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Warfarin associated with higher upper GI bleeding rates, compared with DOACs
Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.
In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.
“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.
“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.
“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing bleed rates
Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.
Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.
Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.
In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.
Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.
Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.
Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.
“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.
Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.
“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
Considering future research
In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.
“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.
Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.
In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.
“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”
Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.
“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”
The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.
In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.
“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.
“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.
“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing bleed rates
Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.
Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.
Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.
In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.
Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.
Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.
Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.
“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.
Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.
“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
Considering future research
In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.
“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.
Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.
In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.
“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”
Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.
“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”
The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Warfarin is associated with higher rates of upper gastrointestinal bleeding but not overall or lower GI bleeding rates, compared with direct oral anticoagulants (DOACs), according to a new nationwide report from Iceland.
In addition, warfarin is associated with higher rates of major GI bleeding, compared with apixaban.
“Although there has been a myriad of studies comparing GI bleeding rates between warfarin and DOACs, very few studies have compared upper and lower GI bleeding rates specifically,” Arnar Ingason, MD, PhD, a gastroenterology resident at the University of Iceland and Landspitali University Hospital, Reykjavik, said in an interview.
“Knowing whether the risk of upper and lower GI bleeding differs between warfarin and DOACs is important, as it can help guide oral anticoagulant selection,” he said.
“Given that warfarin was associated with higher rates of upper GI bleeding compared to DOACs in our study, warfarin may not be optimal for patients with high risk of upper GI bleeding, such as patients with previous history of upper GI bleeding,” Dr. Ingason added.
The study was published online in Clinical Gastroenterology and Hepatology.
Analyzing bleed rates
Dr. Ingason and colleagues analyzed data from electronic medical records for more than 7,000 patients in Iceland who began a prescription for oral anticoagulants between 2014 and 2019. They used inverse probability weighting to yield balanced study groups and calculate the rates of overall, major, upper, and lower GI bleeding. All events of gastrointestinal bleeding were manually confirmed by chart review.
Clinically relevant GI bleeding was defined as bleeding that led to medical intervention, unscheduled physician contact, or temporary cessation of treatment. Upper GI bleeding was defined as hematemesis or a confirmed upper GI bleed site on endoscopy, whereas lower gastrointestinal bleeding was defined as hematochezia or a confirmed lower GI bleed site on endoscopy. Patients with melena and uncertain bleeding site on endoscopy were classified as having a gastrointestinal bleed of unknown location.
Major bleeding was defined as a drop in hemoglobin of at least 20 g/L, transfusion of two or more packs of red blood cells, or bleeding into a closed compartment such as the retroperitoneum.
In total, 295 gastrointestinal bleed events were identified, with 150 events (51%) classified as lower, 105 events (36%) classified as upper, and 40 events (14%) of an unknown location. About 71% required hospitalization, and 63% met the criteria for major bleeding. Five patients died, including three taking warfarin and the other two taking apixaban and rivaroxaban.
Overall, warfarin was associated with double the rate of upper GI bleeding, with 1.7 events per 100 person-years, compared with 0.8 events per 100 person-years for DOACs. The rates of lower GI bleeding were similar for the drugs.
Specifically, warfarin was associated with nearly 5.5 times higher rates of upper gastrointestinal bleeding, compared with dabigatran (Pradaxa, Boehringer Ingelheim), 2.6 times higher than apixaban (Eliquis, Bristol-Myers Squibb), and 1.7 times higher than rivaroxaban (Xarelto, Janssen). The risk for upper GI bleeding also was higher in men taking warfarin.
Warfarin was associated with higher rates of major bleeding, compared with apixaban, with 2.3 events per 100 person-years versus 1.5 events per 100 person-years. Otherwise, overall and major bleed rates were similar for users of warfarin and DOACs.
“GI bleeding among cardiac patients on anticoagulants and antiplatelets is the fastest growing group of GI bleeders,” Neena Abraham, MD, professor of medicine and a gastroenterologist at the Mayo Clinic in Scottsdale, Ariz., said in an interview.
Dr. Abraham, who wasn’t involved with this study, runs a dedicated cardiogastroenterology practice and has studied these patients’ bleeding risk for 20 years.
“This is a group that is ever increasing with aging baby boomers,” she said. “It is anticipated by 2040 that more than 40% of the U.S. adult population will have one or more cardiovascular conditions requiring the chronic prescription of anticoagulant or antiplatelet drugs.”
Considering future research
In this study, peptic ulcer disease was a proportionally less common cause of upper GI bleeding for warfarin at 18%, compared with DOACs at 39%. At the same time, the absolute propensity-weighted incidence rates of peptic ulcer–induced bleeding were similar, with 0.3 events per 100 person-years for both groups.
“As warfarin is not thought to induce peptic ulcer disease but rather promote bleeding from pre-existing lesions, one explanation may be that peptic ulcer disease almost always leads to overt bleeding in anticoagulated patients, while other lesions, such as mucosal erosions and angiodysplasias, may be more likely to lead to overt bleeding in warfarin patients due to a potentially more intense anticoagulation,” Dr. Ingason said.
Dr. Ingason and colleagues now plan to compare GI bleeding severity between warfarin and DOACs. Previous studies have suggested that GI bleeding may be more severe in patients receiving warfarin than in those receiving DOACs, he said.
In addition, large studies with manual verification of GI bleed events could better estimate the potential differences in the sources of upper and lower bleeding between warfarin and DOACs, Dr. Ingason noted.
“Some DOACs, specifically dabigatran, are known to have a mucosal effect on the luminal GI tract, as well as a systemic effect,” Dr. Abraham said. “This pharmacologic effect may contribute to an increase in lower gastrointestinal bleeding in the setting of colonic diverticulosis or mucosal injuries from inflammatory processes.”
Ongoing research should also look at different ways to reduce anticoagulant-related GI bleeding among cardiac patients, she noted.
“Our research group continues to study the risk of cardiac and bleeding adverse events in patients prescribed to DOACs compared to those patients who receive a left atrial appendage occlusion device,” Dr. Abraham said. “This device often permits patients at high risk of GI bleeding to transition off anticoagulant and antiplatelet drugs.”
The study was funded by the Icelandic Centre for Research and the Landspitali University Hospital Research Fund. The funders had no role in the design, conduct, or reporting of the study. The authors declared no competing interests. Dr. Abraham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Early rhythm control improves cardiovascular outcomes in AFib patients regardless of stroke risk
These findings broaden support for early rhythm control, suggesting that physicians should be presenting the option to all patients diagnosed with AFib in routine clinical practice, lead author Daehoon Kim, MD, of Yonsei University, Seoul, South Korea, and colleagues reported.
In 2020, the EAST-AFNET 4 trial showed that early rhythm control was better than rate control for reducing adverse cardiovascular outcomes, but the trial only included patients at risk of stroke with a CHA2DS2-VASc score of at least 2, leaving it unclear whether healthier patients might benefit from the same approach.
“Although the primary indication for rhythm control is to alleviate AF[ib]-related symptoms and improve quality of life, the current guidelines suggest younger age and no or few comorbid conditions as factors favoring rhythm control,” the investigators wrote in Annals of Internal Medicine. “Thus, the effect of rhythm control on cardiovascular outcomes in this population requires elucidation.”
Methods and results
The present study aimed to address this knowledge gap by reviewing data from 54,216 patients with AFib who had rhythm control (ablation or medication) or rate control within one year of diagnosis. Among these patients, 69.3% would have qualified for the EAST-AFNET 4 trial based on higher stroke risk, while the remaining 30.7% of patients would not have been eligible because of lower stroke risk. Median age, consequently, was higher in the former group, at 70 years, versus 54 years in the latter group.
Evaluating the same primary composite outcome as the EAST-AFNET 4 trial (cardiovascular death, ischemic stroke, hospitalization for heart failure, or MI) showed that patients benefited from rhythm control over rate control regardless of risk group.
Those in the higher risk group had a 14% reduced risk of negative cardiovascular outcomes (weighted hazard ratio, 0.86; 95% confidence interval, 0.81-0.92), while those in the lower risk group had a 19% reduced risk of adverse cardiovascular outcomes (weighted HR, 0.81; 95% CI, 0.66-0.98). Safety profiles were similar across groups and management strategies.
Rhythm control well supported from statistical perspective
“We think that physicians should pursue early rhythm control in all patients diagnosed with AF[ib],” principal author Boyoung Joung, MD, PhD, of Yonsei University said in an interview. “Like catheter ablation, we support the idea that early rhythm control can be more effective and safely performed in younger and less frail populations.”
Xiaoxi Yao, PhD, MPH, associate professor of health services research at Mayo Clinic, Rochester, Minn., agreed that rhythm control is now well supported from a statistical perspective, but patients and physicians need to look beyond relative risk improvements, and remain pragmatic.
“There is a benefit, but the benefit is consistent in terms of hazard ratio, or relative risk,” Dr. Yao said in an interview. “You still find a smaller absolute risk difference.”
Patients in the United States – versus Korea where the investigators are based – also need to consider the out-of-pocket costs involved in rhythm control, Dr. Yao said, noting that unclear cost effectiveness may also prevent changes to American guidelines. Medication side effects and procedural risks should also be considered, she added, as well as time off from work needed for ablation.
Dr. Yao, who published a similar paper in June and previously evaluated the role of catheter ablation in routine practice, suggested that the youngest patients may have the most to gain from rhythm control. This is because even a small absolute benefit is magnified with time, she said.
“Since [younger patients] have another several decades to live ... then yes, there might be very significant long-term effects in terms of both symptom control and cardiovascular death and stroke,” Dr. Yao said.
For optimal patient selection, however, more advanced tools are needed, which is why Dr. Yao and her colleagues are exploring new technologies to improve risk-benefit analysis.
“We are not only interested in [a patient’s] baseline high or low risk, but also the extent of risk reduction [that rhythm control provides],” Dr. Yao said. “We are trying to see if there is an [artificial intelligence] or machine-learning approach that can help us provide each patient with a more accurate, individualized estimate to help them make their decision.”
Until then, Dr. Yao encouraged physicians to engage in shared decision-making with patients, making sure to discuss both statistical and practical considerations.
The study was funded by the Ministry of Health and Welfare and the Ministry of Food and Drug Safety of the Republic of Korea. The investigators and Dr. Yao reported no conflicts.
These findings broaden support for early rhythm control, suggesting that physicians should be presenting the option to all patients diagnosed with AFib in routine clinical practice, lead author Daehoon Kim, MD, of Yonsei University, Seoul, South Korea, and colleagues reported.
In 2020, the EAST-AFNET 4 trial showed that early rhythm control was better than rate control for reducing adverse cardiovascular outcomes, but the trial only included patients at risk of stroke with a CHA2DS2-VASc score of at least 2, leaving it unclear whether healthier patients might benefit from the same approach.
“Although the primary indication for rhythm control is to alleviate AF[ib]-related symptoms and improve quality of life, the current guidelines suggest younger age and no or few comorbid conditions as factors favoring rhythm control,” the investigators wrote in Annals of Internal Medicine. “Thus, the effect of rhythm control on cardiovascular outcomes in this population requires elucidation.”
Methods and results
The present study aimed to address this knowledge gap by reviewing data from 54,216 patients with AFib who had rhythm control (ablation or medication) or rate control within one year of diagnosis. Among these patients, 69.3% would have qualified for the EAST-AFNET 4 trial based on higher stroke risk, while the remaining 30.7% of patients would not have been eligible because of lower stroke risk. Median age, consequently, was higher in the former group, at 70 years, versus 54 years in the latter group.
Evaluating the same primary composite outcome as the EAST-AFNET 4 trial (cardiovascular death, ischemic stroke, hospitalization for heart failure, or MI) showed that patients benefited from rhythm control over rate control regardless of risk group.
Those in the higher risk group had a 14% reduced risk of negative cardiovascular outcomes (weighted hazard ratio, 0.86; 95% confidence interval, 0.81-0.92), while those in the lower risk group had a 19% reduced risk of adverse cardiovascular outcomes (weighted HR, 0.81; 95% CI, 0.66-0.98). Safety profiles were similar across groups and management strategies.
Rhythm control well supported from statistical perspective
“We think that physicians should pursue early rhythm control in all patients diagnosed with AF[ib],” principal author Boyoung Joung, MD, PhD, of Yonsei University said in an interview. “Like catheter ablation, we support the idea that early rhythm control can be more effective and safely performed in younger and less frail populations.”
Xiaoxi Yao, PhD, MPH, associate professor of health services research at Mayo Clinic, Rochester, Minn., agreed that rhythm control is now well supported from a statistical perspective, but patients and physicians need to look beyond relative risk improvements, and remain pragmatic.
“There is a benefit, but the benefit is consistent in terms of hazard ratio, or relative risk,” Dr. Yao said in an interview. “You still find a smaller absolute risk difference.”
Patients in the United States – versus Korea where the investigators are based – also need to consider the out-of-pocket costs involved in rhythm control, Dr. Yao said, noting that unclear cost effectiveness may also prevent changes to American guidelines. Medication side effects and procedural risks should also be considered, she added, as well as time off from work needed for ablation.
Dr. Yao, who published a similar paper in June and previously evaluated the role of catheter ablation in routine practice, suggested that the youngest patients may have the most to gain from rhythm control. This is because even a small absolute benefit is magnified with time, she said.
“Since [younger patients] have another several decades to live ... then yes, there might be very significant long-term effects in terms of both symptom control and cardiovascular death and stroke,” Dr. Yao said.
For optimal patient selection, however, more advanced tools are needed, which is why Dr. Yao and her colleagues are exploring new technologies to improve risk-benefit analysis.
“We are not only interested in [a patient’s] baseline high or low risk, but also the extent of risk reduction [that rhythm control provides],” Dr. Yao said. “We are trying to see if there is an [artificial intelligence] or machine-learning approach that can help us provide each patient with a more accurate, individualized estimate to help them make their decision.”
Until then, Dr. Yao encouraged physicians to engage in shared decision-making with patients, making sure to discuss both statistical and practical considerations.
The study was funded by the Ministry of Health and Welfare and the Ministry of Food and Drug Safety of the Republic of Korea. The investigators and Dr. Yao reported no conflicts.
These findings broaden support for early rhythm control, suggesting that physicians should be presenting the option to all patients diagnosed with AFib in routine clinical practice, lead author Daehoon Kim, MD, of Yonsei University, Seoul, South Korea, and colleagues reported.
In 2020, the EAST-AFNET 4 trial showed that early rhythm control was better than rate control for reducing adverse cardiovascular outcomes, but the trial only included patients at risk of stroke with a CHA2DS2-VASc score of at least 2, leaving it unclear whether healthier patients might benefit from the same approach.
“Although the primary indication for rhythm control is to alleviate AF[ib]-related symptoms and improve quality of life, the current guidelines suggest younger age and no or few comorbid conditions as factors favoring rhythm control,” the investigators wrote in Annals of Internal Medicine. “Thus, the effect of rhythm control on cardiovascular outcomes in this population requires elucidation.”
Methods and results
The present study aimed to address this knowledge gap by reviewing data from 54,216 patients with AFib who had rhythm control (ablation or medication) or rate control within one year of diagnosis. Among these patients, 69.3% would have qualified for the EAST-AFNET 4 trial based on higher stroke risk, while the remaining 30.7% of patients would not have been eligible because of lower stroke risk. Median age, consequently, was higher in the former group, at 70 years, versus 54 years in the latter group.
Evaluating the same primary composite outcome as the EAST-AFNET 4 trial (cardiovascular death, ischemic stroke, hospitalization for heart failure, or MI) showed that patients benefited from rhythm control over rate control regardless of risk group.
Those in the higher risk group had a 14% reduced risk of negative cardiovascular outcomes (weighted hazard ratio, 0.86; 95% confidence interval, 0.81-0.92), while those in the lower risk group had a 19% reduced risk of adverse cardiovascular outcomes (weighted HR, 0.81; 95% CI, 0.66-0.98). Safety profiles were similar across groups and management strategies.
Rhythm control well supported from statistical perspective
“We think that physicians should pursue early rhythm control in all patients diagnosed with AF[ib],” principal author Boyoung Joung, MD, PhD, of Yonsei University said in an interview. “Like catheter ablation, we support the idea that early rhythm control can be more effective and safely performed in younger and less frail populations.”
Xiaoxi Yao, PhD, MPH, associate professor of health services research at Mayo Clinic, Rochester, Minn., agreed that rhythm control is now well supported from a statistical perspective, but patients and physicians need to look beyond relative risk improvements, and remain pragmatic.
“There is a benefit, but the benefit is consistent in terms of hazard ratio, or relative risk,” Dr. Yao said in an interview. “You still find a smaller absolute risk difference.”
Patients in the United States – versus Korea where the investigators are based – also need to consider the out-of-pocket costs involved in rhythm control, Dr. Yao said, noting that unclear cost effectiveness may also prevent changes to American guidelines. Medication side effects and procedural risks should also be considered, she added, as well as time off from work needed for ablation.
Dr. Yao, who published a similar paper in June and previously evaluated the role of catheter ablation in routine practice, suggested that the youngest patients may have the most to gain from rhythm control. This is because even a small absolute benefit is magnified with time, she said.
“Since [younger patients] have another several decades to live ... then yes, there might be very significant long-term effects in terms of both symptom control and cardiovascular death and stroke,” Dr. Yao said.
For optimal patient selection, however, more advanced tools are needed, which is why Dr. Yao and her colleagues are exploring new technologies to improve risk-benefit analysis.
“We are not only interested in [a patient’s] baseline high or low risk, but also the extent of risk reduction [that rhythm control provides],” Dr. Yao said. “We are trying to see if there is an [artificial intelligence] or machine-learning approach that can help us provide each patient with a more accurate, individualized estimate to help them make their decision.”
Until then, Dr. Yao encouraged physicians to engage in shared decision-making with patients, making sure to discuss both statistical and practical considerations.
The study was funded by the Ministry of Health and Welfare and the Ministry of Food and Drug Safety of the Republic of Korea. The investigators and Dr. Yao reported no conflicts.
FROM ANNALS OF INTERNAL MEDICINE
Acute myocarditis a possible complication of monkeypox
Clinicians in Portugal say a 31-year-old man with confirmed monkeypox developed acute myocarditis roughly 1 week after the eruption of the characteristic skin lesions of the disease.
Ana Isabel Pinho, MD, department of cardiology, São João University Hospital Centre, Porto, Portugal, said in a news release.
“We believe that reporting this potential causal relationship can raise more awareness of the scientific community and health professionals for acute myocarditis as a possible complication associated with monkeypox and might be helpful for close monitoring of affected patients for further recognition of other complications in the future,” Dr. Pinho adds.
Dr. Pinho and colleagues describe the case in a report published in JACC: Case Reports.
Case details
The patient presented with a 5-day history of malaise, myalgias, and fever followed by the eruption of multiple swollen skin lesions on his face, hands, and genitalia.
Monkeypox was confirmed by positive polymerase chain reaction assay of a swab sample from a skin lesion.
Three days later, the patient developed chest tightness that radiated through the left arm and which awoke him during the night. He was admitted to an intensive care unit with clinical suspicion of acute myocarditis.
The patient’s initial electrocardiogram showed sinus rhythm with nonspecific ventricular repolarization abnormalities.
On chest x-ray, the cardiothoracic index was normal, with no interstitial infiltrates, pleural effusion, or masses. On transthoracic echocardigraphy, biventricular systolic function was preserved, and there was no pericardial effusion.
Routine laboratory tests revealed elevated levels of C-reactive protein, creatine phosphokinase, high-sensitivity troponin I, and brain natriuretic peptide, suggesting stress injury to the heart.
Findings on cardiac magnetic resonance were consistent with myocardial inflammation and acute myocarditis.
The patient was treated with supportive care, and he made a full clinical recovery. He was discharged after 1 week. On discharge, cardiac enzymes were within the normal range. The patient showed sustained electric and hemodynamic stability, and the skin lesions had healed.
“Through this important case study, we are developing a deeper understanding of monkeypox, viral myocarditis, and how to accurately diagnose and manage this disease,” Julia Grapsa, MD, PhD, editor-in-chief of JACC: Case Reports, commented in the news release.
“I commend the authors on this valuable clinical case during a critical time as monkeypox continues to spread globally,” Dr. Grapsa added.
The researchers say further research is needed to identify the pathologic mechanism underlying monkeypox-associated cardiac injury.
By the numbers
According to the latest data, California has reported 3,629 cases, followed closely by New York with 3,367 cases, Florida with 1,957 cases, Texas with 1,698, Georgia with 1,418, and Illinois with 1,081. The other states have reported fewer than 600 cases.
The CDC says that globally, more than 52,000 monkeypox cases have been reported.
Monkeypox case counts appear to be slowing in the United States and globally.
Last week, the World Health Organization said the number of new cases worldwide declined by 21% between Aug. 15 and 21 after increasing for 4 straight weeks.
The research had no funding. Dr. Pinho and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians in Portugal say a 31-year-old man with confirmed monkeypox developed acute myocarditis roughly 1 week after the eruption of the characteristic skin lesions of the disease.
Ana Isabel Pinho, MD, department of cardiology, São João University Hospital Centre, Porto, Portugal, said in a news release.
“We believe that reporting this potential causal relationship can raise more awareness of the scientific community and health professionals for acute myocarditis as a possible complication associated with monkeypox and might be helpful for close monitoring of affected patients for further recognition of other complications in the future,” Dr. Pinho adds.
Dr. Pinho and colleagues describe the case in a report published in JACC: Case Reports.
Case details
The patient presented with a 5-day history of malaise, myalgias, and fever followed by the eruption of multiple swollen skin lesions on his face, hands, and genitalia.
Monkeypox was confirmed by positive polymerase chain reaction assay of a swab sample from a skin lesion.
Three days later, the patient developed chest tightness that radiated through the left arm and which awoke him during the night. He was admitted to an intensive care unit with clinical suspicion of acute myocarditis.
The patient’s initial electrocardiogram showed sinus rhythm with nonspecific ventricular repolarization abnormalities.
On chest x-ray, the cardiothoracic index was normal, with no interstitial infiltrates, pleural effusion, or masses. On transthoracic echocardigraphy, biventricular systolic function was preserved, and there was no pericardial effusion.
Routine laboratory tests revealed elevated levels of C-reactive protein, creatine phosphokinase, high-sensitivity troponin I, and brain natriuretic peptide, suggesting stress injury to the heart.
Findings on cardiac magnetic resonance were consistent with myocardial inflammation and acute myocarditis.
The patient was treated with supportive care, and he made a full clinical recovery. He was discharged after 1 week. On discharge, cardiac enzymes were within the normal range. The patient showed sustained electric and hemodynamic stability, and the skin lesions had healed.
“Through this important case study, we are developing a deeper understanding of monkeypox, viral myocarditis, and how to accurately diagnose and manage this disease,” Julia Grapsa, MD, PhD, editor-in-chief of JACC: Case Reports, commented in the news release.
“I commend the authors on this valuable clinical case during a critical time as monkeypox continues to spread globally,” Dr. Grapsa added.
The researchers say further research is needed to identify the pathologic mechanism underlying monkeypox-associated cardiac injury.
By the numbers
According to the latest data, California has reported 3,629 cases, followed closely by New York with 3,367 cases, Florida with 1,957 cases, Texas with 1,698, Georgia with 1,418, and Illinois with 1,081. The other states have reported fewer than 600 cases.
The CDC says that globally, more than 52,000 monkeypox cases have been reported.
Monkeypox case counts appear to be slowing in the United States and globally.
Last week, the World Health Organization said the number of new cases worldwide declined by 21% between Aug. 15 and 21 after increasing for 4 straight weeks.
The research had no funding. Dr. Pinho and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians in Portugal say a 31-year-old man with confirmed monkeypox developed acute myocarditis roughly 1 week after the eruption of the characteristic skin lesions of the disease.
Ana Isabel Pinho, MD, department of cardiology, São João University Hospital Centre, Porto, Portugal, said in a news release.
“We believe that reporting this potential causal relationship can raise more awareness of the scientific community and health professionals for acute myocarditis as a possible complication associated with monkeypox and might be helpful for close monitoring of affected patients for further recognition of other complications in the future,” Dr. Pinho adds.
Dr. Pinho and colleagues describe the case in a report published in JACC: Case Reports.
Case details
The patient presented with a 5-day history of malaise, myalgias, and fever followed by the eruption of multiple swollen skin lesions on his face, hands, and genitalia.
Monkeypox was confirmed by positive polymerase chain reaction assay of a swab sample from a skin lesion.
Three days later, the patient developed chest tightness that radiated through the left arm and which awoke him during the night. He was admitted to an intensive care unit with clinical suspicion of acute myocarditis.
The patient’s initial electrocardiogram showed sinus rhythm with nonspecific ventricular repolarization abnormalities.
On chest x-ray, the cardiothoracic index was normal, with no interstitial infiltrates, pleural effusion, or masses. On transthoracic echocardigraphy, biventricular systolic function was preserved, and there was no pericardial effusion.
Routine laboratory tests revealed elevated levels of C-reactive protein, creatine phosphokinase, high-sensitivity troponin I, and brain natriuretic peptide, suggesting stress injury to the heart.
Findings on cardiac magnetic resonance were consistent with myocardial inflammation and acute myocarditis.
The patient was treated with supportive care, and he made a full clinical recovery. He was discharged after 1 week. On discharge, cardiac enzymes were within the normal range. The patient showed sustained electric and hemodynamic stability, and the skin lesions had healed.
“Through this important case study, we are developing a deeper understanding of monkeypox, viral myocarditis, and how to accurately diagnose and manage this disease,” Julia Grapsa, MD, PhD, editor-in-chief of JACC: Case Reports, commented in the news release.
“I commend the authors on this valuable clinical case during a critical time as monkeypox continues to spread globally,” Dr. Grapsa added.
The researchers say further research is needed to identify the pathologic mechanism underlying monkeypox-associated cardiac injury.
By the numbers
According to the latest data, California has reported 3,629 cases, followed closely by New York with 3,367 cases, Florida with 1,957 cases, Texas with 1,698, Georgia with 1,418, and Illinois with 1,081. The other states have reported fewer than 600 cases.
The CDC says that globally, more than 52,000 monkeypox cases have been reported.
Monkeypox case counts appear to be slowing in the United States and globally.
Last week, the World Health Organization said the number of new cases worldwide declined by 21% between Aug. 15 and 21 after increasing for 4 straight weeks.
The research had no funding. Dr. Pinho and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low physical function tied to cardiac events in older adults
including coronary heart disease (CHD), stroke, and heart failure (HF) in older adults, according to new observational data from the Atherosclerosis Risk in Communities (ARIC) study.
“We found that physical function in older adults predicts future cardiovascular disease (CVD) beyond traditional heart disease risk factors, regardless of whether an individual has a history of cardiovascular disease,” senior author Kunihiro Matsushita, MD, PhD, division of cardiology, Johns Hopkins University, Baltimore, said in a news release.
The study was published online in the Journal of the American Heart Association.
Keeping fit with age
The researchers analyzed health data collected between 2011 and 2013 for 5,570 ARIC participants (mean age, 75 years; 58% women, 22% Black persons). They assessed physical function using the Short Physical Performance Battery (SPPB), which measures walking speed, leg strength, and balance.
On the basis of the results, participants were categorized into three physical function groups: low (score, 0-6; 13% of the cohort), intermediate (score, 7-9; 30%) and high (score, 10-12; 57%).
During a median follow up of 7 years, there were 930 composite CVD events (386 CHD, 251 stroke, and 529 HF).
Adults with lower SPPB scores had a higher cumulative incidence of composite CVD outcomes.
The 5-year cumulative incidence of the composite CVD outcome in the low- and intermediate-SPPB categories was about three times (23.4%) and two times (15.3%) higher than in the high-SPPB category (8.6%), the researchers reported.
In addition, continuous SPPB scores showed significant associations with composite and individual CVD outcomes in all models. A 1-point lower SPPB score was associated with 6%-10% higher risk for CVD events after adjusting for potential confounders.
In the fully adjusted model, the risk for composite CVD outcomes was 47% higher (hazard ratio, 1.47; 95% confidence interval, 1.20-1.79) in those with low physical function and 25% higher in those with intermediate physical function (HR, 1.25; 95% CI, 1.07-1.46) compared with peers with high physical function.
For the individual outcomes, low physical function was associated with higher risk for stroke (HR, 1.81; 95% CI, 1.24-2.64) and HF (HR, 1.33; 95% CI, 1.02-1.73), whereas the association for CHD was not significant.
The associations were largely consistent across subgroups, including those with CVD at baseline.
The addition of SPPB scores significantly improved risk prediction of CVD events beyond traditional CVD risk factors in adults regardless of prior CVD history, suggesting that this tool may be useful for classifying CVD risk in older adults, the researchers said.
Meaningful impact on care?
“Our findings highlight the value of assessing the physical function level of older adults in clinical practice,” lead author Xiao Hu, MHS, with the department of epidemiology at Johns Hopkins, said in the news release. “In addition to heart health, older adults are at higher risk for falls and disability. The assessment of physical function may also inform the risk of these concerning conditions in older adults.”
Weighing in on the study, Jonathan Halperin, MD, cardiologist at Mount Sinai Heart and professor of medicine (cardiology) at the Icahn School of Medicine at Mount Sinai, both in New York, said that “It’s known that cardiorespiratory fitness is an important predictor of cardiovascular risk, but it is one of the few physiological risk factors that are subjectively queried but not objectively assessed in routine clinical practice.”
In this study, Dr. Halperin noted, the investigators found that a battery of physical performance assessments, including a walk test, chair standing, and balance testing, improved cardiovascular risk prediction.
Dr. Halperin cautioned, however, that “since even the short sequence of tests takes time to perform and interpret, and is not currently reimbursed under most health insurance policies, it is not clear whether the report will have a meaningful impact on patient care.”
This research was funded by the National Institutes of Health. Dr. Matsushita and Dr. Halperin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
including coronary heart disease (CHD), stroke, and heart failure (HF) in older adults, according to new observational data from the Atherosclerosis Risk in Communities (ARIC) study.
“We found that physical function in older adults predicts future cardiovascular disease (CVD) beyond traditional heart disease risk factors, regardless of whether an individual has a history of cardiovascular disease,” senior author Kunihiro Matsushita, MD, PhD, division of cardiology, Johns Hopkins University, Baltimore, said in a news release.
The study was published online in the Journal of the American Heart Association.
Keeping fit with age
The researchers analyzed health data collected between 2011 and 2013 for 5,570 ARIC participants (mean age, 75 years; 58% women, 22% Black persons). They assessed physical function using the Short Physical Performance Battery (SPPB), which measures walking speed, leg strength, and balance.
On the basis of the results, participants were categorized into three physical function groups: low (score, 0-6; 13% of the cohort), intermediate (score, 7-9; 30%) and high (score, 10-12; 57%).
During a median follow up of 7 years, there were 930 composite CVD events (386 CHD, 251 stroke, and 529 HF).
Adults with lower SPPB scores had a higher cumulative incidence of composite CVD outcomes.
The 5-year cumulative incidence of the composite CVD outcome in the low- and intermediate-SPPB categories was about three times (23.4%) and two times (15.3%) higher than in the high-SPPB category (8.6%), the researchers reported.
In addition, continuous SPPB scores showed significant associations with composite and individual CVD outcomes in all models. A 1-point lower SPPB score was associated with 6%-10% higher risk for CVD events after adjusting for potential confounders.
In the fully adjusted model, the risk for composite CVD outcomes was 47% higher (hazard ratio, 1.47; 95% confidence interval, 1.20-1.79) in those with low physical function and 25% higher in those with intermediate physical function (HR, 1.25; 95% CI, 1.07-1.46) compared with peers with high physical function.
For the individual outcomes, low physical function was associated with higher risk for stroke (HR, 1.81; 95% CI, 1.24-2.64) and HF (HR, 1.33; 95% CI, 1.02-1.73), whereas the association for CHD was not significant.
The associations were largely consistent across subgroups, including those with CVD at baseline.
The addition of SPPB scores significantly improved risk prediction of CVD events beyond traditional CVD risk factors in adults regardless of prior CVD history, suggesting that this tool may be useful for classifying CVD risk in older adults, the researchers said.
Meaningful impact on care?
“Our findings highlight the value of assessing the physical function level of older adults in clinical practice,” lead author Xiao Hu, MHS, with the department of epidemiology at Johns Hopkins, said in the news release. “In addition to heart health, older adults are at higher risk for falls and disability. The assessment of physical function may also inform the risk of these concerning conditions in older adults.”
Weighing in on the study, Jonathan Halperin, MD, cardiologist at Mount Sinai Heart and professor of medicine (cardiology) at the Icahn School of Medicine at Mount Sinai, both in New York, said that “It’s known that cardiorespiratory fitness is an important predictor of cardiovascular risk, but it is one of the few physiological risk factors that are subjectively queried but not objectively assessed in routine clinical practice.”
In this study, Dr. Halperin noted, the investigators found that a battery of physical performance assessments, including a walk test, chair standing, and balance testing, improved cardiovascular risk prediction.
Dr. Halperin cautioned, however, that “since even the short sequence of tests takes time to perform and interpret, and is not currently reimbursed under most health insurance policies, it is not clear whether the report will have a meaningful impact on patient care.”
This research was funded by the National Institutes of Health. Dr. Matsushita and Dr. Halperin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
including coronary heart disease (CHD), stroke, and heart failure (HF) in older adults, according to new observational data from the Atherosclerosis Risk in Communities (ARIC) study.
“We found that physical function in older adults predicts future cardiovascular disease (CVD) beyond traditional heart disease risk factors, regardless of whether an individual has a history of cardiovascular disease,” senior author Kunihiro Matsushita, MD, PhD, division of cardiology, Johns Hopkins University, Baltimore, said in a news release.
The study was published online in the Journal of the American Heart Association.
Keeping fit with age
The researchers analyzed health data collected between 2011 and 2013 for 5,570 ARIC participants (mean age, 75 years; 58% women, 22% Black persons). They assessed physical function using the Short Physical Performance Battery (SPPB), which measures walking speed, leg strength, and balance.
On the basis of the results, participants were categorized into three physical function groups: low (score, 0-6; 13% of the cohort), intermediate (score, 7-9; 30%) and high (score, 10-12; 57%).
During a median follow up of 7 years, there were 930 composite CVD events (386 CHD, 251 stroke, and 529 HF).
Adults with lower SPPB scores had a higher cumulative incidence of composite CVD outcomes.
The 5-year cumulative incidence of the composite CVD outcome in the low- and intermediate-SPPB categories was about three times (23.4%) and two times (15.3%) higher than in the high-SPPB category (8.6%), the researchers reported.
In addition, continuous SPPB scores showed significant associations with composite and individual CVD outcomes in all models. A 1-point lower SPPB score was associated with 6%-10% higher risk for CVD events after adjusting for potential confounders.
In the fully adjusted model, the risk for composite CVD outcomes was 47% higher (hazard ratio, 1.47; 95% confidence interval, 1.20-1.79) in those with low physical function and 25% higher in those with intermediate physical function (HR, 1.25; 95% CI, 1.07-1.46) compared with peers with high physical function.
For the individual outcomes, low physical function was associated with higher risk for stroke (HR, 1.81; 95% CI, 1.24-2.64) and HF (HR, 1.33; 95% CI, 1.02-1.73), whereas the association for CHD was not significant.
The associations were largely consistent across subgroups, including those with CVD at baseline.
The addition of SPPB scores significantly improved risk prediction of CVD events beyond traditional CVD risk factors in adults regardless of prior CVD history, suggesting that this tool may be useful for classifying CVD risk in older adults, the researchers said.
Meaningful impact on care?
“Our findings highlight the value of assessing the physical function level of older adults in clinical practice,” lead author Xiao Hu, MHS, with the department of epidemiology at Johns Hopkins, said in the news release. “In addition to heart health, older adults are at higher risk for falls and disability. The assessment of physical function may also inform the risk of these concerning conditions in older adults.”
Weighing in on the study, Jonathan Halperin, MD, cardiologist at Mount Sinai Heart and professor of medicine (cardiology) at the Icahn School of Medicine at Mount Sinai, both in New York, said that “It’s known that cardiorespiratory fitness is an important predictor of cardiovascular risk, but it is one of the few physiological risk factors that are subjectively queried but not objectively assessed in routine clinical practice.”
In this study, Dr. Halperin noted, the investigators found that a battery of physical performance assessments, including a walk test, chair standing, and balance testing, improved cardiovascular risk prediction.
Dr. Halperin cautioned, however, that “since even the short sequence of tests takes time to perform and interpret, and is not currently reimbursed under most health insurance policies, it is not clear whether the report will have a meaningful impact on patient care.”
This research was funded by the National Institutes of Health. Dr. Matsushita and Dr. Halperin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
AHA guidance on infective endocarditis with injection drug use
Prompted by the “unprecedented” increase in the occurrence of infective endocarditis (IE) cases among people who inject drugs, the American Heart Association has issued a scientific statement devoted solely to this challenging patient population.
The statement provides a more in-depth focus on the management of IE among this unique population than what has been provided in prior AHA IE-related documents.
The statement stresses that managing IE in people who inject drugs is complex and requires a unique multidisciplinary approach that includes consultation with an addiction specialist.
The statement was published online in Circulation.
Poor long-term prognosis
In the United States from 2002 to 2016, the proportion of patients hospitalized with IE related to injection drug use doubled from 8% to about 16%.
The long-term prognosis for this population is “currently dismal for this relatively young group of individuals,” writing group Chair Daniel C. DeSimone, MD, with the Mayo Clinic in Rochester, Minn., notes in a news release.
as well as addiction medicine or addiction psychiatry specialists, pharmacists, social workers, and nurse specialists.
Nurse specialists can coordinate care from the initial IE hospitalization to outpatient and community care to support substance use disorder.
“Clinical teams must recognize that substance use disorder is a treatable chronic, relapsing medical illness and many people are able to enter sustained remission, particularly when they receive effective treatments,” the writing group emphasizes.
Although not all patients with injection drug–related IE have opioid addiction, for those who do, the “best practice” is to offer buprenorphine or methadone “as soon as possible” after the patient presents to the hospital, they advise.
Antimicrobial therapy
The writing group says it’s “reasonable” to offer people with injection drug–related IE standard treatment for IE, which is 6 weeks of intravenous antibiotics. They recognize, however, that this regimen is often not feasible in this patient population and say there is growing evidence that partial intravenous therapy followed by oral antibiotic treatment to complete a total of 6 weeks is a possible option.
They also highlight the “critical” importance of preventive measures in people who inject drugs who are successfully treated for an initial bout of IE because they remain at “extremely” high risk for subsequent bouts of IE, regardless of whether injection drug use is continued.
The writing group also stresses that people with IE who inject drugs should be considered for heart valve repair or replacement surgery regardless of current drug use if they have indications for valve surgery.
“There’s no evidence that indications for valve surgery are different for people who inject drugs compared to those who don’t, however, some treatment centers don’t offer surgery, especially if the patient currently injects drugs or has had a previous valve surgery,” Dr. DeSimone says in the release.
“Those who develop infective endocarditis require complex care delivered by professionals who look beyond stigma and bias to provide optimal and equitable care,” Dr. DeSimone adds.
The writing group acknowledges that while addiction medicine and addiction psychiatry expertise are critical to managing IE in injection drug users, these specific resources are currently not widely available.
They call on health care systems to attract individuals with addiction training and support addiction medicine consultative services, particularly in centers where drug use–related IE is common and expected to continue to increase.
This AHA scientific statement was prepared by the volunteer writing group on behalf of the AHA Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiovascular and Stroke Nursing; the Council on Clinical Cardiology; and the Council on Peripheral Vascular Disease.
This research had no commercial funding. Dr. DeSimone has no relevant disclosures.
A version of this article first appeared on Medscape.com.
Prompted by the “unprecedented” increase in the occurrence of infective endocarditis (IE) cases among people who inject drugs, the American Heart Association has issued a scientific statement devoted solely to this challenging patient population.
The statement provides a more in-depth focus on the management of IE among this unique population than what has been provided in prior AHA IE-related documents.
The statement stresses that managing IE in people who inject drugs is complex and requires a unique multidisciplinary approach that includes consultation with an addiction specialist.
The statement was published online in Circulation.
Poor long-term prognosis
In the United States from 2002 to 2016, the proportion of patients hospitalized with IE related to injection drug use doubled from 8% to about 16%.
The long-term prognosis for this population is “currently dismal for this relatively young group of individuals,” writing group Chair Daniel C. DeSimone, MD, with the Mayo Clinic in Rochester, Minn., notes in a news release.
as well as addiction medicine or addiction psychiatry specialists, pharmacists, social workers, and nurse specialists.
Nurse specialists can coordinate care from the initial IE hospitalization to outpatient and community care to support substance use disorder.
“Clinical teams must recognize that substance use disorder is a treatable chronic, relapsing medical illness and many people are able to enter sustained remission, particularly when they receive effective treatments,” the writing group emphasizes.
Although not all patients with injection drug–related IE have opioid addiction, for those who do, the “best practice” is to offer buprenorphine or methadone “as soon as possible” after the patient presents to the hospital, they advise.
Antimicrobial therapy
The writing group says it’s “reasonable” to offer people with injection drug–related IE standard treatment for IE, which is 6 weeks of intravenous antibiotics. They recognize, however, that this regimen is often not feasible in this patient population and say there is growing evidence that partial intravenous therapy followed by oral antibiotic treatment to complete a total of 6 weeks is a possible option.
They also highlight the “critical” importance of preventive measures in people who inject drugs who are successfully treated for an initial bout of IE because they remain at “extremely” high risk for subsequent bouts of IE, regardless of whether injection drug use is continued.
The writing group also stresses that people with IE who inject drugs should be considered for heart valve repair or replacement surgery regardless of current drug use if they have indications for valve surgery.
“There’s no evidence that indications for valve surgery are different for people who inject drugs compared to those who don’t, however, some treatment centers don’t offer surgery, especially if the patient currently injects drugs or has had a previous valve surgery,” Dr. DeSimone says in the release.
“Those who develop infective endocarditis require complex care delivered by professionals who look beyond stigma and bias to provide optimal and equitable care,” Dr. DeSimone adds.
The writing group acknowledges that while addiction medicine and addiction psychiatry expertise are critical to managing IE in injection drug users, these specific resources are currently not widely available.
They call on health care systems to attract individuals with addiction training and support addiction medicine consultative services, particularly in centers where drug use–related IE is common and expected to continue to increase.
This AHA scientific statement was prepared by the volunteer writing group on behalf of the AHA Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiovascular and Stroke Nursing; the Council on Clinical Cardiology; and the Council on Peripheral Vascular Disease.
This research had no commercial funding. Dr. DeSimone has no relevant disclosures.
A version of this article first appeared on Medscape.com.
Prompted by the “unprecedented” increase in the occurrence of infective endocarditis (IE) cases among people who inject drugs, the American Heart Association has issued a scientific statement devoted solely to this challenging patient population.
The statement provides a more in-depth focus on the management of IE among this unique population than what has been provided in prior AHA IE-related documents.
The statement stresses that managing IE in people who inject drugs is complex and requires a unique multidisciplinary approach that includes consultation with an addiction specialist.
The statement was published online in Circulation.
Poor long-term prognosis
In the United States from 2002 to 2016, the proportion of patients hospitalized with IE related to injection drug use doubled from 8% to about 16%.
The long-term prognosis for this population is “currently dismal for this relatively young group of individuals,” writing group Chair Daniel C. DeSimone, MD, with the Mayo Clinic in Rochester, Minn., notes in a news release.
as well as addiction medicine or addiction psychiatry specialists, pharmacists, social workers, and nurse specialists.
Nurse specialists can coordinate care from the initial IE hospitalization to outpatient and community care to support substance use disorder.
“Clinical teams must recognize that substance use disorder is a treatable chronic, relapsing medical illness and many people are able to enter sustained remission, particularly when they receive effective treatments,” the writing group emphasizes.
Although not all patients with injection drug–related IE have opioid addiction, for those who do, the “best practice” is to offer buprenorphine or methadone “as soon as possible” after the patient presents to the hospital, they advise.
Antimicrobial therapy
The writing group says it’s “reasonable” to offer people with injection drug–related IE standard treatment for IE, which is 6 weeks of intravenous antibiotics. They recognize, however, that this regimen is often not feasible in this patient population and say there is growing evidence that partial intravenous therapy followed by oral antibiotic treatment to complete a total of 6 weeks is a possible option.
They also highlight the “critical” importance of preventive measures in people who inject drugs who are successfully treated for an initial bout of IE because they remain at “extremely” high risk for subsequent bouts of IE, regardless of whether injection drug use is continued.
The writing group also stresses that people with IE who inject drugs should be considered for heart valve repair or replacement surgery regardless of current drug use if they have indications for valve surgery.
“There’s no evidence that indications for valve surgery are different for people who inject drugs compared to those who don’t, however, some treatment centers don’t offer surgery, especially if the patient currently injects drugs or has had a previous valve surgery,” Dr. DeSimone says in the release.
“Those who develop infective endocarditis require complex care delivered by professionals who look beyond stigma and bias to provide optimal and equitable care,” Dr. DeSimone adds.
The writing group acknowledges that while addiction medicine and addiction psychiatry expertise are critical to managing IE in injection drug users, these specific resources are currently not widely available.
They call on health care systems to attract individuals with addiction training and support addiction medicine consultative services, particularly in centers where drug use–related IE is common and expected to continue to increase.
This AHA scientific statement was prepared by the volunteer writing group on behalf of the AHA Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiovascular and Stroke Nursing; the Council on Clinical Cardiology; and the Council on Peripheral Vascular Disease.
This research had no commercial funding. Dr. DeSimone has no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
MR and PET perform similarly for assessing CAD
BARCELONA – Two noninvasive imaging methods for assessing coronary artery disease – cardiac magnetic resonance (CMR) and positron emission tomography using rubidium stress (RbPET) – had nearly identical accuracy for ruling-in or ruling-out coronary disease, making them for at least the time being equally appropriate to use when assessing low- or intermediate-risk patients with symptoms suggestive of possible coronary disease in a prospective, multicenter study with 372 patients.
that used fractional flow reserve assessment via invasive coronary angiography in each patient in the study as the arbiter of the true extent of coronary disease, reported Morten Bøttcher, MD, PhD, at the annual congress of the European Society of Cardiology.
This result is good news for practice because clinicians can feel free to use whichever of the two assessment methods is most feasible for each patient, said Dr. Bøttcher, a researcher at Aarhus (Denmark) University Hospital. But the study was limited by its size, and he hopes to run a future study with many more patients to try to more definitively compare RbPET and CMR.
‘The techniques are probably interchangeable’
“There is a very clear result from the data: The performance of the two modalities is similar in the population studied,” commented Colin Berry, MBChB, PhD, professor of cardiology and imaging at the University of Glasgow (Scotland), and designated discussant for the report. “The techniques are probably interchangeable,” he said.
Dr. Bøttcher and his associates designed the Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 (Dan-NICAD 2) to address a knowledge gap highlighted in the 2019 guidelines of the European Society of Cardiology for the management of patients with chronic coronary syndromes, specifically low- or intermediate-risk patients who present with symptoms of possible coronary disease who have been identified as having possibly stenotic coronary lesions using coronary CT angiography. The guidelines cite using noninvasive imaging at this point prior to invasive angiography, but note that the relative performance of the various imaging options available for this step in unknown, said Dr. Bøttcher.
The researchers enrolled 372 patients at any of four hospitals in Denmark who agreed to participate and had a positive result on a coronary CT examination performed to assess their symptoms of coronary disease. (These 372 patients came from an initial pool of people that was fourfold larger, but three-quarters had negative findings on their coronary CT examination.) Clinicians had referred all of these patients to invasive angiography with fractional flow reserve assessment, and prior to that procedure they each underwent both a RbPET and a CMR examination for the purpose of this study. The researchers used each patient’s eventual invasive angiography result as the definitive determinant of their coronary disease. These patients averaged 64 years old, and 71% were men.
This analysis showed that for all 372 patients RbPET had 63% sensitivity and 87% specificity for identifying hemodynamically obstructive coronary disease, with rates of 60% and 85%, respectively, for CMR. In the subgroup of 71 patients (19%) who had obstructive coronary disease when examined by invasive angiography the sensitivity and specificity of the RbPET examination was 90% and 78%, and for CMR the sensitivity and specificity was 83% and 76%, Dr. Bøttcher reported.
Negative imaging, positive FFR
He also noted that it remains unclear how to best manage patients who show no signs of ischemia when examined by RbPET or CMR, but have an apparently hemodynamically meaningful coronary lesion when assessed by invasive angiography and fractional flow reserve. “We don’t know whether we should be guided by the negative scan or by the positive FFR result,” Dr. Bøttcher said. “There is a challenge when you get different results.”
In addition, the two compared imaging methods both have logistical limitations. RbPET involved radiation exposure, and CMR performed with a 3-tesla device may not be as widely available and requires more expensive equipment.
Dr. Berry also noted that imaging methods continue to advance. For example, the CMR examinations used in the study involved qualitative assessments, but quantitative CMR is now becoming more widely available and may provide enhanced diagnostic capabilities. Dr. Berry added that patients with symptoms of coronary disease but without an identifiable coronary obstruction may have microvascular coronary disease, a disorder that he has been at the forefront of describing.
Dan-NICAD 2 received no commercial funding. Dr. Bøttcher has been an adviser to Acarix, Amgen, AstraZeneca, Bayer, and Novo Nordisk. Dr. Berry had no disclosures.
BARCELONA – Two noninvasive imaging methods for assessing coronary artery disease – cardiac magnetic resonance (CMR) and positron emission tomography using rubidium stress (RbPET) – had nearly identical accuracy for ruling-in or ruling-out coronary disease, making them for at least the time being equally appropriate to use when assessing low- or intermediate-risk patients with symptoms suggestive of possible coronary disease in a prospective, multicenter study with 372 patients.
that used fractional flow reserve assessment via invasive coronary angiography in each patient in the study as the arbiter of the true extent of coronary disease, reported Morten Bøttcher, MD, PhD, at the annual congress of the European Society of Cardiology.
This result is good news for practice because clinicians can feel free to use whichever of the two assessment methods is most feasible for each patient, said Dr. Bøttcher, a researcher at Aarhus (Denmark) University Hospital. But the study was limited by its size, and he hopes to run a future study with many more patients to try to more definitively compare RbPET and CMR.
‘The techniques are probably interchangeable’
“There is a very clear result from the data: The performance of the two modalities is similar in the population studied,” commented Colin Berry, MBChB, PhD, professor of cardiology and imaging at the University of Glasgow (Scotland), and designated discussant for the report. “The techniques are probably interchangeable,” he said.
Dr. Bøttcher and his associates designed the Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 (Dan-NICAD 2) to address a knowledge gap highlighted in the 2019 guidelines of the European Society of Cardiology for the management of patients with chronic coronary syndromes, specifically low- or intermediate-risk patients who present with symptoms of possible coronary disease who have been identified as having possibly stenotic coronary lesions using coronary CT angiography. The guidelines cite using noninvasive imaging at this point prior to invasive angiography, but note that the relative performance of the various imaging options available for this step in unknown, said Dr. Bøttcher.
The researchers enrolled 372 patients at any of four hospitals in Denmark who agreed to participate and had a positive result on a coronary CT examination performed to assess their symptoms of coronary disease. (These 372 patients came from an initial pool of people that was fourfold larger, but three-quarters had negative findings on their coronary CT examination.) Clinicians had referred all of these patients to invasive angiography with fractional flow reserve assessment, and prior to that procedure they each underwent both a RbPET and a CMR examination for the purpose of this study. The researchers used each patient’s eventual invasive angiography result as the definitive determinant of their coronary disease. These patients averaged 64 years old, and 71% were men.
This analysis showed that for all 372 patients RbPET had 63% sensitivity and 87% specificity for identifying hemodynamically obstructive coronary disease, with rates of 60% and 85%, respectively, for CMR. In the subgroup of 71 patients (19%) who had obstructive coronary disease when examined by invasive angiography the sensitivity and specificity of the RbPET examination was 90% and 78%, and for CMR the sensitivity and specificity was 83% and 76%, Dr. Bøttcher reported.
Negative imaging, positive FFR
He also noted that it remains unclear how to best manage patients who show no signs of ischemia when examined by RbPET or CMR, but have an apparently hemodynamically meaningful coronary lesion when assessed by invasive angiography and fractional flow reserve. “We don’t know whether we should be guided by the negative scan or by the positive FFR result,” Dr. Bøttcher said. “There is a challenge when you get different results.”
In addition, the two compared imaging methods both have logistical limitations. RbPET involved radiation exposure, and CMR performed with a 3-tesla device may not be as widely available and requires more expensive equipment.
Dr. Berry also noted that imaging methods continue to advance. For example, the CMR examinations used in the study involved qualitative assessments, but quantitative CMR is now becoming more widely available and may provide enhanced diagnostic capabilities. Dr. Berry added that patients with symptoms of coronary disease but without an identifiable coronary obstruction may have microvascular coronary disease, a disorder that he has been at the forefront of describing.
Dan-NICAD 2 received no commercial funding. Dr. Bøttcher has been an adviser to Acarix, Amgen, AstraZeneca, Bayer, and Novo Nordisk. Dr. Berry had no disclosures.
BARCELONA – Two noninvasive imaging methods for assessing coronary artery disease – cardiac magnetic resonance (CMR) and positron emission tomography using rubidium stress (RbPET) – had nearly identical accuracy for ruling-in or ruling-out coronary disease, making them for at least the time being equally appropriate to use when assessing low- or intermediate-risk patients with symptoms suggestive of possible coronary disease in a prospective, multicenter study with 372 patients.
that used fractional flow reserve assessment via invasive coronary angiography in each patient in the study as the arbiter of the true extent of coronary disease, reported Morten Bøttcher, MD, PhD, at the annual congress of the European Society of Cardiology.
This result is good news for practice because clinicians can feel free to use whichever of the two assessment methods is most feasible for each patient, said Dr. Bøttcher, a researcher at Aarhus (Denmark) University Hospital. But the study was limited by its size, and he hopes to run a future study with many more patients to try to more definitively compare RbPET and CMR.
‘The techniques are probably interchangeable’
“There is a very clear result from the data: The performance of the two modalities is similar in the population studied,” commented Colin Berry, MBChB, PhD, professor of cardiology and imaging at the University of Glasgow (Scotland), and designated discussant for the report. “The techniques are probably interchangeable,” he said.
Dr. Bøttcher and his associates designed the Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 (Dan-NICAD 2) to address a knowledge gap highlighted in the 2019 guidelines of the European Society of Cardiology for the management of patients with chronic coronary syndromes, specifically low- or intermediate-risk patients who present with symptoms of possible coronary disease who have been identified as having possibly stenotic coronary lesions using coronary CT angiography. The guidelines cite using noninvasive imaging at this point prior to invasive angiography, but note that the relative performance of the various imaging options available for this step in unknown, said Dr. Bøttcher.
The researchers enrolled 372 patients at any of four hospitals in Denmark who agreed to participate and had a positive result on a coronary CT examination performed to assess their symptoms of coronary disease. (These 372 patients came from an initial pool of people that was fourfold larger, but three-quarters had negative findings on their coronary CT examination.) Clinicians had referred all of these patients to invasive angiography with fractional flow reserve assessment, and prior to that procedure they each underwent both a RbPET and a CMR examination for the purpose of this study. The researchers used each patient’s eventual invasive angiography result as the definitive determinant of their coronary disease. These patients averaged 64 years old, and 71% were men.
This analysis showed that for all 372 patients RbPET had 63% sensitivity and 87% specificity for identifying hemodynamically obstructive coronary disease, with rates of 60% and 85%, respectively, for CMR. In the subgroup of 71 patients (19%) who had obstructive coronary disease when examined by invasive angiography the sensitivity and specificity of the RbPET examination was 90% and 78%, and for CMR the sensitivity and specificity was 83% and 76%, Dr. Bøttcher reported.
Negative imaging, positive FFR
He also noted that it remains unclear how to best manage patients who show no signs of ischemia when examined by RbPET or CMR, but have an apparently hemodynamically meaningful coronary lesion when assessed by invasive angiography and fractional flow reserve. “We don’t know whether we should be guided by the negative scan or by the positive FFR result,” Dr. Bøttcher said. “There is a challenge when you get different results.”
In addition, the two compared imaging methods both have logistical limitations. RbPET involved radiation exposure, and CMR performed with a 3-tesla device may not be as widely available and requires more expensive equipment.
Dr. Berry also noted that imaging methods continue to advance. For example, the CMR examinations used in the study involved qualitative assessments, but quantitative CMR is now becoming more widely available and may provide enhanced diagnostic capabilities. Dr. Berry added that patients with symptoms of coronary disease but without an identifiable coronary obstruction may have microvascular coronary disease, a disorder that he has been at the forefront of describing.
Dan-NICAD 2 received no commercial funding. Dr. Bøttcher has been an adviser to Acarix, Amgen, AstraZeneca, Bayer, and Novo Nordisk. Dr. Berry had no disclosures.
AT ESC CONGRESS 2022
AI-assisted reading of echocardiograms readily detects severe aortic stenosis
AI might facilitate early intervention
Patients with aortic stenosis (AS) of sufficient severity to portend a high likelihood of early mortality can be detected by an artificial intelligence (AI) algorithm employed in the reading of routine echocardiograms, according to a study that tested this tool in a large national database.
The artificial intelligence decision support algorithm (AI-DSA) “automatically identified patients with moderate to severe forms of AS associated with poor survival if left untreated,” reported Geoffrey A. Strange, PhD, professor, faculty of medicine, University of Sydney.
The AS-DSA was trained not only to recognize adverse changes in aortic valve morphology but to evaluate indices of impaired valve function, including those related to the left ventricle, the left atrium, and pulmonary circulation, according to Dr. Strange.
AI algorithm based on more than 800K echos
The training was performed on more than 1 million echocardiograms obtained from 630,000 patients in the National Echo Database (NEDA) of Australia. The testing phase of the study, called AI ENHANCED AS, was carried out on 179,054 individuals from the same database.
In the testing phase, mortality was compared for those determined by AI to have a low probability of clinically significant AS, a moderate to severe AS, or severe AS.
In the nearly 200,000 patients evaluated from the database, the AI-DSA classified 2.5% as having moderate to severe AS and 1.4% as having severe AS. Relative to a 22.9% mortality at 5 years in the low-risk reference group, the rates were 56.2% and 67.9% in the moderate to severe and severe groups, respectively.
When expressed as odds ratios, the mortality risk for the moderate to severe group (OR, 1.8; P < .001) and severe group (HR, 2.8; P < .001) “were about two to three times higher than the low probability group,” Dr. Strange reported.
All severe AS by guidelines AI identified
The algorithm picked up all patients identified with severe AS in current guidelines, but it also identified patients “missed by conventional definitions,” Dr. Strange reported.
The findings support the idea “that the AI algorithm could be used in clinical practice to alert physicians to patients who should undergo further investigations to determine if they qualify for aortic valve replacement,” he added.
Missing clinically significant AS is an important clinical problem, according to Catherine Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle.
“We focus on the patients who already have a diagnosis of AS,” she said. “The bigger issue is identification of patients with unknown AS.”
She praised the effort to develop AI that improves detection of AS, but also said that there are immediate steps to improve detection of AS even in the absence of AI support. In addition to the variability in the quality of how echocardiograms are read, she said a substantial proportion of echo reports omit key variables.
“We do not need AI to measure the aortic valve. It is simple to do in clinical practice,” she said. However, studies have repeatedly shown that values, such as maximal aortic jet velocity (Vmax) and the pressure difference across the ventricular septal defect (delta P), are not included. When AS is present, some reports do not include a characterization of the severity.
The AI-DSA described by Dr. Strange takes into account all of these variables along with additional information, but he acknowledged that it does have limitations. For example, the presence of cardiac impairments other than AS will not be included, and these can be relevant to prognostication and treatment.
AI does not eliminate clinical decision-making
“This algorithm is definitely not meant to take away from clinical decision-making,” Dr. Strange said, but he argued that there is an unmet need to do better in the detection of AS. He presented data to show that “even moderate AS is not benign” in regard to 5-year outcomes, and he believes AI-DSA can allow clinicians to detect significant disease earlier and intervene in a timelier manner.
“It is time to revisit the practice of watchful waiting and consider more proactive attempts to identify those at risk,” he said.
The next step is to determine if AI-DSA makes a clinical difference,
“Research is now needed to determine if aortic valve replacement in patients identified as being at risk by AI-DSA improves survival and quality of life, particularly in those who do not meet current guideline definitions of clinically significant disease,” he said.
Dr. Strange reports financial relationships with Edwards, Medtronic, Novartis, Pfizer, and Echo IQ, which is developing the artificial algorithm studied in this trial. Dr. Otto reports no relevant conflicts of interest.
AI might facilitate early intervention
AI might facilitate early intervention
Patients with aortic stenosis (AS) of sufficient severity to portend a high likelihood of early mortality can be detected by an artificial intelligence (AI) algorithm employed in the reading of routine echocardiograms, according to a study that tested this tool in a large national database.
The artificial intelligence decision support algorithm (AI-DSA) “automatically identified patients with moderate to severe forms of AS associated with poor survival if left untreated,” reported Geoffrey A. Strange, PhD, professor, faculty of medicine, University of Sydney.
The AS-DSA was trained not only to recognize adverse changes in aortic valve morphology but to evaluate indices of impaired valve function, including those related to the left ventricle, the left atrium, and pulmonary circulation, according to Dr. Strange.
AI algorithm based on more than 800K echos
The training was performed on more than 1 million echocardiograms obtained from 630,000 patients in the National Echo Database (NEDA) of Australia. The testing phase of the study, called AI ENHANCED AS, was carried out on 179,054 individuals from the same database.
In the testing phase, mortality was compared for those determined by AI to have a low probability of clinically significant AS, a moderate to severe AS, or severe AS.
In the nearly 200,000 patients evaluated from the database, the AI-DSA classified 2.5% as having moderate to severe AS and 1.4% as having severe AS. Relative to a 22.9% mortality at 5 years in the low-risk reference group, the rates were 56.2% and 67.9% in the moderate to severe and severe groups, respectively.
When expressed as odds ratios, the mortality risk for the moderate to severe group (OR, 1.8; P < .001) and severe group (HR, 2.8; P < .001) “were about two to three times higher than the low probability group,” Dr. Strange reported.
All severe AS by guidelines AI identified
The algorithm picked up all patients identified with severe AS in current guidelines, but it also identified patients “missed by conventional definitions,” Dr. Strange reported.
The findings support the idea “that the AI algorithm could be used in clinical practice to alert physicians to patients who should undergo further investigations to determine if they qualify for aortic valve replacement,” he added.
Missing clinically significant AS is an important clinical problem, according to Catherine Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle.
“We focus on the patients who already have a diagnosis of AS,” she said. “The bigger issue is identification of patients with unknown AS.”
She praised the effort to develop AI that improves detection of AS, but also said that there are immediate steps to improve detection of AS even in the absence of AI support. In addition to the variability in the quality of how echocardiograms are read, she said a substantial proportion of echo reports omit key variables.
“We do not need AI to measure the aortic valve. It is simple to do in clinical practice,” she said. However, studies have repeatedly shown that values, such as maximal aortic jet velocity (Vmax) and the pressure difference across the ventricular septal defect (delta P), are not included. When AS is present, some reports do not include a characterization of the severity.
The AI-DSA described by Dr. Strange takes into account all of these variables along with additional information, but he acknowledged that it does have limitations. For example, the presence of cardiac impairments other than AS will not be included, and these can be relevant to prognostication and treatment.
AI does not eliminate clinical decision-making
“This algorithm is definitely not meant to take away from clinical decision-making,” Dr. Strange said, but he argued that there is an unmet need to do better in the detection of AS. He presented data to show that “even moderate AS is not benign” in regard to 5-year outcomes, and he believes AI-DSA can allow clinicians to detect significant disease earlier and intervene in a timelier manner.
“It is time to revisit the practice of watchful waiting and consider more proactive attempts to identify those at risk,” he said.
The next step is to determine if AI-DSA makes a clinical difference,
“Research is now needed to determine if aortic valve replacement in patients identified as being at risk by AI-DSA improves survival and quality of life, particularly in those who do not meet current guideline definitions of clinically significant disease,” he said.
Dr. Strange reports financial relationships with Edwards, Medtronic, Novartis, Pfizer, and Echo IQ, which is developing the artificial algorithm studied in this trial. Dr. Otto reports no relevant conflicts of interest.
Patients with aortic stenosis (AS) of sufficient severity to portend a high likelihood of early mortality can be detected by an artificial intelligence (AI) algorithm employed in the reading of routine echocardiograms, according to a study that tested this tool in a large national database.
The artificial intelligence decision support algorithm (AI-DSA) “automatically identified patients with moderate to severe forms of AS associated with poor survival if left untreated,” reported Geoffrey A. Strange, PhD, professor, faculty of medicine, University of Sydney.
The AS-DSA was trained not only to recognize adverse changes in aortic valve morphology but to evaluate indices of impaired valve function, including those related to the left ventricle, the left atrium, and pulmonary circulation, according to Dr. Strange.
AI algorithm based on more than 800K echos
The training was performed on more than 1 million echocardiograms obtained from 630,000 patients in the National Echo Database (NEDA) of Australia. The testing phase of the study, called AI ENHANCED AS, was carried out on 179,054 individuals from the same database.
In the testing phase, mortality was compared for those determined by AI to have a low probability of clinically significant AS, a moderate to severe AS, or severe AS.
In the nearly 200,000 patients evaluated from the database, the AI-DSA classified 2.5% as having moderate to severe AS and 1.4% as having severe AS. Relative to a 22.9% mortality at 5 years in the low-risk reference group, the rates were 56.2% and 67.9% in the moderate to severe and severe groups, respectively.
When expressed as odds ratios, the mortality risk for the moderate to severe group (OR, 1.8; P < .001) and severe group (HR, 2.8; P < .001) “were about two to three times higher than the low probability group,” Dr. Strange reported.
All severe AS by guidelines AI identified
The algorithm picked up all patients identified with severe AS in current guidelines, but it also identified patients “missed by conventional definitions,” Dr. Strange reported.
The findings support the idea “that the AI algorithm could be used in clinical practice to alert physicians to patients who should undergo further investigations to determine if they qualify for aortic valve replacement,” he added.
Missing clinically significant AS is an important clinical problem, according to Catherine Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle.
“We focus on the patients who already have a diagnosis of AS,” she said. “The bigger issue is identification of patients with unknown AS.”
She praised the effort to develop AI that improves detection of AS, but also said that there are immediate steps to improve detection of AS even in the absence of AI support. In addition to the variability in the quality of how echocardiograms are read, she said a substantial proportion of echo reports omit key variables.
“We do not need AI to measure the aortic valve. It is simple to do in clinical practice,” she said. However, studies have repeatedly shown that values, such as maximal aortic jet velocity (Vmax) and the pressure difference across the ventricular septal defect (delta P), are not included. When AS is present, some reports do not include a characterization of the severity.
The AI-DSA described by Dr. Strange takes into account all of these variables along with additional information, but he acknowledged that it does have limitations. For example, the presence of cardiac impairments other than AS will not be included, and these can be relevant to prognostication and treatment.
AI does not eliminate clinical decision-making
“This algorithm is definitely not meant to take away from clinical decision-making,” Dr. Strange said, but he argued that there is an unmet need to do better in the detection of AS. He presented data to show that “even moderate AS is not benign” in regard to 5-year outcomes, and he believes AI-DSA can allow clinicians to detect significant disease earlier and intervene in a timelier manner.
“It is time to revisit the practice of watchful waiting and consider more proactive attempts to identify those at risk,” he said.
The next step is to determine if AI-DSA makes a clinical difference,
“Research is now needed to determine if aortic valve replacement in patients identified as being at risk by AI-DSA improves survival and quality of life, particularly in those who do not meet current guideline definitions of clinically significant disease,” he said.
Dr. Strange reports financial relationships with Edwards, Medtronic, Novartis, Pfizer, and Echo IQ, which is developing the artificial algorithm studied in this trial. Dr. Otto reports no relevant conflicts of interest.
FROM ESC CONGRESS 2022
New ESC cardio-oncology guideline aims to reduce cardiotoxicity
BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.
The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.
Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”
because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.
“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.
“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.
The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”
“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
Steady decline in cancer-related mortality
The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”
Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.
He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.
“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”
Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.
Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.
Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”
That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.
The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.
“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”
Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.
She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.
Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.
There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.
To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.
They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.
The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.
They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.
A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.
Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.
He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.
Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.
In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.
These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.
Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.
Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.
The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.
A version of this article first appeared on Medscape.com.
BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.
The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.
Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”
because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.
“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.
“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.
The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”
“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
Steady decline in cancer-related mortality
The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”
Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.
He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.
“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”
Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.
Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.
Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”
That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.
The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.
“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”
Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.
She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.
Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.
There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.
To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.
They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.
The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.
They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.
A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.
Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.
He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.
Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.
In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.
These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.
Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.
Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.
The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.
A version of this article first appeared on Medscape.com.
BARCELONA – Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy–related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.
The guidelines were presented at the annual congress of the European Society of Cardiology and published simultaneously in the European Heart Journal.
Guideline cochair Alexander R. Lyon, MD, PhD, told this news organization that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment ... because it’s not one size fits all.”
because how you manage someone who’s at high risk is going to be different” than managing someone who is at moderate or low risk, he said.
“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Dr. Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.
“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.
The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”
“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Dr. Lyon said.
Steady decline in cancer-related mortality
The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”
Dr. Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.
He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.
“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”
Combined with the aging population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.
Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.
Dr. Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15%-20% of the women taking it and can cause severe heart failure if it is missed.”
That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.
The final reason for the greater interest in cardio-oncology, Dr. Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.
“We have been reaching out to our oncology and hematology colleagues over the last 5-10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”
Presenting the guidelines, cochair Teresa López-Fernández, MD, cardiology department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.
She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase but is not entirely diminished once it is over, then typically accumulates during long-term follow-up.
Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and previous cardiotoxic cancer therapy.
There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.
To those ends, Dr. López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.
They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.
The guidelines provide a range of recommendations for primary and secondary cancer therapy–related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use of angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.
They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.
A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation or the amount of radiation exposure to the heart during treatment.
Next, Dr. Lyon looked at recommendations for the management of cardiovascular disease and cancer therapy–related cardiovascular toxicity in patients receiving anticancer treatment.
He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug-drug interactions, and patient preferences.
Dr. Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.
In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.
These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.
Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.
Finally, Dr. Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.
The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Dr. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm, and Myocardial Solutions. Dr. López-Fernández declares relationships with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.
A version of this article first appeared on Medscape.com.
Majority of muscle symptoms with statins not caused by treatment
In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.
The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.
“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.
After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.
Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.
It was also simultaneously published online in The Lancet.
Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).
The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.
In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.
“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.
Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).
In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy.
“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added.
After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.
“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”
“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.
“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”
The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.
But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
Better patient information needed
Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.
“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.
“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”
Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.
“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.
The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).
In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
‘Reassuring information’
Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.
She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”
Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”
Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.
“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”
The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.
The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.
“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.
After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.
Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.
It was also simultaneously published online in The Lancet.
Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).
The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.
In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.
“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.
Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).
In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy.
“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added.
After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.
“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”
“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.
“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”
The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.
But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
Better patient information needed
Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.
“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.
“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”
Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.
“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.
The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).
In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
‘Reassuring information’
Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.
She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”
Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”
Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.
“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”
The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
In the vast majority of people who experience muscle pain or weakness while taking a statin, those symptoms are not related to the statin, a new individual patient data meta-analysis of randomized controlled trials shows.
The Cholesterol Trialists Collaboration meta-analysis examined 19 large randomized double-blind trials that compared statin therapy with placebo and involved almost 124,000 patients.
“Our results show that, in people who experience muscle symptoms in the first year of taking a statin, those symptoms are actually due to the statin in only 1 of 15 of those people. For the other 14 of the 15 people who experience muscle symptoms in the first year of taking a statin, that muscle pain is not due to the statin,” lead investigator Colin Baigent, MD, said.
After the first year, there was no difference in muscle symptoms between patients taking a statin or those taking placebo.
Dr. Baigent, who is director of the Population Health Research Unit at the University of Oxford (England), presented the data on Aug. 29 at the European Society of Cardiology 2022 Congress.
It was also simultaneously published online in The Lancet.
Dr. Baigent explained that statins very rarely cause serious muscle adverse effects with biochemical evidence of cellular damage, such as myopathy (which occurs in less than 1 in 10,000 patients per year) and rhabdomyolysis (which occurs in about 0.2 per 10,000 patients per year).
The effect of statins on other less serious muscle symptoms without biochemical evidence of cellular damage is less clear, but misinformation about the risks have arisen from nonrandomized studies, with social media and press reports suggesting that the risk for muscle symptoms with statins is extremely common, Dr. Baigent said.
In response to this, the Cholesterol Trialists Collaboration put together a new program of data collection, validation, and analysis to provide reliable information from large double-blind randomized trials that are free from bias and confounding.
“Overall, when we look at all these data, we find there is about a 3% relative increase in the risks of experiencing muscle pain or weakness with a statin versus with placebo,” Dr. Baigent reported.
Muscle pain or weakness was reported by 16,835 of 62,028 patients taking a statin, (27.1%), compared with 16,446 of 61,912 patients taking placebo (26.6%), for a rate ratio of 1.03 (95% confidence interval, 1.01-1.06).
In absolute terms, the results show a rate of 166 reports of muscle symptoms per 1,000 patient-years in those taking a statin, compared with 155 per 1,000-patient-years in those taking placebo in the first year. This gives a rate ratio of 1.07 and an excess of 11 cases of muscle pain or weakness per 1,000 patients in the first year of statin therapy.
“The very small excess of muscle symptoms in the statin patients were generally mild, with most patients able to continue treatment,” Dr. Baigent added.
After the first year, the rate of muscle pain or weakness was exactly the same in the statin and placebo groups, at 50 per 1,000 patient-years.
“Therefore, for the vast majority of people who experience muscle pain or weakness on a statin, those symptoms are not due to the statin itself. It is due to something else, which could be ageing, thyroid disease, or exercise,” Dr. Baigent said. “After the first year of taking a statin, there is no excess risk of muscle pain or weakness at all.”
“To summarize, the excess risk of muscle pain or weakness with statin use is tiny, and almost nonexistent after the first year,” he added.
“Muscle pain is very common in the general population, and it was very common in both patients taking a statin and those given placebo in these randomized trials. We can only detect a difference by looking at all the data combined in this enormous study. And we now know for sure that over 90% of cases of muscle symptoms experienced by people taking a statin are not due to the statin.”
The researchers also looked at statin intensity and found that the more intense statins tend to cause slightly more muscle pain. “There was also some evidence, although this was not very clear, that the muscle pain with the more intensive statins may persist for longer than 1 year,” Dr. Baigent said.
But in terms of different moderate-intensity and high-intensity statins, there was no evidence of differences in muscle pain between the individual statin brands, he added.
Better patient information needed
Dr. Baigent called for better information in statin package inserts about the real risk for muscle symptoms with these drugs.
“We need to do a better job of communicating the real risk of muscle symptom to patients who are taking statins and to their doctors. At the moment, doctors often stop statins if patients complain of muscle pain, but our data show that in 14 out of 15 times, they would be wrong for doing that. Stopping the statin is nearly always a mistake,” he commented.
“At present, the package inserts include a whole load of rubbish from observational studies, which are completely unreliable,” he added. “This is of no value to patients. They go through this information and find several symptoms they are experiencing, which they attribute to the drugs. We really need to divide up the information into the evidence that we really know for sure and then the more speculative stuff.”
Dr. Baigent also highlighted the large benefits of statins, compared with the small risk for muscle symptoms.
“While statins may cause 11 patients per 1,000 to experience some mild muscle pain in the first year of taking these drugs, and this was reduced to none in subsequent years, statins, when used for the primary prevention of cardiovascular disease, prevent 25 cardiovascular events per 1,000 patients every year they are taken. And for secondary prevention this rises to 50 events prevented per 1,000 patients each year,” he noted.
The individual participant data meta-analysis involved 23 trials with information on almost 155,000 patients. All trials included at least 1,000 patients and at least 2 years of scheduled treatment. Adverse-event data were collected for all individual participants in 19 large randomized double-blind trials comparing statin therapy with placebo (123,940 patients) and in four randomized double-blind trials comparing more-intensive with less-intensive statin therapy (30,724 patients).
In the four trials of more-intensive versus less-intensive statin therapy, high-intensity regimens (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) resulted in a larger relative increase in the rate of muscle pain or weakness than moderate-intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.
‘Reassuring information’
Discussant of the study at the ESC Hotline session, Erin Bohula, MD, Brigham and Women’s Hospital, Boston, said this new analysis had many strengths and used a rigorous approach to look at the issue of muscle symptoms with statins.
She pointed out some challenges, including the fact that the definition of adverse muscle events has changed over time and differed in the various trials, with heterogeneous data capture across trials. “So, this was a Herculean task to harmonize this very complicated dataset.”
Dr. Bohula concluded: “I think this is a very significant undertaking, resulting in a rich dataset that enhances our understanding of muscle symptoms related to statin use. The take-home for me is that muscle symptoms are a common complaint in the general population but are very rarely attributable to statins. This is very reassuring to me, and I hope it is reassuring to patients and can help us encourage them with adherence, given the clear cardiovascular benefits of statins.”
Chair of the ESC Hotline session at which the study was presented, Gabriel Steg, MD, Hôpital Bichat, Paris, asked whether some statin patients who experienced muscle symptoms with the drugs in active run-in periods in the trials may have been excluded from the main trials, so that this information might not have been captured, but Dr. Baigent replied that they also examined those data, which had been accounted for in the analysis.
“That’s really good news,” Dr. Steg commented. “This study is going to be one more tool in our response to statin skeptics and I think, as such, this work is a really a service to public health.”
The meta-analysis was funded by the British Heart Foundation, the U.K. Medical Research Council, and the Australian National Health and Medical Research Council.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022
Evolocumab benefits accrue with longer follow-up: FOURIER OLE
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022