Heart Failure

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

Hyperkalemia is the most common adverse event associated with spironolactone use in women, but is uncommon in women aged 45 years or younger, according to new research.

Spironolactone, which is approved to treat heart failure, hypertension, edema, and primary hyperaldosteronism, has antagonistic effects on progesterone and androgen receptors and has been used as an off-label treatment for acne in women. “Numerous guidelines have recommended its off-label use for acne therapy to avoid antibiotic resistance and potential side effects,” wrote Yu Wang of Stony Brook (N.Y.) University and Shari R. Lipner MD, PhD, of Weill Cornell Medicine, New York. Their report is in the International Journal of Women’s Dermatology.

In a retrospective study, the investigators analyzed 7,920 adverse events with spironolactone reported by women of all ages between Jan. 1, 1969, and Dec. 30, 2018, to the Food and Drug Administration’s Adverse Event Reporting System database, for all indications. The most common adverse event was hyperkalemia, reported in 16.1%, followed by kidney injury (15.2%) and drug interactions (9%). Of the 1,272 cases of hyperkalemia reported, 25 occurred in women aged 45 years or younger; 59.3% occurred in women aged 65-85 years.

While spironolactone prescribing information was not available, the investigators compared yearly reports of adverse events with annual public interest in spironolactone using the Google Trends search term spironolactone and annual scholarly mentions of spironolactone in the Altmetric database. There was a strong correlation between the number of cases reported to the FDA and the Google Trends search (Spearman coefficient, 0.94; P less than .001) and to the Altmetric database (Spearman coefficient, 0.64; P less than .01).

Noting that hyperkalemia is “exceptionally uncommon” in women aged 45 years and younger, the investigators concluded that “in the absence of risk factors for hyperkalemia or reduced renal function, potassium laboratory monitoring is unnecessary in younger females taking spironolactone.” Because the incidence increases with age, “interval laboratory monitoring is recommended for females older than 45 years old,” they noted.

Limitations of the study, they noted, include the retrospective design and no available data before 1969. “In addition, since the [FDA Adverse Event Reporting System] data does not differentiate whether spironolactone was prescribed for heart failure, hypertension, edema, primary hyperaldosteronism, or for acne,” the study could not control for these or other confounding comorbidities or associated therapies.

“For future studies, it is important to analyze drug interactions more carefully to determine which other medications may potentiate the risk for hyperkalemia in patients taking spironolactone. It is also important to quantitate overall U.S. prescription data to better understand the relative frequency of these adverse effects reported to the FDA,” they wrote.

The investigators reported that they had no conflicts of interest; the study had no funding.

lfranki@mdedge.com

SOURCE: Wang Y, Lipner SR. Int J Womens Dermatol. 2020 May 18. doi: 10.1016/j.ijwd.2020.05.002.

Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.

The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.

The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.

The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.

The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.

Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.

A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.

Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.

bjancin@mdedge.com

Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.

The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.

The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.

The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.

The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.

Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.

A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.

Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.

bjancin@mdedge.com

Angiotensin receptor blocker therapy was not associated with any hint of increased risk of suicide, compared with treatment with an ACE inhibitor, in a large national Veterans Affairs study, Kallisse R. Dent, MPH, reported at the virtual annual meeting of the American Association of Suicidology.

The VA study thus fails to confirm the results of an earlier Canadian, population-based, nested case-control study, which concluded that exposure to an angiotensin receptor blocker (ARB) was independently associated with an adjusted 63% increase risk of death by suicide, compared with ACE inhibitor users. The Canadian study drew considerable attention, noted Ms. Dent, of the VA Office of Mental Health and Suicide Prevention.

The Canadian study included 964 Ontario residents who died by suicide within 100 days of receiving an ACE inhibitor or ARB. They were matched by age, sex, and the presence of hypertension and diabetes to 3,856 controls, all of whom were on an ACE inhibitor or ARB for the 100 days prior to the patient’s suicide. All subjects were aged at least 66 years.

The Canadian investigators recommended that ACE inhibitors should be used instead of ARBs whenever possible, particularly in patients with major mental illness (JAMA Netw Open. 2019 Oct 2;2[10]:e1913304). This was a study that demanded replication because of the enormous potential impact that recommendation could have upon clinical care. ACE inhibitors and ARBs are among the most widely prescribed of all medications, with approved indications for treatment of hypertension, chronic kidney disease, diabetes, and heart failure, Ms. Dent observed.

The Canadian investigators noted that a differential effect on suicide risk for the two drug classes was mechanistically plausible. Those drugs can cross the blood-brain barrier to varying extents, where they could conceivably interfere with central angiotensin II activity, which in turn could result in increased activity of substance P, as well as anxiety and stress secondary to increased activity of the hypothalamic-pituitary-adrenal axis.

Ms. Dent and coinvestigators harnessed VA suicide surveillance resources to conduct a nested case-control study that included all 1,311 deaths by suicide during 2015-2017 among patients in the VA system who had an active prescription for an ACE inhibitor or ARB during the 100 days immediately prior to death. As in the Canadian study, these individuals were matched 4:1 to 5,243 controls who did not die by suicide and had an active prescription for an ARB or ACE inhibitor during the 100 days prior to the date of suicide.

Among the veterans who died by suicide, 19.6% were on an ARB and 80.4% were on an ACE inhibitor. Those rates were not significantly different from the rates found in controls, 21.6% of whom were on an ARB and 78.4% were on an ACE inhibitor. In a multivariate analysis adjusted for the same potential confounders included in the Canadian study – including Charlson Comorbidity Index score; drug use; and diagnosis of alcohol use disorder, coronary artery disease, stroke, and chronic liver or kidney disease – being on an ARB was associated with a 9% lower risk of suicide than being on an ACE inhibitor, a nonsignificant difference.

A point of pride for the investigators was that, because of the VA’s sophisticated patient care database and comprehensive suicide analytics, the VA researchers were able to very quickly determine the lack of generalizability of the Canadian findings to a different patient population. Indeed, the entire VA case-control study was completed in less than 2 months.

Ms. Dent reported having no financial conflicts regarding the study, which was sponsored by the Department of Veterans Affairs.

bjancin@mdedge.com

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

Patients with obstructive hypertrophic cardiomyopathy (HCM) who took an investigational agent that targets cardiac myosin over about 7 months showed across-the-board improvements in functional capacity, symptoms, and left ventricular outflow obstruction in a randomized, controlled trial.

Treatment with the oral drug mavacamten (or MYK-461) was well tolerated and showed no untoward safety issues, compared with placebo in the phase 3 EXPLORER-HCM trial, its developer, MyoKardia, announced in a press release. The top-line trial results were made public in advance of a more expansive presentation at a later date.

The company describes mavacamten as an allosteric modulator of cardiac myosin that “reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance.”

In the EXPLORER-HCM trial, with its 251 patients with symptomatic obstructive HCM, 37% of those randomly assigned to receive once-daily mavacamten and 17% of those given placebo (P =.0005) reached the functional primary endpoint by 30 weeks, the company reported.

The primary endpoint was a composite of either a ≥1.5 mL/kg per min improvement in peak VO2 along with symptomatic improvement or ≥3.0 mL/kg per min improvement without deterioration of symptom status.

Patients taking mavacamten also showed significant improvement in the secondary endpoints of left ventricular outflow tract peak gradient after exercise, NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary scores, and HCM Symptom Questionnaire Shortness of Breath Domain score, all at P = .0001, and peak VO₂ at P = .0006, MyoKardia reported.

The company said beyond its bid to have the drug approved for obstructive HCM, based on its mechanism of action it foresees the drug as a potential treatment for nonobstructive HCM and for some patients with heart failure with preserved ejection fraction.

This article first appeared on Medscape.com.

Patients with obstructive hypertrophic cardiomyopathy (HCM) who took an investigational agent that targets cardiac myosin over about 7 months showed across-the-board improvements in functional capacity, symptoms, and left ventricular outflow obstruction in a randomized, controlled trial.

Treatment with the oral drug mavacamten (or MYK-461) was well tolerated and showed no untoward safety issues, compared with placebo in the phase 3 EXPLORER-HCM trial, its developer, MyoKardia, announced in a press release. The top-line trial results were made public in advance of a more expansive presentation at a later date.

The company describes mavacamten as an allosteric modulator of cardiac myosin that “reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance.”

In the EXPLORER-HCM trial, with its 251 patients with symptomatic obstructive HCM, 37% of those randomly assigned to receive once-daily mavacamten and 17% of those given placebo (P =.0005) reached the functional primary endpoint by 30 weeks, the company reported.

The primary endpoint was a composite of either a ≥1.5 mL/kg per min improvement in peak VO2 along with symptomatic improvement or ≥3.0 mL/kg per min improvement without deterioration of symptom status.

Patients taking mavacamten also showed significant improvement in the secondary endpoints of left ventricular outflow tract peak gradient after exercise, NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary scores, and HCM Symptom Questionnaire Shortness of Breath Domain score, all at P = .0001, and peak VO₂ at P = .0006, MyoKardia reported.

The company said beyond its bid to have the drug approved for obstructive HCM, based on its mechanism of action it foresees the drug as a potential treatment for nonobstructive HCM and for some patients with heart failure with preserved ejection fraction.

This article first appeared on Medscape.com.

Patients with obstructive hypertrophic cardiomyopathy (HCM) who took an investigational agent that targets cardiac myosin over about 7 months showed across-the-board improvements in functional capacity, symptoms, and left ventricular outflow obstruction in a randomized, controlled trial.

Treatment with the oral drug mavacamten (or MYK-461) was well tolerated and showed no untoward safety issues, compared with placebo in the phase 3 EXPLORER-HCM trial, its developer, MyoKardia, announced in a press release. The top-line trial results were made public in advance of a more expansive presentation at a later date.

The company describes mavacamten as an allosteric modulator of cardiac myosin that “reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation that results in hypercontractility, left ventricular hypertrophy and reduced compliance.”

In the EXPLORER-HCM trial, with its 251 patients with symptomatic obstructive HCM, 37% of those randomly assigned to receive once-daily mavacamten and 17% of those given placebo (P =.0005) reached the functional primary endpoint by 30 weeks, the company reported.

The primary endpoint was a composite of either a ≥1.5 mL/kg per min improvement in peak VO2 along with symptomatic improvement or ≥3.0 mL/kg per min improvement without deterioration of symptom status.

Patients taking mavacamten also showed significant improvement in the secondary endpoints of left ventricular outflow tract peak gradient after exercise, NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary scores, and HCM Symptom Questionnaire Shortness of Breath Domain score, all at P = .0001, and peak VO₂ at P = .0006, MyoKardia reported.

The company said beyond its bid to have the drug approved for obstructive HCM, based on its mechanism of action it foresees the drug as a potential treatment for nonobstructive HCM and for some patients with heart failure with preserved ejection fraction.

This article first appeared on Medscape.com.

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

mzoler@mdedge.com

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

The Food and Drug Administration has come through with the widely anticipated approval of dapagliflozin (Farxiga, AstraZeneca) for heart failure and reduced ejection fraction (HFrEF), adding to the rich array of medications lately available for this indication.

The approval follows the agency’s priority review of the sodium-glucose cotransporter 2 (SGLT2) inhibitor for reducing the risk of cardiovascular death and heart-failure hospitalization in adults with HFrEF following last year’s seminal results of the DAPA-HF trial.

In that study, treatment with dapagliflozin led to about a one-fourth reduction in risk of a primary endpoint consisting primarily of CV death or heart failure hospitalization in patients with chronic HFrEF, in both those with and without diabetes. The randomized, placebo-controlled trial had entered more than 4,700 patients.

Soon after, the FDA approved dapagliflozin for reducing the risk of heart failure hospitalization in adults with type 2 diabetes and other CV risk factors.

And of course, dapagliflozin – traditionally viewed only as an antidiabetic agent – has long been indicated for improvement of glycemic control in adults with type 2 diabetes.

The latest approval for patients with New York Heart Association functional class III-IV HFrEF makes dapagliflozin the only SGLT2 inhibitor to be indicated for heart failure in the absence of diabetes.

Soon after the DAPA-HF results had been unveiled at a major meeting, heart failure expert Christopher O’Connor, MD, expressed concern that dapagliflozin’s uptake for patients with HFrEF would be slow once it gained approval for patients without diabetes.

“We have to think of this as a drug that you would prescribe like an ACE inhibitor, or a beta-blocker, or a mineralocorticoid receptor antagonist, or sacubitril/valsartan [Entresto, Novartis],” Dr. O’Connor, of the Inova Heart and Vascular Institute, Falls Church, Va., said in an interview.

Dr. O’Connor was not associated with DAPA-HF and had previously disclosed no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

A just-launched study of the type 2 diabetes agent dapagliflozin (Farxiga, AstraZeneca) in patients with mild to moderate COVID-19 is raising eyebrows, given that several expert groups have advised that drugs in this class – the sodium-glucose cotransporter 2 (SGLT2) inhibitors – be stopped in all patients hospitalized with COVID-19 because of the increased risk for diabetic ketoacidosis (DKA).

The randomized, double-blind, placebo-controlled, phase 3 Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) study is sponsored by AstraZeneca and Saint Luke’s Mid America Heart Institute.

The trial will assess whether dapagliflozin reduces the risks of disease progression, clinical complications, and death because of COVID-19 in patients with type 2 diabetes, cardiovascular disease, and/or mild to moderate chronic kidney disease (CKD).

“Dapagliflozin has demonstrated cardio- and renal-protective benefits and improved outcomes in high-risk patients with type 2 diabetes, heart failure with reduced ejection fraction, and CKD,” said the principal investigator of DARE-19, Mikhail N. Kosiborod, MD, a cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

And “patients with COVID-19 and underlying cardiometabolic disease appear to be at the highest risk of morbid complications,” he explained in an AstraZeneca statement.

“Through DARE-19, we hope to decrease the severity of illness, and prevent cardiovascular, respiratory, and kidney decompensation, which are common in patients with COVID-19,” Dr. Kosiborod continued.

However, advice to stop SGLT2 inhibitors in patients hospitalized with COVID-19 because of its associated DKA risk has come from several channels.

These include initial guidance from Diabetes UK; experts who spoke during an American Diabetes Association webinar; and most recently, an international panel of diabetes experts.

Some clinicians went so far as to say that they view the trial as potentially dangerous, while others said they could see some logic to it, as long as it is carefully managed.
 

“A dangerous proposition – a DARE I would not take”

Partha Kar, MD, of Portsmouth Hospitals NHS Trust and national clinical director of diabetes at NHS England, said in an interview: “It’s interesting to see [AstraZeneca] embark on a study with a particular class of drug whereby ... [in] the UK we have said that if you get sent to hospital with COVID-19 you should stop [SGLT2 inhibitors] immediately.”

It “sounds like a risky proposition to go ahead with, [and it] definitely made me raise an eyebrow,” he added.

Nephrologist Bruce R. Leslie, MD, of Seventh Doctor Consulting in Princeton, N.J., agreed with Dr. Kar.

“Giving SGLT2 inhibitors to patients in the DARE-19 study is a dangerous proposition because these drugs can induce ketoacidosis during the stress of acute illness such as COVID-19. ... Moreover, ketoacidosis is associated with hypercoagulability which could be especially dangerous in COVID-19, given that it has been causing thrombophilia with large-vessel occlusive strokes in young patients,” he said in an interview.

“One wonders how these risks were assessed by the authorities that approved the DARE-19 study,” said Dr. Leslie, who formerly worked for Bristol-Myers Squibb.

“How does the sponsor intend to secure informed consent given the risks? This is a DARE I would not take,” he said.

Asked to address these concerns, Dr. Kosiborod said in an interview that “the DARE-19 trial will assess both the efficacy and the safety of dapagliflozin in this patient population in a closely monitored environment of a rigorously designed randomized clinical trial. The trial protocol excludes patients with type 1 diabetes or at high risk for DKA.

“Furthermore, the protocol includes detailed specific instructions to ensure careful monitoring for DKA, including frequent assessments of acid-base status in the hospital setting. The safety data will be closely monitored by an independent data-monitoring committee,” he continued.

Dr. Kosiborod also pointed out that there is “no systematically collected information on the use of dapagliflozin or any other SGLT2 inhibitor in patients being treated for COVID-19, including the associated potential benefits, possible risks such as DKA, and the balance of these potential benefits and risks.”

DARE-19 design: Several outcomes will be examined

The DARE-19 trial is designed to enroll 900 adults with confirmed SARS-CoV-2 infection and oxygen saturation of 94% or greater.

Inclusion criteria include a medical history of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or stage 3-4 CKD. Exclusion criteria include current SGLT2 inhibitor treatment, type 1 diabetes, severe CKD, and severe COVID-19.

Dapagliflozin is approved in the EU for use in some patients with type 1 diabetes; this is not the case in the United States, although SGLT2 inhibitors in general are sometimes used off label in these patients.

Patients in DARE-19 will be randomized to 10 mg/day dapagliflozin or placebo for 30 days, in addition to standard care, in participating hospital. Primary outcomes are time to first occurrence of either death or new or worsened organ dysfunction, including respiratory decompensation, new or worsening heart failure, requirement for vasopressor therapy, ventricular tachycardia, and renal failure.

Secondary outcomes include a composite of time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30, and time to hospital discharge.

Rationale for the study

Irl B. Hirsch, MD, professor and diabetes treatment and teaching chair at the University of Washington, Seattle, said in an interview that he does see some logic to the trial.

Admitting that he doesn’t know much about “COVID-19 cardiomyopathy” – which would be one of the targets of dapagliflozin – other than it is quite common, he said that this, along with the potential renal benefits of dapagliflozin in the setting of COVID-19, make the study “intriguing.”

“Perhaps there is some rationale to it,” he said. However, “my concern is these sick COVID-19 patients are often acidemic, and besides the very complex acid-base challenges we see with intubated patients, these patients likely have combination lactic and ketoacidemia, the latter at least some from starvation.

“Still, if enough dextrose and insulin are provided to prevent ketoacid accumulation, my guess is it would do at least as well as hydroxychloroquine,” he said.

And Simon Heller, MD, professor of clinical diabetes at the University of Sheffield (England), said in an interview: “I think it is quite a brave study, mainly because of the increased risk of DKA.

“However, on the basis that these patients will be carefully monitored, the risk of DKA shouldn’t be great. I think it is important that patients with type 2 diabetes can participate whenever possible in such trials,” he said.

The estimated completion date for DARE-19 is December 2020.

Dr. Kosiborod has reported receiving grant support, honoraria, and/or research support from AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck, Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia Therapeutics, Novartis, Applied Therapeutics, Amarin, and Eli Lilly. Dr. Leslie has reported owning stock in Bristol-Myers Squibb, Pfizer, and Lilly. Dr. Hirsch has reported consulting for Abbott Diabetes Care, Roche, and Bigfoot Biomedical, conducting research for Medtronic, and is a diabetes editor for UpToDate. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, MSD, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic UK. He is on the advisory board for Medscape. Dr. Kar has reported no relevant financial relationships.

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

Redo transcatheter aortic valve replacement (TAVR) is a reasonably safe and effective option for selected patients with valve dysfunction after TAVR, new registry data suggest.

“Redo TAVR is about to become a much more common procedure and it’s reassuring to see that the outcomes that can be achieved by these procedures are quite good,” said Uri Landes, MD, Vancouver General Hospital, British Columbia, Canada.

Landes and colleagues reported results from the Redo-TAVR Registry in the April 28 issue of the Journal of the American College of Cardiology.

The Redo-TAVR Registry is an investigator-initiated effort designed to collect information on patients who undergo a second TAVR within a dysfunctional transcatheter heart valve (THV).

From 63,876 TAVR procedures done at 37 participating centers, 212 (0.33%) were redo-TAVR procedures. Seventy-four of the redo procedures were done within 1 year of the initial TAVR and the remaining 138 were beyond 1 year. Median time from TAVR-to-redo-TAVR for these two groups was 68 (38 to 154) days and 5 (3 to 6) years, respectively.

“It’s important to understand that this is probably a highly selected group of patients and these numbers do no reliably reflect the ratio of patients who will need a redo TAVR,” said Landes in an interview with theheart.org | Medscape Cardiology.

“We don’t know how many patients were excluded from redo TAVR because of prohibitive anatomical factors, such as an anticipated high risk for coronary occlusion, or a patient prosthesis mismatch. Also, some of these individuals received their THVs more recently, so if they will suffer THV valve dysfunction, it may not have happened yet,” he added.

In the early redo group, the indication for redo-TAVR was most often combined aortic THV stenosis and regurgitation (83.8%). Pure THV stenosis was seen in only 16.2% of patients.

For those with redo procedures after 1 year, THV stenosis was seen in 51 (37.0%) patients and regurgitation or combined stenosis-regurgitation in 86 (62.3%).

Device success using VARC-2 criteria was achieved in 85.1%, with no difference seen between those presenting within or beyond 1 year. Most failures were attributable to high residual gradients (14.1%) or regurgitation (8.9%).

No significant difference was seen in 30-day (94.6% and 98.5%) and 1-year survival (83.6% and 88.3%) in patients who presented within 1 year or later.

At 30-day and 1-year follow-up, residual gradients were 12.6 ± 7.5 mm Hg and 12.9 ± 9.0 mm Hg, respectively. High residual gradients (³20 mm Hg) were seen in about 14% of patients.

Aortic valve areas were 1.63 ± 0.61 cm2 at 30 days and 1.51 ± 0.57 cm2 at 1 year. Regurgitation was mild or less in 91% of patients at both time points.

Periprocedural complication rates were relatively low. There were three strokes (1.4%), one valve malposition (3.3%), two coronary obstructions (0.9%), and 20 new permanent pacemaker implants (9.6%). Importantly, no procedure-related mortality was seen, only one patient converted to open heart surgery, and symptomatic improvements were substantial.

“We are currently working on an analysis that compares TAVI-in-TAVI versus TAVI in surgical valves, and we are happy to see that it appears as if TAVI-in-TAVI outcomes don’t fall short,” said Landes. More analysis is also needed to see if perhaps some THVs work better or worse for redo procedures.

“We also want to understand which of the many combinations of heart valves available are better than others, thinking that supra-annular leaflets inside intra-annular leaflet devices may function differently than vice versa,” said Landes.

Vinod Thourani, MD, chief of cardiovascular surgery at Piedmont Heart Institute, Atlanta, considers these new observational data “reassuring” and “robust,” albeit with some limitations. He was first author on an editorial comment on this paper and spoke to theheart.org | Medscape Cardiology.

“This is unadjudicated registry data but you can’t lie about death and I feel good seeing that if you need a second TAVR inside of a TAVR, your mortality risk is pretty good,” said Thourani.

That said, he questions whether these data can really be extrapolated to lower-risk patients. “I think this is an early snapshot and it’s a relatively big sample, but it’s a selected sample and we don’t know how many patients needed redo TAVR and didn’t get it or didn’t want it,” he added.

On the comforting side, there has been ongoing concern that a redo procedure that involves “propping open” a degenerated TAVR prosthesis’s leaflets with a new TAVR valve may occlude the coronary ostium by closing the flow within the open cells.

“Luckily, the investigators show an extremely low risk of coronary obstruction of only 0.9% in an anatomically high-risk patient population,” he said. This incidence, however, may increase as the use of TAVR rises in younger and less risky patients, he added.

Thourani would also like to see a longer follow-up on these patients. Median follow-up post redo TAVR was 15 months in this analysis.

“What I think we need to concentrate on as we do these studies is the life-long management of aortic stenosis wherein we try to minimize the overall number of invasive procedures as much as we can,” said Thourani.

Landes reported no conflict of interest. Thourani reported he is an advisor and/or researcher for Abbott Vascular, Boston Scientific, and Edwards Lifesciences.

This article first appeared on Medscape.com.

Redo transcatheter aortic valve replacement (TAVR) is a reasonably safe and effective option for selected patients with valve dysfunction after TAVR, new registry data suggest.

“Redo TAVR is about to become a much more common procedure and it’s reassuring to see that the outcomes that can be achieved by these procedures are quite good,” said Uri Landes, MD, Vancouver General Hospital, British Columbia, Canada.

Landes and colleagues reported results from the Redo-TAVR Registry in the April 28 issue of the Journal of the American College of Cardiology.

The Redo-TAVR Registry is an investigator-initiated effort designed to collect information on patients who undergo a second TAVR within a dysfunctional transcatheter heart valve (THV).

From 63,876 TAVR procedures done at 37 participating centers, 212 (0.33%) were redo-TAVR procedures. Seventy-four of the redo procedures were done within 1 year of the initial TAVR and the remaining 138 were beyond 1 year. Median time from TAVR-to-redo-TAVR for these two groups was 68 (38 to 154) days and 5 (3 to 6) years, respectively.

“It’s important to understand that this is probably a highly selected group of patients and these numbers do no reliably reflect the ratio of patients who will need a redo TAVR,” said Landes in an interview with theheart.org | Medscape Cardiology.

“We don’t know how many patients were excluded from redo TAVR because of prohibitive anatomical factors, such as an anticipated high risk for coronary occlusion, or a patient prosthesis mismatch. Also, some of these individuals received their THVs more recently, so if they will suffer THV valve dysfunction, it may not have happened yet,” he added.

In the early redo group, the indication for redo-TAVR was most often combined aortic THV stenosis and regurgitation (83.8%). Pure THV stenosis was seen in only 16.2% of patients.

For those with redo procedures after 1 year, THV stenosis was seen in 51 (37.0%) patients and regurgitation or combined stenosis-regurgitation in 86 (62.3%).

Device success using VARC-2 criteria was achieved in 85.1%, with no difference seen between those presenting within or beyond 1 year. Most failures were attributable to high residual gradients (14.1%) or regurgitation (8.9%).

No significant difference was seen in 30-day (94.6% and 98.5%) and 1-year survival (83.6% and 88.3%) in patients who presented within 1 year or later.

At 30-day and 1-year follow-up, residual gradients were 12.6 ± 7.5 mm Hg and 12.9 ± 9.0 mm Hg, respectively. High residual gradients (³20 mm Hg) were seen in about 14% of patients.

Aortic valve areas were 1.63 ± 0.61 cm2 at 30 days and 1.51 ± 0.57 cm2 at 1 year. Regurgitation was mild or less in 91% of patients at both time points.

Periprocedural complication rates were relatively low. There were three strokes (1.4%), one valve malposition (3.3%), two coronary obstructions (0.9%), and 20 new permanent pacemaker implants (9.6%). Importantly, no procedure-related mortality was seen, only one patient converted to open heart surgery, and symptomatic improvements were substantial.

“We are currently working on an analysis that compares TAVI-in-TAVI versus TAVI in surgical valves, and we are happy to see that it appears as if TAVI-in-TAVI outcomes don’t fall short,” said Landes. More analysis is also needed to see if perhaps some THVs work better or worse for redo procedures.

“We also want to understand which of the many combinations of heart valves available are better than others, thinking that supra-annular leaflets inside intra-annular leaflet devices may function differently than vice versa,” said Landes.

Vinod Thourani, MD, chief of cardiovascular surgery at Piedmont Heart Institute, Atlanta, considers these new observational data “reassuring” and “robust,” albeit with some limitations. He was first author on an editorial comment on this paper and spoke to theheart.org | Medscape Cardiology.

“This is unadjudicated registry data but you can’t lie about death and I feel good seeing that if you need a second TAVR inside of a TAVR, your mortality risk is pretty good,” said Thourani.

That said, he questions whether these data can really be extrapolated to lower-risk patients. “I think this is an early snapshot and it’s a relatively big sample, but it’s a selected sample and we don’t know how many patients needed redo TAVR and didn’t get it or didn’t want it,” he added.

On the comforting side, there has been ongoing concern that a redo procedure that involves “propping open” a degenerated TAVR prosthesis’s leaflets with a new TAVR valve may occlude the coronary ostium by closing the flow within the open cells.

“Luckily, the investigators show an extremely low risk of coronary obstruction of only 0.9% in an anatomically high-risk patient population,” he said. This incidence, however, may increase as the use of TAVR rises in younger and less risky patients, he added.

Thourani would also like to see a longer follow-up on these patients. Median follow-up post redo TAVR was 15 months in this analysis.

“What I think we need to concentrate on as we do these studies is the life-long management of aortic stenosis wherein we try to minimize the overall number of invasive procedures as much as we can,” said Thourani.

Landes reported no conflict of interest. Thourani reported he is an advisor and/or researcher for Abbott Vascular, Boston Scientific, and Edwards Lifesciences.

This article first appeared on Medscape.com.

Redo transcatheter aortic valve replacement (TAVR) is a reasonably safe and effective option for selected patients with valve dysfunction after TAVR, new registry data suggest.

“Redo TAVR is about to become a much more common procedure and it’s reassuring to see that the outcomes that can be achieved by these procedures are quite good,” said Uri Landes, MD, Vancouver General Hospital, British Columbia, Canada.

Landes and colleagues reported results from the Redo-TAVR Registry in the April 28 issue of the Journal of the American College of Cardiology.

The Redo-TAVR Registry is an investigator-initiated effort designed to collect information on patients who undergo a second TAVR within a dysfunctional transcatheter heart valve (THV).

From 63,876 TAVR procedures done at 37 participating centers, 212 (0.33%) were redo-TAVR procedures. Seventy-four of the redo procedures were done within 1 year of the initial TAVR and the remaining 138 were beyond 1 year. Median time from TAVR-to-redo-TAVR for these two groups was 68 (38 to 154) days and 5 (3 to 6) years, respectively.

“It’s important to understand that this is probably a highly selected group of patients and these numbers do no reliably reflect the ratio of patients who will need a redo TAVR,” said Landes in an interview with theheart.org | Medscape Cardiology.

“We don’t know how many patients were excluded from redo TAVR because of prohibitive anatomical factors, such as an anticipated high risk for coronary occlusion, or a patient prosthesis mismatch. Also, some of these individuals received their THVs more recently, so if they will suffer THV valve dysfunction, it may not have happened yet,” he added.

In the early redo group, the indication for redo-TAVR was most often combined aortic THV stenosis and regurgitation (83.8%). Pure THV stenosis was seen in only 16.2% of patients.

For those with redo procedures after 1 year, THV stenosis was seen in 51 (37.0%) patients and regurgitation or combined stenosis-regurgitation in 86 (62.3%).

Device success using VARC-2 criteria was achieved in 85.1%, with no difference seen between those presenting within or beyond 1 year. Most failures were attributable to high residual gradients (14.1%) or regurgitation (8.9%).

No significant difference was seen in 30-day (94.6% and 98.5%) and 1-year survival (83.6% and 88.3%) in patients who presented within 1 year or later.

At 30-day and 1-year follow-up, residual gradients were 12.6 ± 7.5 mm Hg and 12.9 ± 9.0 mm Hg, respectively. High residual gradients (³20 mm Hg) were seen in about 14% of patients.

Aortic valve areas were 1.63 ± 0.61 cm2 at 30 days and 1.51 ± 0.57 cm2 at 1 year. Regurgitation was mild or less in 91% of patients at both time points.

Periprocedural complication rates were relatively low. There were three strokes (1.4%), one valve malposition (3.3%), two coronary obstructions (0.9%), and 20 new permanent pacemaker implants (9.6%). Importantly, no procedure-related mortality was seen, only one patient converted to open heart surgery, and symptomatic improvements were substantial.

“We are currently working on an analysis that compares TAVI-in-TAVI versus TAVI in surgical valves, and we are happy to see that it appears as if TAVI-in-TAVI outcomes don’t fall short,” said Landes. More analysis is also needed to see if perhaps some THVs work better or worse for redo procedures.

“We also want to understand which of the many combinations of heart valves available are better than others, thinking that supra-annular leaflets inside intra-annular leaflet devices may function differently than vice versa,” said Landes.

Vinod Thourani, MD, chief of cardiovascular surgery at Piedmont Heart Institute, Atlanta, considers these new observational data “reassuring” and “robust,” albeit with some limitations. He was first author on an editorial comment on this paper and spoke to theheart.org | Medscape Cardiology.

“This is unadjudicated registry data but you can’t lie about death and I feel good seeing that if you need a second TAVR inside of a TAVR, your mortality risk is pretty good,” said Thourani.

That said, he questions whether these data can really be extrapolated to lower-risk patients. “I think this is an early snapshot and it’s a relatively big sample, but it’s a selected sample and we don’t know how many patients needed redo TAVR and didn’t get it or didn’t want it,” he added.

On the comforting side, there has been ongoing concern that a redo procedure that involves “propping open” a degenerated TAVR prosthesis’s leaflets with a new TAVR valve may occlude the coronary ostium by closing the flow within the open cells.

“Luckily, the investigators show an extremely low risk of coronary obstruction of only 0.9% in an anatomically high-risk patient population,” he said. This incidence, however, may increase as the use of TAVR rises in younger and less risky patients, he added.

Thourani would also like to see a longer follow-up on these patients. Median follow-up post redo TAVR was 15 months in this analysis.

“What I think we need to concentrate on as we do these studies is the life-long management of aortic stenosis wherein we try to minimize the overall number of invasive procedures as much as we can,” said Thourani.

Landes reported no conflict of interest. Thourani reported he is an advisor and/or researcher for Abbott Vascular, Boston Scientific, and Edwards Lifesciences.

This article first appeared on Medscape.com.