to spend billions more.

However, 80% of the 660,000 doses delivered by the two companies are still sitting on shelves, federal officials said in a press briefing last week, because of doubts about efficacy, lack of resources for infusion centers, and questions on reimbursement.

“While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit,” Dr. Malani and Dr. Golub wrote.

This trial was sponsored and funded by Eli Lilly. Dr. Gottlieb disclosed personal fees and nonfinancial support (medication for another trial) from Gilead Sciences and serving on an advisory board for Sentinel. Several coauthors have financial ties to Eli Lilly. Dr. Malani reported serving on the National Institute of Allergy and Infectious Diseases COVID-19 Preventive Monoclonal Antibody data and safety monitoring board but was not compensated. Dr. Golub disclosed no relevant financial relationships.

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

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Severe renal arteriosclerosis was associated with a ninefold increased risk of atherosclerotic cardiovascular disease in patients with lupus nephritis, based on data from an observational study of 189 individuals.

Mohammed Haneefa Nizamudeen/Getty Images

Atherosclerotic cardiovascular disease (ASCVD) has traditionally been thought to be a late complication of systemic lupus erythematosus (SLE), but this has been challenged in recent population-based studies of patients with SLE and lupus nephritis (LN) that indicated an early and increased risk of ASCVD at the time of diagnosis. However, it is unclear which early risk factors may predispose patients to ASCVD, Shivani Garg, MD, of the University of Wisconsin, Madison, and colleagues wrote in a study published in Arthritis Care & Research.

In patients with IgA nephropathy and renal transplantation, previous studies have shown that severe renal arteriosclerosis (r-ASCL) based on kidney biopsies at the time of diagnosis predicts ASCVD, but “a few studies including LN biopsies failed to report a similar association between the presence of severe r-ASCL and ASCVD occurrence,” possibly because of underreporting of r-ASCL. Dr. Garg and colleagues also noted the problem of underreporting of r-ASCL in their own previous study of its prevalence in LN patients at the time of diagnosis.

To get a more detailed view of how r-ASCL may be linked to early occurrence of ASCVD in LN patients, Dr. Garg and coauthors identified 189 consecutive patients with incident LN who underwent diagnostic biopsies between 1994 and 2017. The median age of the patients was 25 years, 78% were women, and 73% were white. The researchers developed a composite score for r-ASCL severity based on reported and overread biopsies.

Overall, 31% of the patients had any reported r-ASCL, and 7% had moderate-severe r-ASCL. After incorporating systematically reexamined r-ASCL grades, the prevalence of any and moderate-severe r-ASCL increased to 39% and 12%, respectively.

Based on their composite of reported and overread r-ASCL grade, severe r-ASCL in diagnostic LN biopsies was associated with a ninefold increased risk of ASCVD.

The researchers identified 22 incident ASCVD events over an 11-year follow-up for an overall 12% incidence of ASCVD in LN. ASCVD was defined as ischemic heart disease (including myocardial infarction, coronary artery revascularization, abnormal stress test, abnormal angiogram, and events documented by a cardiologist); stroke and transient ischemic attack (TIA); and peripheral vascular disease. Incident ASCVD was defined as the first ASCVD event between 1 and 10 years after LN diagnosis.

The most common ASCVD events were stroke or TIA (12 patients), events related to ischemic heart disease (7 patients), and events related to peripheral vascular disease (3 patients).

Lack of statin use

The researchers also hypothesized that the presence of gaps in statin use among eligible LN patients would be present in their study population. “Among the 20 patients with incident ASCVD events after LN diagnosis in our cohort, none was on statin therapy at the time of LN diagnosis,” the researchers said, noting that current guidelines from the American College of Rheumatology and the European League Against Rheumatism (now known as the European Alliance of Associations for Rheumatology) recommend initiating statin therapy at the time of LN diagnosis in all patients who have hyperlipidemia and chronic kidney disease (CKD) stage ≥3. “Further, 11 patients (55%) met high-risk criteria (hyperlipidemia and CKD stage ≥3) to implement statin therapy at the time of LN diagnosis, yet only one patient (9%) was initiated on statin therapy.” In addition, patients with stage 3 or higher CKD were more likely to develop ASCVD than patients without stage 3 or higher CKD, they said.

The study findings were limited by several factors including the majority white study population, the ability to overread only 25% of the biopsies, and the lack of data on the potential role of chronic lesions in ASCVD, the researchers noted. However, the results were strengthened by the use of a validated LN cohort, and the data provide “the basis to establish severe composite r-ASCL as a predictor of ASCVD events using a larger sample size in different cohorts,” they said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

In the midst of a pandemic, the biggest changes health care leaders reported in their medical practices last year revolved around staffing, cost and revenue, practice transformation, information technology, and operations, according to a December 2020 report from the Medical Group Management Association.

The report was assembled from the results of weekly Stat polls by MGMA, which consists of 15,000 group practices representing more than 350,000 physicians. During the course of the year, more than 4,800 practice leaders were surveyed, but the individual polls had far fewer respondents.

The 2020 data represents snapshots from different points in the developing public health crisis. Still, much of what practices experienced earlier in the pandemic continues to apply, and it’s likely to persist this year as long as the coronavirus spreads and its toll deepens.

One top-line conclusion of the report: the economic pain felt by practices has resulted in layoffs, furloughs, and/or reduced compensation for providers and staff.

In the May 19 weekly survey, 82% of respondents said some or all of their providers’ compensation had been affected by the crisis. About 62% said every provider had been affected. Provider compensation was cut in several ways, including reduced hours and salaries, reduced or eliminated bonuses, and lower allowances for continuing medical education.

About 61% of health care leaders said in the June 26 poll that their own compensation had decreased.

In the following week’s survey, one in three managers said their organization had reduced staff compensation. Nearly all of the respondents in this category predicted the salary reductions would be temporary.

As of March 17, early in the pandemic, 40% of health care leaders said they were experiencing staff shortages. An April 21 poll found that 53% of health care leaders were taking steps to address their providers’ and staffers’ mental health.

“The mental and emotional toll on everyone continues to be a concern, as public health authorities continue to report alarming numbers of new [COVID-19] cases, hospitalizations, and deaths,” MGMA commented.
 

Telehealth and remote monitoring

Nearly all of the health care leaders surveyed on March 31 reported that their practices had expanded telehealth access because of COVID-19. The percentage of patient visits handled remotely had dropped substantially by the fall, according to a Harvard University/Commonwealth Fund/Phreesia survey. Still, it remains significantly higher than it was before the pandemic.

“At the end of 2020, telemedicine continues to play a vital role in everyday practice operations and long-term planning,” the MGMA report said. One indication of this, the association said, is that health care leaders are recognizing new best practices in specialty telemedicine, such as pediatrics and ob.gyn.

According to an April 28 poll, the top three coding/billing challenges for telehealth and telephone visits amid COVID-19 were inconsistent payer rules, pay parity and accuracy, and documentation of virtual visits.

While the Centers for Medicare & Medicaid Services has loosened its regulations to allow reimbursement of telehealth in all locations and at the same level as in-person visits, most of those changes will not last beyond the public health crisis without new legislation.

More health care leaders are considering the use of remote patient monitoring, MGMA said, but only 21% of practices offered such services as of Sept. 15. The report drew a connection between these plans and the current challenge of deferred care.

In the July 21 poll, 87% of health care leaders reported that safety concerns were the top reason that patients deferred care amid COVID-19. The MGMA report quoted JaeLynn Williams, CEO of Air Methods, which provides helicopter ambulance services, as saying that many people are staying home even when they face life-threatening conditions such as chest pain, drug symptoms, inflamed appendix, and gallbladder pain.
 

Operational issues

Overall, MGMA said, practices that have taken a financial risk have done better during the pandemic than fee-for-service practices because their monthly capitation revenue has continued unabated. In contrast, “most groups’ struggles to sustain visits and procedures meant less revenue and lower compensation,” the report said.

In the August 18 survey, one in three health care leaders reported their practices were changing their operational metrics and how often they looked at those measures because of the pandemic. “Practice managers are asking for dashboard data in weeks instead of months to measure the drop in charges and forecast the resulting change in collections,” MGMA noted. “The type of data practice managers are asking for has also changed.”

Among the new metrics that practices are interested in, according to an MGMA article, are measures that track telehealth visits, the productivity of staff working at home, and the number of ancillary services and procedures that new patients might need based on historical data.

Nearly all health care leaders surveyed on Aug. 11 said the cost of obtaining personal protective equipment had increased during 2020. MGMA said it expects this situation to worsen if the pandemic lasts through the summer of 2021.

While everyone is talking about the botched launch of the COVID-19 vaccination campaign, there were also problems with flu vaccination in 2020. In the Sept. 25 poll, 34% of health care leaders reported their practices were experiencing delays in getting the flu vaccine.
 

Looking ahead

Looking further ahead, the report recommended that practices make plans to boost staff morale by restoring bonuses.

In addition, MGMA suggested that physician groups reassess their space needs. “The equation is simple – fewer nonclinical staff members at your facility means you should repurpose that office space or consider finding a better fit for your new real estate needs in 2021.”

Finally, MGMA noted that the practices expanding rather than contracting their business are those increasing their value-based revenues by taking on more risk. For those groups, “growing the patient panel can help [them] seek better rates in contract negotiations.”

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

In the midst of a pandemic, the biggest changes health care leaders reported in their medical practices last year revolved around staffing, cost and revenue, practice transformation, information technology, and operations, according to a December 2020 report from the Medical Group Management Association.

The report was assembled from the results of weekly Stat polls by MGMA, which consists of 15,000 group practices representing more than 350,000 physicians. During the course of the year, more than 4,800 practice leaders were surveyed, but the individual polls had far fewer respondents.

The 2020 data represents snapshots from different points in the developing public health crisis. Still, much of what practices experienced earlier in the pandemic continues to apply, and it’s likely to persist this year as long as the coronavirus spreads and its toll deepens.

One top-line conclusion of the report: the economic pain felt by practices has resulted in layoffs, furloughs, and/or reduced compensation for providers and staff.

In the May 19 weekly survey, 82% of respondents said some or all of their providers’ compensation had been affected by the crisis. About 62% said every provider had been affected. Provider compensation was cut in several ways, including reduced hours and salaries, reduced or eliminated bonuses, and lower allowances for continuing medical education.

About 61% of health care leaders said in the June 26 poll that their own compensation had decreased.

In the following week’s survey, one in three managers said their organization had reduced staff compensation. Nearly all of the respondents in this category predicted the salary reductions would be temporary.

As of March 17, early in the pandemic, 40% of health care leaders said they were experiencing staff shortages. An April 21 poll found that 53% of health care leaders were taking steps to address their providers’ and staffers’ mental health.

“The mental and emotional toll on everyone continues to be a concern, as public health authorities continue to report alarming numbers of new [COVID-19] cases, hospitalizations, and deaths,” MGMA commented.
 

Telehealth and remote monitoring

Nearly all of the health care leaders surveyed on March 31 reported that their practices had expanded telehealth access because of COVID-19. The percentage of patient visits handled remotely had dropped substantially by the fall, according to a Harvard University/Commonwealth Fund/Phreesia survey. Still, it remains significantly higher than it was before the pandemic.

“At the end of 2020, telemedicine continues to play a vital role in everyday practice operations and long-term planning,” the MGMA report said. One indication of this, the association said, is that health care leaders are recognizing new best practices in specialty telemedicine, such as pediatrics and ob.gyn.

According to an April 28 poll, the top three coding/billing challenges for telehealth and telephone visits amid COVID-19 were inconsistent payer rules, pay parity and accuracy, and documentation of virtual visits.

While the Centers for Medicare & Medicaid Services has loosened its regulations to allow reimbursement of telehealth in all locations and at the same level as in-person visits, most of those changes will not last beyond the public health crisis without new legislation.

More health care leaders are considering the use of remote patient monitoring, MGMA said, but only 21% of practices offered such services as of Sept. 15. The report drew a connection between these plans and the current challenge of deferred care.

In the July 21 poll, 87% of health care leaders reported that safety concerns were the top reason that patients deferred care amid COVID-19. The MGMA report quoted JaeLynn Williams, CEO of Air Methods, which provides helicopter ambulance services, as saying that many people are staying home even when they face life-threatening conditions such as chest pain, drug symptoms, inflamed appendix, and gallbladder pain.
 

Operational issues

Overall, MGMA said, practices that have taken a financial risk have done better during the pandemic than fee-for-service practices because their monthly capitation revenue has continued unabated. In contrast, “most groups’ struggles to sustain visits and procedures meant less revenue and lower compensation,” the report said.

In the August 18 survey, one in three health care leaders reported their practices were changing their operational metrics and how often they looked at those measures because of the pandemic. “Practice managers are asking for dashboard data in weeks instead of months to measure the drop in charges and forecast the resulting change in collections,” MGMA noted. “The type of data practice managers are asking for has also changed.”

Among the new metrics that practices are interested in, according to an MGMA article, are measures that track telehealth visits, the productivity of staff working at home, and the number of ancillary services and procedures that new patients might need based on historical data.

Nearly all health care leaders surveyed on Aug. 11 said the cost of obtaining personal protective equipment had increased during 2020. MGMA said it expects this situation to worsen if the pandemic lasts through the summer of 2021.

While everyone is talking about the botched launch of the COVID-19 vaccination campaign, there were also problems with flu vaccination in 2020. In the Sept. 25 poll, 34% of health care leaders reported their practices were experiencing delays in getting the flu vaccine.
 

Looking ahead

Looking further ahead, the report recommended that practices make plans to boost staff morale by restoring bonuses.

In addition, MGMA suggested that physician groups reassess their space needs. “The equation is simple – fewer nonclinical staff members at your facility means you should repurpose that office space or consider finding a better fit for your new real estate needs in 2021.”

Finally, MGMA noted that the practices expanding rather than contracting their business are those increasing their value-based revenues by taking on more risk. For those groups, “growing the patient panel can help [them] seek better rates in contract negotiations.”

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

In the midst of a pandemic, the biggest changes health care leaders reported in their medical practices last year revolved around staffing, cost and revenue, practice transformation, information technology, and operations, according to a December 2020 report from the Medical Group Management Association.

The report was assembled from the results of weekly Stat polls by MGMA, which consists of 15,000 group practices representing more than 350,000 physicians. During the course of the year, more than 4,800 practice leaders were surveyed, but the individual polls had far fewer respondents.

The 2020 data represents snapshots from different points in the developing public health crisis. Still, much of what practices experienced earlier in the pandemic continues to apply, and it’s likely to persist this year as long as the coronavirus spreads and its toll deepens.

One top-line conclusion of the report: the economic pain felt by practices has resulted in layoffs, furloughs, and/or reduced compensation for providers and staff.

In the May 19 weekly survey, 82% of respondents said some or all of their providers’ compensation had been affected by the crisis. About 62% said every provider had been affected. Provider compensation was cut in several ways, including reduced hours and salaries, reduced or eliminated bonuses, and lower allowances for continuing medical education.

About 61% of health care leaders said in the June 26 poll that their own compensation had decreased.

In the following week’s survey, one in three managers said their organization had reduced staff compensation. Nearly all of the respondents in this category predicted the salary reductions would be temporary.

As of March 17, early in the pandemic, 40% of health care leaders said they were experiencing staff shortages. An April 21 poll found that 53% of health care leaders were taking steps to address their providers’ and staffers’ mental health.

“The mental and emotional toll on everyone continues to be a concern, as public health authorities continue to report alarming numbers of new [COVID-19] cases, hospitalizations, and deaths,” MGMA commented.
 

Telehealth and remote monitoring

Nearly all of the health care leaders surveyed on March 31 reported that their practices had expanded telehealth access because of COVID-19. The percentage of patient visits handled remotely had dropped substantially by the fall, according to a Harvard University/Commonwealth Fund/Phreesia survey. Still, it remains significantly higher than it was before the pandemic.

“At the end of 2020, telemedicine continues to play a vital role in everyday practice operations and long-term planning,” the MGMA report said. One indication of this, the association said, is that health care leaders are recognizing new best practices in specialty telemedicine, such as pediatrics and ob.gyn.

According to an April 28 poll, the top three coding/billing challenges for telehealth and telephone visits amid COVID-19 were inconsistent payer rules, pay parity and accuracy, and documentation of virtual visits.

While the Centers for Medicare & Medicaid Services has loosened its regulations to allow reimbursement of telehealth in all locations and at the same level as in-person visits, most of those changes will not last beyond the public health crisis without new legislation.

More health care leaders are considering the use of remote patient monitoring, MGMA said, but only 21% of practices offered such services as of Sept. 15. The report drew a connection between these plans and the current challenge of deferred care.

In the July 21 poll, 87% of health care leaders reported that safety concerns were the top reason that patients deferred care amid COVID-19. The MGMA report quoted JaeLynn Williams, CEO of Air Methods, which provides helicopter ambulance services, as saying that many people are staying home even when they face life-threatening conditions such as chest pain, drug symptoms, inflamed appendix, and gallbladder pain.
 

Operational issues

Overall, MGMA said, practices that have taken a financial risk have done better during the pandemic than fee-for-service practices because their monthly capitation revenue has continued unabated. In contrast, “most groups’ struggles to sustain visits and procedures meant less revenue and lower compensation,” the report said.

In the August 18 survey, one in three health care leaders reported their practices were changing their operational metrics and how often they looked at those measures because of the pandemic. “Practice managers are asking for dashboard data in weeks instead of months to measure the drop in charges and forecast the resulting change in collections,” MGMA noted. “The type of data practice managers are asking for has also changed.”

Among the new metrics that practices are interested in, according to an MGMA article, are measures that track telehealth visits, the productivity of staff working at home, and the number of ancillary services and procedures that new patients might need based on historical data.

Nearly all health care leaders surveyed on Aug. 11 said the cost of obtaining personal protective equipment had increased during 2020. MGMA said it expects this situation to worsen if the pandemic lasts through the summer of 2021.

While everyone is talking about the botched launch of the COVID-19 vaccination campaign, there were also problems with flu vaccination in 2020. In the Sept. 25 poll, 34% of health care leaders reported their practices were experiencing delays in getting the flu vaccine.
 

Looking ahead

Looking further ahead, the report recommended that practices make plans to boost staff morale by restoring bonuses.

In addition, MGMA suggested that physician groups reassess their space needs. “The equation is simple – fewer nonclinical staff members at your facility means you should repurpose that office space or consider finding a better fit for your new real estate needs in 2021.”

Finally, MGMA noted that the practices expanding rather than contracting their business are those increasing their value-based revenues by taking on more risk. For those groups, “growing the patient panel can help [them] seek better rates in contract negotiations.”

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

The BRACE-CORONA trial, the first randomized trial to address the question of whether patients with COVID-19 should continue to take ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) – has now been published.

The study, which was conducted in patients hospitalized with COVID-19 who were taking ACEIs or ARBs before hospitalization, showed no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue versus those assigned to continue these medications.

There were, however, hints that continuing to take ACEIs or ARBs may be beneficial for patients with more severe COVID-19.

The study was first presented at last year’s European Society of Cardiology Congress and was reported by this news organization at that time. The study was published online in JAMA on Jan. 19, 2021.

“These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment,” the authors concluded.

Led by Renato D. Lopes, MD, Duke Clinical Research Institute, Durham, N.C., the researchers explained that there has been conflicting speculation about the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on the course of COVID-19.

On the one hand, observations from animal models suggest that ACEIs and ARBs up-regulate the expression of ACE2, a receptor involved in SARS-CoV-2 infection of host target cells. This led to suggestions that these medications may enhance viral binding and cell entry. Conversely, RAAS inhibitors could benefit patients with COVID-19 through effects on angiotensin II expression and subsequent increases in angiotensin 1-7 and 1-9, which have vasodilatory and anti-inflammatory effects that might attenuate lung injury.

The BRACE-CORONA trial included 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization. The median age of the patients was 55 years. Of these patients, 57.1% were considered to have mild cases at hospital admission, and 42.9% were considered to have moderate cases.

Results showed no significant difference in the number of days alive and out of the hospital for patients in the discontinuation group (mean, 21.9 days) in comparison with patients in the continuation group (mean, 22.9 days). The mean ratio was 0.95 (95% confidence interval, 0.90-1.01).

There also was no statistically significant difference in deaths (2.7% of the discontinuation group vs. 2.8% for the continuation group); cardiovascular death (0.6% vs. 0.3%), or COVID-19 progression (38.3% vs. 32.3%).

The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs. 7.7% in the continuation group), shock requiring vasopressors (8.4% vs. 7.1%), acute MI (7.5% vs. 4.6%), new or worsening heart failure (4.2% vs. 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs. 2.8%).

The authors note that hypertension is an important comorbidity in patients with COVID-19. Recent data suggest that immune dysfunction may contribute to poor outcomes among patients who have COVID-19 and hypertension.

It has been shown that, when use of long-term medications is discontinued during hospitalization, the use of those medications is often not resumed, owing to clinical inertia. Long-term outcomes worsen as a result, the authors reported. In the current study, all patients had hypertension, and more than 50% were obese; both of these comorbidities increase the risk for poor outcomes with COVID-19.

The investigators pointed out that a sensitivity analysis in which site was regarded as a random effect showed a statistically significant finding in favor of the group that continued ACEIs or ARBs. This finding was similar to that of the on-treatment analysis. There were also statistically significant interactions between treatment effect and some subgroups, such as patients with lower oxygen saturation and greater disease severity at hospital admission. For these patients, continuing ACEIs or ARBs may be beneficial.

“The primary analyses with the null results but wide 95% confidence intervals suggest that the study might have been underpowered to detect a statistically significant benefit of continuing ACEIs or ARBs,” they said.

Dr. Lopes has received grant support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi and consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola, and Sanofi.

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

The BRACE-CORONA trial, the first randomized trial to address the question of whether patients with COVID-19 should continue to take ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) – has now been published.

The study, which was conducted in patients hospitalized with COVID-19 who were taking ACEIs or ARBs before hospitalization, showed no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue versus those assigned to continue these medications.

There were, however, hints that continuing to take ACEIs or ARBs may be beneficial for patients with more severe COVID-19.

The study was first presented at last year’s European Society of Cardiology Congress and was reported by this news organization at that time. The study was published online in JAMA on Jan. 19, 2021.

“These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment,” the authors concluded.

Led by Renato D. Lopes, MD, Duke Clinical Research Institute, Durham, N.C., the researchers explained that there has been conflicting speculation about the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on the course of COVID-19.

On the one hand, observations from animal models suggest that ACEIs and ARBs up-regulate the expression of ACE2, a receptor involved in SARS-CoV-2 infection of host target cells. This led to suggestions that these medications may enhance viral binding and cell entry. Conversely, RAAS inhibitors could benefit patients with COVID-19 through effects on angiotensin II expression and subsequent increases in angiotensin 1-7 and 1-9, which have vasodilatory and anti-inflammatory effects that might attenuate lung injury.

The BRACE-CORONA trial included 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization. The median age of the patients was 55 years. Of these patients, 57.1% were considered to have mild cases at hospital admission, and 42.9% were considered to have moderate cases.

Results showed no significant difference in the number of days alive and out of the hospital for patients in the discontinuation group (mean, 21.9 days) in comparison with patients in the continuation group (mean, 22.9 days). The mean ratio was 0.95 (95% confidence interval, 0.90-1.01).

There also was no statistically significant difference in deaths (2.7% of the discontinuation group vs. 2.8% for the continuation group); cardiovascular death (0.6% vs. 0.3%), or COVID-19 progression (38.3% vs. 32.3%).

The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs. 7.7% in the continuation group), shock requiring vasopressors (8.4% vs. 7.1%), acute MI (7.5% vs. 4.6%), new or worsening heart failure (4.2% vs. 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs. 2.8%).

The authors note that hypertension is an important comorbidity in patients with COVID-19. Recent data suggest that immune dysfunction may contribute to poor outcomes among patients who have COVID-19 and hypertension.

It has been shown that, when use of long-term medications is discontinued during hospitalization, the use of those medications is often not resumed, owing to clinical inertia. Long-term outcomes worsen as a result, the authors reported. In the current study, all patients had hypertension, and more than 50% were obese; both of these comorbidities increase the risk for poor outcomes with COVID-19.

The investigators pointed out that a sensitivity analysis in which site was regarded as a random effect showed a statistically significant finding in favor of the group that continued ACEIs or ARBs. This finding was similar to that of the on-treatment analysis. There were also statistically significant interactions between treatment effect and some subgroups, such as patients with lower oxygen saturation and greater disease severity at hospital admission. For these patients, continuing ACEIs or ARBs may be beneficial.

“The primary analyses with the null results but wide 95% confidence intervals suggest that the study might have been underpowered to detect a statistically significant benefit of continuing ACEIs or ARBs,” they said.

Dr. Lopes has received grant support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi and consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola, and Sanofi.

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

The BRACE-CORONA trial, the first randomized trial to address the question of whether patients with COVID-19 should continue to take ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) – has now been published.

The study, which was conducted in patients hospitalized with COVID-19 who were taking ACEIs or ARBs before hospitalization, showed no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue versus those assigned to continue these medications.

There were, however, hints that continuing to take ACEIs or ARBs may be beneficial for patients with more severe COVID-19.

The study was first presented at last year’s European Society of Cardiology Congress and was reported by this news organization at that time. The study was published online in JAMA on Jan. 19, 2021.

“These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment,” the authors concluded.

Led by Renato D. Lopes, MD, Duke Clinical Research Institute, Durham, N.C., the researchers explained that there has been conflicting speculation about the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on the course of COVID-19.

On the one hand, observations from animal models suggest that ACEIs and ARBs up-regulate the expression of ACE2, a receptor involved in SARS-CoV-2 infection of host target cells. This led to suggestions that these medications may enhance viral binding and cell entry. Conversely, RAAS inhibitors could benefit patients with COVID-19 through effects on angiotensin II expression and subsequent increases in angiotensin 1-7 and 1-9, which have vasodilatory and anti-inflammatory effects that might attenuate lung injury.

The BRACE-CORONA trial included 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization. The median age of the patients was 55 years. Of these patients, 57.1% were considered to have mild cases at hospital admission, and 42.9% were considered to have moderate cases.

Results showed no significant difference in the number of days alive and out of the hospital for patients in the discontinuation group (mean, 21.9 days) in comparison with patients in the continuation group (mean, 22.9 days). The mean ratio was 0.95 (95% confidence interval, 0.90-1.01).

There also was no statistically significant difference in deaths (2.7% of the discontinuation group vs. 2.8% for the continuation group); cardiovascular death (0.6% vs. 0.3%), or COVID-19 progression (38.3% vs. 32.3%).

The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs. 7.7% in the continuation group), shock requiring vasopressors (8.4% vs. 7.1%), acute MI (7.5% vs. 4.6%), new or worsening heart failure (4.2% vs. 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs. 2.8%).

The authors note that hypertension is an important comorbidity in patients with COVID-19. Recent data suggest that immune dysfunction may contribute to poor outcomes among patients who have COVID-19 and hypertension.

It has been shown that, when use of long-term medications is discontinued during hospitalization, the use of those medications is often not resumed, owing to clinical inertia. Long-term outcomes worsen as a result, the authors reported. In the current study, all patients had hypertension, and more than 50% were obese; both of these comorbidities increase the risk for poor outcomes with COVID-19.

The investigators pointed out that a sensitivity analysis in which site was regarded as a random effect showed a statistically significant finding in favor of the group that continued ACEIs or ARBs. This finding was similar to that of the on-treatment analysis. There were also statistically significant interactions between treatment effect and some subgroups, such as patients with lower oxygen saturation and greater disease severity at hospital admission. For these patients, continuing ACEIs or ARBs may be beneficial.

“The primary analyses with the null results but wide 95% confidence intervals suggest that the study might have been underpowered to detect a statistically significant benefit of continuing ACEIs or ARBs,” they said.

Dr. Lopes has received grant support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi and consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola, and Sanofi.

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

President Joe Biden signed 10 new executive orders on his second day in office that are designed to help roll out his broader plan to fight COVID-19.

Whitehouse.gov

“For the past year, we couldn’t rely on the federal government to act with the urgency and focus and coordination we needed, and we have seen the tragic cost of that failure,” Mr. Biden said in remarks from the White House, unveiling his 198-page National Strategy for the COVID-19 Response and Pandemic Preparedness.

He said as many as 500,000 Americans will have died by February. “It’s going to take months for us to turn things around,” he said.

“Our national strategy is comprehensive – it’s based on science, not politics; it’s based on truth, not denial,” Mr. Biden said. He also promised to restore public trust, in part by having scientists and public health experts speak to the public. “That’s why you’ll be hearing a lot more from Dr. Fauci again, not from the president,” he said, adding that the experts will be “free from political interference.”

While the president’s executive orders can help accomplish some of the plan’s proposals, the majority will require new funding from Congress and will be included in the $1.9 trillion American Rescue package that Mr. Biden hopes legislators will approve.
 

Ten new orders

The 10 new pandemic-related orders Biden signed on Jan. 21 follow two he signed on his first day in office.

One establishes a COVID-19 Response Office responsible for coordinating the pandemic response across all federal departments and agencies and also reestablishes the White House Directorate on Global Health Security and Biodefense, which was disabled by the Trump administration.

The other order requires masks and physical distancing in all federal buildings, on all federal lands, and by federal employees and contractors.

Among the new orders will be directives that:

• Require individuals to also wear masks in airports and planes, and when using other modes of public transportation including trains, boats, and intercity buses, and also require international travelers to produce proof of a recent negative COVID-19 test prior to entry and to quarantine after entry.
• Federal agencies use all powers, including the Defense Production Act, to accelerate manufacturing and delivery of supplies such as N95 masks, gowns, gloves, swabs, reagents, pipette tips, rapid test kits, and nitrocellulose material for rapid antigen tests, and all equipment and material needed to accelerate manufacture, delivery, and administration of COVID-19 vaccine.
• Create a Pandemic Testing Board to expand supply and access, to promote more surge capacity, and to ensure equitable access to tests.
• Facilitate discovery, development, and trials of potential COVID-19 treatments, as well as expand access to programs that can meet the long-term health needs of those recovering from the disease.
• Facilitate more and better data sharing that will allow businesses, schools, hospitals, and individuals to make real-time decisions based on spread in their community.
• Direct the Education and Health & Human Services departments to provide schools and child-care operations guidance on how to reopen and operate safely.
• Direct the Occupational Safety and Health Administration (OSHA) to immediately release clear guidance for employers to help keep workers safe and to enforce health and safety requirements.

The plan also sets goals for vaccination – including 100 million shots in the administration’s first 100 days. President Biden had already previewed his goals for vaccination, including setting up mass vaccination sites and mobile vaccination sites. During his remarks, Mr. Biden said that he had already directed the Federal Emergency Management Agency (FEMA) to begin setting up the vaccination centers.

The administration is also going to look into improving reimbursement for giving vaccines. As a start, the HHS will ask the Centers for Medicare & Medicaid Services to consider if a higher rate “may more accurately compensate providers,” according to the Biden plan.

“But the brutal truth is it will take months before we can get the majority of Americans vaccinated,” said Mr. Biden.

As part of the goal of ensuring an equitable pandemic response, the president will sign an order that establishes a COVID-19 Health Equity Task Force. The task force is charged with providing recommendations for allocating resources and funding in communities with inequities in COVID-19 outcomes by race, ethnicity, geography, disability, and other considerations.

Finally, the administration has committed to being more transparent and sharing more information. The national plan calls for the federal government to conduct regular, expert-led, science-based public briefings and to release regular reports on the pandemic. The administration said it will launch massive science-based public information campaigns – in multiple languages – to educate Americans on masks, testing, and vaccines, and also work to counter misinformation and disinformation.

The American Academy of Family Physicians (AAFP) applauded Mr. Biden’s initiative. “If enacted, this bold legislative agenda will provide much-needed support to American families struggling during the pandemic – especially communities of color and those hardest hit by the virus,” Ada D. Stewart, MD, AAFP president, said in a statement.

Dr. Stewart also noted that family physicians “are uniquely positioned in their communities to educate patients, prioritize access, and coordinate administration of the COVID-19 vaccines,” and urged the administration to ensure that family physicians and staff be vaccinated as soon as possible, to help them “more safely provide care to their communities.”

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

President Joe Biden signed 10 new executive orders on his second day in office that are designed to help roll out his broader plan to fight COVID-19.

Whitehouse.gov

“For the past year, we couldn’t rely on the federal government to act with the urgency and focus and coordination we needed, and we have seen the tragic cost of that failure,” Mr. Biden said in remarks from the White House, unveiling his 198-page National Strategy for the COVID-19 Response and Pandemic Preparedness.

He said as many as 500,000 Americans will have died by February. “It’s going to take months for us to turn things around,” he said.

“Our national strategy is comprehensive – it’s based on science, not politics; it’s based on truth, not denial,” Mr. Biden said. He also promised to restore public trust, in part by having scientists and public health experts speak to the public. “That’s why you’ll be hearing a lot more from Dr. Fauci again, not from the president,” he said, adding that the experts will be “free from political interference.”

While the president’s executive orders can help accomplish some of the plan’s proposals, the majority will require new funding from Congress and will be included in the $1.9 trillion American Rescue package that Mr. Biden hopes legislators will approve.
 

Ten new orders

The 10 new pandemic-related orders Biden signed on Jan. 21 follow two he signed on his first day in office.

One establishes a COVID-19 Response Office responsible for coordinating the pandemic response across all federal departments and agencies and also reestablishes the White House Directorate on Global Health Security and Biodefense, which was disabled by the Trump administration.

The other order requires masks and physical distancing in all federal buildings, on all federal lands, and by federal employees and contractors.

Among the new orders will be directives that:

• Require individuals to also wear masks in airports and planes, and when using other modes of public transportation including trains, boats, and intercity buses, and also require international travelers to produce proof of a recent negative COVID-19 test prior to entry and to quarantine after entry.
• Federal agencies use all powers, including the Defense Production Act, to accelerate manufacturing and delivery of supplies such as N95 masks, gowns, gloves, swabs, reagents, pipette tips, rapid test kits, and nitrocellulose material for rapid antigen tests, and all equipment and material needed to accelerate manufacture, delivery, and administration of COVID-19 vaccine.
• Create a Pandemic Testing Board to expand supply and access, to promote more surge capacity, and to ensure equitable access to tests.
• Facilitate discovery, development, and trials of potential COVID-19 treatments, as well as expand access to programs that can meet the long-term health needs of those recovering from the disease.
• Facilitate more and better data sharing that will allow businesses, schools, hospitals, and individuals to make real-time decisions based on spread in their community.
• Direct the Education and Health & Human Services departments to provide schools and child-care operations guidance on how to reopen and operate safely.
• Direct the Occupational Safety and Health Administration (OSHA) to immediately release clear guidance for employers to help keep workers safe and to enforce health and safety requirements.

The plan also sets goals for vaccination – including 100 million shots in the administration’s first 100 days. President Biden had already previewed his goals for vaccination, including setting up mass vaccination sites and mobile vaccination sites. During his remarks, Mr. Biden said that he had already directed the Federal Emergency Management Agency (FEMA) to begin setting up the vaccination centers.

The administration is also going to look into improving reimbursement for giving vaccines. As a start, the HHS will ask the Centers for Medicare & Medicaid Services to consider if a higher rate “may more accurately compensate providers,” according to the Biden plan.

“But the brutal truth is it will take months before we can get the majority of Americans vaccinated,” said Mr. Biden.

As part of the goal of ensuring an equitable pandemic response, the president will sign an order that establishes a COVID-19 Health Equity Task Force. The task force is charged with providing recommendations for allocating resources and funding in communities with inequities in COVID-19 outcomes by race, ethnicity, geography, disability, and other considerations.

Finally, the administration has committed to being more transparent and sharing more information. The national plan calls for the federal government to conduct regular, expert-led, science-based public briefings and to release regular reports on the pandemic. The administration said it will launch massive science-based public information campaigns – in multiple languages – to educate Americans on masks, testing, and vaccines, and also work to counter misinformation and disinformation.

The American Academy of Family Physicians (AAFP) applauded Mr. Biden’s initiative. “If enacted, this bold legislative agenda will provide much-needed support to American families struggling during the pandemic – especially communities of color and those hardest hit by the virus,” Ada D. Stewart, MD, AAFP president, said in a statement.

Dr. Stewart also noted that family physicians “are uniquely positioned in their communities to educate patients, prioritize access, and coordinate administration of the COVID-19 vaccines,” and urged the administration to ensure that family physicians and staff be vaccinated as soon as possible, to help them “more safely provide care to their communities.”

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

President Joe Biden signed 10 new executive orders on his second day in office that are designed to help roll out his broader plan to fight COVID-19.

Whitehouse.gov

“For the past year, we couldn’t rely on the federal government to act with the urgency and focus and coordination we needed, and we have seen the tragic cost of that failure,” Mr. Biden said in remarks from the White House, unveiling his 198-page National Strategy for the COVID-19 Response and Pandemic Preparedness.

He said as many as 500,000 Americans will have died by February. “It’s going to take months for us to turn things around,” he said.

“Our national strategy is comprehensive – it’s based on science, not politics; it’s based on truth, not denial,” Mr. Biden said. He also promised to restore public trust, in part by having scientists and public health experts speak to the public. “That’s why you’ll be hearing a lot more from Dr. Fauci again, not from the president,” he said, adding that the experts will be “free from political interference.”

While the president’s executive orders can help accomplish some of the plan’s proposals, the majority will require new funding from Congress and will be included in the $1.9 trillion American Rescue package that Mr. Biden hopes legislators will approve.
 

Ten new orders

The 10 new pandemic-related orders Biden signed on Jan. 21 follow two he signed on his first day in office.

One establishes a COVID-19 Response Office responsible for coordinating the pandemic response across all federal departments and agencies and also reestablishes the White House Directorate on Global Health Security and Biodefense, which was disabled by the Trump administration.

The other order requires masks and physical distancing in all federal buildings, on all federal lands, and by federal employees and contractors.

Among the new orders will be directives that:

• Require individuals to also wear masks in airports and planes, and when using other modes of public transportation including trains, boats, and intercity buses, and also require international travelers to produce proof of a recent negative COVID-19 test prior to entry and to quarantine after entry.
• Federal agencies use all powers, including the Defense Production Act, to accelerate manufacturing and delivery of supplies such as N95 masks, gowns, gloves, swabs, reagents, pipette tips, rapid test kits, and nitrocellulose material for rapid antigen tests, and all equipment and material needed to accelerate manufacture, delivery, and administration of COVID-19 vaccine.
• Create a Pandemic Testing Board to expand supply and access, to promote more surge capacity, and to ensure equitable access to tests.
• Facilitate discovery, development, and trials of potential COVID-19 treatments, as well as expand access to programs that can meet the long-term health needs of those recovering from the disease.
• Facilitate more and better data sharing that will allow businesses, schools, hospitals, and individuals to make real-time decisions based on spread in their community.
• Direct the Education and Health & Human Services departments to provide schools and child-care operations guidance on how to reopen and operate safely.
• Direct the Occupational Safety and Health Administration (OSHA) to immediately release clear guidance for employers to help keep workers safe and to enforce health and safety requirements.

The plan also sets goals for vaccination – including 100 million shots in the administration’s first 100 days. President Biden had already previewed his goals for vaccination, including setting up mass vaccination sites and mobile vaccination sites. During his remarks, Mr. Biden said that he had already directed the Federal Emergency Management Agency (FEMA) to begin setting up the vaccination centers.

The administration is also going to look into improving reimbursement for giving vaccines. As a start, the HHS will ask the Centers for Medicare & Medicaid Services to consider if a higher rate “may more accurately compensate providers,” according to the Biden plan.

“But the brutal truth is it will take months before we can get the majority of Americans vaccinated,” said Mr. Biden.

As part of the goal of ensuring an equitable pandemic response, the president will sign an order that establishes a COVID-19 Health Equity Task Force. The task force is charged with providing recommendations for allocating resources and funding in communities with inequities in COVID-19 outcomes by race, ethnicity, geography, disability, and other considerations.

Finally, the administration has committed to being more transparent and sharing more information. The national plan calls for the federal government to conduct regular, expert-led, science-based public briefings and to release regular reports on the pandemic. The administration said it will launch massive science-based public information campaigns – in multiple languages – to educate Americans on masks, testing, and vaccines, and also work to counter misinformation and disinformation.

The American Academy of Family Physicians (AAFP) applauded Mr. Biden’s initiative. “If enacted, this bold legislative agenda will provide much-needed support to American families struggling during the pandemic – especially communities of color and those hardest hit by the virus,” Ada D. Stewart, MD, AAFP president, said in a statement.

Dr. Stewart also noted that family physicians “are uniquely positioned in their communities to educate patients, prioritize access, and coordinate administration of the COVID-19 vaccines,” and urged the administration to ensure that family physicians and staff be vaccinated as soon as possible, to help them “more safely provide care to their communities.”

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

People with type 2 diabetes who develop COVID-19 show a substantially reduced risk of dying if they are taking metformin, shows a study that adds to prior research indicating the drug might somehow play a role in reducing the severity of infection.

“Unlike several previous analyses, this was a study in a racially diverse population with a high proportion of Blacks/African Americans and [it] revealed that metformin treatment of diabetes prior to diagnosis with COVID-19 was associated with a dramatic threefold reduced mortality in subjects with type 2 diabetes, even after correcting for multiple covariates,” first author Anath Shalev, MD, of the Comprehensive Diabetes Center at the University of Alabama at Birmingham, said in an interview.

But Anne Peters, MD, a professor of clinical medicine at the University of Southern California, Los Angeles, said caution is needed when interpreting these findings.

“It’s hard to tease out the true effects because, for instance, those treated with insulin may be a sicker subset of patients with diabetes than those on metformin, or those with comorbidities such as renal insufficiency may not be treated with metformin” she said in an interview.

“In general, though, treatment obviously matters and people who are better treated tend to do better, so while I think this study raises the question of what role metformin plays in the risk of mortality and COVID-19, I don’t think it necessarily proves the association,” Dr. Peters asserted.
 

Diverse population

The new study, published this month in Frontiers of Endocrinology, included 25,326 individuals who were tested for COVID-19 at the University of Alabama at Birmingham Hospital between February and June 2020.

Overall, 2.4% tested positive for COVID-19 (n = 604), which the authors note is likely a low figure because screening included asymptomatic hospital staff and patients having elective procedures.

Black/African American patients had a significantly higher risk of COVID-19 positivity, compared with White patients (odds ratio, 2.6; P < .0001). Rates were also higher among those with hypertension (OR, 2.46), diabetes (OR, 2.11), and obesity (OR, 1.93), compared with those without each condition (all P < .0001).

The overall mortality rate in COVID-19-positive patients was 11%. Diabetes was associated with a dramatically increased risk of death (OR, 3.62; P < .0001), and remained an independent risk factor even after adjusting for age, race, sex, obesity, and hypertension.

Notably, the reduction in mortality among those with diabetes taking metformin prior to COVID-19 diagnosis was significant: 11% of those patients died, compared with 23% of those with diabetes not taking metformin (OR, 0.33; P = .021).
 

Similar findings reported across varied populations

The study adds to mounting research suggesting metformin could have a protective effect on COVID-19 mortality, including an early report from Wuhan, China, findings from the French CORONADO study, and a U.S. study linking treatment with decreased mortality among women with COVID-19.

Of note, the effects of metformin on mortality in the current study were observed in men and women alike, as well as in high-risk subgroups including African Americans.

“The fact that such similar results were obtained in different populations from around the world suggests that the observed reduction in mortality risk, associated with metformin use in subjects with type 2 diabetes and COVID-19, might be generalizable,” the authors wrote.

“Furthermore, these findings underline the importance of following general diabetes treatment and prevention guidelines and not delaying or discontinuing any metformin treatment,” they add.
 

Speculation of mechanisms includes anti-inflammatory effects

While the mechanisms behind metformin’s potential role in reducing mortality risk in COVID-19 are unknown, the authors note that the most obvious assumption – that improved glycemic control may be a key factor – is disputed by the study’s finding that blood glucose levels and hemoglobin A1c were not significantly different among COVID-19 survivors taking versus not taking metformin.

They point instead to metformin’s known anti-inflammatory and antithrombotic properties.

“We therefore hypothesize that, by exerting some of these effects, metformin might improve outcomes and we are now in the process of investigating this possibility further,” Dr. Shalev said.

Dr. Peters noted that anti-inflammatory properties, themselves, are not necessarily unique to metformin in the treatment of diabetes.

“Many other agents, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce inflammation, so I don’t know if that would explain it, but it certainly could help,” she said. “[Reducing inflammation] is a hypothesis you see commonly with diabetes drugs, but I think there are also a lot of metabolic benefits from metformin.”

“It was fascinating that they had the A1c data and that survival with metformin didn’t appear to be as related to A1c levels as one might think,” she added.

Notably, a key advantage, should the effects and mechanisms be validated, is metformin’s high accessibility, Dr. Peters added.

“This doesn’t necessarily tell us what we can do to reduce the health care disparities surrounding COVID-19, but the fact that metformin is low cost and easily available is very important, so maybe it will help as we try to grapple with other risk factors.”

The authors have reported no relevant financial relationships.

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

People with type 2 diabetes who develop COVID-19 show a substantially reduced risk of dying if they are taking metformin, shows a study that adds to prior research indicating the drug might somehow play a role in reducing the severity of infection.

“Unlike several previous analyses, this was a study in a racially diverse population with a high proportion of Blacks/African Americans and [it] revealed that metformin treatment of diabetes prior to diagnosis with COVID-19 was associated with a dramatic threefold reduced mortality in subjects with type 2 diabetes, even after correcting for multiple covariates,” first author Anath Shalev, MD, of the Comprehensive Diabetes Center at the University of Alabama at Birmingham, said in an interview.

But Anne Peters, MD, a professor of clinical medicine at the University of Southern California, Los Angeles, said caution is needed when interpreting these findings.

“It’s hard to tease out the true effects because, for instance, those treated with insulin may be a sicker subset of patients with diabetes than those on metformin, or those with comorbidities such as renal insufficiency may not be treated with metformin” she said in an interview.

“In general, though, treatment obviously matters and people who are better treated tend to do better, so while I think this study raises the question of what role metformin plays in the risk of mortality and COVID-19, I don’t think it necessarily proves the association,” Dr. Peters asserted.
 

Diverse population

The new study, published this month in Frontiers of Endocrinology, included 25,326 individuals who were tested for COVID-19 at the University of Alabama at Birmingham Hospital between February and June 2020.

Overall, 2.4% tested positive for COVID-19 (n = 604), which the authors note is likely a low figure because screening included asymptomatic hospital staff and patients having elective procedures.

Black/African American patients had a significantly higher risk of COVID-19 positivity, compared with White patients (odds ratio, 2.6; P < .0001). Rates were also higher among those with hypertension (OR, 2.46), diabetes (OR, 2.11), and obesity (OR, 1.93), compared with those without each condition (all P < .0001).

The overall mortality rate in COVID-19-positive patients was 11%. Diabetes was associated with a dramatically increased risk of death (OR, 3.62; P < .0001), and remained an independent risk factor even after adjusting for age, race, sex, obesity, and hypertension.

Notably, the reduction in mortality among those with diabetes taking metformin prior to COVID-19 diagnosis was significant: 11% of those patients died, compared with 23% of those with diabetes not taking metformin (OR, 0.33; P = .021).
 

Similar findings reported across varied populations

The study adds to mounting research suggesting metformin could have a protective effect on COVID-19 mortality, including an early report from Wuhan, China, findings from the French CORONADO study, and a U.S. study linking treatment with decreased mortality among women with COVID-19.

Of note, the effects of metformin on mortality in the current study were observed in men and women alike, as well as in high-risk subgroups including African Americans.

“The fact that such similar results were obtained in different populations from around the world suggests that the observed reduction in mortality risk, associated with metformin use in subjects with type 2 diabetes and COVID-19, might be generalizable,” the authors wrote.

“Furthermore, these findings underline the importance of following general diabetes treatment and prevention guidelines and not delaying or discontinuing any metformin treatment,” they add.
 

Speculation of mechanisms includes anti-inflammatory effects

While the mechanisms behind metformin’s potential role in reducing mortality risk in COVID-19 are unknown, the authors note that the most obvious assumption – that improved glycemic control may be a key factor – is disputed by the study’s finding that blood glucose levels and hemoglobin A1c were not significantly different among COVID-19 survivors taking versus not taking metformin.

They point instead to metformin’s known anti-inflammatory and antithrombotic properties.

“We therefore hypothesize that, by exerting some of these effects, metformin might improve outcomes and we are now in the process of investigating this possibility further,” Dr. Shalev said.

Dr. Peters noted that anti-inflammatory properties, themselves, are not necessarily unique to metformin in the treatment of diabetes.

“Many other agents, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce inflammation, so I don’t know if that would explain it, but it certainly could help,” she said. “[Reducing inflammation] is a hypothesis you see commonly with diabetes drugs, but I think there are also a lot of metabolic benefits from metformin.”

“It was fascinating that they had the A1c data and that survival with metformin didn’t appear to be as related to A1c levels as one might think,” she added.

Notably, a key advantage, should the effects and mechanisms be validated, is metformin’s high accessibility, Dr. Peters added.

“This doesn’t necessarily tell us what we can do to reduce the health care disparities surrounding COVID-19, but the fact that metformin is low cost and easily available is very important, so maybe it will help as we try to grapple with other risk factors.”

The authors have reported no relevant financial relationships.

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

People with type 2 diabetes who develop COVID-19 show a substantially reduced risk of dying if they are taking metformin, shows a study that adds to prior research indicating the drug might somehow play a role in reducing the severity of infection.

“Unlike several previous analyses, this was a study in a racially diverse population with a high proportion of Blacks/African Americans and [it] revealed that metformin treatment of diabetes prior to diagnosis with COVID-19 was associated with a dramatic threefold reduced mortality in subjects with type 2 diabetes, even after correcting for multiple covariates,” first author Anath Shalev, MD, of the Comprehensive Diabetes Center at the University of Alabama at Birmingham, said in an interview.

But Anne Peters, MD, a professor of clinical medicine at the University of Southern California, Los Angeles, said caution is needed when interpreting these findings.

“It’s hard to tease out the true effects because, for instance, those treated with insulin may be a sicker subset of patients with diabetes than those on metformin, or those with comorbidities such as renal insufficiency may not be treated with metformin” she said in an interview.

“In general, though, treatment obviously matters and people who are better treated tend to do better, so while I think this study raises the question of what role metformin plays in the risk of mortality and COVID-19, I don’t think it necessarily proves the association,” Dr. Peters asserted.
 

Diverse population

The new study, published this month in Frontiers of Endocrinology, included 25,326 individuals who were tested for COVID-19 at the University of Alabama at Birmingham Hospital between February and June 2020.

Overall, 2.4% tested positive for COVID-19 (n = 604), which the authors note is likely a low figure because screening included asymptomatic hospital staff and patients having elective procedures.

Black/African American patients had a significantly higher risk of COVID-19 positivity, compared with White patients (odds ratio, 2.6; P < .0001). Rates were also higher among those with hypertension (OR, 2.46), diabetes (OR, 2.11), and obesity (OR, 1.93), compared with those without each condition (all P < .0001).

The overall mortality rate in COVID-19-positive patients was 11%. Diabetes was associated with a dramatically increased risk of death (OR, 3.62; P < .0001), and remained an independent risk factor even after adjusting for age, race, sex, obesity, and hypertension.

Notably, the reduction in mortality among those with diabetes taking metformin prior to COVID-19 diagnosis was significant: 11% of those patients died, compared with 23% of those with diabetes not taking metformin (OR, 0.33; P = .021).
 

Similar findings reported across varied populations

The study adds to mounting research suggesting metformin could have a protective effect on COVID-19 mortality, including an early report from Wuhan, China, findings from the French CORONADO study, and a U.S. study linking treatment with decreased mortality among women with COVID-19.

Of note, the effects of metformin on mortality in the current study were observed in men and women alike, as well as in high-risk subgroups including African Americans.

“The fact that such similar results were obtained in different populations from around the world suggests that the observed reduction in mortality risk, associated with metformin use in subjects with type 2 diabetes and COVID-19, might be generalizable,” the authors wrote.

“Furthermore, these findings underline the importance of following general diabetes treatment and prevention guidelines and not delaying or discontinuing any metformin treatment,” they add.
 

Speculation of mechanisms includes anti-inflammatory effects

While the mechanisms behind metformin’s potential role in reducing mortality risk in COVID-19 are unknown, the authors note that the most obvious assumption – that improved glycemic control may be a key factor – is disputed by the study’s finding that blood glucose levels and hemoglobin A1c were not significantly different among COVID-19 survivors taking versus not taking metformin.

They point instead to metformin’s known anti-inflammatory and antithrombotic properties.

“We therefore hypothesize that, by exerting some of these effects, metformin might improve outcomes and we are now in the process of investigating this possibility further,” Dr. Shalev said.

Dr. Peters noted that anti-inflammatory properties, themselves, are not necessarily unique to metformin in the treatment of diabetes.

“Many other agents, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce inflammation, so I don’t know if that would explain it, but it certainly could help,” she said. “[Reducing inflammation] is a hypothesis you see commonly with diabetes drugs, but I think there are also a lot of metabolic benefits from metformin.”

“It was fascinating that they had the A1c data and that survival with metformin didn’t appear to be as related to A1c levels as one might think,” she added.

Notably, a key advantage, should the effects and mechanisms be validated, is metformin’s high accessibility, Dr. Peters added.

“This doesn’t necessarily tell us what we can do to reduce the health care disparities surrounding COVID-19, but the fact that metformin is low cost and easily available is very important, so maybe it will help as we try to grapple with other risk factors.”

The authors have reported no relevant financial relationships.

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

President Joe Biden has come into office after an unexpected shift in Congress. On Jan. 5, Democrats scored an upset by winning two U.S. Senate seats in runoff elections in Georgia, giving them control of the Senate.

Now the Democrats have control of all three levers of power – the Senate, the House, and the presidency – for the first time since the early years of the Obama administration.

How will President Biden use this new concentration of power to shape health care policy?

Democrats’ small majorities in both houses of Congress suggest that moderation and bipartisanship will be necessary to get things done. Moreover, Mr. Biden himself is calling for bipartisanship. “On this January day,” he said in his inauguration speech, “my whole soul is in this: Bringing America together, uniting our people, uniting our nation.”

Key health care actions that Mr. Biden could pursue include the following.
 

1. Passing a new COVID-19 relief bill

Above all, Mr. Biden is focused on overcoming the COVID-19 pandemic, which has been registering record deaths recently, and getting newly released vaccines to Americans.

“Dealing with the coronavirus pandemic is one of the most important battles our administration will face, and I will be informed by science and by experts,” the president said.

“There is no question that the pandemic is the highest priority for the Biden administration,” said Larry Levitt, executive vice president for health policy at the Henry J. Kaiser Family Foundation. “COVID will dominate the early weeks and months of this administration. His success rests, in particular, on improving the rollout of vaccines.”

Five days before his inauguration, the president-elect unveiled the American Rescue Plan, a massive, $1.9 trillion legislative package intended to hasten rollout of COVID-19 vaccines, improve COVID-19 testing, and provide financial help to businesses and individuals, among many other things.

The bill would add $1,400 to the recently passed $600 government relief payments for each American, amounting to a $2,000 check. It would also enact many non-COVID-19 measures, such as a $15-an-hour minimum wage and measures to bolster the Affordable Care Act (ACA).

If Democrats cannot reach a deal with the Republicans, they might turn the proposal into a reconciliation bill, which could then be passed with a simple majority. However, drafting a reconciliation bill is a long, complicated process that would require removing provisions that don’t meet the requirements of reconciliation, said Hazen Marshall, a Washington lobbyist and former staffer for Sen. Mitch McConnell.

Most importantly, Mr. Marshall said, reconciliation bills bring out diehard partisanship. “They involve a sledgehammer mentality,” he says. “You’re telling the other side that their views aren’t going to matter.” The final version of the ACA, for example, was passed as a reconciliation bill, with not one Republican vote.

In the Trump years, “the last four reconciliation bills did not get any votes from the minority,” added Rodney Whitlock, PhD, a political consultant at McDermott+Consulting, who worked 21 years for Republicans in the House. “When the majority chooses to use reconciliation, it is an admission that it has no interest in working with the minority.”

Hammering out a compromise will be tough, but Robert Pearl MD, former CEO of the Permanente Medical Group and a professor at Stanford (Calif.) University, said that if anyone can do it, it would be President Biden. Having served in the Senate for 36 years, “Biden knows Congress better than any president since Lyndon Johnson,” he said. “He can reach across the aisle and get legislation passed as much as anyone could these days.”
 

2. Restoring Obamacare

Mr. Biden has vowed to undo a gradual dismantling of the ACA that went on during the Trump administration through executive orders, rule-making, and new laws. “Reinvigorating the ACA was a central part of Biden’s platform as a candidate,” Mr. Levitt said.

Each Trump action against the ACA must be undone in the same way. Presidential orders must be met with presidential orders, regulations with regulations, and legislation with legislation.

The ACA is also being challenged in the Supreme Court. Republicans under Trump passed a law that reduced the penalty for not buying health insurance under the ACA to zero. Then a group of 20 states, led by Texas, filed a lawsuit asserting that this change makes the ACA unconstitutional.

The lawsuit was heard by the Supreme Court in November. From remarks made by the justices then, it appears that the court might well uphold the law when a verdict comes down in June.

But just in case, Mr. Biden wants Congress to enact a small penalty for not buying health insurance, which would remove the basis of the lawsuit.

Mr. Biden’s choice for secretary of Health and Human Services shows his level of commitment to protecting the ACA. His HHS nominee is California Attorney General Xavier Becerra, who led a group of 17 states defending the ACA in the current lawsuit.

In addition to undoing Trump’s changes, Mr. Biden plans to expand the ACA beyond the original legislation. The new COVID-19 bill contains provisions that would expand subsidies to buy insurance on the exchanges and would lower the maximum percentage of income that anyone has to pay for health insurance to 8.5%.

Dealing with Medicaid is also related to the ACA. In 2012, the Supreme Court struck down a mandate that states expand their Medicaid programs, with substantial funding from the federal government.

To date, 12 states still do not participate in the Medicaid expansion. To lure them into the expansion, the Democrat-controlled House last session passed a bill that would offer to pay the entire bill for the first 3 years of Medicaid expansion if they chose to enact an expansion.
 

3. Undoing other Trump actions in health care

In addition to changes in the ACA, Trump also enacted a number of other changes in health care that President Biden could undo. For example, Mr. Biden says he will reenter the World Health Organization (WHO) so that the United States could better coordinate a COVID-19 response with other nations. Trump exited the WHO with the stroke of a pen, and Mr. Biden can do the same in reverse.

Under Trump, the Centers for Medicare & Medicaid Services used waivers to weaken the ACA and allow states to alter their Medicaid programs. One waiver allows Georgia to leave the ACA exchanges and put brokers in charge of buying coverage. Other waivers allow states to transform federal Medicaid payments into block grants, which several states are planning to do.

The Trump CMS has allowed several states to use Medicaid waivers to add work requirements for Medicaid recipients. The courts have blocked the work rules so far, and the Biden CMS may decide to reverse these waivers or modify them.

“Undoing waivers is normally a fairly simple thing,” Mr. Levitt said. In January, however, the Trump CMS asked some waiver states to sign new contracts in which the CMS pledges not to end a waiver without 9 months’ notice. It’s unclear how many states signed such contracts and what obligation the Biden CMS has to enforce them.

The Trump CMS also stopped reimbursing insurers for waiving deductibles and copayments for low-income customers, as directed by the ACA. Without federal reimbursement, some insurers raised premiums by as much as 20% to cover the costs. It is unclear how the Biden CMS would tackle this change.
 

4. Negotiating lower drug prices

Allowing Medicare to negotiate drug prices, a major plank in Mr. Biden’s campaign, would seem like a slam dunk for the Democrats. This approach is backed by 89% of Americans, including 84% of Republicans, according to a Kaiser Family Foundation survey in December.

“With that level of support, it’s hard to go wrong politically on this issue,” Mr. Levitt said.

Many Republicans, however, do not favor negotiating drug prices, and the two parties continue to be far apart on how to control drug prices. Trump signed an action that allows Americans to buy cheaper drugs abroad, an approach that Mr. Biden also supports, but it is now tied up in the courts.

“A drug pricing bill has always been difficult to pass,” Dr. Whitlock said. “The issue is popular with the public, but change does not come easily. The drug lobby is one the strongest in Washington, and now it may be even stronger, since it was the drug companies that gave us the COVID vaccines.”

Dr. Whitlock said Republicans will want Democrats to compromise on drug pricing, but he doubts they will do so. The House passed a bill to negotiate drug prices last year, which never was voted on in the Senate. “It is difficult to imagine that the Democrats will be able to move rightward from that House bill,” Dr. Whitlock said. “Democrats are likely to stand pat on drug pricing.”
 

5. Introducing a public option

President Biden’s campaign proposal for a public option – health insurance offered by the federal government – and to lower the age for Medicare eligibility from 65 years to 60 years, resulted from a compromise between two factions of the Democratic party on how to expand coverage.

Although Mr. Biden and other moderates wanted to focus on fixing the ACA, Democrats led by Sen. Bernie Sanders of Vermont called for a single-payer system, dubbed “Medicare for all.” A public option was seen as the middle ground between the two camps.

“A public option would be a very controversial,” Dr. Whitlock said. Critics say it would pay at Medicare rates, which would reduce doctors’ reimbursements, and save very little money compared with a single-payer system.

Dr. Pearl sees similar problems with lowering the Medicare age. “This would be an expensive change that the federal government could not afford, particularly with all the spending on the pandemic,” he said. “And it would be tough on doctors and hospitals, because Medicare pays less than the private insurance payment they are now getting.”

“The public option is likely to get serious discussion within the Democratic caucus and get onto the Senate floor,” Mr. Levitt said. “The party won’t ignore it.” He notes that in the new Senate, Sen. Sanders chairs the budget committee, and from that position he is likely to push for expanding access to care.

Mr. Levitt says the Biden CMS might allow states to experiment with a statewide public option or even a single-payer model, but he concedes that states, with their budgets ravaged by COVID-19, do not currently have the money to launch such programs.
 

6. Reviving the CMS

Under President Obama, the CMS was the engine that implemented the ACA and shepherded wider use of value-based reimbursements, which reward providers for quality and outcomes rather than volume.

Under the Trump administration, CMS leadership continued to uphold value-based reimbursement, Dr. Pearl observed. “CMS leadership championed value-based payments, but they encountered a lot of pushback from doctors and hospitals and had to scale back their goals,” he said.

On the other hand, the Trump CMS took a 180-degree turn on the ACA and worked to take it apart. This took a toll on staff morale, according to Donald M. Berwick, MD, who ran the CMS under President Obama. “Many people in CMS did not feel supported during the Trump administration, and some of them left,” Dr. Berwick said.

The CMS needs experienced staff on board to write comprehensible rules and regulations that can overcome court challenges.

Having a fully functioning CMS also requires consistent leadership, which was a problem for Obama. When Mr. Obama nominated Dr. Berwick, 60 Senate votes were needed to confirm him, and Republicans would not vote for him. Mr. Obama eventually brought Dr. Berwick in as a recess appointment, but it meant he could serve for only 17 months.

Since then, Senate confirmation rules have changed so that only a simple majority is needed to confirm appointments. This is important for Biden’s nominees, Dr. Berwick said. “For a president, having your team in place means you are able to execute the policies you want,” he said. “You need to have consistent leadership.”
 

7. Potentially changing health care without Congress

Even with their newly won control of the Senate, the Democrats’ thin majorities in both houses of Congress may not be enough to pass much legislation if Republicans are solidly opposed.

Democrats in the House also have a narrow path this session in which to pass legislation. The Democratic leadership has an 11-vote majority, but it must contend with 15 moderate representatives in purple districts (where Democrats and Republicans have about equal support).

A bigger problem looms before the Democrats. In 2022, the party may well lose its majorities in both houses. Mr. Whitlock notes that the party of an incoming president normally loses seats in the first midterm election. “The last incoming president to keep both houses of Congress in his first midterm was Jimmy Carter,” he said.

If this happens, President Biden would have to govern without the support of Congress, which is what Barack Obama had to do through most of his presidency. As Mr. Obama’s vice president, Mr. Biden is well aware how that goes. Governing without Congress means relying on presidential orders and decrees.

In health care, Mr. Biden has a powerful policy-making tool, the Center for Medicare & Medicaid Innovation (CMMI). The CMMI was empowered by the ACA to initiate pilot programs for new payment models.

So far, the CMMI’s work has been mainly limited to accountable care organizations, bundled payments, and patient-centered medical homes, but it could also be used to enact new federal policies that would normally require Congressional action, Mr. Levitt said.
 

Conclusion

Expectations have been very high for what President Joe Biden can do in health care. He needs to unite a very divided political system to defeat a deadly pandemic, restore Obamacare, and sign landmark legislation, such as a drug-pricing bill.

But shepherding bills through Congress will be a challenge. “You need to have accountability, unity, and civility, which is a Herculean task,” Mr. Whitlock said. “You have to keep policies off the table that could blow up the bipartisanship.”

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

President Joe Biden has come into office after an unexpected shift in Congress. On Jan. 5, Democrats scored an upset by winning two U.S. Senate seats in runoff elections in Georgia, giving them control of the Senate.

Now the Democrats have control of all three levers of power – the Senate, the House, and the presidency – for the first time since the early years of the Obama administration.

How will President Biden use this new concentration of power to shape health care policy?

Democrats’ small majorities in both houses of Congress suggest that moderation and bipartisanship will be necessary to get things done. Moreover, Mr. Biden himself is calling for bipartisanship. “On this January day,” he said in his inauguration speech, “my whole soul is in this: Bringing America together, uniting our people, uniting our nation.”

Key health care actions that Mr. Biden could pursue include the following.
 

1. Passing a new COVID-19 relief bill

Above all, Mr. Biden is focused on overcoming the COVID-19 pandemic, which has been registering record deaths recently, and getting newly released vaccines to Americans.

“Dealing with the coronavirus pandemic is one of the most important battles our administration will face, and I will be informed by science and by experts,” the president said.

“There is no question that the pandemic is the highest priority for the Biden administration,” said Larry Levitt, executive vice president for health policy at the Henry J. Kaiser Family Foundation. “COVID will dominate the early weeks and months of this administration. His success rests, in particular, on improving the rollout of vaccines.”

Five days before his inauguration, the president-elect unveiled the American Rescue Plan, a massive, $1.9 trillion legislative package intended to hasten rollout of COVID-19 vaccines, improve COVID-19 testing, and provide financial help to businesses and individuals, among many other things.

The bill would add $1,400 to the recently passed $600 government relief payments for each American, amounting to a $2,000 check. It would also enact many non-COVID-19 measures, such as a $15-an-hour minimum wage and measures to bolster the Affordable Care Act (ACA).

If Democrats cannot reach a deal with the Republicans, they might turn the proposal into a reconciliation bill, which could then be passed with a simple majority. However, drafting a reconciliation bill is a long, complicated process that would require removing provisions that don’t meet the requirements of reconciliation, said Hazen Marshall, a Washington lobbyist and former staffer for Sen. Mitch McConnell.

Most importantly, Mr. Marshall said, reconciliation bills bring out diehard partisanship. “They involve a sledgehammer mentality,” he says. “You’re telling the other side that their views aren’t going to matter.” The final version of the ACA, for example, was passed as a reconciliation bill, with not one Republican vote.

In the Trump years, “the last four reconciliation bills did not get any votes from the minority,” added Rodney Whitlock, PhD, a political consultant at McDermott+Consulting, who worked 21 years for Republicans in the House. “When the majority chooses to use reconciliation, it is an admission that it has no interest in working with the minority.”

Hammering out a compromise will be tough, but Robert Pearl MD, former CEO of the Permanente Medical Group and a professor at Stanford (Calif.) University, said that if anyone can do it, it would be President Biden. Having served in the Senate for 36 years, “Biden knows Congress better than any president since Lyndon Johnson,” he said. “He can reach across the aisle and get legislation passed as much as anyone could these days.”
 

2. Restoring Obamacare

Mr. Biden has vowed to undo a gradual dismantling of the ACA that went on during the Trump administration through executive orders, rule-making, and new laws. “Reinvigorating the ACA was a central part of Biden’s platform as a candidate,” Mr. Levitt said.

Each Trump action against the ACA must be undone in the same way. Presidential orders must be met with presidential orders, regulations with regulations, and legislation with legislation.

The ACA is also being challenged in the Supreme Court. Republicans under Trump passed a law that reduced the penalty for not buying health insurance under the ACA to zero. Then a group of 20 states, led by Texas, filed a lawsuit asserting that this change makes the ACA unconstitutional.

The lawsuit was heard by the Supreme Court in November. From remarks made by the justices then, it appears that the court might well uphold the law when a verdict comes down in June.

But just in case, Mr. Biden wants Congress to enact a small penalty for not buying health insurance, which would remove the basis of the lawsuit.

Mr. Biden’s choice for secretary of Health and Human Services shows his level of commitment to protecting the ACA. His HHS nominee is California Attorney General Xavier Becerra, who led a group of 17 states defending the ACA in the current lawsuit.

In addition to undoing Trump’s changes, Mr. Biden plans to expand the ACA beyond the original legislation. The new COVID-19 bill contains provisions that would expand subsidies to buy insurance on the exchanges and would lower the maximum percentage of income that anyone has to pay for health insurance to 8.5%.

Dealing with Medicaid is also related to the ACA. In 2012, the Supreme Court struck down a mandate that states expand their Medicaid programs, with substantial funding from the federal government.

To date, 12 states still do not participate in the Medicaid expansion. To lure them into the expansion, the Democrat-controlled House last session passed a bill that would offer to pay the entire bill for the first 3 years of Medicaid expansion if they chose to enact an expansion.
 

3. Undoing other Trump actions in health care

In addition to changes in the ACA, Trump also enacted a number of other changes in health care that President Biden could undo. For example, Mr. Biden says he will reenter the World Health Organization (WHO) so that the United States could better coordinate a COVID-19 response with other nations. Trump exited the WHO with the stroke of a pen, and Mr. Biden can do the same in reverse.

Under Trump, the Centers for Medicare & Medicaid Services used waivers to weaken the ACA and allow states to alter their Medicaid programs. One waiver allows Georgia to leave the ACA exchanges and put brokers in charge of buying coverage. Other waivers allow states to transform federal Medicaid payments into block grants, which several states are planning to do.

The Trump CMS has allowed several states to use Medicaid waivers to add work requirements for Medicaid recipients. The courts have blocked the work rules so far, and the Biden CMS may decide to reverse these waivers or modify them.

“Undoing waivers is normally a fairly simple thing,” Mr. Levitt said. In January, however, the Trump CMS asked some waiver states to sign new contracts in which the CMS pledges not to end a waiver without 9 months’ notice. It’s unclear how many states signed such contracts and what obligation the Biden CMS has to enforce them.

The Trump CMS also stopped reimbursing insurers for waiving deductibles and copayments for low-income customers, as directed by the ACA. Without federal reimbursement, some insurers raised premiums by as much as 20% to cover the costs. It is unclear how the Biden CMS would tackle this change.
 

4. Negotiating lower drug prices

Allowing Medicare to negotiate drug prices, a major plank in Mr. Biden’s campaign, would seem like a slam dunk for the Democrats. This approach is backed by 89% of Americans, including 84% of Republicans, according to a Kaiser Family Foundation survey in December.

“With that level of support, it’s hard to go wrong politically on this issue,” Mr. Levitt said.

Many Republicans, however, do not favor negotiating drug prices, and the two parties continue to be far apart on how to control drug prices. Trump signed an action that allows Americans to buy cheaper drugs abroad, an approach that Mr. Biden also supports, but it is now tied up in the courts.

“A drug pricing bill has always been difficult to pass,” Dr. Whitlock said. “The issue is popular with the public, but change does not come easily. The drug lobby is one the strongest in Washington, and now it may be even stronger, since it was the drug companies that gave us the COVID vaccines.”

Dr. Whitlock said Republicans will want Democrats to compromise on drug pricing, but he doubts they will do so. The House passed a bill to negotiate drug prices last year, which never was voted on in the Senate. “It is difficult to imagine that the Democrats will be able to move rightward from that House bill,” Dr. Whitlock said. “Democrats are likely to stand pat on drug pricing.”
 

5. Introducing a public option

President Biden’s campaign proposal for a public option – health insurance offered by the federal government – and to lower the age for Medicare eligibility from 65 years to 60 years, resulted from a compromise between two factions of the Democratic party on how to expand coverage.

Although Mr. Biden and other moderates wanted to focus on fixing the ACA, Democrats led by Sen. Bernie Sanders of Vermont called for a single-payer system, dubbed “Medicare for all.” A public option was seen as the middle ground between the two camps.

“A public option would be a very controversial,” Dr. Whitlock said. Critics say it would pay at Medicare rates, which would reduce doctors’ reimbursements, and save very little money compared with a single-payer system.

Dr. Pearl sees similar problems with lowering the Medicare age. “This would be an expensive change that the federal government could not afford, particularly with all the spending on the pandemic,” he said. “And it would be tough on doctors and hospitals, because Medicare pays less than the private insurance payment they are now getting.”

“The public option is likely to get serious discussion within the Democratic caucus and get onto the Senate floor,” Mr. Levitt said. “The party won’t ignore it.” He notes that in the new Senate, Sen. Sanders chairs the budget committee, and from that position he is likely to push for expanding access to care.

Mr. Levitt says the Biden CMS might allow states to experiment with a statewide public option or even a single-payer model, but he concedes that states, with their budgets ravaged by COVID-19, do not currently have the money to launch such programs.
 

6. Reviving the CMS

Under President Obama, the CMS was the engine that implemented the ACA and shepherded wider use of value-based reimbursements, which reward providers for quality and outcomes rather than volume.

Under the Trump administration, CMS leadership continued to uphold value-based reimbursement, Dr. Pearl observed. “CMS leadership championed value-based payments, but they encountered a lot of pushback from doctors and hospitals and had to scale back their goals,” he said.

On the other hand, the Trump CMS took a 180-degree turn on the ACA and worked to take it apart. This took a toll on staff morale, according to Donald M. Berwick, MD, who ran the CMS under President Obama. “Many people in CMS did not feel supported during the Trump administration, and some of them left,” Dr. Berwick said.

The CMS needs experienced staff on board to write comprehensible rules and regulations that can overcome court challenges.

Having a fully functioning CMS also requires consistent leadership, which was a problem for Obama. When Mr. Obama nominated Dr. Berwick, 60 Senate votes were needed to confirm him, and Republicans would not vote for him. Mr. Obama eventually brought Dr. Berwick in as a recess appointment, but it meant he could serve for only 17 months.

Since then, Senate confirmation rules have changed so that only a simple majority is needed to confirm appointments. This is important for Biden’s nominees, Dr. Berwick said. “For a president, having your team in place means you are able to execute the policies you want,” he said. “You need to have consistent leadership.”
 

7. Potentially changing health care without Congress

Even with their newly won control of the Senate, the Democrats’ thin majorities in both houses of Congress may not be enough to pass much legislation if Republicans are solidly opposed.

Democrats in the House also have a narrow path this session in which to pass legislation. The Democratic leadership has an 11-vote majority, but it must contend with 15 moderate representatives in purple districts (where Democrats and Republicans have about equal support).

A bigger problem looms before the Democrats. In 2022, the party may well lose its majorities in both houses. Mr. Whitlock notes that the party of an incoming president normally loses seats in the first midterm election. “The last incoming president to keep both houses of Congress in his first midterm was Jimmy Carter,” he said.

If this happens, President Biden would have to govern without the support of Congress, which is what Barack Obama had to do through most of his presidency. As Mr. Obama’s vice president, Mr. Biden is well aware how that goes. Governing without Congress means relying on presidential orders and decrees.

In health care, Mr. Biden has a powerful policy-making tool, the Center for Medicare & Medicaid Innovation (CMMI). The CMMI was empowered by the ACA to initiate pilot programs for new payment models.

So far, the CMMI’s work has been mainly limited to accountable care organizations, bundled payments, and patient-centered medical homes, but it could also be used to enact new federal policies that would normally require Congressional action, Mr. Levitt said.
 

Conclusion

Expectations have been very high for what President Joe Biden can do in health care. He needs to unite a very divided political system to defeat a deadly pandemic, restore Obamacare, and sign landmark legislation, such as a drug-pricing bill.

But shepherding bills through Congress will be a challenge. “You need to have accountability, unity, and civility, which is a Herculean task,” Mr. Whitlock said. “You have to keep policies off the table that could blow up the bipartisanship.”

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

President Joe Biden has come into office after an unexpected shift in Congress. On Jan. 5, Democrats scored an upset by winning two U.S. Senate seats in runoff elections in Georgia, giving them control of the Senate.

Now the Democrats have control of all three levers of power – the Senate, the House, and the presidency – for the first time since the early years of the Obama administration.

How will President Biden use this new concentration of power to shape health care policy?

Democrats’ small majorities in both houses of Congress suggest that moderation and bipartisanship will be necessary to get things done. Moreover, Mr. Biden himself is calling for bipartisanship. “On this January day,” he said in his inauguration speech, “my whole soul is in this: Bringing America together, uniting our people, uniting our nation.”

Key health care actions that Mr. Biden could pursue include the following.
 

1. Passing a new COVID-19 relief bill

Above all, Mr. Biden is focused on overcoming the COVID-19 pandemic, which has been registering record deaths recently, and getting newly released vaccines to Americans.

“Dealing with the coronavirus pandemic is one of the most important battles our administration will face, and I will be informed by science and by experts,” the president said.

“There is no question that the pandemic is the highest priority for the Biden administration,” said Larry Levitt, executive vice president for health policy at the Henry J. Kaiser Family Foundation. “COVID will dominate the early weeks and months of this administration. His success rests, in particular, on improving the rollout of vaccines.”

Five days before his inauguration, the president-elect unveiled the American Rescue Plan, a massive, $1.9 trillion legislative package intended to hasten rollout of COVID-19 vaccines, improve COVID-19 testing, and provide financial help to businesses and individuals, among many other things.

The bill would add $1,400 to the recently passed $600 government relief payments for each American, amounting to a $2,000 check. It would also enact many non-COVID-19 measures, such as a $15-an-hour minimum wage and measures to bolster the Affordable Care Act (ACA).

If Democrats cannot reach a deal with the Republicans, they might turn the proposal into a reconciliation bill, which could then be passed with a simple majority. However, drafting a reconciliation bill is a long, complicated process that would require removing provisions that don’t meet the requirements of reconciliation, said Hazen Marshall, a Washington lobbyist and former staffer for Sen. Mitch McConnell.

Most importantly, Mr. Marshall said, reconciliation bills bring out diehard partisanship. “They involve a sledgehammer mentality,” he says. “You’re telling the other side that their views aren’t going to matter.” The final version of the ACA, for example, was passed as a reconciliation bill, with not one Republican vote.

In the Trump years, “the last four reconciliation bills did not get any votes from the minority,” added Rodney Whitlock, PhD, a political consultant at McDermott+Consulting, who worked 21 years for Republicans in the House. “When the majority chooses to use reconciliation, it is an admission that it has no interest in working with the minority.”

Hammering out a compromise will be tough, but Robert Pearl MD, former CEO of the Permanente Medical Group and a professor at Stanford (Calif.) University, said that if anyone can do it, it would be President Biden. Having served in the Senate for 36 years, “Biden knows Congress better than any president since Lyndon Johnson,” he said. “He can reach across the aisle and get legislation passed as much as anyone could these days.”
 

2. Restoring Obamacare

Mr. Biden has vowed to undo a gradual dismantling of the ACA that went on during the Trump administration through executive orders, rule-making, and new laws. “Reinvigorating the ACA was a central part of Biden’s platform as a candidate,” Mr. Levitt said.

Each Trump action against the ACA must be undone in the same way. Presidential orders must be met with presidential orders, regulations with regulations, and legislation with legislation.

The ACA is also being challenged in the Supreme Court. Republicans under Trump passed a law that reduced the penalty for not buying health insurance under the ACA to zero. Then a group of 20 states, led by Texas, filed a lawsuit asserting that this change makes the ACA unconstitutional.

The lawsuit was heard by the Supreme Court in November. From remarks made by the justices then, it appears that the court might well uphold the law when a verdict comes down in June.

But just in case, Mr. Biden wants Congress to enact a small penalty for not buying health insurance, which would remove the basis of the lawsuit.

Mr. Biden’s choice for secretary of Health and Human Services shows his level of commitment to protecting the ACA. His HHS nominee is California Attorney General Xavier Becerra, who led a group of 17 states defending the ACA in the current lawsuit.

In addition to undoing Trump’s changes, Mr. Biden plans to expand the ACA beyond the original legislation. The new COVID-19 bill contains provisions that would expand subsidies to buy insurance on the exchanges and would lower the maximum percentage of income that anyone has to pay for health insurance to 8.5%.

Dealing with Medicaid is also related to the ACA. In 2012, the Supreme Court struck down a mandate that states expand their Medicaid programs, with substantial funding from the federal government.

To date, 12 states still do not participate in the Medicaid expansion. To lure them into the expansion, the Democrat-controlled House last session passed a bill that would offer to pay the entire bill for the first 3 years of Medicaid expansion if they chose to enact an expansion.
 

3. Undoing other Trump actions in health care

In addition to changes in the ACA, Trump also enacted a number of other changes in health care that President Biden could undo. For example, Mr. Biden says he will reenter the World Health Organization (WHO) so that the United States could better coordinate a COVID-19 response with other nations. Trump exited the WHO with the stroke of a pen, and Mr. Biden can do the same in reverse.

Under Trump, the Centers for Medicare & Medicaid Services used waivers to weaken the ACA and allow states to alter their Medicaid programs. One waiver allows Georgia to leave the ACA exchanges and put brokers in charge of buying coverage. Other waivers allow states to transform federal Medicaid payments into block grants, which several states are planning to do.

The Trump CMS has allowed several states to use Medicaid waivers to add work requirements for Medicaid recipients. The courts have blocked the work rules so far, and the Biden CMS may decide to reverse these waivers or modify them.

“Undoing waivers is normally a fairly simple thing,” Mr. Levitt said. In January, however, the Trump CMS asked some waiver states to sign new contracts in which the CMS pledges not to end a waiver without 9 months’ notice. It’s unclear how many states signed such contracts and what obligation the Biden CMS has to enforce them.

The Trump CMS also stopped reimbursing insurers for waiving deductibles and copayments for low-income customers, as directed by the ACA. Without federal reimbursement, some insurers raised premiums by as much as 20% to cover the costs. It is unclear how the Biden CMS would tackle this change.
 

4. Negotiating lower drug prices

Allowing Medicare to negotiate drug prices, a major plank in Mr. Biden’s campaign, would seem like a slam dunk for the Democrats. This approach is backed by 89% of Americans, including 84% of Republicans, according to a Kaiser Family Foundation survey in December.

“With that level of support, it’s hard to go wrong politically on this issue,” Mr. Levitt said.

Many Republicans, however, do not favor negotiating drug prices, and the two parties continue to be far apart on how to control drug prices. Trump signed an action that allows Americans to buy cheaper drugs abroad, an approach that Mr. Biden also supports, but it is now tied up in the courts.

“A drug pricing bill has always been difficult to pass,” Dr. Whitlock said. “The issue is popular with the public, but change does not come easily. The drug lobby is one the strongest in Washington, and now it may be even stronger, since it was the drug companies that gave us the COVID vaccines.”

Dr. Whitlock said Republicans will want Democrats to compromise on drug pricing, but he doubts they will do so. The House passed a bill to negotiate drug prices last year, which never was voted on in the Senate. “It is difficult to imagine that the Democrats will be able to move rightward from that House bill,” Dr. Whitlock said. “Democrats are likely to stand pat on drug pricing.”
 

5. Introducing a public option

President Biden’s campaign proposal for a public option – health insurance offered by the federal government – and to lower the age for Medicare eligibility from 65 years to 60 years, resulted from a compromise between two factions of the Democratic party on how to expand coverage.

Although Mr. Biden and other moderates wanted to focus on fixing the ACA, Democrats led by Sen. Bernie Sanders of Vermont called for a single-payer system, dubbed “Medicare for all.” A public option was seen as the middle ground between the two camps.

“A public option would be a very controversial,” Dr. Whitlock said. Critics say it would pay at Medicare rates, which would reduce doctors’ reimbursements, and save very little money compared with a single-payer system.

Dr. Pearl sees similar problems with lowering the Medicare age. “This would be an expensive change that the federal government could not afford, particularly with all the spending on the pandemic,” he said. “And it would be tough on doctors and hospitals, because Medicare pays less than the private insurance payment they are now getting.”

“The public option is likely to get serious discussion within the Democratic caucus and get onto the Senate floor,” Mr. Levitt said. “The party won’t ignore it.” He notes that in the new Senate, Sen. Sanders chairs the budget committee, and from that position he is likely to push for expanding access to care.

Mr. Levitt says the Biden CMS might allow states to experiment with a statewide public option or even a single-payer model, but he concedes that states, with their budgets ravaged by COVID-19, do not currently have the money to launch such programs.
 

6. Reviving the CMS

Under President Obama, the CMS was the engine that implemented the ACA and shepherded wider use of value-based reimbursements, which reward providers for quality and outcomes rather than volume.

Under the Trump administration, CMS leadership continued to uphold value-based reimbursement, Dr. Pearl observed. “CMS leadership championed value-based payments, but they encountered a lot of pushback from doctors and hospitals and had to scale back their goals,” he said.

On the other hand, the Trump CMS took a 180-degree turn on the ACA and worked to take it apart. This took a toll on staff morale, according to Donald M. Berwick, MD, who ran the CMS under President Obama. “Many people in CMS did not feel supported during the Trump administration, and some of them left,” Dr. Berwick said.

The CMS needs experienced staff on board to write comprehensible rules and regulations that can overcome court challenges.

Having a fully functioning CMS also requires consistent leadership, which was a problem for Obama. When Mr. Obama nominated Dr. Berwick, 60 Senate votes were needed to confirm him, and Republicans would not vote for him. Mr. Obama eventually brought Dr. Berwick in as a recess appointment, but it meant he could serve for only 17 months.

Since then, Senate confirmation rules have changed so that only a simple majority is needed to confirm appointments. This is important for Biden’s nominees, Dr. Berwick said. “For a president, having your team in place means you are able to execute the policies you want,” he said. “You need to have consistent leadership.”
 

7. Potentially changing health care without Congress

Even with their newly won control of the Senate, the Democrats’ thin majorities in both houses of Congress may not be enough to pass much legislation if Republicans are solidly opposed.

Democrats in the House also have a narrow path this session in which to pass legislation. The Democratic leadership has an 11-vote majority, but it must contend with 15 moderate representatives in purple districts (where Democrats and Republicans have about equal support).

A bigger problem looms before the Democrats. In 2022, the party may well lose its majorities in both houses. Mr. Whitlock notes that the party of an incoming president normally loses seats in the first midterm election. “The last incoming president to keep both houses of Congress in his first midterm was Jimmy Carter,” he said.

If this happens, President Biden would have to govern without the support of Congress, which is what Barack Obama had to do through most of his presidency. As Mr. Obama’s vice president, Mr. Biden is well aware how that goes. Governing without Congress means relying on presidential orders and decrees.

In health care, Mr. Biden has a powerful policy-making tool, the Center for Medicare & Medicaid Innovation (CMMI). The CMMI was empowered by the ACA to initiate pilot programs for new payment models.

So far, the CMMI’s work has been mainly limited to accountable care organizations, bundled payments, and patient-centered medical homes, but it could also be used to enact new federal policies that would normally require Congressional action, Mr. Levitt said.
 

Conclusion

Expectations have been very high for what President Joe Biden can do in health care. He needs to unite a very divided political system to defeat a deadly pandemic, restore Obamacare, and sign landmark legislation, such as a drug-pricing bill.

But shepherding bills through Congress will be a challenge. “You need to have accountability, unity, and civility, which is a Herculean task,” Mr. Whitlock said. “You have to keep policies off the table that could blow up the bipartisanship.”

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