Treatment with the SGLT2 inhibitor empagliflozin led to significant reductions in both left ventricular end systolic and diastolic volumes in two independent randomized studies of patients with heart failure with reduced ejection fraction.

These results provide important new evidence that one way a drug from this class exerts its beneficial effects on cardiovascular outcomes in these patients is by producing favorable left-ventricular remodeling.

One of the two studies involved only patients with heart failure with reduced ejection fraction (HFrEF) with diabetes and examined treatment impact after 36 weeks. The second study focused exclusively on HFrEF patients without diabetes and followed patients for 6 months. Both studies also generated additional significant evidence of favorable left-ventricular effects. 

“The results of these two new trials are incredibly important, as they tell cardiologists one of the mechanisms by which SGLT2 [sodium glucose co-transporter 2] inhibitors reduce heart failure hospitalizations and cardiovascular death,” said Mark C. Petrie,  MBChB, professor at the Institute of Cardiovascular & Medical Sciences at the University of Glasgow, and principal investigator for one of the two studies.

“Many cardiologists want to know mechanisms as well as clinical benefit. These remodeling data showing that these drugs reduce the size of abnormally large hearts [and] are also very important for patients,” Dr. Petrie said in an interview. “There have been more than 50 publications on potential mechanisms of benefit of SGLT2 inhibitors in HFrEF, but these are the first randomized, mechanistic data.”

Mechanistic clues follow large cardiovascular outcome trials

Results from a large randomized trial, EMPEROR-Reduced, recently showed that treatment with empagliflozin (Jardiance) on top of standard HFrEF treatment led to significant benefits in patients with or without type 2 diabetes (T2D), compared with placebo, for major cardiovascular and renal endpoints, including the combination of cardiovascular death or hospitalization for heart failure. And results from a second large randomized trial, DAPA-HF, showed similar results with a different drug from the same class, dapagliflozin (Farxiga), in an earlier report.

But while these reports led to quick uptake of these two drugs for the treatment of patients with HFrEF, the means by which these agents exert their HFrEF benefits have been unclear.

“Our study identifies why this drug [empagliflozin] is effective – because it improves heart function, something that has not been understood until now,” Carlos G. Santos-Gallego, MD, lead investigator for the second new report, said in a written statement. “Many doctors are afraid of prescribing a drug they do not understand, and our findings will help clinicians feel more comfortable giving this to patients once approved.”

On the strength of the DAPA-HF results, dapagliflozin received a revised U.S. label in May 2020 that added the indication for treating patients with HFrEF regardless of the whether patients also have T2D, the original indication for prescribing the drug. Many experts anticipate that a similar addition to the label for empagliflozin will soon occur.

EMPA-TROPISM examines patients with no T2D

The single-center study reported by Dr. Santos-Gallego randomized 84 patients with HFrEF and no diabetes to standard treatment with empagliflozin or placebo and measured several parameters in 80 patients who completed the planned 6 months of treatment. The primary endpoints were the changes in both left ventricular end systolic and diastolic volume from baseline in the empagliflozin-treated patients compared with patients on placebo, measured by cardiac MR.

The results showed an average reduction of end systolic volume of 26.6 mL from baseline compared with a small rise in the placebo patients, and an average drop in end diastolic volume of 25.1 mL from baseline compared again with a small increase in the controls. Both differences were statistically significant, reported the senior author of the study, Juan J. Badimon, PhD, in a talk at the virtual scientific sessions of the American Heart Association. Concurrently, the results were published online in the Journal of the American College of Cardiology.

Results from the EMPA-TROPISM study also showed several other significant benefits from empagliflozin treatment, both to left ventricular shape and function as well as to other measures of patient well being. The drug regimen led to an increase in left ventricular ejection fraction, a decrease in left ventricular mass, reduced myocardial fibrosis and aortic stiffness, increased peak oxygen consumption, an increased distance traveled in a 6-minute walk test, and improved quality of life, said Dr. Badimon, professor of medicine and director of the Atherothrombosis Research Unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai in New York.

SUGAR-DM-HF enrolled only T2D patients

The second study, SUGAR-DM-HF, randomized 105 patients with HFrEF and T2D to treatment with empagliflozin or placebo at any of 15 centers in Scotland, with 92 patients completing the full 36 weeks on treatment. One of the study’s two primary endpoints was the change in left ventricular end systolic volume index, which dropped by an average of 7.9 mL/m2 in patients who received empagliflozin and by 1.5 mL/m2 in the controls, a significant average between-group difference of 6.0 mL/m2, reported Matthew M.Y. Lee, MBChB, at the same meeting.

However, the second primary endpoint, change in left ventricular global longitudinal strain, showed no significant difference in effect on empagliflozin compared with placebo, said Dr. Lee, a cardiologist at the University of Glasgow. Concurrently with his report the results appeared in an article published online in Circulation.

The results also showed a significant drop in left ventricular end diastolic volume index from baseline compared with the control patients, with an average between-group difference in the reduction from baseline of 8.2 mL/m2.
“Reverse cardiac remodeling is a mechanism by which SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular mortality,” Dr. Lee concluded during his presentation at the meeting.

Although the findings from both studies together provide strong evidence for an effect by empagliflozin on left ventricular shape and function, neither study provides much insight into how this drug exerts these effects. The authors of both studies agreed on several potential explanations, including reductions in cardiac preload and afterload that could reduce left ventricular stretch and volume; a change triggered in myocardial energetics that switches from a metabolism mostly dependent on glucose to one more geared to using fatty acids, ketone bodies, and branched chain amino acids; and a possible drug-induced reduction in oxidative stress and inflammation.

SUGAR-DM-HF was sponsored by a grant from Boehringer Ingelheim, the company that along with Eli Lilly markets empagliflozin (Jardiance). Dr. Lee had no disclosures. Dr. Petrie has been a consultant to Boehringer Ingelheim and Eli Lilly and to several other companies. EMPA-TROPISM was sponsored by a grant from Boehringer Ingelheim. Dr. Badimon and Dr. Santos-Gallego had no disclosures.

[email protected] 

Treatment with the SGLT2 inhibitor empagliflozin led to significant reductions in both left ventricular end systolic and diastolic volumes in two independent randomized studies of patients with heart failure with reduced ejection fraction.

These results provide important new evidence that one way a drug from this class exerts its beneficial effects on cardiovascular outcomes in these patients is by producing favorable left-ventricular remodeling.

One of the two studies involved only patients with heart failure with reduced ejection fraction (HFrEF) with diabetes and examined treatment impact after 36 weeks. The second study focused exclusively on HFrEF patients without diabetes and followed patients for 6 months. Both studies also generated additional significant evidence of favorable left-ventricular effects. 

“The results of these two new trials are incredibly important, as they tell cardiologists one of the mechanisms by which SGLT2 [sodium glucose co-transporter 2] inhibitors reduce heart failure hospitalizations and cardiovascular death,” said Mark C. Petrie,  MBChB, professor at the Institute of Cardiovascular & Medical Sciences at the University of Glasgow, and principal investigator for one of the two studies.

“Many cardiologists want to know mechanisms as well as clinical benefit. These remodeling data showing that these drugs reduce the size of abnormally large hearts [and] are also very important for patients,” Dr. Petrie said in an interview. “There have been more than 50 publications on potential mechanisms of benefit of SGLT2 inhibitors in HFrEF, but these are the first randomized, mechanistic data.”

Mechanistic clues follow large cardiovascular outcome trials

Results from a large randomized trial, EMPEROR-Reduced, recently showed that treatment with empagliflozin (Jardiance) on top of standard HFrEF treatment led to significant benefits in patients with or without type 2 diabetes (T2D), compared with placebo, for major cardiovascular and renal endpoints, including the combination of cardiovascular death or hospitalization for heart failure. And results from a second large randomized trial, DAPA-HF, showed similar results with a different drug from the same class, dapagliflozin (Farxiga), in an earlier report.

But while these reports led to quick uptake of these two drugs for the treatment of patients with HFrEF, the means by which these agents exert their HFrEF benefits have been unclear.

“Our study identifies why this drug [empagliflozin] is effective – because it improves heart function, something that has not been understood until now,” Carlos G. Santos-Gallego, MD, lead investigator for the second new report, said in a written statement. “Many doctors are afraid of prescribing a drug they do not understand, and our findings will help clinicians feel more comfortable giving this to patients once approved.”

On the strength of the DAPA-HF results, dapagliflozin received a revised U.S. label in May 2020 that added the indication for treating patients with HFrEF regardless of the whether patients also have T2D, the original indication for prescribing the drug. Many experts anticipate that a similar addition to the label for empagliflozin will soon occur.

EMPA-TROPISM examines patients with no T2D

The single-center study reported by Dr. Santos-Gallego randomized 84 patients with HFrEF and no diabetes to standard treatment with empagliflozin or placebo and measured several parameters in 80 patients who completed the planned 6 months of treatment. The primary endpoints were the changes in both left ventricular end systolic and diastolic volume from baseline in the empagliflozin-treated patients compared with patients on placebo, measured by cardiac MR.

The results showed an average reduction of end systolic volume of 26.6 mL from baseline compared with a small rise in the placebo patients, and an average drop in end diastolic volume of 25.1 mL from baseline compared again with a small increase in the controls. Both differences were statistically significant, reported the senior author of the study, Juan J. Badimon, PhD, in a talk at the virtual scientific sessions of the American Heart Association. Concurrently, the results were published online in the Journal of the American College of Cardiology.

Results from the EMPA-TROPISM study also showed several other significant benefits from empagliflozin treatment, both to left ventricular shape and function as well as to other measures of patient well being. The drug regimen led to an increase in left ventricular ejection fraction, a decrease in left ventricular mass, reduced myocardial fibrosis and aortic stiffness, increased peak oxygen consumption, an increased distance traveled in a 6-minute walk test, and improved quality of life, said Dr. Badimon, professor of medicine and director of the Atherothrombosis Research Unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai in New York.

SUGAR-DM-HF enrolled only T2D patients

The second study, SUGAR-DM-HF, randomized 105 patients with HFrEF and T2D to treatment with empagliflozin or placebo at any of 15 centers in Scotland, with 92 patients completing the full 36 weeks on treatment. One of the study’s two primary endpoints was the change in left ventricular end systolic volume index, which dropped by an average of 7.9 mL/m2 in patients who received empagliflozin and by 1.5 mL/m2 in the controls, a significant average between-group difference of 6.0 mL/m2, reported Matthew M.Y. Lee, MBChB, at the same meeting.

However, the second primary endpoint, change in left ventricular global longitudinal strain, showed no significant difference in effect on empagliflozin compared with placebo, said Dr. Lee, a cardiologist at the University of Glasgow. Concurrently with his report the results appeared in an article published online in Circulation.

The results also showed a significant drop in left ventricular end diastolic volume index from baseline compared with the control patients, with an average between-group difference in the reduction from baseline of 8.2 mL/m2.
“Reverse cardiac remodeling is a mechanism by which SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular mortality,” Dr. Lee concluded during his presentation at the meeting.

Although the findings from both studies together provide strong evidence for an effect by empagliflozin on left ventricular shape and function, neither study provides much insight into how this drug exerts these effects. The authors of both studies agreed on several potential explanations, including reductions in cardiac preload and afterload that could reduce left ventricular stretch and volume; a change triggered in myocardial energetics that switches from a metabolism mostly dependent on glucose to one more geared to using fatty acids, ketone bodies, and branched chain amino acids; and a possible drug-induced reduction in oxidative stress and inflammation.

SUGAR-DM-HF was sponsored by a grant from Boehringer Ingelheim, the company that along with Eli Lilly markets empagliflozin (Jardiance). Dr. Lee had no disclosures. Dr. Petrie has been a consultant to Boehringer Ingelheim and Eli Lilly and to several other companies. EMPA-TROPISM was sponsored by a grant from Boehringer Ingelheim. Dr. Badimon and Dr. Santos-Gallego had no disclosures.

[email protected] 

Treatment with the SGLT2 inhibitor empagliflozin led to significant reductions in both left ventricular end systolic and diastolic volumes in two independent randomized studies of patients with heart failure with reduced ejection fraction.

These results provide important new evidence that one way a drug from this class exerts its beneficial effects on cardiovascular outcomes in these patients is by producing favorable left-ventricular remodeling.

One of the two studies involved only patients with heart failure with reduced ejection fraction (HFrEF) with diabetes and examined treatment impact after 36 weeks. The second study focused exclusively on HFrEF patients without diabetes and followed patients for 6 months. Both studies also generated additional significant evidence of favorable left-ventricular effects. 

“The results of these two new trials are incredibly important, as they tell cardiologists one of the mechanisms by which SGLT2 [sodium glucose co-transporter 2] inhibitors reduce heart failure hospitalizations and cardiovascular death,” said Mark C. Petrie,  MBChB, professor at the Institute of Cardiovascular & Medical Sciences at the University of Glasgow, and principal investigator for one of the two studies.

“Many cardiologists want to know mechanisms as well as clinical benefit. These remodeling data showing that these drugs reduce the size of abnormally large hearts [and] are also very important for patients,” Dr. Petrie said in an interview. “There have been more than 50 publications on potential mechanisms of benefit of SGLT2 inhibitors in HFrEF, but these are the first randomized, mechanistic data.”

Mechanistic clues follow large cardiovascular outcome trials

Results from a large randomized trial, EMPEROR-Reduced, recently showed that treatment with empagliflozin (Jardiance) on top of standard HFrEF treatment led to significant benefits in patients with or without type 2 diabetes (T2D), compared with placebo, for major cardiovascular and renal endpoints, including the combination of cardiovascular death or hospitalization for heart failure. And results from a second large randomized trial, DAPA-HF, showed similar results with a different drug from the same class, dapagliflozin (Farxiga), in an earlier report.

But while these reports led to quick uptake of these two drugs for the treatment of patients with HFrEF, the means by which these agents exert their HFrEF benefits have been unclear.

“Our study identifies why this drug [empagliflozin] is effective – because it improves heart function, something that has not been understood until now,” Carlos G. Santos-Gallego, MD, lead investigator for the second new report, said in a written statement. “Many doctors are afraid of prescribing a drug they do not understand, and our findings will help clinicians feel more comfortable giving this to patients once approved.”

On the strength of the DAPA-HF results, dapagliflozin received a revised U.S. label in May 2020 that added the indication for treating patients with HFrEF regardless of the whether patients also have T2D, the original indication for prescribing the drug. Many experts anticipate that a similar addition to the label for empagliflozin will soon occur.

EMPA-TROPISM examines patients with no T2D

The single-center study reported by Dr. Santos-Gallego randomized 84 patients with HFrEF and no diabetes to standard treatment with empagliflozin or placebo and measured several parameters in 80 patients who completed the planned 6 months of treatment. The primary endpoints were the changes in both left ventricular end systolic and diastolic volume from baseline in the empagliflozin-treated patients compared with patients on placebo, measured by cardiac MR.

The results showed an average reduction of end systolic volume of 26.6 mL from baseline compared with a small rise in the placebo patients, and an average drop in end diastolic volume of 25.1 mL from baseline compared again with a small increase in the controls. Both differences were statistically significant, reported the senior author of the study, Juan J. Badimon, PhD, in a talk at the virtual scientific sessions of the American Heart Association. Concurrently, the results were published online in the Journal of the American College of Cardiology.

Results from the EMPA-TROPISM study also showed several other significant benefits from empagliflozin treatment, both to left ventricular shape and function as well as to other measures of patient well being. The drug regimen led to an increase in left ventricular ejection fraction, a decrease in left ventricular mass, reduced myocardial fibrosis and aortic stiffness, increased peak oxygen consumption, an increased distance traveled in a 6-minute walk test, and improved quality of life, said Dr. Badimon, professor of medicine and director of the Atherothrombosis Research Unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai in New York.

SUGAR-DM-HF enrolled only T2D patients

The second study, SUGAR-DM-HF, randomized 105 patients with HFrEF and T2D to treatment with empagliflozin or placebo at any of 15 centers in Scotland, with 92 patients completing the full 36 weeks on treatment. One of the study’s two primary endpoints was the change in left ventricular end systolic volume index, which dropped by an average of 7.9 mL/m2 in patients who received empagliflozin and by 1.5 mL/m2 in the controls, a significant average between-group difference of 6.0 mL/m2, reported Matthew M.Y. Lee, MBChB, at the same meeting.

However, the second primary endpoint, change in left ventricular global longitudinal strain, showed no significant difference in effect on empagliflozin compared with placebo, said Dr. Lee, a cardiologist at the University of Glasgow. Concurrently with his report the results appeared in an article published online in Circulation.

The results also showed a significant drop in left ventricular end diastolic volume index from baseline compared with the control patients, with an average between-group difference in the reduction from baseline of 8.2 mL/m2.
“Reverse cardiac remodeling is a mechanism by which SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular mortality,” Dr. Lee concluded during his presentation at the meeting.

Although the findings from both studies together provide strong evidence for an effect by empagliflozin on left ventricular shape and function, neither study provides much insight into how this drug exerts these effects. The authors of both studies agreed on several potential explanations, including reductions in cardiac preload and afterload that could reduce left ventricular stretch and volume; a change triggered in myocardial energetics that switches from a metabolism mostly dependent on glucose to one more geared to using fatty acids, ketone bodies, and branched chain amino acids; and a possible drug-induced reduction in oxidative stress and inflammation.

SUGAR-DM-HF was sponsored by a grant from Boehringer Ingelheim, the company that along with Eli Lilly markets empagliflozin (Jardiance). Dr. Lee had no disclosures. Dr. Petrie has been a consultant to Boehringer Ingelheim and Eli Lilly and to several other companies. EMPA-TROPISM was sponsored by a grant from Boehringer Ingelheim. Dr. Badimon and Dr. Santos-Gallego had no disclosures.

[email protected] 

Ticagrelor failed to unseat clopidogrel as the guideline-recommended P2Y12 inhibitor of choice in patients undergoing elective percutaneous coronary intervention for stable CAD in the randomized ALPHEUS trial.

“The higher level of platelet inhibition obtained with ticagrelor does not translate into a reduction of periprocedural MI or myocardial injury within 48 hours of high-risk PCI performed in stable coronary patients,” reported Johanne Silvain, MD, PhD, professor of cardiology at the Sorbonne University and director of the ICU at Pitie-Salpetriere Hospital, Paris, at the virtual American Heart Association scientific sessions.

American Heart Association

Myonecrosis hypothesis falls flat

The primary endpoint was the occurrence of major myocardial injury, defined as a periprocedural troponin elevated greater than 5 times the upper limit of normal within 48 hours of PCI; type 4a MI, defined as major myocardial injury plus signs or symptoms of ischemia; or stent thrombosis.

The rates were closely similar: 35.5% with ticagrelor, 36.2% with clopidogrel. The bulk of events consisted of major myocardial injury, with an incidence of 26.7% in the ticagrelor group and 27.7% with clopidogrel. Stent thrombosis occurred in 0.3% of patients in each group. Type 4a MI occurred in 8.5% of the ticagrelor group and 8.2% of patients on clopidogrel.

The study hypothesis was that a substantial portion of periprocedural myonecrosis may be thrombotic in nature, and that a stronger P2Y12 inhibitor could reduce the occurrence of these mini-infarcts and thus provide patient benefit. But the hypothesis was not borne out.

“We don’t know if these events are a risk factor or just a marker of risk,” Dr. Silvain said.

There were no between-group differences in major bleeding events at 48 hours or 30 days. However, the rate of nuisance or minor bleeding at 30 days was 11.2% in the ticagrelor arm, significantly higher than the 7.5% incidence with clopidogrel. Moreover, dyspnea occurred in 11.2% of patients on ticagrelor, compared to 0.2% with clopidogrel. Study drug discontinuation was more frequent in the ticagrelor arm: 2.2%, versus 0.4%.

Dr. Silvain also presented a pooled analysis of the 1,883 patients in ALPHEUS plus 781 from the similarly designed SASSICAIA trial, which compared prasugrel (Effient) to clopidogrel. Neither of the more potent P2Y12 inhibitors showed superiority over clopidogrel.

American Heart Association

Discussant Stephen D. Wiviott, MD, summed things up: “With no evidence for ischemic benefit and higher rates of low-severity bleeding, this trial does not support the use of more potent P2Y12 antagonists for elective PCI. Based on these results, and consistent with SASSICAIA, aspirin with clopidogrel should remain the standard of care in this population.”
 

Troponin response may vary

A striking finding in ALPHEUS was the discrepancy between very high rates of periprocedural troponin elevation and very low rates of clinical events through 30 days of follow-up. “When you look at these modest elevations of troponin it appears that there is a lot of noise here,” said Dr. Wiviott, vice president for clinical trials research and administration at Massachusetts General Hospital and Brigham and Women’s Hospital and a cardiologist at Harvard Medical School, Boston.

Troponin elevations in stable coronary patients undergoing PCI may have a different underlying mechanism than elevated troponins in patients undergoing PCI for an acute coronary syndrome, he added. In stable CAD patients, the phenomenon may be more related to atherosclerosis than to platelet activation and thrombosis.

During a panel discussion, Sunil V. Rao, MD, said cardiologists are “probably going to have to go back to the drawing board and think about what kinds of events are really, really important.”

American Heart Association

[email protected]

SOURCE: Silvain J. AHA 2020. Session LBS 3.

Ticagrelor failed to unseat clopidogrel as the guideline-recommended P2Y12 inhibitor of choice in patients undergoing elective percutaneous coronary intervention for stable CAD in the randomized ALPHEUS trial.

“The higher level of platelet inhibition obtained with ticagrelor does not translate into a reduction of periprocedural MI or myocardial injury within 48 hours of high-risk PCI performed in stable coronary patients,” reported Johanne Silvain, MD, PhD, professor of cardiology at the Sorbonne University and director of the ICU at Pitie-Salpetriere Hospital, Paris, at the virtual American Heart Association scientific sessions.

American Heart Association

Myonecrosis hypothesis falls flat

The primary endpoint was the occurrence of major myocardial injury, defined as a periprocedural troponin elevated greater than 5 times the upper limit of normal within 48 hours of PCI; type 4a MI, defined as major myocardial injury plus signs or symptoms of ischemia; or stent thrombosis.

The rates were closely similar: 35.5% with ticagrelor, 36.2% with clopidogrel. The bulk of events consisted of major myocardial injury, with an incidence of 26.7% in the ticagrelor group and 27.7% with clopidogrel. Stent thrombosis occurred in 0.3% of patients in each group. Type 4a MI occurred in 8.5% of the ticagrelor group and 8.2% of patients on clopidogrel.

The study hypothesis was that a substantial portion of periprocedural myonecrosis may be thrombotic in nature, and that a stronger P2Y12 inhibitor could reduce the occurrence of these mini-infarcts and thus provide patient benefit. But the hypothesis was not borne out.

“We don’t know if these events are a risk factor or just a marker of risk,” Dr. Silvain said.

There were no between-group differences in major bleeding events at 48 hours or 30 days. However, the rate of nuisance or minor bleeding at 30 days was 11.2% in the ticagrelor arm, significantly higher than the 7.5% incidence with clopidogrel. Moreover, dyspnea occurred in 11.2% of patients on ticagrelor, compared to 0.2% with clopidogrel. Study drug discontinuation was more frequent in the ticagrelor arm: 2.2%, versus 0.4%.

Dr. Silvain also presented a pooled analysis of the 1,883 patients in ALPHEUS plus 781 from the similarly designed SASSICAIA trial, which compared prasugrel (Effient) to clopidogrel. Neither of the more potent P2Y12 inhibitors showed superiority over clopidogrel.

American Heart Association

Discussant Stephen D. Wiviott, MD, summed things up: “With no evidence for ischemic benefit and higher rates of low-severity bleeding, this trial does not support the use of more potent P2Y12 antagonists for elective PCI. Based on these results, and consistent with SASSICAIA, aspirin with clopidogrel should remain the standard of care in this population.”
 

Troponin response may vary

A striking finding in ALPHEUS was the discrepancy between very high rates of periprocedural troponin elevation and very low rates of clinical events through 30 days of follow-up. “When you look at these modest elevations of troponin it appears that there is a lot of noise here,” said Dr. Wiviott, vice president for clinical trials research and administration at Massachusetts General Hospital and Brigham and Women’s Hospital and a cardiologist at Harvard Medical School, Boston.

Troponin elevations in stable coronary patients undergoing PCI may have a different underlying mechanism than elevated troponins in patients undergoing PCI for an acute coronary syndrome, he added. In stable CAD patients, the phenomenon may be more related to atherosclerosis than to platelet activation and thrombosis.

During a panel discussion, Sunil V. Rao, MD, said cardiologists are “probably going to have to go back to the drawing board and think about what kinds of events are really, really important.”

American Heart Association

[email protected]

SOURCE: Silvain J. AHA 2020. Session LBS 3.

Ticagrelor failed to unseat clopidogrel as the guideline-recommended P2Y12 inhibitor of choice in patients undergoing elective percutaneous coronary intervention for stable CAD in the randomized ALPHEUS trial.

“The higher level of platelet inhibition obtained with ticagrelor does not translate into a reduction of periprocedural MI or myocardial injury within 48 hours of high-risk PCI performed in stable coronary patients,” reported Johanne Silvain, MD, PhD, professor of cardiology at the Sorbonne University and director of the ICU at Pitie-Salpetriere Hospital, Paris, at the virtual American Heart Association scientific sessions.

American Heart Association

Myonecrosis hypothesis falls flat

The primary endpoint was the occurrence of major myocardial injury, defined as a periprocedural troponin elevated greater than 5 times the upper limit of normal within 48 hours of PCI; type 4a MI, defined as major myocardial injury plus signs or symptoms of ischemia; or stent thrombosis.

The rates were closely similar: 35.5% with ticagrelor, 36.2% with clopidogrel. The bulk of events consisted of major myocardial injury, with an incidence of 26.7% in the ticagrelor group and 27.7% with clopidogrel. Stent thrombosis occurred in 0.3% of patients in each group. Type 4a MI occurred in 8.5% of the ticagrelor group and 8.2% of patients on clopidogrel.

The study hypothesis was that a substantial portion of periprocedural myonecrosis may be thrombotic in nature, and that a stronger P2Y12 inhibitor could reduce the occurrence of these mini-infarcts and thus provide patient benefit. But the hypothesis was not borne out.

“We don’t know if these events are a risk factor or just a marker of risk,” Dr. Silvain said.

There were no between-group differences in major bleeding events at 48 hours or 30 days. However, the rate of nuisance or minor bleeding at 30 days was 11.2% in the ticagrelor arm, significantly higher than the 7.5% incidence with clopidogrel. Moreover, dyspnea occurred in 11.2% of patients on ticagrelor, compared to 0.2% with clopidogrel. Study drug discontinuation was more frequent in the ticagrelor arm: 2.2%, versus 0.4%.

Dr. Silvain also presented a pooled analysis of the 1,883 patients in ALPHEUS plus 781 from the similarly designed SASSICAIA trial, which compared prasugrel (Effient) to clopidogrel. Neither of the more potent P2Y12 inhibitors showed superiority over clopidogrel.

American Heart Association

Discussant Stephen D. Wiviott, MD, summed things up: “With no evidence for ischemic benefit and higher rates of low-severity bleeding, this trial does not support the use of more potent P2Y12 antagonists for elective PCI. Based on these results, and consistent with SASSICAIA, aspirin with clopidogrel should remain the standard of care in this population.”
 

Troponin response may vary

A striking finding in ALPHEUS was the discrepancy between very high rates of periprocedural troponin elevation and very low rates of clinical events through 30 days of follow-up. “When you look at these modest elevations of troponin it appears that there is a lot of noise here,” said Dr. Wiviott, vice president for clinical trials research and administration at Massachusetts General Hospital and Brigham and Women’s Hospital and a cardiologist at Harvard Medical School, Boston.

Troponin elevations in stable coronary patients undergoing PCI may have a different underlying mechanism than elevated troponins in patients undergoing PCI for an acute coronary syndrome, he added. In stable CAD patients, the phenomenon may be more related to atherosclerosis than to platelet activation and thrombosis.

During a panel discussion, Sunil V. Rao, MD, said cardiologists are “probably going to have to go back to the drawing board and think about what kinds of events are really, really important.”

American Heart Association

[email protected]

SOURCE: Silvain J. AHA 2020. Session LBS 3.

Iron supplementation reduces heart failure (HF) readmissions in iron-deficient patients hospitalized for acute HF, according to results of the AFFIRM-AHF trial.

After 52 weeks, intravenous ferric carboxymaltose (Ferinject) reduced the risk of total HF hospitalizations and cardiovascular (CV) death by 21% compared with placebo (293 vs 372 events; rate ratio [RR] 0.79; 95% CI, 0.62 - 1.01).

Although the composite primary endpoint failed to achieve statistical significance, it was driven by a significant 26% reduction in the risk of total HF hospital readmissions (P = .013) without an effect on CV mortality (P =.809).

Because the management and follow-up of patients was affected by the COVID-19 pandemic, a prespecified sensitivity analysis was performed that censored patients in each country at the date when its first COVID-19 patient was reported, explained principal investigator Piotr Ponikowski, MD, PhD, Wroclaw Medical University, Wroclaw, Poland.

That analysis revealed a significant 30% reduction in total HF readmissions (P = .005) in patients receiving ferric carboxymaltose (FCM), as well as significant benefits on the primary composite and secondary endpoints.

Notably, 80% of patients required only one or two injections and HF hospitalizations were reduced irrespective of anemia status.

“Iron deficiency should be searched in patients hospitalized with acute heart failure — assessed using a simple blood test — and is now an important therapeutic target,” Ponikowski said at the virtual American Heart Association (AHA) Scientific Sessions 2020.

The results were also published simultaneously in The Lancet.

Iron deficiency is present in up to 70% of patients with acute HF and a predictor of poor outcome, independent of anemia and ejection fraction, he noted.

The FAIR-HF, CONFIRM-HF, and EFFECT-HF trials demonstrated that IV iron supplementation improves exercise capacity, symptoms, and quality of life in iron-deficient HF patients.

The study was sponsored by Vifor International. Ponikowski has received research grants and personal fees from Vifor Pharma; and personal fees from Amgen, Bayer, Novartis, Abbott Vascular, Boehringer Ingelheim, Merck, Pfizer, Servier, AstraZeneca, Berlin Chemie, Cibiem, Renal Guard Solutions Bristol-Myers Squibb, and Impulse Dynamics.

Pfeffer reported honoraria from AstraZeneca, Corvidia, GlaxoSmithKline, Jazz, MyoKardia, Novartis, Roche, Sanofi, and Servier; other relationships with DalCor and Novo Nordisk; research grants from Novartis; and an ownership interest in DalCor. Sweitzer reported research payments from Merck and Novartis; and consulting fees from Myocardia.

McMurray reported relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Novartis, and Servier. Yancy reported a relationship with Abbott and JAMA Network.

Lancet. Published online November 13, 2020. Full text


American Heart Association Scientific Sessions 2020: Presented November 13, 2020.


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

Iron supplementation reduces heart failure (HF) readmissions in iron-deficient patients hospitalized for acute HF, according to results of the AFFIRM-AHF trial.

After 52 weeks, intravenous ferric carboxymaltose (Ferinject) reduced the risk of total HF hospitalizations and cardiovascular (CV) death by 21% compared with placebo (293 vs 372 events; rate ratio [RR] 0.79; 95% CI, 0.62 - 1.01).

Although the composite primary endpoint failed to achieve statistical significance, it was driven by a significant 26% reduction in the risk of total HF hospital readmissions (P = .013) without an effect on CV mortality (P =.809).

Because the management and follow-up of patients was affected by the COVID-19 pandemic, a prespecified sensitivity analysis was performed that censored patients in each country at the date when its first COVID-19 patient was reported, explained principal investigator Piotr Ponikowski, MD, PhD, Wroclaw Medical University, Wroclaw, Poland.

That analysis revealed a significant 30% reduction in total HF readmissions (P = .005) in patients receiving ferric carboxymaltose (FCM), as well as significant benefits on the primary composite and secondary endpoints.

Notably, 80% of patients required only one or two injections and HF hospitalizations were reduced irrespective of anemia status.

“Iron deficiency should be searched in patients hospitalized with acute heart failure — assessed using a simple blood test — and is now an important therapeutic target,” Ponikowski said at the virtual American Heart Association (AHA) Scientific Sessions 2020.

The results were also published simultaneously in The Lancet.

Iron deficiency is present in up to 70% of patients with acute HF and a predictor of poor outcome, independent of anemia and ejection fraction, he noted.

The FAIR-HF, CONFIRM-HF, and EFFECT-HF trials demonstrated that IV iron supplementation improves exercise capacity, symptoms, and quality of life in iron-deficient HF patients.

The study was sponsored by Vifor International. Ponikowski has received research grants and personal fees from Vifor Pharma; and personal fees from Amgen, Bayer, Novartis, Abbott Vascular, Boehringer Ingelheim, Merck, Pfizer, Servier, AstraZeneca, Berlin Chemie, Cibiem, Renal Guard Solutions Bristol-Myers Squibb, and Impulse Dynamics.

Pfeffer reported honoraria from AstraZeneca, Corvidia, GlaxoSmithKline, Jazz, MyoKardia, Novartis, Roche, Sanofi, and Servier; other relationships with DalCor and Novo Nordisk; research grants from Novartis; and an ownership interest in DalCor. Sweitzer reported research payments from Merck and Novartis; and consulting fees from Myocardia.

McMurray reported relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Novartis, and Servier. Yancy reported a relationship with Abbott and JAMA Network.

Lancet. Published online November 13, 2020. Full text


American Heart Association Scientific Sessions 2020: Presented November 13, 2020.


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

Iron supplementation reduces heart failure (HF) readmissions in iron-deficient patients hospitalized for acute HF, according to results of the AFFIRM-AHF trial.

After 52 weeks, intravenous ferric carboxymaltose (Ferinject) reduced the risk of total HF hospitalizations and cardiovascular (CV) death by 21% compared with placebo (293 vs 372 events; rate ratio [RR] 0.79; 95% CI, 0.62 - 1.01).

Although the composite primary endpoint failed to achieve statistical significance, it was driven by a significant 26% reduction in the risk of total HF hospital readmissions (P = .013) without an effect on CV mortality (P =.809).

Because the management and follow-up of patients was affected by the COVID-19 pandemic, a prespecified sensitivity analysis was performed that censored patients in each country at the date when its first COVID-19 patient was reported, explained principal investigator Piotr Ponikowski, MD, PhD, Wroclaw Medical University, Wroclaw, Poland.

That analysis revealed a significant 30% reduction in total HF readmissions (P = .005) in patients receiving ferric carboxymaltose (FCM), as well as significant benefits on the primary composite and secondary endpoints.

Notably, 80% of patients required only one or two injections and HF hospitalizations were reduced irrespective of anemia status.

“Iron deficiency should be searched in patients hospitalized with acute heart failure — assessed using a simple blood test — and is now an important therapeutic target,” Ponikowski said at the virtual American Heart Association (AHA) Scientific Sessions 2020.

The results were also published simultaneously in The Lancet.

Iron deficiency is present in up to 70% of patients with acute HF and a predictor of poor outcome, independent of anemia and ejection fraction, he noted.

The FAIR-HF, CONFIRM-HF, and EFFECT-HF trials demonstrated that IV iron supplementation improves exercise capacity, symptoms, and quality of life in iron-deficient HF patients.

The study was sponsored by Vifor International. Ponikowski has received research grants and personal fees from Vifor Pharma; and personal fees from Amgen, Bayer, Novartis, Abbott Vascular, Boehringer Ingelheim, Merck, Pfizer, Servier, AstraZeneca, Berlin Chemie, Cibiem, Renal Guard Solutions Bristol-Myers Squibb, and Impulse Dynamics.

Pfeffer reported honoraria from AstraZeneca, Corvidia, GlaxoSmithKline, Jazz, MyoKardia, Novartis, Roche, Sanofi, and Servier; other relationships with DalCor and Novo Nordisk; research grants from Novartis; and an ownership interest in DalCor. Sweitzer reported research payments from Merck and Novartis; and consulting fees from Myocardia.

McMurray reported relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Novartis, and Servier. Yancy reported a relationship with Abbott and JAMA Network.

Lancet. Published online November 13, 2020. Full text


American Heart Association Scientific Sessions 2020: Presented November 13, 2020.


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

A once-daily polypill containing four drugs to lower blood pressure and LDL cholesterol reduced major adverse cardiovascular events by 21% relative to placebo in people at intermediate cardiovascular risk in the landmark TIPS-3 trial.

And with the addition of aspirin at 75 mg per day the combination achieved an even more robust 31% relative risk reduction, investigators reported at the.

“Aspirin contributes importantly to the benefits,” Salim Yusuf, MD, DPhil, emphasized in presenting the International Polycap Study (TIPS-3) results jointly with study coprincipal investigator Prem Pais, MD, at the virtual American Heart Association scientific sessions.

The multinational study provides powerful new support for a broad, population health–based approach to primary cardiovascular prevention.

“If half of eligible people [were to] use a polypill with aspirin, 3-5 million cardiovascular events per year would be avoided globally,” according to Dr. Yusuf, professor of medicine and director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“This is likely a cost-effective strategy to meet global targets of reducing cardiovascular disease by 30% by 2020,” added Dr. Pais of St. John’s Research Institute in Bangalore, India.

TIPS-3 included 5,713 participants at intermediate cardiovascular risk, with an estimated event risk of 1.8% per year using the INTERHEART Risk Score. Half were women. More than 80% of participants had hypertension, and nearly 40% had diabetes or impaired fasting glucose. Nearly 90% of participants came from India, the Philippines, Malaysia, Indonesia, or Bangladesh. All participants received advice about lifestyle management.

They were then randomized to receive a polypill or placebo, and then each group was further randomized to receive 75 mg/day of aspirin or matching placebo. The polypill contained 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril.

During a mean 4.6 years of follow-up, the primary composite major adverse cardiovascular event rate occurred in 4.4% of the polypill group, 4.1% of the polypill-plus-aspirin group, and 5.8% of the double-placebo group. This translated to a 21% reduction in cardiovascular disease with the polypill, a 31% reduction with polypill plus aspirin, and a 14% reduction in the composite of cardiovascular death, MI, or stroke with aspirin alone.

The polypill and placebo groups diverged in terms of the primary outcome starting about 6 months into the study, Dr. Pais noted.

Serious adverse events were less common with the polypill than with placebo. Importantly, there was no difference in major, minor, or GI bleeding between the polypill-plus-aspirin group and placebo-treated controls. Dr. Yusuf attributed the lack of excess bleeding in aspirin recipients to two factors: people with a history of bleeding or GI symptoms were excluded from TIPS-3, and the dose of aspirin used was lower than in other primary prevention trials, where bleeding offset the reduction in cardiovascular events.

Nonadherence was a major issue in TIPS-3, mainly because of delays in polypill production and distribution, coupled late in the trial with the COVID-19 pandemic. The nonadherence rate was 19% at 2 years, 32% at 4 years, and 43% at the study’s end. Only 5% of discontinuations were due to side effects. In a sensitivity analysis carried out in participants without discontinuation for nonmedical reasons, the benefits of the polypill plus aspirin were larger than in the overall study: a 39% relative risk reduction in the primary endpoint that probably offers a more accurate picture of the combination’s likely real-world performance.

Discussant Anushka Patel, MBBS, PhD, noted that TIPS-3 is the third randomized trial to provide direct evidence that a polypill-based strategy improves clinical outcomes. The effect sizes of the benefits – a 20%-30% reduction in major cardiovascular events – has been consistent in TIPS-3, PolyIran, and HOPE-3, each of which tested a different polypill drug combination.

“If implementation and adherence challenges can be addressed at the system, prescriber, and patient levels, and if high-quality polypills can be made affordable, the public health impact could actually be enormous,” said Dr. Patel, chief scientist at the George Institute for Global Health and professor of medicine at the University of New South Wales in Sydney, Australia.

However, she parted company with Dr. Yusuf regarding routine incorporation of aspirin into polypills.

“I think the totality of evidence would still probably favor taking an individualized approach that also considers bleeding risk,” the cardiologist said.

Donald Lloyd-Jones, MD, who chaired a press conference highlighting TIPS-3, declared, “You’re seeing a paradigm shift right here in front of your eyes today. This could be a game changer in terms of preventing large numbers of cardiovascular events.”

While TIPS-3 was conducted mainly in low- and middle-income countries, it’s important to recognize that’s where 75% of cardiovascular events and cardiovascular deaths now occur.

“This is very much a disease that has emerged in the developing world,” commented Dr. Lloyd-Jones, the AHA president-elect, chair of the AHA Council on Scientific Sessions Programming, and professor and chair of the department of preventive medicine at Northwestern University, Chicago.

He also sees a polypill strategy for primary cardiovascular prevention as highly viable in high-resource countries. It makes sense to employ it there initially in underserved communities, where a polypill-based approach sidesteps difficulties in monitoring care and adjusting medication doses due to reduced access to health care while minimizing cost and adherence issues, he added.

Dr. Yusuf and Dr. Pais reported receiving institutional research support from the TIPS-3 major sponsors: the Wellcome Trust, Cadila Pharmaceuticals, the Canadian Institutes of Health Research, and the Heart and Stroke Foundation of Canada.

Simultaneously with their presentation at AHA 2020, the TIPS-3 results were published online in the New England Journal of Medicine.
 

[email protected]

SOURCE: Yusuf, S. AHA 2020. Session LBS.02.

A once-daily polypill containing four drugs to lower blood pressure and LDL cholesterol reduced major adverse cardiovascular events by 21% relative to placebo in people at intermediate cardiovascular risk in the landmark TIPS-3 trial.

And with the addition of aspirin at 75 mg per day the combination achieved an even more robust 31% relative risk reduction, investigators reported at the.

“Aspirin contributes importantly to the benefits,” Salim Yusuf, MD, DPhil, emphasized in presenting the International Polycap Study (TIPS-3) results jointly with study coprincipal investigator Prem Pais, MD, at the virtual American Heart Association scientific sessions.

The multinational study provides powerful new support for a broad, population health–based approach to primary cardiovascular prevention.

“If half of eligible people [were to] use a polypill with aspirin, 3-5 million cardiovascular events per year would be avoided globally,” according to Dr. Yusuf, professor of medicine and director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“This is likely a cost-effective strategy to meet global targets of reducing cardiovascular disease by 30% by 2020,” added Dr. Pais of St. John’s Research Institute in Bangalore, India.

TIPS-3 included 5,713 participants at intermediate cardiovascular risk, with an estimated event risk of 1.8% per year using the INTERHEART Risk Score. Half were women. More than 80% of participants had hypertension, and nearly 40% had diabetes or impaired fasting glucose. Nearly 90% of participants came from India, the Philippines, Malaysia, Indonesia, or Bangladesh. All participants received advice about lifestyle management.

They were then randomized to receive a polypill or placebo, and then each group was further randomized to receive 75 mg/day of aspirin or matching placebo. The polypill contained 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril.

During a mean 4.6 years of follow-up, the primary composite major adverse cardiovascular event rate occurred in 4.4% of the polypill group, 4.1% of the polypill-plus-aspirin group, and 5.8% of the double-placebo group. This translated to a 21% reduction in cardiovascular disease with the polypill, a 31% reduction with polypill plus aspirin, and a 14% reduction in the composite of cardiovascular death, MI, or stroke with aspirin alone.

The polypill and placebo groups diverged in terms of the primary outcome starting about 6 months into the study, Dr. Pais noted.

Serious adverse events were less common with the polypill than with placebo. Importantly, there was no difference in major, minor, or GI bleeding between the polypill-plus-aspirin group and placebo-treated controls. Dr. Yusuf attributed the lack of excess bleeding in aspirin recipients to two factors: people with a history of bleeding or GI symptoms were excluded from TIPS-3, and the dose of aspirin used was lower than in other primary prevention trials, where bleeding offset the reduction in cardiovascular events.

Nonadherence was a major issue in TIPS-3, mainly because of delays in polypill production and distribution, coupled late in the trial with the COVID-19 pandemic. The nonadherence rate was 19% at 2 years, 32% at 4 years, and 43% at the study’s end. Only 5% of discontinuations were due to side effects. In a sensitivity analysis carried out in participants without discontinuation for nonmedical reasons, the benefits of the polypill plus aspirin were larger than in the overall study: a 39% relative risk reduction in the primary endpoint that probably offers a more accurate picture of the combination’s likely real-world performance.

Discussant Anushka Patel, MBBS, PhD, noted that TIPS-3 is the third randomized trial to provide direct evidence that a polypill-based strategy improves clinical outcomes. The effect sizes of the benefits – a 20%-30% reduction in major cardiovascular events – has been consistent in TIPS-3, PolyIran, and HOPE-3, each of which tested a different polypill drug combination.

“If implementation and adherence challenges can be addressed at the system, prescriber, and patient levels, and if high-quality polypills can be made affordable, the public health impact could actually be enormous,” said Dr. Patel, chief scientist at the George Institute for Global Health and professor of medicine at the University of New South Wales in Sydney, Australia.

However, she parted company with Dr. Yusuf regarding routine incorporation of aspirin into polypills.

“I think the totality of evidence would still probably favor taking an individualized approach that also considers bleeding risk,” the cardiologist said.

Donald Lloyd-Jones, MD, who chaired a press conference highlighting TIPS-3, declared, “You’re seeing a paradigm shift right here in front of your eyes today. This could be a game changer in terms of preventing large numbers of cardiovascular events.”

While TIPS-3 was conducted mainly in low- and middle-income countries, it’s important to recognize that’s where 75% of cardiovascular events and cardiovascular deaths now occur.

“This is very much a disease that has emerged in the developing world,” commented Dr. Lloyd-Jones, the AHA president-elect, chair of the AHA Council on Scientific Sessions Programming, and professor and chair of the department of preventive medicine at Northwestern University, Chicago.

He also sees a polypill strategy for primary cardiovascular prevention as highly viable in high-resource countries. It makes sense to employ it there initially in underserved communities, where a polypill-based approach sidesteps difficulties in monitoring care and adjusting medication doses due to reduced access to health care while minimizing cost and adherence issues, he added.

Dr. Yusuf and Dr. Pais reported receiving institutional research support from the TIPS-3 major sponsors: the Wellcome Trust, Cadila Pharmaceuticals, the Canadian Institutes of Health Research, and the Heart and Stroke Foundation of Canada.

Simultaneously with their presentation at AHA 2020, the TIPS-3 results were published online in the New England Journal of Medicine.
 

[email protected]

SOURCE: Yusuf, S. AHA 2020. Session LBS.02.

A once-daily polypill containing four drugs to lower blood pressure and LDL cholesterol reduced major adverse cardiovascular events by 21% relative to placebo in people at intermediate cardiovascular risk in the landmark TIPS-3 trial.

And with the addition of aspirin at 75 mg per day the combination achieved an even more robust 31% relative risk reduction, investigators reported at the.

“Aspirin contributes importantly to the benefits,” Salim Yusuf, MD, DPhil, emphasized in presenting the International Polycap Study (TIPS-3) results jointly with study coprincipal investigator Prem Pais, MD, at the virtual American Heart Association scientific sessions.

The multinational study provides powerful new support for a broad, population health–based approach to primary cardiovascular prevention.

“If half of eligible people [were to] use a polypill with aspirin, 3-5 million cardiovascular events per year would be avoided globally,” according to Dr. Yusuf, professor of medicine and director of the Population Health Research Institute at McMaster University in Hamilton, Ont.

“This is likely a cost-effective strategy to meet global targets of reducing cardiovascular disease by 30% by 2020,” added Dr. Pais of St. John’s Research Institute in Bangalore, India.

TIPS-3 included 5,713 participants at intermediate cardiovascular risk, with an estimated event risk of 1.8% per year using the INTERHEART Risk Score. Half were women. More than 80% of participants had hypertension, and nearly 40% had diabetes or impaired fasting glucose. Nearly 90% of participants came from India, the Philippines, Malaysia, Indonesia, or Bangladesh. All participants received advice about lifestyle management.

They were then randomized to receive a polypill or placebo, and then each group was further randomized to receive 75 mg/day of aspirin or matching placebo. The polypill contained 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril.

During a mean 4.6 years of follow-up, the primary composite major adverse cardiovascular event rate occurred in 4.4% of the polypill group, 4.1% of the polypill-plus-aspirin group, and 5.8% of the double-placebo group. This translated to a 21% reduction in cardiovascular disease with the polypill, a 31% reduction with polypill plus aspirin, and a 14% reduction in the composite of cardiovascular death, MI, or stroke with aspirin alone.

The polypill and placebo groups diverged in terms of the primary outcome starting about 6 months into the study, Dr. Pais noted.

Serious adverse events were less common with the polypill than with placebo. Importantly, there was no difference in major, minor, or GI bleeding between the polypill-plus-aspirin group and placebo-treated controls. Dr. Yusuf attributed the lack of excess bleeding in aspirin recipients to two factors: people with a history of bleeding or GI symptoms were excluded from TIPS-3, and the dose of aspirin used was lower than in other primary prevention trials, where bleeding offset the reduction in cardiovascular events.

Nonadherence was a major issue in TIPS-3, mainly because of delays in polypill production and distribution, coupled late in the trial with the COVID-19 pandemic. The nonadherence rate was 19% at 2 years, 32% at 4 years, and 43% at the study’s end. Only 5% of discontinuations were due to side effects. In a sensitivity analysis carried out in participants without discontinuation for nonmedical reasons, the benefits of the polypill plus aspirin were larger than in the overall study: a 39% relative risk reduction in the primary endpoint that probably offers a more accurate picture of the combination’s likely real-world performance.

Discussant Anushka Patel, MBBS, PhD, noted that TIPS-3 is the third randomized trial to provide direct evidence that a polypill-based strategy improves clinical outcomes. The effect sizes of the benefits – a 20%-30% reduction in major cardiovascular events – has been consistent in TIPS-3, PolyIran, and HOPE-3, each of which tested a different polypill drug combination.

“If implementation and adherence challenges can be addressed at the system, prescriber, and patient levels, and if high-quality polypills can be made affordable, the public health impact could actually be enormous,” said Dr. Patel, chief scientist at the George Institute for Global Health and professor of medicine at the University of New South Wales in Sydney, Australia.

However, she parted company with Dr. Yusuf regarding routine incorporation of aspirin into polypills.

“I think the totality of evidence would still probably favor taking an individualized approach that also considers bleeding risk,” the cardiologist said.

Donald Lloyd-Jones, MD, who chaired a press conference highlighting TIPS-3, declared, “You’re seeing a paradigm shift right here in front of your eyes today. This could be a game changer in terms of preventing large numbers of cardiovascular events.”

While TIPS-3 was conducted mainly in low- and middle-income countries, it’s important to recognize that’s where 75% of cardiovascular events and cardiovascular deaths now occur.

“This is very much a disease that has emerged in the developing world,” commented Dr. Lloyd-Jones, the AHA president-elect, chair of the AHA Council on Scientific Sessions Programming, and professor and chair of the department of preventive medicine at Northwestern University, Chicago.

He also sees a polypill strategy for primary cardiovascular prevention as highly viable in high-resource countries. It makes sense to employ it there initially in underserved communities, where a polypill-based approach sidesteps difficulties in monitoring care and adjusting medication doses due to reduced access to health care while minimizing cost and adherence issues, he added.

Dr. Yusuf and Dr. Pais reported receiving institutional research support from the TIPS-3 major sponsors: the Wellcome Trust, Cadila Pharmaceuticals, the Canadian Institutes of Health Research, and the Heart and Stroke Foundation of Canada.

Simultaneously with their presentation at AHA 2020, the TIPS-3 results were published online in the New England Journal of Medicine.
 

[email protected]

SOURCE: Yusuf, S. AHA 2020. Session LBS.02.

While Phi (or the Golden Ratio) and Leonardo da Vinci’s neoclassical canons have been used as traditional mathematical approaches to assess and calculate beauty, there may be more than meets the eye.

VLG/Getty Images

A novel model to describe or measure attractiveness has been described by Chicago plastic surgeon Steven Dayan, MD, whereby attractiveness is defined as a 3-dimensional model defined by beauty, genuineness, and self-esteem.¹ This model was created to denote “natural beauty,” both at baseline and after cosmetic procedures, which is what many physicians and patients ideally want to achieve after any aesthetic procedure.

In this model, when all three variables are at a maximum, a desirable attractive appearance is achieved that can be interpreted as “natural.” In his paper introducing this novel model, Dr. Dayan wrote that similar to the time-space dilemma, attractiveness “is relative, dynamic, and highly dependent on the position of the projector and the interpreter.” The 3-D cube of attractiveness “is therefore contained within a fourth dimension that takes into account the perspective of the judger.”

Similarly, in a pilot study,² Dr. Dayan and colleagues also demonstrated that visually blind individuals can detect beauty. “This study further isolates the nature of beauty as a primal form of messaging that is subconsciously appreciated via embodied senses other than vision,” he and his coauthors wrote.

This observational study consisted of 8 blind and 10 nonblind test subjects and 6 models who were categorized into predetermined beauty categories. Test subjects were blindfolded and unblindfolded during their assessments. All groups rated those models, who were preselected as more beautiful, higher, except for the blindfolded, nonblind group – demonstrating a primal or neural pathway ability to perceive attractiveness in blind individuals. The study, “revealed that beauty is not only detected by visual sense but also through embodied senses other than sight,” the authors commented.

It should be noted that sometimes ethnic features and features that are unique outside of the neoclassical canons or golden ratio can also uniquely make people look more attractive. Ethnic variations in beauty standards exist and need to be further studied and celebrated. There is certainly high expertise and an art required to perceiving aesthetics and performing aesthetic procedures, further exemplified by the complex nature of the different models and mathematical approaches of assessing it. These newer models account for attractiveness that may also start on the inside or beyond purely visual perception.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References:

1. Dayan S, Romero DH. J Cosmet Dermatol. 2018 Oct;17(5):925-30.

2. Dayan SH et al. Dermatol Surg. 2020 Oct;46(10):1317-22.

While Phi (or the Golden Ratio) and Leonardo da Vinci’s neoclassical canons have been used as traditional mathematical approaches to assess and calculate beauty, there may be more than meets the eye.

VLG/Getty Images

A novel model to describe or measure attractiveness has been described by Chicago plastic surgeon Steven Dayan, MD, whereby attractiveness is defined as a 3-dimensional model defined by beauty, genuineness, and self-esteem.¹ This model was created to denote “natural beauty,” both at baseline and after cosmetic procedures, which is what many physicians and patients ideally want to achieve after any aesthetic procedure.

In this model, when all three variables are at a maximum, a desirable attractive appearance is achieved that can be interpreted as “natural.” In his paper introducing this novel model, Dr. Dayan wrote that similar to the time-space dilemma, attractiveness “is relative, dynamic, and highly dependent on the position of the projector and the interpreter.” The 3-D cube of attractiveness “is therefore contained within a fourth dimension that takes into account the perspective of the judger.”

Similarly, in a pilot study,² Dr. Dayan and colleagues also demonstrated that visually blind individuals can detect beauty. “This study further isolates the nature of beauty as a primal form of messaging that is subconsciously appreciated via embodied senses other than vision,” he and his coauthors wrote.

This observational study consisted of 8 blind and 10 nonblind test subjects and 6 models who were categorized into predetermined beauty categories. Test subjects were blindfolded and unblindfolded during their assessments. All groups rated those models, who were preselected as more beautiful, higher, except for the blindfolded, nonblind group – demonstrating a primal or neural pathway ability to perceive attractiveness in blind individuals. The study, “revealed that beauty is not only detected by visual sense but also through embodied senses other than sight,” the authors commented.

It should be noted that sometimes ethnic features and features that are unique outside of the neoclassical canons or golden ratio can also uniquely make people look more attractive. Ethnic variations in beauty standards exist and need to be further studied and celebrated. There is certainly high expertise and an art required to perceiving aesthetics and performing aesthetic procedures, further exemplified by the complex nature of the different models and mathematical approaches of assessing it. These newer models account for attractiveness that may also start on the inside or beyond purely visual perception.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References:

1. Dayan S, Romero DH. J Cosmet Dermatol. 2018 Oct;17(5):925-30.

2. Dayan SH et al. Dermatol Surg. 2020 Oct;46(10):1317-22.

While Phi (or the Golden Ratio) and Leonardo da Vinci’s neoclassical canons have been used as traditional mathematical approaches to assess and calculate beauty, there may be more than meets the eye.

VLG/Getty Images

A novel model to describe or measure attractiveness has been described by Chicago plastic surgeon Steven Dayan, MD, whereby attractiveness is defined as a 3-dimensional model defined by beauty, genuineness, and self-esteem.¹ This model was created to denote “natural beauty,” both at baseline and after cosmetic procedures, which is what many physicians and patients ideally want to achieve after any aesthetic procedure.

In this model, when all three variables are at a maximum, a desirable attractive appearance is achieved that can be interpreted as “natural.” In his paper introducing this novel model, Dr. Dayan wrote that similar to the time-space dilemma, attractiveness “is relative, dynamic, and highly dependent on the position of the projector and the interpreter.” The 3-D cube of attractiveness “is therefore contained within a fourth dimension that takes into account the perspective of the judger.”

Similarly, in a pilot study,² Dr. Dayan and colleagues also demonstrated that visually blind individuals can detect beauty. “This study further isolates the nature of beauty as a primal form of messaging that is subconsciously appreciated via embodied senses other than vision,” he and his coauthors wrote.

This observational study consisted of 8 blind and 10 nonblind test subjects and 6 models who were categorized into predetermined beauty categories. Test subjects were blindfolded and unblindfolded during their assessments. All groups rated those models, who were preselected as more beautiful, higher, except for the blindfolded, nonblind group – demonstrating a primal or neural pathway ability to perceive attractiveness in blind individuals. The study, “revealed that beauty is not only detected by visual sense but also through embodied senses other than sight,” the authors commented.

It should be noted that sometimes ethnic features and features that are unique outside of the neoclassical canons or golden ratio can also uniquely make people look more attractive. Ethnic variations in beauty standards exist and need to be further studied and celebrated. There is certainly high expertise and an art required to perceiving aesthetics and performing aesthetic procedures, further exemplified by the complex nature of the different models and mathematical approaches of assessing it. These newer models account for attractiveness that may also start on the inside or beyond purely visual perception.
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References:

1. Dayan S, Romero DH. J Cosmet Dermatol. 2018 Oct;17(5):925-30.

2. Dayan SH et al. Dermatol Surg. 2020 Oct;46(10):1317-22.

Omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, safely produced a significant but modest improvement in heart failure events or cardiovascular death in a pivotal trial with HFrEF patients, leaving experts unsure about the role this drug could have on top of an already crowded list of four first-line drug classes for this condition.

“It remains to be investigated and discussed where omecamtiv mecarbil fits in” the overall approach to treating patients with heart failure with reduced ejection fraction (HFrEF), commented Paul Heidenreich, MD, designated discussant for the report at the virtual scientific sessions of the American Heart Association.

Room for a fifth HFrEF drug?

In addition to the limited benefit, another question raised by the trial is how OM would perform when used on top of what is now considered standard, quadruple therapy for most HFrEF patients: a beta-blocker, a mineralocorticoid receptor antagonist, sacubitril-valsartan (Entresto), and an agent from the sodium glucose co-transporter 2 (SGLT2) inhibitor class, specifically dapagliflozin (Farxiga) or empagliflozin (Jardiance). During the period when the new OM trial was run, 2017-2019, the SGLT2 inhibitors had not yet been established as a key part of standard HFrEF treatment, and hence fewer than 3% of enrolled patients were on one of these drugs.

Because of this evidence gap, OM “can’t be across the board a fifth drug on top of standard treatment,” based on the new results, cautioned Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University School of Medicine.

The positives of omecamtiv mercarbil

But in addition to its positive result in the GALACTIC-HF trial, treatment with OM showed other attractive characteristics in a study that treated a wide spectrum of 4,120 patients with HFrEF as well as including 4,112 patients randomized to placebo. Most notably, OM had a very clean safety profile, with adverse event rates similar to placebo patients across all adverse event subtypes, as well as causing no drop in blood pressure and actually an average 2.0–mm Hg increase in systolic blood pressure, no increase in potassium, no apparent impact on renal function, and a small but significant decline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) compared with placebo.

This coupled with the novel mechanism of action of OM – direct augmentation of cardiac sarcomere function by increasing myosin attachment to actin – suggests that OM can be safely added on top of existing HFrEF treatment to provide an unique and incremental benefit.

“Other heart failure drugs [like beta-blockers and sacubitril-valsartan] lower blood pressure, so what can happen is that clinicians run out of room to add full dosages” when patients’ pressures fall too low, commented Gregory D. Lewis, MD, head of Heart Failure at Massachusetts General Hospital in Boston. He is principle investigator for another OM trial, METEORIC-HF, which is examining the possible impact of the drug on exercise capacity in a randomized study with about 270 HFrEF patients.

If the METEORIC-HF results can could confirm some of the GALACTIC-HF results that suggested improvements in patient function, the combined data could potentially lead to regulatory approval for U.S. marketing of the drug, Dr. Lewis suggested. Results from that study are expected in 2021, he said in an interview.

The GALACTIC-HF results hinted at possible functional improvement after 24 weeks on treatment among patients who required hospitalization as measured by the Kansas City Cardiomyopathy Questionnaire, which measures quality life. However, this difference failed to meet the study’s prespecified definition of a significant effect.

Another intriguing suggestion of focused benefit was in patients with a left ventricular ejection fraction at or below the median in GALACTIC-HF of 28%. In that subgroup, OM treatment was linked with a significant 16% relative reduction in the primary endpoint compared with placebo, while it had no significant effect in the other 50% of patients with higher ejection fractions. (The maximum left ventricular ejection fraction for enrollment was 35%.) This apparent subgroup interaction was statistically significant, reported Dr. Teerlink, a professor of medicine at the University of California, San Francisco, and director of Heart Failure at the San Francisco V.A. Medical Center.

Further analysis of the study data “will provide greater insight into subgroups who may demonstrate greater benefit, such as patients with lower ejection fraction in whom improving cardiac function may have a greater role,” he said. The idea that a drug that improves myocyte function at the molecular level could especially benefit patients with the lowest ejection fractions is “biologically plausible,” Dr. Teerlink said.

This scenario looks reasonable, and could make OM something of a niche drug for at least the near term, said Dr. Mann.

The world’s first myotropic drug

Possibly the most notable aspect of GALACTIC-HF is that it proved the efficacy, modest though it was, of a novel drug mechanism that fulfills a decades-long quest of heart failure researchers: a safe way to improve the heart’s pumping action.

“For years, the heart failure community struggled with treatment to improve cardiac performance, but invariably it ended in disaster by worsening cardiac deaths,” problems that led to abandonment of early inotropic drugs more than a generation ago, noted Dr. Mann.

But a more nuanced approach to inotropic agents recently has emerged from Dr. Teerlink and his associates, built on the premise that the dangers seen years ago related to the calcium modulations they caused. Their new paradigm is that the dangers of these “calcitropic” agents can be sidestepped with different agents that either mediate their effects via myosin, the myotropes like OM, or mitochondrial effects from mitotropic drugs.

The inotrope debacle from the 1990s made that drug-class name “a dirty word that causes fear and loathing in the heart failure community,” observed Dr. Mann. While the term myotrope has not yet really caught on, “If omecamtiv mecarbil starts getting used in routine practice, then I think you’ll start seeing uptake of the term myotrope,” he predicted.

GALACTIC-HF was sponsored by Amgen, Cytokinetics, and Servier, the companies developing omecamtiv mecarbil. Dr. Teerlink has received research support from and been a consultant to Amgen, Cytokinetics, and Servier, as well as Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Merck, and Novartis. Dr. Heidenreich had no disclosures. Dr. Mann is on a steering committee for a trial sponsored by Novartis and has no other commercial disclosures. Dr. Lewis is principal investigator for a trial of omecamtiv mecarbil and has no other commercial disclosures.

[email protected]

On Twitter @mitchelzoler

Omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, safely produced a significant but modest improvement in heart failure events or cardiovascular death in a pivotal trial with HFrEF patients, leaving experts unsure about the role this drug could have on top of an already crowded list of four first-line drug classes for this condition.

“It remains to be investigated and discussed where omecamtiv mecarbil fits in” the overall approach to treating patients with heart failure with reduced ejection fraction (HFrEF), commented Paul Heidenreich, MD, designated discussant for the report at the virtual scientific sessions of the American Heart Association.

Room for a fifth HFrEF drug?

In addition to the limited benefit, another question raised by the trial is how OM would perform when used on top of what is now considered standard, quadruple therapy for most HFrEF patients: a beta-blocker, a mineralocorticoid receptor antagonist, sacubitril-valsartan (Entresto), and an agent from the sodium glucose co-transporter 2 (SGLT2) inhibitor class, specifically dapagliflozin (Farxiga) or empagliflozin (Jardiance). During the period when the new OM trial was run, 2017-2019, the SGLT2 inhibitors had not yet been established as a key part of standard HFrEF treatment, and hence fewer than 3% of enrolled patients were on one of these drugs.

Because of this evidence gap, OM “can’t be across the board a fifth drug on top of standard treatment,” based on the new results, cautioned Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University School of Medicine.

The positives of omecamtiv mercarbil

But in addition to its positive result in the GALACTIC-HF trial, treatment with OM showed other attractive characteristics in a study that treated a wide spectrum of 4,120 patients with HFrEF as well as including 4,112 patients randomized to placebo. Most notably, OM had a very clean safety profile, with adverse event rates similar to placebo patients across all adverse event subtypes, as well as causing no drop in blood pressure and actually an average 2.0–mm Hg increase in systolic blood pressure, no increase in potassium, no apparent impact on renal function, and a small but significant decline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) compared with placebo.

This coupled with the novel mechanism of action of OM – direct augmentation of cardiac sarcomere function by increasing myosin attachment to actin – suggests that OM can be safely added on top of existing HFrEF treatment to provide an unique and incremental benefit.

“Other heart failure drugs [like beta-blockers and sacubitril-valsartan] lower blood pressure, so what can happen is that clinicians run out of room to add full dosages” when patients’ pressures fall too low, commented Gregory D. Lewis, MD, head of Heart Failure at Massachusetts General Hospital in Boston. He is principle investigator for another OM trial, METEORIC-HF, which is examining the possible impact of the drug on exercise capacity in a randomized study with about 270 HFrEF patients.

If the METEORIC-HF results can could confirm some of the GALACTIC-HF results that suggested improvements in patient function, the combined data could potentially lead to regulatory approval for U.S. marketing of the drug, Dr. Lewis suggested. Results from that study are expected in 2021, he said in an interview.

The GALACTIC-HF results hinted at possible functional improvement after 24 weeks on treatment among patients who required hospitalization as measured by the Kansas City Cardiomyopathy Questionnaire, which measures quality life. However, this difference failed to meet the study’s prespecified definition of a significant effect.

Another intriguing suggestion of focused benefit was in patients with a left ventricular ejection fraction at or below the median in GALACTIC-HF of 28%. In that subgroup, OM treatment was linked with a significant 16% relative reduction in the primary endpoint compared with placebo, while it had no significant effect in the other 50% of patients with higher ejection fractions. (The maximum left ventricular ejection fraction for enrollment was 35%.) This apparent subgroup interaction was statistically significant, reported Dr. Teerlink, a professor of medicine at the University of California, San Francisco, and director of Heart Failure at the San Francisco V.A. Medical Center.

Further analysis of the study data “will provide greater insight into subgroups who may demonstrate greater benefit, such as patients with lower ejection fraction in whom improving cardiac function may have a greater role,” he said. The idea that a drug that improves myocyte function at the molecular level could especially benefit patients with the lowest ejection fractions is “biologically plausible,” Dr. Teerlink said.

This scenario looks reasonable, and could make OM something of a niche drug for at least the near term, said Dr. Mann.

The world’s first myotropic drug

Possibly the most notable aspect of GALACTIC-HF is that it proved the efficacy, modest though it was, of a novel drug mechanism that fulfills a decades-long quest of heart failure researchers: a safe way to improve the heart’s pumping action.

“For years, the heart failure community struggled with treatment to improve cardiac performance, but invariably it ended in disaster by worsening cardiac deaths,” problems that led to abandonment of early inotropic drugs more than a generation ago, noted Dr. Mann.

But a more nuanced approach to inotropic agents recently has emerged from Dr. Teerlink and his associates, built on the premise that the dangers seen years ago related to the calcium modulations they caused. Their new paradigm is that the dangers of these “calcitropic” agents can be sidestepped with different agents that either mediate their effects via myosin, the myotropes like OM, or mitochondrial effects from mitotropic drugs.

The inotrope debacle from the 1990s made that drug-class name “a dirty word that causes fear and loathing in the heart failure community,” observed Dr. Mann. While the term myotrope has not yet really caught on, “If omecamtiv mecarbil starts getting used in routine practice, then I think you’ll start seeing uptake of the term myotrope,” he predicted.

GALACTIC-HF was sponsored by Amgen, Cytokinetics, and Servier, the companies developing omecamtiv mecarbil. Dr. Teerlink has received research support from and been a consultant to Amgen, Cytokinetics, and Servier, as well as Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Merck, and Novartis. Dr. Heidenreich had no disclosures. Dr. Mann is on a steering committee for a trial sponsored by Novartis and has no other commercial disclosures. Dr. Lewis is principal investigator for a trial of omecamtiv mecarbil and has no other commercial disclosures.

[email protected]

On Twitter @mitchelzoler

Omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, safely produced a significant but modest improvement in heart failure events or cardiovascular death in a pivotal trial with HFrEF patients, leaving experts unsure about the role this drug could have on top of an already crowded list of four first-line drug classes for this condition.

“It remains to be investigated and discussed where omecamtiv mecarbil fits in” the overall approach to treating patients with heart failure with reduced ejection fraction (HFrEF), commented Paul Heidenreich, MD, designated discussant for the report at the virtual scientific sessions of the American Heart Association.

Room for a fifth HFrEF drug?

In addition to the limited benefit, another question raised by the trial is how OM would perform when used on top of what is now considered standard, quadruple therapy for most HFrEF patients: a beta-blocker, a mineralocorticoid receptor antagonist, sacubitril-valsartan (Entresto), and an agent from the sodium glucose co-transporter 2 (SGLT2) inhibitor class, specifically dapagliflozin (Farxiga) or empagliflozin (Jardiance). During the period when the new OM trial was run, 2017-2019, the SGLT2 inhibitors had not yet been established as a key part of standard HFrEF treatment, and hence fewer than 3% of enrolled patients were on one of these drugs.

Because of this evidence gap, OM “can’t be across the board a fifth drug on top of standard treatment,” based on the new results, cautioned Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University School of Medicine.

The positives of omecamtiv mercarbil

But in addition to its positive result in the GALACTIC-HF trial, treatment with OM showed other attractive characteristics in a study that treated a wide spectrum of 4,120 patients with HFrEF as well as including 4,112 patients randomized to placebo. Most notably, OM had a very clean safety profile, with adverse event rates similar to placebo patients across all adverse event subtypes, as well as causing no drop in blood pressure and actually an average 2.0–mm Hg increase in systolic blood pressure, no increase in potassium, no apparent impact on renal function, and a small but significant decline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) compared with placebo.

This coupled with the novel mechanism of action of OM – direct augmentation of cardiac sarcomere function by increasing myosin attachment to actin – suggests that OM can be safely added on top of existing HFrEF treatment to provide an unique and incremental benefit.

“Other heart failure drugs [like beta-blockers and sacubitril-valsartan] lower blood pressure, so what can happen is that clinicians run out of room to add full dosages” when patients’ pressures fall too low, commented Gregory D. Lewis, MD, head of Heart Failure at Massachusetts General Hospital in Boston. He is principle investigator for another OM trial, METEORIC-HF, which is examining the possible impact of the drug on exercise capacity in a randomized study with about 270 HFrEF patients.

If the METEORIC-HF results can could confirm some of the GALACTIC-HF results that suggested improvements in patient function, the combined data could potentially lead to regulatory approval for U.S. marketing of the drug, Dr. Lewis suggested. Results from that study are expected in 2021, he said in an interview.

The GALACTIC-HF results hinted at possible functional improvement after 24 weeks on treatment among patients who required hospitalization as measured by the Kansas City Cardiomyopathy Questionnaire, which measures quality life. However, this difference failed to meet the study’s prespecified definition of a significant effect.

Another intriguing suggestion of focused benefit was in patients with a left ventricular ejection fraction at or below the median in GALACTIC-HF of 28%. In that subgroup, OM treatment was linked with a significant 16% relative reduction in the primary endpoint compared with placebo, while it had no significant effect in the other 50% of patients with higher ejection fractions. (The maximum left ventricular ejection fraction for enrollment was 35%.) This apparent subgroup interaction was statistically significant, reported Dr. Teerlink, a professor of medicine at the University of California, San Francisco, and director of Heart Failure at the San Francisco V.A. Medical Center.

Further analysis of the study data “will provide greater insight into subgroups who may demonstrate greater benefit, such as patients with lower ejection fraction in whom improving cardiac function may have a greater role,” he said. The idea that a drug that improves myocyte function at the molecular level could especially benefit patients with the lowest ejection fractions is “biologically plausible,” Dr. Teerlink said.

This scenario looks reasonable, and could make OM something of a niche drug for at least the near term, said Dr. Mann.

The world’s first myotropic drug

Possibly the most notable aspect of GALACTIC-HF is that it proved the efficacy, modest though it was, of a novel drug mechanism that fulfills a decades-long quest of heart failure researchers: a safe way to improve the heart’s pumping action.

“For years, the heart failure community struggled with treatment to improve cardiac performance, but invariably it ended in disaster by worsening cardiac deaths,” problems that led to abandonment of early inotropic drugs more than a generation ago, noted Dr. Mann.

But a more nuanced approach to inotropic agents recently has emerged from Dr. Teerlink and his associates, built on the premise that the dangers seen years ago related to the calcium modulations they caused. Their new paradigm is that the dangers of these “calcitropic” agents can be sidestepped with different agents that either mediate their effects via myosin, the myotropes like OM, or mitochondrial effects from mitotropic drugs.

The inotrope debacle from the 1990s made that drug-class name “a dirty word that causes fear and loathing in the heart failure community,” observed Dr. Mann. While the term myotrope has not yet really caught on, “If omecamtiv mecarbil starts getting used in routine practice, then I think you’ll start seeing uptake of the term myotrope,” he predicted.

GALACTIC-HF was sponsored by Amgen, Cytokinetics, and Servier, the companies developing omecamtiv mecarbil. Dr. Teerlink has received research support from and been a consultant to Amgen, Cytokinetics, and Servier, as well as Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Merck, and Novartis. Dr. Heidenreich had no disclosures. Dr. Mann is on a steering committee for a trial sponsored by Novartis and has no other commercial disclosures. Dr. Lewis is principal investigator for a trial of omecamtiv mecarbil and has no other commercial disclosures.

[email protected]

On Twitter @mitchelzoler

A panel convened by The Lancet has published a comprehensive report calling for major initiatives to improve diabetes prevention and care around the world.

The article was published online Nov. 12, just ahead of World Diabetes Day.

Of the 463 million people with diabetes worldwide in 2019, 80% live in low- and middle-income countries. The condition reduces life expectancy in middle-aged adults by 4-10 years, including increasing the risk of death from cardiovascular disease, kidney disease, and cancer by up to threefold. It is also a leading cause of nontraumatic amputation and blindness.

Use of evidence-based interventions, if implemented and managed properly, could prevent thousands of deaths globally every day, stressed the commission.

“There is an enormous amount of knowledge that we have amassed over the years. We need good preventive care and we need to ensure that diabetes patients, once diagnosed, have good continuous care. There is an urgent need for decision-makers, policymakers, and payers to make things happen,” the leader of the multidisciplinary commission, Juliana C.N. Chan, MBChB, MD, said in an interview.

And now diabetes has emerged as a major risk factor for death from COVID-19, particularly in the setting of inadequate glycemic control.

“COVID-19 has exposed the vulnerability of individuals with diabetes,” said Dr. Chan, of the Hong Kong Institute of Diabetes and Obesity. “We should use the pandemic as an opportunity to implement solutions.”
 

Physician education key, trickling down to field workers and patients

First on the agenda, she says, should be “physician education. There are many primary care providers and internal medicine physicians whose knowledge needs to be updated.”

“Then doctors need to transfer this information to other people, such as nurses and community field workers. We cannot just rely on doctors; we need to train nonmedics” so that knowledge about how to prevent, treat, and manage diabetes long term is communicated right down the health care chain, she explained.

“They need to know how to look at people’s eyes and feet, how to do blood and urine tests, and how to collect data. Then they need to educate patients on what they should be doing, on how to practice self-care,” she added.

“We need to change our way of thinking, redesign clinic flow and how you build a team. And those care teams need to know how to collect data, and then use that data to monitor patients and to stratify individual risk, to ensure that what has been said has been done, as well as to inform practice and policies” through, for example, the establishment of diabetes registers.

The focus needs to be on “lifelong integrated care, the right treatment at the right time,” she emphasized. History-taking, clinical and laboratory assessments, as well as monitoring of macrovascular and microvascular complications, comorbidities, and medications, are all key.

Just a few simple things, if properly implemented, could make a big difference, Dr. Chan stressed.

For example, implementing a structured lifestyle intervention and use of metformin can each prevent or delay type 2 diabetes in individuals with impaired glucose tolerance by 30%-50%, and sustained weight reduction in patients with obesity by 15 kg (33 lb) or more can induce remission of type 2 diabetes for up to 2 years.

And there are plenty of medications that are “very affordable even in low- and middle-income countries” to treat diabetes and associated risk factors, including metformin, “statins, and RAS inhibitors,” she noted.

For instance, the 10 low- and middle-income countries with the greatest burden of diabetes (China, India, Brazil, Mexico, Indonesia, Egypt, Pakistan, Bangladesh, Turkey, Thailand) account for 217 million cases of type 2 diabetes, representing nearly 50% of all diabetes cases.

The commission estimated that 3.2 million of these individuals would die in 3 years if not treated, with 1.3 million of these deaths due to cardiovascular disease.

By reducing hemoglobin A1c, blood pressure, and LDL-cholesterol through achieving a diagnosis rate of 50%, ensuring access to essential medicines in at least 70% of patients, and with a support system to sustain reductions in these risk factors over 3 years, up to 800,000 premature deaths could be avoided.
 

People with type 1 diabetes dying; WHO launches initiative

In an accompanying commentary (2020 Nov 12. doi: 10.1016/S0140-6736[20]32378-3), Katie Dain, chief executive officer of the Noncommunicable Diseases (NCD) Alliance, points out that only half of people living with diabetes around the world – and just one in seven in Africa – have reliable access to insulin.

“Lots of people with type 1 diabetes are still dying due to lack of insulin,” Dr. Chan said in an interview. “We need to elevate basic care to intermediate and ensure that basal-bolus insulin and glucose-monitoring tools are available and that patients are trained in self-care. In that way, 80% of type 1 diabetes deaths could be prevented.”

Ms. 3Dain agrees, stressing, “Political rhetoric and commitments have yet to translate into sufficient and sustainable action for people living with diabetes worldwide, and particularly for those in [low- and middle-income countries].”

The Lancet Commission document also emphasizes the importance of support for pregnant women with diabetes and attention to the psychosocial needs of people with diabetes.

And it stresses society-, population-, and community-based strategies for type 2 diabetes prevention including health awareness programs, food policies, and broad use of nonphysician personnel to deliver diabetes prevention efforts.

In tandem with World Diabetes Day, the World Health Organization will announce the development of the WHO Global Diabetes Compact, which will be launched in April 2021.

This will aim to implement the commission’s recommendations through partnerships with governments, care providers, patient advocates, and nongovernmental organizations.

Together, they will “support countries to mobilize resources and accelerate structural transformations, which will enable the scale-up of access to essential diabetes medicines and technologies, inclusion of diagnosis and treatment of diabetes in primary health care and universal health coverage packages, and reduction of major population-level diabetes risk factors such as obesity,” according to another Lancet editorial accompanying the report.

“The evidence-base for improving diabetes prevention and care is strong. The question now for diabetes advocates is how to achieve the comprehensive, systems-level change needed to translate this evidence into action.”

Dr. Chan has reported receiving grants from AstraZeneca, Lilly, Lee Powder, Hua Medicine, and Qualigenics, as well as grants and personal fees from Bayer, Boehringer Ingelheim, Sanofi, Novartis, Merck, and MSD outside the submitted work. She has reported being the chief executive officer (pro bono) of the Asia Diabetes Foundation and a cofounder of GemVCare. She also holds a patent for genetic markers for diabetes and its complications. Ms. Dain has reported no relevant financial relationships.
 

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

A panel convened by The Lancet has published a comprehensive report calling for major initiatives to improve diabetes prevention and care around the world.

The article was published online Nov. 12, just ahead of World Diabetes Day.

Of the 463 million people with diabetes worldwide in 2019, 80% live in low- and middle-income countries. The condition reduces life expectancy in middle-aged adults by 4-10 years, including increasing the risk of death from cardiovascular disease, kidney disease, and cancer by up to threefold. It is also a leading cause of nontraumatic amputation and blindness.

Use of evidence-based interventions, if implemented and managed properly, could prevent thousands of deaths globally every day, stressed the commission.

“There is an enormous amount of knowledge that we have amassed over the years. We need good preventive care and we need to ensure that diabetes patients, once diagnosed, have good continuous care. There is an urgent need for decision-makers, policymakers, and payers to make things happen,” the leader of the multidisciplinary commission, Juliana C.N. Chan, MBChB, MD, said in an interview.

And now diabetes has emerged as a major risk factor for death from COVID-19, particularly in the setting of inadequate glycemic control.

“COVID-19 has exposed the vulnerability of individuals with diabetes,” said Dr. Chan, of the Hong Kong Institute of Diabetes and Obesity. “We should use the pandemic as an opportunity to implement solutions.”
 

Physician education key, trickling down to field workers and patients

First on the agenda, she says, should be “physician education. There are many primary care providers and internal medicine physicians whose knowledge needs to be updated.”

“Then doctors need to transfer this information to other people, such as nurses and community field workers. We cannot just rely on doctors; we need to train nonmedics” so that knowledge about how to prevent, treat, and manage diabetes long term is communicated right down the health care chain, she explained.

“They need to know how to look at people’s eyes and feet, how to do blood and urine tests, and how to collect data. Then they need to educate patients on what they should be doing, on how to practice self-care,” she added.

“We need to change our way of thinking, redesign clinic flow and how you build a team. And those care teams need to know how to collect data, and then use that data to monitor patients and to stratify individual risk, to ensure that what has been said has been done, as well as to inform practice and policies” through, for example, the establishment of diabetes registers.

The focus needs to be on “lifelong integrated care, the right treatment at the right time,” she emphasized. History-taking, clinical and laboratory assessments, as well as monitoring of macrovascular and microvascular complications, comorbidities, and medications, are all key.

Just a few simple things, if properly implemented, could make a big difference, Dr. Chan stressed.

For example, implementing a structured lifestyle intervention and use of metformin can each prevent or delay type 2 diabetes in individuals with impaired glucose tolerance by 30%-50%, and sustained weight reduction in patients with obesity by 15 kg (33 lb) or more can induce remission of type 2 diabetes for up to 2 years.

And there are plenty of medications that are “very affordable even in low- and middle-income countries” to treat diabetes and associated risk factors, including metformin, “statins, and RAS inhibitors,” she noted.

For instance, the 10 low- and middle-income countries with the greatest burden of diabetes (China, India, Brazil, Mexico, Indonesia, Egypt, Pakistan, Bangladesh, Turkey, Thailand) account for 217 million cases of type 2 diabetes, representing nearly 50% of all diabetes cases.

The commission estimated that 3.2 million of these individuals would die in 3 years if not treated, with 1.3 million of these deaths due to cardiovascular disease.

By reducing hemoglobin A1c, blood pressure, and LDL-cholesterol through achieving a diagnosis rate of 50%, ensuring access to essential medicines in at least 70% of patients, and with a support system to sustain reductions in these risk factors over 3 years, up to 800,000 premature deaths could be avoided.
 

People with type 1 diabetes dying; WHO launches initiative

In an accompanying commentary (2020 Nov 12. doi: 10.1016/S0140-6736[20]32378-3), Katie Dain, chief executive officer of the Noncommunicable Diseases (NCD) Alliance, points out that only half of people living with diabetes around the world – and just one in seven in Africa – have reliable access to insulin.

“Lots of people with type 1 diabetes are still dying due to lack of insulin,” Dr. Chan said in an interview. “We need to elevate basic care to intermediate and ensure that basal-bolus insulin and glucose-monitoring tools are available and that patients are trained in self-care. In that way, 80% of type 1 diabetes deaths could be prevented.”

Ms. 3Dain agrees, stressing, “Political rhetoric and commitments have yet to translate into sufficient and sustainable action for people living with diabetes worldwide, and particularly for those in [low- and middle-income countries].”

The Lancet Commission document also emphasizes the importance of support for pregnant women with diabetes and attention to the psychosocial needs of people with diabetes.

And it stresses society-, population-, and community-based strategies for type 2 diabetes prevention including health awareness programs, food policies, and broad use of nonphysician personnel to deliver diabetes prevention efforts.

In tandem with World Diabetes Day, the World Health Organization will announce the development of the WHO Global Diabetes Compact, which will be launched in April 2021.

This will aim to implement the commission’s recommendations through partnerships with governments, care providers, patient advocates, and nongovernmental organizations.

Together, they will “support countries to mobilize resources and accelerate structural transformations, which will enable the scale-up of access to essential diabetes medicines and technologies, inclusion of diagnosis and treatment of diabetes in primary health care and universal health coverage packages, and reduction of major population-level diabetes risk factors such as obesity,” according to another Lancet editorial accompanying the report.

“The evidence-base for improving diabetes prevention and care is strong. The question now for diabetes advocates is how to achieve the comprehensive, systems-level change needed to translate this evidence into action.”

Dr. Chan has reported receiving grants from AstraZeneca, Lilly, Lee Powder, Hua Medicine, and Qualigenics, as well as grants and personal fees from Bayer, Boehringer Ingelheim, Sanofi, Novartis, Merck, and MSD outside the submitted work. She has reported being the chief executive officer (pro bono) of the Asia Diabetes Foundation and a cofounder of GemVCare. She also holds a patent for genetic markers for diabetes and its complications. Ms. Dain has reported no relevant financial relationships.
 

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

A panel convened by The Lancet has published a comprehensive report calling for major initiatives to improve diabetes prevention and care around the world.

The article was published online Nov. 12, just ahead of World Diabetes Day.

Of the 463 million people with diabetes worldwide in 2019, 80% live in low- and middle-income countries. The condition reduces life expectancy in middle-aged adults by 4-10 years, including increasing the risk of death from cardiovascular disease, kidney disease, and cancer by up to threefold. It is also a leading cause of nontraumatic amputation and blindness.

Use of evidence-based interventions, if implemented and managed properly, could prevent thousands of deaths globally every day, stressed the commission.

“There is an enormous amount of knowledge that we have amassed over the years. We need good preventive care and we need to ensure that diabetes patients, once diagnosed, have good continuous care. There is an urgent need for decision-makers, policymakers, and payers to make things happen,” the leader of the multidisciplinary commission, Juliana C.N. Chan, MBChB, MD, said in an interview.

And now diabetes has emerged as a major risk factor for death from COVID-19, particularly in the setting of inadequate glycemic control.

“COVID-19 has exposed the vulnerability of individuals with diabetes,” said Dr. Chan, of the Hong Kong Institute of Diabetes and Obesity. “We should use the pandemic as an opportunity to implement solutions.”
 

Physician education key, trickling down to field workers and patients

First on the agenda, she says, should be “physician education. There are many primary care providers and internal medicine physicians whose knowledge needs to be updated.”

“Then doctors need to transfer this information to other people, such as nurses and community field workers. We cannot just rely on doctors; we need to train nonmedics” so that knowledge about how to prevent, treat, and manage diabetes long term is communicated right down the health care chain, she explained.

“They need to know how to look at people’s eyes and feet, how to do blood and urine tests, and how to collect data. Then they need to educate patients on what they should be doing, on how to practice self-care,” she added.

“We need to change our way of thinking, redesign clinic flow and how you build a team. And those care teams need to know how to collect data, and then use that data to monitor patients and to stratify individual risk, to ensure that what has been said has been done, as well as to inform practice and policies” through, for example, the establishment of diabetes registers.

The focus needs to be on “lifelong integrated care, the right treatment at the right time,” she emphasized. History-taking, clinical and laboratory assessments, as well as monitoring of macrovascular and microvascular complications, comorbidities, and medications, are all key.

Just a few simple things, if properly implemented, could make a big difference, Dr. Chan stressed.

For example, implementing a structured lifestyle intervention and use of metformin can each prevent or delay type 2 diabetes in individuals with impaired glucose tolerance by 30%-50%, and sustained weight reduction in patients with obesity by 15 kg (33 lb) or more can induce remission of type 2 diabetes for up to 2 years.

And there are plenty of medications that are “very affordable even in low- and middle-income countries” to treat diabetes and associated risk factors, including metformin, “statins, and RAS inhibitors,” she noted.

For instance, the 10 low- and middle-income countries with the greatest burden of diabetes (China, India, Brazil, Mexico, Indonesia, Egypt, Pakistan, Bangladesh, Turkey, Thailand) account for 217 million cases of type 2 diabetes, representing nearly 50% of all diabetes cases.

The commission estimated that 3.2 million of these individuals would die in 3 years if not treated, with 1.3 million of these deaths due to cardiovascular disease.

By reducing hemoglobin A1c, blood pressure, and LDL-cholesterol through achieving a diagnosis rate of 50%, ensuring access to essential medicines in at least 70% of patients, and with a support system to sustain reductions in these risk factors over 3 years, up to 800,000 premature deaths could be avoided.
 

People with type 1 diabetes dying; WHO launches initiative

In an accompanying commentary (2020 Nov 12. doi: 10.1016/S0140-6736[20]32378-3), Katie Dain, chief executive officer of the Noncommunicable Diseases (NCD) Alliance, points out that only half of people living with diabetes around the world – and just one in seven in Africa – have reliable access to insulin.

“Lots of people with type 1 diabetes are still dying due to lack of insulin,” Dr. Chan said in an interview. “We need to elevate basic care to intermediate and ensure that basal-bolus insulin and glucose-monitoring tools are available and that patients are trained in self-care. In that way, 80% of type 1 diabetes deaths could be prevented.”

Ms. 3Dain agrees, stressing, “Political rhetoric and commitments have yet to translate into sufficient and sustainable action for people living with diabetes worldwide, and particularly for those in [low- and middle-income countries].”

The Lancet Commission document also emphasizes the importance of support for pregnant women with diabetes and attention to the psychosocial needs of people with diabetes.

And it stresses society-, population-, and community-based strategies for type 2 diabetes prevention including health awareness programs, food policies, and broad use of nonphysician personnel to deliver diabetes prevention efforts.

In tandem with World Diabetes Day, the World Health Organization will announce the development of the WHO Global Diabetes Compact, which will be launched in April 2021.

This will aim to implement the commission’s recommendations through partnerships with governments, care providers, patient advocates, and nongovernmental organizations.

Together, they will “support countries to mobilize resources and accelerate structural transformations, which will enable the scale-up of access to essential diabetes medicines and technologies, inclusion of diagnosis and treatment of diabetes in primary health care and universal health coverage packages, and reduction of major population-level diabetes risk factors such as obesity,” according to another Lancet editorial accompanying the report.

“The evidence-base for improving diabetes prevention and care is strong. The question now for diabetes advocates is how to achieve the comprehensive, systems-level change needed to translate this evidence into action.”

Dr. Chan has reported receiving grants from AstraZeneca, Lilly, Lee Powder, Hua Medicine, and Qualigenics, as well as grants and personal fees from Bayer, Boehringer Ingelheim, Sanofi, Novartis, Merck, and MSD outside the submitted work. She has reported being the chief executive officer (pro bono) of the Asia Diabetes Foundation and a cofounder of GemVCare. She also holds a patent for genetic markers for diabetes and its complications. Ms. Dain has reported no relevant financial relationships.
 

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

Dr. Karen Breach Washington returns to the Pediatric News editorial advisory board after a 10-year hiatus. She currently is employed as a medical director at WellCare of North Carolina/Centene. Her career spans 32 years in Charlotte, N.C., where she has practiced pediatrics and held medical director positions in a large health care system and a managed care organization, as well as worked in private practice and in a public health clinic.

A native of North Babylon, N.Y., she received her undergraduate degree at Hofstra University, Hempstead, N.Y., and her medical degree at George Washington University, Washington. Dr. Breach Washington has been an advocate for children, access to health care, and diversity and inclusion.

An active member of the American Academy of Pediatrics, Dr. Breach Washington served as an elected representative to the AAP National Nominating Committee, following her term as president of the North Carolina chapter of the AAP.

She is a past pediatric section chair of the National Medical Association and past president of the Charlotte Medical, Dental, and Pharmaceutical Society. She has served on the boards of the Simmons Branch YMCA, the Mecklenburg County Medical Society, and the Teen Health Connection (a facility of Carolinas Medical Center), plus many associated committees.

Dr. Breach Washington serves the community as an active life member of Alpha Kappa Alpha Sorority, Jack and Jill of America, and a member of The Links. She is the recipient of several awards for her commitment to diversity and inclusion, philanthropy, and community service.

Dr. Breach Washington is married and has an adult daughter. She is an avid fan of all sports, a dancer, and enjoys theater, fine dining, and travel.

Dr. Karen Breach Washington returns to the Pediatric News editorial advisory board after a 10-year hiatus. She currently is employed as a medical director at WellCare of North Carolina/Centene. Her career spans 32 years in Charlotte, N.C., where she has practiced pediatrics and held medical director positions in a large health care system and a managed care organization, as well as worked in private practice and in a public health clinic.

A native of North Babylon, N.Y., she received her undergraduate degree at Hofstra University, Hempstead, N.Y., and her medical degree at George Washington University, Washington. Dr. Breach Washington has been an advocate for children, access to health care, and diversity and inclusion.

An active member of the American Academy of Pediatrics, Dr. Breach Washington served as an elected representative to the AAP National Nominating Committee, following her term as president of the North Carolina chapter of the AAP.

She is a past pediatric section chair of the National Medical Association and past president of the Charlotte Medical, Dental, and Pharmaceutical Society. She has served on the boards of the Simmons Branch YMCA, the Mecklenburg County Medical Society, and the Teen Health Connection (a facility of Carolinas Medical Center), plus many associated committees.

Dr. Breach Washington serves the community as an active life member of Alpha Kappa Alpha Sorority, Jack and Jill of America, and a member of The Links. She is the recipient of several awards for her commitment to diversity and inclusion, philanthropy, and community service.

Dr. Breach Washington is married and has an adult daughter. She is an avid fan of all sports, a dancer, and enjoys theater, fine dining, and travel.

Dr. Karen Breach Washington returns to the Pediatric News editorial advisory board after a 10-year hiatus. She currently is employed as a medical director at WellCare of North Carolina/Centene. Her career spans 32 years in Charlotte, N.C., where she has practiced pediatrics and held medical director positions in a large health care system and a managed care organization, as well as worked in private practice and in a public health clinic.

A native of North Babylon, N.Y., she received her undergraduate degree at Hofstra University, Hempstead, N.Y., and her medical degree at George Washington University, Washington. Dr. Breach Washington has been an advocate for children, access to health care, and diversity and inclusion.

An active member of the American Academy of Pediatrics, Dr. Breach Washington served as an elected representative to the AAP National Nominating Committee, following her term as president of the North Carolina chapter of the AAP.

She is a past pediatric section chair of the National Medical Association and past president of the Charlotte Medical, Dental, and Pharmaceutical Society. She has served on the boards of the Simmons Branch YMCA, the Mecklenburg County Medical Society, and the Teen Health Connection (a facility of Carolinas Medical Center), plus many associated committees.

Dr. Breach Washington serves the community as an active life member of Alpha Kappa Alpha Sorority, Jack and Jill of America, and a member of The Links. She is the recipient of several awards for her commitment to diversity and inclusion, philanthropy, and community service.

Dr. Breach Washington is married and has an adult daughter. She is an avid fan of all sports, a dancer, and enjoys theater, fine dining, and travel.

"The writing is on the wall” that virtual care is not meeting the needs of people with HIV who struggled with viral suppression even before the COVID-19 pandemic, said Jason Farley, PhD, ANP-BC, AACRN, associate professor of nursing at Johns Hopkins University, Baltimore. So it’s time for HIV care teams, especially clinics in the Ryan White HIV/AIDS Program, to get creative in bringing wraparound services to patients.

That may mean reallocating the workforce so that one person serves as a community health worker. Or it could mean increasing texts and video calls; helping patients find online support groups to address problems with alcohol or drug use; and conducting an overall assessment of patients’ needs as the pandemic continues.

“The virtual patient-centered medical home may be the new normal after COVID-19, and we have to be thinking about how we use this model with patients for whom it works, but supplement this model in patients that it does not,” Farley said at the virtual Association of Nurses in AIDS Care (ANAC) 2020 Annual Meeting. That work “is essential to our being able to facilitate the best patient outcomes possible.”
 

Early data, tiered interventions

Farley referred to an article published in September in the Journal AIDS that confirmed unpublished data mentioned at the International AIDS Conference 2020. The article reported that viral suppression rates among people with HIV who attended San Francisco’s Ward 86 HIV clinic dropped by 31% from pre-COVID levels.

Of the 1766 people who attended the clinic, about 1 in 5 had detectable HIV viral loads at any point in 2019. But that rate was 31% higher after shelter-in-place orders were issued. And although patients participated in telemedicine visits at more or less the same rate before and after the pandemic (31% vs. 30% no-shows), viral suppression rates dropped. The impact was especially acute for homeless individuals.

“This destabilization occurred despite our population attending telemedicine visits at a higher rate than expected, given the 60% drop in ambulatory care visit volume nationwide,” the authors stated in their article. “Telehealth visits, while offering greater patient convenience, may lead to less access to clinic-based social support services essential to achieving viral suppression among vulnerable groups.”

That’s the challenge HIV clinics now face, Farley said at the ANAC meeting.

He suggested a differentiated care approach in which there are four tiers of care, starting with the standard level of outreach, which may include email, electronic health record blasts, and robo-calls to remind people of their appointments and to refill their medications. Those with sustained viral suppression may only need 90-day automatic refills of their medications. Those who are vulnerable to nonadherence may need to be contacted weekly or more often by the clinic. Such contact could be made by a social worker, a community health worker, or through some form of virtual support.

Patients at tier 4, who have labile viral suppression, need far more than that. These are the 15% of patients with HIV who struggled with viral suppression before the pandemic. They are the patients that Farley’s team focuses on at Baltimore’s John G. Bartlett Specialty Clinic for Infectious Disease.

“We’ve completely deconstructed the patient-centered medical home,” he said of the early move to virtual care. He suggested that clinicians assess their services and ask themselves some questions:

• Has someone on the team reached out to every patient and checked in to see what their biggest needs are, medical or not, during the pandemic? Have they assessed the patient’s ability to receive video calls or text messages?
• How have group-support programs that address stigma or the social determinants of health fared in the transition to virtual medicine?
• Are patients who are in recovery being supported in order that they may engage with recovery programs online?
• How well have counseling services done in engaging people in virtual care? Currently, given the overall increase in mental health challenges during the pandemic, one would expect that the use of mental health counseling is increasing. “If they’re stagnant or going down, someone needs to be reflecting on that issue internally in the clinic,” he said.
• Are patients being contacted regarding the effects that isolation is having on their lives? “The things that would normally allow us to self-mitigate and self-manage these conditions, like going to the gym, meeting with friends, religious services – all of those are being cut,” he said.
• Is there an early alert from an in-person pharmacy to trigger outreach via a community health worker for patients who haven’t picked up their medications in a week or more?

Farley pointed to a 2015 model for an enhanced e-health approach to chronic care management that called for e-support from the community and that was enhanced through virtual communities.

These are some of the approaches Farley has taken at his clinic. He leads a team that focuses specifically on patients who struggled with engagement before the pandemic. Through a grant from the US Department of Health & Human Services’ Health Resources and Services Administration – even before the pandemic – that team has been funding community health workers who have multiple contacts with patients online and virtually and are able to offer what he calls “unapologetically enabling” support for patients so that they are able to focus on their health.

He gave the following example. Before the pandemic, a community health worker on the team had been working with a patient who showed up at every scheduled visit and swore that she was taking her medications, although clearly she was not. A community health worker, who was made available through the grant, was able to recognize that the patient’s biggest challenge in her life was providing childcare for her special-needs child. The community health worker worked with the patient for months to find stable childcare for the child, paid 2 months of rent for the patient so that she would not become homeless, and helped her find transitional housing. When the pandemic hit, the community health worker was already texting and conducting video calls with the patient regularly.

For the past 9 months, that patient has had an undetectable viral load, Farley said.

“Nine months during a pandemic,” Farley reiterated, “and the community health worker keeps working with her, keeps meeting with her.”
 

Stigma on stigma

The need for this level of support from the clinic may be even more important for people with HIV who acquire COVID-19, said Orlando Harris, PhD, assistant professor of community health systems at the University of California, San Francisco, (UCSF) School of Nursing. HIV-related stigma is a well-known deterrent to care for people living with the virus. During the presentation, Harris asked Farley about the impact of COVID-19 stigma on people with both HIV and COVID-19.

Farley said that patients at his clinic have told him that they have “ostracized” friends who have tested positive for COVID-19. Harris remembered a person with HIV who participated in one of his trials telling the researchers that despite all his precautions – wearing a mask, staying socially distant – he still acquired COVID-19. There was nothing he could have done, Harris said, other than just not go to the grocery store.

The fear of contracting another disease that is associated with stigma, as well as the need to disclose it, can inflame memories of the trauma of being diagnosed with HIV, Harris said. And with patient-centered medical homes struggling to reconstitute their wraparound services via telehealth, he said he wonders whether clinicians should be doing more.

“I worry about people who have survived being diagnosed with HIV in the ‘80s and the ‘90s before antiretroviral therapy showed up on the scene,” he told Medscape Medical News. “I worry that the folks that survived one pandemic [may] be feeling fearful or living in that fear that this new pandemic might take them out. That’s why I’m stressing the need for us to really consider, as clinicians and also as researchers the support systems, the coping mechanisms, the counseling, or what have you to support those living with HIV and vulnerable to COVID-19.”

During telehealth visits, that can be achieved simply by asking people how they are really doing and what their coping mechanisms are.

For their part, the clinicians at San Francisco’s Ward 86 are not trying to provide that support through telehealth on the same level as they were at the beginning of the pandemic, said Matthew Spinelli, MD, assistant professor of medicine, and Monica Gandhi, MD, associate chief of the Division of HIV, Infectious Diseases and Global Medicine, who are both at UCSF and are coauthors of the study.

They still offer telemedicine appointments to patients who request them, said Spinelli. He said about one-third of his patients still prefer to receive their care virtually. The rest have gone back to face-to-face support.

“The analysis led us to promptly open up care as much as possible to our patients, with the idea that telehealth is not cutting it for vulnerable patients with HIV,” Gandhi told Medscape Medical News via email. “We don’t think it’s right for a population who relies on social support from the clinic.”
 

This article first appeared on Medscape.com.

"The writing is on the wall” that virtual care is not meeting the needs of people with HIV who struggled with viral suppression even before the COVID-19 pandemic, said Jason Farley, PhD, ANP-BC, AACRN, associate professor of nursing at Johns Hopkins University, Baltimore. So it’s time for HIV care teams, especially clinics in the Ryan White HIV/AIDS Program, to get creative in bringing wraparound services to patients.

That may mean reallocating the workforce so that one person serves as a community health worker. Or it could mean increasing texts and video calls; helping patients find online support groups to address problems with alcohol or drug use; and conducting an overall assessment of patients’ needs as the pandemic continues.

“The virtual patient-centered medical home may be the new normal after COVID-19, and we have to be thinking about how we use this model with patients for whom it works, but supplement this model in patients that it does not,” Farley said at the virtual Association of Nurses in AIDS Care (ANAC) 2020 Annual Meeting. That work “is essential to our being able to facilitate the best patient outcomes possible.”
 

Early data, tiered interventions

Farley referred to an article published in September in the Journal AIDS that confirmed unpublished data mentioned at the International AIDS Conference 2020. The article reported that viral suppression rates among people with HIV who attended San Francisco’s Ward 86 HIV clinic dropped by 31% from pre-COVID levels.

Of the 1766 people who attended the clinic, about 1 in 5 had detectable HIV viral loads at any point in 2019. But that rate was 31% higher after shelter-in-place orders were issued. And although patients participated in telemedicine visits at more or less the same rate before and after the pandemic (31% vs. 30% no-shows), viral suppression rates dropped. The impact was especially acute for homeless individuals.

“This destabilization occurred despite our population attending telemedicine visits at a higher rate than expected, given the 60% drop in ambulatory care visit volume nationwide,” the authors stated in their article. “Telehealth visits, while offering greater patient convenience, may lead to less access to clinic-based social support services essential to achieving viral suppression among vulnerable groups.”

That’s the challenge HIV clinics now face, Farley said at the ANAC meeting.

He suggested a differentiated care approach in which there are four tiers of care, starting with the standard level of outreach, which may include email, electronic health record blasts, and robo-calls to remind people of their appointments and to refill their medications. Those with sustained viral suppression may only need 90-day automatic refills of their medications. Those who are vulnerable to nonadherence may need to be contacted weekly or more often by the clinic. Such contact could be made by a social worker, a community health worker, or through some form of virtual support.

Patients at tier 4, who have labile viral suppression, need far more than that. These are the 15% of patients with HIV who struggled with viral suppression before the pandemic. They are the patients that Farley’s team focuses on at Baltimore’s John G. Bartlett Specialty Clinic for Infectious Disease.

“We’ve completely deconstructed the patient-centered medical home,” he said of the early move to virtual care. He suggested that clinicians assess their services and ask themselves some questions:

• Has someone on the team reached out to every patient and checked in to see what their biggest needs are, medical or not, during the pandemic? Have they assessed the patient’s ability to receive video calls or text messages?
• How have group-support programs that address stigma or the social determinants of health fared in the transition to virtual medicine?
• Are patients who are in recovery being supported in order that they may engage with recovery programs online?
• How well have counseling services done in engaging people in virtual care? Currently, given the overall increase in mental health challenges during the pandemic, one would expect that the use of mental health counseling is increasing. “If they’re stagnant or going down, someone needs to be reflecting on that issue internally in the clinic,” he said.
• Are patients being contacted regarding the effects that isolation is having on their lives? “The things that would normally allow us to self-mitigate and self-manage these conditions, like going to the gym, meeting with friends, religious services – all of those are being cut,” he said.
• Is there an early alert from an in-person pharmacy to trigger outreach via a community health worker for patients who haven’t picked up their medications in a week or more?

Farley pointed to a 2015 model for an enhanced e-health approach to chronic care management that called for e-support from the community and that was enhanced through virtual communities.

These are some of the approaches Farley has taken at his clinic. He leads a team that focuses specifically on patients who struggled with engagement before the pandemic. Through a grant from the US Department of Health & Human Services’ Health Resources and Services Administration – even before the pandemic – that team has been funding community health workers who have multiple contacts with patients online and virtually and are able to offer what he calls “unapologetically enabling” support for patients so that they are able to focus on their health.

He gave the following example. Before the pandemic, a community health worker on the team had been working with a patient who showed up at every scheduled visit and swore that she was taking her medications, although clearly she was not. A community health worker, who was made available through the grant, was able to recognize that the patient’s biggest challenge in her life was providing childcare for her special-needs child. The community health worker worked with the patient for months to find stable childcare for the child, paid 2 months of rent for the patient so that she would not become homeless, and helped her find transitional housing. When the pandemic hit, the community health worker was already texting and conducting video calls with the patient regularly.

For the past 9 months, that patient has had an undetectable viral load, Farley said.

“Nine months during a pandemic,” Farley reiterated, “and the community health worker keeps working with her, keeps meeting with her.”
 

Stigma on stigma

The need for this level of support from the clinic may be even more important for people with HIV who acquire COVID-19, said Orlando Harris, PhD, assistant professor of community health systems at the University of California, San Francisco, (UCSF) School of Nursing. HIV-related stigma is a well-known deterrent to care for people living with the virus. During the presentation, Harris asked Farley about the impact of COVID-19 stigma on people with both HIV and COVID-19.

Farley said that patients at his clinic have told him that they have “ostracized” friends who have tested positive for COVID-19. Harris remembered a person with HIV who participated in one of his trials telling the researchers that despite all his precautions – wearing a mask, staying socially distant – he still acquired COVID-19. There was nothing he could have done, Harris said, other than just not go to the grocery store.

The fear of contracting another disease that is associated with stigma, as well as the need to disclose it, can inflame memories of the trauma of being diagnosed with HIV, Harris said. And with patient-centered medical homes struggling to reconstitute their wraparound services via telehealth, he said he wonders whether clinicians should be doing more.

“I worry about people who have survived being diagnosed with HIV in the ‘80s and the ‘90s before antiretroviral therapy showed up on the scene,” he told Medscape Medical News. “I worry that the folks that survived one pandemic [may] be feeling fearful or living in that fear that this new pandemic might take them out. That’s why I’m stressing the need for us to really consider, as clinicians and also as researchers the support systems, the coping mechanisms, the counseling, or what have you to support those living with HIV and vulnerable to COVID-19.”

During telehealth visits, that can be achieved simply by asking people how they are really doing and what their coping mechanisms are.

For their part, the clinicians at San Francisco’s Ward 86 are not trying to provide that support through telehealth on the same level as they were at the beginning of the pandemic, said Matthew Spinelli, MD, assistant professor of medicine, and Monica Gandhi, MD, associate chief of the Division of HIV, Infectious Diseases and Global Medicine, who are both at UCSF and are coauthors of the study.

They still offer telemedicine appointments to patients who request them, said Spinelli. He said about one-third of his patients still prefer to receive their care virtually. The rest have gone back to face-to-face support.

“The analysis led us to promptly open up care as much as possible to our patients, with the idea that telehealth is not cutting it for vulnerable patients with HIV,” Gandhi told Medscape Medical News via email. “We don’t think it’s right for a population who relies on social support from the clinic.”
 

This article first appeared on Medscape.com.

"The writing is on the wall” that virtual care is not meeting the needs of people with HIV who struggled with viral suppression even before the COVID-19 pandemic, said Jason Farley, PhD, ANP-BC, AACRN, associate professor of nursing at Johns Hopkins University, Baltimore. So it’s time for HIV care teams, especially clinics in the Ryan White HIV/AIDS Program, to get creative in bringing wraparound services to patients.

That may mean reallocating the workforce so that one person serves as a community health worker. Or it could mean increasing texts and video calls; helping patients find online support groups to address problems with alcohol or drug use; and conducting an overall assessment of patients’ needs as the pandemic continues.

“The virtual patient-centered medical home may be the new normal after COVID-19, and we have to be thinking about how we use this model with patients for whom it works, but supplement this model in patients that it does not,” Farley said at the virtual Association of Nurses in AIDS Care (ANAC) 2020 Annual Meeting. That work “is essential to our being able to facilitate the best patient outcomes possible.”
 

Early data, tiered interventions

Farley referred to an article published in September in the Journal AIDS that confirmed unpublished data mentioned at the International AIDS Conference 2020. The article reported that viral suppression rates among people with HIV who attended San Francisco’s Ward 86 HIV clinic dropped by 31% from pre-COVID levels.

Of the 1766 people who attended the clinic, about 1 in 5 had detectable HIV viral loads at any point in 2019. But that rate was 31% higher after shelter-in-place orders were issued. And although patients participated in telemedicine visits at more or less the same rate before and after the pandemic (31% vs. 30% no-shows), viral suppression rates dropped. The impact was especially acute for homeless individuals.

“This destabilization occurred despite our population attending telemedicine visits at a higher rate than expected, given the 60% drop in ambulatory care visit volume nationwide,” the authors stated in their article. “Telehealth visits, while offering greater patient convenience, may lead to less access to clinic-based social support services essential to achieving viral suppression among vulnerable groups.”

That’s the challenge HIV clinics now face, Farley said at the ANAC meeting.

He suggested a differentiated care approach in which there are four tiers of care, starting with the standard level of outreach, which may include email, electronic health record blasts, and robo-calls to remind people of their appointments and to refill their medications. Those with sustained viral suppression may only need 90-day automatic refills of their medications. Those who are vulnerable to nonadherence may need to be contacted weekly or more often by the clinic. Such contact could be made by a social worker, a community health worker, or through some form of virtual support.

Patients at tier 4, who have labile viral suppression, need far more than that. These are the 15% of patients with HIV who struggled with viral suppression before the pandemic. They are the patients that Farley’s team focuses on at Baltimore’s John G. Bartlett Specialty Clinic for Infectious Disease.

“We’ve completely deconstructed the patient-centered medical home,” he said of the early move to virtual care. He suggested that clinicians assess their services and ask themselves some questions:

• Has someone on the team reached out to every patient and checked in to see what their biggest needs are, medical or not, during the pandemic? Have they assessed the patient’s ability to receive video calls or text messages?
• How have group-support programs that address stigma or the social determinants of health fared in the transition to virtual medicine?
• Are patients who are in recovery being supported in order that they may engage with recovery programs online?
• How well have counseling services done in engaging people in virtual care? Currently, given the overall increase in mental health challenges during the pandemic, one would expect that the use of mental health counseling is increasing. “If they’re stagnant or going down, someone needs to be reflecting on that issue internally in the clinic,” he said.
• Are patients being contacted regarding the effects that isolation is having on their lives? “The things that would normally allow us to self-mitigate and self-manage these conditions, like going to the gym, meeting with friends, religious services – all of those are being cut,” he said.
• Is there an early alert from an in-person pharmacy to trigger outreach via a community health worker for patients who haven’t picked up their medications in a week or more?

Farley pointed to a 2015 model for an enhanced e-health approach to chronic care management that called for e-support from the community and that was enhanced through virtual communities.

These are some of the approaches Farley has taken at his clinic. He leads a team that focuses specifically on patients who struggled with engagement before the pandemic. Through a grant from the US Department of Health & Human Services’ Health Resources and Services Administration – even before the pandemic – that team has been funding community health workers who have multiple contacts with patients online and virtually and are able to offer what he calls “unapologetically enabling” support for patients so that they are able to focus on their health.

He gave the following example. Before the pandemic, a community health worker on the team had been working with a patient who showed up at every scheduled visit and swore that she was taking her medications, although clearly she was not. A community health worker, who was made available through the grant, was able to recognize that the patient’s biggest challenge in her life was providing childcare for her special-needs child. The community health worker worked with the patient for months to find stable childcare for the child, paid 2 months of rent for the patient so that she would not become homeless, and helped her find transitional housing. When the pandemic hit, the community health worker was already texting and conducting video calls with the patient regularly.

For the past 9 months, that patient has had an undetectable viral load, Farley said.

“Nine months during a pandemic,” Farley reiterated, “and the community health worker keeps working with her, keeps meeting with her.”
 

Stigma on stigma

The need for this level of support from the clinic may be even more important for people with HIV who acquire COVID-19, said Orlando Harris, PhD, assistant professor of community health systems at the University of California, San Francisco, (UCSF) School of Nursing. HIV-related stigma is a well-known deterrent to care for people living with the virus. During the presentation, Harris asked Farley about the impact of COVID-19 stigma on people with both HIV and COVID-19.

Farley said that patients at his clinic have told him that they have “ostracized” friends who have tested positive for COVID-19. Harris remembered a person with HIV who participated in one of his trials telling the researchers that despite all his precautions – wearing a mask, staying socially distant – he still acquired COVID-19. There was nothing he could have done, Harris said, other than just not go to the grocery store.

The fear of contracting another disease that is associated with stigma, as well as the need to disclose it, can inflame memories of the trauma of being diagnosed with HIV, Harris said. And with patient-centered medical homes struggling to reconstitute their wraparound services via telehealth, he said he wonders whether clinicians should be doing more.

“I worry about people who have survived being diagnosed with HIV in the ‘80s and the ‘90s before antiretroviral therapy showed up on the scene,” he told Medscape Medical News. “I worry that the folks that survived one pandemic [may] be feeling fearful or living in that fear that this new pandemic might take them out. That’s why I’m stressing the need for us to really consider, as clinicians and also as researchers the support systems, the coping mechanisms, the counseling, or what have you to support those living with HIV and vulnerable to COVID-19.”

During telehealth visits, that can be achieved simply by asking people how they are really doing and what their coping mechanisms are.

For their part, the clinicians at San Francisco’s Ward 86 are not trying to provide that support through telehealth on the same level as they were at the beginning of the pandemic, said Matthew Spinelli, MD, assistant professor of medicine, and Monica Gandhi, MD, associate chief of the Division of HIV, Infectious Diseases and Global Medicine, who are both at UCSF and are coauthors of the study.

They still offer telemedicine appointments to patients who request them, said Spinelli. He said about one-third of his patients still prefer to receive their care virtually. The rest have gone back to face-to-face support.

“The analysis led us to promptly open up care as much as possible to our patients, with the idea that telehealth is not cutting it for vulnerable patients with HIV,” Gandhi told Medscape Medical News via email. “We don’t think it’s right for a population who relies on social support from the clinic.”
 

This article first appeared on Medscape.com.

Over the last 40 years, there has been a doubling in the incidence of testicular cancer. Over the same period, there has been a 20-fold increase in the use of diagnostic radiation, and the doses of radiation used have increased sevenfold. Perhaps the two are related?

The suggestion comes from researchers reporting a new case-control study in which they show that repeated diagnostic radiation below the waist was associated with an increase in the risk of testicular germ cell tumor (TGCT).

The study involved 315 men with TGCT and 931 controls from hospital and population-based settings. Researchers analyzed medical records and individuals’ recall of diagnostic radiation, such as CT scans, x-rays, and barium enema.

Compared with men who did not undergo any diagnostic radiation, the risk of testicular cancer was nearly twofold higher among men who had undergone three or more diagnostic x-rays and CT scans, and more than fourfold higher among men who had undergone three or more lower gastrointestinal series or barium enema.

The study was published online Nov. 11 in PLoS ONE.

Testicular cancer, the most common cancer in white men aged 15-44 years, has steadily increased in incidence in the United States over the past 3 or 4 decades. The rate has jumped from 3 out of 100,000 men in 1975 to 6 out of 100,000 men today, said senior author Katherine Nathanson, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“Our data suggests that the increased use of diagnostic radiation below the waist in men over that same time may contribute to the increase in incidence,” Dr. Nathanson said in a press statement.

Reducing diagnostic radiation doses to the testes “should be prioritized,” said the investigators, if these results are validated by additional research.

It’s “undoubtedly prudent” to reduce those doses “as much as possible,” said David Brenner, PhD, director of the Center for Radiological Research, Columbia University Medical Center, New York.

However, Dr. Brenner also had reservations about the new study. “I do find the results quite surprising,” given what is known historically about testicular cancer and radiation exposure.

Higher radiation doses (than in the current study) in two other settings (among post–atomic bomb survivors and in the treatment of ankylosing spondylitis) are not associated with an increased risk of testicular cancer, Dr. Brenner said in an interview.

“Underlying conditions for which the individual received radiation imaging,” may be one potential explanation for the increased testicular cancer risk seen in this study, he added.

Dr. Nathanson responded to Dr. Brenner’s critique by focusing on atomic bomb survivors and pointing out that the baseline rate of testicular cancer in Asia, including Japan, is “very, very low” and therefore that population, including bomb survivors, is not a highly applicable comparison.
 

Take-home message: Testicular shielding

Dr. Nathanson noted that diagnostic imaging below the waist is most commonly administered as a result of GI tract complaints such as constipation and abdominal pain. For clinicians, the study’s take-home message supports testicular shielding.

Testicular shielding during diagnostic imaging can be protective, but audits show that correct use and positioning occurs in just 25% of pediatric diagnostic scans, the authors commented.

Recent epidemiologic studies support a tie between diagnostic radiation and other cancers, the authors also pointed out.

For example, women undergoing frequent x-rays for scoliosis may have an increased risk of breast cancer, and likewise for individuals undergoing repeat routine dental x-rays and thyroid cancer. Additionally, a National Health Service study among 175,000 children revealed an excess risk of subsequent brain tumors and leukemia tied to CT scans, said Dr. Nathanson and coauthors.

Total dose and number of exposures were associated with an increasing cancer risk in each of the aforementioned studies.

Dr. Nathanson pointed out that Penn researchers have collected testicular cancer data since 2001 for the sake of research on related, inherited risk. The new study is an outgrowth of those efforts and is a rare effort in this subject area, in part, because testicular cancer is a very treatable rare cancer, with a 95% survival rate at 5 years.

A larger prospective study of the association between diagnostic radiation and testicular cancer would be better for determining causality, but is impractical given the needed time and associated costs. “A case-control design is a methodology that is ideally suited for studies investigating rare disease outcomes such as TGCT,” the authors comment.

The study was supported with grants from the National Cancer Institute and the National Institutes of Health. The study authors and Dr. Brenner disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Over the last 40 years, there has been a doubling in the incidence of testicular cancer. Over the same period, there has been a 20-fold increase in the use of diagnostic radiation, and the doses of radiation used have increased sevenfold. Perhaps the two are related?

The suggestion comes from researchers reporting a new case-control study in which they show that repeated diagnostic radiation below the waist was associated with an increase in the risk of testicular germ cell tumor (TGCT).

The study involved 315 men with TGCT and 931 controls from hospital and population-based settings. Researchers analyzed medical records and individuals’ recall of diagnostic radiation, such as CT scans, x-rays, and barium enema.

Compared with men who did not undergo any diagnostic radiation, the risk of testicular cancer was nearly twofold higher among men who had undergone three or more diagnostic x-rays and CT scans, and more than fourfold higher among men who had undergone three or more lower gastrointestinal series or barium enema.

The study was published online Nov. 11 in PLoS ONE.

Testicular cancer, the most common cancer in white men aged 15-44 years, has steadily increased in incidence in the United States over the past 3 or 4 decades. The rate has jumped from 3 out of 100,000 men in 1975 to 6 out of 100,000 men today, said senior author Katherine Nathanson, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“Our data suggests that the increased use of diagnostic radiation below the waist in men over that same time may contribute to the increase in incidence,” Dr. Nathanson said in a press statement.

Reducing diagnostic radiation doses to the testes “should be prioritized,” said the investigators, if these results are validated by additional research.

It’s “undoubtedly prudent” to reduce those doses “as much as possible,” said David Brenner, PhD, director of the Center for Radiological Research, Columbia University Medical Center, New York.

However, Dr. Brenner also had reservations about the new study. “I do find the results quite surprising,” given what is known historically about testicular cancer and radiation exposure.

Higher radiation doses (than in the current study) in two other settings (among post–atomic bomb survivors and in the treatment of ankylosing spondylitis) are not associated with an increased risk of testicular cancer, Dr. Brenner said in an interview.

“Underlying conditions for which the individual received radiation imaging,” may be one potential explanation for the increased testicular cancer risk seen in this study, he added.

Dr. Nathanson responded to Dr. Brenner’s critique by focusing on atomic bomb survivors and pointing out that the baseline rate of testicular cancer in Asia, including Japan, is “very, very low” and therefore that population, including bomb survivors, is not a highly applicable comparison.
 

Take-home message: Testicular shielding

Dr. Nathanson noted that diagnostic imaging below the waist is most commonly administered as a result of GI tract complaints such as constipation and abdominal pain. For clinicians, the study’s take-home message supports testicular shielding.

Testicular shielding during diagnostic imaging can be protective, but audits show that correct use and positioning occurs in just 25% of pediatric diagnostic scans, the authors commented.

Recent epidemiologic studies support a tie between diagnostic radiation and other cancers, the authors also pointed out.

For example, women undergoing frequent x-rays for scoliosis may have an increased risk of breast cancer, and likewise for individuals undergoing repeat routine dental x-rays and thyroid cancer. Additionally, a National Health Service study among 175,000 children revealed an excess risk of subsequent brain tumors and leukemia tied to CT scans, said Dr. Nathanson and coauthors.

Total dose and number of exposures were associated with an increasing cancer risk in each of the aforementioned studies.

Dr. Nathanson pointed out that Penn researchers have collected testicular cancer data since 2001 for the sake of research on related, inherited risk. The new study is an outgrowth of those efforts and is a rare effort in this subject area, in part, because testicular cancer is a very treatable rare cancer, with a 95% survival rate at 5 years.

A larger prospective study of the association between diagnostic radiation and testicular cancer would be better for determining causality, but is impractical given the needed time and associated costs. “A case-control design is a methodology that is ideally suited for studies investigating rare disease outcomes such as TGCT,” the authors comment.

The study was supported with grants from the National Cancer Institute and the National Institutes of Health. The study authors and Dr. Brenner disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Over the last 40 years, there has been a doubling in the incidence of testicular cancer. Over the same period, there has been a 20-fold increase in the use of diagnostic radiation, and the doses of radiation used have increased sevenfold. Perhaps the two are related?

The suggestion comes from researchers reporting a new case-control study in which they show that repeated diagnostic radiation below the waist was associated with an increase in the risk of testicular germ cell tumor (TGCT).

The study involved 315 men with TGCT and 931 controls from hospital and population-based settings. Researchers analyzed medical records and individuals’ recall of diagnostic radiation, such as CT scans, x-rays, and barium enema.

Compared with men who did not undergo any diagnostic radiation, the risk of testicular cancer was nearly twofold higher among men who had undergone three or more diagnostic x-rays and CT scans, and more than fourfold higher among men who had undergone three or more lower gastrointestinal series or barium enema.

The study was published online Nov. 11 in PLoS ONE.

Testicular cancer, the most common cancer in white men aged 15-44 years, has steadily increased in incidence in the United States over the past 3 or 4 decades. The rate has jumped from 3 out of 100,000 men in 1975 to 6 out of 100,000 men today, said senior author Katherine Nathanson, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“Our data suggests that the increased use of diagnostic radiation below the waist in men over that same time may contribute to the increase in incidence,” Dr. Nathanson said in a press statement.

Reducing diagnostic radiation doses to the testes “should be prioritized,” said the investigators, if these results are validated by additional research.

It’s “undoubtedly prudent” to reduce those doses “as much as possible,” said David Brenner, PhD, director of the Center for Radiological Research, Columbia University Medical Center, New York.

However, Dr. Brenner also had reservations about the new study. “I do find the results quite surprising,” given what is known historically about testicular cancer and radiation exposure.

Higher radiation doses (than in the current study) in two other settings (among post–atomic bomb survivors and in the treatment of ankylosing spondylitis) are not associated with an increased risk of testicular cancer, Dr. Brenner said in an interview.

“Underlying conditions for which the individual received radiation imaging,” may be one potential explanation for the increased testicular cancer risk seen in this study, he added.

Dr. Nathanson responded to Dr. Brenner’s critique by focusing on atomic bomb survivors and pointing out that the baseline rate of testicular cancer in Asia, including Japan, is “very, very low” and therefore that population, including bomb survivors, is not a highly applicable comparison.
 

Take-home message: Testicular shielding

Dr. Nathanson noted that diagnostic imaging below the waist is most commonly administered as a result of GI tract complaints such as constipation and abdominal pain. For clinicians, the study’s take-home message supports testicular shielding.

Testicular shielding during diagnostic imaging can be protective, but audits show that correct use and positioning occurs in just 25% of pediatric diagnostic scans, the authors commented.

Recent epidemiologic studies support a tie between diagnostic radiation and other cancers, the authors also pointed out.

For example, women undergoing frequent x-rays for scoliosis may have an increased risk of breast cancer, and likewise for individuals undergoing repeat routine dental x-rays and thyroid cancer. Additionally, a National Health Service study among 175,000 children revealed an excess risk of subsequent brain tumors and leukemia tied to CT scans, said Dr. Nathanson and coauthors.

Total dose and number of exposures were associated with an increasing cancer risk in each of the aforementioned studies.

Dr. Nathanson pointed out that Penn researchers have collected testicular cancer data since 2001 for the sake of research on related, inherited risk. The new study is an outgrowth of those efforts and is a rare effort in this subject area, in part, because testicular cancer is a very treatable rare cancer, with a 95% survival rate at 5 years.

A larger prospective study of the association between diagnostic radiation and testicular cancer would be better for determining causality, but is impractical given the needed time and associated costs. “A case-control design is a methodology that is ideally suited for studies investigating rare disease outcomes such as TGCT,” the authors comment.

The study was supported with grants from the National Cancer Institute and the National Institutes of Health. The study authors and Dr. Brenner disclosed no relevant financial relationships.

This article first appeared on Medscape.com.