Heart Failure

An 88-year-old man comes for clinic follow up. He has a medical history of type 2 diabetes, hypertension, heart failure with reduced ejection fraction, and chronic kidney disease. He recently had laboratory tests done: BUN, 32 mg/dL; creatinine, 2.3 mg/dL; potassium, 4.5 mmol/L; bicarbonate, 22 Eq/L; and A1c, 8.2%.

He checks his blood glucose daily (alternating between fasting blood glucose and before dinner) and his fasting blood glucose levels are around 130 mg/dL. His highest glucose reading was 240 mg/dL. He does not have polyuria or visual changes. Current medications: atorvastatin, irbesartan, empagliflozin, and amlodipine. On physical exam his blood pressure is 130/70 mm Hg, pulse is 80, and his BMI 20.

What medication adjustments would you recommend?

A. Begin insulin glargine at bedtime

B. Begin mealtime insulin aspart

C. Begin semaglutide

D. Begin metformin

E. No changes

I think the correct approach here would be no changes. Most physicians know guideline recommendations for A1c of less than 7% are used for patients with diabetes with few comorbid conditions, normal cognition, and functional status. Many of our elderly patients do not meet these criteria and the goal of intense medical treatment of diabetes is different in those patients. The American Diabetes Association has issued a thoughtful paper on treatment of diabetes in elderly people, stressing that patients should have very individualized goals, and that there is no one-size-fits all A1c goal.¹

In this patient I would avoid adding insulin, given hypoglycemia risk. A GLP-1 agonist might appear attractive given his multiple cardiovascular risk factors, but his low BMI is a major concern for frailty that may well be worsened with reduced nutrient intake. Diabetes is the chronic condition that probably has the most guidance for management in elderly patients.

I recently saw a 92-year-old man with heart failure with reduced ejection fraction and atrial fibrillation who had been losing weight and becoming weaker. He had suffered several falls in the previous 2 weeks. His medication list included amiodarone, apixaban, sacubitril/valsartan, carvedilol, empagliflozin, spironolactone, and furosemide. He was extremely frail and had stopped eating. He was receiving all guideline-directed therapies, yet he was miserable and dying. Falls in this population are potentially as fatal as decompensated heart disease.

I stopped his amiodarone, furosemide, and spironolactone, and reduced his doses of sacubitril/valsartan and carvedilol. His appetite returned and his will to live returned. Heart failure guidelines do not include robust studies of very elderly patients because few studies exist in this population. Frailty assessment is crucial in decision making in your elderly patients.^2,3 and frequent check-ins to make sure that they are not suffering from the effects of polypharmacy are crucial. Our goal in our very elderly patients is quality life-years. Polypharmacy has the potential to decrease the quality of life, as well as potentially shorten life.

The very elderly are at risk of the negative consequences of polypharmacy, especially if they have several diseases like diabetes, congestive heart failure, and hypertension that may require multiple medications. Gutierrez-Valencia and colleagues performed a systematic review of 25 articles on frailty and polypharmacy.⁴ Their findings demonstrated a significant association between an increased number of medications and frailty. They postulated that polypharmacy could actually be a contributor to frailty. There just isn’t enough evidence for the benefit of guidelines in the very aged and the risks of polypharmacy are real. We should use the lowest possible doses of medications in this population, frequently reassess goals, and monitor closely for side effects.


Pearl: Always consider the risks of polypharmacy when considering therapies for your elderly patients.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Older Adults: Standards of Medical Care in Diabetes — 2021. Diabetes Care 2021;44(Suppl 1):S168–S179.

2. Gaur A et al. Cardiogeriatrics: The current state of the art. Heart. 2024 Jan 11:heartjnl-2022-322117.

3. Denfeld QE et al. Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2023 Nov 29:S1053-2498(23)02028-4.

4. Gutiérrez-Valencia M et al. The relationship between frailty and polypharmacy in older people: A systematic review. Br J Clin Pharmacol. 2018 Jul;84(7):1432-44.

An 88-year-old man comes for clinic follow up. He has a medical history of type 2 diabetes, hypertension, heart failure with reduced ejection fraction, and chronic kidney disease. He recently had laboratory tests done: BUN, 32 mg/dL; creatinine, 2.3 mg/dL; potassium, 4.5 mmol/L; bicarbonate, 22 Eq/L; and A1c, 8.2%.

He checks his blood glucose daily (alternating between fasting blood glucose and before dinner) and his fasting blood glucose levels are around 130 mg/dL. His highest glucose reading was 240 mg/dL. He does not have polyuria or visual changes. Current medications: atorvastatin, irbesartan, empagliflozin, and amlodipine. On physical exam his blood pressure is 130/70 mm Hg, pulse is 80, and his BMI 20.

What medication adjustments would you recommend?

A. Begin insulin glargine at bedtime

B. Begin mealtime insulin aspart

C. Begin semaglutide

D. Begin metformin

E. No changes

I think the correct approach here would be no changes. Most physicians know guideline recommendations for A1c of less than 7% are used for patients with diabetes with few comorbid conditions, normal cognition, and functional status. Many of our elderly patients do not meet these criteria and the goal of intense medical treatment of diabetes is different in those patients. The American Diabetes Association has issued a thoughtful paper on treatment of diabetes in elderly people, stressing that patients should have very individualized goals, and that there is no one-size-fits all A1c goal.¹

In this patient I would avoid adding insulin, given hypoglycemia risk. A GLP-1 agonist might appear attractive given his multiple cardiovascular risk factors, but his low BMI is a major concern for frailty that may well be worsened with reduced nutrient intake. Diabetes is the chronic condition that probably has the most guidance for management in elderly patients.

I recently saw a 92-year-old man with heart failure with reduced ejection fraction and atrial fibrillation who had been losing weight and becoming weaker. He had suffered several falls in the previous 2 weeks. His medication list included amiodarone, apixaban, sacubitril/valsartan, carvedilol, empagliflozin, spironolactone, and furosemide. He was extremely frail and had stopped eating. He was receiving all guideline-directed therapies, yet he was miserable and dying. Falls in this population are potentially as fatal as decompensated heart disease.

I stopped his amiodarone, furosemide, and spironolactone, and reduced his doses of sacubitril/valsartan and carvedilol. His appetite returned and his will to live returned. Heart failure guidelines do not include robust studies of very elderly patients because few studies exist in this population. Frailty assessment is crucial in decision making in your elderly patients.^2,3 and frequent check-ins to make sure that they are not suffering from the effects of polypharmacy are crucial. Our goal in our very elderly patients is quality life-years. Polypharmacy has the potential to decrease the quality of life, as well as potentially shorten life.

The very elderly are at risk of the negative consequences of polypharmacy, especially if they have several diseases like diabetes, congestive heart failure, and hypertension that may require multiple medications. Gutierrez-Valencia and colleagues performed a systematic review of 25 articles on frailty and polypharmacy.⁴ Their findings demonstrated a significant association between an increased number of medications and frailty. They postulated that polypharmacy could actually be a contributor to frailty. There just isn’t enough evidence for the benefit of guidelines in the very aged and the risks of polypharmacy are real. We should use the lowest possible doses of medications in this population, frequently reassess goals, and monitor closely for side effects.


Pearl: Always consider the risks of polypharmacy when considering therapies for your elderly patients.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Older Adults: Standards of Medical Care in Diabetes — 2021. Diabetes Care 2021;44(Suppl 1):S168–S179.

2. Gaur A et al. Cardiogeriatrics: The current state of the art. Heart. 2024 Jan 11:heartjnl-2022-322117.

3. Denfeld QE et al. Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2023 Nov 29:S1053-2498(23)02028-4.

4. Gutiérrez-Valencia M et al. The relationship between frailty and polypharmacy in older people: A systematic review. Br J Clin Pharmacol. 2018 Jul;84(7):1432-44.

An 88-year-old man comes for clinic follow up. He has a medical history of type 2 diabetes, hypertension, heart failure with reduced ejection fraction, and chronic kidney disease. He recently had laboratory tests done: BUN, 32 mg/dL; creatinine, 2.3 mg/dL; potassium, 4.5 mmol/L; bicarbonate, 22 Eq/L; and A1c, 8.2%.

He checks his blood glucose daily (alternating between fasting blood glucose and before dinner) and his fasting blood glucose levels are around 130 mg/dL. His highest glucose reading was 240 mg/dL. He does not have polyuria or visual changes. Current medications: atorvastatin, irbesartan, empagliflozin, and amlodipine. On physical exam his blood pressure is 130/70 mm Hg, pulse is 80, and his BMI 20.

What medication adjustments would you recommend?

A. Begin insulin glargine at bedtime

B. Begin mealtime insulin aspart

C. Begin semaglutide

D. Begin metformin

E. No changes

I think the correct approach here would be no changes. Most physicians know guideline recommendations for A1c of less than 7% are used for patients with diabetes with few comorbid conditions, normal cognition, and functional status. Many of our elderly patients do not meet these criteria and the goal of intense medical treatment of diabetes is different in those patients. The American Diabetes Association has issued a thoughtful paper on treatment of diabetes in elderly people, stressing that patients should have very individualized goals, and that there is no one-size-fits all A1c goal.¹

In this patient I would avoid adding insulin, given hypoglycemia risk. A GLP-1 agonist might appear attractive given his multiple cardiovascular risk factors, but his low BMI is a major concern for frailty that may well be worsened with reduced nutrient intake. Diabetes is the chronic condition that probably has the most guidance for management in elderly patients.

I recently saw a 92-year-old man with heart failure with reduced ejection fraction and atrial fibrillation who had been losing weight and becoming weaker. He had suffered several falls in the previous 2 weeks. His medication list included amiodarone, apixaban, sacubitril/valsartan, carvedilol, empagliflozin, spironolactone, and furosemide. He was extremely frail and had stopped eating. He was receiving all guideline-directed therapies, yet he was miserable and dying. Falls in this population are potentially as fatal as decompensated heart disease.

I stopped his amiodarone, furosemide, and spironolactone, and reduced his doses of sacubitril/valsartan and carvedilol. His appetite returned and his will to live returned. Heart failure guidelines do not include robust studies of very elderly patients because few studies exist in this population. Frailty assessment is crucial in decision making in your elderly patients.^2,3 and frequent check-ins to make sure that they are not suffering from the effects of polypharmacy are crucial. Our goal in our very elderly patients is quality life-years. Polypharmacy has the potential to decrease the quality of life, as well as potentially shorten life.

The very elderly are at risk of the negative consequences of polypharmacy, especially if they have several diseases like diabetes, congestive heart failure, and hypertension that may require multiple medications. Gutierrez-Valencia and colleagues performed a systematic review of 25 articles on frailty and polypharmacy.⁴ Their findings demonstrated a significant association between an increased number of medications and frailty. They postulated that polypharmacy could actually be a contributor to frailty. There just isn’t enough evidence for the benefit of guidelines in the very aged and the risks of polypharmacy are real. We should use the lowest possible doses of medications in this population, frequently reassess goals, and monitor closely for side effects.


Pearl: Always consider the risks of polypharmacy when considering therapies for your elderly patients.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. Older Adults: Standards of Medical Care in Diabetes — 2021. Diabetes Care 2021;44(Suppl 1):S168–S179.

2. Gaur A et al. Cardiogeriatrics: The current state of the art. Heart. 2024 Jan 11:heartjnl-2022-322117.

3. Denfeld QE et al. Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement. J Heart Lung Transplant. 2023 Nov 29:S1053-2498(23)02028-4.

4. Gutiérrez-Valencia M et al. The relationship between frailty and polypharmacy in older people: A systematic review. Br J Clin Pharmacol. 2018 Jul;84(7):1432-44.

A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).

But what exactly is CHIP, and what is its potential value in CVD risk and management?

CHIP is an age-related condition marked by clonal expansion of blood stem cells with leukemia-associated mutations in individuals without evidence of hematologic malignancy. CHIP is estimated to affect about 10% of people aged 70 years and older.

First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.

CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.

“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.

Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.

To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).

In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.

“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.

In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.

Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”

He cautioned, however, that the findings need to be validated in other studies.

“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.

Targeted Treatment?

Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.

Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.

For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.

“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.

“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.

“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.

“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added. 

Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).

But what exactly is CHIP, and what is its potential value in CVD risk and management?

CHIP is an age-related condition marked by clonal expansion of blood stem cells with leukemia-associated mutations in individuals without evidence of hematologic malignancy. CHIP is estimated to affect about 10% of people aged 70 years and older.

First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.

CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.

“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.

Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.

To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).

In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.

“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.

In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.

Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”

He cautioned, however, that the findings need to be validated in other studies.

“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.

Targeted Treatment?

Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.

Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.

For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.

“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.

“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.

“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.

“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added. 

Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).

But what exactly is CHIP, and what is its potential value in CVD risk and management?

CHIP is an age-related condition marked by clonal expansion of blood stem cells with leukemia-associated mutations in individuals without evidence of hematologic malignancy. CHIP is estimated to affect about 10% of people aged 70 years and older.

First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.

CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.

“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.

Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.

To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).

In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.

“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.

In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.

Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”

He cautioned, however, that the findings need to be validated in other studies.

“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.

Targeted Treatment?

Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.

Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.

For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.

“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.

“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.

“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.

“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added. 

Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

Over just a decade, sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the second-line treatment of type 2 diabetes by improving the control of blood sugar, and they’re also being used to treat heart failure and chronic kidney disease. Now, there’s growing evidence that the medications have the potential to play a role in the treatment of a variety of rheumatologic diseases — gout, systemic lupus erythematosus (SLE), and lupus nephritis.

“I suspect that SGLT2 inhibitors may have a role in multiple rheumatic diseases,” said rheumatologist April Jorge, MD, of Harvard Medical School and Massachusetts General Hospital, Boston.

In gout, for example, “SGLT2 inhibitors hold great promise as a multipurpose treatment option,” said rheumatologist Chio Yokose, MD, MSc, also of Harvard Medical School and Massachusetts General Hospital. Both Dr. Jorge and Dr. Yokose spoke at recent medical conferences and in interviews about the potential value of the drugs in rheumatology.
 

There’s a big caveat. For the moment, SGLT2 inhibitors aren’t cleared for use in the treatment of rheumatologic conditions, and neither physician is ready to recommend prescribing them off-label outside of their FDA-approved indications.

But studies could pave the way toward more approved uses in rheumatology. And there’s good news for now: Many rheumatology patients may already be eligible to take the drugs because of other medical conditions. In gout, for example, “sizable proportions of patients have comorbidities for which they are already indicated,” Dr. Yokose said.
 

Research Hints at Gout-Busting Potential

The first SGLT2 inhibitor canagliflozin (Invokana), received FDA approval in 2013, followed by dapagliflozin (Farxiga), empagliflozin (Jardiance), ertugliflozin (Steglatro), and bexagliflozin (Brenzavvy). The drugs “lower blood sugar by causing the kidneys to remove sugar from the body through urine,” reports the National Kidney Foundation, and they “help to protect the kidneys and heart in people with CKD [chronic kidney disease].”

As Dr. Yokose noted in a presentation at the 2023 Gout Hyperuricemia and Crystal Associated Disease Network research symposium, SGLT2 inhibitors “have really become blockbuster drugs, and they’ve now been integrated into multiple professional society guidelines and recommendations.”

These drugs should not be confused with the wildly popular medications known as glucagon-like peptide-1 (GLP1) agonists, which include medications such as semaglutide (Ozempic and Wegovy). These drugs are generally administered via injection — unlike the oral SGLT2 inhibitors — and they’re variously indicated for type 2 diabetes and obesity.

Dr. Yokose highlighted research findings about the drugs in gout. A 2020 study, for example, tracked 295,907 US adults with type 2 diabetes who received a new prescription for an SGLT2 inhibitor or GLP1 agonist during 2013-2017. Those in the SGLT2 inhibitor group had a 36% lower risk of newly diagnosed gout (hazard ratio [HR], 0.64; 95% CI, 0.57-0.72), the researchers reported.

A similar study, a 2021 report from Taiwan, also linked SGLT2 inhibitors to improvement in gout incidence vs. dipeptidyl peptidase 4 (DPP4) inhibitors, diabetes drugs that are not linked to lower serum urate levels. In an adjusted analysis, the risk of gout was 11% lower in the SGLT2 inhibitor group (adjusted HR, 0.86; 95% CI, 0.78-0.95).

What about recurrent gout? In a 2023 study, Dr. Yokose and colleagues tracked patients with type 2 diabetes who began SGLT2 inhibitors or DPP4 inhibitors. Over the period from 2013 to 2017, those who took SGLT2 inhibitors were less likely to have gout flares (rate ratio [RR], 0.66; 95% CI, 0.57-0.75) and gout-primary emergency department visits/hospitalizations (RR, 0.52; 95% CI, 0.32-0.84).

“This finding requires further replication in other populations and compared to other drugs,” Dr. Yokose cautioned.

Another 2023 study analyzed UK data and reached similar results regarding risk of recurrent gout.

Lower Urate Levels and Less Inflammation Could Be Key

How might SGLT2 inhibitors reduce the risk of gout? Multiple studies have linked the drugs to lower serum urate levels, Dr. Yokose said, but researchers often excluded patients with gout.

For a small new study presented at the 2023 annual meeting of the American College of Rheumatology but not yet published, Dr. Yokose and colleagues reported that patients with gout who began SGLT2 inhibitors had lower urate levels than those who began a sulfonylurea, another second-line agent for type 2 diabetes. During the study period, up to 3 months before and after initiation, 43.5% of patients in the SGLT2 inhibitor group reached a target serum urate of < 6 mg/dL vs. 4.2% of sulfonylurea initiators.

“The magnitude of this reduction, while not as large as what can be achieved with appropriately titrated urate-lowering therapy such as allopurinol or febuxostat, is also not negligible. It’s believed to be between 1.5-2.0 mg/dL among patients with gout,” Dr. Yokose said. “Also, SGLT2 inhibitors are purported to have some anti-inflammatory effects that may target the same pathways responsible for the profound inflammation associated with acute gout flares. However, both the exact mechanisms underlying the serum urate-lowering and anti-inflammatory effects of SGLT2 [inhibitors] require further research and clarification.”

Moving forward, she said, “I would love to see some prospective studies of SGLT2 inhibitor use among patients with gout, looking at serum urate and clinical gout endpoints, as well as biomarkers to understand better the beneficial effects of SGLT2 inhibitors as it pertains to patients with gout.”

In Lupus, Findings Are More Mixed

Studies of SGLT2 inhibitors have excluded patients with lupus, limiting insight into their benefits in that specific population, said Dr. Jorge of Massachusetts General Hospital and Harvard Medical School. However, “one small phase I/II trial showed an acceptable safety profile of dapagliflozin add-on therapy in adult patients with SLE,” she said.

Her team is working to expand understanding about the drugs in people with lupus. At the 2023 ACR annual meeting, she presented the findings of a study that tracked patients with SLE who took SGLT2 inhibitors (n = 426, including 154 with lupus nephritis) or DPP4 inhibitors (n = 865, including 270 with lupus nephritis). Patients who took SGLT2 inhibitors had lower risks of major adverse cardiac events (HR, 0.69; 95% CI, 0.48-0.99) and renal progression (HR, 0.71; 95% CI, 0.51-0.98).

“Our results are promising, but the majority of patient with lupus who had received SGLT2 inhibitors also had the comorbidity of type 2 diabetes as a separate indication for SGLT2 inhibitor use,” Dr. Jorge said. “We still need to study the impact of SGLT2 inhibitors in patients with SLE and lupus nephritis who do not have a separate indication for the medication.”

Dr. Jorge added that “we do not yet know the ideal time to initiate SGLT2 inhibitors in the treatment of lupus nephritis. Specifically, it is not yet known whether these medications should be used in patients with persistent proteinuria due to damage from lupus nephritis or whether there is also a role to start these medications in patients with active lupus nephritis who are undergoing induction immunosuppression regimens.”

However, another study released at the 2023 ACR annual meeting suggested that SGLT2 inhibitors may not have a beneficial effect in lupus nephritis: “We observed a reduction in decline in eGFR [estimated glomerular filtration rate] after starting SGLT2 inhibitors; however, this reduction was not statistically significant … early experience suggested marginal benefit of SGLT2 inhibitors in SLE,” researchers from Johns Hopkins University, and the University of Maryland, Baltimore, reported.

“My cohort is not showing miracles from SGLT2 inhibitors,” study lead author Michelle Petri, MD, MPH, of Johns Hopkins, said in an interview.

Still, new European Alliance of Associations for Rheumatology recommendations for SLE now advise to consider the use of the drugs in patients with lupus nephritis who have reduced eGFR. Meanwhile, “the American College of Rheumatology is currently developing new treatment guidelines for SLE and for lupus nephritis, and SGLT2 inhibitors will likely be a topic of consideration,” Dr. Jorge added.

As for mechanism, Dr. Jorge said it’s not clear how the drugs may affect lupus. “It’s proposed that they have benefits in hemodynamic effects as well as potentially anti-inflammatory effects. The hemodynamic effects, including reducing intraglomerular hyperfiltration and reducing blood pressure, likely have similar benefits in patients with chronic kidney disease due to diabetic nephropathy or due to lupus nephritis with damage/scarring and persistent proteinuria. Patients with SLE and other chronic, systemic rheumatic diseases such as ANCA [antineutrophilic cytoplasmic antibody]-associated vasculitis also develop kidney disease and cardiovascular events mediated by inflammatory processes.”
 

Side Effects and Cost: Where Do They Fit In?

According to Dr. Yokose, SGLT2 inhibitors “are generally quite well-tolerated, and very serious adverse effects are rare.” Side effects include disrupted urination, increased thirst, genital infections, flu-like symptoms, and swelling.

Urinary-related problems are understandable “because these drugs cause the kidneys to pass more glucose into the urine,” University of Hong Kong cardiac specialist Bernard Cheung, MBBCh, PhD, who has studied SGLT2 inhibitors, said in an interview.

In Dr. Yokose’s 2023 study of SGLT2 inhibitors in recurrent gout, patients who took the drugs were 2.15 times more likely than the comparison group to have genital infections (hazard ratio, 2.15; 95% CI, 1.39-3.30). This finding “was what we’d expect,” she said.

She added that genital infection rates were higher among patients with diabetes, women, and uncircumcised men. “Fortunately, most experienced just a single mild episode that can readily be treated with topical therapy. There does not appear to be an increased risk of urinary tract infections.”

Dr. Cheung added that “doctors should be aware of a rare adverse effect called euglycemic ketoacidosis, in which the patient has increased ketones in the blood causing it to be more acidic than normal, but the blood glucose remains within the normal range.”

As for cost, goodrx.com reports that several SGLT2 inhibitors run about $550-$683 per month, making them expensive but still cheaper than GLP-1 agonists, which can cost $1,000 or more per month. Unlike the most popular GLP-1 agonists such as Ozempic, none of the SGLT2 inhibitors are in short supply, according to the American Society of Health-System Pharmacists.

“If someone with gout already has a cardiovascular-kidney-metabolic indication for SGLT2 inhibitors and also stands to benefit in terms of lowering serum urate and risk of recurrent gout flares, there is potential for high benefit relative to cost,” Dr. Yokose said.

She added: “It is well-documented that current gout care is suboptimal, and many patients end up in the emergency room or hospitalized for gout, which in and of itself is quite costly both for the patient and the health care system. Therefore, streamlining or integrating gout and comorbidity care with SGLT2 inhibitors could potentially be quite beneficial for patients with gout.”

In regard to lupus, “many patients with lupus undergo multiple hospitalizations related to their disease, which is a source of high health care costs,” Dr. Jorge said. “Additionally, chronic kidney disease and cardiovascular disease are major causes of disability and premature mortality. Further studies will be needed to better understand whether benefits of SGLT2 inhibitors may outweigh the costs of treatment.”

As for prescribing the drugs in lupus now, Dr. Jorge said they can be an option in lupus nephritis. “There is not a clear consensus of the ideal timing to initiate SGLT2 inhibitors — e.g., degree of proteinuria or eGFR range,” she said. “However, it is less controversial that SGLT2 inhibitors should be considered in particular for patients with lupus nephritis with ongoing proteinuria despite adequate treatment with conventional therapies.”

As for gout, Dr. Yokose isn’t ready to prescribe the drugs to patients who don’t have comorbidities that can be treated by the medications. However, she noted that those patients are rare.

“If I see a patient with gout with one or more of these comorbidities, and I see that they are not already on an SGLT2 inhibitor, I definitely take the time to talk to the patient about this exciting class of drugs and will consult with their other physicians about getting them started on an SGLT2 inhibitor.”

Dr. Yokose, Dr. Petri, and Dr. Cheung have no relevant disclosures. Dr. Jorge disclosed serving as a site investigator for SLE clinical trials funded by Bristol-Myers Squibb and Cabaletta Bio; the trials are not related to SGLT2 inhibitors.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

For smokers, deaths with a cardiovascular or cancer-related cause, or ones that can be attributed to a respiratory disease such as chronic obstructive pulmonary disease, are significantly more common than for nonsmokers. It is widely recognized that stopping smoking leads to a reduction in mortality risk. To make reliable statements on the timeline of this reduction, researchers analyzed interview data and death rates from 438,015 adult US citizens from 1997 to the end of 2019.

The analyses show that it takes 30 years for the mortality risk of ex-smokers to resemble that of people who never regularly smoked. Blake Thomson, PhD, and Fahrad Islami, MD, PhD, both members of the Department of Surveillance and Health Equity Science of the American Cancer Society in Atlanta, Georgia, published their results as a research letter in JAMA Internal Medicine.
 

After Smoking Cessation

Overall, 11,860 cardiovascular, 10,935 cancer-related, and 2,060 respiratory-related deaths were considered from over 5 million patient years. Taken from these figures, the mortality risks of continuous smokers were 2.3 times (cardiovascular), 3.4 times (cancer-related), and 13.3 times (respiratory-related) higher than those of continuous nonsmokers.

Within 10 years of stopping smoking, the following occurred:

• The cardiovascular mortality risk fell by 1.47 times, compared with nonsmokers (by 36% compared with smokers).
• The cancer-related mortality risk fell by 2.13 times, compared with nonsmokers (by 47% compared with smokers).
• The respiratory-related mortality risk fell by 6.35 times, compared with nonsmokers (by 43% compared with smokers).

In the second decade after stopping smoking, the risk dropped even further. The researchers observed the following trends:

• The cardiovascular mortality risk fell by 1.26 times.
• The cancer-related mortality risk fell by 1.59 times.
• The respiratory-related mortality risk fell by 3.63 times — each time compared with nonsmokers.

During the third decade after stopping smoking, the risk continued to decrease. The trends were as follows:

• The cardiovascular mortality risk fell by 1.07 times.
• The cancer-related mortality risk fell by 1.34 times.
• The respiratory-related mortality risk fell by 2.34 times, compared with nonsmokers.

30 Years Later

Only after more than 30 years of not smoking was the cardiovascular-related mortality risk 0.96 and, therefore, no longer significant. Compared with nonsmokers, the cancer-related mortality risk was 1.16, and the respiratory-related mortality risk was 1.31.

Therefore, former smokers can reduce their cardiovascular mortality risk by 100%, the cancer-related by 93%, and the respiratory-related mortality risk by 97%.

The result reinforces earlier analyses on the reduction in mortality risks by stopping smoking, with fewer participants. Smokers, therefore, benefit more the longer that they can refrain from using tobacco. “The earlier in life that smoking is given up, the better,” the authors wrote. But even in the first 10 years, the mortality risks examined decreased by a statistically significant 36% (cardiovascular) to 47% (cancer-related).
 

An Underestimation?

One disadvantage of the study is that the participants’ data were collected using personal questionnaires. For this reason, participants may have reported their tobacco consumption as being lower than it was, particularly because these questionnaires are often answered in hindsight, the authors pointed out.

In addition, some of the participants who reported stopping smoking completely may have only reduced their consumption. However, both circumstances would cause the results of the analysis to be even clearer, compared with reality, and therefore better.

This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Removing race and incorporating social determinants of health (SDOH) into the pooled cohort risk equations (PCEs) for predicting atherosclerotic cardiovascular disease (ASCVD) outcomes made no difference to patients’ risk scores.

METHODOLOGY:

• Primary prevention guidelines recommend using risk prediction algorithms to assess the 10-year ASCVD risk, with the currently recommended PCEs including race.
• Researchers evaluated the incremental value of revised risk prediction equations excluding race and introducing SDOH in 11,638 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.
• Participants were aged between 45 and 79 years, had no history of ASCVD, and were not taking statins.
• Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke.

TAKEAWAY:

• Risk prediction equations performed similarly in race- and sex-stratified PCEs (C-statistic [95% CI])
• Black female: 0.71 (0.68-0.75); Black male: 0.68 (0.64-0.73); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)
• Race-free sex-specific PCEs yielded similar discrimination as race- and sex-stratified PCEs (C-statistic [95% CI]):
• Black female: 0.71 (0.67-0.75); Black male: 0.68 (0.63-0.72); White female: 0.76 (0.73-0.80); White male: 0.68 (0.65-0.71)
• The addition of SDOH to race-free sex-specific PCEs did not improve model performance (C-statistic [95% CI]):
• Black female: 0.72 (0.68-0.76); Black male: 0.68 (0.64-0.72); White female: 0.77 (0.74-0.80); White male: 0.68 (0.65-0.71)

IN PRACTICE:

“The major takeaway is we need to rethink the idea of race in cardiovascular risk prediction,” lead author Arnab Ghosh, MD, assistant professor of medicine at Weill Cornell Medical College and a hospitalist at New York-Presbyterian/Weill Cornell Medical Center, said in a press release.

“It’s essential for clinicians and scientists to consider how to appropriately address the health effects of race as a social construct, which has contributed to health disparities in cardiovascular outcomes,” Dr. Ghosh added.

SOURCE:

The study led by Dr. Ghosh was published online on December 6, 2023, in JAMA Cardiology with an Editor’s Note.

LIMITATIONS:

The study required informed consent for inclusion, which may have led to selection bias.

The REGARDS cohort’s SDOH may not have captured all social and socioeconomic influences on ASCVD outcomes.

DISCLOSURES:

The research was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health, Department of Health and Human Services, and others. Some authors declared receiving funding, grants, or personal fees from various sources.
 

A version of this article appeared on Medscape.com.

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

Systematically biased artificial intelligence (AI) models did not improve clinicians’ accuracy in diagnosing hospitalized patients, based on data from more than 450 clinicians.

“Artificial Intelligence (AI) could support clinicians in their diagnostic decisions of hospitalized patients but could also be biased and cause potential harm,” said Sarah Jabbour, MSE, a PhD candidate in computer science and engineering at the University of Michigan, Ann Arbor, in an interview.

“Regulatory guidance has suggested that the use of AI explanations could mitigate these harms, but the effectiveness of using AI explanations has not been established,” she said.

To examine whether AI explanations can be effective in mitigating the potential harms of systemic bias in AI models, Ms. Jabbour and colleagues conducted a randomized clinical vignette survey study. The survey was administered between April 2022 and January 2023 across 13 states, and the study population included hospitalist physicians, nurse practitioners, and physician assistants. The results were published in JAMA.

Participants were randomized to AI predictions with AI explanations (226 clinicians) or without AI explanations (231 clinicians).

The primary outcome was diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease, defined as the number of correct diagnoses over the total number of assessments, the researchers wrote.

The clinicians viewed nine clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians viewed two vignettes with no AI model input to establish baseline diagnostic accuracy. They made three assessments in each vignette, one for each diagnosis. The order of the vignettes was two without AI predictions (to establish baseline diagnostic accuracy), six with AI predictions, and one with a clinical consultation by a hypothetical colleague. The vignettes included standard and systematically biased AI models.

The baseline diagnostic accuracy was 73% for the diagnoses of pneumonia, heart failure, and chronic obstructive pulmonary disease. Clinicians’ accuracy increased by 2.9% when they viewed a standard diagnostic AI model without explanations and by 4.4% when they viewed models with AI explanations.

However, clinicians’ accuracy decreased by 11.3% after viewing systematically biased AI model predictions without explanations compared with baseline, and biased AI model predictions with explanations decreased accuracy by 9.1%.

The decrease in accuracy with systematically biased AI predictions without explanations was mainly attributable to a decrease in the participants’ diagnostic specificity, the researchers noted, but the addition of explanations did little to improve it, the researchers said.

Potentially Useful but Still Imperfect

The findings were limited by several factors including the use of a web-based survey, which differs from surveys in a clinical setting, the researchers wrote. Other limitations included the younger than average study population, and the focus on the clinicians making treatment decisions, vs other clinicians who might have a better understanding of the AI explanations.

“In our study, explanations were presented in a way that were considered to be obvious, where the AI model was completely focused on areas of the chest X-rays unrelated to the clinical condition,” Ms. Jabbour told this news organization. “We hypothesized that if presented with such explanations, the participants in our study would notice that the model was behaving incorrectly and not rely on its predictions. This was surprisingly not the case, and the explanations when presented alongside biased AI predictions had seemingly no effect in mitigating clinicians’ overreliance on biased AI,” she said.

“AI is being developed at an extraordinary rate, and our study shows that it has the potential to improve clinical decision-making. At the same time, it could harm clinical decision-making when biased,” Ms. Jabbour said. “We must be thoughtful about how to carefully integrate AI into clinical workflows, with the goal of improving clinical care while not introducing systematic errors or harming patients,” she added.

Looking ahead, “There are several potential research areas that could be explored,” said Ms. Jabbour. “Researchers should focus on careful validation of AI models to identify biased model behavior prior to deployment. AI researchers should also continue including and communicating with clinicians during the development of AI tools to better understand clinicians’ needs and how they interact with AI,” she said. “This is not an exhaustive list of research directions, and it will take much discussion between experts across disciplines such as AI, human computer interaction, and medicine to ultimately deploy AI safely into clinical care.”

Don’t Overestimate AI

“With the increasing use of artificial intelligence and machine learning in other spheres, there has been an increase in interest in exploring how they can be utilized to improve clinical outcomes,” said Suman Pal, MD, assistant professor in the division of hospital medicine at the University of New Mexico, Albuquerque, in an interview. “However, concerns remain regarding the possible harms and ways to mitigate them,” said Dr. Pal, who was not involved in the current study.

In the current study, “It was interesting to note that explanations did not significantly mitigate the decrease in clinician accuracy from systematically biased AI model predictions,” Dr. Pal said.

“For the clinician, the findings of this study caution against overreliance on AI in clinical decision-making, especially because of the risk of exacerbating existing health disparities due to systemic inequities in existing literature,” Dr. Pal told this news organization.

“Additional research is needed to explore how clinicians can be better trained in identifying both the utility and the limitations of AI and into methods of validation and continuous quality checks with integration of AI into clinical workflows,” he noted.

The study was funded by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

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

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

Bariatric surgery continues to play a major role in obesity management despite the emergence of potent new weight-loss medications, according to two experts who spoke at an Endocrine Society science writers briefing.

“Bariatric surgery is safe, effective, and unfortunately underutilized for treating obesity and its complications,” said Jaime Almandoz, MD, medical director of the Weight Wellness Program at the University of Texas Southwestern Medical Center, Dallas.

Added Dr. Almandoz, who is triple board-certified in internal medicine, endocrinology, and obesity medicine, “Sometimes this gets presented in a linear fashion. ‘We’ll try lifestyle first, and if that doesn’t work, we’ll try medications, and if that doesn’t work, we’ll try surgery.’ But sometimes we might need to go straight to surgery instead of going through medications first, because it may be the most effective and evidence-based treatment for the person in the office in front of you.”

Moreover, he pointed out that currently, Medicare and many private insurers don’t cover antiobesity medications but do cover bariatric surgery.

Indeed, Srividya Kidambi, MD, professor and chief of endocrinology and molecular medicine at the Medical College of Wisconsin/Froedtert Hospital, Milwaukee, said there are certain types of patients for whom she might consider bariatric surgery first. One would be a person with a body mass index (BMI) greater than 40 kg/m² or with a BMI greater than 35 kg/m² and severe comorbidities.

Another, she said, would be young, relatively healthy people with obesity who have no comorbid conditions. “We know that if we stop the medication, the weight comes back. So, if I see a 20- to 25-year-old, am I really to commit them to lifelong therapy, or is bariatric surgery a better option in these cases? These drugs have not been around that long ... so I tend to recommend bariatric surgery in some patients.”

During the recent briefing, Dr. Almandoz summarized the evidence base for the benefits of bariatric surgery beyond weight loss, which include remission of type 2 diabetes and fatty liver disease, reduction of the risks of cardiovascular disease and cancer, and increased life expectancy.

“Everyone seems to be talking about GLP-1s for facilitating weight loss and treating obesity. ... What I want to do is provide a counterpoint to accessible therapies that are covered by more insurance plans and that may, in fact, have a better evidence base for treating obesity and its related complications,” he said in his introduction.

Bariatric surgery has been used for decades, and many centers of excellence perform it, with greatly reduced complication rates seen today than in the past. “It’s comparable to having a gallbladder surgery in terms of perioperative risk,” he noted.

Medicare and private insurers generally cover bariatric surgery for people with BMI greater than 40 kg/m2 or 35-39 kg/m² and at least one weight-related comorbidity, including type 2 diabetes, obstructive sleep apnea, hypertension, atherosclerotic disease, hyperlipidemia, and fatty liver disease.

Data suggest that weight reduction of about 3% can lead to meaningful reductions in blood glucose and triglyceride levels, but weight loss of 15% or greater is associated with reductions in cardiovascular events and type 2 diabetes remission. Lifestyle modification typically produces about 5% weight loss, compared with 20%-35% with bariatric surgery with sleeve gastrectomy or gastric bypass.

Older weight loss medications produced weight loss of 5%-10%; only the newer medications, semaglutide 2.4 mg and tirzepatide, come close to that. Weight loss with semaglutide is about 15%, while tirzepatide can produce weight loss of up to 22%. But, there are still issues with affordability, access, and lack of coverage, Dr. Almandoz noted.

One recent randomized trial of more than 400 individuals showed that bariatric surgery was more effective than lifestyle and medical therapies for treating metabolic-associated steatohepatitis without worsening of fibrosis.

Another showed that the surgery was associated with fewer major adverse liver outcomes among people who already had MASH. That same study showed a 70% reduction in cardiovascular events with bariatric surgery.

For patients with type 2 diabetes, numerous trials have demonstrated long-term remission and reduced A1c at 5 years and 10 years post surgery, along with reductions in microvascular and macrovascular complications.

Other data suggest that a shorter history of type 2 diabetes is among the factors predicting remission with bariatric surgery. “Oftentimes, both patients and providers will wait until the diabetes is quite advanced before they even have the conversation about weight loss or even bariatric surgery. This suggests that if we intervene earlier in the course of disease, when it is less severe and less advanced, we have a higher rate of causing remission in the diabetes,” Dr. Almandoz said.

The American Diabetes Association’s Standards of Care incorporate bariatric surgery as either “recommended” or “may be considered” to treat type 2 diabetes, depending on BMI level, for those who don’t achieve durable weight loss with nonsurgical methods, he noted.

A retrospective cohort study showed significant reductions in cardiovascular outcomes with bariatric surgery among people with baseline cardiovascular disease. “This is not just about bariatric surgery to cause weight loss. This is about the multitude of effects that happen when we treat obesity as a disease with highly effective therapies such as surgery,” he said.

Even cancer risk and cancer-related mortality were significantly reduced with bariatric surgery, another study found.

And in the long-term Swedish Obese Subjects Study, among people with obesity, bariatric surgery was associated with a 3-year increase in life expectancy, compared with not undergoing surgery.

However, Dr. Almandoz also pointed out that some patients may benefit from both weight-loss medication and bariatric surgery. “Once someone has undergone pharmacotherapy, there may still be a role for bariatric procedures in helping to optimize body weight and control body weight long term. And likewise for those who have undergone bariatric surgery, there’s also a role for pharmacotherapy in terms of treating insufficient weight loss or weight recurrence after bariatric surgery. ... So I think there’s clearly a role for integration of therapies.”

Dr. Almandoz serves as consultant/advisory board member for Novo Nordisk, Boehringer Ingelheim, and Eli Lilly. Dr. Kidambi is director of TOPS Center for Metabolic Research and is medical editor of TOPS Magazine, for which her institution receives an honorarium.

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

PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.

The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.

“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview. “The study was positive in that perspective; we saw an increase of about 19% in the encounters that had cost conversations related to heart failure medication.”

The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.

The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
 

Fewer in-pharmacy adjustments

“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”

The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.

Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.

For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.

Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”

Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.

“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
 

Study strengths and limitations

Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.

“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.

“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”

POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.

One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.

The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.

PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.

The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.

“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview. “The study was positive in that perspective; we saw an increase of about 19% in the encounters that had cost conversations related to heart failure medication.”

The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.

The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
 

Fewer in-pharmacy adjustments

“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”

The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.

Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.

For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.

Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”

Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.

“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
 

Study strengths and limitations

Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.

“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.

“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”

POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.

One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.

The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.

PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.

The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.

“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview. “The study was positive in that perspective; we saw an increase of about 19% in the encounters that had cost conversations related to heart failure medication.”

The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.

The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
 

Fewer in-pharmacy adjustments

“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”

The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.

Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.

For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.

Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”

Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.

“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
 

Study strengths and limitations

Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.

“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.

“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”

POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.

One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.

The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.

Worsening heart failure is accompanied by a build-up of fluid in the lungs. An AI smartphone app that picks up changes in a heart failure patient’s voice quality caused by this fluid accumulation and then alerts the physician about them – nearly 3 weeks before that ongoing decompensation would necessitate hospitalization and/or lead the physician to urgently introduce intravenous diuretics – is getting experts to sit up and take notice.

“In this incredibly prevalent waxing and waning condition, finding ways to identify worsening heart failure to prevent hospitalization and progressive disease is incredibly important,” observed American Heart Association (AHA)-appointed discussant David Ouyang, MD, assistant professor, Smidt Heart Institute, Division of Artificial Intelligence in Medicine, Cedars Sinai, Los Angeles. “Heart failure remains among the most common causes of hospitalization for older adults in the United States.

“The other standout feature is that we all use our cell phones on a daily basis,” Dr. Ouyang said at a late-breaking trial press briefing at the AHA 2023 annual meeting where results of the HearO Community Study were presented. “The ability to capture data from routine speech (patients speak five sentences into their phones every morning) is remarkable ... The HearO^® technology was able to detect a substantial proportion of worsening heart failure events, with an average per individual of only three false positives over the course of a year. And, adherence to the study protocol was 81%. That’s higher than in many other kinds of routine patient monitoring studies,” he added.
 

Accumulating fluid changes speech

Increased hydration may affect speech parameters such as pitch, volume, and dynamics through swelling of soft tissues in the vocal tract (e.g., pharynx, velum, tongue, and vocal folds). In the Israeli study, investigators enrolled 416 adults (75% were male, average age was 68 years) whose New York Heart Association (NYHA) 2-3 heart failure with either reduced or preserved ejection fraction was stable but placed them at-risk for heart failure events. The study goal was to analyze their speech data using the HearO^® system to refine and test its ability to detect impending heart failure deterioration. Patients recorded five sentences in their native language (Hebrew, Russian, Arabic, or English) into the smartphone app daily. In a training phase of the study, distinct speech measures from 263 participants were used to develop the AI algorithm. Then, the algorithm was used in the remaining 153 participants to validate the tool’s effectiveness. In its ultimate form, once a deviation from the patient’s predefined baseline is detected, the app will generate a notice and send it to the health care practitioners.

Lead study author William T. Abraham, MD, FAHA, professor of medicine, physiology, and cell biology; and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University in Columbus, reported that between Mar. 27, 2018, and Nov. 30, 2021, subjects in the training phase made recordings on 83% of days. They were followed for up to 44 months. The test group made recordings on 81% of days between Feb. 1, 2020, and Apr. 30, 2023, and were followed for up to 31 months. Heart failure events were defined as hospitalization or outpatient intravenous diuretic treatment for worsening heart failure.

In the training phase, the app accurately predicted 44 of 58 heart failure events (76%) and 81% of first events (n = 35) on average 24 days before hospitalization or need for intravenous fluids. In the validation phase, the app was 71% accurate in detecting 10 of 14 heart failure events and 77% of first events (n = 10) on average 26 days in advance of events. In both periods, the app generated about 3 unnecessary alerts per patient year.

Dr. Abraham concluded, “This technology has the potential to improve patient outcomes, keeping patients well and out of the hospital, through the implementation of proactive, outpatient care in response to voice changes.”

The HearO^® technology is being evaluated in an ongoing pivotal trial in the United State4s, Dr. Abraham said. The study is limited, he added, by the small number of patients and heart failure events, particularly in the test group.

“We continue to struggle with the burden of heart failure morbidity,” observed AHA press briefing moderator (and past AHA president) Clyde Yancy, MD, Magerstadt Professor at Northwestern University, Chicago. “So any tool that we can utilize and further refine that helps us address the need for hospitalization becomes very important. The idea that speech evaluation might give us sufficient early warning to forestall any admissions – and consider the cost savings attributable to that – is a very credible goal that we should continue to follow.” He pointed out that the technology enables assessments in the home environment for older patients who are less mobile.

In response to a press briefing question about the potential for physicians to be trained to hear early subtle voice changes on their own, Dr. Abraham stated, “I guess that is unknown, but the important difference is the system’s ability to take data in every day from patients and then process it automatically with AI.”

Joining in, Dr. Yancy said, “You know, this is interesting because even if you saw a patient once a month, which is an incredible frequency for any practice, there’s still 353 days that you haven’t seen the patient.” He noted that the AHA had just announced a multi-million dollar program to more deeply understand telemanagement. “So I think this is here to stay,” Dr. Yancy said.

Dr. Ouyang posed a further question. “Like with most AI recognition tools, we can now identify individuals at risk. How do we get from that step of identifying those at risk to improving their outcomes? This has been a critical question about heart failure, remote management, and remote monitoring, and I think it is a critical question for many of our AI tools.”

Dr. Abraham disclosed that he has received personal fees from Cordio Medical. Dr. Ouyang said that he had no disclosures relevant to this presentation.