Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

Older people with prediabetes who followed a diet rich in sardines for 1 year show significant reductions in risk of developing type 2 diabetes compared with those placed on a similarly healthy diet but without the sardines, results from a new randomized trial show. 

“A 1-year, sardine-enriched type 2 diabetes-preventive diet in an elderly population with prediabetes exerts a greater protective effect against developing type 2 diabetes and cardiovascular events, by improving anthropometric parameters, blood chemistry profile, lipid composition in erythrocytes membranes, and metabolomics data,” report the authors in research published in Clinical Nutrition by Diana Díaz-Rizzolo, PhD, of the Hospital Clinic of Barcelona, Spain, and colleagues.

While cardiovascular and other health benefits of unsaturated fats in oily fish are well-established and are a key component in diets such as the highly recommended Mediterranean diet, the authors note that the consumption of sardines for the prevention of type 2 diabetes has not previously been studied.

In addition to being rich in healthy omega-3 fatty acids, sardines have high concentrations of taurine – approximately 147 mg per 100 g serving – which, depending on the sardine species, is believed to have hypoglycemic, antioxidant, and anti-inflammatory benefits, the authors note.
 

Participants advised to consume the whole sardine, bones and all

To evaluate the effects, researchers enrolled 152 patients aged 65 and older who had been diagnosed with prediabetes (blood glucose levels between 100-124 mg/dL) and placed them all on a nutritional program to reduce the risk of diabetes for 1 year.

In addition, about half (n = 75) were also instructed to consume 200 g of canned sardines in olive oil per week, in 100 g servings consumed twice per week.

Those participants were recommended to consume the entire sardine, without removal of bones, due to their rich content of calcium and vitamin D. They were also provided with recipes that used canned sardines.

At 1 year, the percentage of participants classified as being at a very high risk of type 2 diabetes, assessed by the Finnish Diabetes Risk Score (FINDRISC), compared with baseline, had declined to a much greater degree in the sardine consumption group (37% at baseline vs. 8% at 1 year) compared with those in the control group, who only consumed the nutritional diet (27% vs. 22%) (P = .021).

In addition, those in the sardine group had greater increases in healthy HDL cholesterol and the glucose-regulating protein hormone adiponectin, with decreases in triglycerides compared with the nonsardine group (all P < .005).

Furthermore, the sardine consumption group had a greater decrease in insulin resistance, assessed by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; P = .032).
 

Sardines are cheap and reduce blood pressure too

“Not only are sardines reasonably priced and easy to find, but they are safe and help to prevent the onset of type 2 diabetes,” said Dr. Díaz-Rizzolo in a press statement.

Those in the sardine group also showed significant decreases in systolic blood pressure (P = .014) and diastolic blood pressure (P = .020) versus baseline, while no significant changes were observed in the control group. The authors suggest that sardines’ rich taurine concentrations could play a role in those effects.

“Previously, only lean fish consumption had demonstrated an improvement in blood pressure, not fatty fish consumption, perhaps because the species studied excluded those with a higher taurine content such as sardines,” they speculate.

In addition to showing improvements in levels of taurine, those in the sardine group also showed increases in nutrients that have been linked to health benefits, including omega-3 EPA and DHA, vitamin D, and fluorine (all P < .05).

The authors note that the increases could be attributed to sardines’ rich concentration of those nutrients, as well as to the olive oil that is present in the sardine can.
 

Some benefits seen in both groups

The patients in the study were a mean age of 71 and had been in a prediabetic state for an average of 4.8 years at the beginning of the study. They were 55% male and there were no other significant differences in characteristics between the groups.

While the conversion from being prediabetic to type 2 diabetes in the adult population has been reported to be about 10.6%, and the risk has been observed to be even higher in the 65 and older population, rates were lower than that in both groups.

“At the end of our 1-year study, we observed a [rate of] new-onset type 2 diabetes of 2.7% and 5.2% in the sardine group and control group, respectively,” the authors note. They add the differences were not statistically significant.

Both the sardine consumption and control groups showed significant reductions in A1c versus baseline (P = .011 and P = .010, respectively), as well as significant reductions in glucose fasting concentrations (P = .020 and P = .040, respectively).

And while the sardine group showed greater improvements in HDL versus the control group (P = .045), only the control group showed a significant decrease in total cholesterol versus baseline (P = .032).

Both groups showed improvements in the management of body weight, body mass index, and waist and hip circumference, in addition to improvement in body composition – despite no physical activity components in the programs, the authors note.

“This is probably because both groups followed the same base type 2 diabetes-preventive diet, with the one exception of sardine supplementation, and, although they did not modify their physical activity, both groups reduced their daily caloric intake through food,” the authors note.

The possibility of reducing diabetes risk through dietary changes as opposed to weight loss is especially important in the older population, the authors note, as some studies suggest a link between weight loss in the elderly and an increased risk of mortality.

In a second phase of the study, the researchers say they are evaluating the effect of sardines on the intestinal microbiota, “since it affects the regulation of many biological processes, and we need to understand if they have played a part in this protective effect against type 2 diabetes,” Dr. Díaz-Rizzolo concluded.

The study was funded by RecerCaixa 2013. The authors report that “no industry sponsorship was received for this work that could have influenced its outcome.”

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

A new analysis from the TWILIGHT study has shown that, in the high-risk population undergoing percutaneous coronary intervention (PCI) enrolled in the study, the benefits of early aspirin withdrawal and continuation on ticagrelor monotherapy were similar in women and men.

But there were some interesting observations in the analysis suggesting possible additional benefits of this strategy for women.

“These data support the use of ticagrelor monotherapy in women and men, and importantly show that the absolute risk reduction of bleeding was higher in women, as their bleeding rates were higher,” senior author Roxana Mehran, MD, the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“These data also support the need for prospective dual antiplatelet therapy deescalation studies in women,” Dr. Mehran added.

The main results of the TWILIGHT study showed that after a short period of dual antiplatelet therapy, a strategy of ticagrelor monotherapy, compared with continued dual therapy led to reduced bleeding without an increase in ischemic events among patients at high risk for bleeding or ischemic events after PCI.

The new gender-based analysis was presented by Birgit Vogel, MD, on May 15 at the annual scientific sessions of the American College of Cardiology. It was also published online in JAMA Cardiology to coincide with the ACC presentation.

Dr. Vogel, also from Wiener Cardiovascular Institute, explained that the current analysis was undertaken to investigate whether the TWILIGHT results varied in relation to sex, given that women are believed to have an increased risk for bleeding after PCI, compared with men.

“The current analysis showed that, while women did have a higher bleeding risk, compared to men, this was no longer significant after adjustment for baseline characteristics; and ischemic events were similar between the two sexes,” she reported.

“Results showed that withdrawing aspirin while continuing ticagrelor after 3 months of dual antiplatelet therapy was associated with a reduction in bleeding and preserved ischemic benefits in both women and men,” she added.

The TWILIGHT trial randomized 7,119 patients at high risk of ischemic or bleeding events who had undergone successful PCI with at least one drug-eluting stent and had completed 3 months of dual antiplatelet therapy to aspirin or placebo for an additional 12 months plus open-label ticagrelor.

The main results showed that the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding at 1 year was almost halved with ticagrelor monotherapy, occurring in 4% of these patients, compared with 7.1% of the ticagrelor/aspirin group (hazard ratio, 0.56). Ischemic events were similar in the two groups.

The current analysis focused on whether these effects varied in relation to sex.

Dr. Vogel noted that women made up 23.9% of the study population, were older than the men, and were more likely to have diabetes, chronic kidney disease, anemia and hypertension, while the men were more likely to be current smokers. Men had a higher incidence of coronary heart disease history, while women were more likely to have an ACS indication for PCI.

Unadjusted results showed a higher rate of BARC 2, 3, or 5 bleeding at 1 year in women (6.8%) versus men (5.2%), giving an HR of 1.32 (95% CI, 1.06-1.64).

But after adjustment for baseline characteristics, this became nonsignificant (HR, 1.20; 95% CI, 0.95-1.52).

Dr. Vogel pointed out that the most severe type of bleeding (BARC 3 and 5) was not attenuated as much by adjustment for baseline characteristics, with the HR reducing from 1.57 to 1.49.

The ischemic endpoint of death/stroke or MI was similar in men (4.0%) and women (3.5%), and this did not change after adjustment for baseline characteristics.

In terms of the two treatment groups, BARC 2, 3, or 5 bleeding was reduced to a similar extent with ticagrelor monotherapy in both men and women. This endpoint decreased from 8.6% in women on dual-antiplatelet therapy to 5.0% in women on ticagrelor alone (adjusted HR, 0.62) and from 6.6% to 3.7% in men (aHR, 0.57). But she noted that the absolute risk reduction in bleeding was greater in women (3.6%) versus men (2.9%).

“If we have a relative risk reduction in bleeding with early withdrawal of aspirin that is similar between the sexes but an overall higher risk of bleeding in women, that results in a greater absolute risk reduction,” Dr. Vogel commented.

The primary ischemic endpoint of death/MI/stroke was not increased in the ticagrelor group vs the dual antiplatelet group in either men (aHR, 1.06) or women (aHR, 1.04).
 

Greater reduction in mortality in women?

However, Dr. Vogel reported that there was a suggestion of a greater reduction in all-cause mortality with ticagrelor monotherapy in women versus men. “We found a significant interaction for treatment effect and sex for all-cause mortality, a prespecified endpoint, which was significantly lower in women treated with ticagrelor monotherapy, compared to dual antiplatelet therapy, but this was not the case in men.”

However, this observation was based on few events and should not be considered definitive, she added.

Dr. Vogel noted that the analysis had the limitations of the study not being powered to show differences in men versus women, and the results are only applicable to the population studied who were at high risk of bleeding post PCI.

Commenting on the study at the ACC session, Jacqueline Tamis-Holland, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, described the presentation as “very interesting.”

“We know that women notoriously have higher bleeding risk than men, but this particular study did not show a difference in bleeding risk after adjusting for other confounding variables,” she said.

“In fact, one would think that the relative benefit of a treatment designed to decrease bleeding would be more favorable to women, but this analysis didn’t show that,” she added.

Dr. Vogel replied that the HR of the most serious type of bleeding (BARC 3 and 5) in women versus men was only reduced minimally after adjustment for baseline characteristics, “which still makes us think that there are additional factors that might be important and contribute to an increased risk for bleeding and especially more serous types of bleeding in women.”

She pointed out that, while there was a similar risk reduction in bleeding in women and men, there was a potential mortality benefit in women. “The question is whether this mortality benefit is due to reduced bleeding that might be greater in women than men, and the reality is we don’t have a lot of data on that.”

Dr. Vogel added: “We know about the relationship between bleeding and mortality very well but the impact of sex on this is really not well investigated. It would be worth investigating this further to come up with bleeding reduction strategies for women because this is a really important issue.”

This work was supported by an investigator-initiated grant from AstraZeneca. Dr. Mehran reported grants and personal fees (paid to the institution) from Abbott, Abiomed, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Chiesi, Concept Medical Research, Medtronic, Novartis and DSI Research; grants from Applied Therapeutics, AstraZeneca, Cerecor, CSL Behring, OrbusNeich, and Zoll; personal fees from Boston Scientific, California Institute for Regenerative Medicine, Cine-Med Research, Janssen Scientific Affairs, ACC, and WebMD; personal fees paid to the institution from CardiaWave, Duke University, and Idorsia Pharmaceuticals; serving as a consultant or committee or advisory board member for Society for Cardiovascular Angiography and Interventions, the American Medical Association, and Regeneron Pharmaceuticals; and owning stock in ControlRad, Elixir Medical, and STEL outside the submitted work. Dr. Vogel disclosed no relevant financial relationships.

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

A new analysis from the TWILIGHT study has shown that, in the high-risk population undergoing percutaneous coronary intervention (PCI) enrolled in the study, the benefits of early aspirin withdrawal and continuation on ticagrelor monotherapy were similar in women and men.

But there were some interesting observations in the analysis suggesting possible additional benefits of this strategy for women.

“These data support the use of ticagrelor monotherapy in women and men, and importantly show that the absolute risk reduction of bleeding was higher in women, as their bleeding rates were higher,” senior author Roxana Mehran, MD, the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“These data also support the need for prospective dual antiplatelet therapy deescalation studies in women,” Dr. Mehran added.

The main results of the TWILIGHT study showed that after a short period of dual antiplatelet therapy, a strategy of ticagrelor monotherapy, compared with continued dual therapy led to reduced bleeding without an increase in ischemic events among patients at high risk for bleeding or ischemic events after PCI.

The new gender-based analysis was presented by Birgit Vogel, MD, on May 15 at the annual scientific sessions of the American College of Cardiology. It was also published online in JAMA Cardiology to coincide with the ACC presentation.

Dr. Vogel, also from Wiener Cardiovascular Institute, explained that the current analysis was undertaken to investigate whether the TWILIGHT results varied in relation to sex, given that women are believed to have an increased risk for bleeding after PCI, compared with men.

“The current analysis showed that, while women did have a higher bleeding risk, compared to men, this was no longer significant after adjustment for baseline characteristics; and ischemic events were similar between the two sexes,” she reported.

“Results showed that withdrawing aspirin while continuing ticagrelor after 3 months of dual antiplatelet therapy was associated with a reduction in bleeding and preserved ischemic benefits in both women and men,” she added.

The TWILIGHT trial randomized 7,119 patients at high risk of ischemic or bleeding events who had undergone successful PCI with at least one drug-eluting stent and had completed 3 months of dual antiplatelet therapy to aspirin or placebo for an additional 12 months plus open-label ticagrelor.

The main results showed that the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding at 1 year was almost halved with ticagrelor monotherapy, occurring in 4% of these patients, compared with 7.1% of the ticagrelor/aspirin group (hazard ratio, 0.56). Ischemic events were similar in the two groups.

The current analysis focused on whether these effects varied in relation to sex.

Dr. Vogel noted that women made up 23.9% of the study population, were older than the men, and were more likely to have diabetes, chronic kidney disease, anemia and hypertension, while the men were more likely to be current smokers. Men had a higher incidence of coronary heart disease history, while women were more likely to have an ACS indication for PCI.

Unadjusted results showed a higher rate of BARC 2, 3, or 5 bleeding at 1 year in women (6.8%) versus men (5.2%), giving an HR of 1.32 (95% CI, 1.06-1.64).

But after adjustment for baseline characteristics, this became nonsignificant (HR, 1.20; 95% CI, 0.95-1.52).

Dr. Vogel pointed out that the most severe type of bleeding (BARC 3 and 5) was not attenuated as much by adjustment for baseline characteristics, with the HR reducing from 1.57 to 1.49.

The ischemic endpoint of death/stroke or MI was similar in men (4.0%) and women (3.5%), and this did not change after adjustment for baseline characteristics.

In terms of the two treatment groups, BARC 2, 3, or 5 bleeding was reduced to a similar extent with ticagrelor monotherapy in both men and women. This endpoint decreased from 8.6% in women on dual-antiplatelet therapy to 5.0% in women on ticagrelor alone (adjusted HR, 0.62) and from 6.6% to 3.7% in men (aHR, 0.57). But she noted that the absolute risk reduction in bleeding was greater in women (3.6%) versus men (2.9%).

“If we have a relative risk reduction in bleeding with early withdrawal of aspirin that is similar between the sexes but an overall higher risk of bleeding in women, that results in a greater absolute risk reduction,” Dr. Vogel commented.

The primary ischemic endpoint of death/MI/stroke was not increased in the ticagrelor group vs the dual antiplatelet group in either men (aHR, 1.06) or women (aHR, 1.04).
 

Greater reduction in mortality in women?

However, Dr. Vogel reported that there was a suggestion of a greater reduction in all-cause mortality with ticagrelor monotherapy in women versus men. “We found a significant interaction for treatment effect and sex for all-cause mortality, a prespecified endpoint, which was significantly lower in women treated with ticagrelor monotherapy, compared to dual antiplatelet therapy, but this was not the case in men.”

However, this observation was based on few events and should not be considered definitive, she added.

Dr. Vogel noted that the analysis had the limitations of the study not being powered to show differences in men versus women, and the results are only applicable to the population studied who were at high risk of bleeding post PCI.

Commenting on the study at the ACC session, Jacqueline Tamis-Holland, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, described the presentation as “very interesting.”

“We know that women notoriously have higher bleeding risk than men, but this particular study did not show a difference in bleeding risk after adjusting for other confounding variables,” she said.

“In fact, one would think that the relative benefit of a treatment designed to decrease bleeding would be more favorable to women, but this analysis didn’t show that,” she added.

Dr. Vogel replied that the HR of the most serious type of bleeding (BARC 3 and 5) in women versus men was only reduced minimally after adjustment for baseline characteristics, “which still makes us think that there are additional factors that might be important and contribute to an increased risk for bleeding and especially more serous types of bleeding in women.”

She pointed out that, while there was a similar risk reduction in bleeding in women and men, there was a potential mortality benefit in women. “The question is whether this mortality benefit is due to reduced bleeding that might be greater in women than men, and the reality is we don’t have a lot of data on that.”

Dr. Vogel added: “We know about the relationship between bleeding and mortality very well but the impact of sex on this is really not well investigated. It would be worth investigating this further to come up with bleeding reduction strategies for women because this is a really important issue.”

This work was supported by an investigator-initiated grant from AstraZeneca. Dr. Mehran reported grants and personal fees (paid to the institution) from Abbott, Abiomed, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Chiesi, Concept Medical Research, Medtronic, Novartis and DSI Research; grants from Applied Therapeutics, AstraZeneca, Cerecor, CSL Behring, OrbusNeich, and Zoll; personal fees from Boston Scientific, California Institute for Regenerative Medicine, Cine-Med Research, Janssen Scientific Affairs, ACC, and WebMD; personal fees paid to the institution from CardiaWave, Duke University, and Idorsia Pharmaceuticals; serving as a consultant or committee or advisory board member for Society for Cardiovascular Angiography and Interventions, the American Medical Association, and Regeneron Pharmaceuticals; and owning stock in ControlRad, Elixir Medical, and STEL outside the submitted work. Dr. Vogel disclosed no relevant financial relationships.

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

A new analysis from the TWILIGHT study has shown that, in the high-risk population undergoing percutaneous coronary intervention (PCI) enrolled in the study, the benefits of early aspirin withdrawal and continuation on ticagrelor monotherapy were similar in women and men.

But there were some interesting observations in the analysis suggesting possible additional benefits of this strategy for women.

“These data support the use of ticagrelor monotherapy in women and men, and importantly show that the absolute risk reduction of bleeding was higher in women, as their bleeding rates were higher,” senior author Roxana Mehran, MD, the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“These data also support the need for prospective dual antiplatelet therapy deescalation studies in women,” Dr. Mehran added.

The main results of the TWILIGHT study showed that after a short period of dual antiplatelet therapy, a strategy of ticagrelor monotherapy, compared with continued dual therapy led to reduced bleeding without an increase in ischemic events among patients at high risk for bleeding or ischemic events after PCI.

The new gender-based analysis was presented by Birgit Vogel, MD, on May 15 at the annual scientific sessions of the American College of Cardiology. It was also published online in JAMA Cardiology to coincide with the ACC presentation.

Dr. Vogel, also from Wiener Cardiovascular Institute, explained that the current analysis was undertaken to investigate whether the TWILIGHT results varied in relation to sex, given that women are believed to have an increased risk for bleeding after PCI, compared with men.

“The current analysis showed that, while women did have a higher bleeding risk, compared to men, this was no longer significant after adjustment for baseline characteristics; and ischemic events were similar between the two sexes,” she reported.

“Results showed that withdrawing aspirin while continuing ticagrelor after 3 months of dual antiplatelet therapy was associated with a reduction in bleeding and preserved ischemic benefits in both women and men,” she added.

The TWILIGHT trial randomized 7,119 patients at high risk of ischemic or bleeding events who had undergone successful PCI with at least one drug-eluting stent and had completed 3 months of dual antiplatelet therapy to aspirin or placebo for an additional 12 months plus open-label ticagrelor.

The main results showed that the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding at 1 year was almost halved with ticagrelor monotherapy, occurring in 4% of these patients, compared with 7.1% of the ticagrelor/aspirin group (hazard ratio, 0.56). Ischemic events were similar in the two groups.

The current analysis focused on whether these effects varied in relation to sex.

Dr. Vogel noted that women made up 23.9% of the study population, were older than the men, and were more likely to have diabetes, chronic kidney disease, anemia and hypertension, while the men were more likely to be current smokers. Men had a higher incidence of coronary heart disease history, while women were more likely to have an ACS indication for PCI.

Unadjusted results showed a higher rate of BARC 2, 3, or 5 bleeding at 1 year in women (6.8%) versus men (5.2%), giving an HR of 1.32 (95% CI, 1.06-1.64).

But after adjustment for baseline characteristics, this became nonsignificant (HR, 1.20; 95% CI, 0.95-1.52).

Dr. Vogel pointed out that the most severe type of bleeding (BARC 3 and 5) was not attenuated as much by adjustment for baseline characteristics, with the HR reducing from 1.57 to 1.49.

The ischemic endpoint of death/stroke or MI was similar in men (4.0%) and women (3.5%), and this did not change after adjustment for baseline characteristics.

In terms of the two treatment groups, BARC 2, 3, or 5 bleeding was reduced to a similar extent with ticagrelor monotherapy in both men and women. This endpoint decreased from 8.6% in women on dual-antiplatelet therapy to 5.0% in women on ticagrelor alone (adjusted HR, 0.62) and from 6.6% to 3.7% in men (aHR, 0.57). But she noted that the absolute risk reduction in bleeding was greater in women (3.6%) versus men (2.9%).

“If we have a relative risk reduction in bleeding with early withdrawal of aspirin that is similar between the sexes but an overall higher risk of bleeding in women, that results in a greater absolute risk reduction,” Dr. Vogel commented.

The primary ischemic endpoint of death/MI/stroke was not increased in the ticagrelor group vs the dual antiplatelet group in either men (aHR, 1.06) or women (aHR, 1.04).
 

Greater reduction in mortality in women?

However, Dr. Vogel reported that there was a suggestion of a greater reduction in all-cause mortality with ticagrelor monotherapy in women versus men. “We found a significant interaction for treatment effect and sex for all-cause mortality, a prespecified endpoint, which was significantly lower in women treated with ticagrelor monotherapy, compared to dual antiplatelet therapy, but this was not the case in men.”

However, this observation was based on few events and should not be considered definitive, she added.

Dr. Vogel noted that the analysis had the limitations of the study not being powered to show differences in men versus women, and the results are only applicable to the population studied who were at high risk of bleeding post PCI.

Commenting on the study at the ACC session, Jacqueline Tamis-Holland, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, described the presentation as “very interesting.”

“We know that women notoriously have higher bleeding risk than men, but this particular study did not show a difference in bleeding risk after adjusting for other confounding variables,” she said.

“In fact, one would think that the relative benefit of a treatment designed to decrease bleeding would be more favorable to women, but this analysis didn’t show that,” she added.

Dr. Vogel replied that the HR of the most serious type of bleeding (BARC 3 and 5) in women versus men was only reduced minimally after adjustment for baseline characteristics, “which still makes us think that there are additional factors that might be important and contribute to an increased risk for bleeding and especially more serous types of bleeding in women.”

She pointed out that, while there was a similar risk reduction in bleeding in women and men, there was a potential mortality benefit in women. “The question is whether this mortality benefit is due to reduced bleeding that might be greater in women than men, and the reality is we don’t have a lot of data on that.”

Dr. Vogel added: “We know about the relationship between bleeding and mortality very well but the impact of sex on this is really not well investigated. It would be worth investigating this further to come up with bleeding reduction strategies for women because this is a really important issue.”

This work was supported by an investigator-initiated grant from AstraZeneca. Dr. Mehran reported grants and personal fees (paid to the institution) from Abbott, Abiomed, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Chiesi, Concept Medical Research, Medtronic, Novartis and DSI Research; grants from Applied Therapeutics, AstraZeneca, Cerecor, CSL Behring, OrbusNeich, and Zoll; personal fees from Boston Scientific, California Institute for Regenerative Medicine, Cine-Med Research, Janssen Scientific Affairs, ACC, and WebMD; personal fees paid to the institution from CardiaWave, Duke University, and Idorsia Pharmaceuticals; serving as a consultant or committee or advisory board member for Society for Cardiovascular Angiography and Interventions, the American Medical Association, and Regeneron Pharmaceuticals; and owning stock in ControlRad, Elixir Medical, and STEL outside the submitted work. Dr. Vogel disclosed no relevant financial relationships.

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

Combined data from five implantable cardioverter-defibrillator (ICD) trials suggest that it is the underlying arrhythmic disorder, rather than the ICD therapy itself, that affects mortality in these patients.

Analysis of the MADIT II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID trials showed that the major determinant of mortality in patients receiving a primary prevention ICD was the arrhythmic substrate that leads to occurrence of fast ventricular tachycardia (VT), defined as ≥ 200 bpm, or ventricular fibrillation (VF), not adverse effects of the ICD shock therapy itself.

Patients experiencing an episode of VT had more than a twofold increased risk for death during a follow-up of 2½ years; however, ICD therapies for VT less than 200 bpm and inappropriate ICD shocks were not associated with a higher risk for death.

The findings were published online in the Journal of the American College of Cardiology.

“We know that patients receiving an ICD shock have increased mortality during subsequent follow-up,” first author Mehmet K. Aktas, MD, MBA, University of Rochester (N.Y.), said in an interview.

“There are conflicting data on the impact of ICD shocks on subsequent mortality, and in this study, we aimed to determine whether shocks per se increase subsequent mortality risk or whether the arrhythmic substrate that leads to ICD therapy results in subsequent risk of death,” Dr. Aktas said.

He and his team evaluated the association of ICD therapy with subsequent mortality according to the type of ICD therapy (model I), type of arrhythmia for which ICD therapy was delivered (model II), combined assessment of all arrhythmia and therapy types during follow-up (model III), and incremental risk associated with repeated ICD shocks (model IV).

The study cohort included 5,516 patients. Of these, 1,001 patients (18%) received appropriate ICD therapy and 561 (10%) received inappropriate ICD therapy during an average of 2.4 years.

Patients receiving an appropriate ICD therapy were more likely to be male and to have prior atrial arrhythmia and nonsustained VT compared with those without ICD therapy.

Patients receiving an inappropriate shock were more likely to be younger, to be African American, and to be less likely to have prior nonsustained VT, compared with those without ICD therapy.

Most patients (90%) were receiving beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers regardless of device therapy during follow-up, and 10% of patients were treated with amiodarone.

In model I, at 3 years, the cumulative probability of death following an appropriate ICD shock was 38% compared with no appropriate ICD shock (P < .001). Inappropriate shock alone was not associated with mortality risk.

In model II, which looked at the type of arrhythmia for which ICD therapy was delivered, the cumulative death rate at 3 years following the first occurrence of ICD therapy for VT ≥ 200 beats/min or VF was 27%, compared with 10% in patients not experiencing VT ≥ 200 beats/min or VF (P < .001).

In model III, the highest risk for death was observed following shocks delivered after a failed antitachycardia pacing (ATP) for fast VT (hazard ratio [HR], 3.05), followed by ICD shock for VF (HR, 2.86), ICD shock for fast VT without a prior ATP (HR, 2.83), and ICD shock for slower VT (< 200 beats/min) without a prior ATP (HR, 2.39).

In contrast, other types of appropriate and inappropriate shock or ATP therapies were not associated with a significant risk increase.

In model IV, which assessed the association of shock therapy counts with the risk for death, two or more ICD appropriate shocks were not associated with increased risk after the first appropriate ICD shock.

“Our findings shed light on the mechanisms associated with increased mortality risk in primary prevention ICD recipients,” Dr. Aktas said.

“Studies that evaluate interventions focused on treating and stabilizing the myocardial substrate, which promotes ventricular tachyarrhythmias, such as catheter ablation, are needed to improve survival in heart failure patients,” he added.
 

Thoughtful study design

In an accompanying editorial, Rajat Deo, MD, and Naga Venkata K. Pothineni, MD, both from the University of Pennsylvania, Philadelphia, praised the researchers for their “thoughtful study design.”

“The take-home message that is most relevant to our clinical practice is clear: Sustained ventricular arrhythmias are a prognostic marker of death and heart failure hospitalization,” they wrote.

The editorialists also commented on the higher rate of inappropriate ICD therapies in African Americans.

“It is concerning to observe that Black patients had a markedly higher rate of inappropriate ICD therapies compared with White patients – and this was in the setting of some of the most respectable, established, and well-funded clinical trials,” they wrote.

Reasons for disparities in outcomes include access to appropriate and affordable medical therapies, access to specialty clinics and caregivers, remote ICD monitoring, and compliance issues.

“Future work will need to understand how the social determinants of health including race affect the treatment and outcomes of our primary prevention ICD population,” they wrote.

Identifying and characterizing the arrhythmic substrate will become a key component of sudden cardiac death risk stratification, the editorialists predicted.

“Concurrently, we must continue to partner with industry colleagues and work with our professional societies to ensure health equity across our patient population,” they concluded.

Dr. Aktas has received research grants from Boston Scientific and Medtronic. Dr. Deo and his coeditorialists report no relevant financial relationships. The MADIT trials were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center. The RAID trial was funded by the National Institutes of Health.

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

Combined data from five implantable cardioverter-defibrillator (ICD) trials suggest that it is the underlying arrhythmic disorder, rather than the ICD therapy itself, that affects mortality in these patients.

Analysis of the MADIT II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID trials showed that the major determinant of mortality in patients receiving a primary prevention ICD was the arrhythmic substrate that leads to occurrence of fast ventricular tachycardia (VT), defined as ≥ 200 bpm, or ventricular fibrillation (VF), not adverse effects of the ICD shock therapy itself.

Patients experiencing an episode of VT had more than a twofold increased risk for death during a follow-up of 2½ years; however, ICD therapies for VT less than 200 bpm and inappropriate ICD shocks were not associated with a higher risk for death.

The findings were published online in the Journal of the American College of Cardiology.

“We know that patients receiving an ICD shock have increased mortality during subsequent follow-up,” first author Mehmet K. Aktas, MD, MBA, University of Rochester (N.Y.), said in an interview.

“There are conflicting data on the impact of ICD shocks on subsequent mortality, and in this study, we aimed to determine whether shocks per se increase subsequent mortality risk or whether the arrhythmic substrate that leads to ICD therapy results in subsequent risk of death,” Dr. Aktas said.

He and his team evaluated the association of ICD therapy with subsequent mortality according to the type of ICD therapy (model I), type of arrhythmia for which ICD therapy was delivered (model II), combined assessment of all arrhythmia and therapy types during follow-up (model III), and incremental risk associated with repeated ICD shocks (model IV).

The study cohort included 5,516 patients. Of these, 1,001 patients (18%) received appropriate ICD therapy and 561 (10%) received inappropriate ICD therapy during an average of 2.4 years.

Patients receiving an appropriate ICD therapy were more likely to be male and to have prior atrial arrhythmia and nonsustained VT compared with those without ICD therapy.

Patients receiving an inappropriate shock were more likely to be younger, to be African American, and to be less likely to have prior nonsustained VT, compared with those without ICD therapy.

Most patients (90%) were receiving beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers regardless of device therapy during follow-up, and 10% of patients were treated with amiodarone.

In model I, at 3 years, the cumulative probability of death following an appropriate ICD shock was 38% compared with no appropriate ICD shock (P < .001). Inappropriate shock alone was not associated with mortality risk.

In model II, which looked at the type of arrhythmia for which ICD therapy was delivered, the cumulative death rate at 3 years following the first occurrence of ICD therapy for VT ≥ 200 beats/min or VF was 27%, compared with 10% in patients not experiencing VT ≥ 200 beats/min or VF (P < .001).

In model III, the highest risk for death was observed following shocks delivered after a failed antitachycardia pacing (ATP) for fast VT (hazard ratio [HR], 3.05), followed by ICD shock for VF (HR, 2.86), ICD shock for fast VT without a prior ATP (HR, 2.83), and ICD shock for slower VT (< 200 beats/min) without a prior ATP (HR, 2.39).

In contrast, other types of appropriate and inappropriate shock or ATP therapies were not associated with a significant risk increase.

In model IV, which assessed the association of shock therapy counts with the risk for death, two or more ICD appropriate shocks were not associated with increased risk after the first appropriate ICD shock.

“Our findings shed light on the mechanisms associated with increased mortality risk in primary prevention ICD recipients,” Dr. Aktas said.

“Studies that evaluate interventions focused on treating and stabilizing the myocardial substrate, which promotes ventricular tachyarrhythmias, such as catheter ablation, are needed to improve survival in heart failure patients,” he added.
 

Thoughtful study design

In an accompanying editorial, Rajat Deo, MD, and Naga Venkata K. Pothineni, MD, both from the University of Pennsylvania, Philadelphia, praised the researchers for their “thoughtful study design.”

“The take-home message that is most relevant to our clinical practice is clear: Sustained ventricular arrhythmias are a prognostic marker of death and heart failure hospitalization,” they wrote.

The editorialists also commented on the higher rate of inappropriate ICD therapies in African Americans.

“It is concerning to observe that Black patients had a markedly higher rate of inappropriate ICD therapies compared with White patients – and this was in the setting of some of the most respectable, established, and well-funded clinical trials,” they wrote.

Reasons for disparities in outcomes include access to appropriate and affordable medical therapies, access to specialty clinics and caregivers, remote ICD monitoring, and compliance issues.

“Future work will need to understand how the social determinants of health including race affect the treatment and outcomes of our primary prevention ICD population,” they wrote.

Identifying and characterizing the arrhythmic substrate will become a key component of sudden cardiac death risk stratification, the editorialists predicted.

“Concurrently, we must continue to partner with industry colleagues and work with our professional societies to ensure health equity across our patient population,” they concluded.

Dr. Aktas has received research grants from Boston Scientific and Medtronic. Dr. Deo and his coeditorialists report no relevant financial relationships. The MADIT trials were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center. The RAID trial was funded by the National Institutes of Health.

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

Combined data from five implantable cardioverter-defibrillator (ICD) trials suggest that it is the underlying arrhythmic disorder, rather than the ICD therapy itself, that affects mortality in these patients.

Analysis of the MADIT II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID trials showed that the major determinant of mortality in patients receiving a primary prevention ICD was the arrhythmic substrate that leads to occurrence of fast ventricular tachycardia (VT), defined as ≥ 200 bpm, or ventricular fibrillation (VF), not adverse effects of the ICD shock therapy itself.

Patients experiencing an episode of VT had more than a twofold increased risk for death during a follow-up of 2½ years; however, ICD therapies for VT less than 200 bpm and inappropriate ICD shocks were not associated with a higher risk for death.

The findings were published online in the Journal of the American College of Cardiology.

“We know that patients receiving an ICD shock have increased mortality during subsequent follow-up,” first author Mehmet K. Aktas, MD, MBA, University of Rochester (N.Y.), said in an interview.

“There are conflicting data on the impact of ICD shocks on subsequent mortality, and in this study, we aimed to determine whether shocks per se increase subsequent mortality risk or whether the arrhythmic substrate that leads to ICD therapy results in subsequent risk of death,” Dr. Aktas said.

He and his team evaluated the association of ICD therapy with subsequent mortality according to the type of ICD therapy (model I), type of arrhythmia for which ICD therapy was delivered (model II), combined assessment of all arrhythmia and therapy types during follow-up (model III), and incremental risk associated with repeated ICD shocks (model IV).

The study cohort included 5,516 patients. Of these, 1,001 patients (18%) received appropriate ICD therapy and 561 (10%) received inappropriate ICD therapy during an average of 2.4 years.

Patients receiving an appropriate ICD therapy were more likely to be male and to have prior atrial arrhythmia and nonsustained VT compared with those without ICD therapy.

Patients receiving an inappropriate shock were more likely to be younger, to be African American, and to be less likely to have prior nonsustained VT, compared with those without ICD therapy.

Most patients (90%) were receiving beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers regardless of device therapy during follow-up, and 10% of patients were treated with amiodarone.

In model I, at 3 years, the cumulative probability of death following an appropriate ICD shock was 38% compared with no appropriate ICD shock (P < .001). Inappropriate shock alone was not associated with mortality risk.

In model II, which looked at the type of arrhythmia for which ICD therapy was delivered, the cumulative death rate at 3 years following the first occurrence of ICD therapy for VT ≥ 200 beats/min or VF was 27%, compared with 10% in patients not experiencing VT ≥ 200 beats/min or VF (P < .001).

In model III, the highest risk for death was observed following shocks delivered after a failed antitachycardia pacing (ATP) for fast VT (hazard ratio [HR], 3.05), followed by ICD shock for VF (HR, 2.86), ICD shock for fast VT without a prior ATP (HR, 2.83), and ICD shock for slower VT (< 200 beats/min) without a prior ATP (HR, 2.39).

In contrast, other types of appropriate and inappropriate shock or ATP therapies were not associated with a significant risk increase.

In model IV, which assessed the association of shock therapy counts with the risk for death, two or more ICD appropriate shocks were not associated with increased risk after the first appropriate ICD shock.

“Our findings shed light on the mechanisms associated with increased mortality risk in primary prevention ICD recipients,” Dr. Aktas said.

“Studies that evaluate interventions focused on treating and stabilizing the myocardial substrate, which promotes ventricular tachyarrhythmias, such as catheter ablation, are needed to improve survival in heart failure patients,” he added.
 

Thoughtful study design

In an accompanying editorial, Rajat Deo, MD, and Naga Venkata K. Pothineni, MD, both from the University of Pennsylvania, Philadelphia, praised the researchers for their “thoughtful study design.”

“The take-home message that is most relevant to our clinical practice is clear: Sustained ventricular arrhythmias are a prognostic marker of death and heart failure hospitalization,” they wrote.

The editorialists also commented on the higher rate of inappropriate ICD therapies in African Americans.

“It is concerning to observe that Black patients had a markedly higher rate of inappropriate ICD therapies compared with White patients – and this was in the setting of some of the most respectable, established, and well-funded clinical trials,” they wrote.

Reasons for disparities in outcomes include access to appropriate and affordable medical therapies, access to specialty clinics and caregivers, remote ICD monitoring, and compliance issues.

“Future work will need to understand how the social determinants of health including race affect the treatment and outcomes of our primary prevention ICD population,” they wrote.

Identifying and characterizing the arrhythmic substrate will become a key component of sudden cardiac death risk stratification, the editorialists predicted.

“Concurrently, we must continue to partner with industry colleagues and work with our professional societies to ensure health equity across our patient population,” they concluded.

Dr. Aktas has received research grants from Boston Scientific and Medtronic. Dr. Deo and his coeditorialists report no relevant financial relationships. The MADIT trials were funded by an unrestricted research grant from Boston Scientific to the University of Rochester Medical Center. The RAID trial was funded by the National Institutes of Health.

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

Key clinical point: Erenumab significantly reduced acute medication use and health care resource utilization (HCRU) among patients with migraine in a real-world setting in the U.S.A.

Major finding: The mean number of claims (rate ratio [RR], 0.77) and number of patients using acute medication (both P less than .0001) significantly declined in 6 months postinitiation of erenumab. Similarly, 6-month HCRU of migraine-specific office visits (RR, 0.77) and all-cause office visits (RR, 0.92) decreased significantly (both P less than .0001).

Study details: Data come from a retrospective, exploratory analysis of 3,171 adult patients with migraine who initiated erenumab and had at least 3 doses in the 6 months post-index period.

Disclosures: The study was supported by Novartis Pharma AG. SJ Tepper reported serving as a consultant and/or on advisory boards, receiving grants, and CME honoraria from multiple sources. Some of the authors declared being employees and shareholders of Novartis.

Source: Tepper SJ et al. J Headache Pain. 2021 Apr 19. doi: 10.1186/s10194-021-01238-2.

Key clinical point: Erenumab significantly reduced acute medication use and health care resource utilization (HCRU) among patients with migraine in a real-world setting in the U.S.A.

Major finding: The mean number of claims (rate ratio [RR], 0.77) and number of patients using acute medication (both P less than .0001) significantly declined in 6 months postinitiation of erenumab. Similarly, 6-month HCRU of migraine-specific office visits (RR, 0.77) and all-cause office visits (RR, 0.92) decreased significantly (both P less than .0001).

Study details: Data come from a retrospective, exploratory analysis of 3,171 adult patients with migraine who initiated erenumab and had at least 3 doses in the 6 months post-index period.

Disclosures: The study was supported by Novartis Pharma AG. SJ Tepper reported serving as a consultant and/or on advisory boards, receiving grants, and CME honoraria from multiple sources. Some of the authors declared being employees and shareholders of Novartis.

Source: Tepper SJ et al. J Headache Pain. 2021 Apr 19. doi: 10.1186/s10194-021-01238-2.

Key clinical point: Erenumab significantly reduced acute medication use and health care resource utilization (HCRU) among patients with migraine in a real-world setting in the U.S.A.

Major finding: The mean number of claims (rate ratio [RR], 0.77) and number of patients using acute medication (both P less than .0001) significantly declined in 6 months postinitiation of erenumab. Similarly, 6-month HCRU of migraine-specific office visits (RR, 0.77) and all-cause office visits (RR, 0.92) decreased significantly (both P less than .0001).

Study details: Data come from a retrospective, exploratory analysis of 3,171 adult patients with migraine who initiated erenumab and had at least 3 doses in the 6 months post-index period.

Disclosures: The study was supported by Novartis Pharma AG. SJ Tepper reported serving as a consultant and/or on advisory boards, receiving grants, and CME honoraria from multiple sources. Some of the authors declared being employees and shareholders of Novartis.

Source: Tepper SJ et al. J Headache Pain. 2021 Apr 19. doi: 10.1186/s10194-021-01238-2.

Key clinical point: In patients with migraine, most calcitonin gene-related peptide (CGRP) monoclonal antibodies were similarly effective; however, galcanezumab was more likely to cause treatment-emerging adverse events (TEAEs).

Major finding: Fremanezumab vs. placebo had the highest probability to reduce monthly migraine days (mean difference [MD], −2.19; 95% credible interval [95% CrI], −3.15 to −1.25) followed by galcanezumab (MD, −2.10; 95% CrI, −2.76 to −1.45), erenumab (MD, −1.61; 95% CrI, −2.40 to −0.84), and eptinezumab (MD, −1.43; 95% CrI, −2.59 to −0.36). However, galcanezumab was more likely to cause TEAEs (relative risk, 1.11; 95% CrI, 1.01-1.22).

Study details: Findings are from a systematic review and network meta-analysis of 18 randomized clinical trials involving 8,926 patients with migraine.

Disclosures: No information on funding was available. The authors had no commercial or financial disclosures.

Source: Wang X et al. Front Pharmacol. 2021 Mar 25. doi: 10.3389/fphar.2021.649143.

Key clinical point: In patients with migraine, most calcitonin gene-related peptide (CGRP) monoclonal antibodies were similarly effective; however, galcanezumab was more likely to cause treatment-emerging adverse events (TEAEs).

Major finding: Fremanezumab vs. placebo had the highest probability to reduce monthly migraine days (mean difference [MD], −2.19; 95% credible interval [95% CrI], −3.15 to −1.25) followed by galcanezumab (MD, −2.10; 95% CrI, −2.76 to −1.45), erenumab (MD, −1.61; 95% CrI, −2.40 to −0.84), and eptinezumab (MD, −1.43; 95% CrI, −2.59 to −0.36). However, galcanezumab was more likely to cause TEAEs (relative risk, 1.11; 95% CrI, 1.01-1.22).

Study details: Findings are from a systematic review and network meta-analysis of 18 randomized clinical trials involving 8,926 patients with migraine.

Disclosures: No information on funding was available. The authors had no commercial or financial disclosures.

Source: Wang X et al. Front Pharmacol. 2021 Mar 25. doi: 10.3389/fphar.2021.649143.

Key clinical point: In patients with migraine, most calcitonin gene-related peptide (CGRP) monoclonal antibodies were similarly effective; however, galcanezumab was more likely to cause treatment-emerging adverse events (TEAEs).

Major finding: Fremanezumab vs. placebo had the highest probability to reduce monthly migraine days (mean difference [MD], −2.19; 95% credible interval [95% CrI], −3.15 to −1.25) followed by galcanezumab (MD, −2.10; 95% CrI, −2.76 to −1.45), erenumab (MD, −1.61; 95% CrI, −2.40 to −0.84), and eptinezumab (MD, −1.43; 95% CrI, −2.59 to −0.36). However, galcanezumab was more likely to cause TEAEs (relative risk, 1.11; 95% CrI, 1.01-1.22).

Study details: Findings are from a systematic review and network meta-analysis of 18 randomized clinical trials involving 8,926 patients with migraine.

Disclosures: No information on funding was available. The authors had no commercial or financial disclosures.

Source: Wang X et al. Front Pharmacol. 2021 Mar 25. doi: 10.3389/fphar.2021.649143.

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

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

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

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

Final results from the landmark SPRINT study confirm that aggressive blood pressure (BP) management, targeting a systolic blood pressure (SBP) below 120 mm Hg, significantly reduces the risk for heart disease, stroke, and death from these diseases, as well as death from all causes.

The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.

The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.

Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.

For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).

In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.

All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.

“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.

She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.

“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.

“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.

After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.

“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.

In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
 

Manageable risk

The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.

As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”

“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.

Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.

“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.

“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.

“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.

The potential adverse effects of intensive blood pressure control are “very manageable,” he added.

Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.

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

In the wake of the COVID-19 pandemic, a population of patients has arisen with a range of symptoms and complications after surviving the acute phase of illness, according to Mezgebe Berhe, MD, of Baylor University Medical Center, Dallas.

Different terms have been used to describe this condition, including post COVID, long COVID, chronic COVID, and long-haulers, Dr. Berhe said in a presentation at SHM Converge, the annual conference of the Society of Hospital Medicine. However, the current medical consensus for a definition is post–acute COVID-19 syndrome.

Acute COVID-19 generally lasts for about 4 weeks after the onset of symptoms, and post–acute COVID-19 is generally defined as “persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms,” he said. The postacute period may be broken into a subacute phase with symptoms and abnormalities present from 4-12 weeks beyond the acute phase, and then a chronic or post–acute COVID-19 syndrome, with symptoms and abnormalities present beyond 12 weeks after the onset of acute COVID-19.

Patients in the subacute or post–COVID-19 phase of illness are polymerase chain reaction negative and may have multiorgan symptomatology, said Dr. Berhe. Physical symptoms include fatigue, decline in quality of life, joint pain, and muscle weakness; reported mental symptoms include anxiety and depression; sleep disturbance; PTSD; cognitive disturbance (described by patients as “brain fog”); and headaches.

Pulmonary symptoms in post–acute COVID-19 patients include dyspnea, cough, and persistent oxygen requirements; patients also have reported palpitations and chest pain. Thromboembolism, chronic kidney disease, and hair loss also have been reported in COVID-19 patients in the postacute period.
 

What studies show

Early reports on postacute consequences of COVID-19 have been reported in published studies from the United States, Europe, and China, and the current treatment recommendations are based on findings from these studies, Dr. Berhe said.

In an observational cohort study from 38 hospitals in Michigan, researchers assessed 60-day outcomes for 1,250 COVID-19 patients who were discharged alive from the hospital. The researchers used medical record abstraction and telephone surveys to assess long-term symptoms. Overall, 6.7% of the patients died and 15.1% required hospital readmission. A total of 488 patients completed the telephone survey. Of these, 32.6% reported persistent symptoms, 18.9% reported new or worsening symptoms, 22.9% reported dyspnea while walking up stairs, 15.4% reported a cough, and 13.1% reported a persistent loss of taste or smell.

Data from multiple countries in Europe have shown similar prevalence of post–acute COVID-19 syndrome, but Dr. Berhe highlighted an Italian study in which 87% of 143 patients discharged from hospitals after acute COVID-19 reported at least one symptom at 60 day. “A decline in quality of life, as measured by the EuroQol visual analog scale, was reported by 44.1% of patients” in the Italian study, Dr. Berhe noted.

In a prospective cohort study conducted in Wuhan, China, researchers conducted a comprehensive in-person evaluation of symptoms in 1,733 COVID-19 patients at 6 months from symptom onset, and found that 76% reported at least one symptom, said Dr. Berhe. “Similar to other studies, muscle weakness and fatigue were the most common symptoms, followed by sleep problems and anxiety/depression. 

Dr. Berhe also cited a literature review published in Clinical Infectious Diseases that addressed COVID-19 in children; in one study of postacute COVID-19, approximately 12% of children had 5 weeks’ prevalence of persistent symptoms, compared with 22% of adults. This finding should remind clinicians that “Children can have devastating persistent symptoms following acute COVID-19 disease,” Dr. Berhe said.

In the post–acute COVID clinic

“Multidisciplinary collaboration is essential to provide integrated outpatient care to survivors of acute COVID-19,” Dr. Berhe said. Such collaboration includes pulmonary and cardiovascular symptom assessment through virtual or in-person follow-up at 4-6 weeks and at 12 weeks after hospital discharge. For those with dyspnea and persistent oxygen requirements at 12 weeks, consider the 6-minute walk test, pulmonary function test, chest x-ray, pulmonary embolism work-up, echocardiogram, and high-resolution CT of the chest as indicated.

With regard to neuropsychiatry, patients should be screened for anxiety, depression, PTSD, sleep disturbance, and cognitive impairment, said Dr. Berhe.

For hematology, “consider extended thromboprophylaxis for high-risk survivors based on shared decision-making,” he said. The incidence of thrombotic events post COVID is less than 5% so you have to be very selective and they should be in the highest-risk category.

COVID-19 patients with acute kidney infections should have a follow-up with a nephrologist soon after hospital discharge, he added.

From a primary care standpoint, early rehabilitation and patient education are important for managing symptoms; also consider recommending patient enrollment in research studies, Dr. Berhe said.

Dr. Berhe has been involved in multiple clinical trials of treating acute COVID-19 patients, but had no financial conflicts to disclose.

In the wake of the COVID-19 pandemic, a population of patients has arisen with a range of symptoms and complications after surviving the acute phase of illness, according to Mezgebe Berhe, MD, of Baylor University Medical Center, Dallas.

Different terms have been used to describe this condition, including post COVID, long COVID, chronic COVID, and long-haulers, Dr. Berhe said in a presentation at SHM Converge, the annual conference of the Society of Hospital Medicine. However, the current medical consensus for a definition is post–acute COVID-19 syndrome.

Acute COVID-19 generally lasts for about 4 weeks after the onset of symptoms, and post–acute COVID-19 is generally defined as “persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms,” he said. The postacute period may be broken into a subacute phase with symptoms and abnormalities present from 4-12 weeks beyond the acute phase, and then a chronic or post–acute COVID-19 syndrome, with symptoms and abnormalities present beyond 12 weeks after the onset of acute COVID-19.

Patients in the subacute or post–COVID-19 phase of illness are polymerase chain reaction negative and may have multiorgan symptomatology, said Dr. Berhe. Physical symptoms include fatigue, decline in quality of life, joint pain, and muscle weakness; reported mental symptoms include anxiety and depression; sleep disturbance; PTSD; cognitive disturbance (described by patients as “brain fog”); and headaches.

Pulmonary symptoms in post–acute COVID-19 patients include dyspnea, cough, and persistent oxygen requirements; patients also have reported palpitations and chest pain. Thromboembolism, chronic kidney disease, and hair loss also have been reported in COVID-19 patients in the postacute period.
 

What studies show

Early reports on postacute consequences of COVID-19 have been reported in published studies from the United States, Europe, and China, and the current treatment recommendations are based on findings from these studies, Dr. Berhe said.

In an observational cohort study from 38 hospitals in Michigan, researchers assessed 60-day outcomes for 1,250 COVID-19 patients who were discharged alive from the hospital. The researchers used medical record abstraction and telephone surveys to assess long-term symptoms. Overall, 6.7% of the patients died and 15.1% required hospital readmission. A total of 488 patients completed the telephone survey. Of these, 32.6% reported persistent symptoms, 18.9% reported new or worsening symptoms, 22.9% reported dyspnea while walking up stairs, 15.4% reported a cough, and 13.1% reported a persistent loss of taste or smell.

Data from multiple countries in Europe have shown similar prevalence of post–acute COVID-19 syndrome, but Dr. Berhe highlighted an Italian study in which 87% of 143 patients discharged from hospitals after acute COVID-19 reported at least one symptom at 60 day. “A decline in quality of life, as measured by the EuroQol visual analog scale, was reported by 44.1% of patients” in the Italian study, Dr. Berhe noted.

In a prospective cohort study conducted in Wuhan, China, researchers conducted a comprehensive in-person evaluation of symptoms in 1,733 COVID-19 patients at 6 months from symptom onset, and found that 76% reported at least one symptom, said Dr. Berhe. “Similar to other studies, muscle weakness and fatigue were the most common symptoms, followed by sleep problems and anxiety/depression. 

Dr. Berhe also cited a literature review published in Clinical Infectious Diseases that addressed COVID-19 in children; in one study of postacute COVID-19, approximately 12% of children had 5 weeks’ prevalence of persistent symptoms, compared with 22% of adults. This finding should remind clinicians that “Children can have devastating persistent symptoms following acute COVID-19 disease,” Dr. Berhe said.

In the post–acute COVID clinic

“Multidisciplinary collaboration is essential to provide integrated outpatient care to survivors of acute COVID-19,” Dr. Berhe said. Such collaboration includes pulmonary and cardiovascular symptom assessment through virtual or in-person follow-up at 4-6 weeks and at 12 weeks after hospital discharge. For those with dyspnea and persistent oxygen requirements at 12 weeks, consider the 6-minute walk test, pulmonary function test, chest x-ray, pulmonary embolism work-up, echocardiogram, and high-resolution CT of the chest as indicated.

With regard to neuropsychiatry, patients should be screened for anxiety, depression, PTSD, sleep disturbance, and cognitive impairment, said Dr. Berhe.

For hematology, “consider extended thromboprophylaxis for high-risk survivors based on shared decision-making,” he said. The incidence of thrombotic events post COVID is less than 5% so you have to be very selective and they should be in the highest-risk category.

COVID-19 patients with acute kidney infections should have a follow-up with a nephrologist soon after hospital discharge, he added.

From a primary care standpoint, early rehabilitation and patient education are important for managing symptoms; also consider recommending patient enrollment in research studies, Dr. Berhe said.

Dr. Berhe has been involved in multiple clinical trials of treating acute COVID-19 patients, but had no financial conflicts to disclose.

In the wake of the COVID-19 pandemic, a population of patients has arisen with a range of symptoms and complications after surviving the acute phase of illness, according to Mezgebe Berhe, MD, of Baylor University Medical Center, Dallas.

Different terms have been used to describe this condition, including post COVID, long COVID, chronic COVID, and long-haulers, Dr. Berhe said in a presentation at SHM Converge, the annual conference of the Society of Hospital Medicine. However, the current medical consensus for a definition is post–acute COVID-19 syndrome.

Acute COVID-19 generally lasts for about 4 weeks after the onset of symptoms, and post–acute COVID-19 is generally defined as “persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms,” he said. The postacute period may be broken into a subacute phase with symptoms and abnormalities present from 4-12 weeks beyond the acute phase, and then a chronic or post–acute COVID-19 syndrome, with symptoms and abnormalities present beyond 12 weeks after the onset of acute COVID-19.

Patients in the subacute or post–COVID-19 phase of illness are polymerase chain reaction negative and may have multiorgan symptomatology, said Dr. Berhe. Physical symptoms include fatigue, decline in quality of life, joint pain, and muscle weakness; reported mental symptoms include anxiety and depression; sleep disturbance; PTSD; cognitive disturbance (described by patients as “brain fog”); and headaches.

Pulmonary symptoms in post–acute COVID-19 patients include dyspnea, cough, and persistent oxygen requirements; patients also have reported palpitations and chest pain. Thromboembolism, chronic kidney disease, and hair loss also have been reported in COVID-19 patients in the postacute period.
 

What studies show

Early reports on postacute consequences of COVID-19 have been reported in published studies from the United States, Europe, and China, and the current treatment recommendations are based on findings from these studies, Dr. Berhe said.

In an observational cohort study from 38 hospitals in Michigan, researchers assessed 60-day outcomes for 1,250 COVID-19 patients who were discharged alive from the hospital. The researchers used medical record abstraction and telephone surveys to assess long-term symptoms. Overall, 6.7% of the patients died and 15.1% required hospital readmission. A total of 488 patients completed the telephone survey. Of these, 32.6% reported persistent symptoms, 18.9% reported new or worsening symptoms, 22.9% reported dyspnea while walking up stairs, 15.4% reported a cough, and 13.1% reported a persistent loss of taste or smell.

Data from multiple countries in Europe have shown similar prevalence of post–acute COVID-19 syndrome, but Dr. Berhe highlighted an Italian study in which 87% of 143 patients discharged from hospitals after acute COVID-19 reported at least one symptom at 60 day. “A decline in quality of life, as measured by the EuroQol visual analog scale, was reported by 44.1% of patients” in the Italian study, Dr. Berhe noted.

In a prospective cohort study conducted in Wuhan, China, researchers conducted a comprehensive in-person evaluation of symptoms in 1,733 COVID-19 patients at 6 months from symptom onset, and found that 76% reported at least one symptom, said Dr. Berhe. “Similar to other studies, muscle weakness and fatigue were the most common symptoms, followed by sleep problems and anxiety/depression. 

Dr. Berhe also cited a literature review published in Clinical Infectious Diseases that addressed COVID-19 in children; in one study of postacute COVID-19, approximately 12% of children had 5 weeks’ prevalence of persistent symptoms, compared with 22% of adults. This finding should remind clinicians that “Children can have devastating persistent symptoms following acute COVID-19 disease,” Dr. Berhe said.

In the post–acute COVID clinic

“Multidisciplinary collaboration is essential to provide integrated outpatient care to survivors of acute COVID-19,” Dr. Berhe said. Such collaboration includes pulmonary and cardiovascular symptom assessment through virtual or in-person follow-up at 4-6 weeks and at 12 weeks after hospital discharge. For those with dyspnea and persistent oxygen requirements at 12 weeks, consider the 6-minute walk test, pulmonary function test, chest x-ray, pulmonary embolism work-up, echocardiogram, and high-resolution CT of the chest as indicated.

With regard to neuropsychiatry, patients should be screened for anxiety, depression, PTSD, sleep disturbance, and cognitive impairment, said Dr. Berhe.

For hematology, “consider extended thromboprophylaxis for high-risk survivors based on shared decision-making,” he said. The incidence of thrombotic events post COVID is less than 5% so you have to be very selective and they should be in the highest-risk category.

COVID-19 patients with acute kidney infections should have a follow-up with a nephrologist soon after hospital discharge, he added.

From a primary care standpoint, early rehabilitation and patient education are important for managing symptoms; also consider recommending patient enrollment in research studies, Dr. Berhe said.

Dr. Berhe has been involved in multiple clinical trials of treating acute COVID-19 patients, but had no financial conflicts to disclose.

Before 2001, HER2/neu-positive breast cancer (HER2+) was one of the most dreaded diagnoses a woman could face, as treatment was largely ineffective. The discovery of trastuzumab changed that dramatically.

Over the next 20 years, two additional HER2-targeted therapies – lapatinib and trastuzumab emtansine (TDM-1) – earned approval from the Food and Drug Administration for selected patients with early and late HER2+ breast cancer.

Since 2019, four additional HER2-targeted therapies have been approved by the FDA for HER2+ metastatic breast cancer (MBC), changing the treatment paradigm for those patients substantially.

The new agents are especially useful in certain patient populations. The agents offer the promise of improved survival for patients with recurrent metastatic disease and the potential for further reductions in relapse rates in earlier settings.
 

Trastuzumab deruxtecan

Trastuzumab deruxtecan is an antibody-drug conjugate that links three components: an anti-HER2 monoclonal antibody, a highly potent topoisomerase I inhibitor payload, and a tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan has a high drug-to-antibody ratio. A membrane-permeable payload offers the potential for activity against adjacent HER2-negative cells in heterogeneous tumors. It has a long half-life (6 days).

Trastuzumab deruxtecan received accelerated approval from the FDA in December 2019 to treat patients with HER2+ MBC who have received two or more prior HER2-targeted regimens, based on the results of the DESTINY-Breast 01 trial.
 

DESTINY-Breast 01 trial

In the phase 2 DESTINY-Breast 01 trial, 184 patients with a median of six previous treatments received trastuzumab deruxtecan (5.4 mg/kg) intravenously every 21 days. There were 24 patients with treated, asymptomatic brain metastases who participated. Patients with untreated or symptomatic brain metastases were excluded.

Overall, a response to therapy was reported in 112 patients (60.9%), with 6.0% complete and 54.9% partial responses. Most of the patients for whom both baseline and postbaseline data were available had a reduction in tumor size.

The median time until response was 1.6 months, an interval that corresponded to the time until the first scheduled imaging. Three patients (1.6%) had progressive disease, and two patients (1.1%) could not be evaluated.

The median duration of follow-up was 11.1 months, and the median response duration was 14.8 months.

The median progression-free survival (PFS) was 16.4 months, and the median overall survival (OS) was not reached. The median PFS in the patients with brain involvement was 18.1 months.

The most common adverse events of grade 3 or higher were a decreased neutrophil count (20.7%), anemia (8.7%), and nausea (7.6%). Most concerning was that trastuzumab deruxtecan was associated with interstitial lung disease in 13.6% of patients.
 

Tucatinib

Tucatinib is an oral, highly selective HER2 tyrosine kinase inhibitor (TKI). In April 2020, it was approved by the FDA, in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2+ breast cancer who have received one or more prior anti-HER2–based regimens for MBC. The approval included patients with brain metastases.

The recommended tucatinib dose is 300 mg orally twice a day in combination with trastuzumab (at the standard dose) and capecitabine (1,000 mg/m² given orally twice daily on days 1-14) on a 21-day cycle, until disease progression or unacceptable toxicity.
 

HER2CLIMB trial

The study that led to the approval of tucatinib was the HER2CLIMB trial. The trial enrolled 612 HER2+ MBC patients who had prior treatment with trastuzumab, pertuzumab, and T-DM1. Patients had received a median of 4 (range, 2-17) prior lines of HER2-targeted therapy.

The patients were randomized 2:1 to receive trastuzumab plus capecitabine and either tucatinib or an identical placebo twice daily.

The primary endpoint was PFS, evaluated in the initial 480 randomized patients. The median PFS was 7.8 months in the tucatinib arm and 5.6 months in the control arm (hazard ratio, 0.54; 95% confidence interval, 0.42-0.71; P < .001).

The confirmed overall response rate for patients with measurable disease was 40.6% in the tucatinib arm and 22.8% in the control arm (P = .001). The proportion of patients still in response at 12 months was 33.1% and 12.3%, respectively.

The median OS was 21.9 months in the tucatinib arm and 17.4 months in the placebo arm (HR, 0.66; 95% CI, 0.50-0.88; P = .005). At 24 months, 44.9% and 26.6% of patients, respectively, were still alive.

The most common grade 3 or higher adverse events (in the tucatinib and placebo arms, respectively) were palmar-plantar erythrodysesthesia syndrome (13.1% vs. 9.1%), diarrhea (12.9% vs. 8.6%), elevations in ALT and AST (approximately 5% vs. 0.5% for each), and fatigue (4.7% vs. 4.1%).
 

Tucatinib in patients with brain involvement

A unique feature of the HER2CLIMB study was that patients with MBC and untreated, symptomatic brain metastases were eligible. Patients with active, untreated central nervous system disease are excluded from virtually all other trials, especially drug-approval trials.

There were 291 patients with brain metastases in HER2CLIMB, 198 (48%) in the tucatinib arm and 93 (46%) in the control arm.

The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (HR, 0.32; 95% CI, 0.22 to 0.48; P  < .0001).

The 1-year CNS-PFS rate was 40.2% in the tucatinib arm and 0% in the placebo arm. The median duration of CNS-PFS was 9.9 months and 4.2 months, respectively.

The risk of death was reduced by 42% in the tucatinib arm (HR, 0.58; 95% CI, 0.40-0.85; P = .005). The median OS was 18.1 months and 12.0 months, respectively.

There were more objective responses in the brain with tucatinib (47.3%) than with placebo (20.0%; P = .03). The median duration of response was 6.8 months and 3.0 months, respectively.

Particularly because of its CNS activity and lack of serious, long-term toxicity, tucatinib combination therapy represents an attractive new option for patients with HER2+ MBC.
 

Neratinib

Neratinib is an irreversible pan-HER TKI that was approved by the FDA in July 2017 for extended adjuvant therapy in patients with early-stage HER2+ breast cancer, following the use of trastuzumab-based therapy.

Long-term results of the ExteNet study led to the approval for use as extended adjuvant therapy.

In February 2020, neratinib was FDA approved in combination with capecitabine for patients with HER2+ MBC after two or more prior anti-HER2–based regimens. The more recent FDA approval was based on results of the NALA trial.
 

NALA trial

The phase 3 NALA trial included 621 patients with HER2+ MBC who had received at least two prior anti-HER2 based regimens.

Patients were randomized 1:1 to receive neratinib at 240 mg orally once daily on days 1-21 with capecitabine at 750 mg/m² orally twice daily on days 1-14 or lapatinib at 1,250 mg orally once daily on days 1-21 with capecitabine at 1,000 mg/m² orally twice daily on days 1-14 for each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity.

The primary endpoints were PFS and OS by blinded, independent, central review.

The median PFS was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (HR, 0.76; 95% CI, 0.63-0.93; P = .0059). The PFS rate at 12 months was 28.8% and 14.8%, respectively.

The median OS was 21.0 months in the neratinib arm and 18.7 months in the lapatinib arm (HR, 0.88; 95% CI, 0.72-1.07; P = .2086). The ORR was 32.8% and 26.7%, respectively. The median response duration was 8.5 months and 5.6 months, respectively.

Fewer interventions for CNS disease were required in the neratinib arm than in the lapatinib arm (cumulative incidence, 22.8% vs. 29.2%; P = .043). 

The most frequently reported grade 3-4 adverse reactions for the neratinib combination were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

Grade 3 diarrhea occurred in 24.4% of those in the neratinib arm and 12.5% of those in the lapatinib arm. Antidiarrheal medication was used by 98.3% of patients receiving neratinib and 62.1% of patients receiving lapatinib.
 

Margetuximab-cmkb

Margetuximab is a chimeric Fc-engineered anti-HER2 monoclonal antibody that targets the same epitope as trastuzumab and exerts similar antiproliferative effects.

Compared with trastuzumab, margetuximab has higher affinity for both 158V (high-binding) and 158F (low-binding) alleles of the activating Fc receptor, CD16A. As a result, margetuximab enhances innate immunity, including CD16A-mediated antibody-dependent cellular cytotoxicity, more effectively than trastuzumab. Margetuximab also potentiates adaptive immunity, including enhanced clonality of the T-cell repertoire and induction of HER2-specific T- and B-cell responses.

In December 2020, margetuximab, in combination with chemotherapy, was approved by the FDA for patients with HER2+ MBC after two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The approved dose is 15 mg/kg IV every 3 weeks.

The study that led to margetuximab’s approval was the phase 3 SOPHIA trial.
 

SOPHIA trial

SOPHIA was a randomized trial of 536 patients with HER2+ MBC who had received prior treatment with other anti-HER2 therapies, including one to three lines of therapy for MBC.

Patients were randomly assigned 1:1 to receive margetuximab plus chemotherapy or trastuzumab plus chemotherapy. Assignment was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), the number of previous lines of therapy for MBC, and disease extent.

Co–primary outcome measures were PFS by blinded, independent, central review and OS.

At the second interim analysis, the median PFS was 5.8 months in the margetuximab arm and 4.9 months in the trastuzumab arm (HR, 0.76; 95% CI, 0.59-0.98; P = .033). Results were more impressive in patients with CD16A genotypes containing a 158F allele. In this group, the median PFS was 6.9 months with margetuximab and 5.1 months with trastuzumab (HR, 0.68, 95% CI, 0.52-0.90; P = .005).

At the second interim analysis, the median OS was 21.6 months in the margetuximab arm and 19.8 months in the trastuzumab arm (HR, 0.89; 95% CI, 0.69-1.13; P = .33).

Subgroup data showed no differences in OS between the two arms for any subgroup except HER2+ MBC patients with an IHC score of 2 or higher. This is consistent with the postulated mechanism of action of margetuximab.

The confirmed ORR was 25% in the margetuximab arm and 14% in the trastuzumab arm, with similar durations of response between the study arms.

The most common adverse events in both arms (≥20%), regardless of causality, were fatigue, nausea, diarrhea, and neutropenia. Vomiting was common in the margetuximab arm, and anemia was common in the trastuzumab arm.

Grade 3 or higher adverse events occurred in 53.8% of patients receiving margetuximab and 52.6% of those receiving trastuzumab.

In view of margetuximab’s modest benefits in the SOPHIA trial, the ultimate role for margetuximab in HER2+ MBC may be restricted to patients with the CD16A-158F allele. A neoadjuvant trial is planned in that population.
 

Take-home messages

There are legitimate arguments regarding whether curing MBC is within reach for certain patient subsets, but there is no argument about whether the outlook for patients with HER2+ MBC has improved dramatically in recent years; it has.

The approval of four unique, new agents for the treatment of women with HER2+ MBC in relapse provides further improvements in outcome for these patients and distinctly different opportunities for tailoring treatment to the special circumstances of each patient (e.g., whether brain metastases are present, desire for oral therapy, comorbidities, experience with prior chemotherapy, etc).

When considered along with the potential for incorporating these drugs in earlier settings in well-designed clinical trials, these new drugs offer great promise to a group of patients who faced a dismal outcome just 2 decades ago.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Before 2001, HER2/neu-positive breast cancer (HER2+) was one of the most dreaded diagnoses a woman could face, as treatment was largely ineffective. The discovery of trastuzumab changed that dramatically.

Over the next 20 years, two additional HER2-targeted therapies – lapatinib and trastuzumab emtansine (TDM-1) – earned approval from the Food and Drug Administration for selected patients with early and late HER2+ breast cancer.

Since 2019, four additional HER2-targeted therapies have been approved by the FDA for HER2+ metastatic breast cancer (MBC), changing the treatment paradigm for those patients substantially.

The new agents are especially useful in certain patient populations. The agents offer the promise of improved survival for patients with recurrent metastatic disease and the potential for further reductions in relapse rates in earlier settings.
 

Trastuzumab deruxtecan

Trastuzumab deruxtecan is an antibody-drug conjugate that links three components: an anti-HER2 monoclonal antibody, a highly potent topoisomerase I inhibitor payload, and a tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan has a high drug-to-antibody ratio. A membrane-permeable payload offers the potential for activity against adjacent HER2-negative cells in heterogeneous tumors. It has a long half-life (6 days).

Trastuzumab deruxtecan received accelerated approval from the FDA in December 2019 to treat patients with HER2+ MBC who have received two or more prior HER2-targeted regimens, based on the results of the DESTINY-Breast 01 trial.
 

DESTINY-Breast 01 trial

In the phase 2 DESTINY-Breast 01 trial, 184 patients with a median of six previous treatments received trastuzumab deruxtecan (5.4 mg/kg) intravenously every 21 days. There were 24 patients with treated, asymptomatic brain metastases who participated. Patients with untreated or symptomatic brain metastases were excluded.

Overall, a response to therapy was reported in 112 patients (60.9%), with 6.0% complete and 54.9% partial responses. Most of the patients for whom both baseline and postbaseline data were available had a reduction in tumor size.

The median time until response was 1.6 months, an interval that corresponded to the time until the first scheduled imaging. Three patients (1.6%) had progressive disease, and two patients (1.1%) could not be evaluated.

The median duration of follow-up was 11.1 months, and the median response duration was 14.8 months.

The median progression-free survival (PFS) was 16.4 months, and the median overall survival (OS) was not reached. The median PFS in the patients with brain involvement was 18.1 months.

The most common adverse events of grade 3 or higher were a decreased neutrophil count (20.7%), anemia (8.7%), and nausea (7.6%). Most concerning was that trastuzumab deruxtecan was associated with interstitial lung disease in 13.6% of patients.
 

Tucatinib

Tucatinib is an oral, highly selective HER2 tyrosine kinase inhibitor (TKI). In April 2020, it was approved by the FDA, in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2+ breast cancer who have received one or more prior anti-HER2–based regimens for MBC. The approval included patients with brain metastases.

The recommended tucatinib dose is 300 mg orally twice a day in combination with trastuzumab (at the standard dose) and capecitabine (1,000 mg/m² given orally twice daily on days 1-14) on a 21-day cycle, until disease progression or unacceptable toxicity.
 

HER2CLIMB trial

The study that led to the approval of tucatinib was the HER2CLIMB trial. The trial enrolled 612 HER2+ MBC patients who had prior treatment with trastuzumab, pertuzumab, and T-DM1. Patients had received a median of 4 (range, 2-17) prior lines of HER2-targeted therapy.

The patients were randomized 2:1 to receive trastuzumab plus capecitabine and either tucatinib or an identical placebo twice daily.

The primary endpoint was PFS, evaluated in the initial 480 randomized patients. The median PFS was 7.8 months in the tucatinib arm and 5.6 months in the control arm (hazard ratio, 0.54; 95% confidence interval, 0.42-0.71; P < .001).

The confirmed overall response rate for patients with measurable disease was 40.6% in the tucatinib arm and 22.8% in the control arm (P = .001). The proportion of patients still in response at 12 months was 33.1% and 12.3%, respectively.

The median OS was 21.9 months in the tucatinib arm and 17.4 months in the placebo arm (HR, 0.66; 95% CI, 0.50-0.88; P = .005). At 24 months, 44.9% and 26.6% of patients, respectively, were still alive.

The most common grade 3 or higher adverse events (in the tucatinib and placebo arms, respectively) were palmar-plantar erythrodysesthesia syndrome (13.1% vs. 9.1%), diarrhea (12.9% vs. 8.6%), elevations in ALT and AST (approximately 5% vs. 0.5% for each), and fatigue (4.7% vs. 4.1%).
 

Tucatinib in patients with brain involvement

A unique feature of the HER2CLIMB study was that patients with MBC and untreated, symptomatic brain metastases were eligible. Patients with active, untreated central nervous system disease are excluded from virtually all other trials, especially drug-approval trials.

There were 291 patients with brain metastases in HER2CLIMB, 198 (48%) in the tucatinib arm and 93 (46%) in the control arm.

The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (HR, 0.32; 95% CI, 0.22 to 0.48; P  < .0001).

The 1-year CNS-PFS rate was 40.2% in the tucatinib arm and 0% in the placebo arm. The median duration of CNS-PFS was 9.9 months and 4.2 months, respectively.

The risk of death was reduced by 42% in the tucatinib arm (HR, 0.58; 95% CI, 0.40-0.85; P = .005). The median OS was 18.1 months and 12.0 months, respectively.

There were more objective responses in the brain with tucatinib (47.3%) than with placebo (20.0%; P = .03). The median duration of response was 6.8 months and 3.0 months, respectively.

Particularly because of its CNS activity and lack of serious, long-term toxicity, tucatinib combination therapy represents an attractive new option for patients with HER2+ MBC.
 

Neratinib

Neratinib is an irreversible pan-HER TKI that was approved by the FDA in July 2017 for extended adjuvant therapy in patients with early-stage HER2+ breast cancer, following the use of trastuzumab-based therapy.

Long-term results of the ExteNet study led to the approval for use as extended adjuvant therapy.

In February 2020, neratinib was FDA approved in combination with capecitabine for patients with HER2+ MBC after two or more prior anti-HER2–based regimens. The more recent FDA approval was based on results of the NALA trial.
 

NALA trial

The phase 3 NALA trial included 621 patients with HER2+ MBC who had received at least two prior anti-HER2 based regimens.

Patients were randomized 1:1 to receive neratinib at 240 mg orally once daily on days 1-21 with capecitabine at 750 mg/m² orally twice daily on days 1-14 or lapatinib at 1,250 mg orally once daily on days 1-21 with capecitabine at 1,000 mg/m² orally twice daily on days 1-14 for each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity.

The primary endpoints were PFS and OS by blinded, independent, central review.

The median PFS was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (HR, 0.76; 95% CI, 0.63-0.93; P = .0059). The PFS rate at 12 months was 28.8% and 14.8%, respectively.

The median OS was 21.0 months in the neratinib arm and 18.7 months in the lapatinib arm (HR, 0.88; 95% CI, 0.72-1.07; P = .2086). The ORR was 32.8% and 26.7%, respectively. The median response duration was 8.5 months and 5.6 months, respectively.

Fewer interventions for CNS disease were required in the neratinib arm than in the lapatinib arm (cumulative incidence, 22.8% vs. 29.2%; P = .043). 

The most frequently reported grade 3-4 adverse reactions for the neratinib combination were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

Grade 3 diarrhea occurred in 24.4% of those in the neratinib arm and 12.5% of those in the lapatinib arm. Antidiarrheal medication was used by 98.3% of patients receiving neratinib and 62.1% of patients receiving lapatinib.
 

Margetuximab-cmkb

Margetuximab is a chimeric Fc-engineered anti-HER2 monoclonal antibody that targets the same epitope as trastuzumab and exerts similar antiproliferative effects.

Compared with trastuzumab, margetuximab has higher affinity for both 158V (high-binding) and 158F (low-binding) alleles of the activating Fc receptor, CD16A. As a result, margetuximab enhances innate immunity, including CD16A-mediated antibody-dependent cellular cytotoxicity, more effectively than trastuzumab. Margetuximab also potentiates adaptive immunity, including enhanced clonality of the T-cell repertoire and induction of HER2-specific T- and B-cell responses.

In December 2020, margetuximab, in combination with chemotherapy, was approved by the FDA for patients with HER2+ MBC after two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The approved dose is 15 mg/kg IV every 3 weeks.

The study that led to margetuximab’s approval was the phase 3 SOPHIA trial.
 

SOPHIA trial

SOPHIA was a randomized trial of 536 patients with HER2+ MBC who had received prior treatment with other anti-HER2 therapies, including one to three lines of therapy for MBC.

Patients were randomly assigned 1:1 to receive margetuximab plus chemotherapy or trastuzumab plus chemotherapy. Assignment was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), the number of previous lines of therapy for MBC, and disease extent.

Co–primary outcome measures were PFS by blinded, independent, central review and OS.

At the second interim analysis, the median PFS was 5.8 months in the margetuximab arm and 4.9 months in the trastuzumab arm (HR, 0.76; 95% CI, 0.59-0.98; P = .033). Results were more impressive in patients with CD16A genotypes containing a 158F allele. In this group, the median PFS was 6.9 months with margetuximab and 5.1 months with trastuzumab (HR, 0.68, 95% CI, 0.52-0.90; P = .005).

At the second interim analysis, the median OS was 21.6 months in the margetuximab arm and 19.8 months in the trastuzumab arm (HR, 0.89; 95% CI, 0.69-1.13; P = .33).

Subgroup data showed no differences in OS between the two arms for any subgroup except HER2+ MBC patients with an IHC score of 2 or higher. This is consistent with the postulated mechanism of action of margetuximab.

The confirmed ORR was 25% in the margetuximab arm and 14% in the trastuzumab arm, with similar durations of response between the study arms.

The most common adverse events in both arms (≥20%), regardless of causality, were fatigue, nausea, diarrhea, and neutropenia. Vomiting was common in the margetuximab arm, and anemia was common in the trastuzumab arm.

Grade 3 or higher adverse events occurred in 53.8% of patients receiving margetuximab and 52.6% of those receiving trastuzumab.

In view of margetuximab’s modest benefits in the SOPHIA trial, the ultimate role for margetuximab in HER2+ MBC may be restricted to patients with the CD16A-158F allele. A neoadjuvant trial is planned in that population.
 

Take-home messages

There are legitimate arguments regarding whether curing MBC is within reach for certain patient subsets, but there is no argument about whether the outlook for patients with HER2+ MBC has improved dramatically in recent years; it has.

The approval of four unique, new agents for the treatment of women with HER2+ MBC in relapse provides further improvements in outcome for these patients and distinctly different opportunities for tailoring treatment to the special circumstances of each patient (e.g., whether brain metastases are present, desire for oral therapy, comorbidities, experience with prior chemotherapy, etc).

When considered along with the potential for incorporating these drugs in earlier settings in well-designed clinical trials, these new drugs offer great promise to a group of patients who faced a dismal outcome just 2 decades ago.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Before 2001, HER2/neu-positive breast cancer (HER2+) was one of the most dreaded diagnoses a woman could face, as treatment was largely ineffective. The discovery of trastuzumab changed that dramatically.

Over the next 20 years, two additional HER2-targeted therapies – lapatinib and trastuzumab emtansine (TDM-1) – earned approval from the Food and Drug Administration for selected patients with early and late HER2+ breast cancer.

Since 2019, four additional HER2-targeted therapies have been approved by the FDA for HER2+ metastatic breast cancer (MBC), changing the treatment paradigm for those patients substantially.

The new agents are especially useful in certain patient populations. The agents offer the promise of improved survival for patients with recurrent metastatic disease and the potential for further reductions in relapse rates in earlier settings.
 

Trastuzumab deruxtecan

Trastuzumab deruxtecan is an antibody-drug conjugate that links three components: an anti-HER2 monoclonal antibody, a highly potent topoisomerase I inhibitor payload, and a tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan has a high drug-to-antibody ratio. A membrane-permeable payload offers the potential for activity against adjacent HER2-negative cells in heterogeneous tumors. It has a long half-life (6 days).

Trastuzumab deruxtecan received accelerated approval from the FDA in December 2019 to treat patients with HER2+ MBC who have received two or more prior HER2-targeted regimens, based on the results of the DESTINY-Breast 01 trial.
 

DESTINY-Breast 01 trial

In the phase 2 DESTINY-Breast 01 trial, 184 patients with a median of six previous treatments received trastuzumab deruxtecan (5.4 mg/kg) intravenously every 21 days. There were 24 patients with treated, asymptomatic brain metastases who participated. Patients with untreated or symptomatic brain metastases were excluded.

Overall, a response to therapy was reported in 112 patients (60.9%), with 6.0% complete and 54.9% partial responses. Most of the patients for whom both baseline and postbaseline data were available had a reduction in tumor size.

The median time until response was 1.6 months, an interval that corresponded to the time until the first scheduled imaging. Three patients (1.6%) had progressive disease, and two patients (1.1%) could not be evaluated.

The median duration of follow-up was 11.1 months, and the median response duration was 14.8 months.

The median progression-free survival (PFS) was 16.4 months, and the median overall survival (OS) was not reached. The median PFS in the patients with brain involvement was 18.1 months.

The most common adverse events of grade 3 or higher were a decreased neutrophil count (20.7%), anemia (8.7%), and nausea (7.6%). Most concerning was that trastuzumab deruxtecan was associated with interstitial lung disease in 13.6% of patients.
 

Tucatinib

Tucatinib is an oral, highly selective HER2 tyrosine kinase inhibitor (TKI). In April 2020, it was approved by the FDA, in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2+ breast cancer who have received one or more prior anti-HER2–based regimens for MBC. The approval included patients with brain metastases.

The recommended tucatinib dose is 300 mg orally twice a day in combination with trastuzumab (at the standard dose) and capecitabine (1,000 mg/m² given orally twice daily on days 1-14) on a 21-day cycle, until disease progression or unacceptable toxicity.
 

HER2CLIMB trial

The study that led to the approval of tucatinib was the HER2CLIMB trial. The trial enrolled 612 HER2+ MBC patients who had prior treatment with trastuzumab, pertuzumab, and T-DM1. Patients had received a median of 4 (range, 2-17) prior lines of HER2-targeted therapy.

The patients were randomized 2:1 to receive trastuzumab plus capecitabine and either tucatinib or an identical placebo twice daily.

The primary endpoint was PFS, evaluated in the initial 480 randomized patients. The median PFS was 7.8 months in the tucatinib arm and 5.6 months in the control arm (hazard ratio, 0.54; 95% confidence interval, 0.42-0.71; P < .001).

The confirmed overall response rate for patients with measurable disease was 40.6% in the tucatinib arm and 22.8% in the control arm (P = .001). The proportion of patients still in response at 12 months was 33.1% and 12.3%, respectively.

The median OS was 21.9 months in the tucatinib arm and 17.4 months in the placebo arm (HR, 0.66; 95% CI, 0.50-0.88; P = .005). At 24 months, 44.9% and 26.6% of patients, respectively, were still alive.

The most common grade 3 or higher adverse events (in the tucatinib and placebo arms, respectively) were palmar-plantar erythrodysesthesia syndrome (13.1% vs. 9.1%), diarrhea (12.9% vs. 8.6%), elevations in ALT and AST (approximately 5% vs. 0.5% for each), and fatigue (4.7% vs. 4.1%).
 

Tucatinib in patients with brain involvement

A unique feature of the HER2CLIMB study was that patients with MBC and untreated, symptomatic brain metastases were eligible. Patients with active, untreated central nervous system disease are excluded from virtually all other trials, especially drug-approval trials.

There were 291 patients with brain metastases in HER2CLIMB, 198 (48%) in the tucatinib arm and 93 (46%) in the control arm.

The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (HR, 0.32; 95% CI, 0.22 to 0.48; P  < .0001).

The 1-year CNS-PFS rate was 40.2% in the tucatinib arm and 0% in the placebo arm. The median duration of CNS-PFS was 9.9 months and 4.2 months, respectively.

The risk of death was reduced by 42% in the tucatinib arm (HR, 0.58; 95% CI, 0.40-0.85; P = .005). The median OS was 18.1 months and 12.0 months, respectively.

There were more objective responses in the brain with tucatinib (47.3%) than with placebo (20.0%; P = .03). The median duration of response was 6.8 months and 3.0 months, respectively.

Particularly because of its CNS activity and lack of serious, long-term toxicity, tucatinib combination therapy represents an attractive new option for patients with HER2+ MBC.
 

Neratinib

Neratinib is an irreversible pan-HER TKI that was approved by the FDA in July 2017 for extended adjuvant therapy in patients with early-stage HER2+ breast cancer, following the use of trastuzumab-based therapy.

Long-term results of the ExteNet study led to the approval for use as extended adjuvant therapy.

In February 2020, neratinib was FDA approved in combination with capecitabine for patients with HER2+ MBC after two or more prior anti-HER2–based regimens. The more recent FDA approval was based on results of the NALA trial.
 

NALA trial

The phase 3 NALA trial included 621 patients with HER2+ MBC who had received at least two prior anti-HER2 based regimens.

Patients were randomized 1:1 to receive neratinib at 240 mg orally once daily on days 1-21 with capecitabine at 750 mg/m² orally twice daily on days 1-14 or lapatinib at 1,250 mg orally once daily on days 1-21 with capecitabine at 1,000 mg/m² orally twice daily on days 1-14 for each 21-day cycle. Patients were treated until disease progression or unacceptable toxicity.

The primary endpoints were PFS and OS by blinded, independent, central review.

The median PFS was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (HR, 0.76; 95% CI, 0.63-0.93; P = .0059). The PFS rate at 12 months was 28.8% and 14.8%, respectively.

The median OS was 21.0 months in the neratinib arm and 18.7 months in the lapatinib arm (HR, 0.88; 95% CI, 0.72-1.07; P = .2086). The ORR was 32.8% and 26.7%, respectively. The median response duration was 8.5 months and 5.6 months, respectively.

Fewer interventions for CNS disease were required in the neratinib arm than in the lapatinib arm (cumulative incidence, 22.8% vs. 29.2%; P = .043). 

The most frequently reported grade 3-4 adverse reactions for the neratinib combination were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

Grade 3 diarrhea occurred in 24.4% of those in the neratinib arm and 12.5% of those in the lapatinib arm. Antidiarrheal medication was used by 98.3% of patients receiving neratinib and 62.1% of patients receiving lapatinib.
 

Margetuximab-cmkb

Margetuximab is a chimeric Fc-engineered anti-HER2 monoclonal antibody that targets the same epitope as trastuzumab and exerts similar antiproliferative effects.

Compared with trastuzumab, margetuximab has higher affinity for both 158V (high-binding) and 158F (low-binding) alleles of the activating Fc receptor, CD16A. As a result, margetuximab enhances innate immunity, including CD16A-mediated antibody-dependent cellular cytotoxicity, more effectively than trastuzumab. Margetuximab also potentiates adaptive immunity, including enhanced clonality of the T-cell repertoire and induction of HER2-specific T- and B-cell responses.

In December 2020, margetuximab, in combination with chemotherapy, was approved by the FDA for patients with HER2+ MBC after two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The approved dose is 15 mg/kg IV every 3 weeks.

The study that led to margetuximab’s approval was the phase 3 SOPHIA trial.
 

SOPHIA trial

SOPHIA was a randomized trial of 536 patients with HER2+ MBC who had received prior treatment with other anti-HER2 therapies, including one to three lines of therapy for MBC.

Patients were randomly assigned 1:1 to receive margetuximab plus chemotherapy or trastuzumab plus chemotherapy. Assignment was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), the number of previous lines of therapy for MBC, and disease extent.

Co–primary outcome measures were PFS by blinded, independent, central review and OS.

At the second interim analysis, the median PFS was 5.8 months in the margetuximab arm and 4.9 months in the trastuzumab arm (HR, 0.76; 95% CI, 0.59-0.98; P = .033). Results were more impressive in patients with CD16A genotypes containing a 158F allele. In this group, the median PFS was 6.9 months with margetuximab and 5.1 months with trastuzumab (HR, 0.68, 95% CI, 0.52-0.90; P = .005).

At the second interim analysis, the median OS was 21.6 months in the margetuximab arm and 19.8 months in the trastuzumab arm (HR, 0.89; 95% CI, 0.69-1.13; P = .33).

Subgroup data showed no differences in OS between the two arms for any subgroup except HER2+ MBC patients with an IHC score of 2 or higher. This is consistent with the postulated mechanism of action of margetuximab.

The confirmed ORR was 25% in the margetuximab arm and 14% in the trastuzumab arm, with similar durations of response between the study arms.

The most common adverse events in both arms (≥20%), regardless of causality, were fatigue, nausea, diarrhea, and neutropenia. Vomiting was common in the margetuximab arm, and anemia was common in the trastuzumab arm.

Grade 3 or higher adverse events occurred in 53.8% of patients receiving margetuximab and 52.6% of those receiving trastuzumab.

In view of margetuximab’s modest benefits in the SOPHIA trial, the ultimate role for margetuximab in HER2+ MBC may be restricted to patients with the CD16A-158F allele. A neoadjuvant trial is planned in that population.
 

Take-home messages

There are legitimate arguments regarding whether curing MBC is within reach for certain patient subsets, but there is no argument about whether the outlook for patients with HER2+ MBC has improved dramatically in recent years; it has.

The approval of four unique, new agents for the treatment of women with HER2+ MBC in relapse provides further improvements in outcome for these patients and distinctly different opportunities for tailoring treatment to the special circumstances of each patient (e.g., whether brain metastases are present, desire for oral therapy, comorbidities, experience with prior chemotherapy, etc).

When considered along with the potential for incorporating these drugs in earlier settings in well-designed clinical trials, these new drugs offer great promise to a group of patients who faced a dismal outcome just 2 decades ago.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Federal Practitioner Supplement: Advances in Hematology and Oncology

• Impact of an Oral Antineoplastic Renewal Clinic
• Implementing Comprehensive Geriatric Assessments for Oncology Patients
• Radiation Toxicity and Survival in Patients with Presumed Early-Stage NCSLC
• Screening High-Risk Women Veterans for Breast Cancer
• Standardizing the Discharge Process for Inpatient Hem/Onc
• Massive Retroperitoneal Liposarcoma Masquerading as Meralgia Paresthetica
• Delayed Coronary Vasospasm in Metastatic Gastric Cancer

THIS ISSUE WAS PRODUCED IN COLLABORATION WITH AVAHO

Federal Practitioner Supplement: Advances in Hematology and Oncology

• Impact of an Oral Antineoplastic Renewal Clinic
• Implementing Comprehensive Geriatric Assessments for Oncology Patients
• Radiation Toxicity and Survival in Patients with Presumed Early-Stage NCSLC
• Screening High-Risk Women Veterans for Breast Cancer
• Standardizing the Discharge Process for Inpatient Hem/Onc
• Massive Retroperitoneal Liposarcoma Masquerading as Meralgia Paresthetica
• Delayed Coronary Vasospasm in Metastatic Gastric Cancer

THIS ISSUE WAS PRODUCED IN COLLABORATION WITH AVAHO

Federal Practitioner Supplement: Advances in Hematology and Oncology

• Impact of an Oral Antineoplastic Renewal Clinic
• Implementing Comprehensive Geriatric Assessments for Oncology Patients
• Radiation Toxicity and Survival in Patients with Presumed Early-Stage NCSLC
• Screening High-Risk Women Veterans for Breast Cancer
• Standardizing the Discharge Process for Inpatient Hem/Onc
• Massive Retroperitoneal Liposarcoma Masquerading as Meralgia Paresthetica
• Delayed Coronary Vasospasm in Metastatic Gastric Cancer

THIS ISSUE WAS PRODUCED IN COLLABORATION WITH AVAHO

A parenting assessment can add value to a clinic visit by facilitating conversations about discipline and potentially mitigating adverse childhood experiences, based on survey data from 167 health care providers.

“Some of the most modifiable adverse childhood experiences (ACEs) are unhealthy parenting behaviors,” according to Amber J. Cooke, MD, of Vanderbilt University, Nashville, Tenn., and colleagues. “Despite the widespread use of standardized health assessment tools in pediatrics, a gap in services is that parenting assessments are not routinely administered,” they said.

In a study presented at the virtual meeting of the Pediatric Academic Societies, the researchers assessed clinicians’ perspectives on the use of the Quick Parenting Assessment (QPA), a validated 13-item parent support tool designed to identify children exposed to unhealthy parenting practices such as yelling, threatening, humiliating language, and physical punishment.

The researchers surveyed clinicians about how they integrated the QPA into a 15-month or 30-month well-child visit. Clinicians were trained to review the QPA and respond to parents during the visit.

Overall, the health care providers reported that the QPA could be reviewed with parents in less than 3 minutes for more than 80% of encounters.

The QPA takes approximately 1 minute for parents or caregivers to complete. Participating clinicians underwent training to learn how to interpret and respond to the QPA, and responded to a survey based on their inclusion of it in clinical visits. Key factors measured in the survey included the time needed for the clinician to review the QPA with the parent; whether the QPA increased clinicians’ objectivity about the level of support needed for the caregivers, whether the QPA affected communications with the caregiver about parenting, and whether the QPA added value to the well-child visit.

The survey respondents included resident physicians, nurse practitioners, and attending physicians. Approximately 75% of the providers said they were able to review the QPA in 1 minute or less; approximately 24% took 1-5 minutes, and less than 1% took longer than 5 minutes.

A majority of respondents (79%) said that the parent or caregiver was receptive to the QPA, and 74% said that the QPA facilitated communications with caregivers about parenting. In addition, 61% and 60% said the QPA improved the quality and value, respectively, of the visit, and 64% of the respondents said that the QPA increased their objectivity in assessing the level of support needed by caregivers.

Responses were similar, but slightly higher, in each category when the researchers compared providers who reviewed three or more QPAs with parents to those who reviewed less than three QPAs with parents.

The study findings were limited by several factors including the use of data from a single clinic site serving primarily low-income families, which might affect the generalizability of the results, the researchers noted. A lack of data on all QPA encounters might result in a participation bias as well, they said.

However, the results support the feasibility of the QPA, and clinical implications include mitigating ACEs, preventing child abuse, and enhancing the value of the well-child visit, they said. Next steps for research include integrating the QPA into 5-year and 8-year well-child visits, they concluded.
 

Data support value of parenting assessment screening tool

“In order to be useful, a screening tool has to be validated, not add significant time to the well-child visit, and result in useful data for the clinician to more effectively serve their families,” Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. “The Quick Parenting Assessment Screen was developed at Vanderbilt, is free for clinicians to use, and takes an average of 1 minute to assess,” she noted. “This poster highlights a study that was done by residents and attendings at Vanderbilt who administered the tool to caregivers attending their well child clinics.”

Dr. Boulter explained the study was important because “there is increased emphasis on the social determinants of health within the context of well child care, and discipline is one aspect of significance in the assessment of adverse childhood experiences,” she said. “The practitioners overall felt that the tool improved communication with their caregivers, which increased the quality of the visit. It was also surprising that 79% of the providers noted that the caregiver was receptive to the assessment tool,” Dr. Boulter added. 

“In general, this tool offers clinicians a quick overview of disciplinary practices in the households of their patients. It would be useful, as a next step, to expand the testing to a wider socioeconomic population of families,” she concluded.

The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

A parenting assessment can add value to a clinic visit by facilitating conversations about discipline and potentially mitigating adverse childhood experiences, based on survey data from 167 health care providers.

“Some of the most modifiable adverse childhood experiences (ACEs) are unhealthy parenting behaviors,” according to Amber J. Cooke, MD, of Vanderbilt University, Nashville, Tenn., and colleagues. “Despite the widespread use of standardized health assessment tools in pediatrics, a gap in services is that parenting assessments are not routinely administered,” they said.

In a study presented at the virtual meeting of the Pediatric Academic Societies, the researchers assessed clinicians’ perspectives on the use of the Quick Parenting Assessment (QPA), a validated 13-item parent support tool designed to identify children exposed to unhealthy parenting practices such as yelling, threatening, humiliating language, and physical punishment.

The researchers surveyed clinicians about how they integrated the QPA into a 15-month or 30-month well-child visit. Clinicians were trained to review the QPA and respond to parents during the visit.

Overall, the health care providers reported that the QPA could be reviewed with parents in less than 3 minutes for more than 80% of encounters.

The QPA takes approximately 1 minute for parents or caregivers to complete. Participating clinicians underwent training to learn how to interpret and respond to the QPA, and responded to a survey based on their inclusion of it in clinical visits. Key factors measured in the survey included the time needed for the clinician to review the QPA with the parent; whether the QPA increased clinicians’ objectivity about the level of support needed for the caregivers, whether the QPA affected communications with the caregiver about parenting, and whether the QPA added value to the well-child visit.

The survey respondents included resident physicians, nurse practitioners, and attending physicians. Approximately 75% of the providers said they were able to review the QPA in 1 minute or less; approximately 24% took 1-5 minutes, and less than 1% took longer than 5 minutes.

A majority of respondents (79%) said that the parent or caregiver was receptive to the QPA, and 74% said that the QPA facilitated communications with caregivers about parenting. In addition, 61% and 60% said the QPA improved the quality and value, respectively, of the visit, and 64% of the respondents said that the QPA increased their objectivity in assessing the level of support needed by caregivers.

Responses were similar, but slightly higher, in each category when the researchers compared providers who reviewed three or more QPAs with parents to those who reviewed less than three QPAs with parents.

The study findings were limited by several factors including the use of data from a single clinic site serving primarily low-income families, which might affect the generalizability of the results, the researchers noted. A lack of data on all QPA encounters might result in a participation bias as well, they said.

However, the results support the feasibility of the QPA, and clinical implications include mitigating ACEs, preventing child abuse, and enhancing the value of the well-child visit, they said. Next steps for research include integrating the QPA into 5-year and 8-year well-child visits, they concluded.
 

Data support value of parenting assessment screening tool

“In order to be useful, a screening tool has to be validated, not add significant time to the well-child visit, and result in useful data for the clinician to more effectively serve their families,” Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. “The Quick Parenting Assessment Screen was developed at Vanderbilt, is free for clinicians to use, and takes an average of 1 minute to assess,” she noted. “This poster highlights a study that was done by residents and attendings at Vanderbilt who administered the tool to caregivers attending their well child clinics.”

Dr. Boulter explained the study was important because “there is increased emphasis on the social determinants of health within the context of well child care, and discipline is one aspect of significance in the assessment of adverse childhood experiences,” she said. “The practitioners overall felt that the tool improved communication with their caregivers, which increased the quality of the visit. It was also surprising that 79% of the providers noted that the caregiver was receptive to the assessment tool,” Dr. Boulter added. 

“In general, this tool offers clinicians a quick overview of disciplinary practices in the households of their patients. It would be useful, as a next step, to expand the testing to a wider socioeconomic population of families,” she concluded.

The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

A parenting assessment can add value to a clinic visit by facilitating conversations about discipline and potentially mitigating adverse childhood experiences, based on survey data from 167 health care providers.

“Some of the most modifiable adverse childhood experiences (ACEs) are unhealthy parenting behaviors,” according to Amber J. Cooke, MD, of Vanderbilt University, Nashville, Tenn., and colleagues. “Despite the widespread use of standardized health assessment tools in pediatrics, a gap in services is that parenting assessments are not routinely administered,” they said.

In a study presented at the virtual meeting of the Pediatric Academic Societies, the researchers assessed clinicians’ perspectives on the use of the Quick Parenting Assessment (QPA), a validated 13-item parent support tool designed to identify children exposed to unhealthy parenting practices such as yelling, threatening, humiliating language, and physical punishment.

The researchers surveyed clinicians about how they integrated the QPA into a 15-month or 30-month well-child visit. Clinicians were trained to review the QPA and respond to parents during the visit.

Overall, the health care providers reported that the QPA could be reviewed with parents in less than 3 minutes for more than 80% of encounters.

The QPA takes approximately 1 minute for parents or caregivers to complete. Participating clinicians underwent training to learn how to interpret and respond to the QPA, and responded to a survey based on their inclusion of it in clinical visits. Key factors measured in the survey included the time needed for the clinician to review the QPA with the parent; whether the QPA increased clinicians’ objectivity about the level of support needed for the caregivers, whether the QPA affected communications with the caregiver about parenting, and whether the QPA added value to the well-child visit.

The survey respondents included resident physicians, nurse practitioners, and attending physicians. Approximately 75% of the providers said they were able to review the QPA in 1 minute or less; approximately 24% took 1-5 minutes, and less than 1% took longer than 5 minutes.

A majority of respondents (79%) said that the parent or caregiver was receptive to the QPA, and 74% said that the QPA facilitated communications with caregivers about parenting. In addition, 61% and 60% said the QPA improved the quality and value, respectively, of the visit, and 64% of the respondents said that the QPA increased their objectivity in assessing the level of support needed by caregivers.

Responses were similar, but slightly higher, in each category when the researchers compared providers who reviewed three or more QPAs with parents to those who reviewed less than three QPAs with parents.

The study findings were limited by several factors including the use of data from a single clinic site serving primarily low-income families, which might affect the generalizability of the results, the researchers noted. A lack of data on all QPA encounters might result in a participation bias as well, they said.

However, the results support the feasibility of the QPA, and clinical implications include mitigating ACEs, preventing child abuse, and enhancing the value of the well-child visit, they said. Next steps for research include integrating the QPA into 5-year and 8-year well-child visits, they concluded.
 

Data support value of parenting assessment screening tool

“In order to be useful, a screening tool has to be validated, not add significant time to the well-child visit, and result in useful data for the clinician to more effectively serve their families,” Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. “The Quick Parenting Assessment Screen was developed at Vanderbilt, is free for clinicians to use, and takes an average of 1 minute to assess,” she noted. “This poster highlights a study that was done by residents and attendings at Vanderbilt who administered the tool to caregivers attending their well child clinics.”

Dr. Boulter explained the study was important because “there is increased emphasis on the social determinants of health within the context of well child care, and discipline is one aspect of significance in the assessment of adverse childhood experiences,” she said. “The practitioners overall felt that the tool improved communication with their caregivers, which increased the quality of the visit. It was also surprising that 79% of the providers noted that the caregiver was receptive to the assessment tool,” Dr. Boulter added. 

“In general, this tool offers clinicians a quick overview of disciplinary practices in the households of their patients. It would be useful, as a next step, to expand the testing to a wider socioeconomic population of families,” she concluded.

The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.